信息编号11357051至11357100间共50条。
☉ 11357052:Internet access is a socioeconomic issue
EDITOR—The paper by Christensen et al on delivering interventions for depression by using the internet is encouraging.1 Researchers are starting to probe more deeply into the potential the internet has to offer in medical care. Since the rise and fall of the dotcom bubble over the past few years, much has been promised by this new technology, but the research evidence has been slower to follow. This paper, however, further confirms my suspicion that use of the internet continues to be socioeconomically determined.2 Christensen et al show that the people who gained the most from their internet intervention were well educated women in their late 30s. This is particularly worrying as groups well recognised to be particularly affected by mood disorders—namely, old and poor people—do not seem to be represented. The explanation may be that old and poor people in Australia have a similar pattern of internet access to that of those in the United Kingdom. In the United Kingdom old and poor people have poor internet access. Of those over 65 years of age, only 7% have ever accessed the internet.3 Of the poorest 10% of the United Kingdom's population, only 12% have ever accessed the internet.4 The internet has the potential to offer much, but access to this resource continues to be a problem for those who most need it. Until access issues are addressed, it is hard to imagine that it will ever replace more traditional face to face services, and mental health service providers must resist the temptation to use it as a cut price way of providing their psychological treatments. Geoff Wong, general practitioner principal Daleham Gardens Surgery, London NW3 5BY Geoffrey.Wong@gp-F83633.nhs.uk Competing interests: None declared. References Christensen H, Griffiths K, Jorm A. Delivering interventions for depression by using the internet: randomised controlled trial. BMJ 2004;328: 265-8. (31 January.) Wong G. Increasing email consultations may marginalise more people. BMJ 2001;323: 1189. National Statistics. Households with internet access: by household type: social trends 34. www.statistics.gov.uk/STATBASE/ssdataset.asp?vlnk=7203&More=Y (accessed 1 Feb 2004). National Statistics. Households with home access to the internet by gross income decile group: household internet access. www.statistics.gov.uk/STATBASE/ssdataset.asp?vlnk=6937&More=Y (accessed 1 Feb 2004)....查看详细 (2453字节)

☉ 11357053:Traumatic brain injury and haemorrhagic complications after intracranial pressure monitoring
Department of Neurological Surgery, University of Washington School of Medicine, Seattle, Washington, USA Correspondence to: Dr M Blaha Neurosurgery Department, Central Military Hospital, U Vojenske nemocnice 1200, Prague, Stresovice 169 02, Czech Republic; drmartinblaha@yahoo.com Keywords: complications; intracranial haemorrhages; intracranial pressure monitoring; traumatic brain injury Intracranial pressure (ICP) monitoring is now a widely Materials and methods Patients Over 5 months, the Neurosurgery Service at Harborview Medical Center treated 314 patients with traumatic head injury. There were 247 males and 67 females with a median (SD) age of 35.16 (22.9) years (range 0.4 to 102 years), and all were admitted to the hospital. Placement of an ICP monitor (CaminoTM, intraparenchymal) was undertaken in 130 of these patients. We retrospectively analysed the patient’s hospital charts and all available radiological studies, with particular attention paid to our own interpretation of CT scans before and after ICP monitor insertion. The final numbers in the study were 101 males and 29 females with a median (SD) age of 36.6 (21.9) years (range 1.8 to 102 years). ICP monitoring Indications for ICP monitoring followed the head injuries (ICP monitoring) guidelines:5 (a) patients with severe head injury, GCS8 with an abnormal head CT; (b) patients with severe head injury, GCS8 with a normal head CT, and having two or more of the following: age >40 years, systolic blood pressure <90, or posturing; (c) patients with GCS 9–12 and abnormal head CT, if undergoing therapies for other injuries with possible deleterious effects on ICP; and (d) subsequent to removal of intracranial mass. The fibre optic device was placed at the bedside (intensive care unit, emergency room) or at completion of the surgery in the operating theatre. Some patients needed replacement of an ICP device because of technical problems with the device. The right side was preferred for the insertion of the ICP monitor. CT scanning The institutional protocol was to perform CT scanning during the first 24 hours after the insertion of ICP device. We were not able to obtain CT in this time frame in four cases. A grading system for haemorrhages after ICP monitor insertion from our institution was used (fig 1). Grade 0 was used to report patients with no complications on post-placement studies. Grade 1 is a small punctuate haemorrhage or localised subarachnoid haemorrhage (SAH). Grade 2 haemorrhage is an intracranial bleed, diffuse SAH or extra-axial haematoma without a new neurological deficit and does not require operative intervention. In a case of grade 3 complication, revision craniotomy is required or there is a new neurological deficit, even a death. Figure 1 The different degrees of post-insertion haemorrhages. Results Of the 314 patients with traumatic head injury, ICP monitor insertion was performed in 130 (41%). Nineteen patients had more than one ICP monitor inserted; altogether, 155 procedures were carried out. Right sided procedures prevailed (n = 102, 66%). The majority of the patients in this study were admitted with the diagnosis of a closed head injury (n = 116, 89.2%), 10 patients had open head injury, and four suffered a gunshot wound to the head. One hundred and six procedures (68%) were performed at the bedside, and 49 insertions (32%) took place in the operating theatre. We retrospectively analysed the patient’s hospital charts and all available radiological studies. There were 140 procedures performed without any haemorrhagic complications on follow up radiological studies (grade 0). After 10 insertions (6.5%), a small punctuate haemorrhage or localised subarachnoid haemorrhage occurred. These complications were classified as grade 1 haemorrhages. Five patients (3.2%) sustained an intracerebral haematoma that did not necessitate evacuation or manifest as a new neurological deficit (grade 2). There were no haemorrhagic complications requiring evacuation or resulting in a noticeable change in the patient’s clinical condition (grade 3). Altogether, the complication rate was 9.7% for this study. More haemorrhagic complications occurred after ICP monitor placement in the operating theatre (n = 8/49, 16.3%), compare the bedside procedures (n = 7/106, 6.6%). This distribution did not reach statistical significance (p = 0.057). Conclusions There is a wide range (0–15.3%) in the literature of reported incidences of intracranial haemorrhages following placement of an ICP monitoring device.3,4 However, most studies had multiple targets such as outcome, different treatment options or indication criteria and these published reports failed to distinguish between large haematomas requiring surgical evacuation and small punctuate haemorrhages picked up incidentally only on imaging. In head trauma, there are multiple lesions on radiological examinations, and without detailed knowledge of the patient’s surgical procedures, a punctuate haemorrhage can be counted as an evolving contusion or go unnoticed. Due to previous metal artefacts from tip of the ICP monitor catheter, some small lesions were detected only after its removal. In our traumatic brain injury group, we found a complication rate of 9.7% with no grade 3 haemorrhage. Although the most common grade 1 haemorrhage seems to be unimportant, we do not know its long term consequences and it may cause a false reading of a high ICP with subsequent unnecessary therapeutic interventions. The incidence of grade 3 haemorrhage was 0.15% (1 in 684 procedures) in our institution for the general neurosurgical population (trauma, tumors, cerebrovascular),4 and there is a similar complication rate and stratification for the paediatric subpopulation.4 Although intracranial pressure monitoring plays an indispensable role in the management of head injuries, the indications for this invasive neurosurgical procedure should always be carefully considered. Even with the utmost precautions, haemoragic complications may occur. Classification of the complications in the clinically relevant scheme may help to compare results of future studies. References Poca MA, Sahuquillo J, Arribas M, et al. Fiberoptic intraparenchymal brain monitoring with the Camino V420 monitor: reflections on our experience in severely head-injured patients. J Neurotrauma 2002;19:439–48. Segal S, Gallagher AC, Shefler AG, et al. Survey of the use of intracranial pressure monitoring in children in the United Kingdom. Intensive Care Med 2001;27:236–9. Martinez-Manas RM, Santamarta D, de Campos JM, et al. Camino intracranial pressure monitor: prospective study of accuracy and complications. J Neurol Neurosurg Psychiatry 2000;69:82–6. Blaha M, Lazar D, Winn RH, et al. Hemorrhagic complications of intracranial pressure monitors in children. Pediatr Neurosurg 2003;39:27–31. Narayan RK, Kishore PR, Becker DP, et al. Intracranial pressure: to monitor or not to monitor? A review of our experience with severe head injury. J Neurosurg 1982;56:650–9....查看详细 (7182字节)
☉ 11357054:NHS national programme for information technology
EDITOR—At the same time as the Data Protection Act and the Human Tissue Bill are making life difficult for doctors and researchers in a misguided and unwanted effort to protect patients' rights,1 the NHS is eroding the confidentiality of medical records. A process of linking hospital computerised record systems has been going on for a few years. This entails a huge increase in the number of people who are authorised to access sensitive medical data—most obviously pathology data. This obviously reduces the security of the data, but no consultation process has taken place about the wisdom of doing it. Similarly, and much worse, the national programme for information technology proposes that all medical data including general practice records should be accessible by doctors across the whole of England by linking all medical computer systems. It takes only one corrupt user to access any medical data for anyone on the system, however careful the password system. What seems to be lacking in the present NHS is common sense and balanced judgment. We risk a situation in which no one will be bothered to do medical research apart from well financed pharmaceutical companies, while patients ask us not to keep computer records for fear they will be made public. Ted A Willis, general practitioner Bridge Street Surgery, Brigg, North Lincolnshire DN20 8NT tedw@onetel.net.uk Competing interests: None declared. References Peto J, Fletcher O, Gilham C. Data protection, informed consent, and research. BMJ 2004;328: 1029-30. (1 May.)...查看详细 (1583字节)

☉ 11357055:An unusual cause of dysphagia
St Thomas’ Hospital, London Correspondence to: Dr Sarah Payne St Bartholomew’s Hospital, West Smithfield, London EC1A 7BE; sarah_146@hotmail.com Keywords: Lambert-Eaton Myasthenic Syndrome (LEMS); dysphagia; paraneoplastic syndromes We report a case of a patient with Lambert Eaton Myasthenic Syndrome (LEMS) associated with small cell lung cancer (SCLC) presenting with a 2 year history of dysphagia. This presentation has not been described in previous literature. Case A 71 year old right handed deck worker initially presented with a 6 month history of dysphagia, weight loss, nausea, and fatigue. He was cachetic with no other clinical signs to be found on examination. Baseline blood tests were unremarkable. Upper gastrointestinal (GI) endoscopy revealed a small hiatus hernia only. Subsequent investigations included a barium swallow, computer tomography (CT) scans of the chest and abdomen, oesophageal manometry, small bowel follow through, and laparoscopy, which were all normal. He was empirically started on cisapride and managed on an appropriate pureed diet. Eighteen months after his initial presentation the patient complained of a gradual deterioration in his speech and problems with proximal muscle weakness. Clinical examination demonstrated an obvious dysarthria and broad based gait. There was no limb weakness or sensory neuropathy and reflexes were preserved with no post-tetanic potentiation. There was no disturbance of extraocular eye movements or ptosis. The patient did not display any cognitive impairment. He subsequently developed involuntary choreo-athetoid movements. Baseline blood tests and chest x ray (CXR) were again normal. Magnetic resonance imaging of the brain demonstrated evidence of small vessel disease. Electromyography and nerve conduction studies were performed. Sensory conduction velocities were within normal limits. Motor conduction velocities demonstrated a clear and reproducible decremental response to repetitive stimulation in the right ulnar nerve (32%) and in the right median nerve (25%), maximal at 3 Hz stimulation. Compound action potentials in the muscles tested increased by more than 50% following a period of exercise (right ulnar nerve 0.9 to 2.8 mV, right median nerve 1.7 to 2.8 mV). Electromyogram (EMG) of the right biceps and 1st dorsal interosseous muscles were normal. Overall the results were felt to be consistent with a diagnosis of Lambert-Eaton Myasthenic Syndrome (LEMS). The presence of anti-voltage gated calcium channel antibodies confirmed the diagnosis. Repeat CT scanning in combination with positron emission tomography (PET) scanning revealed enlarged subcarinal lymph nodes only. A transbronchial lymph node aspiration confirmed the diagnosis of small cell lung cancer. Anti-Hu antibodies were found to be positive. The patient initially Discussion Dysphagia occurs in 24–34% of patients with LEMS.1 This usually develops late in the course of the disease, but may be present at the onset.2 Dysphagia as the sole presenting symptom of LEMS is extremely rare however. Proximal lower limb girdle weakness is the most frequent presentation. In a case series of 50 consecutive patients, leg weakness was the presenting complaint in 62% of patients.1 Less frequent presentations are generalised weakness, aching and stiffness, autonomic symptoms (impotence, dry mouth, constipation), arm weakness, diplopia, and dysarthria. Guruprakash et al reported a case of a 59 year old man presenting with dysphagia who was subsequently found to have LEMS.3 Further investigation revealed adenocarcinoma of the prostate with bony metastases. The dysphagia resolved completely with a combination of preoperative guanidine hydrochloride, followed by bilateral orchidectomy and diethylstilbestrol diphosphate. Recognising LEMS swiftly is important, as it may be an early warning sign of an underlying malignancy. Approximately 60% of LEMS patients have cancer, usually SCLC.4 Other less commonly associated malignancies include lymphoproliferative disorders, carcinoma of the breast, colon, stomach, gall bladder, kidney and bladder, adenocarcinoma of the lung, pancreas and prostate, and intrathoracic carcinoid. The diagnosis of LEMS usually precedes the cancer diagnosis by a median of 6 months.4 Carcinoma associated LEMS patients tend to present at an older age than LEMS without carcinoma. A male predominance has been noted in the past, but more recent epidemiology does not support this, likely reflecting the changes in smoking patterns. Our patient also developed chorea. Multiple paraneoplastic syndromes are very rare but have been previously described. Vernino et al reported a series of 16 patients with paraneoplastic chorea, of which one patient in the series also had a diagnosis of LEMS.5 Currently an autoimmune aetiology is favoured for the development of paraneoplastic syndromes. Antibodies have been demonstrated against calcium channel antigens shared between SCLC and presynaptic cholinergic synapses in LEMS. Anti-HuD antibodies have also been detected in patients with SCLC presenting with other paraneoplastic syndromes. This antigen is common to SCLC cells and the nuclei of neurones in the central and peripheral nervous systems. Management of LEMS includes the use of 3,4 Diaminopyridine, which provides symptomatic improvement in patients with or without a neoplasm. Steroids and immunosuppression with azathioprine or cyclosporin are of particular value in patients with non-cancer associated LEMS. Our patient was successfully treated with IVIg and chemoradiotherapy. This resulted in resolution of the dysphagia and some improvement in the chorea. The role of IVIg in treating LEMS is established. It is also recognised that treatment of the underlying tumour can result in improvement or remission of symptoms relating to the paraneoplastic syndromes. This case illustrates that LEMS is an unusual but important cause of swallowing difficulties. In the present patient, establishing the cause of dysphagia led to the diagnosis and treatment of the underlying SCLC. ACKNOWLEDGEMENTS Thank you to Mr R Mason (Consultant General Surgeon, St Thomas’ Hospital, Lambeth Palace Road, London SE1 7EH) and Mr J Prendeville (Consultant Medical Oncologist, Guys Hospital, St Thomas Street, London SE1 9RT) for their review of this case. References O’Neill JH, Murray NM, Newsom-Davis J. The Lambert-Eaton myasthenic syndrome. A review of fifty cases. Brain 1988;111:577–96. Heath JP, Ewing DJ, Cull RE. Abnormalities of autonomic function in the Lambert-Eaton myasthenic syndrome. J Neurol Neurosurg Psychiatry 1988;51:436–9. Guruprakash GH, Ahmed I, Shadchehr A. Report of a case presenting with dyshagia due to Eaton-Lambert Syndrome. J Kans Med Soc 1982;83:617–9. Wirtz PW, Smallegange TM, Wintzen AR, et al. Differences in clinical features between the Lambert-Eaton myasthenic syndrome with and without cancer: an analysis of 227 published cases. Clin Neurol Neurosurg 2002;104:359–63. Vernino S, Tuite P, Adler CH, et al. Paraneoplastic chorea associated with CRMP- 5 neuronal antibody and lung carcinoma. Annal Neurol 2002;51:625–30....查看详细 (7298字节)
☉ 11357057:Is the rapid assessment stroke clinic rapid enough in assessing transient ischaemic attack and minor stroke?
1 Department of Radiology, Sheffield Teaching Hospitals NHS Trust, Sheffield, UK 2 Medical School, University of Sheffield 3 Academic Section of Radiology, University of Sheffield 4 Department of Neurology, Sheffield Teaching Hospitals NHS Trust Correspondence to: Dr E Widjaja Radiology Department, Royal Hallamshire Hospital, Glossop Rd, Sheffield S10 2JF, UK; Elysa.Widjaja@sth.nhs.uk Keywords: transient ischaemic attacks; stroke; stroke prevention Our rapid assessment stroke clinic (RASC) was established as part of a single point of access for general practitioners to refer patients with suspected transient cerebral or ocular ischaemic attacks (TIA) or recovered non-hospitalised stroke in response to the publication of the National Clinical Guidelines for Stroke1 and the National Service Framework for Older People.2 Similar rapid access neurovascular clinics have been set up throughout the United Kingdom to provide readily available access to primary care for the management of similar patients. These clinics have significant revenue costs for the NHS, and hence the importance of reviewing their process and outcome. We now report the fate of non-attendees to highlight the risk of early stroke. Between October 2000 and December 2002, 1460 patients were referred to the RASC. When a referral (usually by phone or fax) is In all, 1460 patients were referred during the 27 months study period and 121 failed to attend in spite of being sent two appointment. The median waiting time from referral to appointment was 17 days (range 0 to 96); 47.6% of patients were seen within two weeks of referral. The mean age of the non-attendees was 71 years (29 to 93); 44 were male and 77 female. Risk factors for TIA or minor stroke included atrial fibrillation (5.7%), hypertension (14%), diabetes (5.7%), and hypercholesterolaemia (11.5%). Reasons for non-attendance included 39 (32%) who had a stroke requiring admission to hospital, of which 27 (69%) occurred during the first three days after referral (fig 1). Thirteen of the 39 strokes (33%) were fatal. CT showed evidence of infarction in 31 (80%), intracranial haemorrhage in 2 (5%), and was normal or not undertaken in 6 (15%). Seventeen patients (44%) had carotid Doppler ultrasound, and of these, four had stenosis exceeding 50%. Figure 1 Time interval between referral and stroke occurrence. Patients with TIA are at significant short term risk of stroke, previously reported as ranging from 4% to 8% in the first month.3 Therefore the National Service Framework and National Clinical Guidelines for Stroke recommended the setting up of rapid access neurovascular clinics in which patients should be seen within 14 days of referral. In a study of patients presenting to an emergency department—almost all of whom were enrolled within 24 hours of the TIA—the reported stroke risk was 5% in the first two days.4 The Oxfordshire community stroke project (OCSP) prospectively followed a population of patients presenting to their primary care provider with a TIA or completed stroke reported a 4.4% risk of stroke in the first month following a recent TIA.5 In the subsequent OCSP study, which redefined the index event, the authors suggested that the risk was much higher than the initial estimate, lying at 8.6% and 12.0% at seven and 30 days, respectively.6 In our present review, 32% of patients who failed to attend the clinic did so because they had a stroke requiring hospital admission in the interval between seeing their general practitioners and the clinic appointment; 27 occurred in the first three days after referral, suggesting that the recommendation in the National Clinical Guidelines for Stroke about the timing of referrals to neurovascular clinics may need revision. Our study may be criticised on the grounds that information about the timing of the index event was not included; however, we regard this report as being a pragmatic view of what is happening in reality. A rapid access neurovascular service is unlikely to be effective in preventing stroke unless patients can be seen and treated on the same day that they present. This study highlights the need for urgent evaluation and treatment of those at risk of stroke, ideally on the same day as the index event. Studies are required to determine the most effective intervention. The challenge for stroke physicians is to test the effects of combination treatment comprising combined antiplatelet therapy, a cholesterol lowering drug, and blood pressure lowering agents given as soon as possible after the index event to reduce the risk of immediate stroke. References Intercollegiate Working Party for Stroke, Clinical Effectiveness and Evaluation Unit. National Clinical Guidelines for Stroke: Update 2002. London: Royal College of Physicians, 2002. Department of Health. National service framework for older people. Standard Five. London: DoH, 2001:61–75. Feinberg W, Albers G, Barnett H, et al. Guidelines for the management of transient ischemic attacks. Circulation 1994;89:2950–65. Johnston SC, Gress DR, Browner WS, et al. Short-term prognosis after emergency department diagnosis of TIA. JAMA 2000;284:2901–6. Dennis M, Bamford J, Sandercock P, et al. Prognosis of transient ischemic attacks in the Oxfordshire Communitiy Stroke Project. Stroke 1990;21:848–53. Lovett JK, Dennis MS, Sandercock PAG, et al. Very early risk of stroke after a first transient ischaemic attack. Stroke 2003;34:138–42....查看详细 (5561字节)

☉ 11357058:Anorexia nervosa remission following left thalamic stroke
1 Department of Neuropsychology, Royal Victoria Hospital, Belfast, BT12 6BA, UK 2 Department of Neurology, Royal Victoria Hospital, Belfast, BT12 6BA, UK 3 Department of Neuroradiology, Royal Victoria Hospital, Belfast, BT12 6BA, UK 4 Department of Neurology, Altnagelvin Hospital, Londonderry, BT47 6SB, UK Correspondence to: Dr M McCarron Department of Neurology, Altnagelvin Hospital, Londonderry, BT47 6SB, UK; markmccarron@doctors.org.uk Keywords: anorexia nervosa; thalamic stroke Anorexia nervosa is an intense fear of weight gain, inaccurate perception of body size, weight or shape, amenorrhoea, and a body weight <85% of expected weight (or body mass index (BMI) 17.5). We report a patient who, following a left thalamic stroke demonstrated a remarkable recovery from a 7 year history of anorexia nervosa. The patient grew up in a family with both parents and two older brothers. When she was 14 years old, a young cousin died of a "brain haemorrhage". Six months later the patient started a "healthy eating" regimen. She was first admitted to hospital for her eating disorder in April 1995, aged 15 years, and was prescribed antidepressant medication. The problem continued despite psychiatric and psychological treatment (usual weight 43 kg, BMI 17). In May 2002, aged 22 years, she experienced a sudden onset of right arm and leg weakness with a sensory disturbance of the right face, arm, and leg. There was no history of diabetes, cigarette smoking, illicit drugs, or oral contraceptive use. She was admitted to hospital. She was told that a computerised tomogram (CT) showed that she either had a brain tumour or had suffered a stroke. She was transferred to the regional neurology unit. There she was alert, but had a slight decrease in sensation on the right side of the face; there was no visual field defect. She had a right pronator drift. She had grade 4 strength throughout the right upper limb. Leg strength was normal. The right arm and leg were mildly hyperaesthetic and there was impaired proprioception in the right fingers. There was right sided ataxia. On the right she had brisk reflexes and an extensor plantar response. Her brain CT demonstrated left thalamic hypoattenuation, which on magnetic resonance imaging showed involvement of the left posterolateral thalamus and posterior temporal lobe (fig 1). The infarct area involved the left inferolateral artery territory. Magnetic resonance angiography was normal. Other investigations (chest x ray, electrocardiogram, thoracic echocariogram, full blood profile, thrombophilia screen, glucose, liver function tests, and thyroid function tests) were normal. The patient was extremely anxious and thought frequently about her cousin’s death. However, she gradually improved and reported to a neuropsychologist that she no longer had an eating disorder. Her realisation came quite suddenly 3 days after her transfer to the neurology service. She chose cauliflower cheese for her evening meal and asked a visitor for a chocolate chip biscuit; neither of these foods would have been acceptable as part of her anorexic diet. Figure 1 Axial T2 magnetic resonance images demonstrating high signal and mild mass effect in the posterolateral thalamus and posteromedial temporal lobe consistent with recent infarction. The infarct distribution corresponds to thalamogeniculate branches of the posterior cerebral artery. Within 6 months the patient gained 4 kg in weight (41 kg to 45 kg, BMI 18.7). Regular menses returned after two years of amenorrhoea. Eight months after the stroke she wrote the following descriptions of her feelings before and after her stroke: Pre-stroke: "Anorexia controlled my life and influenced things which I did or did not do." "... relationships – lost interest in them. Only interested in anorexia." Of her post-stroke state she said, "I have no feelings of guilt. I no longer count calories. I am relaxed about eating/around food. I can eat out in restaurants now." She continued with antidepressant medication and her mood remained stable. The patient completed the Eating Disorders Inventory-21 from the perspectives of pre-stroke and 13 months post-stroke. The bulimia and interpersonal trust scales were at the mean for non-patient college females both pre- and post-stroke. Drive for thinness and body dissatisfaction were high pre-stroke, even in comparison with the eating disorder group. The scores on drive for thinness, body dissatisfaction, ineffectiveness, and interoceptive awareness all fell dramatically post-stroke, and her post-stroke scores were close to the mean for non-patient college females. Discussion Our patient demonstrated sustained remission from anorexia nervosa for a 13 month period following a left posterolateral thalamic stroke. She reported significantly changed attitudes to food. Clearly the pre-stroke assessment, completed retrospectively, has to be interpreted cautiously. Nevertheless, the findings strongly suggest important shifts in her attitudes. There are two possible hypotheses to account for her anorexia remission: (a) the cerebral infarct switched off her anorexia; or (b) the personal trauma of the stroke, including being told that she might have a brain tumour or had had a stroke. Thalamic pathways have been implicated in the control of normal eating. As part of Papez circuit, the anterior thalamus projects to the cingulate gyrus and the dorsomedial thalamus projects to the basal nuclei of Meynert. The thalamus may have an integrative role with higher order somatosensory and visuospatial function. Neuroimaging techniques have demonstrated several abnormalities in the anorectic state, some of which are reversible with treatment. The smaller size of the thalamus2 and thalamic perfusion changes in anorexics3 suggest that the thalamus plays an important role in anorexia nervosa. Our patient demonstrated the usual clinical features of lateral thalamic infarction: hemiataxia, and hemisensory and motor deficit. Hyperphagia has been reported with a variety of lesions in the thalamus, hypothalamus and frontal lobe. Lesions in these areas have also been implicated in the onset of anorexia nervosa. In contrast to our patient’s remission from anorexia with a left posterolateral thalamic infarct, anorexia has been associated with dorsomedial thalamic infarction. Stereotactic thalamotomy has been used as a treatment of anorexia nervosa.4,5The right dorsomedial and intralaminar thalamic nuclei were lesioned in one patient,4 while a bilateral procedure was performed in two;5 all three made a sustained improvement. There are other reports of improvements following an encephalitic illness and a right thalamic haemorrhage. Trauma may contribute to the development of anorexia nervosa. However, there are no reports, to our knowledge, of a traumatic event leading directly to the cessation of an eating disorder. Our patient was traumatised by the sudden death of a 21 year old cousin from a "brain haemorrhage" when she was aged 13 years. A change in her eating pattern developed into anorexia nervosa over subsequent months. Whether this sudden and sustained recovery from an eating disorder was due to a psychologically traumatic event or to the direct effect of the left thalamic stroke is not certain. The abruptness of the change, and reported functional thalamic abnormalities in anorectics that reverse in remission, lends weight to the latter hypothesis. References Garner DM. Eating disorder inventory – 2. Psychological Assessment Resources Inc., 1990. Husain MM, Black KJ, Doraiswamy PM, et al. Subcortical brain anatomy in anorexia and bulimia. Biol Psychiatry 1992;31:735–8. Chowdhury U, Gordon I, Lask B, et al. Early-onset anorexia nervosa: is there evidence of limbic system imbalance? Int J Eat Disord 2003;33:388–96. D’Andrea F, De Divitiis E, Megna G, et al. Remission of "mental anorexia" following stereotaxic thalamolysis (previously resistant to other therapies) (author’s translation). (Italian) Rivista di Patologia Nervosa e Mentale 1974;95:579–90. Zamboni R, Larach V, Poblete M, et al. Dorsomedial thalamotomy as a treatment for terminal anorexia: a report of two cases. Acta Neurochir Supp 1993;58:34–5....查看详细 (8352字节)
☉ 11357059:Four rules for the reinvention of health care
1 Centre for Health Informatics, University of New South Wales, Sydney, NSW 2055, Australia e.coiera@unsw.edu.au If health care is to evolve at a pace that will meet the needs of society it will need to embrace this science of sociotechnical design, but ultimately it is our culture's beliefs and values that shape what we will create and what we dream Futurists might like to speculate on what the health services of 2020 look like. The world may be such that as a clinician you work in flexible virtual teams and some of your colleagues are computers. You would of course instinctively mistrust clinicians who always know the answer without consulting the information grid, and patients often choose to be the team leader. Keyboards are banned as harmful and can be found in museums, next to punch cards and spittoons. The health record is a direct multimedia history of conversations, and a software agent is its curator. For the still cognitively limited clinician, your earring whispers your patient's name when you meet. More importantly, in 2020 the health system in most nations will have to treat proportionately more people, with more illness, using relatively fewer tax dollars and workers.1 Given that commentators today are alarmed at the current strains on the health system, we have to assume that by 2020 the healthcare systems in most nations will therefore either have somehow transformed substantially or will have failed. If health care is to flourish in the coming setting of diminished resources and increased demand, then it will do so because we have explicitly designed and implemented new systems of care that are fundamentally sustainable. Given the likely enormity of that task, it may require nothing less than the reinvention of health care. Many of the innovations needed for this reinvention are still unimagined today, but we can predict some of what must come to pass. In 2020 clinicians will care more effectively for more patients than today, because some burden of care has shifted away from individual clinicians. Some of that burden will rest with the consumer, who participates actively in maintaining good health and managing ill health. Some burden of care must also shift to machines, because without computational automation much of what needs to be done to make the system run will otherwise remain undone. Most importantly, our services and systems will need to be "designed" to meet our needs, in contrast to the inherited and patched up system we have at the present. As with other industries, by 2020 our designed processes will need to be certifiably safe and efficient. Prevention needs to be designed into the health system's core, eliminating many of the determinants of ill health that generate the current demand for services. By 2020 the current situation, in which healthcare delivery actually contributes to morbidity and mortality through avoidable error, should be seen as a wretched historical anomaly. The roles of existing healthcare professionals are also bound to change. Biomedical expertise, for example, will no longer be seen to reside in the heads of experts but will rather reside in the system. Knowing "about" is replaced by knowing "how to find out," and clinicians and machines are always "connected" to each other via the information grid to share knowledge and decisions and to form "just in time" teams to deal with specific problems or patients. Since health is so complex and expensive, new roles are needed, including health service brokers who help consumers navigate the health system and identify where the best care can be found. Evidence interpreters will help consumers find the evidence they need to make informed choices and help them understand the meaning of that evidence. This journey to reinvent health care begins by recognising that to design health services, we need to understand systems. The behaviour of a system emerges out of the interaction of its components, and the more components there are, the harder it is to predict the outcome of a seemingly simple change. The nature of complex systems such as health care means that simple fixes will always have unexpected consequences. The web of interactions needed to make anything work in a complex organisation always entails humans solving problems with limited resources and working around imperfect processes. Designing the technological tools that humans will use independently of the way in which the tools will affect the organisation optimises only solutions that are specific to local tasks and ignores global realities. The biggest information repository in most organisations sits in the heads of the people who work there, and the largest communication network is the web of conversations that binds them. Together, people, tools, and conversations—these form the "system."2 Consequently, this science of health service design must be a science of sociotechnical systems,3 and today that science is called informatics.4 This call to design sociotechnical systems is as much a challenge to health care as it is to informatics, which still has a bias to technology driven innovation. Although the sociotechnical viewpoint has been around for about 50 years, technology is still king. The sacred ground of health informatics remains anything to do with the computer, the web, information architectures, the electronic health record, and heroic challenges such as the creation of enormous terminology systems. The profane ground of health informatics, still mostly shunned, is the world of politics, culture and persuasion, complaints from users when systems disappoint them, the messy craft of system implementation, which requires different tactics from one site to the next, and our unacceptably high number of system failures.5 I propose four rules for the new sociotechnical informatics, which could help guide the active design of our health services. Rule 1: Technical systems have social consequences Introducing a technology into a setting affects not only the users it is specifically intended for but also the people surrounding them. For example, a doctor's use of a desktop computer in the consulting room can result in shortened and delayed responses to patients, reduced eye contact with patients, failure to hear patients' comments, and patients trying to judge when to talk to the doctor on the basis of his or her interactions with the computer.6 7 The introduction of a computer based data gathering system for injuries in Kenya required a researcher on a motorbike to go to the injury site and document it by using a global positioning device.8 Unexpectedly, the elders in the villages now report that the number of assaults against women is down because the perpetrators know that every time they injure someone, an "official" on a motorbike comes and puts their name into a computer (W Odero, personal communication, 2003). Rule 2: Social systems have technical consequences The utility of technology is socially shaped. For example, the strongest predictor of email uptake in an organisation is not the software's intrinsic utility to help with communication tasks but whether your manager uses email.9 Similarly, online evidence systems are now increasingly in use, but uptake still varies widely, even between apparently similar organisations. In one study the only variables that seem to explain why some hospitals adopted online evidence systems and others did not had to do with the local culture of the organisations. The existence of local champions, teams that had a climate that supported innovation, and a culture supporting evidence based practice were evident in the organisations that adopted the technologies most readily.10 We can start to understand this class of phenomena by noting that people tend to treat computers and communications media as if they too were people.11 In other words, humans relate to the world with social rules and values and use these same rules to judge and interact with technologies. Rule 3: We don't design technology, we design sociotechnical systems If the social and the technical are inseparable the design of systems needs to change. We should no longer accept designs that are restricted to technological systems alone but broaden the scope of design to include social structures.12 Any new health service might (and probably must) entail innovation in clinical roles, work processes, and culture change as well as the new technologies drawn from the treasure chests of ehealth and bioinformatics. Consider, for example, the designer of an electronic health record who usually focuses on sculpting the interaction between a single clinical user and the record. However, other human agents also populate the interaction space. The user of the electronic medical record is often not the sole author of the content that is captured in the record but is recording the result of a set of discussions with other clinical colleagues. If the goal of designing an electronic medical record is to ensure that highest quality data are entered into the information system it may be even more important to support the collaborative discussion between clinicians than it is to engineer the act of record transcription into the system. Failing to model the wider interaction space for the electronic health record means that we may overengineer some interactions with diminishing returns, when we could be supporting other interactions that may deliver substantial additional benefit to our original design goals.2 Rule 4: To design sociotechnical systems, we must understand how people and technologies interact A sizeable gap exists in the science of informatics relating to our understanding of health systems. Our capacity to model systems and predict the impact of new technologies within existing social systems is also primitive. Before we can rely on modelling and simulation methods, much like engineers use computer aided design (CAD) to design physical objects, we will need the raw data that describe the attributes of clinicians, clinical work, and the way that clinicians perform in a variety of environments. For example, it is now becoming clear that the work environment may impose unacceptable loads on human cognitive abilities and potentially lead to memory overload and error.13 Clinicians placed in an environment where they are busy and constantly interrupted by colleagues or synchronous technologies such as the telephone, pager, and email, are "designed" to produce error and inefficiency. Designers of busy clinical services thus need to factor in human cognitive limits and the work loads generated by other services over which they have no control. If health care is to evolve at a pace that will meet the needs of society it will need to embrace this science of sociotechnical design. Perhaps we begin the journey by designing a sustainable and flexible culture that does not fear innovation and sees the redesign of roles, processes, organisations, and careers as the first amongst all of its duties. Whether we are enraptured by the promise of technology or fear it, the way we choose to head will not be shaped by technology but by our will. It is our culture's beliefs and values that shape what we will create and what we dream.14 Summary points Over the next 20 years, national health systems will have to treat proportionately more people, with more illness, using relatively fewer tax dollars and workers, yet these systems are already under significant strain To flourish in the coming setting of diminished resources and increased demand, we must design new systems of care that are fundamentally sustainable, and this may require nothing less than the reinvention of health care This journey to reinvent health care begins by recognising that to design health services, we need to understand both the behaviour of complex systems and the science of system design, which is increasingly associated with the discipline of health informatics Since health systems are sociotechnical systems, where outcomes emerge from the interaction of people and technologies, we cannot design organisational or technical systems independently of each other Contributors: EC is the sole author. Funding: None Competing interests: None declared. References Costello P. Intergeneration report, 2002-3 budget paper No. 5 Commonwealth of Australia, 2002. www.budget.gov.au/2002-03/bp5/html/index.html Coiera E. Interaction design theory. Int J Med Informatics 2003;69: 205-22. Trist EL. The evolution of sociotechnical systems as a conceptual framework and as an action research program. In: Van de Ven AH, Joyce WF, eds. Perspectives on organization design and behavior. New York: John Wiley, Wiley-Interscience, 1981: 19-75. Coiera E. Guide to health informatics. London: Hodder Arnold, 2003. Kaplan B, Brennan P, Dowling A, Friedman C, Peel V. Toward an informatics research agenda: key people and organizational issues. J Am Med Inform Assoc 2001;8: 235-41. Greatbatch D, Luff P, Heath C, Campion P. Interpersonal communication and human-computer interaction: an examination of the use of computers in medical consultations. Interacting with Computers 1993;5: 193-216. Booth N, Robinson P, Kohannejad J. Identifying successful communication skills in computer use in the consultation—the information in the consulting room project (iiCR), PHCSG Annual Conference Proceedings, Cambridge, United Kingdom, 2001: 90. Rotich J, Hannan T, Smith F, Bii J, Odero W, Vu N, et al. Installing and implementing a computer-based patient record system in sub-Saharan Africa: the Mosoriot medical record system. J Am Med Inform Assoc 2003;10: 295-303. Markus ML. Electronic mail as the medium of managerial choice. Organisation Sci 1994;5: 502-27. Gosling AS, Westbrook JI, Coiera EW. Variation in the use of online clinical evidence: a qualitative analysis. Int J Med Informatics 2003;69: 1-16. Reeves B, Nass C. The media equation. Cambridge: Cambridge University Press, 1996. Bostrom RP, Heinen JS. MIS problems and failures: a socio-technical perspective. Part II: The application of socio-technical theory. MIS Q 1977;December: 11-28. J. Parker, E. Coiera, Improving clinical communication: a view from psychology. J Am Med Informatics Assoc 2000;7: 453-61. Coiera E. The impact of culture on technology. Med J Austr 1999;171: 508-9....查看详细 (14581字节)
☉ 11357060:Congenital dumbbell neuroblastoma mimicking birth trauma
1 Department of Neurosurgery, Children’s Hospital Medical Center, Tehran University of Medical Science, Tehran, Iran 2 Department of Neurosurgery, Mashad University of Medical Science, Mashad, Iran 3 Children’s Hospital Medical Center, Tehran University of Medical Science, Tehran, Iran Correspondence to: Dr F Nejat No 20, West 194 (Alaii Saqarloo) Street, 3rd square of Tehran pars, Tehran, Iran; nejat@sina.tums.ac.ir Keywords: congenital neuroblastoma; neonate; unilateral leg palsy Neuroblastoma is the commonest extracranial malignant tumour in children and neonates.1 It may involve the vertebral bodies or extend into the spinal canal, compressing the spinal cord, or spread into the retroperitoneal space, involving the lumbosacral plexus. Early diagnosis is important for treatment. We report two cases of congenital neuroblastoma mimicking obstetric related palsies. Case 1 A 4 month old baby boy with a diagnosis of unilateral leg palsy due to birth trauma, despite normal vaginal delivery, was admitted because of a palpable abdominal mass. The infant’s left leg lacked spontaneous movement, was flaccid, and deep tendon reflexes were absent. He had poor rectal tone and dribbling of urine. The levels of urinary catecholamine derivatives were increased. Spinal magnetic resonance imaging (MRI) demonstrated a large retroperitoneal mass with thoracolumbar cord involvement. A diagnosis of neuroblastoma was made following biopsy of the abdominal mass. Multiagent chemotherapy proved effective in reducing the size of neuroblastoma. His left leg function returned after several months’ chemotherapy. At present, after two years he is free of disease, he can stand and walk with a brace, and his neurogenic bladder is managed with clean intermittent catheterisation. Case 2 A 10 day old baby boy was seen for evaluation of right lower limb weakness. He had not moved this leg since birth. He was born at full term via a normal vaginal delivery with vertex presentation. He had a hyperextended thigh and decreased tone in the remainder of the leg. Other limbs were normal. Abdominal examination revealed a palpable mass in the right upper quadrant just lateral to the midline. Sonography of the abdomen revealed a unilateral retroperitoneal tumour adjacent to the right kidney with spinal cord involvement. A spinal MRI showed extensive spinal cord compression from T12 to L4 (fig 1). Biopsy of the paravertebral mass revealed neuroblastoma. The neonate was treated with multiagent chemotherapy. However, he developed paresis of the left leg within two weeks of starting chemotherapy. The spinal cord was therefore surgically decompressed through an osteoplastic laminotomy and the extradural mass was fully resected. Although there was partial recovery of left leg function the right limb remained plegic. Figure 1 Case 2: spinal magnetic resonance imaging scan revealed severe cord compression from T12 to L4 and a large intra-abdominal retroperitoneal mass. Discussion Birth trauma causing brachial plexus injury is relatively common where obstetric services are limited, but lumbosacral plexopathy after a normal vaginal delivery is extremely rare. Unilateral lower extremity palsy in a neonate must lead the primary care provider to consider other diseases. The combination of neurological deficits and an abdominal mass should alert the physicians to consider neuroblastoma. Early diagnosis can improve outcome,2,3 and neuroblastoma diagnosed even in the prenatal period has been reported to have excellent prognosis.4 Although congenital dumbbell neuroblastomas are rare, spinal cord compression and involvement of the peripheral nerves or nerve plexus are not uncommon with abdominal neuroblastoma.5 The incidence of intraspinal involvement of neuroblastoma varies between 6% and 24%.6,7 Intraspinal neuroblastoma is a direct extension of a peripheral tumour.8 Dumbbell neuroblastoma is the commonest malignant cause of spinal cord or nerve root compression in young children and is regarded as an unresectable tumour.7 Chemotherapy should be considered for patients with partial deficits and surgical decompression should be reserved for children with recent onset of severe neurological dysfunction or deterioration in a 24–72 hour period.7 We treated case 1 with chemotherapy only, because his neurological deficit had been observed four months ago and was not progressive. After disappearance of the retroperitoneal and intraspinal masses with chemotherapy the deficit improved partially. The second neonate’s condition deteriorated during chemotherapy, and surgical decompression resulted in recovery of one limb although the fixed deficit from birth, in the lower right extremity, did not change. References Kanos CC, Muhlbauer MS. Extramedullary intraspinal and extradural spinal cord tumors. In: McLone DG, ed. Pediatric Neurosurgery, surgery of developing nervous system, 4th edn. WB Saunders: Philadelphia, 2001:873–84. Christiansen GM, Pulley SA. Two cases of neuroblastoma presenting to the emergency department. J Emerg Med 1999;17:265–68. Komuro H, Imiazumi S, Hirata A. Congenital mediastinal dumbbell neuroblastoma with spontaneous regression of liver metastases. Pediatr Surg Int 1998;14:86–8. DeMarco RT, Casale AJ, Davis MM, et al. B. congenital neuroblastoma; A cystic retroperitoneal mass in a 34-week fetus. J Urol 2001;166:2375. Tsademiroglu E, Ayan I, Kebudi R. Extracranial neuroblastoma and neurological complications. Childs Nerv Syst 1998;14:713–18. Massad M, Haddad F, Slim M, et al. Spinal cord compression in neuroblastoma. Surg Neurol 1985;23:567–72. Plantaz D, Rubie H, Michon J. The treatment of neuroblastoma with intraspinal extension with chemotherapy followed by surgical removal of residual disease. Cancer 1997;78:311–19. Hayes FA, Gree AA, O’Connor DM. Chemotherapeutic management of epidural neuroblastoma. Med Pediatr Oncol 1989;17:6–8....查看详细 (6036字节)

☉ 11357061:Digital bridges need concrete foundations: lessons from the Health InterNetwork India
1 Health InterNetwork, World Health Organization, 1211 Geneva, Switzerland, 2 Brown University, Providence, RI 02912, USA, 3 Health InterNetwork India, World Health Organization, New Delhi 110011, India, 4 Foundation for Research in Health Systems, Ahmedabad 380015, India, 5 World Health Organization Liaison for Orissa, Orissa 751009, India, 6 World Health Organization, Geneva Correspondence to: J Dzenowagis, World Health Organization, EIP/HIN, 20 Avenue Appia, 1211 Geneva 27, Switzerland dzenowagisj@who.int The World Health Organization's Health InterNetwork pilot project has shown that national and international partnerships can use information and communication technologies to strengthen the public health system and bridge the digital divide in health Information and communication technologies (ICT) are often promoted as bridges to better governance, economies, and health,1-3 but examples of how these bridges can be successfully built are rare.2 In this context, the United Nations' secretary general, Kofi Annan, launched in 2000 the Health InterNetwork in the Millennium Action Plan "as a concrete demonstration of how we can build bridges over digital divides."4 The initiative proposed to install computers and internet connectivity at thousands of hospitals and health centres in developing countries. The private sector pledged to provide the millions of dollars needed, but the "dot com" bubble burst and the funding never materialised. The challenge of improving the flow of timely, relevant, and reliable health information remained, however. The World Health Organization (WHO), along with other United Nations agencies, technical experts, non-governmental organisations, and national governments, developed a strategy to implement and evaluate a series of pilot projects to better understand and meet those needs, as a basis for expansion.5 An early Health InterNetwork pilot project—to improve access to scientific publications for researchers in developing countries—grew quickly as agencies and publishers formed the Health InterNetwork Access to Research Initiative (HINARI). Coordinated by WHO and the BMJ Publishing Group, HINARI now provides public and non-profit health institutions in 113 countries with free or low cost access to over 2300 biomedical journals from more than 40 of the world's major publishers.6 7 A second pilot project, Health InterNetwork India (HIN India), aimed to show the value of integrating ICT into public health practice. This article describes the Health InterNetwork approach and focuses on lessons from the HIN India pilot project. The "digital divide" The term digital divide often refers to unequal access to the internet in and between countries (table 1).3 8-10 But the divide also refers to inequities in ownership and use of technology, content, and telecommunications infrastructure.2 3 11 Table 1 Estimated internet access worldwide, 2002 The Health InterNetwork initiative focuses on four main components: connectivity (facilitating information access and use through ICT); content (providing timely, relevant, and high quality information); capacity building (developing skills in ICT management and use); and policy (lowering the barriers to ICT integration into public health practice). Background to HIN India India was selected for a Health InterNetwork pilot project because of its public health programmes as well as the availability of resources and skills needed to test the process of establishing, using, and scaling up ICT in a complex environment. A wide range of agencies provides health services in India. Primary and secondary health care—available through a network of government health facilities (table 2)—is free or highly subsidised. Tertiary health care is provided through government medical college hospitals and specialised institutions. A rapidly growing private sector exists alongside traditional systems of medicine and major public health programmes organised by international agencies.12 Table 2 Indian government health service facilities12 Objectives of HIN India The main objective of the 18 month HIN India pilot was to document and analyse the process and impact of using ICT to improve the flow of reliable, timely, and relevant information to support policy making, health services provision, and research. Another objective was to work with local organisations to assure relevance and sustainability. Some 40 partners were coordinated through the office of WHO's representative to India. They included national and state government departments, local United Nations agency offices, nongovernmental organisations, research institutions, health service facilities, universities, and the private sector (see www.hin.org.in for further details).5 HIN India pilot sites included primary health centres and community health centres in the states of Karnataka and Orissa. The selection of these states was based on the contrast in health and socioeconomic status (table 3),13-15 national government priorities, and presence of project champions. Table 3 Key comparisons between Karnataka, Orissa, and India The pilot also supported two national priority public health programmes—tuberculosis control and tobacco control—by including related research institutions in Bombay, Chennai, Bangalore, and Delhi.5 As the Ministry of Health requested that the project strengthen ICT capacity at medical colleges to ensure longer term benefits, selected medical colleges in Orissa and Karnataka participated in the pilot project. Achievements and lessons from HIN India Connectivity HIN India introduced ICT into seven primary health centres and three community health centres and upgraded computers, internet connection, and networks in four research institutes and two medical colleges. It also tested applications such as e-fax (faxing direct from computers), e-consultations, geographic information systems, and handheld computers in these settings. HIN India showed that computers and internet connectivity meet real needs even in remote settings. Assessments and local expertise determined the ICT components for the sites. A basic package consisted of a desktop computer, printer, scanner, electrical and telephone connections, and subscription to an internet service provider at an average cost of $2750 (￡1533; 2275) per site. Six months were allocated to establish connectivity, but at some sites the process took over a year. This was because of difficulties in securing reliable electricity and telephone services, complex bureaucratic processes, and competing demands on over-taxed infrastructure. ICT tools that were tested after connectivity had been established showed some immediate benefits. Every day during the summer, for example, staff at primary health centres used to deliver a daily heatstroke report to the district health office. Given the few buses and lengthy travel time, reporting took most of the day. With e-fax, reporting is instantaneous—provided that electricity is available and telephone lines are functioning. Content HIN India tackled the challenge of identifying and publishing health information to meet the wide range of local needs. One goal was to institute a process for publishing national, peer reviewed journals. As a pilot, HIN India and the Tuberculosis Association of India published online full text versions (all volumes since 1990) of the Indian Journal of Tuberculosis. To improve the capacity of medical colleges, the Rajiv Gandhi University of Health Sciences, as a local champion, led a consortium of Indian medical college libraries in Karnataka—25 in the first phase—to share online subscriptions to 250 biomedical journals. The National Medical Library and medical colleges in Karnataka both established interlibrary loan systems for print and electronic resources. The Indian Council for Medical Research coordinated the development of a prototype National Health Information Collaboration web portal for publishing locally relevant content. The HIN India experience showed that access to relevant content is an important incentive to using ICT. Better access to existing content, however, does not necessarily meet local needs16: long technical reports are not the most effective way to communicate with policy makers; the well documented disparities of the "10/90 gap" in health research (less than 10% of the funding is directed at 90% of the world's health problems) mean that much of the global pool of knowledge is not necessarily relevant; and the use of local languages is essential for community health workers.5 As India is not part of the HINARI scheme, improving access to international scientific publications was also a challenge for HIN India as one full text journal article costs $12 to obtain online or entails a wait of months to be delivered by surface mail.5 6 Sharing resources and costs through consortiums and an interlibrary loan system proved a viable strategy to improve such access in medical colleges. The new and the old are both in use in India Capacity building HIN India set up contracts with local firms to provide training in basic computer and internet skills for over 300 staff and students at pilot sites. This supported local business and facilitated continuing interaction between public health staff and trainers. Faculty members, staff, and students at Orissa medical colleges formed Health InterNetwork clubs to meet operating costs and to provide management, training, and maintenance on a "fee for access" basis. The clubs promoted a strong sense of local involvement and furthered learning among users.5 HIN India and local consultants developed and implemented a suite of tools for programme monitoring and ICT needs assessment at pilot sites, creating new and productive relationships among HIN India partners. The HIN India project showed that local champions at all levels—from a nurse at a primary health centre who worked to excel at computer skills and was willing to teach other staff, to university faculty and government administrators who promoted the project—can make a big difference in the adoption of ICT. Identifying and supporting such champions is vital for improving awareness and adoption at sites and for gaining support at higher administrative and policy levels. One path to improving capacity to integrate ICT in health begins with training in basic computer skills and then developing specific skills in the use of ICT for public health. Introducing ICT into public health settings without effective planning can increase inequities and inefficiencies. Policy HIN India faced many barriers to integrating ICT into public health practice, including cultural and political factors such as a lack of coordination in ICT development activities, poor incentives for cooperation, and entrenched bureaucratic procedures at all levels. In Orissa, HIN India brought together local, national, and international stakeholders to make the best use of limited resources by coordinating ICT strategies. The Danish International Development Agency, for example, reallocated its resources to provide training for health workers instead of duplicating other agencies' efforts to supply computer hardware.5 The Health InterNetwork is founded on the principle of equitable access to information and tries to ensure that new technologies do not exacerbate socio-cultural divides. HIN India found that over 50% of private sector doctors had access to the internet, compared with less than 20% of government doctors. Researchers and administrators reported the highest access (75%). In all settings, professionals of higher rank are predominantly male.5 HIN India showed that it is possible to narrow these gaps—for example, by planning for computer installations in women's residences at medical colleges and ensuring that staff at primary health centres received computers and training. When possible, open access software was used, and efforts were made to ensure that the content is in the public domain. Discussion Strong incentives exist in the market and in society for adopting the newest technology or approach. Using the latest technology to quickly attract interest, participants, and support can be effective, but organisations and governments must understand and plan for the long term. Careful assessment of the programme and the involvement of local partners can achieve an effective balance between short term incentives to adopt ICT and the long term goal of using ICT to strengthen public health practice. Health InterNetwork India was initially conceived as being led by partners in India, with WHO India serving a coordinating role. However, the demands for efficiency in a short term pilot project, combined with the considerable demands on local institutions, made a leadership role by an agency such as WHO almost inevitable. Finding the balance to assure local ownership, control, and sustainability is an ongoing responsibility, as is reconciling the different perspectives, agendas, and approaches to integrating ICT in health settings. The HIN India pilot has shown that those challenges can be overcome through committed partnerships and established mechanisms that facilitate evaluation and coordination. "Without computers and the internet, we are fighting 21st century health problems with 19th century tools" Tuberculosis field officer, Orissa, India Summary points The World Health Organization's Health InterNetwork India pilot project implemented and analysed processes for establishing and using information and communication technologies (ICT) in India's health system The project shows that national and international partnerships can help to do this effectively when connectivity, content, capacity building, and policy components are included Computers and internet connectivity can be provided and meet real needs, even in remote settings Identifying and supporting champions is vital for the successful adoption of ICT Careful assessment and the involvement of local partners can help achieve a balance between short term incentives to adopt ICT and the long term goal of using ICT to strengthen public health practice Conclusion The HIN India pilot has shown that ICT can be adopted and used effectively in local and national public health settings. Further work is needed to evaluate the longer term impact and to establish best practice. An important requirement for bridging the digital divide is to ensure that connectivity, content, capacity building, and policy meet real needs. ICT will not have a major impact without concerted and coordinated efforts to invest in basic infrastructure, develop human resources, provide relevant content, and implement supportive policies. Innovative partnerships such as the Health InterNetwork can be a catalyst for building concrete foundations for digital bridges in health. A full acknowledgment is at bmj.com HIN India consists of many international and national partners, with over 40 partners in India alone (see bmj.com for a full acknowledgment). The editors of this theme issue, the reviewer, Alejandro Jadad, and Thomson Prentice from WHO provided useful suggestions for revision. AD provided the photograph of new technology in use in a primary health centre in Chhatabar, Orissa, and of the traditional ledger still in use. Contributorship: RD was responsible for implementing the HIN India pilot project, and JD oversaw it. SK coordinated with international and national partners; AP was the external evaluator; NM coordinated the needs assessments and project monitoring at local sites; and RS coordinated the project implementation as well as interagency and government collaborations for the project in Orissa. MS underwrote all the project's activities. All authors contributed substantially to the analytical base for this article and approved the final content. SK, JD, and AP drafted this article and incorporated input from the other contributors. SK, JD, and AP are guarantors for the article. Funding: The Bill and Melinda Gates Foundation, the United National Foundation, and the United Nations Fund for International Projects provided and organised project funding. Competing interests: None declared. References www.dotforce.org (Digital Opportunities Task Force). Wade RH. Bridging the digital divide: new route to development or dependency. Global Governance 2002;8: 443-66. International Telecommunication Union. World telecommunications development report. Geneva: ITU, 2002. United Nations. We the peoples: the role of the United Nations in the 21st century. Millennium report of the secretary-general of the United Nations. 2000. www.un.org/millennium/sg/report (accessed 28 Apr 2004) Health InterNetwork. The Health InterNetwork India Pilot Project. 2003. (www.hin.org.in) Aronson B. WHO's access to research initiative (HINARI). Health Info Libr J 2002;19: 164-5. Smith R. Closing the digital divide. BMJ 2003;326: 238. United Nations Conference on Trade and Development (UNCTAD). Millennium Indicators Database, 2004. http://unstats.un.org/unsd/mi/mi_goals.asp (accessed 28 Apr 2004). NUA. How many online? NUA surveys website. 2002. www.nua.ie/surveys/how_many_online (accessed 28 Apr 2004). United Nations Population Division. World population prospects: the 2002 revision. United Nations Population Division website. 2002. http://esa.un.org/unpp (accessed 28 Apr 2004). Lessig L. The future of ideas: the faith of the commons and a connected world. New York: Random House, 2001. Gourie-Devi M, Satishchandra P, Gururaj G. Epilepsy control program in India: a district model. Epilepsia 2003;44: 58-62. National Family Health Survey. National Family Health Survey-2 fact sheet—states. 2000. www.nfhsindia.org/data/india/statfind.pdf (accessed 28 Apr 2004). Registrar General and Census Commissioner, India. Census of India 2001. www.censusindia.net United Nations Development Programme India. Inter-state health statistics. 2001. www.undp.org.in/report/IDF98/idfthlth.htm pdf (accessed 28 Apr 2004). Piotrow PT, Kincaid DL, Rimon II JG, Rinehart W. Health communication, lessons from family planning and reproductive health. Westport, CT: Praeger, 1997....查看详细 (18553字节)
☉ 11357062:Internal jugular vein thrombosis associated with shiatsu massage of the neck
Department of Neurology, Nishi-Kobe Medical Center, Hyogo, Japan Correspondence to: Dr Yuko Wada Department of Neurology, Nishi-Kobe Medical Center, 5-7-1 Kouji-Dai, Nishi-Ku, Kobe, 651-2273, Japan; wada@nmc-kobe.org Keywords: internal jugular vein thrombosis; shiatsu massage Thrombosis of the internal jugular vein is a relatively rare condition that can be induced by a variety of mechanical injuries.1,2 Acupressure, or "shiatsu", is an oriental massage technique and many acupoints on the body surface, known as "tsubos", are used for shiatsu. Shiatsu of tsubos in the nape of the neck is known to improve tension headache due to neck and shoulder aches. However, we recently came across a case of internal jugular vein (IJV) and cerebral sinus thrombosis after shiatsu massage of the neck. Case report A 35 year old man, a non-smoker, was suffering from a stiff neck. He consulted a shiatsu masseur, who performed shiatsu massage on the right side of his neck and right shoulder for 30 minutes. Immediately after the shiatsu massage, the patient noticed pain and swelling of the right side of the neck, both of which subsided within seven days. Two days after the shiatsu massage, he developed a severe, constant right occipital headache and consulted his attending physician. His cervical radiograph was normal. The patient continued to have severe headache, however, and on the seventh day after the massage, he developed blurred vision. On the twentieth day, he developed weakness and paraesthesia of his right arm and leg, and mild agraphia for kanji characters. When he also developed focal motor seizure, he was admitted to our hospital. He underwent a neurological examination on the twenty third day after the shiatsu massage. The patient did not have any history of recent trauma, dental procedures, or upper respiratory infection. There was no history of any other relevant medication including homoeopathic or herbal medicines, or pathologic conditions. There was no family history of premature stroke or thrombotic events. Physical examination was normal and no neck mass was detected. On neurological examination, he showed normal consciousness and orientation. Funduscopic examination revealed bilateral papilloedema without haemorrhage, but the remaining cranial nerves were intact. He had mild muscle weakness and sensory deficit in the right arm and leg. Ataxia was not detected in any of the limbs and trunk. Mild agraphia for kanji characters was observed. Laboratory analysis showed prothrombin time, partial thromboplastin time, antithrombin III, protein C, and protein S were normal, but values for anticardiolipin antibody IgG and lupus anticoagulant were negative. Plasma homocysteine was within normal limits. Autoantibodies and cryoglobulins were absent. No evidence of any systemic disease was found on investigation. Cerebrospinal fluid was clear without pleocytosis, but the cerebrospinal fluid pressure was 350 mm H2O. Magnetic resonance imaging (MRI) scan of the brain showed infarction with haemorrhage in the left parietal lobe and an area of increased signal intensity in the area of the right transverse and superior sagittal sinuses (fig 1). In addition, MRI of the neck with and without enhancement revealed thrombosis of the right IJV, starting from the junction with the right subclavian vein (see fig 1). However, there were no structural abnormalities adjacent to the right IJV, and the carotid arteries were normal. Digital subtraction venous angiography confirmed extensive thrombosis in the right IJV, the right sigmoid sinus, the right transverse sinus, and the superior sagittal sinus (see fig 1). The rest of the intracranial dural sinuses were patent, and no vascular malformation was detected. Figure 1 Top panel: post enhancement T1-weighted magnetic resonance (MR) image of the head (A) axial, (B) coronal, and (C) sagittal. (A) and (B) show the left parietal haemorrhagic infarct. The superior sagittal sinus and right transverse sinus show high intensity signal within the lumen instead of the normal "flow void", indicating thrombosis. Middle panel: MR image of the neck (A) T1-weighted, (B) T2-weighted, (C) post enhancement T1-weighted, and (D) coronal T2-weighted showing right internal jugular vein thrombosis without other structural abnormalities (arrows). Bottom panel: digital subtraction angiogram (A) lateral view of the head during the early venous phase of right carotid digital subtraction angiography confirms the non-opacification of the superior sagittal sinus, the deep cerebral venous system and the transverse sinuses. The predominant venous drainage is via the sphenoparietal sinus (arrow). (B) Anteroposterior view of the neck—the right jugular vein had an area of obstruction at its junction with the right subclavian vein. Phenytoin and valproic acid were promptly administered resulting in improvement in the patient’s focal motor seizures. He was also given heparin and warfarin and the intracranial hypertension was treated with a lumboperitoneal shunt. The headache and papilloedema slowly improved over the next three weeks, after which the patient was discharged. Neurological examinations over the past several months have revealed only mild clumsiness and paraesthesia of his right hand and leg. Discussion Our patient started complaining of a swelling and pain in the right side of the neck immediately after the shiatsu massage of the neck. Subsequently, over a period of about a month, he developed progressive headache, right extremity paralysis, papilloedema, and partial seizures. Although it may be coincidental, the possibility of a causal link between the shiatsu massage and IJV thrombosis is supported by the patient’s claim of a massage induced swelling and pain in his neck, and by the temporal relation between the massage and the onset of symptoms that progressed to IJV and cerebral venous sinus thrombosis. It is difficult to determine the exact mechanism of the IJV thrombosis in our patient. One possibility is that direct trauma or pressure may have induced both venous stasis and vascular injury during the shiatsu massage. The other possibility is that extrinsic compression of the IJV by tissue swelling subsequent to trauma during the shiatsu massage may have induced venous stasis, resulting in thrombosis at this unusual site. Various forms of trauma have been reported in association with IJV thrombosis, such as jugular thrombosis after catheterisation1 and Glisson traction for the neck.2 To the best of our knowledge, IJV and cerebral venous sinus thrombosis possibly caused by shiatsu massage has not been previously reported. Our case may thus represent a newly identified traumatic aetiology. Chiropractice is a popular alternative therapy in Western countries, and there are several reports of a relation between chiropractic manipulation and stroke.3 Shiatsu massage, an oriental technique of massage, is a popular alternative therapy in Japan and other Asian countries. Recently this therapy, including the use of a mechanical shiatsu-type massager, is becoming increasingly popular in Western countries. In addition, it is generally References Larkey D, Williams CR, Fanning J, et al. Fatal superior sagittal sinus thrombosis associated with internal jugular vein catheterization. Am J Obstet Gynecol 1993;169:1612–14. Simmers TA, Bekkenk MW, Vidakovic-Vukic M. Internal jugular vein thrombosis after cervical traction. J Intern Med 1997;241:333–5. Peters M, Bohl J, Thomke F, et al. Dissection of the internal carotid artery after chiropractic manipulation of the neck. Neurology 1995;45:2284–6. Tsuboi K. Retinal and cerebral artery embolism after "shiatsu" on the neck. Stroke 2001;32:2441. Elliott MA, Taylor LP. "Shiatsu" sympathectomy ICA dissection associated with a shiatsu massager. Neurology 2002;58:1302–4....查看详细 (7977字节)
☉ 11357063:HINARI: bridging the global information divide
1 Liverpool L18 9XN vkatikireddi@yahoo.co.uk The unequal distribution of health care is being addressed by an electronic initiative that makes medical journals available free of charge to health workers in developing countries Health care is unequally distributed between the developed and developing worlds, which is matched by unequal distribution of health information. The information gap between rich and poor countries is so great it has been argued that "providing access to reliable health information for health workers in developing countries is potentially the single most cost effective and achievable strategy for sustainable improvement in health care."1 So far, the most successful initiative to bridge this gap is the Health InterNetwork Access to Research Initiative (HINARI). A short history "In HINARI lies the seed of a knowledge revolution," said Gro Harlem Brundtland, director of the World Health Organization. "The knowledge gap between rich and poor must be overcome if we are to reduce poverty. The information made available through HINARI will help developing countries in improving skills, developing research and, by extension, to save lives."2 In April 2000, a group of researchers from developing countries, convened by the World Health Organisation (WHO), concluded that the best way to help with their information problems was to improve their access to the published literature (Aronson B, personal communication). At that time, 56% of institutions in the lowest income countries had no current subscriptions to international journals and 21% averaged only two journal subscriptions.3 WHO realised that the recent revolution in information technology had opened up an opportunity for addressing information poverty. Compared with the ￡50 or more that it costs to send a paper copy of a weekly journal to an institution in Africa for a year, it costs publishers virtually nothing to give that same institution free access to an electronic edition of a journal.4 Publishers in the developed world are unlikely to incur significant financial loss by offering free or reduced price access to their online material, but they may benefit from the raised exposure of their journals and an improved public image. The WHO, in collaboration with the BMJ Publishing Group, approached the world's six largest medical journal publishers to try to improve access to scientific information for researchers in the developing world through online provision.5 In a meeting at the United Nations in March 2001, the six publishers (Blackwell, Elsevier Science, Harcourt Worldwide STM Group, Wolters Kluwer International Health & Science, Springer Verlag, John Wiley) agreed to provide access to all of their online journals for free or at deeply discounted rates through HINARI. HINARI was launched in January 2002 and initially allowed not-for-profit institutions in countries with a gross national product (GNP) per capita of less than US$1000 (￡556; 825) per year (as calculated in the World Bank's report in 2001) to receive free online access to more than 1500 journal titles. In January 2003, the initiative expanded to allow institutions in countries with a GNP per capita of between $1000 and $3000 per year to access the online material now available through HINARI, estimated to be worth more than $750 000, for $1000 (fig 1). Money raised from these small fees is being used to train librarians and researchers in information technology so that the best use can be made of the information now available to them. The number of publishers involved in HINARI has enlarged to 50, providing access to more than 2400 journals and other full text resources. HINARI can now be used by more than 1100 institutions in 102 countries (out of a total of 113 eligible countries). Fig 1 Countries with access to HINARI How HINARI works HINARI allows health and medical institutions to join the initiative by filling in a simple online form.6 After processing and authentication, WHO staff issue the institution with a password. Individuals at the institution wishing to use HINARI then approach their librarian (or equivalent) for the password. Through the HINARI web portal, they have free access to full text biomedical and related social science articles supplied from publishers' websites (fig 2). The portal also allows users to conduct PubMed (Medline) literature searches through the National Library of Medicine, search for journals based on subject, and access the full text papers directly through HINARI. Fig 2 How HINARI works. Individuals receive a password from their institution which allows them to log on to HINARI; through the HINARI web portal they can access publishers' online journal websites Has HINARI worked? It is estimated that HINARI users downloaded more than one million articles in 2003. Usage depends on good internet connectivity rather than the economic strength of the country, with some very low income countries, like Ethiopia, being among the biggest users.3 The high cost of reliable internet access has limited the expansion of services, but some institutions have been able to use their eligibility for HINARI to support their applications for funding from donors. No formal evaluation of HINARI has yet been done; one will start at the end of 2005. Anecdotal feedback has been positive. The box outlines some potential benefits of HINARI, but methodological difficulties in evaluation mean that a direct connection between improved access to scientific information and an improvement in health is unlikely to be proved. Continuing problems HINARI cannot reach everyone who might benefit. In many countries internet access is slow, expensive, and unreliable. Many poor institutions carrying out valuable research in countries with a GNP per capita of over $3000 per year are not eligible to use HINARI Information is often not available in electronic format—especially if it has been produced locally. The electronic format may be unsuitable for certain uses—for example, medical students in the developing world may benefit more from printed textbooks than from virtual textbooks that are only accessible from an unreliable internet connection at medical school. HINARI may also pose problems to researchers and health professionals working in the developing world. Allowing unrestricted access to much of the world's medical literature may produce an information overload and lead to valid and relevant information being difficult to find.7 This is particularly important for people who are not experienced in using information technology and reading primary research (but this problem occurs in the developed world too). Some valuable journals of specific relevance to the developing world (tropical medicine journals, for example) may not be available through HINARI as this may compromise publishers' commercial viability. Also, in a few countries, publishers withhold some journals because the sales of these journals are significant in these countries. However, institutions in these few countries are still able to access at least most of the key general medical and scientific journals without restrictions. Other free initiatives Alternative approaches for providing free or highly discounted rates to online journals exist. They include the Programme for the Enhancement of Research Information (PERI; www.inasp.info/peri/) managed by the International Network for the Availability of Scientific Publications (INASP); Electronic Information for Libraries (eIFL; www.eifl.net/); and the Ptolemy Project (www.utoronto.ca/ois/myweb9/). The BMJ Publishing Group offers free access to its journals for users in the world's 118 poorest countries.8 This differs from HINARI in offering countrywide free access without the need for passwords. Many other journals sharing the group's electronic publisher, Highwire Press, provide a similar service (see http://highwire.stanford.edu/lists/devecon.dtl for a list of these publications). What might HINARI achieve? Reduce feelings of isolation among scientists in the developing world Enable researchers in the developing world to improve the quality of their research Help stop or slow the "brain drain" of scientists from the developing world to the developed world Improve teaching and training of current and future health professionals and scientists Allow developing world scientists to provide more accurate and informed advice to policy makers Reduce the "publishing gap" between researchers in the developed world and developing world by improving the likelihood of publication in international journals Improve quality of locally produced journals Help create an information culture that uses an evidence base rather than inherited knowledge A sister initiative Access to Global Online Research in Agriculture (AGORA; www.aginternetwork.org/) is HINARI's sister initiative, which aims to improve food security by providing free or low cost access to major scientific journals in agriculture and related biological, environmental, and social sciences to public institutions in developing countries.9 AGORA was launched in October 2003 and provides access to over 400 journals related to nutrition. AGORA is spearheaded by the Food and Agriculture Organisation of the United Nations and has received funding and support from Cornell University Mann Library, the Rockefeller Foundation, the UK Department for International Development, WHO, and the US Agency for International Development.10 It builds on the work of The Essential Electronic Agricultural Library (TEEAL), a collection of key agricultural journals distributed to developing countries on CD-ROM, which is available for institutions without adequate access to the internet for AGORA. AGORA operates in a similar way to HINARI. By 1 March 2004, 200 institutions in 47 countries had registered. The future Publishers have committed to the current form of HINARI and AGORA until 2006, when they will be reassessed. It is hoped that they will continue, with the list of eligible countries being reviewed regularly. More publishers and users are being encouraged to take part in HINARI, and in AGORA. HINARI has already held training workshops to help maximise the value of the newly available information. Joint training workshops run by HINARI and AGORA are planned for the future. HINARI and AGORA show what can be achieved in effective public-private partnerships. These initiatives, along with other complementary approaches, are likely to eventually make a real difference to the health of many people in the developing world. Innovative use of information technology is finally beginning to bridge the information gap, to the benefit of the developed and developing worlds. I thank Barbara Aronson at the World Health Organisation for her help. Competing interests: SVK was a BMJ Clegg Scholar. References Pakenham-Walsh N, Priestley C, Smith R. Meeting the information needs of health workers in developing countries. BMJ 1997;314: 90. World Heath Organization. Forty new countries given low cost access to health journals . 17 Jan 2003. www.who.int/mediacentre/releases/2003/pr3/en/print.html (accessed 26 Apr 2004). Aronson B. Improving online access to medical information in low-income countries. N Engl J Med 2004;350: 966-8. Godlee F, Horton R, Smith R. Global information flow. BMJ 1999;321: 776-7. World Heath Organization. WHO and top publishers announce breakthrough on developing countries' access to leading biomedical journals . 9 Jul 2001. www.who.int/inf-pr-2001/en/pr2001-32.html (accessed 26 Apr 2004). Health Internetwork. Special PubMed for HINARI . www.healthinternetwork.org/index.php (accessed 26 Apr 2004). Pakenham-Walsh N, Priestley C. Towards equity in global health knowledge. Q J Med 2002;95: 469-73. BMJ Journals. Countries with free access. www.bmjjournals.com/subscriptions/countries.shtml (accessed 26 Apr 2004). AGORA. www.aginternetwork.org/en/ (accessed 26 Apr 2004). Food and Agriculture Organization. Online scientific information on food and agriculture for poorest countries . 14 Oct 2003. www.fao.org/english/newsroom/news/2003/23019-en.html (accessed 26 Apr 2004)....查看详细 (12452字节)
☉ 11357064:Stiff person syndrome with eye movement abnormality, myasthenia gravis, and thymoma
1 Department of Ophthalmology, University Hospitals Leicester, Leicester, UK 2 Department of Neurology, University Hospitals Leicester 3 Ophthalmology, University of Leicester, Leicester, UK 4 Department of Neurology, University Hospitals Leicester 5 Ophthalmology, University of Leicester 6 Department of Neurology, University of Nottingham, Nottingham, UK 7 Ophthalmology, University of Leicester Correspondence to: Professor I Gottlob University of Leicester, RKCSB, PO Box 65, Leicester, LE2 7LX; ig15@leicester.ac.uk Keywords: stiff-person syndrome; myasthenia; thymoma Stiff person syndrome (SPS) is a rare disorder of the central nervous system characterised by progressive fluctuating rigidity and painful spasms of the body musculature. We describe a patient with SPS with positive glutamic acid decarboxylase (GAD) antibodies who developed diplopia. Thymoma was detected by computed tomography (CT), and after thymectomy his symptoms improved. One month after thymectomy, he tested positive for antiacetylcholine receptor (AchR) antibodies. Case report A 45 year old man presented with a four week history of back pain and stiffness of his trunk causing difficulty in bending forward and turning over while lying down, which he attributed to a minor injury sustained while playing squash. He later developed asymmetrical stiffness of the legs and difficulty walking. His past medical history was notable for an episode of dysphagia (two weeks’ duration) associated with heartburn six months ago; a gastroenterological evaluation and an endoscopy at that time were normal. He recovered spontaneously and there was no recurrence. On examination his mental status, speech, and cranial nerves were normal. He had exaggerated lumbar lordosis. Neurological examination showed normal bulk with increased tone of the flexors and extensors of the knee and ankles. Power and coordination were normal, deep tendon reflexes were brisk, but he had flexor plantar responses. There was no evidence of fatigable muscle weakness. Sensory examination was normal. A chest radiograph and magnetic resonance imaging (MRI) of the brain and the spinal cord were normal. He was anti-GAD antibody positive at 3.4 U/ml (radioimmunoassay; normal 0–1 U/ml). Full blood count, vitamin B12, folate, thyroid function tests, liver function tests, urea, electrolytes, glucose, cortisol, immunoglobulins, and electrophoresis were normal. Antinuclear antibody and smooth muscle, mitochondrial, parietal cell, gliadin, reticulin, microsomal, thyroid peroxidase and antineutrophil cytoplasmic antibodies were negative. Cerebrospinal fluid (CSF) examination revealed 9 lymphocytes/mm3. CSF protein and glucose were normal at 0.31 g/l and 3.1 mmol/l, respectively and oligoclonal bands were absent. The spasms were controlled with diazepam, but his symptoms recurred on reducing the dose. A diagnosis of SPS was made. Treatment with intravenous immunoglobulins (400 mg/kg per day for five days) was not beneficial. He later improved on baclofen 20 mg/day and clonazepam 0.5 mg at bedtime. Four months after the onset of stiffness, he developed diplopia. Visual acuity was 6/4 in both eyes. He had variable alternating esotropia of up to 10 prism dioptres at distance and esophoria at near. Eye movement examination showed bilateral mild abduction deficit, variability of horizontal and vertical saccades with a tendency to be slow, and slight endpoint nystagmus. There was no ptosis or weakness after sustained upgaze for one minute. Eye movement recordings, obtained with a high resolution video pupil tracker (EyeLink, Sensomotoric Instruments, Berlin, Germany; sample rate 250 Hz) confirmed the clinical findings (fig 1, top panel). Anti-AChR antibodies were negative. The neurological findings were unchanged. Figure 1 Horizontal and vertical eye movement recordings during saccades; (top panel) before thymectomy and (bottom panel) after thymectomy. Motor and sensory nerve conduction studies and ulnar and radial repetitive nerve stimulation were normal. Concentric needle electromyography (EMG) showed sporadic fasciculation potentials in the tibialis anterior. Single fibre EMG from 34 potential pairs from the orbicularis oculi revealed only one site with definitely abnormal jitter. A chest CT scan revealed a thymic mass. Histological examination confirmed thymoma with minimal involvement of the perithymic fat. His symptoms improved over a month after thymectomy. One year from the onset of symptoms, one month after thymectomy, he tested positive for anti-AChR antibodies (44x10–10M/l) (radioimmunoassay in the same laboratory, normal 0–5x10–10 M/l) and remained positive for anti-GAD antibodies (2.0 U/ml). His eye movements improved significantly after thymectomy as evidenced by eye movement recordings that showed less variability of saccadic velocity (fig 1, bottom panel). Eighteen months after the onset of symptoms he is off medications and back to his normal routine. He has mild intermittent stiffness of his back, precipitated by anxiety. Occasional mild diplopia at far distance persists. Discussion SPS was first described by Moersch and Woltman in 1956 and was subsequently shown to be associated with anti-GAD antibodies in 40–60% of cases1 and anti-amphiphysin antibodies in some paraneoplastic cases. In 1990, Piccolo et al2 reported a case of generalised myasthenia in a patient with SPS. This patient had radiological evidence of thymoma. A patient in the series of Vincent et al1 had SPS with anti-GAD antibodies, neuromyotonia and myasthenia with anti-AChR antibodies. Nicholas et al3 reported a case of SPS associated with histologically proved thymoma, who developed ocular myasthenia after thymectomy. Hagiwara et al4 described a patient with SPS associated with invasive thymoma but not with myasthenia or anti-AChR antibodies. However, since the patient reported by Piccolo et al2 developed myasthenia six years after spontaneous resolution of SPS, and our patient’s anti-AChR antibodies turned positive after one year, it is possible that the patient reported by Hagiwara et al4 will develop myasthenia in the future. Saravanan et al5 described a patient with SPS associated with ocular myasthenia. Neither anti-AChR nor anti-GAD antibodies were detected. At the time of initial presentation, our patient did not have any clear signs of generalised myasthenia, although the transient dysphagia he experienced prior to the development of symptoms of SPS may have represented symptoms of bulbar myasthenia. Notably, Hagiwara et al’s patient also reported dysarthria,4 which could have been due to myasthenia. The diplopia, variable velocity of saccades and endpoint nystagmus were likely due to ocular myasthenia. This patient became seropositive after 12 months, even though his myasthenic symptoms improved after thymectomy. Five cases of SPS associated with myasthenia gravis have been reported. This is the first report of abnormalities on eye movement recordings strongly suggesting myasthenia gravis in SPS before the patient became seropositive for anti-AChR antibodies. Our patient is probably the third patient with SPS and myasthenia with histologically proven thymoma and the second such patient with positive anti-GAD and anti-AChR antibodies. Our report suggests that patients with SPS can develop other autoantibody mediated disorders even after many months and should be followed up over a long period even if they are asymptomatic. In addition, when patients with SPS have eye movement abnormalities or bulbar symptoms, myasthenia gravis should be suspected even if they are negative for anti-AChR antibodies at presentation. Thymoma should be investigated for, as thymectomy may improve both SPS and myasthenia. References Vincent A, Grimaldi LM, Martino G, et al. Antibodies to I 125I-glutamic acid decarboxylase in patients with stiff man syndrome. J Neurol Neurosurg Psychiatry 1997;62:395–7. Piccolo G, Martino G, Moglia A, et al. Autoimmune myasthenia gravis with thymoma following the spontaneous remission of stiff-man syndrome. Ital J Neurol Sci 1990;11:177–80. Nicholas AP, Chatterjee A, Arnold MM, et al. Stiff-person’s syndrome associated with thymoma and subsequent myasthenia gravis. Muscle Nerve 1997;20:493–8. Hagiwara H, Enomoto-Nakatani S, Sakai K, et al. Stiff-person syndrome associated with invasive thymoma: a case report. J Neurol Sci 2001;193:59–62. Saravanan PK, Paul J, Sayeed ZA. Stiff person syndrome and myasthenia gravis. Neurol India 2002;50:98–100....查看详细 (8685字节)

☉ 11357065:Kinematical analysis of emotionally induced facial expressions: a novel tool to investigate hypomimia in patients suffering from depression
1 Laboratory of Clinical Neurophysiology, Department of Psychiatry, Ludwig-Maximilians-Universit?t München, Nussbaumstr. 7, D-80336 München, Germany 2 Department of Psychiatry, Charité, Wilhelm-von-Humboldt-Universit?t zu Berlin, Schumannstr. 20–21, D-10117 Berlin, Germany Correspondence to: Dr R Mergl Department of Psychiatry, Ludwig-Maximilians-Universit?t München, Nussbaumstr. 7, D-80336 München, Germany; Roland.Mergl@psy.med.uni-muenchen.de ABSTRACT Objective: A novel technique for the kinematic analysis of emotionally induced facial expressions was applied to detect subtle mimic dysfunction in patients with depression. Methods: Using ultrasound markers at certain points on the face, facial movements were exactly measured while subjects watched a witty sketch ("Mr Bean"). Twenty five medicated patients with depression (11 men, 14 women; mean age, 55.8 years; mean total Hamilton Depression Rating Scale score, 17.1) and 25 healthy controls, matched by sex distribution and handedness, were studied. Results: Depressed patients were characterised by abnormally slow velocity at the beginning of laughing and voluntary facial movements, in addition to reduced laughing frequency. A higher severity of symptoms of depression was significantly associated with slow initial velocity of laughing movements of the left mouth angle (r = –0.45). Conclusion: The execution of voluntary and non-voluntary facial movements is abnormally slow in depressed patients, reflecting hypomimia. This mimic slowing is closely associated with the severity of depression. The response of depressed patients to emotional stimuli is also abnormally low, but emotional estimation of the stimuli is similar to normals. This pattern parallels the motor–emotional features known from patients with Parkinson’s disease. Abbreviations: ERT, emotional reaction time; HAMD, Hamilton Depression Rating Scale; IV, initial velocity; PD, Parkinson’s disease; VAS, visual analogue scale Keywords: depression; facial expression; kinematic analysis In many depressed patients, emotionally induced facial expressions are greatly reduced.1 Studies (for example, Katsikitis and Pilowsky2) have demonstrated a reduced number of facial movements in depressed patients. However, this finding is unspecific. Therefore, methods are needed that can separate the facial abnormalities in depression from those in other diseases and that can distinguish between drug induced and disease related facial abnormalities. A new computer aided method3,4 for the exact measurement of the initial velocity (IV) of laughing movements triggered by emotional (humorous) stimuli might be useful in this respect. Using kinematic analysis, Juckel et al separated unmedicated schizophrenic patients who had an abnormally fast IV of laughing from schizophrenic patients treated with typical neuroleptics, such as haloperidol, who had an abnormally slow IV.5 In view of these promising results, we aimed to investigate facial movements elicited by humorous film stimuli in depressed patients and healthy subjects, using a computer based approach. Facial activity was expected to be abnormally reduced in depression. SUBJECTS AND METHODS Twenty five adult inpatients suffering from depression (14 women; all right handed; mean age, 55.8; SD, 14.8 years) and 25 healthy controls (14 women; two left handed; mean age, 46.0; SD, 13.7 years) participated in our study. Patients and controls were comparable with regard to sex distribution and percentage of left handedness. However, the controls were significantly younger than the patients (p = 0.02; t test). Our study was approved by the local ethics committee. All subjects gave written informed consent according to the Declaration of Helsinki.6 The severity of depression was assessed using the Hamilton Depression Rating Scale (21 item version; (HAMD-21)7 (mean total score, 17.1; SD, 10.5)). All patients were diagnosed according to ICD-10 (F31.x, five patients; F32.x, three; and F33.x, 17).8 The mean age at the onset of depression (as determined by asking the patients for the onset of their first depressive episode) was 42.9 (SD, 12.6) years, the mean duration of disease was 12.9 (SD, 10.0) years, and the mean number of relapses was 2.5 (SD, 1.4). Five patients had a history of attempted suicide. Fourteen patients were treated with psychotropic drugs, namely: tricyclic antidepressants (nine), atypical antidepressants (such as mirtazapine) (three), and lithium or carbamazepine (nine). Benzodiazepines were prescribed in two cases. No patient had undergone electroconvulsive treatment. Exclusion criteria were: neurological disease, severe organic disease, reactive depression, depression with organic aetiology, substance abuse, low level of intelligence, and neuroleptic drugs. An active device for the three dimensional measurement of movements (CMS 70; Zebris Ltd, Tübingen, Germany) was used to analyse facial movements elicited by humorous film stimuli.4,9 High frequency ultrasonic signals emitted by ultrasonic markers were registered online with a high sampling rate (200 Hz divided by the number of ultrasonic markers). We fixed one reference marker to the forehead by tape, two markers to the mouth angles to register the activity of the zygomaticus major and minor, risorius, and depressor anguli oris muscles, and two other markers to the medial inferior rims of the eyes to register the activity of the orbicularis oculi muscle. These muscles are innervated by the nervus facialis. All subjects sat in front of a device for the registration of ultrasonic signals, a video camera, and a television screen (for presentation of one "Mr Bean" sketch). The subjects assessed how funny the sketch was, using a visual analogue scale (VAS) (minimum value, 0 mm; maximal value, 167 mm). We registered facial activity by applying the ultrasonic measurement system and simultaneous video recording of the face. To separate involuntary facial movements (laughing) from voluntary ones, subjects had to stretch their mouth angles and to close their eyes tightly after watching the sketch. The film, video recording, and facial activity were synchronised using a frame code generator. Using the software 3DA, the digitised signals of the markers were filtered using a special algorithm.10 "Laughing" was evaluated in five especially funny film sequences by identifying synchronous changes of facial activity in the video recordings and ultrasonic markers. We computed the following: Frequency of laughing (number (N) of laughing reactions to the sketch in relation to its length (N/min movie)). IV (mm/s) of the markers at onset of laughing (mean slope through the start and maximum point of the correspondent movement based on three recordings) and that of voluntary facial movements (velocity of the markers at the beginning of these movements = mean slope through the start and maximum point of them). Emotional reaction time (ERT) (time (in seconds) between a funny film stimulus and laughing (average onset of correspondent movements of the mouth angles based on five humorous stimuli)). Using SPSS for Windows (version 11.5), the abovementioned variables were submitted to a multivariate analysis of variance (MANOVA) for group comparisons regarding the mouth angles and the rims of the eye (left, right). The variables (left, right) were correlated (Pearson’s correlation for IV: minimum, 0.65; maximum, 0.96; p < 0.001). For ERT, rp = 0.98 (p < 0.001) was computed. Post hoc t tests were performed to investigate task specific group differences. Mean VAS scores in patients and controls were compared by the Mann-Whitney U test. Associations between metric variables (such as age) and kinematic parameters were investigated using Pearson’s correlation. HAMD-21 scores were correlated with kinematic variables by Spearman-Brown correlation. T tests were applied to compare patients who had previously attempted suicide with those who had not. p Values 0.05 were considered significant. Alpha correction was applied, if necessary. RESULTS The IV of laughing was abnormally low in patients (fig 1A), as shown by MANOVA (table 1) and post hoc tests (mouth angles, p = 0.02; t test). The IV of eye movements during laughing was an exception (fig 1A) (left eye, p = 0.05; right eye, p = 0.56; ANCOVA; covariate, age). Patients also exhibited an abnormally slow IV of voluntary facial movements (fig 1B; closing of the left eye, p = 0.004; closing of the right eye, p = 0.001; stretching of the right mouth angle, p = 0.02; t tests). Figure 1 (A) Mean (SD) initial velocity of involuntary (laughing) movements triggered by watching a humorous film ("Mr Bean") and (B) mean (SD) initial velocity of voluntary movements of the face in 25 patients suffering from depressive disorders and 25 healthy controls, as measured using ultrasonic markers at different positions on the face (right and left angle of the mouth; medial inferior rims of the left and the right eye). Asterisks indicate that healthy subjects conducted involuntary and voluntary movements of the face significantly faster than depressed patients in the experimental situation. Table 1 Results of analysis of variance for comparison of depressed patients and healthy controls regarding facial parameter scores for the right and left side MANOVA revealed no significant group differences in ERT (p = 0.26). Patients laughed significantly less often than controls (p = 0.006; ANCOVA; covariate, age). However, patients and controls did not significantly differ regarding the VAS scores for "degree of funniness" (p = 0.12; Mann-Whitney U test). In patients, no significant association between facial and emotional parameters (VAS score, ERT, laughing frequency, IV) and age, age at onset of depression, duration of depression, and number of relapses was found. The effects of previous suicide attempts on facial activity were small. However, patients with previous suicide attempts were characterised by significantly slower IV of movements of the right mouth angle during laughing (mean, 2.41; SD, 1.08 mm/s), compared with patients who had not attempted suicide (mean, 5.25; SD, 3.35 mm/s) (p = 0.005; t test). In patients, higher HAMD-21 scores were significantly associated with slower IV, especially regarding the left side (left mouth angle (laughing), r = –0.45; p = 0.03; left eye (closing eyes), r = –0.67; p = 0.006 (also significant after Bonferroni correction for multiple comparisons); and right eye (closing eyes), r = –0.56; p = 0.03). DISCUSSION Depressed patients exhibited an abnormally slow IV of involuntary laughing and voluntary facial movements. Slower reactions on emotional stimuli in patients were more pronounced in the mouth corner region than at the inferior rims of the eyes. ERT and VAS judgements of the funniness of the sketch cannot explain this phenomenon because they were normal. However, depressed patients laughed significantly less frequently than did controls. The laughing frequency and IV of laughing movements were not significantly associated in depression. Therefore, they seem to represent different aspects of abnormal facial expression, namely: low susceptibility regarding humorous stimuli and abnormally slow execution of adequate facial reactions. The transformation of the feeling "funny" into the motor reaction "laughing" was undisturbed in depression (normal ERT). The substrate of this transformation process is thought to be the nucleus accumbens.11 In view of normal ERT, functional disturbances of this structure probably do not occur in depressed patients. Instead, their general slowing of facial movements may be interpreted as hypomimia (low degree of facial movements), as part of a parkinsonism with subclinical intensity, because the slowing of voluntary and involuntary movements combined with "normal" processing of emotional stimuli parallels the motor–emotional features seen in patients with Parkinson’s disease (PD).12 It can be assumed that basal ganglia dysfunction underlies these disturbances; several studies suggest that basal ganglia disturbances are a relevant factor in the pathophysiology of depression.13 Moreover, similar to patients with PD, decreased dopamine metabolism has been postulated to occur in patients with depression.14 The IV of facial movements was not associated with age and general clinical variables in depression. Instead, the slower IV of laughing movements of the right mouth angle was significantly associated with suicide attempts. This effect should be regarded with caution: the suicidal patients were hospitalised and the suicide attempts were recent. Therefore, low effect and low attention may have affected the results. The severity of depression was correlated with a slower IV, especially with regard to left sided facial movements. These findings are encouraging, but preliminary. To support them, it will be essential to compare depressed patients directly with patients who have PD. ACKNOWLEDGEMENTS We gratefully acknowledge Dr B Graf for evaluating the kinematical data as part of her MD thesis (Ludwig-Maximilians-Universit?t München, Germany). REFERENCES Bleuler E. Lehrbuch der Psychiatrie. 15th ed. Berlin: Springer, 1983. Katsikitis M, Pilowsky I. A controlled quantitative study of facial expression in Parkinson’s disease and depression. J Nerv Ment Dis 1991;179:683–8. Juckel G, Polzer U. Abnormal facial activity in chronic schizophrenic patients—a pilot study. German Journal of Psychiatry 1998;1:6–8. Padberg F, Juckel G, Pr??l A, et al. Prefrontal cortex modulation of mood and emotionally induced facial expressions: a transcranial magnetic stimulation study. J Neuropsychiatry Clin Neurosci 2001;13:206–12. Juckel G, Pr??l A, Froschmayr S, et al. "Im Gesicht lesen lernen"—Mimikanalyse schizophrener Patienten. In: Machleidt W, Haltenhof H, Garlipp P, eds. Schizophrenie—eine affektive Erkrankung?. Stuttgart: Schattauer, 1999:127–34. WMA. World Medical Association Declaration of Helsinki. Recommendations guiding physicians in biomedical research involving human subjects. JAMA 1997;277:925–6. Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry 1960;23:56–61. Dilling H, Mombour W, Schmidt MH. Internationale Klassifikation psychischer St?rungen ICD-10, V. Kapitel. 2nd ed. Bern: Huber, 1993. Mergl R, Vogel M, Mavrogiorgou P, et al. Kinematical analysis of emotionally induced facial expressions in patients with obsessive-compulsive disorder. Psychol Med 2003;33:1453–62. Hermsd?rfer J, Wack S, Mai N, et al. Dreidimensionale Bewegungsmessung zur Analyse der Handfunktion.. München: EKN—Entwicklungsgruppe Klinische Neuropsychologie, 1996. Mogenson GJ, Jones DL, Yim CY. From motivation to action: functional interface between the limbic system and the motor system. Prog Neurobiol 1980;14:69–97. Marras C, Lang AE. Measuring motor complications in clinical trials for early Parkinson’s disease. J Neurol Neurosurg Psychiatry 2003;74:143–6. Soares JC, Mann JJ. The functional neuroanatomy of mood disorders. J Psychiatr Res 1997;31:393–432. Ebert D, Lammers CH. Das zentrale dopaminerge System und die Depression. Nervenarzt 1997;68:545–55....查看详细 (15533字节)
☉ 11357066:Learning from e-patients at Massachusetts General Hospital
1 Massachusetts General Hospital, Boston, MA 02114, USA, 2 Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA Correspondence to: D Hoch dhoch@partners.org Patients and their care givers have created an impressive array of online health resources. Can healthcare professionals tap into them? In 1994, as a part of an initiative by the department of neurology of the Massachusetts General Hospital to develop promising new ways of using information technology, we began to study how patients with neurological concerns were using online health resources. To our surprise, we found that thousands of patients and their care givers had already created an impressive variety of online health resources. The online support groups, each devoted to a single neurological condition, were especially intriguing. The opportunities that these electronic groups offered for meeting members' needs were more convenient, powerful, and complex than anything we had seen in face to face support groups. For example, patients attending medical centres around the world could compare the treatments their clinicians had recommended. Participants found it easy to send complex medical information (medical journal articles, research reports, etc) to other patients, complete with links to yet other sources. But the groups we observed were scattered and uncoordinated. And although groups existed for most of the common neurological concerns, patients with uncommon conditions had no way of finding one another. We decided that our team of e-health researchers might be able to help—by providing better "homes" for existing support groups, and by encouraging the formation of needed groups. So in March 1995 the hospital's neurology service instituted a family of online groups called the Brain Talk Communities (www.braintalk.org) to support e-patients with neurological concerns. Building from the bottom up Most medical professionals who have set out to develop online resources for patients have created applications and content in a "top down" manner, directed by health professionals. Within such systems, end users (patients, their care givers, and their family members) usually have little or no input or control. Since the communities we had observed seemed to be doing quite well on their own, we chose a different approach. Rather than taking on the traditional "provider as authority" role, we decided that we would think of ourselves as architects and building contractors, creating an online system in response to our end users' requests. Our ultimate goal was neither to direct nor to monitor our e-patients' activities. Instead, we set out to give them exactly what they asked for. Thus, rather than specifying the topic areas and designing the underlying information technology structure ourselves, we asked our e-patients what they wanted and designed the system by following their suggestions. We launched the project by establishing basic discussion groups for epilepsy (DH's primary subspecialty) and 34 other groups specific to conditions or issues ranging from Alzheimer's disease to Tourette's syndrome. These forums were open to the public and were not moderated by the developers. Other than providing the initial topic threads, we stood back and let the users develop and manage the site on their own. Thus from the very beginning, Brain Talk has been a user driven or "bottom up" community space. Patients, not doctors, provide the content and make and administer the rules. What happens when e-patients take the lead? Today, braintalk.org hosts more than 250 communities devoted to neurological and related disorders—from agoraphobia, Alzheimer's, and autism to temporo-mandibular joint disorders, tinnitus, and trigeminal neuralgia. Patients also have created birds-of-a-feather groups that deal with related topics—Single Parents with Disabling Conditions and Teens Helping Teens are two examples. In addition, some groups—also initiated by the patients—focus on issues that cut across a variety of medical concerns, like our very popular Artistic Expression and Therapy community where people use creative writing and art to help them deal with neurological concerns, or the Forget-Me-Not Garden of Memories, where participants share stories of loved ones who have died. Highlights from e-patient survey data For research purposes only, we monitored the postings of the Brain Talk epilepsy support group. Many of the survey data we have collected derive from that population (links to many of our surveys can be found at patientweb.net). Between March 1995 and February 1997, more than a quarter of a million e-patients and family care givers accessed the epilepsy forum to read or contribute.2 Roughly the same proportions of care givers and patients posted messages to the forum Questions regarding treatment, the clinical course of the illness, the experience of having epilepsy, and side effects of drugs were common In 20% of the postings, users incidentally mentioned that their clinicians had not met their information needs A panel of three neurologists and a neurology nurse judged that 6% of the posted information contained factual inaccuracies. In 1998,3 40% of 105 survey respondents said that they used the forum because their clinician did not or could not fulfil their information needs Forum members greatly overestimated the prevalence of inaccurate information in the postings on the forum. Our earlier analysis showed that about 6% of the posted information was inaccurate, yet when polled: - 75% of users felt that 10% or more of the information was inaccurate - 53% felt that 25% or more of the information was inaccurate - 22% felt that 50% or more of the information was inaccurate But 95% said that the presence of inaccurate information on the forum did not negatively affect their experience. In 2001 we surveyed all Brain Talk participants to collect demographic and descriptive data and ask participants about their online experiences. Some of the demographic data can be found at http://fisher.mgh.harvard.edu/cscw/demo_data.html The last time they went on line for health purposes, 46% of the 1281 respondents posted some material for someone else to read, and 19% of people had some kind of online interaction with another person More than two thirds of survey respondents connected with Brain Talk at least once a day and about a third checked in several times a day 57% said that they usually visit more than one forum: 29% visit two, 25% visit three to five forums, and 3% visit six or more The most frequently visited forums were muscular sclerosis, chronic pain, epilepsy, spinal disorders, depression, reflex sympathetic dystrophy, child neurology, Parkinson's disease, thoracic outlet syndrome, fibromyalgia, workman's compensation, chapel, and general neurology At their last visit to their healthcare provider, 39% of respondents felt that they had not been given a chance to completely explain the reasons for their visit, and 40% felt that the provider didn't listen completely to what they did have to say; 6% of these said they felt the provider didn't listen at all 72% felt that they had not received a complete explanation of the potential side effects of the drugs their clinicians prescribed 53% said that when they came to their clinician's office, they had questions about their care or treatment that they wanted to discuss but did not do so. The most commonly cited reasons for failing to discuss these issues were: - Provider didn't have time to listen (47%) - Patient forgot to bring up the questions (37%) - Patient did not have time to bring them up (29%) - Patient was embarrassed about bringing them up (21%) 74% said that they were treated with complete respect and dignity at their last clinician's visit 5% felt that in general their healthcare provider did not treat them with respect and dignity 46% said that they wanted to be more involved in decisions about their care Our members' resourcefulness and creativity continue to astound us. Several dozen housebound patients with multiple sclerosis who were injecting themselves with the drug Avonex (interferon beta-1a) every week recently organised a chat room called Club Avonex. Most members found the self injection process extremely stressful; even though they lived in many different time zones, the group members all agreed to adjust their injection schedules so that they could all log on to the Club Avonex chat room and inject themselves at the same time. This made it possible for participants to offer each other guidance and support before, during, and after the injection. Putting it all together: Lester's law After nearly a decade of e-patient research, we've concluded that what e-patients actually do on line is more complex—and more social—than most health professionals realise. A typical e-patient with multiple sclerosis might say, "First I'm going to check my e-mail—including my mailing list messages—and respond as needed. Then I'll go see if there are any new messages on my three favourite bulletin boards, and maybe post a few comments. Then I'll check my favourite chat room to see who's there, and if I don't get into any interesting discussions, I'll check my MS buddy list to see who's on line right now and see if I can invite some friends to join me there. And after that I'm having lunch with Matt, an MS-er from California, whom I know really well from the group, but whom I've never met before face-to-face. And after lunch I need to go to on line to read the latest issues of the three key medical journals for MS so I can summarise the key articles for my support group." Moreover, online community members can also sometimes provide medical advice to those who can't easily access a clinician themselves. As one e-patient recently explained: "When I talk to my doctor, I hear myself asking questions that my online `family' needs to know. It's as if all these other people—the members of my group—are asking questions through me. And whatever answers I hear from my doctor, I know I'll share with them on line." Much of what we have learnt in our collaborations with e-patients can be summed up in what has come to be known as Lester's law: "Medical knowledge is a social process: the conversations that occur around artefactual data are always more important than the data themselves."1 Practical advice for doctors Health professionals interested in observing e-patient dynamics can learn a good deal from going out into the self help neighbourhoods of cyberspace as observers. Find a few of the most impressive e-patient pioneers within your own areas of interest. Observe them, and if appropriate, communicate with them. See if you can find some low profile way to support their efforts, such as referring your patients to the group, answering group members' questions, or providing small scale sponsorships or grants. But please don't attempt to direct or control their efforts. And don't even think about attempting to put your advertising on their sites. The things you learn from observing and communicating with the e-patients you find on line may prove invaluable in your future work. This has certainly been true with us. One of us (DH) is a neurologist specialising in epilepsy. Having learnt about the value and dynamics of online groups through our e-patient research, he now routinely encourages all of his epilepsy patients to participate in a private in-house online support community. He participates in the discussions too, and as his patients get to know one another and become familiar with each group member's unique neurological conditions, he's working with them to develop and explore more sophisticated ways in which he and the group can collaborate. In the next phase of our e-patient research, we hope to explore these new types of online co-care in which e-patients, online support groups, and clinicians can collaborate in unprecedented ways. Summary points Patients reach out and connect with others over the internet in a complicated, highly organised social support network Doctors can find ways to help patient online communities and explore them without being intrusive The impact and importance that online communities may have on patients should not be underestimated We are indebted to Tom Ferguson for his many helpful suggestions. Contributors and sources: Ellie Vogel conceived and co-designed the 2001 Brain Talk survey; SLP and DBH analysed the data. JL, SLP, YF and DBH jointly wrote this paper. DBH is guarantor. Funding: Some of the work described here was supported by a grant from the National Library of Medicine, G03 LM06964. Competing interests: None declared. References Ferguson T. Medical knowledge as a social process: an interview with John Lester. The Ferguson Report, issue 9, Sep 2002. www.fergusonreport.com/articles/fr00902.htm (accessed 22 Apr 2004). Hoch D, Norris D, Marcus AD, Information exchange in an epilepsy forum on the world wide web. Seizure 1999;8: 30-4. Norris D, Lester JE, Hoch DB. An internet forum for epilepsy support: a survey of users. Epilepsia 1998;39(suppl 6): 229....查看详细 (13432字节)
☉ 11357067:Severe tick borne encephalitis with simultaneous brain stem, bithalamic, and spinal cord involvement documented by MRI
1 Department of Neurology, University of Munich, Klinikum Grosshadern, Munich, Germany 2 Department of Neuroradiology, University of Munich Correspondence to: Dr Andreas Bender Department of Neurology, University of Munich, Klinikum Grosshadern, Marchioninistr 15, 81377 Munich, Germany; andreas.bender@med.uni-muenchen.de ABSTRACT A case of tick borne encephalitis (TBE) is reported, with simultaneous brain stem, spinal cord, and bilateral thalamic involvement confirmed by magnetic resonance imaging (MRI). After exposure to a TBE endemic region, the patient developed a biphasic clinical course with initial flu-like symptoms followed by a severe brain stem syndrome. The diagnosis of TBE was confirmed serologically. Repeated MRI scans showed brain stem, bithalamic, and spinal cord involvement. The outcome was favourable. TBE cases with concomitant myelitis tend to have a more severe clinical course and more likelihood of needing intensive care support. They should therefore be identified early in order to be prepared for life threatening respiratory complications. Keywords: flavivirus; meningoencephalitis; tick borne encephalitis The tick borne encephalitis (TBE) virus causes the most important arthropod transmitted (tick bite) disease in central and eastern Europe. TBE virus causes a generalised infection primarily affecting the CNS. The most common presentation is meningitis (49%), followed by meningoencephalitis (41%) and meningoencephalomyelitis (10%).1 Polio-like syndromes with a predominantly polyradiculitic course have also been described.2 In endemic areas, TBE has an incidence of 1.2 per 100 000 and a mortality of about 1%.3 Like other flavivirus infections (for example, Japanese encephalitis), TBE can lead to bilateral thalamic lesions that are visible on magnetic resonance imaging (MRI), though neuroradiological abnormalities are found only in a minority of cases. We present a severe TBE case with neuroradiological proof of simultaneous thalamic, brain stem, and spinal cord involvement but a favourable outcome. CASE REPORT A 29 year old, previously healthy young man from southern Germany who had not had TBE immunisation fell ill for two days with flu-like symptoms one week after a short mountain bike trip to Austria in August 2003 (to Oetz in the Tyrol, where there have been documented cases of TBE). He had had contact with ticks (he had noticed them on his clothing but did not recall being bitten). Three weeks later he developed acute headache, nausea, and vomiting (day 1). On the next day, he began to have dysarthria, diplopia, gait ataxia, and clumsiness in both hands. On day 3 he was admitted to hospital. At this time his consciousness was impaired (Glasgow coma scale, 11) and he had moderate meningism and fever (38.5°C). Laboratory findings (normal values in brackets) were abnormal: increased C reactive protein (22.1 mg/dl (4 confirms intrathecal specific antibody production). After the diagnosis of TBE was established, antibiotic therapy was discontinued. The patient slowly recovered. On day 14, he was awake and followed commands, but he had developed a flaccid tetraparesis. Electrophysiological and myographic testing revealed abnormal spontaneous activity in all five muscles examined. Paravertebral muscles were more severely affected than distal muscles. Compound muscle action potentials (CMAP) were decreased in all nerves examined, with normal motor conduction velocity, while sensory neurography was normal. This pattern of acute impairment is compatible with an acute motor neuropathy or affection of the anterior horn cells, but would be unexpected in the most likely differential diagnosis of critical illness polyneuropathy. This spinal involvement was confirmed by spinal MRI on day 21, when the signal on T2 weighted and T1 weighted contrast enhanced images within the anterior part of the cervical cord was increased (fig 2). Serological testing for enterovirus and Borrelia burgdorferi antibodies as other potential sources of myelitis was negative. Follow up MRI of the brain at the same time revealed a reduction of signal alterations in the brain stem (fig 1E–F). This neuroradiological finding correlated well with the clinical improvement of the patient. He was extubated on day 31 and transferred to a rehabilitation unit on day 35. At the time of writing (day 173) he was still suffering from weakness in his left arm but was able to walk and had only minimal neuropsychological deficits (Barthel index 90). Figure 2 Spinal T2 weighted images showing longitudinal involvement of the anterior part of the spinal cord from the C2 level to the C7 level in sagittal view ((A); arrows mark signal alteration) and on corresponding axial images (B). DISCUSSION TBE is usually characterised by a biphasic course with initially flu-like symptoms followed by neurological symptoms—for example, impaired consciousness (31%), ataxia (18%), paresis of the limbs (15%) or the cranial nerves (11%), and tremor (4.3%).1 As there is no specific treatment and as the illness is associated with significant morbidity and neurological sequelae (27% have sequelae lasting more than three months), active immunisation is the most important way to manage TBE.1 TBE virus is part of the flavivirus genus, which includes several significant neurotropic human pathogens that cause TBE-like diseases such as Saint Louis encephalitis, Japanese encephalitis, and West Nile virus infection. A common neuroradiological feature of these diseases is diffuse bilateral thalamic high signal on T2 weighted images.4–6 Contrast enhancement of the affected brain parenchyma is not regularly seen (for a review of MRI abnormalities, see table 1). Table 1 Comparison of MRI findings (increased signal on T2 weighted images, rarely combined with pathological contrast enhancement) in flavivirus infections Pathological MRI changes can be observed in approximately 20% of patients with manifest TBE. In the most comprehensive series of TBE cases published so far, Kaiser found bilateral involvement of the thalamus in 15 of 18 patients, and changes in the cerebellum, brain stem, and caudate nucleus in the remaining three.1 These findings have been confirmed by others, mainly in the form of case reports.12 Data on follow up MRI examinations in TBE are lacking. In the present case, we observed a good correlation between clinical improvement and restitution of the T2 abnormalities of the affected brain parenchyma. To the best of our knowledge, this is the first published case of simultaneous thalamic, brain stem, and especially spinal cord involvement, both clinically and on MRI. Beer et al described a rare case of a TBE patient who had an isolated anterior horn lesion of the C3 to the T1 level.13 Considering that the location of the spinal cord lesion in our patient was nearly identical, we suggest an accurate clinical, electrophysiological, and neuroradiological investigation of the cervical spinal cord when tick borne encephalomyelitis is suspected. Like Beer et al and Kuntzer et al,8,13 we also observed a progression of the neurological deficits after initiating antibiotic treatment, including ceftriaxone. This might have been caused by activation of persisting TBE virus by cephalosporins, as Malenko et al showed in an animal model.14 With increasing intercontinental travel over the past decades, flavivirus infections such as TBE are posing a growing global health threat. This is reflected by a recent outbreak of West Nile virus infection in the New York City area.15 Such infections therefore remain a diagnostic challenge to health care professionals, even outside typical endemic areas. As these viruses seem to lead to a comparable pattern of abnormalities on thalamic and basal ganglia MRI, it is probable that other cases of non-TBE flavivirus infection with brain stem and spinal cord involvement will be found. This hypothesis is supported by a recent paper reporting five cases of acute paralytic poliomyelitis associated with West Nile virus infection.11 Conclusions In cases of suspected encephalitis in association with bilateral lesions in the thalamus or with brain stem involvement, the possibility of a flavivirus infection such as TBE should be considered. Patients with concomitant spinal cord involvement may be affected more severely and should therefore be identified early by means of clinical, electrophysiological, and radiological examinations, in order prepared for the likelihood that they will need mechanical ventilation. ACKNOWLEDGEMENTS We thank Dr Jaeger (Department of Virology, University of Munich), Dr Wick (Department of Laboratory Medicine, University of Munich), and Dr Strauss (Bad Aibling Neurological Clinic) for clinical and laboratory cooperation. REFERENCES Kaiser R. The clinical and epidemiological profile of tick-borne encephalitis in southern Germany 1994–98: a prospective study of 656 patients. Brain 1999;122:2067–78. Aendekerk RP, Schrivers AN, Koehler PJ. Tick-borne encephalitis complicated by a polio-like syndrome following a holiday in central Europe. Clin Neurol Neurosurg 1996;98:262–4. Kaiser R. Tick-borne encephalitis in southwestern Germany. Infection 1996;24:398–9. Alkadhi H, Kollias SS. MRI in tick-borne encephalitis. Neuroradiology 2000;42:753–5. Kalita J, Misra UK. Comparison of CT scan and MRI findings in the diagnosis of Japanese encephalitis. J Neurol Sci 2000;174:3–8. Cerna F, Mehrad B, Luby JP, et al. St. Louis encephalitis and the substantia nigra: MR imaging evaluation. Am J Neuroradiol 1999;20:1281–3. Valdueza JM, Weber JR, Harms L, et al. Severe tick borne encephalomyelitis after tick bite and passive immunisation. J Neurol Neurosurg Psychiatry 1996;60:593–4. Beer S, Brune N, Kesselring J. Detection of anterior horn lesions by MRI in central European tick-borne encephalomyelitis. J Neurol 1999;246:1169–71. Bosanko CM, Gilroy J, Wang AM, et al. West Nile virus encephalitis involving the substantia nigra: neuroimaging and pathologic findings with literature review. Arch Neurol 2003;60:1448–52. Rosas H, Wippold FJ. West Nile virus: case report with MR imaging findings. Am J Neuroradiol 2003;24:1376–8. Al-Shekhlee A, Katirji B. Electrodiagnostic features of acute paralytic poliomyelitis associated with West Nile Virus infection. Muscle Nerve 2004;29:376–80. Pfister HW, Lorenzl S, Yousry T. Neuroradiographic manifestations of encephalitis. N Engl J Med 1997;337:1393–4. Kuntzer T, de Marval F, Ochsner F, et al. Meningoencephalo-myeloradiculitis due to flavivirus: bi-brachial paralysis and respiratory insufficiency. Schweiz Med Wochenschr 1995;125:634–8. Malenko GV, Pogodina VV, Frolova MP, et al. Strategy for choosing antibiotics for treating bacterial infections with chronic tick-borne encephalitis. Vopr Virusol 1996;41:138–41. Nash D, Mostashari F, Fine A, et al. The outbreak of West Nile virus infection in the New York City area in 1999. N Engl J Med 2001;344:1807–14....查看详细 (13488字节)
☉ 11357068:HyperIgEaemia in patients with juvenile muscular atrophy of the distal upper extremity(Hirayama disease)
Department of Neurology, Chiba University Graduate School of Medicine, Chiba, Japan Correspondence to: Dr Shoichi Ito Department of Neurology (D3), Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan; sito@faculty.chiba-u.jp ABSTRACT Background: Juvenile muscular atrophy of the distal upper extremity (Hirayama disease) is characterised by anterior horn cell loss in the lower cervical cord, presumably caused by anterior displacement of the dural sac during neck flexion. A recent report suggests that atopy and IgE may contribute to anterior horn damage. Objective: To investigate whether IgE is a contributing factor in Hirayama disease. Methods: Serum total IgE and allergen specific IgE were examined in 20 consecutive patients, and their correlations with clinical profiles investigated. Results: Past or present history of allergy/atopy was found in only four patients (20%), but serum IgE was raised in 14 (70%). Patients with hyperIgEaemia had more severe clinical disabilities than those without (p = 0.01). In patients whose history of Hirayama disease was less than five years, serum total IgE was higher than in those with the disease for five years or more (p = 0.05). Conclusions: The results suggest that hyperIgEaemia is often associated with Hirayama disease and can facilitate its pathophysiology, particularly in the early phases of the disease. HyperIgEaemia does not appear to involve the anterior horn cells primarily. Keywords: juvenile muscular atrophy of arm; Hirayama disease; IgE; atopy Juvenile muscular atrophy of the distal upper extremity (Hirayama disease) is characterised by muscular weakness and wasting of the distal upper extremity, predominantly in young men,1–3 and is followed by spontaneous arrest within several years.4 Upper extremity involvement is primarily unilateral. The pathophysiology of Hirayama disease has not yet been clarified, but neuroimaging studies suggest that the disorder is a type of flexion myelopathy—abnormal forward displacement of the cervical dural sac during neck flexion results in compression of the lower cervical cord.2,3 Necropsy findings show shrinkage and loss of the anterior horn cells of the cervical cord, possibly caused by circulatory insufficiency in the spinal cord.5 Recently, Kira and Ochi reported five patients with Hirayama disease in association with atopy,6 and raised the possibility that hyperIgEaemia contributes to anterior horn damage. As the frequency of hyperIgEaemia in patients with Hirayama disease and its action on the pathophysiology are currently unknown, we undertook the present study to determine the frequency of hyperIgEaemia and its correlation with the clinical and electrophysiological profiles of patients with Hirayama disease. METHODS We examined 20 consecutive patients with Hirayama disease (19 men, one woman) seen at Chiba University Hospital between 1992 and 2001. Their ages ranged from 17 to 32 years (mean (SD), 20.6 (4.2) years). The age of onset of the disease ranged from 12 to 19 years (15.8 (2.2) years), and the disease duration from 1 to 20 years (4.8 (5.2) years). All patients had typical clinical features of Hirayama disease.2,3 In order to establish the diagnosis we required confirmation of forward displacement of the cervical dural sac during neck flexion on magnetic resonance imaging (MRI) or computed tomographic (CT) myelography (fig 1). Figure 1 T2 weighted magnetic resonance images of the cervical region in a patient with typical features of Hirayama disease. The black arrow indicates the posterior wall of the dural sac. An axial image at the C6 vertebral level at neutral cervical position shows no apparent abnormality of the cervical cord or dural sac (A). During neck flexion, axial (B) and sagittal (C) images show abnormal forward displacement of the dural sac at the lower cervical level with compression of the spinal cord (arrows). Hirayama disease usually involves one upper limb, and this was the case in all 20 of our patients. The clinical severity of the disease was evaluated using the following grading4: grade 1 (n = 8), grip strength of the affected hand more than 50% of the non-affected hand; grade 2 (n = 6), grip strength of the affected hand 30–50% of the non-affected hand; grade 3 (n = 6), grip strength of the affected hand less than 30% of the non-affected hand. We asked patients and their family members whether they had a past, present, or family history of allergy/atopy, such as atopic dermatitis, bronchial asthma, allergic rhinitis, pollinosis, or diet allergy. Serum total IgE and allergen specific IgE concentrations (radioallergosorbent test: RAST) for mites (Dermatophagoides pteronyssinus and Dermatophagoides farinae), house dusts, cedar pollen, and soybean were measured. A serum total IgE level of greater than 170 IU/ml was considered abnormal.7 RAST values of over 0.34 allergen unit (AU)/ml were considered abnormally high; the values were classified as follows: class 1, 0.35 to 0.69; class 2, 0.70 to 3.49; class 3, 3.50 to 17.49; class 4, 17.50 to 49.99; class 5, 50.00 to 99.99; and class 6, over 100.00. Electromyography was carried out in 16 patients, and active denervation was considered to be present when fibrillation potentials or positive sharp waves were found in the first interosseous muscle or flexor carpi ulnaris muscle on the affected side. Eighteen patients underwent motor nerve conduction studies on the ulnar nerve of the affected side. For statistical analyses, differences in medians were tested by the Mann–Whitney U test, and differences in proportions by Fisher’s exact test. RESULTS In our 20 patients, at least one kind of past or present history of allergy/atopy was present in four (20%): atopic dermatitis in three (15%), allergic rhinitis in one (5%), and pollinosis in one (5%). No patient had a history of bronchial asthma or diet allergy. A familial history of at least one kind of allergy/atopy was found in seven patients (35%): atopic dermatitis in three (15%), allergic rhinitis in four (20%), bronchial asthma in four (5%), and diet allergy in four (5%). HyperIgEaemia was present in 14 of the 20 patients (70%) (mean 655 IU/ml; range 180 to 4100 IU/ml). The values of at least one kind of RAST were abnormally high in 16 patients (80%): house dusts in 13 (65%), mites in 13 (65%), cedar pollen in 14 (70%), and soybean in three (15%). Table 1 compares the clinical, immunological, and electrophysiological profiles of patients with hyperIgEaemia and those without. Age, age of onset, male to female ratio, and disease duration did not differ significantly between the two subgroups. With respect to the clinical grade, hyperIgEaemia was found in four of eight grade 1 patients (50%), in three of six grade 2 patients (50%), and in five of six grade 3 patients (83%). Clinical severity was significantly greater in patients with hyperIgEaemia (mean clinical grade, 2.0) than in those without (mean clinical grade, 1.0) (p = 0.01); RAST values for mites and house dusts were also higher in patients with hyperIgEaemia than in those without. Patients with hyperIgEaemia tended to have lower amplitudes of ulnar compound muscle action potentials and more frequent active denervation potentials, but the differences were not statistically significant. The lack of statistical difference in the electrophysiological variables might reflect the small number of patients and muscles examined. Disease duration correlated with the serum IgE concentrations; the patients with Hirayama disease for less than five years had a higher serum IgE than those with the disease for five years or more (917 (1286) v 262 (160) IU/ml; p = 0.05). Table 1 Clinical and laboratory profiles of patients with Hirayama disease DISCUSSION Our study confirms previous findings6 that patients with Hirayama disease often suffer from hyperIgEaemia (70% in this study), and furthermore show that patients with hyperIgEaemia tend to have more severe disabilities than those without. Moreover, serum IgE concentrations are higher in patients with a disease duration less than five years than in those with a duration of five years or more. These findings suggest that IgE may be a facilitating factor in the severity and activity of the disease, especially in its early phases. However, a third of our patients showed no evidence of atopy and had normal serum IgE levels. Recent studies have shown that the prevalence of atopic dermatitis,8 allergic or seasonal rhinitis,9 and pollinosis9,10 in Japan is 11–24%, 29–36%, and 11–23%, respectively. Comparing these data, the frequency of a history of atopy/allergy was considered low in our patients with Hirayama disease, but an asymptomatic increase in serum total IgE (70%) and RAST (80%) was very common. Although various reports have stated that MRI during neck flexion does not show dural sac displacement in some patients with Hirayama disease,11,12 our present study included a uniform group of patients, in all of whom abnormal forward displacement of the cervical dural sac was confirmed. In such patients, dural sac displacement during neck flexion and the resulting cord compression are assumed to contribute to anterior horn cell damage. The relation between dural sac displacement and hyperIgEaemia in Hirayama disease is unknown. The dural sac is normally tightly connected to the spinal canal wall, and its abnormal displacement is probably caused by mechanical or other unknown factors. Eosinophils are known to secrete matrix metalloproteinases, especially matrix metalloproteinase-9,13,14 and we recently reported that cervical intervertebral disc degeneration is common in patients with atopy and hyperIgEaemia,15 suggesting a possible relation between atopy and an abnormality of connective tissues. Atopy or hyperIgEaemia may affect collagen or other connective tissue components of the dural sac in patients with Hirayama disease. It is possible that such involvement of the connective tissues results in impaired dural development. Hirayama disease predominantly affects young male adolescents in their mid-teens,2,3 the age at which their height increases most rapidly. Abnormal dural sac displacement in patients with Hirayama disease may be related to connective tissue abnormalities during this period of rapid growth. Further studies are required to determine the mechanisms of action of IgE on loss of anterior horn cells in Hirayama disease. Although a previous report raised the possibility that IgE directly causes spinal anterior horn damage through circulatory insufficiency resulting from platelet activation and arterial spasm,6 we believe that this is unlikely, because a third of our patients with Hirayama disease had no evidence of atopy or hyperIgEaemia during the progressive phase of the disease, though they did show abnormal dural sac displacement. We speculate that indirect effects on the dural sac by IgE as described above facilitate the mechanical pathophysiology in Hirayama disease. The present study shows that the serum total IgE level is higher in patients who were in their early progressive phase, and is associated with more severe clinical disability; these patients tended to have more prominent electrophysiological abnormalities. Suppression of IgE may be a treatment option, especially in the early phases of the disease. ACKNOWLEDGEMENTS We would like to express our gratitude to Dr Keizo Hirayama for helpful comments on the manuscript. REFERENCES Hirayama K, Toyokura Y, Tsubaki T. Juvenile muscular atrophy of unilateral upper extremity: a new clinical entity. Psychiatr Neurol Jpn 1959;61:2190–8 . Hirayama K. Juvenile muscular atrophy of distal upper extremity (Hirayama disease). Intern Med 2000;39:283–90. Hirayama K, Tokumaru Y. Cervical dural sac and spinal cord in juvenile muscular atrophy of distal upper extremity. Neurology 2000;54:1922–6. Tokumaru Y, Hirayama K. Cervical collar therapy for juvenile muscular atrophy of distal upper extremity (Hirayama disease). Int Med 2000;39:283–90. Hirayama K, Tomonaga M, Kitano K, et al. Focal cervical poliopathy causing juvenile muscular atrophy of distal upper extremity: a pathological study. J Neurol Neurosurg Psychiatry 1987;50:285–90. Kira J, Ochi H. Juvenile muscular atrophy of the distal upper limb (Hirayama disease) associated atopy. J Neurol Neurosurg Psychiatry 2001;70:798–801. Shimazu S, Enomoto T. Serum IgE levels in healthy children. Arerugi no Ryoiki 1995;2:62–7 . Sugiura H, Umemoto N, Deguchi H, et al. Prevalence of child food and adolescent atopic dermatitis in a Japanese population: comparison with the disease frequency examined 20 years ago. Acta Derm Venereol 1998;78:293–4. Sakurai Y, Nakamura K, Teruya K, et al. Prevalence and risk factors of allergic rhinitis and cedar pollinosis among Japanese men. Prev Med 1998;27:617–22. Ozasa K, Dejima K, Takenaka H. Prevalence of Japanese cedar pollinosis among schoolchildren in Japan. Int Arch Allergy 2002;128:165–7. Schr?der R, Keller E, Flacke S, et al. MRI findings in Hirayama’s disease: flexion-induced cervical myelopathy or intrinsic motor neuron disease? J Neurol 1999;246:1069–74. Willeit J, Kiechl S, Kiechl-Kohlendorfer U, et al. Juvenile asymmetric segmental spinal muscular atrophy (Hirayama’s disease). Three cases without evidence of "flexion myelopathy". Acta Neurol Scand 2001;104:320–2. Fujisawa T, Kato Y, Terada A, et al. Matrix metalloproteinase-9 in peripheral blood eosinophils. Int Arch Allergy Immunol 1999;120 (suppl 1) :65–9. Schwingshackl A, Duszyk M, Brown N, et al. Human eosinophils release matrix metalloproteinase-9 on stimulation with TNF-. J Allergy Clin Immunol 1999;104:983–9. Ito S, Hattori T, Fukutake T, et al. Is atopic dermatitis a risk factor for intervertebral disc degeneration? A preliminary clinical and MRI study. J Neurol Sci 2003;206:39–42....查看详细 (14151字节)

☉ 11357069:The clinician's perspective on electronic health records and how they can affect patient care
1 Birmingham Heartlands and Solihull NHS Trust, Solihull Hospital, Solihull B91 2JL stephen.walsh@heartsol.wmids.nhs.uk Introduction Use of narratives in clinical reasoning Patient documentation systems that try to reproduce previously accepted models of clinical reasoning (pattern recognition, algorithms, or hypothetico-deductive models) have achieved limited acceptance. According to Greenhalgh, the medical encounter consists of stories within stories.5 Kay and Purves maintain that narratives are at the heart of clinical decision making and refers to this concept as "narrative reasoning."6 They argue that "every patient tells a story (narrative) and clinicians intuitively use narrative devices in relation to the delivery of patient care." The patient is seen as "a page from the book of nature, a text to be read," and the doctor becomes the author of "stories within the medical record." Kay and Purves make a strong case for retaining information in a conceptual framework and maintain that this is best accomplished by means of narratives rather than "reducing the semantic richness and degrading the story to limited codes and weakly connected phrases." Van Ginneken also states that many computerised medical record systems are rejected by clinicians because they are not based on a story metaphor.7 Frisse and colleagues state that "using conversations as a central metaphor for handling patients' records reflects work flow in a clinical setting" and that "until recently, shortcomings of medical information systems software, computer-human interfaces, and networks forced upon the healthcare community a depersonalised notion of `information' centred upon the interaction between the individual and the `system' rather than upon the interaction of human beings with one another."8 Summary points Narratives are essential to a patient's episode of illness Poor communication is more often detrimental to patients than lack of knowledge Computers should enable clinicians to capture narratives easily The structure of the patient's record strongly influences the ease of information retrieval Impact of construction of patient record on clinical insight Berg argues that, to a large extent, compiling a medical record is a sociological process not a cognitive function.9 Traditionally, the work of clerking a patient was seen as collecting observations, testing diagnostic hypotheses, and reaching treatment decisions by means of logic. Berg maintains, however, that creating the medical record is a "moulding process in which the patient and his situation are reconstructed to render them manageable within existing agency routines." The clinician tries to transform the patient's narrative into an entity which he or she is familiar with and capable of managing. In this process, some aspects of the story are emphasised and others forgotten. The process of creating a patient record changes the clinician's concept of the patient's illness episode. Berg further maintains that failure to appreciate this sociological aspect could partially explain the current paucity of fully integrated, clinically useful electronic records systems. Constructing the patient record "The medical record is a tool... it does not `represent' the work, but it feeds into it, it structures and transforms it in complex ways: it structures that communication between healthcare personnel, shapes medical decision making, and frames relations between personnel and patients." Berg9 Conversational interaction between clinicians Coiera states that most medical interaction is driven by a conversational paradigm, and he points out that communication errors cause twice as many deaths as inadequate clinical skills do.10 He argues that this is where "substantial informatics efforts need to be focused," and he adds that "direct support of the communication between clinicians should substantially improve how our organisations acquire, present, and use information." A patient's computer records should promote seamless transfer of care from one clinical team to another. This is best accomplished by using a conversational or narrative format rather than chunks of information scattered around divergent screen pages. Problems in entering data Data entry has always been a major obstacle to healthcare professionals' acceptance of electronic records. Most input makes use of structured data entry, where the user has to select relevant clinical terms from a predefined list. This is restrictive, and extracting this information from a narrative requires more work from the clinician. Also, entering structured data can subtly change the meaning of the item coded. Furthermore, creating a standardised clinical set of terms and keeping these up to date is resource intensive. Rather than placing the burden of coding on the doctor, the developers of electronic records systems should be "more oriented towards creating tools that support medical work as a social, interactive process."11 Despite much effort to produce friendlier interfaces—including pen based, hand held computers,13 touch screens, and other forms of structured data entry—no generally accepted computer interface has emerged for capturing data. The fastest method for data entry is speech input, but the quickest way to assimilate information is reading structured text. Patients generally accept the use of computers in clinical settings Credit: BSIP, LA/HERRERA/SPL Problems of structured data entry "Most benefits of computer-based records rely on structured, coded data, not free text, but clinicians value the ability of flowing prose to paint an evocative clinical picture. They generally take longer to select computer concepts corresponding to a patient's findings, diagnoses, or tests from long lists of standard terms drawn from controlled vocabularies than to write a summary. Worse, the codes installed with software may constrain clinical language. Developers and purchasers of computer-based record systems must ensure that the disadvantages of capturing structured, coded data are outweighed by more informative displays and automatic processing of data." Powsner et al12 Ease of access to and structure of records Reading text on a computer screen is up to 40% slower than reading printed text. If the computer is used to generate output, the layout and structure of the reports are important as this can influence clinical decisions in sometimes fundamental ways.14 Coiera states: "It is possible for a well-designed set of paper forms to be far more effective in improving the quality of a medical record than a poorly designed computer-based one."15 Despite the ease of creating paper based records, they prove difficult to search. Tang and colleagues found that their physicians could not find relevant patient information in traditional paper based records in 80% of outpatient visits.16 The ease of using computer based output as opposed to the benefits of generating printed reports must be weighed.15 There are obvious benefits of having data available electronically, but having appropriately structured printed output is still far easier for browsing, reading, and finding information. A paperless environment is not necessarily good or desirable. Having the option to use either paper or electronic record output, depending on preference or other clinical constraints, is important. Clinical perspective and potential benefits for patients: practicalities Capturing the patient's narrative Data should be acquired as close to the source as possible.17 The ideal electronic records system should allow the clinician to input narratives effortlessly using handwriting and sketches as well as speech input at the patient's bedside or at the office desk. Some coding by clinicians is unavoidable but should be limited if possible to the problem list (diagnoses) and procedures. Kay and Purves propose a clinical approach in which doctors improve their communication skills and allow "each actor responsible for observations and actions within the patient's care pathway... to record the pertinent information."6 Van Bemmel and colleagues state that coding of data should be done "only if there is no other way to present the data" and preferably "by the person making the observation."17 Several studies have found that computer use in clinical settings has generally been accepted by patients, whether in general practice surgeries,18 19 outpatients departments,20 or examination rooms.21 No degradation of the doctor-patient relationship was noted in these studies. A greater emphasis on patients' narratives should be beneficial: "Patients who are fully able to share their perspective often achieve better outcomes."22 How constructing the electronic record affects clinical insight Handwriting is automatic—you don't have to think about it—but for most people, using a computer is not. Consequently, the cognitive load associated with documenting the details of a patient encounter is smaller if the clinician writes them by hand rather than entering them on a computer. Handwriting potentially allows more thought for focusing on how to diagnose and manage the patient's illness. Clinicians using computers could have more of a cognitive load and would benefit from having tools that stimulate clinical reasoning—such as differential diagnosis, prompting, reminders, mnemonics, algorithms, references, risk calculators, decision trees, and best evidence resources. These are almost impossible to build into conventional handwritten notes. Creating the relevant supportive knowledge structure in an electronic environment is also not easy. Great care is needed when integrating such aids into the clinician's workflow as they could easily hinder rather than benefit patient care.23 The recent development of digital pens that record and transcribe handwriting—such as those made by Logitech (www.logitech.com) and Nokia (www.nokia.com)—might reduce the cognitive load while providing an automated link to electronic aids. Making the right connections with local and national guidelines, stimulating wider thought about the case, and supporting clinical decisions with the best evidence are extremely important elements for patient outcomes. Much more research in this area is needed, however. Communicating clinical data by voice Current technology could easily handle voice on hospital networks or the internet. Some information is important to have in written or printed format to avoid ambiguity. The problem list (diagnoses) probably falls into this category. But much of what clinicians do has relatively shortlived value—for example, "to do" lists and instructions to others. Why not send a recorded request for a consultation across the network rather than fax a handwritten one? The electronic records system could easily incorporate multiple audio files along with the usual textual data. The audio files could be searched using an "audio mining" engine (www.scansoft.com/audiomining). The admitting doctor could record a summary of the patient's admission for the next day's ward round. Recordings could be replayed and critiqued. If required, any good quality voice recording could be transcribed using software or by a secretary. Far more use could be made of asynchronous communication to reduce interruptions. Using the computer to facilitate communication by clinicians should directly improve clinical outcomes.10 Speech: easy for data entry "Speech is natural—we know how to speak before we know how to read and write. Speech is also efficient—most people can speak about five times faster than they type and probably ten times faster than they can write. And speech is flexible—we do not have to touch or see anything to carry on a conversation." Zue24 Facilitating data entry Making data entry as easy as possible is essential if we want clinicians to use electronic means to enter and share accurate patient records on a national network. The easiest way to enter data into an electronic records system is to use speech, followed by handwriting and then typing (if you are not a touch typist). Capturing speech would promote the collection of narrative rather than discrete bits of data. Transcription could be used if required. The recording could be sent through an audio mining engine to index the words it contains and thus facilitate access to its otherwise "invisible" contents. As yet there are no commercially available electronic health records systems that capture voice recordings as a source document. Another important consideration is that medical work is driven by interruptions. Software needs to be able to keep its state when the user is diverted to a telephone call or query and somebody else takes control of the computer or terminal to continue a task they were busy with before being interrupted themselves. Need for easy data access and interpretation It is quicker to retrieve and assimilate information by reading and scanning than by listening to speech. Reading printed material is quicker than reading the same text on a computer screen. However, although paper records are easy to create, they can be difficult to search—particularly if they lack structure. Tange and colleagues found that data retrieval from medical narratives is highly dependent on the granularity of paragraphs used (that is, the number of labelled segments of text). They concluded: "Most benefit can be expected from medical history and examination notes divided into organ systems and progress notes divided into problem segments."25 How information is presented (its context) is an important factor affecting data retrieval and interpretation. Computer systems should be capable of producing well structured screen based and paper based output of narratives. Graphic output of numeric data using visual indicators of normal ranges rather than endless columns of numbers would improve their interpretation. Improving retrieval and assimilation of existing information on patients can reduce duplication, improve comprehension, provide a more holistic view of the patient, and alert clinicians to potential conflicts in management. Future challenges McDonald CJ. The barriers to electronic medical record systems and how to overcome them. J Am Med Inform Assoc 1997;4: 213-21. Trace D, Naeymi-Rad F, Haines D, Roberts JJS, Almeida FD, Carmony L, Evans M. Intelligent medical record-entry (IMR-E). J Med Syst 1993;17(3/4): 139-51. Gilbert JA. Physician data entry: providing options is essential. Health Data Manag 1998 Sep;6(9): 84-92. Kaplan B. Reducing barriers to physician data entry for computer-based patient records. Top Health Inf Manage 1994;15(1): 24-34. Greenhalgh T. Narrative based medicine in an evidence based world. BMJ 1999;318: 323-5. Kay S, Purves IN. Medical records and other stories: a narratological framework. Methods Inf Med 1996;35: 72-87. Van Ginneken A. The physician's flexible narrative. Methods Inf Med 1996;35(2): 98-100. Frisse ME, Schnase JL, Metcalfe ES. Models for patient records. In: Van Bemmel JH, McCray AT, eds. Yearbook of medical informatics. Stuttgart: Schattauer, 1995: 238-42. Berg M. Medical work and the computer-based patient record: a sociological perspective. Methods Inf Med 1998;37: 294-301. Coiera E. When conversation is better than computation. J Am Med Inform Assoc 2000;7: 277-86. Berg M, Langenberg C, vd Berg I, Kwakkernaat J. Considerations for sociotechnical design: experiences with an electronic patient record in a clinical context. Int J Med Inf 1998;52: 243-51. Powsner SM, Wyatt JC, Wright P. Opportunities for and challenges of computerisation. Lancet 1998;352: 1617-22. Poon A, Fagan LM, Shortliffe EH. The PEN-Ivory project: exploring user-interface design for the selection of items from large controlled vocabularies of medicine. J Am Med Inform Assoc 1996;3: 168-83. Wright P, Jansen C, Wyatt J. How to limit clinical errors in interpretation of data. Lancet 1998;352: 1539-43. Coiera E. Guide to medical informatics, the internet and telemedicine. London: Arnold, 1997: 64. Tang PC, Fafchamps D, Shortliffe EH. Traditional hospital records as a source of clinical data in the outpatient setting. Proceedings of the symposium on computer applications in medical care. Philadelphia: Hanley & Belfus, 1994: 575-9. Van Bemmel J, Musen MA. Handbook of medical informatics. Heidelberg: Springer, 1997: 34. Mitchell E, Sullivan F. A descriptive feast but an evaluative famine: systematic review of published articles on primary care computing during 1980-97. BMJ 2001;322: 1369. Solomon GL, Dechter M. Are patients pleased with computer use in the examination room? J Fam Pract 1995;41: 241-4. Gadd CS, Penrod LE. Dichotomy between physicians' and patients' attitudes regarding EMR use during outpatient encounters. Proceedings of the American Medical Informatics Association symposium 2000. Philadelphia: Hanley & Belfus, 2000: 275-9. Aydin CE, Rosen PN, Jewell SM, Felitti VJ. Computers in the examining room: the patient's perspective. Proceedings of the annual symposium of computer applications in medical care. Philadelphia: Hanley & Belfus, 1995: 824-8. Haidet P, Paterniti DA. "Building" a history rather than "taking" one. Arch Intern Med 2003;163: 1134-40. Rousseau N, McColl E, Newton J, Grimshaw J, Eccles M. Practice based, longitudinal, qualitative interview study of computerised evidence based guidelines in primary care. BMJ 2003;326: 314. Zue V. Talking with your computer. Scientific American 1999 Aug: 40-1. Tange HJ, Dreessen VAB, Hasman A, Donkers HHLM. An experimental electronic medical-record system with multiple views on medical narratives. Comput Methods Programs Biomed 1997;54: 157-72. De Lusignan S, Wells SE, Hague NJ, Thiru K. Managers see the problems associated with coding clinical data as a technical issue whilst clinicians also see cultural barriers. Methods Inf Med 2003;42: 416-22. Brown PJB, Warmington V, Laurence M, Prevost AT. Randomised crossover trial comparing the performance of Clinical Terms Version 3 and Read Codes 5 byte set coding schemes in general practice. BMJ 2003;326: 1127-30. Dougherty GE. "Conventional" dictated versus database-generated discharge summaries: timeliness, quality and completeness. CMAJ 1999;160: 345-6. Goss RM. "Now for something completely different"—a patient's eye view of accessing health records. www.doh.gov.uk/ipu/ahr/hrdg1602.pdf (accessed 24 Jan 2004). The NHS Plan. www.nhsia.nhs.uk/nhsplan/nhsplan.pdf (see 4.21, p 48) (accessed 24 Jan 2004)....查看详细 (18928字节)
☉ 11357071:Cerebral correlates of declarative memory dysfunctions in early traumatic brain injury
1 Department of Psychiatry and Clinical Psychobiology. University of Barcelona, Spain 2 Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain 3 Centre de Diagnòstic per la Imatge (CDI), Hospital Clínic de Barcelona, Barcelona Correspondence to: Dr. Josep M Serra-Grabulosa Department of Psychiatry and Clinical Psychobiology, University of Barcelona, Pg. Vall Hebron 171, 08035 Barcelona, Spain; jmserra@ub.edu ABSTRACT We investigated residual brain damage in subjects who suffered severe traumatic brain injury (TBI) in childhood, and its relationship with declarative memory impairment. Magnetic resonance imaging (MRI) volumetric data and memory performance were compared between 16 adolescents with antecedents of severe TBI and 16 matched normal controls. Volumes of grey matter, white matter, cerebrospinal fluid (CSF), hippocampus, and caudate nuclei were measured. Verbal memory was assessed by the Rey’s Auditory Verbal Learning test and visual memory by the Rey’s Complex Figure. TBI patients performed significantly worse than controls in both verbal and visual memory. Patients presented decreased white matter volume and increased CSF. The hippocampus was reduced, but not the caudate nuclei. Memory performance correlated with CSF. Plasticity is incomplete for structural and functional deficits in children with TBI. Hippocampal atrophy, white matter loss, and memory impairment remain until adolescence. Memory sequelae are related more to diffuse brain injury, as reflected by MRI findings of increased CSF, than to hippocampal injury. Abbreviations: CSF, cerebrospinal fluid; MRI, magnetic resonance imaging; RAVLT, Rey’s Auditory Verbal Learning Test; RCF, Rey’s Complex Figure; TBI, traumatic brain injury Keywords: closed head injury; declarative memory; hippocampus; MRI; TBI One of the most important cognitive sequelae of traumatic brain injury (TBI) is memory impairment.1 Post-mortem neuropathological studies,2 neuroimaging findings,3,4 and data from animal models5,6 have shown that the hippocampus is highly susceptible to the effects of TBI. It seems plausible that the damage to this structure may be responsible for memory impairment in TBI subjects. Several studies have found correlations between memory impairment and hippocampal atrophy.3,4 However, learning deficits in TBI have also been related to striatal reductions7 and fornix damage.8 In children, memory deficits have been explained by frontal lobe damage.9 In the only volumetric study of hippocampal atrophy in paediatric TBI published to date,9 the authors reported negative findings. As the immature brain is more plastic than the adult, and as recent data suggest that the hippocampus is a region with neurogenesis,10,11 it may be that hippocampal damage in TBI may be compensated for to a greater extent if the initial injury occurs during childhood rather than later in life. The purpose of this study was to investigate the cerebral correlates of memory impairment in adolescents who suffered severe traumatic closed brain injury in childhood. METHODS Subjects The TBI sample consisted of 16 subjects (14 boys and 2 girls). The patients were taken from a TBI subsample of patients described elsewhere,12,13 who did not present massive focal lesions. None of the subjects had focal lesions greater than 8.5 cm3 measured by Analyze software (version 3.0) routines. Mean (SD) age of subjects at time of study was 17.88 (2.85) years, age at injury 8.18 (3.65) years, time since injury 9.68 (1.88) years, Glasgow Coma Scale 5.63 (1.78), and coma length 161.25 (132.09) hours. Hypoxia was reported in nine subjects. The control group consisted of 16 subjects matched to patients according to gender (14 boys and two girls), age (16.94 (3.21) years), length of education (11.25 (2.84) years), and parents’ socioeconomic status. All subjects or their parents gave their informed consent and the study was approved by the local ethics committee. Neuropsychological assessment Verbal learning was evaluated using a version of Rey’s Auditory Verbal Learning Test (RAVLT) and visual memory by Rey’s Complex Figure (RCF).14 The measures used were: verbal learning (total number of words remembered in trial, 1–5), verbal long term recall (number of words recalled after a 15 minute interval) and visual recall (3 minutes after copying the RCF). Magnetic resonance imaging study All scans were performed using a General Electric Signa 1.5 Tesla scanner (Milwaukee, WI, USA). A set of coronal images was acquired with a FSPGR 3D sequence (repetition time 12 seconds, echo time 5.2 seconds; TI 300 1 nex; field of view 24x24; and 256x256 matrix. This sequence provides a voxel of 1.2x0.9x0.9 mm3. We obtained 124 contiguous slices. The image data sets were processed on a Sun Solaris Ultra 60 workstation (Sun Microsystems Inc.) with the Analyze software (version 3.0; Mayo Foundation, Rochester, MN, USA). Firstly, the images were resized with the cubic force option to obtain an isotropic voxel (1.2x1.2x1.2 mm3). T1 weighted images were processed with the region of interest (ROI) feature of the Analyze program. ROI tracing was drawn manually. The volume measures were then quantified automatically. A trained operator who was blinded to the subjects’ characteristics traced all measures. Intrarater reliability for volumetric measures was established by performing two analyses of 10 images of another sample, and then calculating the intrarater reliability coefficient, which was initially 0.84. After evaluating the differences, 10 more images were measured; the intrarater reliability coefficient was 0.94 for the hippocampus and 0.95 for the caudate nucleus. For the regional measurements of the hippocampus and caudate nucleus we followed the procedures described by Bigler et al3 and Gunning-Dixon et al.15 Frontal lobe volumes were delimited from T2 weighted MRI axial slices by using the region of interest tool of the MRIcro software (Nottingham, UK), creating an individual frontal mask, which was applied to the images. The basal portion of the lateral fissure delimited inferior–posterior boundaries of the frontal lobes. The presence of the basal ganglia or the frontal horn of the lateral ventricles defined medial surface. Normalised frontal brain images were then automatically segmented into separate images representing probability maps for frontal grey matter, white matter, and CSF using the combined pixel intensity and a priori knowledge approach integrated in the SPM99 software (Wellcome Department of Cognitive Neurology, University College, London, UK), and supplemented by the "lots of inhomogeneity corrections" option. We used an automatic MatLab routine to obtain volumetric measurements of the three frontal tissue compartments mentioned above. Regional brain volumes were corrected for brain size following the covariance estimate method proposed by Jack et al and Free et al.16,17 Finally, the intracranial volume was obtained using the automatic image processing approach integrated in SPM99. We used an automatic MatLab routine to obtain volumetric measurements of the aforementioned three tissue compartments. Total brain measures were obtained by adding the values obtained from white matter, grey matter, and CSF values. The automatic segmentation process used in the present report comprises the whole brain including the cerebellum and the brainstem. RESULTS As all the neuropsychological and MRI variables were normally distributed, we used parametric test: two tailed t test for groups comparisons and Pearson’s test for correlation analysis. Bonferroni correction for multiple comparisons was not applied because the exploratory nature of the study and the reduced sample size examined. TBI subjects performed worse than controls in both visual and verbal learning. We observed a bilateral hippocampal reduction in TBI subjects (fig 1) but not in the caudate nucleus. Moreover, TBI subjects had global brain white matter volume atrophy and frontal white matter atrophy. We also observed CSF volume increase (see table). Figure 1 Right (RH) and left (LH) hippocampal volumes for each subject. Black vertical bars indicate volume means (SE). CTL, control subjects; TBI, traumatic brain injury subjects. Correlation analysis showed that verbal long term recall significantly correlated with CSF (r = –0.54; p = 0.029). The hippocampal volume tended to correlate with visual and verbal long term recall (r = 0.45, p = 0.07; r = 0.43, p = 0.097, respectively). Control subjects did not show any significant correlation. DISCUSSION The purpose of our study was to evaluate the long term brain damage of childhood TBI and the relationship of its effects with declarative memory outcome. Our results showed that TBI subjects had clear hippocampal atrophy but that the caudate nuclei remained intact. We also obtained significant between group differences in measures of global subcortical atrophy such as CSF and white matter, and also in frontal white matter. To our knowledge, this is the first study that demonstrates the persistence of hippocampal atrophy in children with TBI. Previously, Di Stefano et al9 had not shown differences in hippocampal volume between 25 children with severe TBI and 25 with mild TBI. The discrepancies in these results may be due to differences in the age at injury, time since injury, methods for MRI measurements, or characteristics of the control group. However, the presence of hippocampal atrophy on MRI in our study is in agreement with previous neuropathological findings in children with fatal TBI2,18 and the findings of adults with TBI.3,4 Interestingly, despite plasticity mechanisms such as maturation of hippocampal formation from childhood to adulthood,19 and hippocampal neurogenesis and glial proliferation,10,11 our sample showed clear hippocampal atrophy after long term evolution from TBI. These results indicate that plasticity does not completely compensate for hippocampal neuronal loss in severe TBI. As in previous investigations in both children and adults we found white matter volume decrease,8,21 CSF increase,8,20 hippocampal atrophy,3,4 and no differences in caudate nucleus size.7 Our results corroborate previous findings that the hippocampus is more sensitive to TBI effects than the striatum. In the neuropsychological assessment, we also observed persistent memory impairment, a finding that challenges previous reports of the reversibility of cognitive impairment in children.12,13,20,22 In the correlation analysis performed to identify the MRI parameter related to this deficit, the only variable to reach significance was CSF, a measure of global atrophy. The CSF increase may be due to either white or grey matter loss, and both of these may be related to learning deficits, in addition to the possible role of the hippocampal damage. However, this correlation should be interpreted with caution, as we did not use the Bonferroni correction for multiple comparisons. As regards the hippocampus, we only observed a trend towards significance in the correlation analysis. Because of the limbic circuitry involving hippocampal output, a number of white matter pathways may be damaged in traumatic brain injury and may be responsible for TBI memory sequelae. In addition to the diffuse white matter volume loss, there is probably white matter loss in the fornix, mammillothalamic track, and anterior thalamus projections to cortex and cingulate gyrus, which may be just as disruptive to memory as a specific hippocampal volume loss.4,8 Finally, this study has several limitations. The sample size precluded a regression analysis searching for contributors to memory loss. We did not measure the fornix, which may be involved in memory impairment in childhood TBI,4 and the neuroimaging tool we used to perform the brain segmentations, SPM, has several limitations in brain damaged subjects.23 Nonetheless, we think that the results obtained can contribute to increasing the knowledge of the brain–behaviour relationship in TBI occurring in the immature brain. Table 1 Neuropsychological and volumetric (mm3) measures in control and TBI subjects ACKNOWLEDGEMENTS This study was supported by grants from the Spanish Ministry of Education and Culture (DGICYT PM-98-0192), and the General Direction of Research from the Generalitat de Catalunya (1999SGR00081 and 2001SGR00139). REFERENCES Bigler. ed. Brain imaging and behavioral outcome in traumatic brain injury. J Learn Dis 1996;29:515–30. Kotapka MJ, Graham DI, Adams JH, et al. Hippocampal damage in fatal paediatric head injury. Neuropath Appl Neurol 1993;19:128–33. Bigler ED, Blatter DD, Anderson CV, et al. Hippocampal volume in normal aging and traumatic brain injury. Am J Neuroradiol 1997;18:11–23. Tate DF, Bigler, eds. Fornix and hippocampal atrophy in traumatic brain injury. Learn Memory 2000;7:442–6. Kotapka MJ, Gennarelli TA, Graham DI, et al. Selective vulnerability of hippocampal neurons in acceleration-induced experimental head injury. J Neurotraum 1991;8:247–58. Hicks RR, Smith DH, Lowenstain DH, et al. Mild experimental brain injury in the rat induces cognitive deficits associated with regional neuronal loss in the hippocampus. J Neurotraum 1993;10:405–14. Primus EA, Bigler ED, Anderson CV, et al. Corpus striatum and traumatic brain injury. Brain Injury 1997;11:577–86. Gale SD, Johnson SC, Bigler ED, et al. Nonspecific white matter degeneration following traumatic brain injury. J Int Neuropsych Soc 1995;1:17–28. Di Stefano G, Bachevalier J, Levin HS, et al. Volume of focal brain lesions and hippocampal formation in relation to memory function after closed head injury in children. J Neurol Neurosurg Psych 2000;69:210–16. Eriksson PS, Perfilieva E, Bjork-Eriksson T, et al. Neurogenesis in the adult human hippocampus. Nat Med 1998;4:1313–17. Gould E, Reeves AJ, Fallah M, et al. Hippocampal neurogenesis in adult old world primates. Proc Natl Acad Sci USA 1999;96:5263–7. Verger K, Junqué C, Jurado MA, et al. Age effects on long-term neuropsychological outcome in paediatric traumatic brain injury. Brain Injury 2000;14:495–503. Verger K, Junqué C, Levin H, et al. Correlation of atrophy measures on MRI with neuropsychological sequelae in children and adolescents with traumatic brain injury. Brain Injury 2001;15:211–21. Lezak M. Neuropsychological Assessment. Oxford: Oxford University Press, 1995. Gunning-Dixon FM, Head D, McQuain J, et al. Differential aging of the human striatum: a prospective MR imaging study. Am J Neuroradiol 1998;19:1501–7. Jack CR, Tworney CK, Zinsmeister AR, et al. Anterior temporal lobes and hippocampal formations: normative volumetric measurements from MR images in young adults. Radiology 1989;172:549–54. Free SL, Bergin PS, Fish DR, et al. Methods for normalization of hippocampal volumes measured with MR. Am J Neuroradiol 1995;16:637–43. Kotapka MJ, Graham DI, Adams JH, et al. Hippocampal pathology in fatal human head injury without high intracranial pressure. J Neurotraum 1994;11:317–24. Benes FM, Turtle M, Khan Y, et al. Myelination of a key relay zone in the hippocampal formation occurs in the human brain during childhood, adolescence, and adulthood. Arch Gen Psychiat 1994;51:477–84. Berryhill P, Lilly MA, Levin HS, et al. Frontal lobe changes after severe diffuse closed head injury in children: a volumetric study of magnetic resonance imaging. Neurosurgery 1995;37:392–400. Blatter DD, Bigler ED, Gale SD, et al. MR-based brain and cerebrospinal fluid measurement after traumatic brain injury: correlation with neuropsychological outcome. Am J Neuroradiol 1997;18:1–10. Levin HS, Culhane KA, Mendelsohn D, et al. Cognition in relation to magnetic resonance imaging in head-injured children and adolescents. Arch Neurol 1993;50:897–905. Good CD, Johnsrude IS, Ashburner J, et al. A voxel-based morphometric study of ageing in 465 normal adult human brains. Neuroimage 2001;14:21–36....查看详细 (16301字节)
☉ 11357072:Handheld computers
1 National Institutes of Health, Bethesda, MD 20814, USA mo@mo.md Introduction Handheld computers have brought important advantages. With a few taps on the screen, for example, you can convert an appointment for Tuesday's outpatients clinic to an outpatients appointment for every Tuesday of this year (this is much quicker than using a paper diary). Ticking off a task hides it from the handheld computer's screen, leaving a tidy, shorter list of tasks for completion; a house officer's paper list of tasks becomes increasingly messy and illegible as tasks are added, amended, and crossed out. I can scribble a note on my handheld almost as fast as scribbling a note on a piece of paper; finding that note on my handheld computer takes a few seconds, but finding that piece of paper after a year is far more difficult. The device also brings up related notes, tasks, addresses, and appointments. Summary points Handheld computers are suited to clinical practice because they are small, affordable, and easy to use; can read handwriting; and have a long battery life They can run a wide range of medical software The devices support clinical teamwork by making it easy to share information with other clinicians' PCs and handheld computers Ensuring security of your patients' data is vital and requires some effort Make sure your budget includes money for software, textbooks, and hardware expansions For many doctors the organiser functions alone have been sufficient justification for buying a handheld computer. Others like using custom designed medical software such as PatientKeeper (www.patientkeeper.com) to keep track of patient records. In the United Kingdom, companies such as EMIS and Torex have handheld computer versions of their software to complement the PC versions (fig 1). Fig 1 Torex produces software for keeping track of patients' records Other software, such as ePocrates Rx (www.epocrates.com), can support prescribing decisions. It is a quick reference of all licensed drugs in the United States and can identify drug interactions.1 Liability insurance companies and governments have understood the potential of the ePocrates Rx. MedAmerica Mutual, for example, provided clinicians with devices running the software (www.medamericamutual.com/news/epocrates.html) because it believed that this would reduce clinical errors. Last year, the US government ran a three month trial with ePocrates DocAlert to provide clinicians with updates on bioterrorism (www.healthcare-informatics.com/issues/2003/01_03/ortiz.htm). In Britain, a handheld computer version of the BNF (the British National Formulary) has been developed by the Swedish company MedHand (www.medhand.com) (fig 2). MedHand's software also includes reference textbooks such as the Oxford Handbook of Clinical Medicine. American publishers such as Franklin (www.franklin.com/medical), Lippincott Williams & Wilkins (www.lwww.com), and Skyscape (www.skyscape.com) have long provided clinical textbooks for a range of specialties and experience levels, and the BMJ Bookshop sells many of these (www.bmjbookshop.com/shop/Collection_Display.asp?CollectionId=%400000005502). Fig 2 Software for the BNF is available for handheld computers Furthermore the improving internet connectivity of handheld computers is improving the contribution they can make to evidence based medicine. Last year, for example, the National Library of Medicine customised PubMed (http://certif.nlm.nih.gov:8080/nlm and http://archive.nlm.nih.gov/proj/pmot/pmot.php) for handheld computers. Sites such as the University of Toronto's Centre for Evidence-Based Medicine provide software for evidence based medicine that is customised for handheld computers. The customisation by Info-POEMs (www.infopoems.com) for handheld computers is well thought out. Its creators provide the POEM ("patient oriented evidence that matters") section in the BMJ, and the software also includes Cochrane Database abstracts and diagnostic test calculators. But the devices really come into their own when you start storing your own local data using databases. At its most basic, a database form looks like a paper form, and a database table stores data in the way a filing cabinet does. Handheld computers allow you to have the right form wherever you need it. Furthermore, software such as HanDBase (www.handbase.com) can speed up completion of forms, for example, by providing a list of ward names. But it is searches that show the biggest advantage of databases—for example, searching a table to identify patients in a particular age range takes only a few seconds. Team work Your biggest worry should be security. Like a PC, a handheld computer's default method for storing data is easily accessible, but unlike a PC, theft or loss of the device is also easy. The easiest way to ensure that sensitive data do not get into the wrong hands is not to store any sensitive data. Keeping a logbook, for example, of all the operations that you carry out is useful for your audits and college membership, but you should not need to store the patients' names and dates of births. If you must store sensitive data, use software that encrypts the data—for example, eWallet (www.iliumsoft.com) allows safer storage of passwords and details of membership and credit cards. HanDBase also has encryption features that you can switch on. And medical record software, such as Pocket Torex, includes encryption. Insist on it when choosing software for dealing with patients' data. Encryption does not solve all problems, however. Synchronising with a PC, for example, means that a copy of the data is stored on the PC, so you must ensure that the PC is secured. And beaming to a handheld means a copy of the data is stored on someone else's handheld, so that handheld must also be secured, and that person must understand security. Your organisation's computer experts are usually helpful and always necessary in matters of security. A more subtle problem comes from the assumption that handheld computers are the same as PCs. Instead, you should think of them as two different surgical instruments. Each is good at handling one part of the operation, but not others. Handheld computers are not good, for example, for writing a lengthy patient history (a PC's keyboard is faster). Nor should you use the device for looking at x rays films (a PC's screen gives you the full picture at a high resolution). But a handheld's portability means that you can read the radiologist's report or dictate your response while you are with the patient. And its simplicity means that ordering an investigation is faster than finding the paper form or an available PC. Furthermore the battery life and responsiveness of handhelds are better than with laptops and tablet PCs (similar to laptops but the user can "write" on the screen), and suited to the continuous interruptions and lengthy shifts of clinical practice. Buying a device In the United States, for $200 (￡113; 169), you can buy a brand new handheld computer that handles all modern clinical software, comes with organiser software, and reads and writes Microsoft Word files. However, you can get by with cheaper or older devices. In Britain, a typical price for a new handheld is ￡120. Handheld computers are useful for accessing and storing data and are easy to carry around Websites for further information www.doctorsgadgets.com—Complete reviews on the latest handheld computers and medical software www.pdaconsult.co.uk/bbs/index.php—UK forum for handheld computing in medicine www.handango.com—Guide and shop for new software. Browse and try before you buy from their secure shop http://pbrain.hypermart.net—The latest news and views on using your Palm Powered device www.medicalpocketpc.com—The latest news and views on using your Pocket PC. A small team of US junior doctors keeps the site fresh and entertaining http://denison.uchsc.edu/evidence_based.html—Includes a good a list of evidence based medicine resources for handheld computers www.handheldsfordoctors.com/book/text/chapter11.htm—Guide to handheld computer software that is suitable for patients One thing that you cannot compromise on is the operating system of the device. This determines what software you can use, which in turn determines how useful the device can be to you. Only devices with the Palm Powered or Pocket PC logos can run the major clinical software, so you should not consider other devices even if they are cheaper or have more impressive hardware. One notable exception is Research In Motion's BlackBerry range of handheld computers (www.blackberry.com). Clinicians like the devices because they provide instant notification of and access to new email messages. IT administrators like the devices because they are easier to administer and secure. However, only a few clinical software applications are available for them (although these do include the excellent Johns Hopkins Antibiotic Guide (http://hopkins-abxguide.org/download_center/learn_to_use.cfm?device=rim&section=pathogen), and clinical software providers are standardising on the Palm Powered and Pocket PC devices. Some software only runs on one type of device—for example, users of EMIS software need a Palm Powered device, while Torex customers need a Pocket PC. But most of the important software products, such as HanDBase, run equally well on both devices. The BNF currently runs on Palm Powered devices made by PalmOne (but not those made by Sony), although a Pocket PC version is planned for release by 2005. There are several features to look out for in the hardware. In the United States, the $200 devices all have bright colour screens for clarity. The screen's pixels affect how much text you can read at one time. Pocket PCs have 240x320 pixels, while a top of the range Palm Powered device has 480x320 pixels. The RAM represents the amount of information that the device can store at any one time, and Pocket PCs tend to have more RAM than other devices. Finally, some models have a built-in camera or phone, or both. In one ongoing clinical trial, paramedics are using these features to provide advance notification to hospital staff from accident scenes. You must budget for other spending too for your handheld computer. Textbooks and software can cost a lot of money—most textbooks in the United States cost at least $60. Textbooks often require an expansion card for storage. Finally, you may find an expandable keyboard useful—this folds to the same pocket size as the handheld but unfolds to match a full size keyboard. Contributors and sources: The information collected in this article is based on over five years' experience I have had with handheld computers, setting up projects, and working with fellow experts in use of handheld computers. The projects include Medical Approaches, a free medical textbook for handheld computers (www.medicalapproaches.org), Project Palm at Cambridge University (www.caret.cam.ac.uk/projects/palm.htm), and working at the Queen Elizabeth Hospital, in King's Lynn. I subsequently wrote the book Handheld Computers for Doctors and continue to develop handheld computer solutions (www.handheldsfordoctors.com). Funding: None. Competing interests: I own the website Handheldsfordoctors.Com. It sells my book and handheld computers. I receive a commission from sales through my site, and from sales of my book. I work at the National Library of Medicine, which created the handheld computer versions of PubMed mentioned in this article....查看详细 (11741字节)
☉ 11357073:Verapamil induced gingival enlargement in cluster headache
1 Headache Group, Institute of Neurology, Queen Square, London, UK 2 Department of Neurology, Leiden University Medical Centre, the Netherlands Correspondence to: Professor P J Goadsby Institute of Neurology, Queen Square, London WC1N 3BG, UK; peterg@ion.ucl.ac.uk ABSTRACT Verapamil is an effective prophylactic treatment for cluster headaches and, therefore, is widely used. This report describes four patients with cluster headache who developed gingival enlargement after initiating treatment with verapamil. In two patients, it was possible to control this side effect adequately by optimising oral hygiene and dental plaque control. In the other two patients, lowering of the verapamil dose, in addition to optimal oral hygiene and dental plaque control, was necessary; in one patient verapamil had to be stopped completely to reverse the gingival enlargement. Doctors treating cluster headache with verapamil need to be aware of this side effect, especially as it may be preventable with good dental hygiene and dental plaque control, is reversible with reduction or cessation of verapamil, and can lead to dental loss. Keywords: headache; cluster headache; verapamil Cluster headache is an excruciating form of primary headache.1,2 Its management includes treatment with abortive and preventive agents.3 Sumatriptan (subcutaneous 6 mg4 and intranasal 20 mg5) and high dose, high flow rate oxygen6 are effective abortive agents in most patients. Several drugs, including verapamil,7,8 methysergide,9 lithium,8 and corticosteroids,10 are reported to be effective in the preventive treatment of cluster headache. Verapamil is an effective preventive agent in both episodic and chronic cluster headache. In an open trial employing verapamil at doses of 240–600 mg daily in episodic cluster headache and 120–1200 mg daily in chronic cluster headache, an improvement of more than 75% was noted in 33 of 48 (69%) patients.7 A recent double blind, placebo controlled, parallel group trial evaluated the efficacy of verapamil 360 mg daily over a two week period in 26 patients with cluster headache. The study showed a statistically significant reduction in the frequency of the headaches and the consumption of analgesics in the patients treated with verapamil.11 Verapamil dosages commonly employed range from 240 mg to 960 mg daily in divided doses.3 In chronic cluster headaches, patients who respond to verapamil are often continued on it indefinitely, and it is generally well tolerated. Constipation is the commonest side effect, although hypotension, conduction defects, bradycardia, ankle oedema, nausea, and fatigue may also occur.12,13 We report four patients with cluster headache who were treated with verapamil and, consequently, developed gingival enlargement. We describe the management of this adverse effect in our patients and discuss what general measures can be taken to minimise gingival enlargement in patients in whom long term verapamil therapy is being considered. CASE REPORTS Case 1 A 32 year old woman developed intermittent daily headaches in 1997 for which she was referred the following year. She was diagnosed as having chronic cluster headache. Her medications included subcutaneous sumatriptan 6 mg prn (when required), which abbreviated the attack, and sodium valproate. In the past she had tried methysergide, sumatriptan tablets 100 mg prn and ergotamine tablets 2 mg prn, all of which were completely ineffective. Sodium valproate was discontinued and the patient started on verapamil, the dose of which was gradually increased to 760 mg daily under regular electrocardiogram (ECG) monitoring. There was a marked improvement with verapamil, resulting in a significant reduction in the frequency, duration, and severity of the cluster attacks. The only side effects she initially reported were mild constipation, lethargy, and ankle oedema. About three months after starting verapamil she noticed that her interdental papillae had enlarged. A further three months later she saw a dentist who diagnosed gingival enlargement secondary to verapamil. However, as verapamil had dramatically improved the cluster headaches, the patient was reluctant to discontinue it. Dental plaque was removed by scaling and the patient was advised to maintain good oral hygiene. Over the next 18 months, despite regular professional dental care, the gingival enlargement continued to worsen gradually, with development of generalised nodular swelling and encroachment of the crowns of the adjacent teeth. In addition, the patient reported intermittent bleeding from the gums, especially after meals. In May 2000, she was persuaded to try other cluster headache preventive agents, while continuing verapamil. She had trials of lithium 400 mg twice daily and topiramate 200 mg twice daily, with which there was no improvement. During this period, the gingival enlargement continued to worsen and, in addition, the patient began to complain of discomfort from her teeth, especially when eating and looseness of the upper incisors. In January 2001, a course of intravenous dihydroergotamine 9 mg over three days was administered with dramatic improvement. The patient now had only two to four cluster attacks per week with each attack lasting only about 15–30 minutes. Verapamil and lithium were stopped without any deterioration in the cluster headaches. Over the next three months, the gingival enlargement, gum bleeding, and dental discomfort and looseness of teeth resolved completely. Case 2 A 40 year old man developed cluster headaches in 1992 for which he was referred in June 2001. He was diagnosed as having chronic cluster headache. His medications included subcutaneous sumatriptan 6 mg prn, high dose and flow rate oxygen, verapamil 240 mg daily, sodium valproate 600 mg daily, lithium 300 mg daily, ergotamine tablets 2 mg daily, methysergide 1 mg daily, and prednisolone 10 mg daily. Subcutaneous sumatriptan and oxygen were effective, abbreviating the attacks to 15–30 minutes. The combination of verapamil, sodium valproate, lithium, ergotamine, methysergide, and prednisolone was ineffective in suppressing the cluster attacks. The patient had started verapamil in December 2000. In the past he had tried indometacin 150 mg daily and amitriptyline. Sodium valproate, lithium, and prednisolone were discontinued. The verapamil dose was gradually increased to 600 mg daily under regular ECG monitoring over two months; there was mild improvement in the cluster headaches. He was then seen elsewhere and lithium 600 mg daily, methysergide 2 mg daily, and prednisolone 15 mg daily were added. In addition, the patient was administered intravenous dihydroergotamine (IV DHE) 17.5 mg over seven days; he was rendered pain free while receiving the IV DHE but the attacks recurred within a day of stopping the infusion. There was no added benefit with this combination of drugs. He consulted again in September 2001, when he was advised to stop lithium, methysergide, and prednisolone. The verapamil dose was increased to 720 mg daily, which completely suppressed the cluster attacks. Unfortunately, two months later the patient noticed gingival enlargement with intermittent bleeding. We advised him to reduce the verapamil dose to 480 mg daily and to see a periodontist. The periodontist diagnosed gingival enlargement secondary to verapamil; the patient was advised to maintain good dental hygiene and given a course of antibiotics for possible infection, although there was no evidence for this. On reducing the verapamil dose, the cluster attacks recurred but, over the next two months, the gingival enlargement resolved completely. Interestingly, in May 2002, he took 1 g of "magic mushrooms" (containing psilocybin) which rendered him pain free for one month; since then he has been taking magic mushrooms 1 g once every one to two months, which renders him pain free for two to six weeks. He continues to take verapamil 480 mg daily and has no gingival problems. Case 3 A 37 year old man developed intermittent daily headaches in 1996 for which he was referred to our clinic and was diagnosed as having chronic cluster headache. In the past he had taken sumatriptan tablets 100 mg prn, pizotifen, atenolol, amitriptyline, carbamazepine, indometacin 50 mg three times daily, paroxetine, and diazepam, none of which produced any benefit. The patient was started on verapamil, the dose of which was increased to 400 mg daily under ECG monitoring over one month. Verapamil 400 mg daily completely suppressed the cluster headaches. He reported no side effects. Reduction of the verapamil dose led to recurrence of the headaches. One year after starting verapamil, the patient noted the onset of gingival enlargement. Two months later, he developed bleeding from the gums, especially after meals and when brushing his teeth; in addition, the gingival enlargement continued to worsen gradually. A further two months later, he began to complain of discomfort from his teeth when eating. He then saw a dentist who diagnosed gingival enlargement secondary to verapamil. Dental plaque was removed and the patient was advised to maintain good oral hygiene by thoroughly brushing his teeth twice a day and rinsing his mouth with plain water after each meal. The possibility of substituting verapamil with another cluster headache preventive agent was raised but the patient declined the offer. Over the next six months all the dental symptoms gradually resolved. Case 4 An 18 year old man developed intermittent daily headaches at the age of 12 years for which he was referred in 1999. His medications included subcutaneous sumatriptan 6 mg prn, indometacin 25 mg four times daily, and amitriptyline 75 mg once daily. Subcutaneous sumatriptan aborted the headache within five minutes. Indometacin and amitriptyline were ineffective. In the past, he had tried prednisolone 60 mg daily, verapamil 240 mg daily, diltiazem 180 mg daily, and propranolol 160 mg daily. The headaches were completely suppressed by prednisolone 60 mg daily but recurred when the dose was reduced. Verapamil 240 mg, diltiazem, and propranolol were completely ineffective. A diagnosis of chronic cluster headache was made. Indometacin and amitriptyline were stopped. The patient was started on verapamil, the dose of which was gradually increased to 480 mg daily under regular ECG monitoring. Verapamil 480 mg daily completely suppressed the cluster attacks. In February 2000, a few days after the patient In April 2000, he had a syncopal episode during which he lost consciousness for a few minutes. The cardiologists advised the patient to reduce the verapamil dose to 480 mg daily while he was being investigated for a cardiac abnormality. The cluster headaches recurred on reducing the verapamil dose. Lithium carbonate 600 mg daily was started and the dose gradually titrated to 1200 mg daily, under serum lithium level monitoring. This combination of verapamil and lithium completely suppressed the cluster attacks. Subsequently, 24 hour ECG monitoring, exercise stress test, and an echocardiogram were reported to be normal. The option of monotherapy with verapamil was raised but the patient chose to continue taking verapamil and lithium as the combination was very effective. In September 2001, the patient reported mild discomfort from his teeth and intermittent bleeding from the gums, especially when eating. He had noticed that he had moderate gingival enlargement, although he remarked that the gingival enlargement had probably been present for several months, but he had paid little notice to it. He had prominent interdental papillae and moderate generalised nodular swelling. He saw a dentist in November 2001 who diagnosed gingival enlargement. Dental plaque was removed and the patient was advised to maintain good oral hygiene. The dental symptoms gradually regressed over the ensuing six months. DISCUSSION Gingival enlargement or overgrowth is a side effect associated with the administration of several drugs. These drugs can be basically divided into three groups: anticonvulsants, the immunosuppressant ciclosporin, and calcium channel blockers. Recent therapeutic trends in the treatment of, particularly chronic, cluster headache14 have led to more widespread use of very high doses of the medicine, up to 960 mg daily, to be used more commonly.15 Our cases illustrate that verapamil can produce gum enlargement and given the exceptional doses of the medicine used in neurological practice it seems important to be aware of this problem and of its management. Of the calcium channel blockers, the commonest agent associated with the development of gingival enlargement is nifedipine,16,17 though similar problems have been associated with the administration of verapamil,18–20 felodipine,21 nitrendipine,22 diltiazem,23 and amlodipine.23 The incidence of verapamil induced gingival hyperplasia is poorly defined. The only study that has addressed this issue identified one patient with gingival enlargement out of 24 dentate patients who used verapamil for more than one year, giving an incidence of 4.2%.19 This is lower than the 14–83% reported incidence of nifedipine induced gingival enlargement.16,24,25 Currently, the aetiology of drug induced gingival enlargement is not entirely understood, but it is clearly multifactorial. Some of the known risk factors include: presence of gingival inflammation (gingivitis due to poor oral hygiene); presence of dental plaque; and the dose and duration of drug therapy.26–28 Gingival enlargement may cause significant morbidity because it poses an oral hygiene and dental plaque control problem; the tooth discomfort may affect mastication; it may alter tooth eruption; it may interfere with speech; and it may cause aesthetic concerns.29 The term "gingival hyperplasia" is inappropriate because enlargement does not result from an increase in the number of cells but rather an increase in extracellular tissue volume with an inflammatory infiltrate of predominantly B lymphocytes.30 Histologically, in verapamil induced gingival enlargement there is highly vascular connective tissue, acanthotic and thickened epithelium with long rete pegs containing dyskeratotic pearls, and varying amounts of subepithelial inflammatory infiltrate.20 The histological picture is strikingly similar to that caused by phenytoin, ciclosporin, and other calcium channel antagonists. The mechanism by which drug induced gingival enlargement occurs is not well understood and may be distinct for each drug. Cell culture studies on gingival fibroblasts from a patient with verapamil induced gingival overgrowth and from control cells obtained from healthy gingiva suggest that verapamil affects the proliferation of selected fibroblasts subpopulations and alters the balance between regeneration and degradation.20 In the treatment of drug induced gingival enlargement, the first consideration should be given to the removal of local factors. The clinician should emphasise the importance of dental plaque control. Although the exact role played by dental plaque in drug induced gingival enlargement is unclear, there is evidence that good oral hygiene and frequent professional removal of plaque decreases the degree of gingival enlargement present and improves overall gingival health.31 The possibility of discontinuing the offending drugs or of changing the medication should be raised.32 Discontinuation of the drug usually results in complete regression of the gingival overgrowth. The options of discontinuing or substituting the medication should be examined in conjunction with the patient. Simple discontinuation of the offending agent is usually not a practical option but replacing it with another medication might be. If the non-surgical approach is not effective, periodontal surgery in the form of gingivectomy or periodontal flap procedures can effectively reduce the enlarged gingival tissues.29 We have described four cases of patients with cluster headache who were treated with verapamil and subsequently developed gingival enlargement. The gingival enlargement was first noted at between three months and two years of starting verapamil. In cases 3 and 4, it was possible to reverse the gingival enlargement with optimum oral hygiene and dental plaque control, without altering the verapamil dose. In case 2, good oral hygiene and dental plaque control together with alterations in the verapamil dose were required to adequately control the gingival symptoms. In case 1, the symptoms were progressive despite good oral hygiene and dental plaque control; verapamil had to be stopped to reverse the symptoms. These case reports highlight the importance of appreciating that verapamil can cause gingival overgrowth. Patients being considered for treatment with verapamil should be made aware of this potential side effect and encouraged to maintain meticulous oral hygiene. They should be advised to regularly consult an oral medicine specialist for control of dental plaque and monitoring for oral complications associated with gingival enlargement such as the gingivitis, bleeding gums, and loosening of teeth. In patients who develop gingival enlargement, it should be borne in mind that the gingival symptoms may be controlled successfully, even under the continuous administration of verapamil, by meticulous individual and professional oral hygiene. If this is not effective, then the verapamil dose can be reduced or the drug stopped completely. The surgical options should only be considered as a last resort in patients responsive to verapamil and unresponsive to other cluster headache preventive treatments in whom newer surgical approaches cannot be easily or appropriately considered.33 REFERENCES Headache Classification Committee of The International Headache Society. Classification and diagnostic criteria for headache disorders, cranial neuralgias and facial pain. Cephalalgia 1988;8 (suppl 7) :1–96. Headache Classification Committee of The International Headache Society.The International Classification of Headache Disorders, 2nd edn. Cephalalgia 2004;24 (suppl 1) :1–160. Dodick DW, Rozen TD, Goadsby PJ, et al. Cluster headache. Cephalalgia 2000;20:787–803. Ekbom K, The Sumatriptan Cluster Headache Study Group. Treatment of acute cluster headache with sumatriptan. N Engl J Med 1991;325:322–6. van Vliet JA, Bahra A, Martin V, et al. Intranasal sumatriptan is effective in the treatment of acute cluster headache—a double-blind placebo-controlled crossover study. Cephalalgia 2001;21:270–1. Fogan L. Treatment of cluster headache: a double blind comparison of oxygen vs air inhalation. Arch Neurol 1985;42:362–3. Gabai IJ, Spierings ELH. Prophylactic treatment of cluster headache with verapamil. Headache 1989;29:167–8. Bussone G, Leone M, Peccarisi C, et al. Double blind comparison of lithium and verapamil in cluster headache prophylaxis. Headache 1990;30:411–17. Curran DA, Hinterberger H, Lance JW. Methysergide. Res Clin Stud Headache 1967;1:74–122. Jammes JL. The treatment of cluster headaches with prednisone. Dis Nerv Syst 1975;36:375–6. Leone M, D’Amico D, Attanasio A. Verapamil is an effective prophylactic for cluster headache: results of a double-blind multicentre study versus placebo. In: Olesen J, Goadsby PJ, eds. Cluster Headache & Related Conditions. Oxford: Oxford University Press, 1999:296–9. Thulin T. Calcium antagonists—assessments of side effects. Scan J Prim Health Care 1990;1:81–4. Dougall HT, McLay J. A comparative review of the adverse effects of calcium antagonists. Drug Saf 1996;15:91–106. Olesen J, Goadsby PJ. Cluster headache and related conditions. In: Olesen J, ed. Frontiers in Headache Research. Oxford: Oxford University Press, 1999;9. Matharu MS, Boes CJ, Goadsby PJ. Management of trigeminal autonomic cephalalgias and hemicrania continua. Drugs 2003;63:1637–77. Barclay S, Thomason JM, Idle JR, et al. The incidence and severity of nifedipine-induced gingival overgrowth. J Clin Periodontol 1992;19:311–14. Bullon P, Machuca G, Martinez-Sahuquillo A, et al. Evaluation of gingival and periodontal conditions following causal periodontal treatment in patients treated with nifedipine and diltiazem. J Clin Periodontol 1996;23:649–57. Mehta AV, Chidambaram B, O’Riordan AC. Verapamil-induced gingival hyperplasia in children. Am Heart J 1992;124:535–6. Miller CS, Damm DD. Incidence of verapamil-induced gingival hyperplasia in a dental population. J Periodontol 1992;63:453–6. Pernu HE, Oikarinen K, Hietanen J, et al. Verapamil-induced gingival overgrowth: a clinical, histologic, and biochemical approach. J Oral Pathol Med 1989;18:422–5. Lombardi T, Fiore-Donno G, Belser U, et al. Felodipine-induced gingival hyperplasia: a clinical and histologic study. J Oral Pathol Med 1991;20:89–92. Brown RS, Sein P, Corio R, et al. Nitrendipine-induced gingival hyperplasia. First case report. Oral Surg Oral Med Oral Pathol 1990;70:593–6. Bullon P, Machuca G, Martinez Sahuquillo A, et al. Clinical assessment of gingival size among patients treated with diltiazem. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1995;79:300–4. Barak S, Engelberg IS, Hiss J. Gingival hyperplasia caused by nifedipine. Histopathologic findings. J Periodontol 1987;58:639–42. Slavin J, Taylor J. Cyclosporin, nifedipine, and gingival hyperplasia. Lancet 1987;2:739. Nuki K, Cooper SH. The role of inflammation in the pathogenesis of gingival enlargement during the administration of diphenylhydantoin sodium in cats. J Periodontal Res 1972;7:102–10. O’Neil TC, Figures KH. The effects of chlorhexidine and mechanical methods of plaque control on the recurrence of gingival hyperplasia in young patients taking phenytoin. BDJ 1982;152:102–10. Fu E, Nieh S, Chang HL, Wang SL. Dose-dependent gingival overgrowth induced by cyclosporin in rats. J Periodontol 1995;66:594–8. Camargo PM, Melnick PR, Pirih FQ, et al. Treatment of drug-induced gingival enlargement: aesthetic and functional considerations. Periodontology 2000;27:131–8. Bullon P, Machuca G, Armas JR, et al. The gingival inflammatory infiltrate in cardiac patients treated with calcium antagonists. J Clin Periodontol 2001;28:897–903. Dongari A, McDonnell HT, Langlais RP. Drug-induced gingival overgrowth. Oral Surg Oral Med Oral Pathol 1993;76:543–8. Harel-Raviv M, Eckler M, Lalani K, et al. Nifedipine-induced gingival hyperplasia. A comprehensive review and analysis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1995;79:715–22. Leone M, Franzini A, Bussone G. Stereotatic stimulation of the posterior hypothalamic gray matter in a patient with intractable cluster headache. N Engl J Med 2001;345:1428–9....查看详细 (23071字节)

☉ 11357074:Critical care medicine mailing list: growth of an online forum
1 Bartimus, Frickleton, Robertson & Obetz, 200 Madison, Suite 1000, Jefferson City, MO 65101, USA, 2 Department of Critical Care Medicine, University of Pittsburgh Medical Center, 646B Scaife Hall, 3550 Terrace Street, Pittsburgh, PA 15261, 3 Faculty of Medicine, Imperial College, London W12 0NN, 4 Department of Critical Care Medicine, Auckland City Hospital, Private Bag 92-024, Auckland 1003, New Zealand Correspondence to: S R Gunn gunnsr@ccm.upmc.edu Introduction Because of its accessibility, the list has given voice to a diverse group of multidisciplinary healthcare providers for the first time. This networking potential facilitates the reinforcement of similar ideas and standards of practice. Other unforeseen applications have developed. During the recent outbreak of severe acute respiratory syndrome (SARS) in Asia, list members initially broke the emerging story from Hong Kong in real time.2 The list has produced other tangible results. Crippen and others recently published the first multinational reference on end of life care using list members as resources.3 We have identified six peer reviewed articles that have resulted from interactions on the list.4-9 Difficulties associated with information sharing Online mail resources continue to grow. Future directions might encompass multinational databases for evaluating new treatments or reporting critical incidents. As these online services grow, critical evaluation and validation of opinions may be necessary. Other possibilities for educational development might include virtual conferences, workshops, or the rotation of list members between different geographical areas. The Critical Care Medicine Listserv can be found at www.pitt.edu/~crippen. All the authors are members of the list. Contributors: All authors collaboratively conceived the idea for the article; SRG, PH, and ALDeW did the literature search; and ALDeW, PH, and SS wrote the article. SRG is the guarantor. Funding: No special funding. Competing interests: None declared. References Crippen D. Critical care and the internet. A clinician's perspective. Critical Care Clinics 1999;15: 605-14. A doctor in Hong Kong deals with SARS. 30 April 2003. www.abc.net.au/abcasiapacific/focus/stories/s847149.htm (accessed 24 Apr 2004). Crippen D, Kilcullen J, Kelly D, eds. Three patients—international perspective on intensive care at the end of life. Boston: Kluwer Academic, 2002. Nagappan R, Riddell T. Pyridoxine therapy in a patient with severe hydrazine sulfate toxicity. Crit Care Med 2000;28: 2116-8. Campbell D, Steinmann M, Porayko L. Nitric oxide and high frequency jet ventilation in a patient with bilateral bronchopleural fistulae and ARDS. Can J Anaesth 2000;47(1): 53-7. Porayko LD, Butler R. Perioperative resuscitation knowledge base. Can J Anaesth 1999;46: 529-35. Porayko LD, Gelb A. Antihypertensive therapy in stroke patients. Eur J Anaesth 1998;15(suppl): 48-9. Hopkins P, Sriskandan. S. Gram-positive bacterial infection in severe sepsis. Clin Intensive Care 2002;13: 147-60. Cassell J, Buchman TG, Streat S, Stewart RM. Surgeons, intensivists, and the covenant of care: administrative models and values affecting care at the end of life. Crit Care Med 2003;31: 1551-7. Caldicott Committee. Report on the review of patient-identifiable information. London: NHS Executive, 1997. Adams v Via Christi Regional Medical Center . In: Kansas Reporter: 824. Kansas Supreme Court. Wild MD v Rarig . In: Northeastern Reporter: 775. 2nd ed. Minnesota Supreme Court....查看详细 (3635字节)
☉ 11357075:The – 148 C/T fibrinogen gene polymorphism and fibrinogen levels in ischaemic stroke: a case–control study
1 Department of Neurology, Erasmus Medical Centre Rotterdam, Rotterdam, Netherlands 2 Department of Haematology, Erasmus Medical Centre Rotterdam Correspondence to: Dr Mary-Lou P J van Goor Erasmus MC Rotterdam, Department of Neurology, PO Box 2040, 3000 CA Rotterdam, Netherlands; m.vangoor@erasmusmc.nl ABSTRACT Background: To determine whether –148 C/T fibrinogen gene promoter polymorphism increases stroke risk by modifying the fibrinogen level. Design: A case–control study of patients with first ever ischaemic stroke, confirmed by computed tomography. Methods: Venous blood samples were collected for fibrinogen and routine coagulation tests one week after the stroke, and after three months in about half the patients. Population controls were age and sex matched. –148 C/T fibrinogen polymorphism was determined by polymerase chain reaction followed by digestion with restriction enzymes HindIII/AluI. Results: There were 124 patients and 125 controls, mean age 56 years (range 18 to 75); 34 patients (27%) and 41 controls (33%) were heterozygous for –148 C/T fibrinogen polymorphism; six patients (5%) and five controls (4%) had the T/T genotype. The odds ratio of ischaemic stroke associated with CC homozygotes v T carriers was 0.8 (95% confidence interval, 0.5 to 1.4). Relative risk for ischaemic stroke associated with fibrinogen levels in the highest quartile was 3.9 (1.9 to 8.4) at one week, decreasing to 1.4 (0.6 to 3.3) at three months. Conclusions: –148 C/T fibrinogen gene polymorphism was not a strong risk factor for ischaemic stroke. High fibrinogen levels early after acute stroke probably represent an acute phase response. Keywords: ischaemic stroke; –148 C/T fibrinogen gene; fibrinogen Fibrinogen is a well known risk factor for myocardial infarction and stroke.1–4 Whether the relation between fibrinogen concentrations and stroke is a marker of the inflammatory status of the vessel wall or contributes causally to the occurrence of ischaemic stroke is much debated.5–8 Fibrinogen promoter polymorphisms are associated with fibrinogen levels in the general population.9–11 These genetic features could therefore increase stroke risk. An alternative view is that fibrinogen is merely a marker of acute phase reactions and hence an innocent bystander rather than a causative agent in stroke. However, a combination of both hypotheses is also possible—that is, the presence of the T allele, which causes higher levels, could also mediate the fibrinogen increase as part of the acute phase response after stroke. Fibrinogen is a glycoprotein consisting of two sets of three polypeptide chains—known as , ?, and chains—which are encoded by three different genes clustered on chromosome 4.12 Several promoter polymorphisms of the ? chain are described which are in almost complete linkage disequilibrium.13 Only a few case–control studies have focused on the possible association between fibrinogen promoter gene polymorphisms and stroke, and their results are contradictory.14–17 The extent to which the increased risk of stroke resulting from raised fibrinogen levels is genetically determined or represents an acute phase response remains unknown. We designed a case–control study to investigate further the association between –148 C/T fibrinogen gene polymorphism, fibrinogen level, and ischaemic stroke. METHODS We carried out a case–control study with prospective inclusion of the participants. Cases were consecutively recruited patients with first ever acute ischaemic stroke, admitted to the neurology department of a university hospital between January 1999 and December 2001. We used population controls—partners, friends, or neighbours of the patients—who were age and sex matched, of the same race, without a history of stroke, and not related to the patient. Patients, controls, and their parents were all white and born in northern Europe. Exclusion criteria were age over 75 years, a definite non-atherosclerotic cause of stroke, and the use of oral anticoagulants. In both patients and controls, we collected detailed information about cardiovascular risk factors. Ischaemic stroke was defined as the acute onset of focal cerebral dysfunction caused by cerebral ischaemia, with symptoms lasting more than 24 hours. In all patients, computed tomography of the brain was done within three days of the onset of symptoms to confirm the diagnosis of ischaemic stroke and to rule out haemorrhagic stroke. The aetiology of the stroke was classified using the TOAST criteria.18 At one week and three months after the stroke, venous blood samples were taken under strictly standardised conditions (the patients were fasted and the sampling took place after 15 minutes of rest). Fibrinogen levels, cholesterol, glycosylated haemoglobin, and C reactive protein levels were determined in the blood samples. C reactive protein was used as a control variable for the acute phase response. Fibrinogen was measured as described by von Clauss19 on an automated coagulation analyser (Sysmex CA 1500, Dade Behring, Leusden, Netherlands) (coefficient of variation, 3.5%) during both acute and convalescent phases. Genomic DNA was isolated from the white cell fraction of citrated blood, using the high salt concentration standard procedure.20 The –148 C/T fibrinogen polymorphism was detected by polymerase chain reaction (PCR) followed by digestion with restriction enzymes HindIII/AluI.13 For the –148 C/T mutation with an expected prevalence of the T allele of about 20% in the control group,21 the minimum detectable odds ratio would be 2.2 (? = 20%, = 5%). The relation between –148 C/T fibrinogen polymorphism and ischaemic stroke was expressed as an odds ratio with 95% confidence interval (CI). The fibrinogen levels were categorised into quartiles and the odds ratio associated with ischaemic stroke for the highest quartile fibrinogen versus the lower three quartiles was estimated. Multiple logistic regression analysis was used to adjust for possible confounding variables, such as smoking and hypertension, as these vascular risk factors are known to affect fibrinogen levels. RESULTS The study population consisted of 123 patients and 123 controls. Their mean age was 56 years (range 18 to 75). Forty seven per cent of the participants were female. Patients were more often smokers and more often had hypertension or diabetes, or to have known cardiovascular disease, than the controls. Thirty four patients (27%) and 41 controls (33%) were heterozygous for –148 C/T fibrinogen gene polymorphism, and six patients (5%) and five controls (4%) were homozygous for the T allele. The genotype frequencies in the controls were in Hardy-Weinberg equilibrium. The odds ratio of ischaemic stroke associated with the –148 C/T genotype was 0.8 (95% CI, 0.4 to 1.3), and with the –148 T/T genotype, 1.1 (0.5 to 1.4). In the stroke patients, the highest fibrinogen levels were found in combination with the TT genotype and the lowest in combination with the CC genotype, but this difference was not statistically significant (table 1). In controls, there was no association between fibrinogen level and genotype. Table 1 Fibrinogen concentrations (g/l) according to genotype in controls and patients one week after the stroke (first blood sample) and three months after the stroke (second blood sample) The mean fibrinogen concentration was higher in patients than in controls (3.7 v 3.4 g/l, p<0.02, Student’s t test). The blood sample could be repeated at least three months after the ischaemic stroke in 64 patients. At that time, the mean fibrinogen concentration had decreased to 3.3 g/l, which did not differ significantly from the level in controls. The odds ratio associated with ischaemic stroke and fibrinogen in the highest quartile fibrinogen versus the lower three quartiles was 3.9 (95% CI, 1.9 to 8.4) at one week after the stroke. After adjustment for smoking and hypertension the odds ratio was 3.5 (1.7 to 7.2). The odds ratio based on fibrinogen levels in the second blood samples, taken three months after the index event, fell to 1.4 (0.6 to 3.3). The mean C reactive protein concentration was 16 mg/l (median 5 mg/l, range 1 to 215) in patients, and 4 mg/l (median 3 mg/l, range 1 to 21) in controls one week after the stroke; after three months the values were equal in both groups and lower than during the first blood examination. The C reactive protein level was strongly related to fibrinogen early after the stroke (r = 0.56, p = 0.001). DISCUSSION We see it as a strong point of this study that cases were included prospectively and consecutively by a neurologist. Furthermore, all patients underwent neuroimaging to rule out haemorrhage. We were able to include population controls, thus avoiding the biases induced by "hospital controls". We collected detailed information about cardiovascular risk factors, medical history, and family history from patients as well as controls. All subjects participating were white north Europeans, and allele frequencies of the polymorphism in the control group were in Hardy-Weinberg equilibrium, indicating that we were studying a representative group. It could be argued that our study was not large enough to exclude an association between ischaemic stroke and –148 C/T fibrinogen gene polymorphism. The odds ratio in our study was 0.8, with a narrow 95% confidence interval of 0.5 to 1.4. The 95% confidence interval indicates that even if the polymorphism is a risk factor, it cannot be a strong one. One other (nested case–control) study confirms this finding.14 We found a statistically significant difference between fibrinogen levels in patients and controls one week after the stroke. This finding confirms the already The fibrinogen concentration in the controls was not related to genotype in our study, in agreement with two other cross sectional cohort studies.9,23 There are several explanations for the differences in fibrinogen levels between stroke patients and controls being highly significant shortly after the event but mostly inapparent after three months. Fibrinogen concentrations increase as a result of an acute phase reaction, which might explain the higher fibrinogen levels in patients one week after the stroke. This is supported by concomitant changes in C reactive protein. Secondly, other cardiovascular risk factors are associated with higher fibrinogen levels and advanced atherosclerosis.24 The lower fibrinogen at three months after the stroke could in theory have resulted from rigorous treatment of these risk factors, particularly smoking. However, only five patients (4%) stopped smoking. This therefore only partly explains our observations. Apart from the cardiovascular risk factors, interleukin-6 (IL-6) increases both fibrinogen and C reactive protein.1,22,25 It may be that a polymorphism of the IL-6 gene is associated with the occurrence of ischaemic stroke. As the –148 C/T polymorphism lies close to the putative IL-6 responsive element in the fibrinogen gene, one could hypothesise that this polymorphism is also within the IL-6 responsive region, and therefore its intrinsic effect on fibrinogen levels—determined by the presence of a C or T allele—is also modulated by IL-6. This might explain why the fibrinogen levels were associated with the –148 C/T fibrinogen promoter polymorphic alleles only in patients and not in the controls. Conclusions The –148 C/T fibrinogen gene polymorphism is not associated with an increased risk of ischaemic stroke in north European white patients. The high fibrinogen levels shortly after the stroke most probably represent a non-specific acute phase response, although a causative role cannot be excluded. Future studies should focus on other polymorphisms, and their phenotypic expression, which may be related to increased acute phase proteins. ACKNOWLEDGEMENTS We thank MPM de Maat (Department of Haematology, Erasmus MC) for critically reviewing the manuscript. This study was supported by a grant from the Revolving Fund of the Erasmus MC, and by the Stichting Neurovasculair Onderzoek Rotterdam. REFERENCES Danesh J, Collins R, Appleby P, et al. Association of fibrinogen, C-reactive protein, albumin, or leukocyte count with coronary heart disease: meta-analyses of prospective studies. JAMA 1998;279:1477–82. Ernst E, Resch KL. Fibrinogen as a cardiovascular risk factor: a meta-analysis and review of the literature. Ann Intern Med 1993;118:956–63. Maresca G, Di Blasio A, Marchioli R, et al. Measuring plasma fibrinogen to predict stroke and myocardial infarction: an update. Arterioscler Thromb Vasc Biol 1999;19:1368–77. Wilhelmsen L, Svardsudd K, Korsan-Bengtsen K, et al. Fibrinogen as a risk factor for stroke and myocardial infarction. N Engl J Med 1984;311:501–5. Folsom AR, Rosamond WD, Shahar E, et al. Prospective study of markers of hemostatic function with risk of ischemic stroke. The Atherosclerosis Risk in Communities (ARIC) Study Investigators. Circulation 1999;100:736–42. Kannel WB, Wolf PA, Castelli WP, et al. Fibrinogen and risk of cardiovascular disease. The Framingham Study. JAMA 1987;258:1183–6. Van der Bom JG, de Maat MP, Bots ML, et al. Elevated plasma fibrinogen: cause or consequence of cardiovascular disease? Arterioscler Thromb Vasc Biol 1998;18:621–5. Tybjaerg-Hansen A, Agerholm-Larsen B, Humphries SE, et al. A common mutation (G-455 A) in the beta-fibrinogen promoter is an independent predictor of plasma fibrinogen, but not of ischemic heart disease. A study of 9,127 individuals based on the Copenhagen City Heart Study. J Clin Invest 1997;99:3034–9. ’t Hooft FM, von Bahr SJ, Silveira A, et al. Two common, functional polymorphisms in the promoter region of the beta-fibrinogen gene contribute to regulation of plasma fibrinogen concentration. Arterioscler Thromb Vasc Biol 1999;19:3063–70. Humphries SE, Ye S, Talmud P, et al. European Atherosclerosis Research Study: genotype at the fibrinogen locus (G-455-A beta-gene) is associated with differences in plasma fibrinogen levels in young men and women from different regions in Europe. Evidence for gender-genotype-environment interaction. Arterioscler Thromb Vasc Biol 1995;15:96–104. Thomas AE, Green FR, Humphries SE. Association of genetic variation at the beta-fibrinogen gene locus and plasma fibrinogen levels; interaction between allele frequency of the G/A-455 polymorphism, age and smoking. Clin Genet 1996;50:184–90. Kant JA, Fornace AJ, Saxe D, et al. Evolution and organization of the fibrinogen locus on chromosome 4: gene duplication accompanied by transposition and inversion. Proc Natl Acad Sci USA 1985;82:2344–8. Thomas A, Lamlum H, Humphries S, et al. Linkage disequilibrium across the fibrinogen locus as shown by five genetic polymorphisms, G/A-455 (HaeIII), C/T-148 (HindIII/AluI), T/G+1689 (AvaII), and BclI (beta-fibrinogen) and TaqI (alpha- fibrinogen), and their detection by PCR. Hum Mutat 1994;3:79–81. Blake GJ, Schmitz C, Lindpaintner K, et al. Mutation in the promoter region of the beta-fibrinogen gene and the risk of future myocardial infarction, stroke and venous thrombosis. Eur Heart J 2001;22:2262–6. Kessler C, Spitzer C, Stauske D, et al. The apolipoprotein E and beta-fibrinogen G/A-455 gene polymorphisms are associated with ischemic stroke involving large-vessel disease. Arterioscler Thromb Vasc Biol 1997;17:2880–4. Martiskainen M, Pohjasvaara T, Mikkelsson J, et al. Fibrinogen gene promoter -455 A allele as a risk factor for lacunar stroke. Stroke 2003;34:886–91. Nishiuma S, Kario K, Yakushijin K, et al. Genetic variation in the promoter region of the beta-fibrinogen gene is associated with ischemic stroke in a Japanese population. Blood Coagul Fibrinolysis 1998;9:373–9. Adams HP, Bendixen BH, Kappelle LJ, et al. Classification of subtype of acute ischemic stroke. Stroke 1993;24:35–41. von Clauss A. Gerinnungsphysiologische schnellmethode zur bestimmung des fibrinogens. Acta Haematol 1957;17:237–46. Sanger F, Nicklen S, Coulson AR. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci USA 1977;74:5463–7. Cook DG, Cappuccio FP, Atkinson RW, et al. Ethnic differences in fibrinogen levels: the role of environmental factors and the beta-fibrinogen gene. Am J Epidemiol 2001;153:799–806. Kannel WB, D’Agostino RB, Belanger AJ, et al. Long-term influence of fibrinogen on initial and recurrent cardiovascular events in men and women. Am J Cardiol 1996;78:90–2. Schmidt H, Schmidt R, Niederkorn K, et al. Beta-fibrinogen gene polymorphism (C148T) is associated with carotid atherosclerosis: results of the Austrian Stroke Prevention Study. Arterioscler Thromb Vasc Biol 1998;18:487–92. Meade TW, Imeson J, Stirling Y. Effects of changes in smoking and other characteristics on clotting factors and the risk of ischaemic heart disease. Lancet 1987;ii:986–8. Sehgal PB, Wang L, Rayanade R, et al. Interleukin-6-type cytokines. Ann NY Acad Sci 1995;762:1–14....查看详细 (17321字节)
☉ 11357076:Advertising campaign on a major internet search engine to promote colorectal cancer screening
1 Division of Cancer Prevention and Control, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevension, 4770 Buford Highway, NE, MS K-55, Atlanta GA30341, USA, 2 Yahoo!, 3715 Northside Parkway NW, Building 300, Suite 800, Atlanta GA 30327, USA, 3 Ogilvy Public Relations Worldwide, 1901 L Street, NW, Suiite 300, Washington DC 20036, USA Correspondence to: C P Cooper ccooper@cdc.gov Introduction From the moment the first advertisement was posted on Yahoo! we tracked the number of times advertisements were displayed ("audience exposures") and the number of visits to the SFL website that resulted from use of the hyperlink in the advertisements. For comparison data, we also monitored daily visits to the website for three months before and after the campaign, so the whole monitoring period lasted 1 March to 31 August. We tracked campaign costs using vendor invoices. During the six week campaign, the advertisements were displayed 29 673 418 times. Of these audience exposures, the CDC paid for 25 495 000 (first phase); Yahoo! donated the rest (second phase). In total, 26 697 visits to the SFL website resulted from use of the hyperlink in the advertisements. The mean number of daily visits during the pre-campaign period was 418; that number tripled (to 1282) during the first (CDC funded) phase and doubled (to 992) during the second (donation) phase (figure). Visits resulting from use of the hyperlink in the advertisements accounted for half of the total website traffic during the six week campaign. By using a "bookmark" or hyperlink established on a personal computer, some visitors continued to enter the SFL website through the hyperlink in the advertisments during periods when the advertisements were not posted on Yahoo!; bookmarked entries accounted for 6% of visits during the break between the two campaign phases and 1% of visits during the post-campaign period. Mean number of visits per day to the Centers for Disease Control and Prevention's "Screen for Life" website, by campaign period, 2002 The total cost of the campaign was $64 627 (￡35 400; 52 500)—$22 127 for converting existing SFL materials into 12 internet advertisements and $42 500 for advertising space on Yahoo!. Thus, the total cost per audience exposure was $0.002 and the total cost per visit resulting from use of the hyperlink in the advertisements was $2.42. Comment Yahoo! Yahoo! First quarter 2003 financial highlights. Sunnyvale, CA: Yahoo!, 2003. Bannan KJ. Search engines' positive results drive price wars. B to B 2003;88(10 Mar): 18-20. Krishnamurthy S. Deciphering the internet advertising puzzle. Marketing Management 2000;9: 34-9. Centers for Disease Control and Prevention. Donated television airplay of colorectal cancer education public service announcements—United States, 1999-2002. MMWR Morb Mortal Wkly Rep 2003;52: 196-9. Jorgensen CM, Gelb CA, Merritt TL, Seeff LC. Observations from the CDC: CDC's Screen for life: a national colorectal cancer action campaign. J Women's Health Gend Based Med 2001;10: 417-22....查看详细 (3155字节)
☉ 11357077:International online discussion lists on chronic myelogenous leukaemia
1 Cancer Resources and Advocacy, 7303 23rd Avenue NE, Seattle 98115 WA, USA, 2 Asian Chronic Myelogenous Leukaemia Support Group, 3 Chronic Myelogenous Leukaemia International Support Group Correspondence to: J D Ramos jdramos3@comcast.net The rise of the internet as a communication tool has resulted in the creation of ehealth interfaces as a service for those with illness. We describe how two online discussion lists for patients with chronic myelogenous leukaemia affect the health care of patients both individually and worldwide. The Chronic Myelogenous Leukaemia International Support Group was formed in 1998 by Robert Neill after his mother was diagnosed as having the condition. The list has 1500 subscribers and averages 28 new postings a day. A major feature of list discussions is the sharing of information and experiences of patients undergoing treatment for disease (figure). Random sampling of topics covered over five years by Chronic Myelogenous Leukaemia International Support Group In 1999, imatinib (Novartis), a drug in the early phase of clinical trials for chronic myelogenous leukaemia, was in short supply. The chronic myelogenous leukaemia list petitioned Novartis to increase production, resulting in the opening of 19 additional clinical trial centres, giving access to patients, many of whom had no other treatment options.1 The sharp rise in advocacy in messages posted on the list in 1999 reflects this mobilisation of patients (figure). This shows how an online support group played a major part in promoting access to treatment. Another topic frequently discussed on the list was the high global price of imatinib and related access problems, especially in developing countries. Again, there was an increase in patient advocacy activity in 2002. The intensity and content of concerns over the topic were such that they became the subject of media attention.2 The Asian Chronic Myelogenous Leukaemia Support Group was formed in February 2003 by Anjana Chaudhuri, a care giver based in Singapore, whose husband was diagnosed as having the condition.3 This list has 240 subscribers and averages 34 new postings a day. To study the impact of online support lists for chronic myelogenous leukaemia on the health care of individual patients, we conducted a survey of 35 patients from the Asian support group (table). Although the number of responses is relatively small, this is not unusual in surveys of this nature.4 Responses to questions asked in survey of 35 patients who use Asian Chronic Myelogenous Leukaemia Support Group discussion list Most patients (74%) joined the list to obtain information on treatment. All patients thought that their mental wellbeing improved because of the camaraderie from peers. A large proportion viewed the list as a lifeline and a better source of support than family. Most preferred online support to group meetings because of its ability to transcend boundaries of time and geography and to be constantly available. Most (77%) patients reported that knowledge gained from online support groups enabled them to make better decisions about treatment. A major drawback of ehealth applications such as these support groups is their inability to serve as a public health interface on an international scale. Because participation requires internet access and literacy in English, participation from developing countries, with the most serious access problems to medicines, has been limited. The groups, however, are important for increasing both patient education and awareness of global issues affecting treatment. The lists put a human face on access difficulties and hopefully will increase broader advocacy efforts by those in countries where treatment, particularly for cancer, may often be viewed as a personal concern. This new kind of community has potential as a positive aspect of globalisation. The Chronic Myelogenous Leukaemia International Support Group can be found at groups.yahoo.com/group/cml, and the Asian Chronic Myelogenous Leukaemia Support Group can be found at asia.groups.yahoo.com/group/AsianCMLSupportGroup. Contributors: ARC conducted the survey and produced the table. All authors wrote the paper. ARC will act as guarantor for the paper. Funding: None. Competing interests: None declared. Ethical approval: Not required. References Boudreau D. Patient power. www.novartis.com/pathways/content/vol2num4/archive/artic2.html (accessed 10 Sep 2003). Strom S, Fleischer-Black M. Company's pledge to donate a drug is falling short. New York Times 5 Jun 2003;A1: C11. Chua Hian Hou. Virtual lifeline: a leukemia patient's desperate on-line search for a cure saved his life. Computer Times 8 Jan 2003. (http://it.asia1.com.sg/specials/spotlight20030108_003.html) Pew Internet and American Life Project. Vital decisions: how internet users decide what information to trust when they or their loved ones are sick, 22 May 2002. www.pewinternet.org/reports/toc.asp?Report=59 (accessed 8 Dec 2003)....查看详细 (5092字节)
☉ 11357078:Soft networks for bridging the gap between research and practice: illuminative evaluation of CHAIN
1 Department of Primary Health Care, University College London, London N19 5LW Correspondence to: J Russell j.russell@pcps.ucl.ac.uk Abstract Although there is widespread support for the concept of evidence based health care, a large gap remains between research and practice.1-3 Various research and development initiatives have sought to close this gap, but their success has been limited.4-6 Insights from knowledge utilisation research (how individuals and teams acquire, construct, synthesise, share, and apply knowledge) have shown that getting evidence into practice requires both explicit and tacit knowledge (box 1).7 Explicit knowledge is only converted to actionable knowledge when it is linked meaningfully with knowledge and when shared meanings are constructed through social interaction and dialogue.7-11 Box 1: Explicit and tacit knowledge Human knowledge has been classified as: Explicit or codified—knowledge that is transmittable in formal, systematic language Tacit—knowledge that has a personal quality, making it hard to formalise and codify.12 This knowledge is rooted in action and involvement in a specific context but does not transmit easily between people or organisations.13 14 It is generally acquired by experience, apprenticeship, and informal discussion with experienced practitioners These terms have been interpreted and extended by many authors and now carry a variety of meanings. We defined tacit knowledge as informal and context specific "know-how" that draws on people's own experiences, perceptions, and insights. We contrast this "soft" knowledge with formal, explicit knowledge, which is systematically codified and accessible through indexing services such as Medline, the Cochrane Library, and the National Electronic Library for Health. Explicit knowledge is easily transferred between people and organisations but may have little meaning for them and not be readily actionable. In 1997 the NHS research and development programme established CHAIN (Contact, Help, Advice and Information Network for Effective Health Care www.nhsu.nhs.uk/chain/), an informal email network for people working in health care with an interest in evidence based health care. Membership is free and voluntary. CHAIN aims to remove barriers between research and practice, facilitate multiprofessional and interorganisational collaboration, and widen access to knowledge by facilitating and enabling the informal processes through which members identify new contacts, exchange expertise, and provide mutual support. We aimed to determine the important features and critical processes of CHAIN through an evaluation. In designing the study, we built upon a preliminary evaluation of CHAIN by the King's Fund15 and our experiences as members of the network. We were careful not to adopt an oversimplistic, linear model of the evidence into practice sequence, but instead attempted to engage with the complexity of the process, and recognised that CHAIN's role was likely to be diffuse, long term, and subtle rather than specific, immediate, and readily auditable. Methods CHAIN is open to anyone working in the NHS "family of organisations" who is willing to share information and experience with other members of the network. At the time of our study, between April 2002 and January 2003, CHAIN had 2800 members. Members contact each other either through the database (which includes searchable fields of members' interests and expertise) or by asking CHAIN's staff to send out on their behalf an email message targeted to a relevant subgroup of members. The originators of CHAIN initially saw the network as a tool for people interested in evidence based health care to make connections themselves. As the network has developed, however, the role of staff in brokering the contact between members has become increasingly prominent, and targeting emails is now the most important part of CHAIN. This became the focus of our evaluation. CHAIN is run by a head of development, a manager, and an administrative officer. Information for dissemination comes from two sources: that circulated by staff about jobs, studentships, courses, conferences, funding opportunities, and key publications (a horizon scanning service); and that from CHAIN members which is checked, edited, and targeted by staff. Messages may be offers of information or requests to network (see bmj.com). Targeting by staff ensures that email is only received by a subset of members (typically 50 to 100) with matching interests. This process is labour intensive and requires expert judgment and skill in database searching (box 2). Targeting also depends on an up to date database to accurately and sensitively capture members' interests. CHAIN aims to keep records that are no more than six months out of date, and has a rolling programme to contact members for updates. Staff and members, however, identified this area as one for improvement. A potential drawback of targeting is that members may fail to receive potentially useful messages. Overall, members commented positively on targeting and compared it favourably with electronic bulletin boards and other email lists to which they belonged. A few respondents thought they might be missing out on potentially interesting information. A notable feature of CHAIN was the willingness and generosity of members' responses to requests to network—we defined this as "reciprocity." Members were typically "overwhelmed by the generosity of responses." CHAIN helps people in practice in four key ways: by providing a rich source of relevant, useful information; by providing access to both information and people with know-how; by enabling collaboration across boundaries; and by enabling participation in networking at a variety of levels. A rich source of relevant, useful information CHAIN members perceived the targeted email service as a valuable source of information about such things as conferences, training events, research calls, funding opportunities, and new publications. This was commonly identified as information they would not otherwise have heard about. A view expressed by several respondents was that "CHAIN is my lifeline to what is going on out there!" Members also acted as a rich source of research evidence and this was commonly identified as evidence that members had not been aware of from formal literature searches. An area identified for future improvement, both by members and staff, was for this horizon scanning service to be extended, possibly by linking up with other, more systematic research and development scanning services. Access to people with know-how Overwhelmingly, members found the opportunity CHAIN provided to tap into other members' experiences, suggestions, and ideas most valuable. Through CHAIN, people are able to make contact with others working on similar initiatives or trying to solve similar problems. Many messages related wholly or partly to the uncodifiable know-how required to obtain or action evidence (see bmj.com). Such information was often requested in the form of contextualised stories (local lessons) embellished with operational details, warnings, troubleshooting advice, humour, and other personalising devices. CHAIN members emphasised the value of this support: Box 2: Example of targeting messages CHAIN received information about a Cochrane meeting on schizophrenia from one of its members, which it wanted to disseminate to interested members. Firstly, it needed to decide on a relevant subgroup. Searching the database with various keywords identified differing numbers of people: "schizophrenia," 25 people; "mental health," 591 people; "researcher" and "mental health," 317 people (this could be reduced to 120 by searching only for those who are part of the Health Service Research Network—a specialist subgroup within CHAIN). Having identified these options, staff made contact with the organiser of the meeting to clarify whether the priority was to have a narrowly focused meeting or a wide audience. The final decision was based on this process. and I are doing a health needs assessment of sex workers in one area, and we asked CHAIN for help. We had 6 replies from people working on similar studies or those who had done similar studies already, and some of them sent us references we could check out straight away. That must have saved us at least a week's work of trawling the net and libraries, and it was very useful because some of the people who responded were happy to talk through some of the issues with us. I can't think of a more direct way to reach people than via CHAIN (unsolicited feedback from a specialist in public health) Other characteristics of this support identified as important by CHAIN members were its availability when required and its boost to both motivation and confidence because the support was perceived to come from like minded people who were more knowledgeable or experienced. Responses to a networking message often included an invitation to liaise further (box 3). Links were forged between two people or sometimes a wider group of people who had responded to a message: Last year we were successful in obtaining funding for a project on falls. We received critical input and advice from CHAIN members prior to submission and after our first reject. CHAIN members were very valuable in discussing ideas and indeed making links. CHAIN members are now on our project contact list for information of the outcome of our work—so it can be used to develop falls services elsewhere (feedback from consultant doctor) Box 3: Soft networking in practice A member of CHAIN sought help from other members: "I have been asked to document the primary care clinical audit criteria (including milestones) for each of the National Service Frameworks. This seems a big job to tackle on my own and I wondered if any CHAIN members had already done this work and would be willing to share it." As part of our tracking of the history of a sample of messages we asked this member to keep us informed of her responses. She sent the following summary of the five responses she received Contained a useful web link and shared the department's strategy for prioritising audits, which was also useful Was a request for further clarification of what I wanted Sent a copy of a data collection tool and report they had produced when conducting a CHD baseline audit, it wasn't what I was looking for, but it was nice they had taken the trouble Had gathered all the relevant information together into a couple of documents with references, etc. This was close to what I was interested in and a useful resource. They also offered further support should I need it and were open and supportive Asked that if I received what I was looking for would I share it with them as they too thought such a piece of work was useful and had made several unsuccessful attempts to produce it themselves. I intend to seek permission from the originators before forwarding the documents and references above In her feedback to us, she wrote: "I was overwhelmed by people's support and kindness. The query was quite straightforward, but I'm fairly new to audit, and a complete stranger to primary care audit, and this was a pretty big piece of work with a tight deadline. I would certainly use CHAIN again and have in fact spoken about the progress of my query to a colleague who has since registered with CHAIN." Diversity of members' backgrounds, expertise, and experience Many respondents explicitly commented on how the network enabled them to access others from different organisations and professional groups: My personal network tends to be limited to people in similar fields to me . I don't tend to know nurses, academics, or social researchers, whereas CHAIN has all of them as members (unsolicited feedback from a specialist in public health) A particular advantage identified by respondents was that researchers were able to communicate directly with practitioners in the service sector and vice versa: CHAIN allows links to be made between researchers and clinical governance leads or practitioners on the ground, and this has the potential to harness and direct research capacity on the one hand, and aid implementation of new findings in the health service on the other (clinical governance facilitator, focus group 3 discussion) The value of this cross boundary networking for our focus group respondents was that it encouraged them to look outside their usual profession or organisation; it prompted them to reconceptualise their problems and therefore produce new potential solutions; it enabled the sharing of innovation and good practice between individuals, professions, and organisations; and it opened up possibilities for research agendas to be directly informed by day to day service needs. Some respondents suggested that an additional benefit of the virtual medium was that it bridged the gap between novice and expert: The informality and professionalism are well combined in CHAIN... I have met with many excellent people at conferences, and have tried to maintain links via email. But people are not very responsive to this, unless you are someone who has written a good book or given the conference presentation. Whereas in CHAIN, I have found that you can be anybody and anyone will reply. It is sort of more equal in status (PhD student in focus group 1 discussion) Flexibility to participate at different levels The most intangible benefit of CHAIN identified by respondents was the value that many attached to just knowing it was there and that it could be used if need be: I have not used CHAIN much but it is a security blanket! I am a novice researcher and not a natural one! Knowing there are a bunch of people out there who would if I asked and if they could share their expertise with me is comforting (general practitioner in focus group 2 discussion) The virtual medium of CHAIN was seen as allowing members to choose to be passive rather than active but to still feel connected to the network and benefiting from it. A minority of respondents were less keen on the virtual medium. Discussion Official strategies to bridge the gap between research and practice have until recently focused almost exclusively on the production, presentation, and distribution of codified knowledge—the evidence itself and codified information on how to get evidence into practice.4 5 It has been argued that evidence based health care is a "contact sport"—that is, a social process involving the exchange and negotiation of knowledge between individuals and groups—and that it is misleading to describe it as a technical process devoid of human interaction.22 A few recent studies have attempted to explore the complex informal social interactions and networks that support or inhibit the process of research into practice.23 24 Our study has produced additional findings on the process of knowledge sharing from a dimension of informal space (email networking) that has been largely unexplored by those researching the research-practice gap in health care, and it has raised some important methodological issues. CHAIN provides an example of how knowledge can be targeted, personalised, and made meaningful through informal social processes. It offers a mechanism for people to span the divisions between organisations and professional groups, to capture obscure items of codified knowledge, to share and shape the know-how and know-what of implementing evidence, and to link novices with experienced practitioners who are motivated to help them solve problems. Nonaka and Takeuchi suggest that the creation of complex knowledge within an organisation occurs as a result of a dynamic interchange between explicit and tacit forms of knowledge.9 13 They identified four modes of knowledge creation: socialisation (tacit knowledge exchanged through the sharing of experiences); externalisation (tacit knowledge articulated into explicit concepts through successive rounds of meaningful dialogue); combination (explicit knowledge systematised and documented into a wider knowledge system); and internalisation (explicit knowledge embodied into tacit operational knowledge). CHAIN has examples of each of these modes. CHAIN provides a mechanism for socialisation—for members simply to make contact with each other or to listen in on others' exchanges and be reassured that there are others with whom they can share experiences. CHAIN also provides a mechanism for the complementary modes of externalisation and internalisation enabling dialogue through which members articulate their own perspectives and reveal tacit knowledge that is otherwise hard to communicate. Others' tacit knowledge can then be internalised and applied to local circumstances. CHAIN also enables the transfer of formal knowledge, with members recommending publications and exchanging protocols and guidelines. Our application of Nonaka and Takeuchi's theoretical model of knowledge creation to the processes within CHAIN illuminates the importance of the interplay between tacit and explicit knowledge and the role of social interaction and informal dialogue in getting evidence into practice. The transfer of complex knowledge between organisations can link to different points in the knowledge creation cycle, but it critically depends on the individual boundary spanner—that is, someone from one organisation who networks with people from other organisations (figure). According to this model, soft networking occurs when such individuals identify the type of knowledge they need as missing and draw effectively on the network to fill the gap. Diagrammatic representation of how boundary spanners can contribute to knowledge creation within their own organisations through exchange and personalisation of knowledge within soft networks Critical success factors Increasing interest has been shown in the use of networks within the NHS, and our study suggests certain critical success factors for such networks to flourish.11 25-27 Firstly, the skilled staff at the centre of CHAIN help establish, maintain, and develop the networking processes. They perform four key functions: ensuring that the database of members is up to date; targeting messages to appropriate subgroups based on members' interests; reminding members of the opportunities for networking; and affirming the principle of reciprocity. Fenton and coworkers also found that successful networks have strong central cultures.26 They describe the centre's role as creating values for members, galvanising interest, setting rules for behaviour, and building capability by linking individuals and groups with opportunities and resources for learning. Secondly, the nature of CHAIN's communication by simple email enables its members to draw on what one author has called "the strength of weak ties."28 This is the notion that people who have little in common have more potential to exchange information. For this reason, the best source of new ideas is often a stranger or, even better, a friend of a friend. Weak ties become evident in CHAIN when, for example, its members forward messages to colleagues or acquaintances who are not themselves members of CHAIN, producing a highly targeted extension of the boundary spanning facility. Thirdly, CHAIN provides both the medium and the impetus for small groups of people to come together and set about making sense of a common problem. These spontaneous groupings can be thought of as emergent virtual communities of practice.29 According to social network theory, successful networks are those that maintain a balance between weak ties and stronger ties and identities forged between more focused subgroups.28 A final critical success factor for CHAIN is silent or passive participation, known as "lurking"—reading the email postings to a group without posting a reply.30 Our respondents, especially those who were newcomers to evidence based health care, seemed to place great value on the network even when they made little active contribution to it. One study describes how "legitimate peripheral participation" encultures novices to general discourses and forms of practice.31 In other words, CHAIN members can begin to learn about evidence based health care and acquire the skills of knowledge sharing by observing others from a peripheral position. This illustrates why, when evaluating electronic soft networks, researchers must not simply quantify the number of messages or the proportion of members who post them but should also explore the more intangible benefits perceived by members. What is already known on this topic The volume and complexity of evidence from research makes it inaccessible to busy practitioners, who often lack sophisticated search and appraisal skills Evidence is usually only available for part of the sequence of decisions and actions in real life clinical problems Evidence might indicate what works but not how to do it, and it cannot take account of local context, resources, and politics What this study adds Bringing researchers and practitioners under the same "virtual roof" in an accessible, low technology email forum can help bridge the gap between research and practice Soft networking enables knowledge for evidence based health care to be personalised and made meaningful through informal social interaction Skilled staff can encourage a strong culture of support and reciprocity within the network and can target messages to individuals with matching interests Our evaluation suggests that, with additional resources, CHAIN might further develop the central support service for a soft network—for example, by providing a more systematic horizon scanning service, making available an archive of collated responses to email inquires, and providing more proactive facilitation of research collaborations. A fine balance, however, exists between a strong centre that enables, facilitates, and supports and one that stifles the energy of networking by too much control.11 Those involved with developing strategies for knowledge transfer and learning within the specialty of health show a growing interest in the CHAIN model. CHAIN Canada is about to be launched (www.epoc.uottawa.ca/CHAINCanada/index.htm), and the NHS University, as well as providing future funding for CHAIN, is extending the model to bring together other interest groups in health and social care. We strongly recommend that these and other future networking initiatives take note of the established literature on knowledge sharing and of the critical success factors for soft networks. We would also note that for such networks to flourish and for their potential benefits to be realised, healthcare organisations will need to provide an enabling environment for participation. Because of the informality of networking, particularly virtual networking by email, there can be a danger that it is perceived as, at best, a marginal activity to be squeezed in if time permits rather than an integral component of the evidence into practice cycle (see figure). Both the methods for evaluation and the critical success factors hypothesised from this preliminary study might prove generalisable to other electronic support networks with similar aims. Further research is needed on how electronic networks support soft social networks; how such facilitated networks can be provided cost effectively; and the implementation dimension (how individuals make use of the knowledge they gain from informal networking, how it feeds into their practice, and how soft networking by individuals contributes to wider team and organisational learning).32 33 Examples of request to network messages are on bmj.com We thank David Evans, Wendy Zhou, Natasha Karpava, and the CHAIN members who contributed to the evaluation and Olympia Kyriakidou, Janet McDonnell, Jeanette Buckingham, and two reviewers for helpful advice on earlier drafts of this paper. Contributors: All authors were involved in the design of the study and its implementation. JR and TG wrote the paper. JR will act as guarantor for the paper. The guarantor accepts full responsibility for the conduct of the study, had access to the data, and controlled the decision to publish. Funding: NHS research and development programme. Competing interests: None declared. Ethical approval: Not required. References Bero LA, Grilli R, Grimshaw JM, Harvey E, Oxman AD, Thomson MA. Closing the gap between research and practice: an overview of systematic reviews of interventions to promote the implementation of research findings. The Cochrane Effective Practice and Organisation of Care Review Group. BMJ 1998;317: 465-8. Grol R. Improving the quality of medical care. Building bridges among professional pride, payer profit and patient satisfaction. JAMA 2001;286: 2578-85. Needham G. Research and practice: making a difference. In: Gomm R, ed. Using evidence in health and social care. London: Sage, 2000. Dopson S, Locock L, Chambers D, Gabbay J. Implementation of evidence-based medicine: evaluation of the promoting action on clinical effectiveness programme. J Health Serv Res Policy 2001;6: 23-31. Dunning M, Abi-Aad G, Gilbert D. Experience, evidence and everyday practice: creating systems for delivering effective health care. London: King's Fund, 1999. Evans D, Haines A. Implementing changes in evidence-based health care. Oxford: Radcliffe, 2000. Wyatt JC. Management of explicit and tacit knowledge. J R Soc Med 2001;94: 6-9. Eraut M. Non-formal learning, implicit learning and tacit knowledge. In: Coldfield F, ed. Informal learning. Bristol: Policy Press, 1999. Nonaka I, Takeuchi H. The knowledge creation company: how Japanese companies create the dynamics of innovation. New York: Oxford, 1995. Brown JS, Duguid KP. The social life of information. Boston, MA: Harvard University Press, 2000. Bate SP, Robert G. Knowledge management and communities of practice in the private sector: lessons for modernizing the NHS in England and Wales. Public Admin 2002;80: 643-63. Polanyi M. The tacit dimension. New York: Anchor Day, 1962. Nonaka I. A dynamic theory of organizational knowledge creation. Organ Sci 1994;5: 14-37. Hippel EV. "Sticky information" and the locus of problem solving. Manage Sci 1991;44: 429-39. Saffron L, Wye L, McLenahan J. The future of CHAIN. An evaluation of CHAIN's first three years with suggestions for development. London: King's Fund, 2000. Guba E, Lincoln Y. Fourth generation evaluation. London: Sage, 1989. Kushner S. The limits of constructivism in evaluation. Evaluation 1996;2: 189-200. Patton M. Utilization-focused evaluation. London: Sage, 1997. Parlett M, Hamilton D. Evaluation as illumination: a new approach to the study of innovatory programmes. In: Hamilton D, ed. Beyond the numbers game: a reader in educational evaluation. London: Macmillan, 1972. Russell J, Boynton P, Greenhalgh T, Rigby M. C.H.A.I.N. evaluation report. London: University College London, 2003. www.nhsu.nhs.uk/chain/ (accessed 1 April 2004). Spencer L, Ritchie J, Lewis J, Dillon L. Quality in qualitative evaluation: a framework for assessing research evidence. London: Cabinet Office, 2003. Lomas J. Improving research dissemination and uptake in the health sector: beyond the sound of one hand clapping. Policy Commentary C97-1. McMaster University, Canada: Centre for Health Economics and Policy Analysis, 1997. Ferlie E, Gabbay J, Fitzgerald L, Locock L, Dopson S. Evidence-based medicine and organisational change: an overview of some recent qualitative research. In: Ashburner L, ed. Organisational behaviour and organisational studies in health care: reflections on the future, Basingstoke: Palgrove, 2001. West E, Barron D, Dowsett J, Newton J. Hierarchies and cliques in the social networks of health care professionals: implications for the design of dissemination strategies. Soc Sci Med 1999;48: 633-46. Edwards N. Clinical networks: a discussion paper. London: NHS Federation, 2001. Fenton E, Harvey J, Griffiths F, Wild A, Sturt J. Reflections from organization science on the development of primary health care research networks. Fam Pract 2001;18: 540-4. Urquhart C, Yeoman A, Sharp S. NeLH communities of practice evaluation report, 2002. Department of Information Studies, University of Wales Aberystwyth. www.nhsia.nhs.uk/nelh/pages/documents/cop.doc Granovetter M. The strength of weak ties. Am J Sociol 1973;78: 1360-80. Wenger E. Communities of practice: learning, meaning and identity. Cambridge: Cambridge University Press, 1996. Nonnecke B, Preece J. Silent participants: getting to know lurkers better. In: Lueg C, Fisher D, eds. From Usenet to CoWebs: interacting with social information spaces. London: Springer, 2002. Lave J, Wenger E. Cognition in practice: mind, mathematics and culture in everyday life. Cambridge: Cambridge University Press, 1988. Wellman B. An electronic group is virtually a social network. In: Kiesler S, ed. Culture of the internet, Hillsdale, New NJ: Lawrence Erlbaum, 1997. Garvin DA. Building a learning organization. Harvard Business Review 1993;71: 78-92....查看详细 (29697字节)
☉ 11357079:Computer aided prescribing leaves holes in the safety net
1 West Midlands Centre for Adverse Drug Reaction Reporting, City Hospital, Birmingham B18 7QH r.e.ferner@bham.ac.uk Patients die from poor prescribing. As with so much else, poor communication is a major culprit. Amoxil (amoxicillin) is misread as Daonil (glibenclamide) because of bad handwriting; 10U is interpreted as 100 because of inappropriate abbreviation; patients are overdosed with a standard release drug when a modified release formulation was intended but not specified.1 The prescribing process is complex, and opportunities for error abound. Patients may be given drugs they are allergic to, or which are contraindicated or have already been prescribed under another name; one drug may interact with another; the dosage, or duration, or formulation, or route may be wrong: in short, anything that can go wrong in prescribing will go wrong. Computers can help. They reduce medication error rates by as much as 60% simply by ensuring that prescriptions are legible, complete, and in a standard format.2 That is encouraging, but patients still die from the remaining errors. The NHS Information Authority requires that systems used in general practice "shall cross check prescriptions for known sensitivities, interactions and active ingredient duplications in the patient record. An appropriate warning to the prescriber shall be given."3 But GP prescribers put their trust in these systems at their patients' peril. Fernando and colleagues tested four computer prescribing systems.4 One failed to meet the NHS requirements; others failed to warn of potentially serious prescribing errors, especially where drugs were contraindicated. Contraindications account for about 4% of adverse drug events in general practice.3 The systems could be improved. They might list every contraindication to a drug whenever it was prescribed. That change would trap more errors but risk overwhelming the user with alerts: primary care physicians ignore alerts from nagging computers.5 Relevance is the key. Prescribers need not be reminded constantly that etoricoxib is contraindicated in inflammatory bowel disease, that nalidixic acid should be withheld from patients with epilepsy or porphyria, or that hyoscine-N-butylbromide should be avoided in patients with myasthenia gravis. Yet timely and relevant warnings will prevent disaster. Hospital systems already exist that link patient history, laboratory results, and prescribing data and that present a hierarchy of warnings to inform, advise, and occasionally forbid the prescriber to continue.6 No human activity is error-free, and we have recognised belatedly that prescribing is complex and prone to error. We need to make it safer—which means increasing the chances that important errors will be avoided or caught by checks before they are translated into harm. We can and should ensure that prescribers—who now include nurses and pharmacists—learn to use medicines safely. Practical examinations in the core skills of therapeutics should help.1 That will still leave patients vulnerable to prescribers' human failings. Computers can improve communications by generating a legible and complete prescription. But Fernando and colleagues show that several widely used systems fail to detect known prescribing errors. Those who walk the therapeutic tightrope in general practice will want the assurance of a safety net that will catch important errors before they harm patients, an assurance that current systems cannot provide. Competing interests: REF is a member of the Medicines Management Working Group of the NHS Information Authority. References Smith J. Building a safer NHS for patients: improving medication safety. London: Department of Health, 2004. Anderson JG, Jay SJ, Anderson M, Hunt TJ. Evaluating the capability of information technology to prevent adverse drug events: a computer simulation approach. J Am Med Inform Assoc 2002;9: 479-90. Australian Department of Health and Ageing. Better medicines management systems. Drug alerts discussion paper. Version 3.0, 11 June 2002. www.mediconnect.gov.au/pdf/dapavers3.pdf (accessed 14 Apr 2004). Fernando B, Savelyich BSP, Avery AJ, Sheikh A, Bainbridge M, Horsfield P, et al. Prescribing safety features of general practice computer systems: evaluation using simulated test cases. BMJ 2004;328: 1171-2. Weingart SN, Toth M, Sands DZ, Aronson M, Davis RB, Phillips RS. Physicians' decisions to override computerized drug alerts in primary care. Arch Intern Med 2003;163: 2625-31. Nightingale PG, Adu D, Richards NT, Peters M. Implementation of rules based computerised bedside prescribing and administration: intervention study. BMJ 2000;320: 750-3....查看详细 (4741字节)
☉ 11357080:Dopamine transporter SPECT in patients with mitochondrial disorders
1 Department of Neurology, University of Bonn, Bonn, Germany 2 Department of Nuclear Medicine, University of Bonn 3 Department of Epileptology, University of Bonn 4 Department of Nuclear Medicine, University of Munich, Munich, Germany Correspondence to: Dr Ullrich Wüllner Department of Neurology, University of Bonn, Sigmund-Freud-Strasse 25, Bonn 53105, Germany; wuellner@uni-bonn.de ABSTRACT Background: Mitochondrial disorders may affect basal ganglia function. In addition, decreased activity of complex I of the mitochondrial electron transport chain has been linked to the pathogenesis of dopaminergic cell loss in Parkinson’s disease. Objective : To investigate the dopaminergic system in patients with known mitochondrial disorders and complex I deficiency. Methods: Dopamine transporter density was studied in 10 female patients with mitochondrial complex I deficiency by 123I-FP-CIT (N-?-fluoropropyl-2?-carbomethyl-3?-(4-iodophenyl)-nortropane) SPECT. Results: No differences in 123I-FP-CIT striatal binding ratios were observed and no correlation of the degree of complex I deficiency and striatal binding ratios could be detected. Conclusions: These data argue against the possibility that mitochondrial complex I deficiency by itself is sufficient to elicit dopaminergic cell loss. Abbreviations: CPEO, chronic progressive external ophthalmoplegia; DAT, dopamine transporter; SPECT, single photon emission computed tomography Keywords: dopamine; 123 I-FP-CIT SPECT; mitochondrial disorders Mitochondrial disorders affect a broad spectrum of central nervous system functions, and parkinsonian signs have been described in Leigh’s disease, Leber’s hereditary optic neuropathy plus dystonia, and other mitochondrial encephalopathies.1,2 In addition, primary pathogenic mitochondrial DNA defects have been reported with parkinsonism.3 On the other hand, decreased activity of complex I of the mitochondrial electron transport chain, mitochondrial DNA damage in tissue samples, and complex I deficiency have been detected in the substantia nigra of patients with Parkinson’s disease at necropsy.4,5 In addition, several compounds that inhibit complex I activity induce nigral neuronal cell death and parkinsonism in humans and non-human primates.6,7 While parkinsonism is not a common feature of mitochondrial disorders, a moderate loss of dopaminergic neurones might have been missed. A loss of approximately 80% of striatal dopamine is required to elicit parkinsonian symptoms.8 Most patients with Parkinson’s disease studied using dopamine transporter (DAT) SPECT show a loss of approximately 50–60% of putamen DAT early in the disease process.9 Data on the state of the dopamine system in patients with mitochondrial disorders are lacking. We therefore investigated the dopaminergic system in 10 female patients with known mitochondrial disorders and complex I deficiency, using 123I-FP-CIT (N-?-fluoropropyl-2?-carbomethyl-3?-(4-iodophenyl)-nortropane) SPECT.10–12123I-FP-CIT binds to membrane dopamine transporters and allows preclinical detection in as yet unaffected family members of patients with Parkinson’s disease.10 METHODS We studied 14 consecutive patients (10 women and four men) from our neuromuscular clinic with mitochondrial disorders but without overt parkinsonian symptoms. A sex specific differential loss of DAT with age has been described previously.13 We therefore included only the women in our final data analysis (range 35 to 69 years, median 48 years) to avoid data inhomogeneity. Nine patients had "CPEO plus" (chronic progressive external ophthalmoplegia with proximal muscular weakness, ataxia, retinopathy, hypacusis or arrhythmia), two of whom fulfilled the criteria of Kearns-Sayre syndrome, and one patient had MELAS syndrome (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes). Histological examination, enzyme histochemical analyses, biochemical analyses, and molecular genetic studies were carried out on serial frozen sections and homogenised muscle tissue from all the patients. Muscle specimens showed ragged red fibres (modified Gomori’s trichrome stain) and COX negative (cytochrome c oxidase stain) fibres in all patients with mitochondrial disorders. Diagnostic muscle biopsies from 21 neurologically normal patients without evidence of a myopathy were used as controls (range 38 to 72 years, median 54). Enzyme activity determinations (rotenone sensitive NADH:CoQ oxidoreductase, cytochrome c oxidase, and citrate synthase) and analysis of mitochondrial DNA (for detection of large scale deletions and the A3243G point mutation) was carried out as described previously.14 All patients were examined using a neuropsychological test battery covering general intellectual capabilities, verbal and visual memory, concentration, vigilance, attention, language, visuospacial perception, visual construction, abstraction, and flexibility. 123I-FP-CIT (DaTSCAN?, Nycomed Amersham, UK) SPECT imaging and evaluation protocol followed the procedure recommended by the 123I-FP-CIT study group.15 All scans were done with a dual or triple headed gamma camera equipped with collimators optimised for iodine-123. Image acquisition started three to four hours after an intravenous injection of 185 MBq 123I-FP-CIT with 120 projections at 3°, a 50 second acquisition time for each step, and a 128x128 matrix. To avoid a systematic bias the acquisition processes were adjusted between both camera systems, employing identical acquisition parameters, number of projections, projection angle, and projection time. The raw data of all patient studies were reconstructed using a low pass filter of seventh order with a cut off frequency of 0.38. Chang’s attenuation correction, with an attenuation coefficient of 0.11, was applied to the reconstructed images. For further processing all datasets were coregistered to a mean template of the healthy controls, which had been coregistered to a normal brain magnetic resonance image (MRI), aligned according to the Talairach coordinates.16 Semiquantitative analysis of striatal FP-CIT binding was done with a standardised three dimensional map of regions of interest (ROI) which had been established on the MRI scan aligned according to the Talairach coordinates. Striatal specific to non-specific binding ratios were calculated by subtracting the mean counts per pixel in an occipital background region of interest (ROI) from the mean counts per pixel in the basal ganglia ROI, and dividing the result by the mean counts per pixel in the background ROI. The specific binding ratios of patients were compared with 13 female control subjects without any clinical signs of Parkinson’s disease (range 20 to 70 years, median 56). A striatal asymmetry index was also calculated according to the formula: / . For statistical analysis unpaired Student’s t tests, regression analyses, and covariance analyses were used where appropriate. The study was approved by the local ethics committee and all subjects gave their informed consent. RESULTS Biochemical analysis of respiratory chain enzyme activities showed complex I and IV deficiency in all patients compared with measurements in healthy controls (table 1). The mitochondrial disorder was the result of heteroplasmic single large scale mitochondrial DNA deletions in seven of the 10 patients, with a deletion size ranging from 3.5 to 7.5 kB. The degree of heteroplasmy identified by Southern blot analysis varied from 16% to 78%. An A3243G point mutation in the tRNA Leu(UUR) gene at position 3243 was found in two patients. In patient No 10, Southern blot analysis detected multiple deletions of the mitochondrial genome with a degree of heteroplasmy below 20%. Neuropsychological deficits were present in eight patients, indicating a significant impairment of central nervous system function, predominantly affecting the frontoparietal region.17 Specific striatal 123I-FP-CIT binding was not significantly different between patients and controls (mean (SD): 3.12 (0.36) v 2.99 (0.41), p = 0.47, unpaired Student’s t test). Analyses of striatal subregions also did not detect differences in specific 123I-FP-CIT binding between patients and controls in putamen (2.93 (0.39) v 2.8 (0.48), p = 0.51) or caudate (3.04 (0.44) v 2.99 (0.39), p = 0.78). Table 1 Specific striatal 123I-FP-CIT binding: clinical data and biochemical data in skeletal muscle DAT density assessed with various PET and SPECT ligands has been shown to decrease with age. Regression analyses showed a similar loss of 123I-FP-CIT binding in caudate and putamen of both patients and controls (fig 1). Figure 1 Decline with age of specific striatal 123I-FP-CIT binding in patients and controls. There were no differences in the striatal asymmetry indices between patients and controls (0.002 (0.03) v 0.0026 (0.03), p = 0.73). Striatal binding ratios were not correlated with the degree of complex I (F(crit) value 0.5), IV deficiency (F(crit) value 0.52), or the degree of heteroplasmy (F(crit) value 0.68). Further subgroup analyses of eight patients with cognitive impairment (3.11 (0.32) v 2.99 (0.40), p = 0.63) and four patients with the most severe complex I deficiencies (<3 SD) revealed no decrease of the striatal binding indices compared with controls (3.02 (0.34) v 2.99 (0.40), p = 0.88). DISCUSSION To investigate the integrity of the dopaminergic system in patients with mitochondrial disorders and complex I deficiency we used the iodine labelled tropane analogue 123I-FP-CIT to determine the density of dopamine transporter terminals in vivo. As direct measurement of complex I activity in the brain, in particular in the substantia nigra, is not possible, we carefully selected patients who displayed CNS involvement clinically—that is, they had neuropsychological deficits, MELAS syndrome, or cerebellar ataxia. However, we did not detect a significant loss of dopaminergic striatal terminals in patients with mitochondrial disorders. Parkinsonism—especially dopa responsive parkinsonism—is not a common symptom in patients with mitochondrial disorders, and there are only case reports about patients with multiple mitochondrial DNA deletions and parkinsonism as a symptom of mitochondrial disorders.18 With respect to the patient with multiple mitochondrial DNA deletions in our study, we must emphasise that the grade of heteroplasmy was low (<20%). Although it remains to be determined whether individual patients will reveal an abnormal loss of 123I-FP-CIT SPECT on follow up, it is unlikely that the present result reflected insufficient sensitivity of the method, as FP-CIT readily allows the detection of dopaminergic terminal loss in clinically unaffected family members of patients with Parkinson’s disease.10 Thus our data suggest that dopaminergic neurones are not exceptionally vulnerable to impairment of the mitochondrial electron transport chain. The data may argue against the hypothesis that mitochondrial defects play a primary role in the pathogenesis of dopaminergic cell death in Parkinson’s disease, although we cannot exclude the possibility that the remaining DAT/dopaminergic terminals are functionally impaired. Indeed, despite ample experimental evidence that complex I inhibition damages dopaminergic neurones, epidemiological studies do not yet unequivocally identify corresponding environmental risk factors that might be responsible for the majority of sporadic cases of Parkinson’s disease.19 Genetic or metabolic factors, in addition to impairment of the mitochondrial electron transport chain, are required for dopaminergic cell death and terminal loss in Parkinson’s disease. ACKNOWLEDGEMENTS We gratefully acknowledge the technical assistance of K Kappes-Horn and Dr R Fimmers (Institute of Medical Bioinformatics). This study was supported by the Bonfor programme of the University of Bonn (UW) and the Kompetenznetz Parkinson (KT and UW) REFERENCES Jun AS, Brown MD, Wallace DC. A mitochondrial DNA mutation at nucleotide pair 14459 of the NADH dehydrogenase subunit 6 gene associated with maternally inherited Leber hereditary optic neuropathy and dystonia. Proc Natl Acad Sci USA 1994;91:6202–10. Lera G, Bhatia K, Marsden CD. Dystonia a s the major manifestation of Leigh’s syndrome. Mov Disord 1994;9:642–9. Checcarelli N, Prelle A, Moggio M, et al. Multiple deletions of mitochondrial DNA in sporadic and atypical cases of encephalomyopathy. J Neurol Sci 1994;23:74–79. Schapira AH, Gu M, Taanman J-W, et al. Mitochondria in the etiology and pathogenesis of Parkinson’s disease. Ann Neurol 1998;44 (suppl 1) :S89–98. Shoffner JM, Watts RL, Juncos JL, et al. Mitochondrial oxidative phosphorylation defects in Parkinson’s disease. Ann Neurol 1991;30:332–9. Betarbet R, Sherer TB, MacKenzie G, et al. Chronic systemic pesticide exposure reproduces features of Parkinson’s disease. Nat Neurosci 2000;3:1301–6. Langston JW, Ballard P, Tetrud JW, et al. Chronic Parkinsonism in humans due to a product of meperidine-analog synthesis. Science 1983;219:979–80. Kish SJ, Shannak K, Hornykiewicz O. Uneven pattern of dopamine loss in the striatum of patients with idiopathic Parkinson’s disease. N Engl J Med 1988;318:876–80. Marek KL, Seibyl JP, Zoghbi SS, et al. ?-CIT/SPECT imaging demonstrates bilateral loss of dopamine transporters in hemi-Parkinson’s disease. Neurology 1996;46:231–7. Berendse HW, Booij J, Francot CMJE, et al. Subclinical dopaminergic dysfunction in asymptomatic Parkinson’s disease patients’ relatives with a decreased sense of smell. Ann Neurol 2001;50:34–41. Booij J, Tissingh G, Boer GJ, et al. FP-CIT SPECT shows a pronounced decline of striatal dopamine transporter labelling in early and advanced Parkinson’s disease. J Neurol Neurosurg Psychiatry 1997;62:133–40. Tissingh G, Booij J, Bergmans P, et al. Iodine-123-N-(fluoropropyl-2?-carbomethoxy-3?-(4-iodophenyl) tropane SPECT in healthy controls and early stage, drug-naive Parkinson’s disease. J Nucl Med 1998;39:1143–8. Lavalaye J, Booij J, Reneman L, et al. Effect of age and gender on dopamine transporter imaging with FP-CIT SPET in healthy volunteers. Eur J Nucl Med 2000;27:867–9. Schr?der R, Vielhaber S, Wiedemann FR, et al. New insights into the metabolic consequences of large-scale mtDNA deletions: a quantitative analysis of biochemical, morphological, and genetic findings in human skeletal muscle. J Neuropathol Exp Neurol 2000;59:353–60. Benamer TS, Patterson J, Grosset DG, et al. Accurate differentiation of parkinsonism and essential tremor using visual assessment of -FP-CIT SPECT imaging: the -FP-CIT study group. Mov Disord 2000;15:503–10. Radau P, Koch W, Holtmannspoetter M, et al. Automated, objective software for 3D registration and analysis of dopamine transporter SPECT studies. J Nucl Med 2003;44 (suppl) :12. Bosbach S, Kornblum C, Schr?der R, et al. Executive and visuospatial deficits in patients with chronic progressive external ophthalmoplegia and Kearns-Sayre syndrome. Brain 2003;126:1231–40. Moslemi AR, Melberg A, Holme E, et al. Autosomal dominant progressive external ophthalmoplegia-distribution of multiple mitochondrial DNA deletions. Neurology 1999;53:79–84. Taylor CA, Saint-Hilaire MH, Cupples LA, et al. Environmental, medical, and family history risk factors for Parkinson’s disease: a New England-based case control study. Am J Med Genet 1999;88:742–9....查看详细 (15704字节)
☉ 11357081:Long duration asymmetrical postural tremor is likely to predict development of Parkinson’s disease and not essential tremor: clinical follow
1 Regional Movement Disorders Unit, King’s College Hospital, London, UK 2 University Hospital Lewisham, Lewisham, UK 3 Guy’s, King’s and St Thomas’ School of Biomedical Medicine, King’s College, London, UK 4 Department of Nuclear Medicine, King’s College Hospital, London, UK 5 MRC Clinical Sciences Centre, Faculty of Medicine, Hammersmith Hospital, London, UK Correspondence to: Dr K Ray Chaudhuri Department of Neurology, King’s College Hospital, Denmark Hill, London, SE5 9RS, UK; Ray.chaudhuri@uhl.nhs.uk ABSTRACT Background: Patients presenting with asymmetrical postural tremor with or without mild rest tremor may be diagnosed as having essential tremor (ET), although there is considerable diagnostic uncertainty as to the long term outcome of these patients. Objective: In this study, retrospective observations were made on 13 patients presenting originally with asymmetrical postural tremor, initially thought to have ET based on tremor characteristics, alcohol responsiveness, and family history but who subsequently met the criteria of Parkinson’s disease (PD). Methods: The patients were observed and followed up clinically with ancillary imaging using dopamine transporter SPECT scan or levodopa challenge tests in some cases. The diagnosis at original presentation with postural tremor was made with retrospective case note review. Results: After a variable and long latent period all patients developed additional signs suggesting a clinical diagnosis of PD although picking up an initial label of ET. Conclusions: We suggest exercising caution regarding a diagnosis of ET in patients presenting with late onset asymmetrical postural tremor even if there is no rest tremor. Alcohol sensitivity of tremor, family history of tremor, or responsiveness to ? blockers may not be helpful in diagnosing ET in these cases and some may develop PD in the long term. Abbreviations: ?-CIT SPECT, 2-?-carbomethoxy-3-?-(4- iodophenyl)tropane single photon emission computed tomography; ET, essential tremor; PD, Parkinson’s disease Keywords: asymmetrical; Parkinson’s disease; postural; rest; tremor Currently, confusion still exists with regard to the diagnosis in patients presenting with later onset unilateral or asymmetrical dominantly postural tremor, and these cases are often labelled as atypical essential tremor (ET). It is known that ET is a heterogeneous disorder, and some workers have suggested that in some cases Parkinson’s disease (PD) overlaps with the presentation of essential tremor—so called "ETPD" cases.1,2 In PD, a 4–8 Hz action tremor is as prevalent as the classic 3–5 Hz rest tremor and the two generally coexist. The postural tremor of PD may be alcohol or ? blocker responsive, and relatives of probands with tremor dominant PD may manifest ET.3–6 Diagnosis of asymmetrical predominantly postural tremor, with or without rest tremor therefore, remains confusing.7,8 Here, we report a clinical follow up study of 13 patients with a history of postural tremor with asymmetry present for at least 10 years, initially labelled as ET, who developed an additional rest tremor in the same arm during follow up resulting in a final diagnosis of tremor dominant PD. To our knowledge this is the first longitudinal clinical study of such a cohort. METHODS From a clinical database of patients with tremor attending our regional movement disorders clinic, we identified 13 patients with a history of postural tremor with asymmetry >10 years and no rest tremor who had an initial diagnosis of probable ET but a final diagnosis of tremor dominant or mixed pattern PD satisfying the UK PD brain bank criteria.9 The database is continually updated and currently holds records of 480 patients with a diagnosis of PD. Patients with a history of neuroleptic or vestibular sedative use were excluded. All 13 patients were examined by KRC and A Forbes (PD nurse specialist) and followed up in PD clinics. As our movement disorders clinic also offers surgical therapy with deep brain stimulation and has an active interest in the treatment of disorders with tremor, most patients with ET are not discharged but followed up at intervals of 6–12 months. Assessments at the time of original referral were ascertained retrospectively by examining case records and patient/caregiver interviews. Five of the 13 patients had striatal dopamine transporter (DAT) binding measured using ?-CIT single photon emission computed tomography (SPECT), and all had trials of levodopa/dopamine agonists. Five patients underwent a levodopa challenge test using a standard protocol.10 RESULTS A total of 13 patients (10 men, three women; mean age at diagnosis of PD 69.8 years, range 51–87) presenting with asymmetrical postural tremor and subsequent development of rest tremor and parkinsonism with a tremor duration of 19.2 years (range 10–50) were included in the study. The duration of tremor could have been skewed by the tremor duration of 50 years in one patient. When this patient was excluded, the mean duration of tremor to final diagnosis was 15.9 years (range 10–26). Mean age at the time of original presentation with asymmetrical postural tremor was 50.6 years (range 36–69). Historical interviews suggested that the tremor pattern had changed from an asymmetrical postural tremor to express additional rest tremor and other signs of parkinsonism for a mean period of 2.5 years (range 1–5) before final presentation to our clinic (fig 1). All patients now had an 8–10 Hz postural tremor and a slower 3–5 Hz rest tremor in addition to bradykinesia and cogwheeling. The patients responded to dopaminergic treatment with levodopa and/or levodopa and dopamine agonist (n = 7), dopamine agonists (n = 5) and benzhexol (n = 1). Patients 9 and 13 were given a trial of dopamine agonists in spite of strongly positive levodopa challenge (table 1) because of their relatively young age; Hoehn and Yahr stage at the time of diagnosis of PD was 2 (range 1.5–3). The levodopa challenge test was positive in all five patients (20–60% improvement). ?-CIT SPECT (n = 5) revealed reduced uptake of ?-CIT in the striatum contralateral to the dominantly affected arm. Cerebral magnetic resonance imaging or computed tomography brain scans were normal in all. Figure 1 Duration of postural tremor (PT) and subsequent development of rest tremor (RT) in the 13 patients reported in this paper. Table 1 Clinical details of the 13 patients included in the study Historically, 6/13 patients were documented to have alcohol induced attenuation of postural tremor while a family history (in first degree relatives) of tremor/parkinsonism was present in 8/13. At initial presentation with postural tremor, all were tried on ? blockers (propranolol) with variable response. At follow up and after re-presentation with parkinsonism only one patient continues on propranolol in addition to dopaminergic treatment. DISCUSSION This clinical observational study has highlighted the following facts: Late onset isolated unilateral or asymmetrical postural tremor may be a predictor of future expression of tremulous PD. There may be a long and variable latent period (up to 50 years in our series) before there is a phenotypic alteration suggesting the development of PD. Alcohol sensitivity and family history, thought to be useful as a diagnostic aid to ET, may also be present in patients with PD presenting initially with postural tremor. These conclusions are supported by the fact that the patients reported in this study presented with an asymmetrical postural tremor without rest tremor and were initially diagnosed as having ET, and all subsequently developed tremulous PD after a variable period averaging 15.9 years after exclusion of one case with a latent period of 50 years. The mean period of change in tremor characteristics and distribution prior to the final diagnosis of PD was 2.5 years and included the development of rest tremor in the arm affected by postural tremor and other signs of parkinsonism. Development of PD was supported by additional ?-CIT changes in some patients, positive levodopa challenge test in others, and sustained response to dopaminergic treatment in all. It may be argued that these patients represent coincidental development of PD in cases of ET, the so called ETPD phenotype as has been suggested by Jankovic,1 or the condition of ET with isolated rest tremor as suggested by Louis and Jurewicz.5 However, the latter is unlikely in our patients as all expressed global signs of parkinsonism and not just rest tremor. Furthermore, development of PD with rest tremor occurring in arms affected by postural tremor is also unlikely to be wholly coincidental in 13 cases from a database sample of 480, although there is the inevitable bias in the ascertainment of these cases from a specialist movement disorders clinic database. We also acknowledge the fact that it is not possible to predict from this study what percentage of people with asymmetrical postural tremor will develop PD in the long term as we did not study a similar group of people with asymmetrical postural tremor who did not develop PD. An overlap of parkinsonism and ET has been suggested previously by many workers and, more recently, electrophysiological means such as H-reflex recovery curves have been put forward as means to distinguish between ET, tremulous PD, and ET with PD although the pathophysiological basis of ET remains unclear.11,12 Overlap of ET and PD is also supported by the findings that occasionally parkinsonian tremors may respond to ? blockers, may be attenuated by alcohol intake (as evident in several of our patients) and a recent description of the PARK4 locus in chromosome 4p in an autosomal dominant family (the Iowa kindred) with parkinsonism and postural tremor suggestive of ET with a good levodopa response.13–15 Yahr and colleagues recently reported a large kindred with co-occurrence of ET and PD.16 Three patients developed signs of ET at an early age but signs of PD became evident only in their fifties. The authors proposed a specific genetic mutation/clustering linking ET with PD. In the present study, 61.5% of patients had a family history of tremor/parkinsonism and thus the genetic basis of this problem needs further exploration. In conclusion, we have presented a clinical case series of 13 patients, all presenting with an asymmetrical postural tremor with or without a family history of tremor/parkinsonism and who after an initial diagnosis of ET and a variable period averaging 19.2 years developed signs of tremulous PD. The final diagnosis of PD was supported by a positive levodopa challenge test/successful dopaminergic treatment in all and supportive ?-CIT SPECT in some cases. We suggest that caution regarding a diagnosis of ET should be exercised in patients presenting with late onset asymmetrical postural tremor even if there is no rest tremor. Alcohol sensitivity of tremor, family history of tremor or responsiveness to ? blockers may not be helpful in such cases while dopamine transporter or fluordopa imaging with SPECT or positron emission tomography may be useful in predicting which patients will develop PD although prospective studies are required to validate this observation. Our clinical study would suggest such cases develop PD after a variable and often a long latent period. Whether this phenotype represents an overlap of ET and PD or whether isolated postural tremor is a marker for tremulous PD remains unclear. ACKNOWLEDGEMENTS The authors thank Mrs A Forbes and Dr S Pal for their help with recruiting and examining patients. REFERENCES Jankovic J. Essential tremor: a heterogenous disorder. Mov Disord 2002;17:638–44. Jankovic J. Essential tremor: clinical characteristics. Neurology 2000;54 (suppl 4) :S21–S25. Sethi KD. Tremor. Curr Opin Neurol 2003;16:481–5. Louis ED, Levy G, Majia-Santana H, et al. Risk of action tremor in relatives of tremor-dominant and postural instability gait disorder PD. Neurology 2003;61:931–6. Louis ED, Jurewicz EC. Olfaction in essential tremor patients with and without isolated rest tremor. Mov Disord 2003;18:1387–9. Findley LJ, Gresty MA, Halmagyi GM. Tremor, the cogwheel phenomenon and clonus in PD. J Neurol Neurosurg Psychiatry 1981;44:534–6. Rajput AH, Rozdlsky B, Ang L, et al. Significance of parkinsonian manifestations in essential tremor. Can J Neurol Sci 1993;20:114–17. Brooks DJ, Playford ED, Ibanez V, et al. Isolated tremor and disruption of the nigrostriatal dopaminergic system: an 18F-dopa PET study. Neurology 2002;42:1554–60. Hughes AJ, Daniel SE, Kilford L, et al. Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: a clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry 1992;55:181–4. Albanese A, Bonuccelli U, Brefel C, et al. Consensus statement on the role of acute dopaminergic challenge in Parkinson’s disease. Mov Disord 2001;16:197–201. Sabbahi M, Etnyre B, Al-Jawayed L, et al. H-relex recovery curves differentiate essential tremor, Parkinson’s disease and the combination of essential tremor Parkinson’s disease. J Clin Neurophysiol 2002;19:245–51. Deuschl G, Bergman H. Pathophysiology of nonparkinsonian tremors. Mov Disord 2002;17 (suppl 3) :S41–S48. Bain PG, Findley LJ, Thompson PD, et al. A study of hereditary essential tremor. Brain 1994;117 (Pt 4) :805–24. Koller WC, Busenbark K, Miner K. The relationship of essential tremor to other movement disorders: report on 678 patients. Essential Tremor Study Group. Ann Neurol 1994;35:717–23. Farrer M, Gwinn-Hardy K, Muenter M, et al. A chromosome 4p haplotype segregating with Parkinson’s disease and postural tremor. Hum Mol Genet 1999;8:81–5. Yahr MD, Orosz D, Purohit DP. Co-occurrence of essential tremor and Parkinson’s disease: clinical study of a large kindred with autopsy findings. Parkinsonism Relat Disord 2003;9:225–31....查看详细 (14184字节)
☉ 11357082:Prescribing safety features of general practice computer systems: evaluation using simulated test cases
1 Thames Avenue Surgery, Rainham, Kent, 2 Division of Primary Care, University of Nottingham, Nottingham NG7 2RD, 3 Division of Community Health Sciences: GP Section, University of Edinburgh, 4 PRIMIS, University of Nottingham Correspondence to: Anthony J Avery tony.avery@nottingham.ac.uk Introduction We used a two round Delphi approach to reach agreement on the most important safety features of general practice computer systems.5 This involved electronically circulating a list of 55 theoretically derived statements related to safety to 22 members of a selected multidisciplinary expert panel. Statements related to eight broad themes covering key areas in the medicines management process: prescriber alerts, reports and clinical audit, user interface, repeat prescribing, decision support, coding, monitoring, and links to laboratories. Over 90% of the panel judged 32 of these statements to be important, and these were then used to develop 18 scenarios, which were tested using dummy patient records on the four computing systems. The systems (labelled A, B, C, and D in order to preserve suppliers' anonymity) were independently evaluated at Primary Care Information Services (PRIMIS) laboratories by two members of the project team. To minimise risk of bias, systems were tested with each of the scenarios in random order and data were recorded on to piloted data extraction sheets. We defined the standards against which the computing systems were to be evaluated. These included appropriate alerts when contraindicated drugs or hazardous drug-drug combinations were prescribed. For each scenario, the safety profile of the computing system was categorised as appropriate or inappropriate. Evaluators compared findings, and an agreed mechanism was available for resolving disagreements should these arise. Finally, to ensure that there were no technical set-up problems that could have accounted for the observed failures, we reported the problems that were identified to the manufacturers and invited comment. None of the systems produced alerts for all of the 18 scenarios (table). In terms of prescription of drugs with similar names, none of the systems warned for all 10 drug pairs considered. Responses of computer systems tested for prescribing scenarios The evaluators produced no discrepancies in assessing the safety of systems. Each of the four system suppliers agreed with our assessments. Comment Department of Health. Delivering 21st century IT support for the NHS: national strategic programme. London: Department of Health, 2002. www.dh.gov.uk/assetRoot/04/06/71/12/04067112.pdf (accessed 23 Apr 2004). Magnus D, Rodger S, Avery AJ. GPs' views on computerised drug interaction alerts: questionnaire survey. J Clin Pharm Ther 2002;27: 377-82. Yen-Fu C, Avery AJ, Neil K, Johnson C. Assessing the occurrence and preventability of prescribing potentially hazardous/contraindicated drug combinations in general (family) practice. Pharmacoepidemiol Drug Safety 2001;10: S53. Wilson T, Sheikh A. Enhancing public safety in primary care. BMJ 2002;324: 584-7. Avery AJ, Savelyich B, Teasdale S. Improving the safety features of general practice computer systems. Informatics Prim Care 2003;11: 203-6....查看详细 (3295字节)
☉ 11357083:Structural correlates of early and late onset Alzheimer’s disease: voxel based morphometric study
1 Laboratory of Epidemiology and Neuroimaging, IRCCS San Giovanni di Dio – FBF, Brescia, Italy 2 AFaR – Associazione Fatebenefratelli per la Ricerca, Rome, Italy 3 Machine Vision Laboratory, Department of Mathematics and Computer Science, University of Udine, Udine, Italy 4 Service of Neuroradiology, Ospedale Maggiore, Verona, Italy 5 Department of Neurology, Kuopio University Hospital, Kuopio, Finland 6 Department of Clinical Radiology, Kuopio University Hospital, Kuopio, Finland Correspondence to: Dr G B Frisoni Laboratory of Epidemiology and Neuroimaging, IRCCS San Giovanni di Dio – FBF, via Pilastroni 4, I-25123 Brescia, Italy; papers@centroAlzheimer.it; http://www.centroAlzheimer.it ABSTRACT Objective: To examine the brain structural correlates of age at onset in patients with Alzheimer’s disease. Methods: We studied nine patients with early onset (age 65 years), nine with late onset (age >65) Alzheimer’s disease (EOAD and LOAD, respectively) of mild-moderate severity, and 26 controls who were stratified into younger (YC, age 65, n = 9) and older (OC, age >65, n = 17) subjects. The patients were closely matched for clinical severity: 3/2/3/1 patients had clinical dementia rating of 0.5/1/2/3, respectively, in both the groups. High resolution magnetic resonance images of the brain of the EOAD and YC groups and the LOAD and OC groups were compared on a voxel by voxel basis with statistical parametric mapping to detect areas specifically atrophic. Results: The patients with EOAD showed greater neocortical atrophy at the temporoparietal junction while the patients with LOAD showed greater hippocampal atrophy. The results could not be accounted for by the apolipoprotein E genotype. Conclusions: Since genetic factors are believed to play a relevant pathogenetic role in EOAD and environmental factors in LOAD, genetic and environmental factors may differentially predispose the neocortical and limbic areas to the development of Alzheimer’s neuropathology. Abbreviations: ApoE, apolipoprotein E; CDR, clinical dementia rating (scale); CT, computed tomography; EO/LOAD, early onset/late onset Alzheimer’s disease; MRI, magnetic resonance imaging; PET, positron emission tomography; SPECT, single photon emission computed tomography; VBM, voxel based morphometry Keywords: age at onset; Alzheimer’s disease; voxel based morphometry Whether or not sporadic early and late onset Alzheimer’s disease (EOAD and LOAD, respectively) are variants of the same disease or two distinct entities is still unknown. Research on the topic has focused on clinical, neuropsychological, and functional and structural imaging features. A higher prevalence of language impairment or other neocortical functions1–3 and faster progression has been reported in EOAD,3,4 but others have failed to confirm these findings.5 Functional imaging with single photon emission computed tomography (SPECT) and positron emission tomography (PET) has more consistently reported more severe perfusional and metabolic deficits in the temporoparietal areas in EOAD,6–8 although only one recent study has found differences in the medial temporal regions.8 The few structural imaging studies published to date have shown greater grey matter atrophy in EOAD. An early computed tomography (CT) study reported atrophy in patients with EOAD but did not compare this with its topographical distribution in LOAD.9 Similar results were later replicated in a magnetic resonance imaging (MRI) study.10 In a serial CT study, Kono and colleagues4 found that progression of cerebral atrophy was greater in patients with EOAD but again they did not study the localisation of the atrophy. Similar results were found in an MRI study by Woo et al.11 In the present study we examined the brain structural correlates of age at onset in patients with EOAD and LOAD to identify specific patterns of grey matter atrophy. We used MR based, voxel based morphometry (VBM), a computerised and largely automated algorithm that allows assessment of structural changes throughout the whole brain with no specific a priori hypothesis.12 METHODS Participants and assessment The patients for this study were selected from a group of 29 patients with NINCDS-ADRDA13 probable AD described in previous reports.14 Age at onset was estimated from the caregiver’s report of memory disturbances exceeding the episodic forgetfulness that might be regarded as usual for the patient or of other disturbances (language, praxis, orientation, visuospatial skills) that proved to be clearly related to the disease.14 None of the EOAD patients had a family history suggestive of autosomal dominant disease, although a few had one or two affected relations. Neuropsychological testing was carried out as previously described.15,16 The 26 control subjects were relatives of the patients (mostly spouses) without cognitive deficits. All patients and controls were right handed. Apolipoprotein E (ApoE) genotyping was carried out as previously described.17 Written informed consent was obtained from both the patients and their primary caregivers or the control subjects. No compensation was provided. The study was approved by the local ethics committee. Of the original 29 patients with AD, nine were 65 years or younger at disease onset (EOAD). Of these, 3, 2, 3, and 1 had clinical dementia rating (CDR)18 of 0.5, 1, 2, and 3, respectively. From the other 20 (LOAD) patients, nine were selected to match the EOAD group on the CDR scale on a 1:1 basis. When more than one matching patient with LOAD was available, the one with the closest matching Mini Mental State Examination (MMSE) was chosen. Controls were stratified into younger (YC, age 65, n = 9) and older (OC, age >65, n = 17) and compared with the patients with EOAD and LOAD, respectively, in the VBM analysis. Magnetic resonance imaging Both the patients and controls underwent high resolution sagittal T1-weighted volumetric MRI as previously described.19 Intracranial volume was measured by manual tracing on 3.9 mm thick coronal slices from anterior to posterior. The average intraclass correlation coefficient was 0.983 (95% C.I. 0.932 to 0.996, p<0.0005). Voxel based morphometry preprocessing This has been described in detailed in previous reports19 and a detailed flow chart is available at http:\\centroalzheimer.supereva.it\additional-data.doc.20 Briefly, MR images were processed with SPM99 following an optimised protocol including (a) generation of a customised template, (b) generation of customised prior probability maps, and (c) the main VBM steps: normalisation of the original MR images, segmentation of normalised images, cleaning of grey matter images, modulation of grey matter images, and smoothing of modulated images. Statistical analysis A "single subject: conditions and covariates" model was used. Intracranial volume and sex were included as nuisance covariates. Regions specifically atrophic in EOAD and LOAD were detected by contrasting EOAD with YC and LOAD with OC, thresholding the resulting T maps at p<0.05 corrected for multiple comparisons. RESULTS The patients with EOAD and the YC did not differ with regard to age (mean (SD), range: 62 (7), 53–70 v 61 (4), 54–64; p = 0.34), sex (78% v 89% women; p = 0.53), education (7 (SD 2) v 8 (4); p = 0.49), and ApoE 4 allele (22% v 6%; p = 0.35). They differed with regard to MMSE (18 (5) v 30 (1); p<0.005). The patients with LOAD when compared with the OC group, showed a trend towards older age (78 (4) 74–86 v 74 (6) 66–86; p = 0.085), had higher 4 allele frequency (39% v 13%; p = 0.071), and had significantly different MMSE (20 (5) v 29 (2); p<0.005) and intracranial volume (ICV) (1056 (76) v 1160 (106) ml; p = 0.03). Patients with EOAD when compared with the patients with LOAD had lower MMSE (18 (5) v 20 (5); p<0.005) and shorter disease duration (2.8 (2.1) v 4.1 (2.8)), but this difference did not reach statistical significance (p = 0.26). The mean age at onset was 59 (6) and 73 (5) (p<0.005), respectively. Patients with EOAD performed less well than the patients with LOAD on non-verbal tasks of constructional apraxia (Rey–Osterrieth figure (copy) 4.8 (11.1) v 20.7 (13.5); p = 0.03, Mann–Whitney U test) and reasoning (Raven’s coloured progressive matrices 12.8 (6.7) v 22.1 (4.1); p = 0.04), while the two groups were not significantly different on the verbal and non-verbal memory tasks as well as verbal fluency tasks. Figure 1A and table 1 show that patients with EOAD had greater atrophy than YC in the temporoparietal cortex. The most significant voxel—that is, the voxel with the highest z score, was in the right temporoparietal junction, and the widest cluster was in the left parietal regions. A relatively small and less significant cluster was located in the head of the hippocampus. In contrast, in the patients with LOAD the largest and most significant clusters of atrophy were located in the hippocampus bilaterally, and smaller and less significant clusters were located in the inferior temporal neocortex (fig 1B and table 1). Figure 1 Regions of atrophy in (A) patients with early onset Alzheimer’s disease compared with younger controls and in (B) patients with late onset Alzheimer’s disease compared with the older controls, with p<0.05 corrected for multiple comparisons. Intracranial volume and sex were included as confounding covariates. Atrophy in patients with early onset involved the temporoparietal junction and the right middle and left inferior frontal gyri (A); those with late onset showed more atrophy in the hippocampus bilaterally and anterior part of the temporal and fusiform gyri (B). Table 1 Atrophic regions in patients with early onset Alzheimer’s disease compared with the younger controls and in patients with late onset Alzheimer’s disease compared with the older controls (p<0.05 corrected for multiple comparisons) To take into account the effect of ApoE polymorphism on brain morphology, the analysis was re-run including the presence of at least one 4 allele as a nuisance covariate, but the results did not change appreciably. DISCUSSION We have shown that patients with early onset Alzheimer’s disease have greater temporoparietal atrophy and patients with late onset Alzheimer’s disease greater medial temporal atrophy than controls. These data suggest that age at onset is associated with the region where the disease strikes in the brain. Since genetic factors are believed to play a relevant role in EOAD even when known mutations cannot be found, while LOAD is believed to be mainly due to environmental factors, these results lead to the hypothesis that genetic and environmental factors may predispose topographically different regions of the brain to AD pathology. The interpretation of the structural patterns in EOAD and LOAD should be addressed separately. In LOAD, the higher frequency of 4 might explain the finding of greater medial temporal lobe atrophy as patients carrying the 4 allele have smaller hippocampi21 and tend to have disproportionate impairment of memory.22 However, accounting for the effect of ApoE genotype in our analysis did not alter the results, indicating that the effect of age at onset on the loss of hippocampal volume is not mediated by the ApoE genotype. Alternatively, the age associated changes known to take place in the medial temporal lobe23 may result in lower functional—and structural—reserve in these areas thus predisposing older patients to development of symptoms related to medial temporal lobe damage, as suggested by some neuropathological studies.23 More intriguing is the interpretation of the selective neocortical involvement in EOAD. Genes play a relevant role in EOAD,24 and yet unknown genetic factors might confer neocortical regions greater susceptibility to AD. This hypothesis is consistent with the twin studies of Thompson and colleagues, who showed that frontal, linguistic, and parieto-occipital areas (including the temporoparietal cortex) are under strict genetic control, with 95–100% of the variance being attributable to genetic factors.25 On the contrary, the hippocampus is genetically controlled to a lesser degree, with genes explaining only about 40% of the variance of hippocampal volumes.26 These observations suggest that genetic factors may drive the susceptibility to developing AD lesions in the neocortex in young age, while environmental factors might exert a similar effect on medial temporal lobe structures at older age. Some limitations of this study should be borne in mind. First, we do not know whether the participants of this study were carriers of certain mutations. Although none of the patients with EOAD had a family history suggestive of autosomal dominant AD, we cannot exclude that some had mutations of APP, PS1, or PS2. Secondly, the history of specific clinical features of dementia (such as early language or visuospatial disturbances) was not collected in a structured way, thus preventing correlations with patterns of structural impairment. Thirdly, it can be problematic to interpret the results of VBM in areas of high anatomical variation such as the medial temporal lobe due to imperfect registration. Lastly, our EOAD group was small, and replication of our findings in studies with larger groups is necessary. ACKNOWLEDGEMENTS Cristina Geroldi, MD, PhD, Roberta Rossi, PsyD, and Lorena Bresciani, PsyD, gave useful suggestions. REFERENCES Seltzer B, Sherwin I. A comparison of clinical features in early- and late-onset primary degenerative dementia. One entity or two? Arch Neurol 1983;40:143–6. Chui HC, Teng EL, Henderson VW, et al. Clinical subtypes of dementia of the Alzheimer type. Neurology 1985;35:1544–50. Jacobs D, Sano M, Marder K, et al. Age at onset of Alzheimer’s disease: relation to the pattern of cognitive dysfunction and rate of decline. Neurology 1994;44:1215–20. Kono K, Kuzuya F, Yamamoto T, et al. Comparative study of cerebral ventricular dilation and cognitive function in patients with Alzheimer’s disease of early versus late onset. J Geriatr Psychiatry Neurol 1994;7:39–45. Haupt M, Pollmann S, Kurz A. Symptom progression in Alzheimer’s disease: relation to onset age and familial aggregation. Results of a longitudinal study. Acta Neurol Scand 1993;88:349–53. Grady CL, Haxby JV, Horwitz B, et al. Neuropsychological and cerebral metabolic function in early vs late onset dementia of the Alzheimer type. Neuropsychologia 1987;25:807–16. Sakamoto S, Ishii K, Sasaki M, et al. Differences in cerebral metabolism between early and late onset types of Alzheimer’s disease. J Neurol Sci 2002;200:27–32. Kemp PM, Holmes C, Hoffmann SM, et al. Alzheimer’s disease: differences in technetium-99m HMPAO SPECT scan findings between early onset and late onset dementia. J Neurol Neurosurg Psychiatry 2003;74:715–19. Drayer BP, Heyman A, Wilkinson W, et al. Early-onset Alzheimer’s disease: an analysis of CT findings. Ann Neurol 1985;17:407–10. McDonald WM, Krishnan KR, Doraiswamy PM, et al. Magnetic resonance findings in patients with early-onset Alzheimer’s disease. Biol Psychiatry 1991;29:799–810. Woo Ji, Kim JH, Lee JH. Age of onset and brain atrophy in Alzheimer’s disease. Int Psychogeriatr 1997;9:183–96. Ashburner J, Csernansky JG, Davatzikos C, et al. Computer-assisted imaging to assess brain structure in healthy and diseased brains. Lancet Neurol 2003;2:79–88. McKhann G, Drachman D, Folstein MF, et al. Clinical diagnosis of Alzheimer’s disease: report of the NINCDS–ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology 1984;34:939–44. Frisoni GB, Beltramello A, Weiss C, et al. Linear measures of atrophy in mild Alzheimer’s disease. AJNR Am J Neuroradiol 1996;17:913–23. Binetti G, Magni E, Padovani A, et al. Neuropsychological heterogeneity in mild Alzheimer’s disease. Dementia 1993;4:321–6. Frisoni GB, Beltramello A, Geroldi C, et al. Brain atrophy in frontotemporal dementia. J Neurol Neurosurg Psychiatry 1996;61:157–65. Kohlmeier M, Drossel H, Sinha P, et al. Rapid and simple method for the identification of ApoE isomorphic phenotype for whole serum. Electrophoresis 1992;13:258–63. Hughes CP, Berg L, Danziger WL, et al. A new clinical scale for the staging of dementia. Br J Psychiatry 1982;140:566–72. Testa C, Laakso MP, Sabattoli F, et al. A comparison between the accuracy of voxel-based morphometry and hippocampal volumetry in Alzheimer’s disease. J Magn Reson Imaging 2004;19:274–82. Frisoni GB, Testa C, Sabattoli F, et al. Flow chart of the VBM preprocessing steps. http:\\centroalzheimer.supereva.it\additional-data.doc (accessed 8 June 2004). Lehtovirta M, Laakso MP, Frisoni GB, et al. How does the apolipoprotein E genotype modulate the brain in aging and Alzheimer’s disease? A review of neuroimaging studies. Neurobiol Aging 2000;21:293–300. Lehtovirta M, Soininen H, Helisalmi S, et al. Clinical and neuropsychological characteristics in familial and sporadic Alzheimer’s disease: relation to apolipoprotein E polymorphism. Neurology 1996;46:413–19. David JP, Ghozali F, Fallet-Bianco C, et al. Glial reaction in the hippocampal formation is highly correlated with aging in human brain. Neurosci Lett 1997;235:53–6. Janssen JC, Beck JA, Campbell TA, et al. Early onset familial Alzheimer’s disease: mutation frequency in 31 families. Neurology 2003;60:235–9. Thompson PM, Cannon TD, Narr KL, et al. Genetic influences on brain structure. Nat Neurosci 2001;4:1253–8. Sullivan EV, Pfefferbaum A, Swan GE, et al. Heritability of hippocampal size in elderly twin men: equivalent influence from genes and environment. Hippocampus 2001;11:754–62....查看详细 (18083字节)
☉ 11357084:EEG coherence reflects regional corpus callosum area in Alzheimer’s disease
1 Department of Psychiatry, Ludwig-Maximilians-University, Munich, Germany 2 Department of Radiology, Ludwig-Maximilians-University, Munich 3 Department of Clinical Neuropsychology, Free University, Amsterdam, Netherlands Correspondence to: Dr Oliver Pogarell Department of Psychiatry, Ludwig-Maximilians-University of Munich, Nussbaumstrasse 7, D-80336 Munich, Germany; oliver.pogarell@med.uni-muenchen.de ABSTRACT Objective: Correlations between corpus callosum size and interhemispheric EEG coherence were investigated as measures of interhemispheric connectivity in patients with Alzheimer’s disease. Methods: 11 patients underwent both magnetic resonance imaging and quantitative electroencephalography to assess corpus callosum size and interhemispheric coherence. For comparison, corpus callosum size was measured in 24 healthy elderly control subjects. Results: Corpus callosum cross sectional area was significantly reduced in Alzheimer patients relative to controls. Posterior interhemispheric coherence ( and ? frequencies) correlated significantly with the size of posterior corpus callosum area, and anterior coherence (, , and frequencies) with the size of anterior corpus callosum area in the Alzheimer patients. Conclusion: Region specific correlations between corpus callosum size and EEG coherence suggest that the decline in interhemispheric connectivity in Alzheimer’s disease results from a specific loss of cortical association neurones projecting through the corpus callosum. Abbreviations: MMSE, mini-mental state examination; MPRAGE, magnetisation prepared rapid acquisition gradient; NINCDS-ADRDA, National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer’s Disease and Related Disorders Association Keywords: Alzheimer’s disease; brain imaging techniques; neurophysiology Corpus callosum atrophy has been shown to occur independently of subcortical fibre degeneration in patients with Alzheimer’s disease.1–3 The commissural fibres of the corpus callosum play a dominant role in the maintenance of interhemispheric connectivity, which can be assessed functionally by EEG coherence analysis,4 a measure of similarity between electrical signals of different electrode positions. Coherence analysis indicates the functional connections between underlying cortical regions and is decreased in patients with dementia.5–8 In this study, we correlated corpus callosum size with measures of interhemispheric coherence in patients with Alzheimer’s disease. A region specific correlation between these two measures would support the hypothesis that corpus callosum atrophy in Alzheimer’s disease results from the loss of interhemispheric projecting neurones, leading to a decline in interhemispheric connectivity. METHODS Subjects We investigated 11 patients (seven male, four female) with probable Alzheimer’s disease according to the NINCDS-ADRDA criteria.9. Their mean (SD) age was 67 (13) years, and they showed mild (short term memory deficits) to moderately severe (assistance needed with household activities) cognitive decline, with a mean mini-mental state examination (MMSE) score of 17.2 (6.6). All patients had been screened to exclude medical comorbidity according to a standard protocol,2 were free of risk factors for cerebrovascular disease, and showed no signs of white matter disease on T2 weighted and FLAIR MRI sequences. They were not on drug treatment at the time of the EEG studies, which followed a drug-free period of at least two weeks. A group of 24 healthy elderly controls (mean age 62 (9) years, MMSE >28), who participated in the MRI study, was included for comparison of the corpus callosum data with the patient group. The ethics committee of the University of Munich approved the study, and all subjects or the holders of their Durable Power of Attorney gave their written informed consent. Magnetic resonance image Images were obtained with a 1.5 T magnetic resonance imaging (MRI) scanner (Magnetom Vision, Siemens, Germany). All subjects underwent a sagittally oriented MPRAGE sequence with 128 partitions and an effective slice thickness of 1.25 mm. We acquired a field of view of 260 mm with a matrix of 256x256 pixels, resulting in an in-plane pixel size of 1.0x1.0 mm. Corpus callosum measurement Areas of the corpus callosum and of five callosal subregions were measured in the midsagittal slice of the MPRAGE sequence, as described elsewhere,2 using ANALYZETM software (Biomedical Imaging Resource, Mayo Foundation, Rochester, Minnesota, USA) on an SGI workstation (Silicon Graphics, Palo Alto, California, USA). Subregions were defined using a simple geometrical construction and were labelled C1 to C5 in the rostral-occipital direction. Region C1 covers the callosal rostrum and genu; regions C2 to C4 the anterior, middle, and posterior truncus, respectively; and region C5, the isthmus and splenium. The number of pixels within each region was summed and multiplied by pixel size to obtain absolute values (mm2). EEG recording and analysis An EEG was digitally recorded from 19 electrodes placed according to the 10/20 system, using a computerised EEG unit (Brain Electrical Signal Topography, Austria, 1993) during five minutes with eyes closed and under resting conditions (impedances of electrodes below 5 k, bandpass 0.16 to 70 Hz, sample rate 256 Hz). Artefact-free data were processed off-line by bipolar transformation and segmentation into two second epochs. According to the protocol, at least 20 artefact-free segments were required from each subject for fast Fourier transform and power spectral analysis. Interhemispheric coherences were computed between anterior (F3–C3/F4–C4), lateral (F7–T5/F8–T6), and posterior (C3–O1/C4–O2) pairs of electrodes, based on the fast Fourier transform for each of the following frequency bands: (1–3 Hz), (4–7 Hz), 1 (8–10 Hz), 2 (10–12 Hz), ?1 (13–18 Hz), ?2 (18–24 Hz), ?3 (24–32 Hz), and total (1–32 Hz). Coherence is a function of power spectral outputs for the two pairs of electrodes (cross-covariance function) with values between 0 and 1 at a given frequency. A coherence value of 0 indicates random relations between the signals (phases are dispersed); a value of 1 means that the correlated signals are phase locked, indicating shared activity of the channels. Thus coherence is a quantitative measure of the similarity of signals in a given frequency band. Statistical analysis Statistical analyses were carried out using the Statistical Package for the Social Sciences (SPSS Inc, Chicago, Illinois, USA). Corpus callosum areas were compared between Alzheimer patients and controls using analysis of covariance (ANCOVA) with diagnosis as between-subjects factor and age as covariate. The patients’ coherences were analysed within the frequency bands for anterior, lateral, and posterior brain regions. Associations between electrophysiological (coherence values) and corpus callosum data were assessed using Spearman’s rank correlation coefficients (). In addition, partial correlations were calculated to control for the effects of age and MMSE scores. Probability (p) values below 0.05 were considered statistically significant. Owing to the exploratory character of the study and the small sample size, no correction was undertaken. RESULTS The mean (SD) cross sectional area of the corpus callosum was 356 (65) mm2 in the Alzheimer group, which was significantly smaller than the area in the control group (454 (70) mm2) as assessed by ANCOVA with the covariate age (F = 13.2, df = 1,32; p = 0.001). In the patient group the sizes of the callosal subregions were 98 (25), 43 (11), 41 (8), 39 (12), and 117 (23) mm2 for C1 through C5, respectively. The mean (SD) values of interhemispheric coherences, averaged for the whole frequency spectrum, ranged between 0.21 (0.14) (lateral) and 0.41 (0.12) (posterior). The frequency distribution revealed the highest interhemispheric coherences for frequency bands in the posterior regions, and for and frequencies in the frontal regions. The posterior interhemispheric coherences (, ? frequency bands) showed strong positive correlations with the total corpus callosum area ( = +0.76 and +0.66, p<0.01, for 2 and ?1 coherences, respectively) (table 1). Table 1 Correlations of mean regional interhemispheric coherences and corpus callosum sizes in patients with Alzheimer’s disease: Following the evidence of an anterior-posterior topography of corpus callosum fibre organisation, we correlated corresponding regional coherences and callosal subregions to investigate regional specificity. We found statistically significant correlations between anterior interhemispheric , , 2 coherences and callosal subregion C2, and between posterior 2, ?1 coherences and callosal area of subregion C5 (table 1). The posterior correlations remained significant after controlling for age and MMSE ( = +0.86, p<0.01; fig 1). Inverse analyses—that is, anterior (posterior) coherences and posterior (anterior) corpus callosum subregions—did not show significant correlations (table 1). Figure 1 Scatterplot of posterior interhemispheric EEG coherences (2 frequency band) and posterior corpus callosum sizes (subregion C5) of 11 patients with Alzheimer’s disease. Partial correlation (controlled for age, MMSE): = +0.86, p<0.01. DISCUSSION We investigated the association between the size of corpus callosum subregions and corresponding regional measures of interhemispheric coherences in patients with Alzheimer’s disease. There were strong positive correlations between the total corpus callosum area and interhemispheric posterior 2 and ?1 coherences. There were also significant positive correlations between anterior/posterior coherences and anterior/posterior callosal subregions. The relevance of the regional distribution of the results was supported by the finding that the inverse analyses showed no significant correlations. The data indicate that corpus callosum area in Alzheimer’s disease is directly related to a decrease in functional hemispheric connectivity. The posterior correlations remained significant after controlling for the effects of aging and dementia severity, which suggests that the associations between regional corpus callosum size and interhemispheric connectivity are not merely a consequence of disease progression, but rather reflect a biologically meaningful interaction between the two variables. The loss of correlations between the size of anterior callosal regions and lower frequency coherences after controlling for age and MMSE is most probably a consequence of the small number of patients under investigation. As the patients showed no sign of subcortical vascular disease on MRI scans, the reduced area of the corpus callosum is likely to reflect a loss of corticocortical projecting neurones, in agreement with previous studies on independent samples showing corpus callosum atrophy in the absence of white matter pathology,1–3 and significant correlations between corpus callosum atrophy and cortical metabolic decline in Alzheimer’s disease.10,11 In addition, the mean cross sectional corpus callosum area of the patients was significantly lower than in a group of healthy elderly controls, indicating callosal atrophy. Coherence analysis is a measure of alterations in brain connectivity, and previous EEG studies have also revealed lower interhemispheric coherences associated with corpus callosum pathology,12–14 providing evidence that interhemispheric coherences are affected by loss or disruption of long axonal connections between the hemispheres. Unfortunately we were unable to investigate more patients using both structural imaging and electrophysiological techniques, and the small number of subjects clearly compromised the statistical power of this investigation. Furthermore, no correction for multiple comparisons (for example, Bonferroni) was done in view of the exploratory character of the study. Nevertheless, our results show a clear correlation between structural and functional measurements which might well have clinical significance, for example in the milder stages of the disease, especially as the loss of functional connectivity assessed by coherence analysis is one of the most sensitive EEG findings in Alzheimer’s disease.5,6 Conclusions Our data suggest that atrophy of the corpus callosum in Alzheimer’s disease results from cortical neuronal degeneration, leading to a reduction in functionally intact commissural fibres and subsequently to an impairment of brain connectivity. This supports the idea that corpus callosum atrophy contributes to the cortical disconnection syndrome in Alzheimer’s disease on a region specific basis. ACKNOWLEDGEMENTS We thank Felician Iancu, Christine S?nger, and Bea Riemenschneider (Ludwig-Maximilians-University of Munich) for technical support. Part of this work was supported by grants from the Medical Faculty of the Ludwig-Maximilians-University, Munich, Germany (SJT), from the Hirnliga eV, Nürmbrecht, Germany (SJT, HH), and from the Competence Network on Dementias funded by the Ministry for Education and Research (BMBF 01 GI 0102), Germany (HH, SJT). REFERENCES Biegon A, Eberling JL, Richardson BC, et al. Human corpus callosum in aging and Alzheimer’s disease: a magnetic resonance imaging study. Neurobiol Aging 1994;15:393–7. Hampel H, Teipel SJ, Alexander GE, et al. Corpus callosum atrophy is a possible indicator of region- and cell type-specific neuronal degeneration in Alzheimer disease: a magnetic resonance imaging analysis. Arch Neurol 1998;55:193–8. Hampel H, Teipel SJ, Alexander GE, et al. Corpus callosum measurement as an in vivo indicator for neocortical neuronal integrity, but not white matter pathology, in Alzheimer’s disease. Ann NY Acad Sci 2000;903:470–6. Zaveri HP, Williams WJ, Sackellares JC, et al. Measuring the coherence of intracranial electroencephalograms. Clin Neurophysiol 1999;110:1717–25. Leuchter AF, Spar JE, Walter DO, et al. Electroencephalographic spectra and coherence in the diagnosis of Alzheimer’s-type and multi-infarct dementia. A pilot study. Arch Gen Psychiatry 1987;44:993–8. Leuchter AF, Newton TF, Cook IA, et al. Changes in brain functional connectivity in Alzheimer-type and multi-infarct dementia. Brain 1992;115:1543–61. Dunkin JJ, Leuchter AF, Newton TF, et al. Reduced EEG coherence in dementia: state or trait marker? Biol Psychiatry 1994;35:870–9. Jelic V, Shigeta M, Julin P, et al. Quantitative electroencephalography power and coherence in Alzheimer’s disease and mild cognitive impairment. Dementia 1996;7:314–23. McKhann G, Drachman D, Folstein M, et al. Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology 1984;34:939–44. Yamauchi H, Fukuyama H, Harada K, et al. Callosal atrophy parallels decreased cortical oxygen metabolism and neuropsychological impairment in Alzheimer’s disease. Arch Neurol 1993;50:1070–4. Teipel SJ, Hampel H, Pietrini P, et al. Region-specific corpus callosum atrophy correlates with the regional pattern of cortical glucose metabolism in Alzheimer disease. Arch Neurol 1999;56:467–73. Montplaisir J, Nielsen T, Cote J, et al. Interhemispheric EEG coherence before and after partial callosotomy. Clin Electroencephalogr 1990;21:42–7. Pinkofsky HB, Struve FA, Meyer MA, et al. Decreased multi-band posterior interhemispheric coherence with a lipoma on the corpus callosum: a case report of a possible association. Clin Electroencephalogr 1997;28:155–9. Knyazeva MG, Innocenti GM. EEG coherence studies in the normal brain and after early-onset cortical pathologies. Brain Res Brain Res Rev 2001;36:119–28....查看详细 (16091字节)
☉ 11357085:Health related virtual communities and electronic support groups: systematic review of the effects of online peer to peer interactions
1 Department of Health Policy, Management and Evaluation, University of Toronto, Centre for Global eHealth Innovation, University Health Network, Toronto General Hospital, Fraser Elliott Bldg, 190 Elizabeth St, Toronto, ON, Canada M5G 2C4, 2 Wessex Institute for Health Research and Development, University of Southampton, Southampton SO16 7PX, 3 Library, University Health Network, Toronto General Hospital, 4 Centre for Global eHealth Innovation, University Health Network, Toronto General Hospital Correspondence to: G Eysenbach geysenba@uhnres.utoronto.ca Abstract Included studies From all databases combined we identified and screened a total of 12 288 abstracts (figure). We selected 76 publications for retrieval of full text versions. Forty five publications met our inclusion criteria, describing 38 distinct studies: 20 randomised controlled trials, three meta-analyses of n of 1 trials, three non-randomised controlled trials, one cohort study, and 11 before and after studies (for included studies see tables A-D, for excluded studies see appendix 2, for multiple publications of the same study see appendix 3, all on bmj.com). CONSORT flow diagram of studies reviewed Only six of these studies dealt with "pure" peer to peer interventions.5-10 One study had a 2x2 factorial design (full or control website combined with or without peer to peer group), enabling the comparison of a peer to peer group with a minimal co-intervention with other arms.11 The remaining 31 studies evaluated complex interventions where the virtual community was only an adjunct to a broader intervention that often included structured psychoeducational components or treatment programmes, entailed giving printed brochures or videos, computers or web television access to participants, incorporated decision support or one to one therapeutic relationships with health professionals, offered personal online diaries, or contained games (table A on bmj.com). Examples of such complex interventions with peer to peer "adjunct" components are CHESS, Computerlink, Starbright World, Bosom Buddies, and Student Bodies. Because of the multiple components within these interventions it is not possible to draw more generalisable conclusions about the value of online peer to peer communication from them, as the results will be confounded by the co-interventions. Virtual communities evaluated as stand alone interventions The six studies evaluating "pure" virtual communities were before and after studies evaluating web based discussion forums,6 10 a chat room,8 or a combination of a chat room and newsgroup,9 with one cohort study evaluating mailing lists7 and one non-randomised controlled trial evaluating a voice bulletin board system.5 We identified no randomised trials evaluating the effects of peer to peer communities alone. We found one factorial design randomised controlled trial that compared the effects of the different components (including the peer to peer component) of a complex intervention with each other.11 The reporting of this trial is incomplete, however, as no P values for all comparisons are provided. Of the six studies, only one7 dealt with unmoderated venues; the remaining studies all reported some degree of facilitation by a health professional. With one exception, even studies coded as "stand alone" peer to peer interventions therefore had involvement from health professionals, with trained individuals leading the groups as moderators or facilitators by stimulating discussions, formulating questions, or posting topics of interest or educational material on the bulletin boards. Impact of virtual communities on health and social outcomes Table B on bmj.com summarises the characteristics of the studies; tables C and D on bmj.com report quantitative and qualitative findings from them, respectively. Tables 1 and 2 summarise the outcome measures reported most often across all studies. Depression and social support (each used in 12 studies) were the most commonly used measures. Only three studies, among them a before and after study and a cohort study, found significant improvements in depression scores, and nine studies (among them eight randomised controlled trials) did not find or report an intervention effect on depression. Similarly conflicting are the data for social support measures; five studies found significant effects and seven studies did not. Table 1 Summary of most often used outcome measures except smoking and their results Table 2 Summary of outcome measures for smoking and their results Measures of healthcare use were obtained in only three studies, with contradicting results: Alemi et al, evaluating a voice bulletin board, reported a significant decrease, Gustafson et al a significant increase in phone calls to providers.5 12 Nine studies focused on structured weight loss or healthy body weight interventions with peer to peer components, again with mixed, but mostly non-significant, results. In one study the internet support group even sustained a significantly smaller weight loss than face to face support groups.13 Five studies evaluated communities for diabetic patients; four of them measured glycosylated haemoglobin as an outcome measure, which has repeatedly been shown to be responsive to educational and behavioural interventions in diabetes.14 Only one study (a before and after study without control) showed a significant improvement.12 Six studies investigated the effect of smoking cessation programmes that included peer to peer groups. In a factorial design randomised controlled trial11 the effect of the two main components (psychoeducation programme on the website and peer to peer group) were evaluated separately. Abstinence rates after 1, 3, and 6 months in the arm with peer to peer group and minimal information intervention were slightly higher than in the arm with no peer to peer group and minimal information (6.8%, 5.5%, 9.3% v 3.6%, 2.9%, 7.6%, no P values reported). Abstinence rates were similar in the arm with peer to peer group and full psychoeducational intervention and the arm with no peer to peer group and full psychoeducational intervention (7.5%, 7.5%, 10% v 6.6%, 6.6%, 10.8%). Similar to many other studies in this field, this randomised controlled trial had methodological problems, with more than half of the participants not responding to follow up surveys and low usage of the intervention (less than 10% used the intervention). Quality of studies Although we did not formally score quality, we coded certain aspects of study quality. Among the 20 randomised controlled trials, only three trials described their randomisation methods in sufficient detail to permit the ascertainment of allocation concealment. One randomised controlled trial had used a clearly inappropriate randomisation method, using the last digit of the Compuserve ID to determine the intervention.11 All studies were necessarily unblinded and most outcomes self reported. Intention to treat analysis had been conducted for only eight randomised controlled trials. Discussion Despite extensive searches in the health, social sciences, communication, and informatics literature we failed to find robust evidence on the health benefits of virtual communities and peer to peer online support. In 31 studies investigators evaluated complex interventions, combining, for example, educational or cognitive behaviour therapy components with peer to peer communities, making it impossible to draw conclusions on the effectiveness of "pure" electronic peer to peer interactions as used daily by millions of people participating in internet discussion groups or mailing lists. The six studies that investigated peer to peer communication as stand alone interventions tended to have less than optimum research designs with few participants. Half of the studies that evaluated "pure" peer to peer interventions were before and after studies. As many participants improve "naturally" over time (regression to the mean), these studies are insufficient to attribute improvements of psychological or health outcomes to the intervention. In those cases where authors found statistically significant effects, no information was given as to whether the (often minimal) group differences were clinically significant. Most studies were exploratory in nature and many investigators administered multiple instruments and made multiple comparisons, diminishing the worth of a "positive" finding (for example, in a study with 20 comparisons one would expect one comparison being "significant" on a 5% level by chance alone). Possible explanations The absence of evidence does not mean that virtual communities have no effect. Several explanations are possible for the lack of studies and evidence. Firstly, there is little commercial or professional interest in evaluating "pure" virtual communities and "unsophisticated" peer to peer interventions such as mailing lists, as opposed to more complex interventions or interventions led by health professionals. Secondly, studies investigating "natural" self helping processes are difficult to recreate in controlled research environments. Many studies seemed underpowered, and only five provided sample size calculations or justifications. Another possible explanation for the failure of many authors to show an effect of virtual communities is that participants may need to have the intrinsic desire to communicate with other people in order for virtual communities to be beneficial. Participants in self help groups may be a self selected subgroup in whom self help processes are effective, and researchers "recruiting from the street" may be looking at the wrong populations. A third possible (but related) reason could be lack of participants' "compliance." Some investigators reported that the virtual community component was not heavily used,6 15-17 making it difficult to show an effect. It was, however, encouraging that some interventions did show an effect, and that in only two instances the control was favourable over the virtual community in terms of a health outcome13 or resource use.12 In some studies7 18-20 an association between greater use of peer to peer groups and better outcomes was observed, indicating a dose-response association, but the direction of causation (whether increased use leads to better outcomes, or whether an improvement in outcomes such as depression due to other factors leads to increased use) is unclear. No negative effects reported It has been argued that online relationships are less valuable than offline ones and detract from social involvement with friends.21 Concerns have also been raised over quality,22-24 extreme verbal inhibition and aggression,25 26 hoaxes and spam,27 encouragement of suicide,28 and privacy issues29 on internet groups. In studies included for this review, no negative effect or harm has been reported. The absence of evidence does, however, not mean that such harm does not exist, in particular as most studies had high dropout rates and did not conduct an intention to treat analysis. We do not know what happened to the people who discontinued the studies and whether their inclusion would have shown a negative "net effect." In view of the wide variation in interventions, measurement tools, and populations studied, and the lack of methodological rigour in the majority of studies reviewed, the effect of online support groups on health related outcomes and healthcare resource use remains unclear. Limitations Only one database (LISA) has a subject heading for virtual communities; we may therefore have missed more complex ehealth systems or interventions that have peer to peer components if these were not evident from the abstract or title. However, we are unlikely to have overlooked studies evaluating "pure" electronic peer to peer interventions, and the paucity of such studies is striking. Another concern is publication bias, which we attempted to minimise by including five dissertations. Their inclusion in this systematic review proved to be crucial. Interestingly, the four dissertations with "negative" (non-significant) findings remained unpublished whereas the one dissertation with positive results was published as a journal article; this implies that more (mostly negative) work may have been conducted but remained unpublished. Implications for future research Virtual communities are promising interventions, used everyday by millions on the internet. Many questions remain and should be the focus of future research. Little is known about the conditions and factors (of the group or individual) influencing outcomes. Whether virtual communities benefit from professional (or laypersons') moderation or facilitation is not clear either. With the exception of two studies, all investigators used professionally moderated or facilitated groups, or the level of moderation remained unclear. It is not clear whether virtual communities can substitute or complement face to face support groups. One study compared a computer mediated (voicemail) support group with a face to face group, noting that participation rates were significantly higher in the virtual group,5 but another study showed that virtual groups may be less effective than face to face groups to sustain weight loss.14 In terms of the outcome measures used, future studies should also include measures of resource use, as it is currently not clear whether participation in a peer to peer group reduces or increases the use of health care. The lack of measurable evidence from controlled studies is in sharp contrast to the increasing body of anecdotal and descriptive information on the self helping processes in virtual communities, indicating that virtual communities are in fact the single most important aspect of the web with the biggest impact on health outcomes.30 31 Although qualitative studies—if conducted ethically—are needed and give fascinating insights into people's self helping processes in virtual communities,29 quantitative research is required to evaluate under which conditions and for whom electronic support groups are effective and how effectiveness in delivering social support can be maximised. Factorial design randomised controlled trials can help to evaluate which components of a complex intervention are contributing to an effect, but many problems remain, as by their nature they are not well defined, reproducible interventions, participants tend to be self selected, and participants for which the groups do not work are often lost to follow up. Given the abundance of unmoderated peer to peer groups on the internet, researchers must focus their efforts not only on sophisticated professionally led systems, but shift their attention to consumer led, self help venues. Perhaps in this way the research community can best help consumers to help themselves, a guiding principle of support groups regardless of the venue in which they occur. What is already known on this topic Thousands of electronic health related peer to peer support groups in the form of mailing lists, chat rooms and discussion forums are available on the internet Anecdotal evidence shows that electronic peer to peer self help groups might be beneficial interventions, although some also warn of the dangers of such groups To our knowledge, no systematic synthesis of the effects of peer to peer support groups has been conducted to date What this study adds Numerous controlled studies with peer to peer components have been conducted, but only a few evaluated the effect of peer to peer groups alone Most studies failed to show an effect, or effects were confounded by potential effects of co-interventions Quantitative studies with factorial design or evaluating pure peer to peer interventions are needed to provide robust evidence on the effects of peer to peer support groups Tables A-D and appendixes 1-3 are on bmj.com Contributors: GE and JP have contributed equally to the study and are joint guarantors. GE wrote the first drafts of the protocol and the manuscript including all online tables, coordinated the research, and obtained funding; JP and AS compiled tables 1 and 2; GE and CR developed the extraction database; CR and AS coordinated obtaining the papers. GE, JP, AS and CR participated in the protocol development, screened abstracts, abstracted papers (GE and JP 15 each, AS 11, CR 7), and revised manuscript drafts. ME developed the search strategies and conducted the searches. ME, AS and CR are listed alphabetical, with the order of authors not necessarily reflecting their contribution Competing interests: None declared. Note about process: While GE has the same departmental affiliation and works (with AS and CR) in the same centre as Alejandro Jadad, guest editor of this theme issue, it was submitted to the BMJ in the normal way, and Jadad neither played any part in the decision making over this paper, nor was he involved in conception or conduct of this study. References Wellman B. An electronic group is virtually a social network. In Kiesler S, ed. Cultures of the internet. Mahwah, NJ: Lawrence Erlbaum, 1997: 170-205. Landro L. Alone together. Cancer patients and survivors find treatment—and support—online. It can make all the difference. Oncologist 1999;4: 59-63. Fearon B. Enter at own risk. Noticeboard 2003; 11. Kraut R, Lundmark V, Patterson M, Kiesler S, Mukopadhyay T, Scherlis W. Internet paradox: a social technology that reduces social involvement and psychological well-being? Am Psychologist 1998;53: 1017-31. Alemi F, Mosavel M, Stephens RC, Ghadiri A, Krishnaswamy J, Thakkar H. Electronic self-help and support groups. Med Care 1996;34: OS32-OS44. Hamman CJ. Effect of a nurse-managed support group via an internet bulletin board on the perception of social support among adolescents with insulin-dependent diabetes mellitus . Texas Tech University, 2000: 1-102. Houston TK, Cooper LA, Ford DE. Internet support groups for depression: a 1-year prospective cohort study. Am J Psychiatry 2002;159: 2062-8. Iafusco D, Ingenito N, Prisco F. The chatline as a communication and educational tool in adolescents with insulin-dependent diabetes: preliminary observations. Diabetes Care 2000;23: 1853. Lieberman MA, Golant M, Giese-Davis J, Winzlenberg A, Benjamin H, Humphreys K, et al. Electronic support groups for breast carcinoma. Cancer 2003;97: 920-5. Quick, Ben Gordon. The role of support groups on the Internet for those suffering from chronic kidney disease . University of the Pacific, 1999: 1-128. Schneider SJ, Walter J, O'Donnell R. Computerized Communication as a medium for behavioral smoking cessation treatment: controlled evaluation. Comp Hum Behav 1990;6: 141-51. Gustafson DH, Hawkins R, Boberg E, Pingree S, Serlin RE, Graziano F, et al. Impact of a patient-centered, computer-based health information/support system. Am J Prev Med 1999;16: 1-9. Harvey-Berino J, Pintauro S, Buzzell P, DiGiulio M, Casey GB, Moldovan C, et al. Does using the internet facilitate the maintenance of weight loss? Int J Obes Relat Metab Disord 2002;26: 1254-60. Gary TL, Genkinger JM, Guallar E, Peyrot M, Brancati FL. Meta-analysis of randomized educational and behavioral interventions in type 2 diabetes. Diabetes Educ. 2003;29: 488-501. Johs-Artisensi JL. The effect of web-based support as an adjunct to a self-help smoking cessation program . University of North Texas, 2002: 1-121. McKay HG, King D, Eakin EG, Seeley JR, Glasgow RE. The diabetes network internet-based physical activity intervention: a randomized pilot study. Diabetes Care 2001;24: 1328-34. Winzelberg AJ, Taylor CB, Sharpe T, Eldredge KL, Dev P, Constantinou PS. Evaluation of a computer-mediated eating disorder intervention program. Int J Eat Disord 1998;24: 339-49. Dunham PJ, Hurshman A, Litwin E, Gusella J, Ellsworth C, Dodd PW. 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☉ 11357086:Disturbance of sensory filtering in dementia with Lewy bodies: comparison with Parkinson’s disease dementia and Alzheimer’s disease
1 Neurology and Movement Disorders Unit, EA2683, University of Lille 2 and Lille University Hospital, Lille, France 2 Psychology Department, Charles De Gaulle University, Lille, France 3 Clinical Neurophysiology Department, EA2683, University of Lille 2 and Lille University Hospital, Lille, France 4 Centre de la Mémoire, EA2691, University of Lille 2 and Lille University Hospital, Lille, France Correspondence to: Marie Pierre Perriol Neurophysiologie clinique, H?pital Salengro, Centre Hospitalier Universitaire, F-59037 Lille Cedex, France; mperriol@yahoo.fr ABSTRACT Introduction: Prepulse inhibition (PPI) is considered to mirror an organism’s ability to filter out irrelevant sensory or cognitive information. The disruption of PPI has never been studied in individuals suffering from dementia with Lewy bodies (DLB). As attention deficits largely contribute to cognitive impairment in DLB, an investigation with a PPI paradigm is useful for differential diagnosis of DLB versus Alzheimer’s disease (AD) and Parkinson’s disease dementia (PDD). Objective and methods: PPI of the N1/P2 component of auditory evoked potentials was used to investigate the early stages of attention selectivity in 10 DLB, 10 AD, and 10 PDD patients, as well as in 10 healthy controls. The PPI paradigm consisted of the presentation of sound pulses (40 ms, 115 dB) preceded by a prepulse (40 ms, 80 dB). Sound stimuli were presented in a total of 80 trials in a pseudo-random order. Results: Non-parametric analyses of variance revealed a significant group effect on the 120 ms lead interval. Retrospective analyses revealed that PPI was significantly reduced in DLB compared to healthy controls and AD. In the PDD group, the disturbance was of intermediate intensity. Conclusion: The present study revealed a severe disturbance of PPI in DLB patients. The DLB patients displayed a specific disruption profile in terms of magnitude as well as time course. Abbreviations: AD, Alzheimer’s disease; AEP, auditory evoked potential; DLB, dementia with Lewy bodies; EEG, electroencephalogram; EOG, electro-oculogram; PDD, Parkinson’s disease dementia; PPI, prepulse inhibition Keywords: pre-pulse inhibition; dementia with lewy bodies; attention deficits The ‘startle response’ to an intense acoustic stimulus is attenuated when a weaker, non-startling stimulus or ‘prepulse’ precedes the startle eliciting stimulus.1 This phenomenon — prepulse inhibition (PPI) — is also observed for cortical responses, such as the N1/P2 component of the auditory evoked potential (AEP).2 PPI is considered to reflect an organism’s ability to ‘gate out’ or ‘filter out’ sensory or cognitive information, and is thought to reflect an automatic, pre-attentive inhibitory process whereby irrelevant stimuli are prevented from influencing ongoing behaviour. 1,3–6 It has been shown that PPI disruption is related to cognitive impairment in schizophrenia and in several basal ganglia disorders.7–9 Studies focusing specifically on neuropsychological performance in dementia with Lewy bodies (DLB) have generally considered that attention deficits contribute significantly to fluctuating cognition and visual hallucinations, which are core criteria for clinical diagnosis of DLB along with extrapyramidal signs.10–12 These findings thus prompted us to investigate such deficits with the PPI paradigm, which does not require deliberate participation by the subject and thus rules out difficulties related to misunderstanding of the task instructions by demented patients. In contrast to numerous clinical tests, the PPI paradigm does not use visuospatial stimuli thereby preventing contamination of the results by the visuoperceptive disruption very commonly observed in these patients.13 Finally, the PPI paradigm enables study of the attention processes on which more elaborated cognitive processes are based. It has been shown that the amplitude of the startle reflex decreases with age even though PPI remains constant;14,15 however, this can constitute a methodological limitation for the use of the PPI paradigm in aged subjects, because the lower the basal amplitude of the startle reflex the more difficult it is to detect further reductions. This age related amplitude reduction also concerns the AEP components, although here the signal to noise ratio remains high. Consequently, PPI of the AEP N1/P2 components can be considered as a better index for observations in elderly subjects. Here, PPI of the AEP N1/P2 component was used to investigate the early stages of attention selectivity in DLB, Parkinson’s disease dementia (PDD), and Alzheimer’s disease (AD). METHODS Participants Ten DLB, 10 PDD, and 10 AD patients participated in the study. The three groups were matched with respect to their score on the Mattis dementia rating scale16 (Mattis DRS) for assessing dementia severity. Ten healthy control subjects (matched to the patients with respect to age and educational level) also participated in the study. The characteristics of the four groups are presented in Table 1. Table 1 Demographical and clinical characteristics of the study participants* (median value and range) PPI paradigm A typical PPI paradigm was used. Eighty sequences of sound stimuli (white noises gated to near instantaneous rise/fall time) were binaurally presented through headphones (Telephonics, TDH 39P). They consisted of 40 ms presentations of a 115 dB pulse (pulse alone trials) or 40 ms presentations of a 80 dB prepulse occurring 60, 120, or 300 ms prior to a 40 ms, 115 dB pulse (prepulse/pulse trials). All trial types were presented a total of 20 times but in a pseudo-random order. The inter-trial interval varied between 15 and 25 s (mean = 20 s). The stimulus sequence was controlled with the STIM package’s Gentask module (Neuroscan Inc., USA). N1/P2 recording An electroencephalogram (EEG) was recorded continuously from three active Ag/AgCl electrodes positioned at Fz, Cz, Pz according to the 10-20 international system, with a linked-ear reference. An electro-oculogram (EOG) was recorded from two miniature electrodes attached above and below the left eye. Eye blink was also measured through the electromyographic activity of the right orbicularis oculi muscle. Electrode impedances were kept below 5 kOhms. The EEG signals were amplified (gain = 1000, band pass of 1–100 Hz) and were continuously digitised at a sampling rate of 2000 Hz. We used a set of SYNAMP amplifiers and the SCAN v3.0 software (Neuroscan Inc., USA). The EOG and EEG were then processed off-line to remove ocular artefacts. Next, AEPs were averaged separately over a 800 ms epoch, beginning 100 ms prior to the stimulus onset, for all trials. The N100 component was defined as the largest negative deviation from baseline in a 80–200 ms window following presentation of the pulse stimuli, whereas the P200 component was defined as the largest positive deviation from baseline in a 130–300 ms window following presentation of the pulse stimuli. The peak N100 and P200 values were measured at Cz, and the amplitude of the N1/P2 component was then computed. The percent PPI of the N1/P2 component was calculated using the following formula: 100x ( / response amplitude in the pulse-alone trials) Data analyses Kruskall-Wallis non-parametric analyses of variance were performed in order to detect any group effects on the percent PPI of the N1/P2 component (%PPI). When appropriate, we performed retrospective analyses (Mann-Whitney tests). A 5% significance level was adopted. RESULTS Kruskall-Wallis non-parametric analyses of variance revealed no significant group effect on the mean N1/P2 component amplitude (H(3) = 4.80, p = 0.187) but a significant group effect on the %PPI at a 120 ms prepulse/pulse interval (H(3) = 12.57, p = 0.005). There was no significant group effect on %PPI at the two other intervals (60 ms: H(3) = 3.23, p = 0.358; 300 ms: H(3) = 5.41, p = 0.144). At the 120 ms prepulse/pulse interval, retrospective analyses revealed that the %PPI was significantly reduced in DLB (p = 0.002) and PDD (p = 0.017) patients compared to healthy control subjects. In AD patients, there was a trend towards a significant reduction (p = .058). Comparison of the patient groups revealed a significantly reduced %PPI in DLB patients compared to AD patients (p = 0.031). The other comparisons were non-significant. When plotting the mean %PPI for each group as a function of the prepulse/pulse interval (fig 1) the usually seen pattern (an inverted U curve) was observed: in every group, %PPI was the highest at the 120 ms interval and decreased at shorter and longer prepulse/pulse intervals. At the 120 ms interval, disruption of the PPI phenomenon varied among the three groups: AD patients showed a slightly reduced %PPI, this was more pronounced and reached the significance level in PDD patients, but the reduction was clearly most severe in DLB patients. Figure 1 Mean %PPI of the participant groups as a function of the prepulse/pulse interval. AD, Alzheimer’s disease; DLB, dementia with Lewy bodies; HC, healthy controls; PDD, Parkinson’s disease dementia; PPI, prepulse inhibition. Even though there was no significant group effect at the other prepulse/pulse intervals, it is interesting to underline that at the 60 ms interval, the %PPI was reduced in the DLB patients compared to the three other groups (within which it was very similar). At very short intervals, DLB patients are thus the only group in which the phenomenon is already disturbed. With the 300 ms interval there was no observable PPI in the DLB and PDD groups, although AD patients showed a %PPI very close to that observed in the healthy controls. DISCUSSION The present study uses a functional approach to show a severe disturbance of attention filtering in DLB patients. The usual attenuation of the cortical response to an intense sound when a ‘prepulse’ precedes this unexpected and intense stimulus is no longer observed thus reflecting a loss of the ability to inhibit irrelevant information. This type of impairment was also observed in PDD patients but was less severe. In AD patients sensory gating appeared to be maintained (despite similar severity of cognitive degradation), because only a trend towards PPI reduction was observed at the 120 ms prepulse/pulse interval — that is, when the phenomenon is maximal in healthy controls. In fact, DLB patients displayed a specific PPI disruption profile in terms not only of magnitude but also time course, which suggests that several processes could be impaired. Indeed, according to Dawson et al,3 PPI is considered as an automatic involuntary phenomenon when prepulse/pulse intervals are shorter than 120 ms thus reflecting exogenous attention. When prepulse/pulse intervals are longer than 120 ms, PPI is considered as reflecting the involvement of attention processes. On this basis, both involuntary and attention-selective processes appear to be impaired in our DLB patients, although the impairment seemed only to concern attention-selective processes in PDD patients. Using a similar paradigm, Golob et al19 suggested that declines in cortico-cortical processing might cause cognitive impairment in patients with AD and mild cognitive impairment because sensory gating phenomenon was observed only when presenting stimulus pairs in different modalities (visual/auditory) and not for stimulus pairs having the same modality (auditory/auditory). In the present study (using auditory stimulus pairs), we reported PPI disruption in DLB and PDD patients although the phenomenon was relatively unchanged in AD patients. This suggests i) involvement of the dopaminergic subcortico-thalamo-cortical networks in PPI regulation and ii) more severe disruption of these networks in DLB than in PDD. Because this study was an initial approach to gauging the utility of PPI for comparing attention disorders in DLB, PDD, and AD, we only included patients who met as many diagnosis criteria as possible. Consequently, the disease was already quite severe, which constitutes an important limitation because all patients ACKNOWLEDGEMENTS The authors thank N El Massioui (NAMC, UMR 8620, CNRS, Orsay, France) for her help in setting up the PPI paradigm. REFERENCES Graham FK. The more or less startling effects of weak prestimulation. Psychophysiology 1975;12 (3) :238–48. Abduljawad KA, Langley RW, Bradshaw CM, et al. Effects of clonidine and diazepam on prepulse inhibition of the acoustic startle response and the N1/P2 auditory evoked potential in man. J Psychopharmacol 2001;15 (4) :237–42. 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Sensory cortical interactions in aging, mild cognitive impairment, and Alzheimer’s disease. Neurobiol Aging 2001;22 (5) :755–63....查看详细 (16028字节)
☉ 11357087:Postmenopausal hormone therapy and Alzheimer’s disease risk: interaction with age
1 Department of Geriatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA 2 Department of Medicine (Genetics Program), Boston University School of Medicine, Boston, MA, USA 3 Department of Neurology, Boston University School of Medicine, Boston, MA, USA 4 Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA Correspondence to: Dr Victor W Henderson Stanford University School of Medicine, 259 Campus Drive, HRP Redwood Building, Stanford University, Stanford, CA 94305-5405, USA; vhenderson@stanford.edu ABSTRACT We examined the relation between oestrogen containing hormone therapy (HT) used for more than 6 months and Alzheimer’s disease (AD) risk in 971 postmenopausal women (426 AD patients, 545 relatives without dementia). There was a significant interaction between age and HT use on AD risk (p = 0.03). In stratified analyses, a significant protective association was seen only in the youngest age tertile (50–63 years; odds ratio = 0.35, 95% confidence interval = 0.19 to 0.66). Results must be considered cautiously in light of recent clinical trial evidence that oestrogen plus progestin increases dementia incidence in older postmenopausal women. However, our observational findings are consistent with the view that HT may protect younger women from AD or reduce the risk of early onset forms of AD, or that HT used during the early postmenopause may reduce AD risk. Abbreviations: AD, Alzheimer’s disease; ApoE, apolipoprotein E; CI, confidence interval; HT, hormone therapy; MIRAGE, Multi-Institutional Research in Alzheimer Genetic Epidemiology; NSAID, non-steroidal anti-inflammatory drug; OR, odds ratio; SD, standard deviation; WHIMS, the Women’s Health Initiative Memory Study Keywords: Alzheimer’s disease; hormone therapy; oestrogen; risk factors The Women’s Health Initiative Memory Study (WHIMS), a randomised double blind placebo controlled primary prevention trial in women 65 years of age or older, reported that oestrogen plus progestin increases overall dementia risk.1 This seminal finding in older postmenopausal women contrasts starkly with observational research that oestrogen containing hormone therapy (HT) is associated with a lower risk of Alzheimer’s disease (AD).2 Few studies have considered HT effects in younger postmenopausal women. Moreover, most observational studies have not reported on possible confounding or effect modification by other AD risk factors, because relevant data were not collected or sample sizes were too small for meaningful analyses. We evaluated the relation between HT and AD with data from AD probands and their relatives in the Multi-Institutional Research in Alzheimer Genetic Epidemiology (MIRAGE) Study. We found that HT was associated with reduced AD risk, but this effect was apparent only among younger women. METHODS Subjects As described elsewhere,3 MIRAGE probands meet criteria for probable or definite AD. Controls are first degree relatives or spouses of probands, whose age was censored at the year of proband symptom onset to guard against bias from temporal patterns in prescribing medications. Controls provided written informed consent; patients provided written consent or assent with proxy informed consent. Studies were approved by institutional review boards at participating sites. A total of 532 female AD patients and 819 female controls without dementia were available for analysis. Risk factor data were collected from primary informants of AD patients, with verification from secondary informants and medical records where possible. Controls without dementia provided their own risk factor information. We studied female MIRAGE participants who were postmenopausal, or, if "unsure" of menopausal status, were at least 60 years of age. Oestrogen exposure was based on the question: "Did you ever take an oestrogen medication or an oestrogen replacement therapy (for example, Premarin, Estradiol, Ortho-Novum, etc) for birth control, menopausal symptoms, osteoporosis, or any other reason on a daily basis for more than 6 months?". Exposed participants (i) responded "yes" and provided a specific valid oestrogen drug or failed to specify a particular oestrogen, and (ii) initiated HT at least 1 year prior to dementia onset/censored age or failed to specify a start date for HT. Unexposed participants (i) responded "no", or (ii) responded "yes" but failed to initiate HT before dementia onset/censored year. Birth control medication when used before age 36 was not considered a valid oestrogen; women who reported birth control medication after age 35 or responded "yes" but provided an invalid oestrogen were excluded. One purpose of this analysis was to evaluate potential interactions between oestrogen and apolipoprotein E (ApoE) genotype,4,5 and the final sample was limited to 426 patients and 545 controls without dementia (13 mothers, 316 sisters, 53 daughters, and 163 spouses of male probands) where oestrogen use, age, education, ethnicity, and ApoE genotype were known. Other factors evaluated as possible confounders or modifiers of the effect of HT on AD risk were alcohol use (nine with missing data), cigarette smoking (one missing), daily use of non-steroidal anti-inflammatory drugs (NSAIDs) for more than 6 months (20 missing), and prior hysterectomy or oophorectomy (11 missing) (table 1). Table 1 Characteristics of Alzheimer cases and family controls without dementia* Statistical analyses Patients and controls were compared with t tests or Wilcoxon rank sum tests (continuous measures) and 2 tests (categorical measures). Crude odds ratios (ORs) were calculated for categorical variables, which were compared to Mantel-Haenszel ORs to evaluate potential confounding. The Breslow Day statistic was used to evaluate whether ORs differed among groups. Multivariate modelling used generalised estimating equations specifying the logit link function for binary responses. The generalised estimating equations procedure accounts for correlation among subjects within families (694 families in this study) and incorporates information from singletons. An independence working correlation structure was assumed; standard errors were calculated using the empirical variance estimator. Marginal expectations for the logarithm of the odds of AD were modelled as a linear function of predictor variables. ORs were adjusted for age, education, and race. Cross product terms were incorporated into models to evaluate statistical interactions. Analyses used SAS software version 8.2 (SAS Institute, Cary, NC, USA). RESULTS AD patients in comparison to controls were older, less well educated, more likely to be African American, and more likely to possess at least one copy of the ApoE 4 allele, but less likely to have used HT or NSAIDs (table 1). Conjugated oestrogens were the most commonly reported HT preparation (61%). In analyses adjusting for age, education, and race, HT was associated with a 30% reduction in AD risk (table 2). There was no interaction between HT use and education or race (p’s0.5), but the interaction with age was significant (p = 0.03), indicating that the protective association of HT was age dependent. Table 2 Age stratified risk of Alzheimer’s disease associated with prior use of hormone therapy In analyses stratified by age tertiles, HT was significantly associated with reduced risk in the youngest tertile (OR = 0.35) but not in the second and third tertiles, where ORs were similar (table 2). Risk estimates were essentially unchanged in analyses that adjusted for alcohol use, smoking history, NSAID use, and hysterectomy/oophorectomy status as possible confounders. There were no significant interactions between HT use and these factors (data not shown). DISCUSSION Similar to previous observational reports,2 HT in the MIRAGE Study was associated with a reduction in AD risk. However, the protective association was modified by age and was limited to younger woman (65% reduction for women aged 50–63; table 2). The relation between HT and AD risk was not confounded by education, race, ApoE genotype, alcohol use, smoking history, NSAID exposure, or hysterectomy/oophorectomy status, nor were there significant interactions between oestrogen use and these variables. Strengths of the MIRAGE Study are large sample size, high HT exposure rate (35% among controls), and the ability to adjust for a number of factors that might confound or modify the relation between HT and AD. A limitation of the MIRAGE Study is that case control studies are susceptible to selection bias. Information on progestin use was not ascertained, and we were therefore unable to distinguish effects of unopposed oestrogen from those of oestrogen plus progestin. HT exposures were not validated against pharmacy or prescription records. Use of a proxy informant for cases but not controls introduced the possibility of exposure misclassification; however, within the MIRAGE Study there is very good agreement between proxy responses and index subject responses for most exposures, including HT.6 Sons and brothers are somewhat less reliable in reporting HT use,6 and in post hoc analyses excluding 48 cases with brother or son informants, age remained a significant modifier of the oestrogen effect on AD risk (p = 0.04). The protective association of oestrogen was still apparent in the lowest age tertile (OR = 0.37, 95% CI = 0.19 to 0.70) but not in the two higher tertiles (OR = 0.88, 95% CI = 0.60 to 1.3). HT was reported to protect against AD in a population based study of AD with age at onset less than 65 years.5 However, an association between HT and AD risk limited to younger postmenopausal women has not been reported previously. This finding differs from, but does not directly conflict with, results of the WHIMS primary prevention trial, where women aged 65 or older given oestrogen plus progestin faced an increased incidence of dementia apparent 1 year after treatment assignment.1 We found no overall increase in AD risk in this older age range (table 2), but confidence intervals overlap with those reported in the WHIMS trial, and we have no valid data on when these older women initiated HT. Effect modification by age could represent a chance finding, or unrecognised bias or confounding. Another interpretation is that protective effects of oestrogen containing HT decline with advancing age as deleterious effects of HT and competing risks assume greater prominence. Younger women exposed to HT necessarily used HT at an early age, but for older women exposure could have occurred at any age. Therefore, another consideration for MIRAGE findings is that HT might influence AD risk when initiated or used during a critical window in the early postmenopause.7 After ovariectomy, for example, oestrogen effects on synaptic density may depend on treatment timing,8 and the ability of oestrogen to enhance memory performance is reduced in older animals compared to younger animals.9 The so called critical window hypothesis should be addressed in cohorts with better information on timing and duration of HT exposures. Finally, pathogenetic mechanisms differ for early and late onset AD,10 and MIRAGE results may be germane only for relatively uncommon early onset disease. Women commonly begin HT for bothersome climacteric symptoms and discontinue therapy within several years.11 In this regard, most studies that have examined the relation between HT and AD have included substantial numbers of former users, and one cohort study reported a protective association specifically among former users.12 Prior reports of greater AD risk reduction with longer durations of HT exposure4,12–14 are also consistent with the view that early HT may be protective, since longer HT use is associated with a younger age of HT initiation.15 Data from the MIRAGE Study do not help us decide among alternative explanations for effect modification by age, since reliable information was unavailable on the duration and timing of HT. However, our results raise the possibility that the protective association of HT might be confined to a subgroup of women characterised by younger age or early HT use. These possibilities can eventually be confirmed or refuted in appropriately designed randomised clinical trials. For the present, adverse findings on dementia from WHIMS in older women1 and other recognised health risks of HT16 dictate that HT should not be recommended for AD prevention at any age. REFERENCES Shumaker SA, Legault C, Rapp SR, et al. Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women: the Women’s Health Initiative Memory Study (WHIMS). JAMA 2003;289:2651–62. LeBlanc ES, Janowsky J, Chan BKS, et al. Hormone replacement therapy and cognition: systematic review and meta-analysis. JAMA 2001;285:1489–99. Lautenschlager NT, Cupples LA, Rao VS, et al. Risk of dementia among relatives of Alzheimer’s disease patients in the MIRAGE study: what is in store for the oldest old? Neurology 1996;46:641–50. Tang M-X, Jacobs D, Stern Y, et al. Effect of oestrogen during menopause on risk and age at onset of Alzheimer’s disease. Lancet 1996;348:429–32. Slooter AJ, Bronzova J, Witteman JC, et al. Estrogen use and early onset Alzheimer’s disease: a population-based study. J Neurol Neurosurg Psychiatry 1999;67:779–81. Demissie S, Green RC, Mucci L, et al. Reliability of information collected by proxy in family studies of Alzheimer’s disease. Neuroepidemiology 2001;20:105–11. Resnick SM, Henderson VW. Hormone therapy and risk of Alzheimer disease: a critical time. JAMA 2002;288:2170–2. Silva I, Mello LEAM, Freymüller E, et al. Onset of estrogen replacement has a critical effect on synaptic density of CA1 hippocampus in ovariectomized adult rats. Menopause 2003;10:406–11. Savonenko AV, Markowska AL. The cognitive effects of ovariectomy and estrogen replacement are modulated by aging. Neuroscience 2003;119:821–30. Selkoe DJ. Alzheimer’s disease: genes, proteins, and therapy. Physiol Rev 2001;81:741–6. den Tonkelaar I, Oddens BJ. Determinants of long-term hormone replacement therapy and reasons for early discontinuation. Obstet Gynecol 2000;95:507–12. Zandi PP, Carlson MC, Plassman BL, et al. Hormone replacement therapy and incidence of Alzheimer’s disease in older women: the Cache County study. JAMA 2002;288:2123–9. Paganini-Hill A, Henderson VW. Estrogen replacement therapy and risk of Alzheimer’s disease. Arch Intern Med 1996;156:2213–7. Waring SC, Rocca WA, Petersen RC, et al. Postmenopausal estrogen replacement therapy and risk of AD: a population-based study. Neurology 1999;52:965–70. Ettinger B, Pressman A, Silver P. Effect of age on reasons for initiation and discontinuation of hormone replacement therapy. Menopause 1999;6:282–9. Writing Group for the Women’s Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women’s Health Initiative randomized controlled trial. JAMA 2002;288:321–33....查看详细 (15345字节)
☉ 11357088:Doctors' experience with handheld computers in clinical practice: qualitative study
1 Division of Health Services Management and Policy, Ohio State University, School of Public Health, 1583 Perry Street, Atwell 246, Columbus, OH 43210-1234, USA, 2 Division of General Internal Medicine, Ohio State University College of Medicine and Public Health, Columbus, OH 43210, USA Correspondence to: A S McAlearney mcalearney.1@osu.edu Abstract Objective To examine doctors' perspectives about their experiences with handheld computers in clinical practice. Design Qualitative study of eight focus groups consisting of doctors with diverse training and practice patterns. Setting Six practice settings across the United States and two additional focus group sessions held at a national meeting of general internists. Participants 54 doctors who did or did not use handheld computers. Results Doctors who used handheld computers in clinical practice seemed generally satisfied with them and reported diverse patterns of use. Users perceived that the devices helped them increase productivity and improve patient care. Barriers to use concerned the device itself and personal and perceptual constraints, with perceptual factors such as comfort with technology, preference for paper, and the impression that the devices are not easy to use somewhat difficult to overcome. Participants suggested that organisations can help promote handheld computers by providing advice on purchase, usage, training, and user support. Participants expressed concern about reliability and security of the device but were particularly concerned about dependency on the device and over-reliance as a substitute for clinical thinking. Conclusions Doctors expect handheld computers to become more useful, and most seem interested in leveraging (getting the most value from) their use. Key opportunities with handheld computers included their use as a stepping stone to build doctors' comfort with other information technology and ehealth initiatives and providing point of care support that helps improve patient care. Introduction Our findings come from doctors' focus groups as one component of a two part qualitative study designed to explore experiences with handheld computers in clinical practice from the perspectives of both organisations and doctors.2 Three broad issues guiding our groups were: how and why doctors use handheld computers in clinical practice, what barriers doctors perceive with their use and how these could be overcome, and what doctors expect from their use in the future. Issues that emerged during the study were also explored. We purposely sampled organisations that were reportedly using handheld computers in clinical practice, and we contacted their affiliated doctors to participate in our study. Focus groups We held eight focus group sessions lasting 60-90 minutes between April 2002 and September 2003. Six sessions were conducted at a medical centre, a children's hospital, an independent practice association, two community based healthcare systems, and a community hospital. Two sessions were conducted at a meeting of general internists. Topics covered included general use of handheld computers, rationale for use, expectations, barriers or challenges, and organisational support. Ongoing analyses led to the inclusion of new topics. These included perceived benefits of handheld computers, behaviour changes with use, and concerns. We asked participants about the specifics of their use of handheld computers and any organisational expectations for their use. Two study investigators conducted each focus group, facilitating discussion with an open ended list of questions, including probes for more detailed information. The sessions were audio-taped, transcribed, and then verified and corrected by one investigator (ASM, SBS, or MAM). Participants Our eight focus groups consisted of 54 doctors. One third of the doctors were women and three quarters were generalists. Nearly half of the participants practised full time, and the remainder were residents or fellows. The groups contained doctors who did or did not use handheld computers, with users representing a variety of levels and patterns of use. One third of participants were affiliated with an academic medical centre and the remainder were affiliated with an independent practice association, community hospital, or children's hospital. Analyses We analysed our data using a combination of deductive and inductive methods.3 The investigators read the transcripts, identified broad themes, and discussed emergent findings. This iterative process allowed new ideas and themes to be presented in subsequent sessions. By the end of the sixth session no new major themes emerged, indicating near saturation.4 The last two sessions completed the deductive part of our analysis. The investigators read the transcripts several times and constructed a preliminary coding frame. This frame was applied to two common transcripts, which enabled decisions on coding to be compared and codes to be clarified. We then identified categories and constructed major themes. Periodic discussions among the investigators ensured consistency of coding and helped us reach agreement on final themes. An ongoing review of the literature helped us to compare, validate, and extend our findings.4 Results How doctors use handheld computers in clinical practice The use of handheld computers varies widely in clinical practice (box 1). Clinicians use administrative functions for the development and sharing of lists and databases to keep track of drug formularies, call schedules, and contact details. Specific applications allow patients to be tracked and clinical results to be monitored. The use of administrative functions linked to clinical activities is expanding, with applications such as electronic prescribing and coding attracting attention because of their potential to increase doctors' productivity. Participants typically used handheld computers at their own initiation, buying devices based on personal preferences or recommendations. An increasing number of organisations are promoting handheld computers as part of the strategy for clinical information technology, with many academic medical centres purchasing devices for their residents. In one institution, doctors use handheld computers to access patients' electronic records through a browser based application, similar to that in a recent study.5 At two organisations we studied, residents use their devices to share patient details between shifts. Patterns of use and characteristics of handheld computer users The frequency and intensity of use of handheld computers varied, and on the basis of these we were able to develop user categories (table). Non-users had never used handheld computers or had abandoned them. Niche users included those whose use was restricted to a single application but reported that this limited functionality was sufficiently valuable such that they would continue use. Routine users had integrated handheld computers into their clinical workflow, using multiple applications on a regular basis. Power users were self described "technophiles" who were eager to showcase their latest device. Patterns and characteristics of users of handheld computers Box 1: Examples of common uses of handheld computers Point of care assistance—drug information, clinical guidelines, decision aids, patient education Patient information—patient tracking, clinical results Administrative functions—electronic prescribing, coding, tracking schedules Research activities—data collection, participant education Medical education—lecture notes, presentations, photographs and diagrams Perceived benefits of handheld computers Users seemed generally satisfied with their handheld computers and perceived many benefits (box 2). We anticipated discussion about productivity gains and convenience, but we also heard many doctors describing how they do things differently and "better" owing to the device. We explored this theme further. One doctor explained "I don't guess that something is not interacting with warfarin and cross my fingers and hope. That's my biggest thing, I don't guess. Or say I will look that up later and not get to it." Similarly, many participants noted how they "look things up more, medication-wise." Across all groups, users reported that handheld computer applications often provided complementary benefits, improving productivity and interactions with patients: "It reminds me to do things that I might forget to do. Not just be at this meeting, but I can get a glance and see that I haven't done the stool occult blood on that patient because they are in front of me." These findings are supported by other studies.6 7 Box 2: Doctor perceived benefits of handheld computers Enhanced productivity It really saves you the aggravation of looking for something and not being able to find it that minute Anything where you don't have to wait for somebody to finish at the terminal and wait in a long line of doctors who don't have handheld devices... You've got your handheld device, you put your orders in and walk away while the other guy is still waiting. You've got an advantage I feel like it saves me time so I don't have to step out of a room and look something up For me, to be able to sync my Palm before I make rounds and have all that information with me, then I don't have to run around and ask the nurse who says, "I'm not a nurse, I'm a respiratory therapist" Enhanced quality of patient care and service You get a phone call from somebody. You have a clue. Right here, right now, right this minute, I have a clue For example, if you were talking to a patient and you came across a medication that you didn't know, if you didn't have a Palm you probably wouldn't go in the other room and go to the PDR and look it up. But if you have the Palm you call pull it out and say, oh yeah, that is a hypertensive medication I think the way to approach it is quality, and the service you are offering, and the timeliness of the information Barriers to use of handheld computers The two main barriers to using handheld computers were personal issues and the device itself. Issues concerning the device included size, limited memory and battery life, and speed of data exchange.8-12 Many participants expressed frustration, especially with data entry: "You know, with the Palm you are trying to write graffiti. And, you know me, I'm going `Oh, that's wrong.' I can't remember what is a seven? It's coming out two! I think the data entry is real tough." Two major personal barriers described by non-users were physical constraints, such as eyesight, and perceptual constraints, including comfort with the device and personal preferences (box 3). In contrast, users rarely reported personal barriers and instead described those device features perceived as problematic by non-users as strengths, such as raving about portability rather than complaining about a small screen. Similarly, although non-users reported that "these things just have to be easier," routine and power users described the operating systems as "intuitive." A major barrier for non-users in all groups was their perception that they did not receive, or expect to receive, enough value from the devices to change their existing patterns of practice. As a former user explained, "it just takes too long and is too disruptive to the day." Another participant said "A lot of residents would open it up and try to load up all the stuff that they need and they would just get so frustrated and didn't know how to do it, that it was taking too much time, that it just wasn't worth it." Furthermore, when computers were readily available, both non-users and former users perceived it as unnecessary to incorporate handheld computers into clinical workflow. Routine and power users, however, provided numerous examples of where devices added value and improved their work routines. Strategies proposed by doctors to overcome barriers Participants suggested several ways in which organisations could help to overcome barriers (box 4). Doctors who had never used handheld computers noted that advice about which device to use might be sufficient to tip them into a user category: "For people who aren't used to using computers, it's just not worth the time to figure all that stuff out." Niche users wanted specific advice about the appropriateness of applications, and our impression was that this might shift them towards routine use. Organisations could provide training and retraining to overcome many barriers. Both niche users and routine users were aware that there was more they could do with the device, if only they knew what and how: "I don't know how to use it to its fullest potential. It's my fault rather than the machine's fault. But I haven't been educated enough to use it to its fullest potential." Participants suggested that training should be available one on one and should involve another clinician (nurse or doctor). With the exception of power users, most users wanted support available constantly from a help desk or expert: "So I guess what we're saying is that maybe there should be like a first aid station... somewhere I can go to, sit down and say this is what I'm trying to do. Why can't I do it? What did I do wrong? How can you help me make it right?" Doctors reported that the more computer friendly their organisation, the more likely they were to keep using or trying to use handheld computers. A few participants noted that an organisation sensitive to their needs would be an appealing place to practise. Concerns about handheld computers Concerns raised in early focus groups were purposely explored further in subsequent groups. We categorised concerns into four areas: the device itself, information security, over-reliance, and potential changes to practice. Doctors' concerns about the device included loss, breakage, and reliability. Less common were concerns about security. Although doctors expressed concern about secure patient data, they seemed unconvinced that handheld computers represented a greater threat than paper records. In most sessions, satisfaction with convenience seemed to compete with concern about security: "You can lock it but I never do. It is a pain to get in." Power users, however, reported reliably adopting security routines. A major concern that emerged in every focus group was dependency, particularly among routine users and power users (box 5): "The Palm runs my life—if I lost it! Ugh." Many users also Box 3: Personal factors creating barriers to handheld computer use Physical constraints Physical factors My fingers are just too big for those buttons I think it will get worse as we start to pull in legacy systems results, and more and more with wireless. I'm not going to be able to see. And I doubt that people without 20/20 vision will be able to read this when we start pulling in information from everywhere Age The problem is that it is hard for me to carry it around. So, I forget it all the time or I don't utilize it and I'm getting old To what extent do people our age actually need to do it? So, if the records aren't all automated and it's a pain in the ass for you, and you've got your list, you know Perceptual constraints Comfort with technology I've talked to a lot of people who have been really disappointed and I think it's just because of lack of experience with computers, and they don't feel comfortable If it doesn't work right, the first time or the second time, it's over Comfort with device But they don't fit in shirt pockets. This thing is just the wrong size for shirt pockets. It fits in pants' pockets. But it goes on and off... so I'm sitting here clicking all day long and wondering what's wrong with my heart valve I found it was cumbersome. I just wasn't really comfortable with it. Heavy. I carried in my suit pocket and was uncomfortable. I carried it in my lab coat and it was uncomfortable Perception that device is not easy to use My partner tried to get it synced, took it home, tried to get it to work the first night. Couldn't do it, quit Preference for paper If you take notes, it's much more practical to take notes on a paper printout and keep your to-do list on that than it is on a palm People like to be able to annotate, they like to have paper. It's tangible. You know, I can write on there "check Mrs. Jones' second potassium," and I can hand that off to someone and they'll do it for me and I can check off if I need to do something. It is very hard to annotate stuff on the Palm yet, I think Preference for personal computers to access information I used it, but I have not found it convenient enough to go and buy one. Where I work we have computers everywhere and I prefer using a keyboard. I have not gotten used to using graffiti. The real estate is so limited on a Palm raised the theoretical concern about becoming over-reliant on the device as a "peripheral brain." Box 4: Organisational strategies to overcome barriers to use of handheld computers Assistance with selection and set-up Make it ready to go out of the box: Set up PDAs with software and make them ready to sync with a PC I mean that's what a lot of doctors want. They want to just turn it on, start using it. They don't want to have to mess with any of that It would be helpful to know what is best. Is there something already out there or is it better to start from scratch and create your own? Training and retraining But you know orientations just stink. Too much information... you know, we had our palms for like half a day when we had that session. So you hadn't really gotten a chance to do anything with it or look through everything at all I guess personally, I would want instructions Local expert or help desk It's gotta be something where you can go back and dialogue with people and say I'm having a problem here or I'm not getting the full advantage of this thing And you know, when it stops working for some reason, there has to be someone who can do it Handheld computer friendly environment It would be nice to have more sync cradles too I think, rather than having to walk all the way over to the chief's office I think once we get the wireless then that could really save time Some doctors were concerned about handheld computers changing clinical practice for the worse. Several doctors were concerned that avid users might continuously collect data without furthering patient care. Others were troubled that patients might look negatively upon them for using the devices. A few respondents in each group remarked that they purposely did not use the devices in front of patients, but others were comfortable doing so: "Initially I was afraid that if I had to use a device, they would think I was stupid. But they don't. It doesn't seem that they feel that way. I think I get credit for having a device, which is trendy. So they think I'm smarter." Another group of doctors voiced concern that these devices may become a tool of administration to further constrain their practice, for example, by enforcing guidelines. Box 5: Doctors' concerns about dependency on handheld computers Dependency I have had them crash before. I don't have another place to look up medications. So I get very dependent on it I am chairman of medicine, director of medical intensive care. I frankly break out in a cold sweat when I lose my Palm. I do. The residents know If I lose this, I get very, very nervous I was surprised how dependent upon it I've become... it's very insidious Over-reliance on device I think.. .there is a part of me that worries that if I become too reliant on the calculator to do all my calculations for me that I will get to the point where I don't have to really remember any formulas and how you look at pH One thing I'm worried about is the fact that I think more and more people are using the Palm as a crutch to a certain extent. And I do the same thing Certain skills you just lose by disuse, basically. Certain things would go away. I mean you would not need to remember. If it's a little esoteric from your mundane use, you will not need to remember it. You won't even try to remember it Expectations about future use of handheld computers Most doctors thought that the trend towards incorporating new electronic technologies into medicine would continue. Participants remarked that new doctors were more comfortable with electronic technologies, and this may help promote the use of handheld computers: "The residents coming out right now aren't at that stage right now, but very soon. Not far behind is a group that will only know computers." The contrasting viewpoint, however, was also expressed: "So the question is, how fast does everybody have to change?... A lot of people are going to get away with not learning." Participants in each group said that handheld computers were destined to become critical because of their potential to improve patient safety and the quality of care. Even when faced with sacrificing personal autonomy, the view for the future was that it is more important to be right and safe (box 6): So in a lot of ways, our world has been our personal autonomy at getting things right. And more and more that paradigm is moving away. And the requirement of precision is much greater. So I'm not really allowed anymore to get the drug interactions wrong. So, I have to have a device that makes it right... So, if you're going to be held to that standard, then you have to have the tools to be held to that standard. So we're talking about standard of care now, which affects all of us. So, whether you're in medical school and everyone has their Palm Pilot and they're whizzes at it, as opposed to somebody like me who's struggling and wants learn to be able to access and to benefit from this technology, we have to do it... writing illegibly is not going to do it anymore Although many users were enthusiastic about the potential for handheld computers, most maintained a sense of balance in their perspective: "Just like anything else, it's a tool. It's not the end all be all. It has its pros and its cons, and you just have to learn to get used to it. In some ways it's made our lives easier, and in others it's a bit more cumbersome." Discussion Doctors seem to expect handheld computers to become increasingly useful, if not ubiquitous. Organisations can help doctors leverage the use of devices in several ways. Firstly, they can develop applications to facilitate the downloading of material otherwise available on paper, such as databases, drug formularies, and schedule information, but organisations must ensure that these resources are accurate or they will be promptly abandoned. Secondly, organisations can provide advice, training, and user support and create opportunities for doctors to learn from each other. Finally, they can develop options for mobile access to essential point of care information that can be used on handheld computers. Box 6: Expectations for change in the future And I think what it all boils down to is just the time. It takes too long to manually enter everything. And... you know, if it could do it automatically, I think everybody would do it Once we go to electronic medical records and vital signs and everything is entered in there and you can be wireless and get everything... You wouldn't need to get the cardex, you wouldn't need to get the vital signs, if all that is electronic, you could get that off the PDA I think every day in medicine there is more stuff that you gotta know and things are more complex. I think electronics is going to be our saviour for our sanity and for medical errors and all that kind of stuff. I think there just has to be a place to deposit data and retrieve it fast. I think it is just inevitable. I think more and more of these requirements are going to come down the pike and everyone is going to have to rely on them. Think about when you have got to screen people who have DVTs. What the hell do you do for somebody who has their first DVT? What things should you order and all that kind of stuff. I hope it is on PDA pretty soon What is already known on this topic Little research has examined doctors' perspectives about experience with handheld computers It is not understood how doctors across practice settings view or value the devices, nor if they have concerns What this study adds Doctors who use handheld computers seem satisfied with them and perceive that they enhance patient care; they expect devices to be more useful in the future when input becomes easier and when organisations offer options for wireless connectivity Concerns about the devices include reliability and dependency Organisations could promote devices by providing training, user support, and advice to build confidence in the technology and its capabilities; organisations can also leverage use by developing handheld formatted databases and options for mobile access to essential point of care information Our sample was limited to the United States. Although we sought representation from users and non-users of handheld computers, participants were self selecting, and participation was voluntary. It is likely that doctors interested in handheld computers would be more inclined to participate, although our groups did include sceptics and non-users. As the use of handheld computers in clinical practice is relatively new, and because organisational use of handheld computers varies widely,13 we included doctors at various stages in both their own and their organisation's learning about the devices. Our findings are therefore in part influenced by each doctor's place on the learning curve. Developing strategies to accommodate handheld computers in clinical practice may be advantageous for both institutions and doctors, especially when the devices are used to access clinical information systems, promoting both enhanced safety and improved time efficiency for doctors. When the expected benefits of electronic health records and other electronic applications largely depend on doctors' use of technology, strategies to promote use of such technologies are critical. For many doctors, handheld computers are emerging as a key means to develop familiarity with and to access electronic clinical information. These devices thus may serve as a technology stepping stone for doctors as they face new ehealth initiatives. Contributors: ASMcA, SBS, and MAM were responsible for the study design, data collection, analysis, data interpretation, writing, and submission of this manuscript; they will act as guarantors for the paper. The guarantors accept full responsibility for the conduct of the study, had access to the data, and controlled the decision to publish. ASMcA led the writing and preparation of the manuscript for publication. Funding: Center for Health Management Research. Competing interests: None declared. Ethical approval: Behavioral and Social Sciences Institutional Review Board, Ohio State University (IRB protocol number 01B012). References Harris Interactive. Doctors' use of handheld personal computing devices increases from 15% in 1999 to 26% in 2001. www.harrisinteractive.com/news/allnewsbydate.asp?NewsID=345 (accessed 1 October 2003). Maxwell J. Qualitative research design. Thousand Oaks, CA: Sage, 1996. Miles M, Huberman A. Qualitative data analysis. Thousand Oaks, CA: Sage, 1994. Glaser B, Strauss A. The discovery of grounded theory: strategies for qualitative research. New York: Aldine de Gruyter, 1967. Chen E, Medonca E, McKnight L, Stetson P, Lei J, Cimino J. PalmCIS: a wireless handheld application for satisfying clinical information needs. J Am Med Inform Assoc 2004;11: 19-28. Doolan D, Bates D, James B. The use of computers for clinical care: a case series of advanced US sites. J Am Med Inform Assoc 2003;10: 94-107. Rothschild J, Lee T, Bae T, Bates D. Clinician use of a palmtop drug reference guide. J Am Med Inform Assoc 2002;9: 223-9. Fischer S, Stewart T, Mehta S, Wax R, Lapinsky S. Handheld computing in medicine. J Am Med Inform Assoc 2003;10: 139-49. Schneider S, Kostecke R, Tokazewski J. Buying your first PDA. Fam Pract Manag 2001;8: 50-1. Embi P. Information at hand: using handheld computers in medicine. Cleve Clin J Med 2001;68: 840-9. Wright P, Bartram C, Rogers N, Emslie H, Evans J, Wilson B, et al. Text entry on handheld computers by older users. Ergonomics 2000;43: 702-16. Wilderman I, Dobrousin A, Cameron S. Which handheld computer is better for doctors? Part 1: comparing models with Palm operating systems. Can Fam Doctor 2003;49: 1507-8, 1510-1. Al-Ubaydli M. Handheld computers for doctors. West Sussex, England: John Wiley, 2003....查看详细 (29404字节)
☉ 11357089:14-3-3 -isoform detection distinguishes sporadic Creutzfeldt–Jakob disease from other dementias
Department of Neurobiology, Born Bunge Foundation, University of Antwerp, Wilrijk, Belgium Correspondence to: B Van Everbroeck Laboratory of Neurobiology, Born Bunge Foundation (BBS), University of Antwerp, Campus Drie Eiken, Universiteitsplein 1, B-2610 Wilrijk, Belgium; bart.vaneverbroeck@ua.ac.be ABSTRACT We developed a polyclonal antiserum directed to the -isoform of the human 14-3-3 protein and compared the immunoreactivity with a commercially available antibody (CG31). We analysed 14-3-3 in 253 cerebrospinal fluid samples blinded for the diagnosis by western blot and ELISA, with a commonly used polyclonal antiserum (Sc-731) and the specific antibodies. Our patient population consisted of 52 patients with definite sporadic Creutzfeldt–Jakob disease (sCJD) and 201 patients with a different final diagnosis. We obtained similar sensitivity, ranging from 96% to 98% with all antibodies. Of all the samples that were false positive with Sc-731, 50% were negative with both -isoform specific antibodies resulting in a significantly higher specificity (85% v 93%, respectively). If only sCJD and patients with dementia differing from sCJD were analysed we found that 64% of false positives were negative which also resulted in significantly increased specificity and positive predictive value. The -isoform specific antibodies strongly improve the specificity of the immunoblot and might improve worldwide acceptance of the use of the 14-3-3 assay in the differential diagnosis of sCJD. Abbreviations: AA, amino acid; AU, arbitrary unit; CSF, cerebrospinal fluid; ELISA, enzyme linked immunoassay; FP, false positives; OD, patients with dementia differing from sCJD; OND, other neurological disorders; sCJD, sporadic Creutzfeldt–Jakob disease; TP, true positives Keywords: cerebrospinal fluid; ELISA; western blot; quantification The commonest human prion disease is sporadic Creutzfeldt–Jakob disease (sCJD), with an approximate incidence of one patient per million inhabitants per year. Definite diagnosis of sCJD requires neuropathological study.1 For ante mortem diagnosis, a positive cerebrospinal fluid (CSF) 14-3-3 assay was added to the criteria for "probable" sCJD by the World Health Organization (WHO).2 Although numerous studies3–8 have reported the importance of the 14-3-3 assay in the diagnosis of sCJD, other studies claim it is not sufficiently specific in large populations to be used as a true diagnostic test.9,10 False positive results were obtained in patients with acute or subacute neuronal destruction and in some patients with dementia.11 False negative results were described mainly in early stages or in sCJD patients with a long disease duration. The interpretation of the assay and the number of false positives continue to be a matter of discussion. The 14-3-3 protein has a molecular weight of 30 kDa and seven known isoforms (?, , , , , and ).12 The isoforms ?, , , and have been identified in the CSF of patients with sCJD.5,13 The aim of this study was to investigate whether antibodies directed specifically against the -isoform could improve the differential diagnosis. We analysed the sensitivity and specificity by using the new antibodies in a population of 52 sCJD and 201 control patients in whom a definite diagnosis had previously been made. Next, we investigated whether a quantitative enzyme linked immunoassay (ELISA) would improve our results compared with the subjective western blot technique. MATERIALS AND METHODS Our laboratory performs the 14-3-3 analyses in CSF for the whole of Belgium. When a clinician suspects sCJD a CSF sample and all relevant clinical data are sent to us. We study the clinical data, carry out the 14-3-3 assay, and discuss the result with the neurologist. Afterwards the clinical status of the patient is followed up. After death or after 6–12 months the clinician reports the final diagnosis, and, if applicable, a neuropathological investigation is done. Since 1998, we have analysed CSF samples of 393 patients diagnosed as having "possible" sCJD.11 For 261 (66%) tested patients a final diagnosis could be made using clinical or neuropathological follow up data. We further excluded three patients with a hereditary prion disease and five patients with sCJD who remained "probable" due to lack of neuropathological confirmation. Thus our final study population consisted of 253 patients. In this series three distinct groups of patients could be identified: patients with sCJD (n = 52), patients with dementia differing from sCJD (OD, n = 140), and patients with other neurological disorders (OND, n = 61) (table 1). Table 1 The patient population and results of the 14-3-3 assay* The standard 14-3-3 assay was performed as previously described.4,14 Blots were incubated with Sc-731 (Santa Cruz Inc, Santa Cruz, CA), which is directed against the -isoform but recognises multiple isoforms.13 Each blot included a human brain homogenate (0.1 mg of total protein) as positive control and CSF of a hydrocephalic patient as negative control. A sample was considered to be positive when the immunoblot showed a reactive band of electrophoretic mobility similar to the positive control. All CSF samples were tested twice and if contradictory, a third test was done for final evaluation. We analysed the amino acid (AA) sequences of all 14-3-3 isoforms using the Swiss Prot data (http://us.expasy.org/sprot/) and selected 2 specific epitopes: AA 2-12 and 235-245. Both peptides were injected into the same rabbit and a pAb mix generated. The obtained antisera were purified by affinity chromatography using the initial peptides. Analysis showed an optimal signal of the 14-3-3 pAb mix at a 1:500 dilution. We further analysed a recently available commercial monoclonal antibody (mAb) and obtained optimal results with 1:750 dilution (CG31, Biocarta Inc, Hamburg, Germany). Next we examined the day to day variance on eight samples (four definite sCJD, two Alzheimer’s disease (AD), one dementia with Lewy bodies and one multiple sclerosis) on three consecutive days and one week later. The visual analysis by two independent observers resulted in the same evaluation on all occasions. Combinations of these antibodies were studied in a sandwich ELISA. The intra- and interassay precision of the ELISA were always below 10%. For both western blot and ELISA we used the same brain homogenate as positive standard. RESULTS We analysed 253 CSF samples for the presence of 14-3-3 using three different antibodies. Using Sc-731 pAb we identified 14-3-3 in 81 samples of which 51 were true positives (TP) and 30 false positives (FP), which meant the final diagnosis was other than sCJD. Applying CG31 we found 50 TP and 16 FP while the 14-3-3 pAb resulted in 50 TP and 15 FP (table 1). We identified similar sensitivity but significantly increased specificity with both the CG31 mAb and the 14-3-3 pAb when compared with the Sc-731 pAb (85% v 92%, respectively table 1). In the OD population we found that nine out of 14 bands (64%) identified with Sc-731 did not show any immunoreactivity with either specific antibody resulting in an increased specificity and positive predictive value (table 1). In the OND group we found that five out of 16 bands (31%) were negative with both specific antibodies compared with Sc-731. This improvement did not result in a significantly increased specificity (74% v 84%, respectively, table 1). In some immunoblots faint bands are visible but are scored as negative (fig 1, lane 4), which indicates the difficulty of using a subjective immunoblot. We therefore developed a "quantitative" sandwich ELISA technique. Figure 1 Western blot detection of 14-3-3 protein using Sc-731 pAb (lanes 1–4) and CC31 mAb (lanes 5–8). The molecular marker is depicted on the left side (end). The bands of the positive control (BH, brain homogenate) and the patient with CJD (CJD) are always scored as positive. With the Sc-731 pAb the sample from a patient with Alzheimer’s disease (AD) is positive and the sample from the patient with Hashimoto’s encephalitis (HE), which resulted in only a very faint band, is scored as negative. With the CG31 mAb the AD and HE samples are negative. The optical density of the positive standard, a brain homogenate, on the ELISA was equalised to 1 arbitrary unit (AU) in all tests. The best signal to noise ratio and standard curve were obtained when the Sc-731 pAb was used for capture and CG31 mAb for detection. We identified a median level of 1.00 AU 14-3-3 protein in sCJD patients using the ELISA (range 0.23–1.96 AU). In the patients with a different final diagnosis we found a median of 0.23 AU (range 0.07–1.90 AU). The results from both groups were significantly different with the Mann–Whitney U test (p85%).3–8 On the other hand, some Asian and American groups have reported low specificity with similar technology.9,10,16,17 These differences are most likely due to the criteria used for sample selection. Our results clearly indicate that some neurological disorders which can temporarily mimic sCJD, such as vascular, infectious, and inflammatory encephalopathies may result in false positives and should be excluded before analysis (table 1). Another pitfall in the 14-3-3 analysis is the existence of weak bands which are regarded as positive and faint bands which are regarded as negative if their signal was identical on all three examined blots. Previously, we showed that densitometric analysis, compared with visual analysis, of 14-3-3 leads to increased specificity and lower sensitivity.4 Therefore, this technique was not further explored. In this study we described an ELISA technique, which has similar specificity and could be a valuable alternative for the western blot.4 Recent studies have also shown that the measurement of tau protein and A?1–42 in CSF has gained acceptance in the differential diagnosis of sCJD.11,15 Unlike A?1–42, which is normal or decreased in sCJD, very high tau protein levels can point the diagnosis towards sCJD.14,18 The combination of clinical data correlation and the availability of the novel -isoform specific antibodies might improve worldwide acceptance of the use of the 14-3-3 assay in the differential diagnosis of sCJD. ACKNOWLEDGEMENTS The authors thank all the physicians who sent CSF samples and clinical information of patients with suspected sCJD and control cases and the Fund for Scientific Research (FWO) for supporting this research. REFERENCES Masters CL, Harris JO, Gajdusek DC, et al. Creutzfeldt–Jakob disease: patterns of worldwide occurrence and the significance of familial and sporadic clustering. Ann Neurol 1979;5:177–88. Zeidler M. 14-3-3 cerebrospinal fluid protein and Creutzfeldt–Jakob disease. Ann Neurol 2000;47:683–4. Zerr I, Pocchiari M, Collins S, et al. Analysis of EEG and CSF 14-3-3 proteins as aids to the diagnosis of Creutzfeldt–Jakob disease. Neurology 2000;55:811–15. Van Everbroeck B, Quoilin S, Boons J, et al. A prospective study of CSF markers in 250 patients with possible Creutzfeldt–Jakob disease. J Neurol Neurosurg Psychiatry 2003;74:1210–14. Sanchez-Valle R, Saiz A, Graus F. 14-3-3 Protein isoforms and atypical patterns of the 14-3-3 assay in the diagnosis of Creutzfeldt–Jakob disease. Neurosci Lett 2002;320:69–72. Peoc’h K, Schroder HC, Laplanche J, et al. Determination of 14-3-3 protein levels in cerebrospinal fluid from Creutzfeldt–Jakob patients by a highly sensitive capture assay. Neurosci Lett 2001;301:167–70. Green AJ. Use of 14-3-3 in the diagnosis of Creutzfeldt–Jakob disease. Biochem Soc Trans 2002;30:382–6. Beaudry P, Cohen P, Brandel JP, et al. 14-3-3 protein, neuron-specific enolase, and S-100 protein in cerebrospinal fluid of patients with Creutzfeldt–Jakob disease. Dement Geriatr Cogn Disord 1999;10:40–6. Chapman T, McKeel DW, Morris JC. Misleading results with the 14-3-3 assay for the diagnosis of Creutzfeldt–Jakob disease. Neurology 2000;55:1396–7. Burkhard PR, Sanchez JC, Landis T, et al. CSF detection of the 14-3-3 protein in unselected patients with dementia. Neurology 2001;56:1528–33. Zerr I, Poser S. Clinical diagnosis and differential diagnosis of CJD and vCJD. With special emphasis on laboratory tests. APMIS 2002;110:88–98. Green AJ. Cerebrospinal fluid brain-derived proteins in the diagnosis of Alzheimer’s disease and Creutzfeldt–Jakob disease. Neuropathol Appl Neurobiol 2002;28:427–40. Wiltfang J, Otto M, Baxter HC, et al. Isoform pattern of 14-3-3 proteins in the cerebrospinal fluid of patients with Creutzfeldt–Jakob disease. J Neurochem 1999;73:2485–90. Van Everbroeck B, Green AJ, Pals P, et al. Decreased levels of amyloid-beta 1-42 in cerebrospinal fluid of Creutzfeldt–Jakob disease patients. J Alzheimer’s Dis 1999;1:419–24. Van Everbroeck B, Dobbeleir I, De Waele M, et al. Differential diagnosis of 201 possible Creutzfeldt–Jakob disease patients. J Neurol 2004;251:298–304. Aksamit AJ, Preissner CM, Homburger HA. Quantitation of 14-3-3 and neuron-specific enolase proteins in CSF in Creutzfeldt–Jakob disease. Neurology 2001;57:728–30. Tyler JW, Lakritz J, Weaver D, et al. The 14-3-3 cerebrospinal fluid immunoassay lacks utility in the diagnosis of clinical scrapie. J Vet Diagn Invest 2001;13:537–9. Otto M, Esselmann H, Schulz-Shaeffer W, et al. Decreased beta-amyloid1-42 in cerebrospinal fluid of patients with Creutzfeldt-Jakob disease. Neurology 2000;54:1099–102....查看详细 (14931字节)
☉ 11357090:Lesional location of lateral medullary infarction presenting hiccups(singultus)
Department of Neurology, Korea University Medical College, Seoul, Republic of Korea Correspondence to: Dr Dae Hie Lee Department of Neurology, Korea University Medical College, 126–1, Anam-dong-5-ga, Sungbuk-gu, Seoul 136–705, Republic of Korea; www@medimail.co.kr ABSTRACT Background: Hiccups are an infrequent result of lateral medullary infarction. Their importance may be underestimated and they can cause distress, exhaustion, and aspiration. Hiccups in lateral medullary infarction remain poorly understood Objective: To evaluate the relation between the lesional loci of lateral medullary infarction and hiccups. Methods: 51 patients with lateral medullary infarction were investigated by magnetic resonance imaging within three days of the onset of infarction. Seven of the 51 patients developed hiccup. Results: All patients with hiccups had middle level lateral medullary lesions, including two with lower level lesions and four with upper level lesions. In the middle level lateral medullary lesions, dorsolateral lesions were most often involved. All patients with lateral medullary infarction presenting with hiccups also had vertigo, dizziness, nausea, vomiting, and dysphagia. Conclusions: The observations suggest that middle level and dorsolateral lesion locations in lateral medullary infarction frequently induce hiccups. Abbreviations: DL, dorsolateral; GCC, glottis closure complex; IC, inspiratory complex; ID, inferior-dorsal; IDL, inferior-dorsolateral; LMI, lateral medullary infarction; ML, midlateral; PM, paramedian Keywords: medulla oblongata; cerebral infarction; hiccup Lateral medullary infarction (LMI) or Wallenberg’s syndrome is one of the best known vascular syndromes of the posterior circulation, along with events such as occlusion of the posterior inferior cerebellar artery or the vertebral artery. The usual symptoms of LMI include vertigo, dizziness, nystagmus, ataxia, nausea and vomiting, dysphagia, hoarseness, hiccups, impaired sensation over half the face, impairment of pain and thermal sensation over the contralateral hemibody and limbs and the ipsilateral face, and Horner’s syndrome.1–3 Among the symptoms, hiccups (medical term, singultus) can easily be overlooked, though among other effects they may cause aspiration pneumonia, respiratory depression, and oesophagitis.4 The aetiology of hiccups includes failure of the digestive organs, irritation of the diaphragm, ingestion of alcohol, excessive smoking, and any disease of the central nervous system that involves the brain stem.5–7 LMI in particular can be accompanied by hiccups. Unlike other symptoms and signs of LMI, however, the anatomical lesion of hiccups is not well known.3 In this study we investigated anatomical lesions in patients with LMI suffering from hiccups, using brain magnetic resonance imaging (MRI). METHODS Subjects We investigated 51 patients with LMI admitted to our department of neurology between 1997 and 2002. All patients underwent MRI, which identified a medullary lesion compatible with the clinical symptoms and signs of LMI. They also had plain x rays of the chest and abdomen and general blood testing. Neurological evaluation sought symptoms and signs of LMI such as vertigo, dizziness, nystagmus, ataxia, nausea and vomiting, dysphagia, hoarseness, hiccups, Horner’s syndrome, impaired sensation over half the face, and impaired sensation over the hemibody and limbs. For the evaluation of neuroanatomical lesions, we excluded any patients who might have had other causes of hiccup, such as gastrointestinal disease, irritation of the diaphragm, mediastinal or cervical disease, other CNS disease, metabolic disorders, drug treatment, and psychogenic causes.5–7 Among LMI patients with hiccups, eight who had other possible causes were excluded: two who had chronic gastritis with gastric distension, one who smoked excessively, and five who had been intubated (intubation may stimulate the glottis). Where a nasogastric tube had been inserted, we only included patients who had hiccups before the tube was inserted and continued to have hiccups for more than 12 hours after it was removed. After these exclusions, only seven patients were chosen for the study (five male, two female), age range 40 to 80 years, mean (SD) age, 58.14 (16.17) years. Neurological lesion All patients had an MRI scan, which was done on a 1.5-Tesla scanner (Vision Plus, Siemens Magnetom, Erlangen, Germany), within three days from the time of admission to hospital. Images were obtained using the fast-spin-echo method. The imaging protocol involved T1 weighted (time of repetition (TR) 570 ms, time of echo (TE) 20 ms) and T2 weighted (TR 4200 ms, TE 96 ms) transverse scan images in the horizontal plane at 5 or 6 mm intervals. Three axial sections of the medulla were identified as the lower, middle, and upper levels based on a study by Bradley.8 Axial cuts were further classified into intralevel lesion loci on the basis of a study by Kim et al.9 The lower level was set at the termination of the fourth ventricle, and was divided into paramedian (PM), inferior-dorsal (ID), and inferior-dorsolateral (IDL) regions. The middle level was set at the centre of the inferior olivary nucleus, and was classified into PM, midlateral (ML), and dorsolateral (DL) regions. The upper level was set at the pontobulbar junction and was split into PM and ML. RESULTS As shown in fig 1, among LMI patients with hiccup, two cases had lesion loci at the middle and lower levels, and four cases at the middle and upper levels. Although one case (patient 6) had lesions over all levels of the medulla, we included this case in the analysis because the lesions were mainly located in the middle level. The lesions in the three cases involving the lower level of the medulla were all in the IDL region. Among the middle level lesions, six were in the DL region, one in the PM region, and one in the ML region. The lesions in the upper level all occurred in the ML region. Figure 1 Characteristics of lateral medullary infarction patients with hiccups. *L, lower; M, middle; and U, upper. L, left; R, right. ID, inferior-dorsal; IDL, inferior-dorsolateral; DL, dorsolateral; PM, paramedian; ML, midlateral. ?DP, dysphagia; GA, gait ataxia; HN, Horner’s sign; HS, hoarseness; IB, impaired sensation over the body; IF, impaired sensation over half the face; NS, nystagmus; N/V, nausea/vomiting; VD, vertigo/dizziness. All seven subjects showed accompanying symptoms such as vertigo, dizziness, nausea/vomiting, and dysphagia. Ataxia was observed in six subjects; five experienced hoarseness, impaired sensation over half the face, and impaired sensation over the body, while three had Horner’s syndrome. One subject had nystagmus. Based on the structural involvement in LMI,1,3 five of the seven cases had involvement the fifth nerve, with, for example, impaired sensation over half the face; six of the seven had involvement of the restiform body and cerebellar connections, with ataxia; variable numbers had involvement of the vestibular nuclei and connections, manifesting as vertigo, nausea and vomiting, and nystagmus; three of the seven cases had involvement of the descending sympathetic tract, with Horner’s syndrome; and all cases had involvement of either the ninth or the tenth cranial nerves or both, with dysphagia and hoarseness. DISCUSSION Hiccups are repeated involuntary, spasmodic, and temporary contractions of the diaphragm accompanied by sudden closure of the glottis, producing a distinguishing "hic" sound.5 It is suggested that hiccups are caused by the failure of the reciprocal inhibition of the valve control of the pharynx and larynx.10 This dynamic valve function is achieved by alternating excitation-inhibition of two structures: the glottis closure complex (GCC) and the inspiratory complex (IC). Activation of the GCC consists of the backward swing of the epiglottis of the vocal cords, contraction of the hyoid muscles and the superior constrictor of the pharynx, relaxation of the upper oesophageal sphincter, and activation of the IC, made up of diaphragmatic, exterior intercostal, sternocleidomastoid, anterior serratal, and scalene contraction. The IC is activated within 30–40 ms. Paradoxical activation of the GCC causes tonic phasic inspiratory obstruction. The hiccup, with its unique sound, then occurs. The physiological purpose of hiccups is uncertain. Because fetuses and premature infants hiccup often, it is suggested that hiccups are a programmed isometric inspiratory muscle exercise, which is useless after the neonatal period but may be restimulated by irritation along the reflex arc.11 The neuroanatomical centre for hiccups is not well known, although the central connection is presumed to be a part of the brain stem which probably interacts with its respiratory centres, phrenic nerve nuclei, medullary reticular formation, and hypothalamus.3,7,12 The afferent pathway is made up of the sensory branches of the phrenic and vagus nerves and the dorsal sympathetic fibres, while the efferent pathway is formed by the motor fibres of the phrenic nerve.13 Hiccups have central and peripheral causes.5,14 Central hiccups occur with lesions between the pathway from the central nervous system to the phrenic nerve, mainly in diseases of the brain stem such as ischaemic stroke, dolichoectatic basilar artery, tumours, encephalitis, and multiple sclerosis.12,13,15,16 The role of the central nervous system is suggested by the complex physiological mechanism of hiccup, which requires an interaction in the supraspinal polysynapsis.13 Peripheral hiccups can be caused by diseases at phrenic nerve level such as gastric distension.5,6 We cannot identify the mechanism of hiccup in patients with LMI, but we can make a few assumptions. First, it is likely that there is denervation supersensitivity because palatal myoclonus is common in such patients.14,15,17 Loss of supranuclear control occurs in the brain stem, especially at ponto-medullary level—the so called myoclonic triangle of Guillan-Mollaret consisting of the dentate nucleus, the inferior olivary nucleus, and the red nucleus. Denervation supersensitivity leads to hiccup. Nonetheless, the region of the myoclonic triangle of Guillan-Mollaret usually involves the peduncle rather than the medulla. Hiccups occur several weeks after the onset of denervation, when enlargement of the inferior olivary nucleus is observed. The patients in our study, however, developed hiccups on the day of the brain infarction or on the next day, and brain MRI did not show any particular lesion in the Guillan-Mollaret triangle. This mechanism was therefore not able to explain hiccups in lateral medullary infarction. Hiccups occur because LMI causes an imbalance between expiration and inspiration.1,18 The expiratory centre and the inspiratory centre are in the central medulla (fig 2). The areas involved are known to overlap, the expiratory area being larger than the inspiratory area and extending more laterally and dorsally in the reticular formation of the medulla. The expiratory centre is also larger, and lies in the outer side of the medulla. Thus, if the lesion is around the nucleus ambiguus of the medulla, the expiratory centre is destroyed, causing an imbalance between expiration and inspiration and consequently leading to hiccups. Figure 2 Major lesions of lateral medullary infarction in patients with hiccups on T2WI magnetic resonance imaging. In addition, hiccups may stem from ischaemia of the dorsal motor nucleus of the vagus or the nucleus of the solitary tract located beneath the lateral part of the floor of the fourth ventricle in the dorsal medulla, medial to the vestibular nuclei.2 As well as being caused by LMI, hiccups reportedly occur because of angiomas in the medulla,5 primary medullary haemorrhage,19 and tumours or tuberculomata in the brain stem.15 These are all located in the dorsolateral medulla. Five cases in our study occurred in the dorsolateral medulla. In animal experiments,20 hiccup-like responses can be generated by electrical stimulation of the medullary reticular formation lateral to the nucleus ambiguus at the rostrocaudal level, between 1 mm and 2.5 mm rostral to the obex of the fourth ventricle of a cat. This is mainly the region of the dorsolateral medulla, where the nucleus ambiguus is located—including the vagal motor neurones projecting to the larynx and the premotor neurones that control the diaphragm.21,22 Thus lesions in this region induce hiccups, as they affect the laryngeal motor neurones which control the glottis and the premotor neurones which control the inspiratory muscles.23 If the nucleus raphé magnus—with GABAergic inhibitory cells in the medullary reticular formation of the outer region of the nucleus ambiguus—is destroyed hiccups are induced.23 The clinical features of hiccups in LMI have been described.1,2,24–26 The frequency of hiccup is around 12–36% in this condition. Nonetheless, the frequency of LMI itself is relatively low, and most studies involved only 20 to 40 patients, with differing frequencies of LMI. Data from a previous study on LMI2 showed that 44 of 172 patients (around 26%) developed hiccup.2 In our study, seven of 51 patients (14%) developed hiccup. Hiccups in LMI are often accompanied by symptoms involving the fifth, ninth, and tenth cranial nerves, with nausea and vomiting.1 In the present study, all the affected patients had symptoms involving either the ninth or the tenth cranial nerve or both, six involved the cerebellar connections, five had symptoms of fifth cranial nerve involvement, and all cases had symptoms caused by involvement of the vestibular nuclei and their connections (figs 2 and 3). From our analyses of symptoms and lesion locations, we thought that the hiccup centre—the possible area of involvement necessary to produce hiccups—was placed in the region of the cerebellar, vestibular, and ninth, tenth, and fifth cranial nerve nuclei, and their connections with the middle part of the medulla. The lesion appears to be mainly in the dorsolateral region of the middle medulla. One might expect that such a lesion could also induce hiccups through an imbalance between expiration and inspiration, because it is situated around the respiratory area. This has been suggested in previous studies.1,18 Figure 3 Schematic transverse section of the medulla. Cell columns related to functional components of important structures are indicated on the left. On the right, the hypothesised critical region involved in the development of hiccups is indicated by the dark oval. Unfortunately, our study has some limitations. Only 1.9% of all cerebral infarcts are in the lateral medulla,24 and our yield of only seven patients reflects this. It is therefore difficult to obtain enough patients for an adequate sample. In addition, few of the patients with LMI developed hiccup. Patients with dysphagia and secondary hiccup caused by oral secretions or irritation of the airway from dysphagia cannot easily be distinguished from those with a central cause. From previous studies, however, LMI patients experience hiccups during sleep before developing dysphagic symptoms, and the hiccups do not cease in parallel with recovery from the dysphagia.1 While MRI is the preferred imaging technique for vertebrobasilar territory infarcts, and we used an anatomical approach at three different levels and two or three intralevel areas in the medulla in order to minimise errors in locating the infarcts, there may nevertheless be sources of investigational bias; these could arise from variations in the thickness of the MRI slices and the gaps between them, and uncertainties in forming the reference line used to section the brain stem. Conclusions Around 14% of patients with lateral medullary infarcts had hiccups in our study, mainly when the lesions occurred in the dorsolateral region of the middle medulla. There was a close correlation between hiccups and symptoms of cerebellar, vestibular, and fifth, ninth, and tenth cranial nerve involvement. Although there may be arguments against assigning a simple lesional location to such a complicated process as hiccup, the development of hiccup does appear to be related to lesions in the dorsolateral region of the middle medulla. A larger study is necessary to define the anatomical correlates of hiccup with more certainty. REFERENCES Currier RD, Giles CL, Dejong RN. Some comments on Wallenberg’s lateral medullary syndrome. Neurology 1961;11:778–91. Caplan LR. Posterior circulation disease: clinical findings, diagnosis, and management. Massachusetts: Blackwell Science, 1996:263–323. Victor M, Ropper AH. Adams and Victor’s principles of neurology. New York: McGraw-Hill, 2001:821–924. Kumar A, Dromerick AW. Intractable hiccups during stroke rehabilitation. Arch Phys Med Rehabil 1998;79:697–9. Launois S, Bizec JL, Whitelaw WA, et al. Hiccup in adults: an overview. Eur Respir J 1993;6:563–75. Loft LM, Ward RF. Hiccups. A case presentation and etiologic review. Arch Otolaryngol Head Neck Surg 1992;118:1115–19. Friedman NL. Hiccups: a treatment review. Pharmacotherapy 1996;16:986–95. Bradley WG. MR of the brain stem: a practical approach. Radiology 1991;179:319–32. Kim H, Chung CS, Lee KH, et al. Aspiration subsequent to a pure medullary infarction: lesion sites, clinical variables, and outcome. Arch Neurol 2000;57:478–83. Askenasy JJ. About the mechanism of hiccup. Eur Neurol 1992;32:159–63. Kahrilas PJ, Shi G. Why do we hiccup? Gut 1997;41:712–13. Marsot-Dupuch K, Bousson V, Cabane J, et al. Intractable hiccups: the role of cerebral MR in cases without systemic cause. Am J Neuroradiol 1995;16:2093–100. Fodstad H, Nilsson S. Intractable singultus: a diagnostic and therapeutic challenge. Br J Neurosurg 1993;7:255–60. Musumeci A, Cristofori L, Bricolo A. Persistent hiccup as presenting symptom in medulla oblongata cavernoma: a case report and review of the literature. Clin Neurol Neurosurg 2000;102:13–17. al Deeb SM, Sharif H, al Moutaery K, et al. Intractable hiccup induced by brainstem lesion. J Neurol Sci 1991;103:144–50. McFarling DA, Susac JO. Hoquet diabolique: intractable hiccups as a manifestation of multiple sclerosis. Neurology 1979;29:797–801. de la Fuente-Fernandez R. . Med Clin (Barc) 1998;110:22–4. Hoff HE, Breckenridge CG. The neurogenesis of respiration. In: Fulton JF, ed. A textbook of physiology. Philadelphia: WB Saunders Co, 1955:843–9. Kumral E, Acarer A. Primary medullary haemorrhage with intractable hiccup. J Neurol 1998;245:620–2. Arita H, Oshima T, Kita I, et al. Generation of hiccup by electrical stimulation in medulla of cats. Neurosci Lett 1994;175:67–70. Arita H, Sakamoto M, Hirokawa Y, et al. Serotonin innervation patterns differ among the various medullary motoneuronal groups involved in upper airway control. Exp Brain Res 1993;95:100–10. Cohen MI. Neurogenesis of respiratory rhythm in the mammal. Physiol Rev 1979;59:1105–73. Oshima T, Sakamoto M, Tatsuta H, et al. GABAergic inhibition of hiccup-like reflex induced by electrical stimulation in medulla of cats. Neurosci Res 1998;30:287–93. Norrving B, Cronqvist S. Lateral medullary infarction: prognosis in an unselected series. Neurology 1991;41:244–8. Sacco RL, Freddo L, Bello JA, et al. Wallenberg’s lateral medullary syndrome. Clinical-magnetic resonance imaging correlations. Arch Neurol 1993;50:609–14. Lee SS, Roh JK, Lee SB, et al. A clinical study of 21 patients with lateral medullary syndrome. J Korean Neurol Assoc 1989;7:42–51....查看详细 (19962字节)
☉ 11357091:Patients' experience with a diabetes support programme based on an interactive electronic medical record: qualitative study
1 Center for Health Studies, Group Health Cooperative, 1730 Minor Avenue, Suite 1600, Seattle, WA 98101-1448, USA, 2 University of Washington, School of Public Health and Community Medicine, Department of Health Services, Box 357660, Seattle, WA 98195-7660, 3 University of Washington, Department of Medical Education and Biomedical Informatics, Box 357240, Seattle, WA 98195-357240, 4 University of Washington, Department of Medicine, Box 359780, Seattle, WA 98195-359780 Correspondence to: J D Ralston ralston.j@ghc.org Abstract Objective To describe the experiences of patients with type 2 diabetes in a web based disease management programme based on an interactive electronic medical record. Design Qualitative analysis of semistructured interviews with patients enrolled in a diabetes care module that included access to their electronic medical record, secure email, ability to upload blood glucose readings, an education site with endorsed content, and an interactive online diary for entering exercise, diet, and medication. Setting Patients' homes in Washington state, United States. Participants Nine participants aged 45-65 completed interviews before and after they used the programme. Results Six themes emerged: feeling that non-acute concerns are uniquely valued; enhanced sense of security about health and health care; frustration with unmet expectations; feeling more able to manage; valuing feedback; and difficulty fitting the programme into activities of daily life. Three themes—valuing non-acute concerns, feeling secure, and unmet expectations—have particular relevance to the design and use of web based tools for care of patients with diabetes and chronic medical conditions. Conclusion Participants' experiences support further study of open access to the electronic medical record and online communication between patients and their care providers. The development of web based disease management programmes should take into account the specific needs and expectations of patients, and patients and providers should have candid discussions about what web based care can and cannot provide. Introduction The living with diabetes programme is a web based disease management module to support the care of patients with type 2 diabetes. A complete description of the module is given elsewhere.3 The programme targets four key domains in Wagner's chronic disease model: self management support for patients; delivery system design; clinical information systems; and clinical decision support (box). The web module itself consists of five web pages within a single secure website that allows patients and providers to communicate over the internet (see bmj.com). The living with diabetes pilot study was run out of a general internal medicine clinic affiliated with the University of Washington; eight general internists were the primary care providers for the participants. All patients lived in the state of Washington, at distances ranging from 5 km to 480 km (3-291 miles) from the clinic. The study used a case manager model of chronic disease care.4 The case manager (a nurse practitioner) encouraged all patients to review their online medical record, upload blood glucose readings weekly, and send secure electronic mail as needed. For each patient in the study, providers responded to patients' messages Monday through Friday and reviewed uploaded blood glucose levels at least once a week. Most components of the module were available to participants throughout the study period. However, two components of the module were delayed. The ability to graphically view blood glucose levels at home was not available until month 4 and the "my diabetes daily diary" did not became fully functional until month 6 of the pilot. Using convenience sampling, we approached 35 patients at the general internal medicine clinic. Fifteen of those approached agreed to participate in the feasibility trial. For the qualitative study, we used purposive sampling to identify a subpopulation of 10 patients from the 15 originally recruited. In selecting these 10 patients we sought to ensure a range of patient characteristics including age, sex, years with diabetes, and distance from the clinic.5 One patient subsequently dropped out of the programme and could not be reached for follow up after the first interview. The remaining nine patients (six men) made up the study sample. Participants were aged 43-65 (median 58) years and had had type 2 diabetes for one to 14 (median four) years. Eight were married or had partners, one was single; two had high school education, one college education, and four graduate school education; eight were white and one was African-American. Patients' degree of interaction with the programme varied. Some patients used it only a few times through the entire six month study period; others used it several times a week. We interviewed the nine participants twice between October 2001 and December 2002—before and six months after enrolment in the programme. Interviews were semistructured and in-depth, and were carried out in patients' homes. In the first interview, the interviewer (JDR) asked participants about their interest in participating in the programme. Follow up questions explored and clarified the content of the programme and asked about the anticipated impact of the programme on participants' experience with diabetes and their relationship with their providers. Six months after the start of the programme, participants were interviewed a second time (by JDR). In the second interview, participants were first asked to describe their experiences with the programme. Follow up questions explored and clarified the content of participants' responses. Participants were also asked about their perception of any impact the programme had had on their life with diabetes and their relationship with their primary care provider. Interviews ranged from 60 to 80 minutes. All interviews were audio taped, transcribed verbatim, and manually edited by the interviewer while listening to the tape of the interview. Design of the living with diabetes management programme (domains and interventions) Self management support Promoted patient review of the electronic medical record at home over the web through My Health Record, a real-time view of the same record and interface used by providers and containing all clinical data since January 199422 Provided remote collaboration and interactive feedback on automatically uploaded blood glucose readings over the internet through My Upload Meter Provided remote collaboration and interactive feedback on nutrition, medications, and exercise using a web based self management tool, My Diabetes Daily Diary Promoted and integrated secure email into ongoing care with diabetes case manager Provided general diabetes educational website with links to information endorsed by the medical director of the University of Washington Diabetes Care Center Delivery system design Used case manager model23 Provided initial weekly follow up over the web for blood glucose levels and other self management needs Provided subsequent proactive follow up based on patient needs Promoted and integrated secure email exchanges into ongoing care Promoted and integrated patients' blood glucose and lifestyle information into ongoing care Clinical information systems Provided ongoing tracking and documentation of patients' evidence based needs and care Used secure email integrated as part of the record Decision support Used an interactive electronic medical record for collaborative decision support shared by both patient and provider: Clinical reminders visible to both patient and provider Single page summary of patient's clinical information relevant to diabetes Established provider decision support through patients' remote transmission of blood glucose readings, daily diary inputs, and secure email exchanges Transcripts from the two interviews were independently read and analysed for common themes by two investigators (JDR, DR) in an approach informed by phenomenology.6-9 One coder was a physician and the other a psychologist. These authors met repeatedly to discuss themes and resolve discrepancies in thematic definitions. If new codes emerged, the codebook was modified and transcripts reread and recoded according to the clarified definitions. Micro codes were consolidated into major themes representing patients' experience. In a third round of interviews with six of the nine participants, these themes were reviewed and further clarified. These six participants were selected during the first two interviews for their ability to describe their lives with diabetes and their interactions with the module. We used QSR-NUD*IST qualitative data analysis software to manually record and compare coding of transcripts. In our analysis, we sought to represent participants' actual experience of the programme by closely analysing their narrative descriptions of their hopes and interactions with the project. Rather than approach the narrative data with preconceived notions about what it might contain, we allowed themes to emerge from the data themselves. Results Three themes emerged as important to the design and evaluation of web based care programmes. Firstly, the living with diabetes programme provided a unique environment where participants' chronic concerns were actively valued. Previous work has documented how our systems of care are poorly designed to meet the needs of patients with chronic illness.2 10 Our findings show that web based programmes such as ours may be particularly successful at dealing with those needs. Secondly, patients experienced an enhanced sense of security about their health and health care. This improved sense of security may promote healthy behaviours and better quality of life in patients with diabetes.11 Finally, participants were profoundly disappointed when their expectations for the technology and communications of the programme were not met. Studies have shown that meeting patients' expectations is important not only for patient satisfaction but also for achieving better resolution of symptoms and reducing further use of healthcare resources.12 Conversations with patients about their expectations for care can be challenging for doctors during office visits13; our study shows that it may be even more difficult to understand and address these expectations in web based health care. The living with diabetes programme provided participants with a connection to providers and healthcare information that was different from their usual healthcare experience. Instead of episodic connections with providers at office visits, a provider was a continuous presence that watched benevolently from a distance as participants engaged in the daily activities of managing their diabetes. Having access to the electronic medical record, and particularly the results of medical testing, was also important to patients. This is consistent with several studies that have shown the value of promoting patient review of the medical record as part of effective management.14-20 interventions in chronic disease What is already known on this topic Web based programmes for management of chronic diseases can shift the focus in health care away from the office and towards patients' daily lives at home Little is known about the impact of using the web in the clinical care of patients with chronic disease What this study adds Web based disease programmes can fill an important gap in how health care is currently provided for patients with chronic medical conditions Programmes that include online communications and open access to the electronic medical record warrant further study in larger trials Before and during the use of web based chronic care, patients and providers should discuss what the programme can and cannot deliver Patients' experience with the living with diabetes programme supports further study of web based programmes that are tightly integrated into patients' overall clinical care. A recent trial looking at web based support for self management of diabetes, separate from patients' usual care, showed that patients benefited from basic web services including general information, automated dietary goal setting, and periodic online assessments. In that trial, adding tailored self management did not show any benefit. Our results are consistent with the authors' conclusions, that benefit from tailored self management in web based diabetes care may require programmes that have stronger links to patients' existing clinical care.21 Limitations Our study has a few limitations. Firstly, it is a pilot study in an academic medical centre; a community setting might have provided different findings. Because the interviewer was a doctor, patients may have responded differently than they would to a non-medical interviewer. Lastly, patients who either declined to participate or who were not approached about participating might have had different experiences with the programme than those who participated. Conclusion and implications Web based chronic care programmes have unique potential to shift care processes towards more continuous collaborative relationships between patients and providers. Our work supports further study of web based diabetes programmes that include online communications and open access to the electronic medical record. Our study also contributes to thinking about how to design future programmes. In particular, our themes highlight the importance of accounting for individual patients' needs. Before and during the use of web based chronic care, patients and providers should have candid discussions about what the programme can and cannot deliver. Screen shots of the web links module are on bmj.com Contributors: JDR, HIG, and LSR conceived and designed the study. JDR, DR, and LSR analysed and interpreted the data. All authors helped prepare and revise the manuscript and reviewed the manuscript before submission and publication. JDR is guarantor. Funding: This study was supported by the Aetna Quality Care Research Fund and the Center for Health Management Research. JD Ralston was additionally supported by a General Medicine Research Fellowship, National Research Service Award grant PHS-5-T-32 PE-10002-10 from the National Institutes of Health, Bethesda, Maryland. All investigators are independent of funders for this study. Competing interests: None declared. Ethical approval: University of Washington Institutional Review Board. References Institute of Medicine. Crossing the quality chasm: a new health system for the 21st century. Washington, DC: National Academy Press, 2001. Bodenheimer T, Wagner EH, Grumbach K. Improving primary care for patients with chronic illness. JAMA 2002;288: 1775-9. Goldberg HI, Ralston JD, Hirsch IB, Hoath JI, Ahmed KI. Using an internet comanagement module to improve the quality of chronic disease care. Joint Commission J Qual Saf 2003;29: 443-51. Aubert RE, Herman WH, Waters J, Moore W, Sutton D, Peterson BL, et al. Nurse case management to improve glycemic control in diabetic patients in a health maintenance organization. A randomized, controlled trial. Ann Intern Med 1998;129: 605-12. Brim JA, Spain DH. Research design in anthropology: paradigms and pragmatics in the testing of hypotheses. New York: Holt, Rinehart and Winston, 1974. Giorgi A. Phenomenology and psychological research. Pittsburgh, PA: Duquesne University Press, 1985. Malterud K. Qualitative research: standards, challenges, and guidelines. Lancet 2001;358: 483-8. Morse JM, Field PA. Qualitative research methods for health professionals. Thousand Oaks, CA: Sage Publications, 1995. Denzin NK, Lincoln YS, eds. Strategies of qualitative inquiry. Thousand Oaks, CA: Sage Publications, 1998. Wagner EH, Austin BT, Davis C, Hindmarsh M, Schaefer J, Bonomi A. Improving chronic illness care: translating evidence into action. Health Aff (Millwood) 2001;20(6): 64-78. Kawachi I, Berkman LF. Social epidemiology. New York: Oxford University Press, 2000. Bell RA, Kravitz RL, Thom D, Krupat E, Azari R. Unmet expectations for care and the patient-physician relationship. J Gen Intern Med 2002;17: 817-24. Clever SL, Tulsky JA. Dreaded conversations: moving beyond discomfort in patient-physician communication. J Gen Intern Med 2002;17: 884-5. Greenfield S, Kaplan S, Ware JE, Jr. Expanding patient involvement in care. Effects on patient outcomes. Ann Intern Med 1985;102: 520-8. Greenfield S, Kaplan SH, Ware JE Jr, Yano EM, Frank HJ. Patients' participation in medical care: effects on blood sugar control and quality of life in diabetes. J Gen Intern Med 1988;3: 448-57. Maly RC, Bourque LB, Engelhardt RF. A randomized controlled trial of facilitating information giving to patients with chronic medical conditions: effects on outcomes of care. J Fam Pract 1999;48: 356-63. Bronson DL, Costanza MC, Tufo HM. Using medical records for older patient education in ambulatory practice. Med Care 1986;24: 332-9. Bronson DL, O'Meara K. The impact of shared medical records on smoking awareness and behavior in ambulatory care. J Gen Intern Med 1986;1: 34-7. Bronson DL, Rubin AS, Tufo HM. Patient education through record sharing. QRB Qual Rev Bull 1978;4(12): 2-4. Rachmani R, Levi Z, Slavachevski I, Avin M, Ravid M. Teaching patients to monitor their risk factors retards the progression of vascular complications in high-risk patients with Type 2 diabetes mellitus—a randomized prospective study. Diabet Med 2002;19: 385-92. Glasgow RE, Boles SM, McKay HG, Feil EG, Barrera M. The D-Net diabetes self-management program: long-term implementation, outcomes, and generalization results. Prev Med 2003;36: 410-9. Goldberg HI, Tarczy-Hornoch P, Stephens K, Larson EB, LoGerfo JP. Internet access to patients' records . Lancet 1998;351: 1811. Aubert RE, Herman WH, Waters J, Moore W, Sutton D, Peterson BL, et al. Nurse case management to improve glycemic control in diabetic patients in a health maintenance organization: a randomized, controlled trial. Ann Intern Med 1998;129: 605-12....查看详细 (18532字节)
☉ 11357092:Spontaneous nystagmus in dorsolateral medullary infarction indicates vestibular semicircular canal imbalance
Department of Neurology, University of Luebeck, Luebeck, Germany Correspondence to: Dr Holger Rambold Department of Neurology, University of Luebeck, Ratzeburger Allee 160, D-23538 Luebeck, Germany; rambold_h@neuro.mu-luebeck.de ABSTRACT Background: Spontaneous nystagmus caused by dorsolateral medullary infarction may be of vestibular origin. Objectives: To test if imbalance of the central pathways of the semicircular canals contributes to spontaneous nystagmus in dorsolateral medullary syndrome. Methods: We examined four patients with dorsolateral medullary syndrome and recorded spontaneous nystagmus binocularly at gaze straight ahead with the three-dimensional search coil technique. The median slow phase velocity of the nystagmus was analysed in the light and in the dark, and the normalised velocity axes were compared with the rotation axes as predicted from anatomical data of the semicircular canal. Results: The slow phase rotation axes of all patients aligned best with the rotation axes resulting from stimulation of the contralesional posterior and horizontal semicircular canals. This alignment cannot be explained by pure otolith imbalance. Conclusion: We propose that vestibular imbalance caused by an ipsilesional lesion of the central semicircular canal pathways of the horizontal and anterior semicircular canals largely accounts for spontaneous nystagmus in dorsolateral medullary syndrome. Abbreviations: MRI, magnetic resonance imaging; OTR, ocular tilt reaction; VN, vestibular nuclei Keywords: binocular; dorsolateral medullary syndrome; nystagmus; vestibular Vertigo, ipsilesional lateropulsion, and ipsilesional ocular tilt reaction (OTR, skew deviation with hypotropia of the eye on the lesion side, ocular torsion, and head tilt to the side of the lesion) are major features of dorsolateral medullary infarction.1,2 These symptoms may be caused by imbalance of central otolith signals due to impairment of the caudal part of the vestibular nucleus complex.3–5 There is some evidence that in addition to central otolith imbalance, imbalance of the central pathways of the semicircular canals also contributes to the vestibular signs in dorsolateral medullary infarction.6,7 In the early phase of dorsolateral medullary infarction, spontaneous nystagmus is often observed at gaze straight ahead with a horizontal,6,7 torsional,6 or mixed torsional, horizontal, and vertical direction component.6,8 The nystagmus normally beats to the intact side,2,6,8 but it may rarely also beat to the side of the infarction.2,7,9 Linear, exponential increasing and decreasing drifts are found during the slow phases. Nystagmus in these patients is often present only in the first days and rapidly declines over the following days. Its pathomechanism could be vestibular imbalance4,6 caused by a lesion of the vestibular nuclei or their commissural pathways in the dorsal medulla. However, analysis of the nystagmus with respect to the rotation axes of the semicircular canals has been missing so far.6,10 To analyse the contribution of the individual semicircular canals to spontaneous nystagmus we recorded binocular, three-dimensional (3-D) eye movements of four patients with dorsolateral medullary infarction under head restrained conditions and analysed the rotation axes of the slow phases. We compared the slow phase axes with those of the semicircular canals obtained from anatomical data.11 Preliminary data have been published in abstract form elsewhere.12 METHODS Patient #1 A 66 year old man presented with left dorsolateral medullary syndrome. On admission he had left Horner’s syndrome, sensory loss of pain and temperature on the left side of his face, right trunk, and limbs, and hemiataxia of the left side. He also showed a falling tendency to the left. Oculomotor examination demonstrated conjugate nystagmus in gaze straight ahead with a clockwise (rightward) torsional (contralesionally beating fast phases; from the subject’s point of view) and a rightward horizontal component. The torsional component was more pronounced in the right eye; it increased in amplitude but decreased in frequency in the dark. There was a small vertical component in the upward direction. The patient had leftward lateropulsion of saccades (hypermetria), saccadic smooth pursuit to the right, skew deviation with hypotropia of the left eye, and a head tilt to the left. Magnetic resonance imaging (MRI) revealed a left dorsolateral medullary infarction (fig 1). Eye movement recordings were performed 1 day after symptom onset. Figure 1 MRI. The T2 weighted axial magnetic resonance images of the medulla oblongata for patients #1 to #4 are shown in the first row. The extent of the lesion (white areas) is projected onto the appropriate anatomical slices (CVII, Tc-30) of the stereotaxic atlas of Schaltenbrand and Wahren.14 The location of the vestibular nuclei (VN) is marked as a black area. The lesion is a dorsal medullary infarction that involves the ipsilesional VN in all four patients. Important landmarks are indicated in the anatomical reconstruction of patient #1 on the intact side. ICP, inferior cerebellar peduncle; IO, inferior olive; OCT, olivocerebellar tract; PT, pyramidal tract; SPCTd, dorsal spinocerebellar tract; SPCTv, ventral spinocerebellar tract; ST, nucleus of the solitary tract; X, dorsal motor vagal nucleus; XII, hypoglossal nucleus. Patient #2 A 64 year old woman presented with left dorsolateral medullary syndrome. Left Horner’s syndrome, sensory loss of pain and temperature on the left side of the face and her right trunk and limbs, and hemiataxia of her left side were present. She also showed a falling tendency to the left. Oculomotor examination detected nystagmus with clockwise (contralesionally beating, rightward) torsional, rightward horizontal, and upward vertical fast phase components that increased in amplitude in the dark. The torsional nystagmus had a larger torsional component in the right eye. The patient had leftward lateropulsion of saccades (hypermetria), saccadic smooth pursuit eye movements to the right, skew deviation with hypotropia of the left eye, and a head tilt to the left. MRI revealed a left dorsolateral medullary infarction (fig 1). Eye movement recordings were performed 1 day after symptom onset. Patient #3 A 73 year old hypertensive man presented with right lateral medullary syndrome. He had mild dysarthria and dysphagia, sensory loss of pain and temperature on the right side of his face, left trunk, and limbs, and hemiataxia of the right side. There was lateropulsion to the right. Oculomotor examination revealed nystagmus with a counterclockwise (contralesionally beating, leftward) torsional and a leftward horizontal component (fast phases) that increased in the dark. There was an upward vertical nystagmus component in both eyes. The nystagmus was conjugate and the amplitudes equal in both eyes. The patient had rightward lateropulsion of saccades (hypermetria), saccadic smooth pursuit eye movements in both directions, skew deviation with hypotropia of the right eye, and a head tilt to the right. MRI revealed a right dorsolateral medullary infarction (fig 1). Eye movement recordings were performed on the third day after symptom onset. Patient #4 A 63 year old man presented 2 days after onset of acute unsteadiness and vertigo with right dorsolateral medullary syndrome. He had right Horner’s syndrome, sensory loss of pain and temperature on the left trunk and limbs, and hemiataxia of the right side. He also had a falling tendency to the right. Oculomotor examination demonstrated conjugate nystagmus with a counterclockwise (contralesionally beating, leftward) torsional, a rightward horizontal, and upward fast phase components in the light, which was more pronounced in the dark. The nystagmus was conjugate. There was also horizontal gaze evoked nystagmus in both horizontal directions. Saccades to the right were hypermetric. Skew deviation with hypotropia of the right eye was found. MRI revealed a right incomplete dorsolateral medullary infarction, with two parts, that is, a more dorsal and a more lateral portion (fig 1). Eye movement recordings were performed 5 days after symptom onset. MRI T1, T2, diffusion, and FLAIR weighted MRI including high resolution axial 3 mm slices of the brainstem were acquired (1.5 Tesla Siemens Magnetom Symphony, Germany). Reconstruction of the lesions was performed using axial and sagittal slices as described14 on the basis of the stereotaxic atlases of Schaltenbrand and Wahren13 and Olszewski and Baxter.15 Individual axial slices were normalised and superimposed on the appropriate level of the anatomy atlas. Tonic ocular torsion Fundus photography was performed during mydriasis for each eye separately to measure tonic ocular torsion. Roll deviation of the fovea-macula intersection was measured in 10 age matched controls. More than 9.7° or less than 1.4° excyclorotation with respect to the horizontal meridian was considered as pathological. Search coil recording After the patients had given their informed consent, binocular, 3-D search coil recordings (Remmel, Ashland, MA, USA, frame size 180 cm cube; combination annulus, Skalar, Delft, the Netherlands) were performed. The head was stabilised comfortably in an upright position by a firm head rest and chin support. In vitro calibration of the coils and fixation at gaze straight ahead (laser target 145 cm distance from the eyes) was used to calibrate each individual eye.16,17 The coil signals were digitised (16 bit AD, NI PCI 6071E, 600 Hz) and filtered by an impulsive response filter at 100 Hz (3 dB level). Eye position was calculated in quaternions with eye velocity measured as angular not as derivative velocity.17 Clockwise (rightward) torsion (movement direction from the upper pole of the eye), downward, and leftward movements from the subject’s view were defined as positive. The difference in vertical eye position between right and left eyes in gaze straight ahead while fixating with one eye was used to quantify the amount of skew deviation. Nystagmus was analysed in the light while the subject fixated at gaze straight ahead and in the dark. To analyse the effect of the neural integrator on the nystagmus a single exponential function was fitted to the horizontal (z), vertical (y), and torsional (x) eye positions of the slow phases using a least square minimisation procedure (E(t) = Off+Ep*e(1/Tc*t); E, eye position; Off, positional offset; Ep, post saccadic eye position; Tc, time constant; t, time).18 Each fit with a linear correlation coefficient over 0.95 was controlled manually and only those which aligned well with the position data were To analyse the vestibular contribution to the nystagmus, the median 3-D velocity of each slow phase in the light and dark was calculated. All slow phases with additional blinks were excluded. The analysis was performed with the fixating eye provided that the horizontal and vertical eye positions deviated less than 5° from gaze straight ahead. The median slow phase velocity of each direction component was normalised by dividing the eye velocity components (z, horizontal; x, torsional; y, vertical) by (x2+y2+z2). The axes were compared to the axes of the semicircular canal stimulation using anatomical data.11 Based on Ewald’s first law19 (stimulation of a particular semicircular canal evokes eye movements in the plane of this semicircular canal, but in the opposite direction), we calculated the expected eye movement axis for individual semicircular canal stimulation. The deviation angle in 3-D of the slow phase eye rotation axis from the canal axes was calculated. RESULTS Three dimensional, binocular eye movements were examined in four patients who had acute dorsolateral medullary infarction and spontaneous jerk nystagmus. All patients had a lesion of the dorsolateral medulla which had been assessed on MRI (3–8 days after symptom onset), two on the right and two on the left side (fig 1). There were no other lesions in the brainstem. Using the atlas of Schaltenbrand and Warren,13 reconstruction of the lesions showed that the vestibular nuclei were involved in all patients (fig 1); however, the lesion only partly involved the vestibular nuclei in two patients (#3 and #4). The medial vestibular nuclei involved in patients #1–4 were identified by using the atlas of Olszewski and Baxter.15 The patients showed typical clinical signs of dorsolateral medullary syndrome. Three out of the four patients exhibited tonic ocular torsion in both eyes, which was always ipsilateral to the lesion. One patient (#3) showed tonic ocular torsion only in one eye (table 1). There was always skew deviation of 1° to 6° with hypotropia ipsilateral and/or hypertropia contralateral to the lesion side (table 1). Table 1 Static binocular misalignment and nystagmus slow phases All patients exhibited nystagmus with torsional, vertical, and horizontal components in gaze straight ahead (fig 2), which were on clinical observation more pronounced under Frenzel’s glasses than in the light. The contralesional eye showed a larger torsional and the ipsilateral eye a larger vertical component in patients #1 and #2. The torsional component of the quick phases always beat to the contralesional side, clockwise (rightward) torsional for left sided lesions (patients #1 and #2) and counterclockwise (leftward) torsional for right sided lesions (patients #3 and #4). The vertical eye movement component was always upward in both eyes, the horizontal component contralesional in three of four subjects, and ipsilesional in one subject. The absolute average (SD) slow phase velocity of nystagmus in all patients in the dark was 7.2 (4.4)°/s (torsional 4.8 (1.8)°/s; vertical 3.4 (3.1)°/s; horizontal 3.4 (3.7)°/s) and 6.2 (4.5)°/s (torsional 5.1 (3.3)°/s; vertical 2.2 (2.1)°/s; horizontal 2.6 (2.6)°/s) in the light (table 1). Figure 2 Nystagmus. Binocular search coil recordings of nystagmus in the light for patient #1 are shown while he fixated at gaze straight ahead. Horizontal (Eh), vertical (Ev), and torsional (Et) eye positions are plotted for the right (solid line) and left (dotted line) eyes separately. Note the vertical skew deviation (second panel). Cw, clockwise (rightward) torsional; Ccw, counterclockwise (leftward) torsional. Analysis of the exponential slow phases of nystagmus Most slow phases of the nystagmus were linear, but some, in all patients, also showed an exponential drift. Exponential increasing, decreasing, and even sigmoid shaped slow phases were found (fig 2). Time constants were calculated for selected single slow phases. Only slow phase fits which reached regression coefficients above 0.95 in all eye movement components were further analysed. In patients #1 and #2 there was more exponential increase in the vertical and torsional direction of the slow phases, in patients #3 and #4 more exponential decrease. However, in all patients some slow phases with either an exponential decrease or an exponential increase were found. Time constants were measured for those slow phases with a large exponential decay. On average the mean (SD) exponential decreasing time constants were: –0.6 (0.2) s for horizontal, –0.7 (0.2) s for vertical, and –1.2 (0.3) s for torsional components; the mean (SD) increasing time constants were: 0.6 (0.1) s for horizontal, 0.3 (0.1) s for vertical, and 0.4 (0.1) s for torsional components. In the majority of slow phases the fit of the single exponential function failed, because they were linear or had a more complex profile with an exponential and a linear component. Because of the linear slow phase, spontaneous nystagmus could not be explained by an unstable or impaired neural integrator alone. Analysis of the rotation axes of the slow phases The normalised slow phase velocity mainly reflects the late drift of the slow phase which is less contaminated by the exponential drifts. To test if the median slow phase velocity could be explained by semicircular canal imbalance,20 we compared the slow phase axes with the eye movement axes according to the stimulation of the individual semicircular canals.11 One example of the median slow phase axes is shown for patient #1 in the light (fig 3A–C) and in the dark (fig 3D–F). For comparison, the expected eye movement axes of different semicircular canal stimulations are plotted. The slow phase axes for the right (filled circles) and left eyes (open squares) aligned between the right posterior (PC r; thick solid line) and the right horizontal semicircular canals (HC r; thick solid line). There was only a small but not significant difference between the axes in the light (fig 3A–C) and dark (fig 3D–F) or between both eyes. This patient (#2) had a left sided lesion of the dorsolateral medulla (fig 1). Accordingly, the axes might reflect contralesional stimulation of the posterior (PC) and horizontal semicircular canals (HC) or an ipsilesional deficit of the anterior semicircular canal (AC) and HC. Figure 3 Rotation axes of spontaneous nystagmus (patient #1). The median slow phases of spontaneous nystagmus are shown normalised (see Methods) for patient #1 in the light (A–C) and the dark (D–F). The right eye (closed circles) and the left eye (open squares) are presented separately for each slow phase in three projections (schematic below). For comparison the expected rotation axes for semicircular canal stimulation of the right (r; solid lines) or left (l; dashed lines) side are included (AC, anterior semicircular canal; HC, horizontal semicircular canal; PC, posterior semicircular canal; LE, left eye; RE, right eye; l, left; r, right; x, torsional coordinate axis; y, vertical coordinate axis; z, horizontal coordinate axis). Slow phases are located in between the rotation axes, as obtained from anatomical data,11 of the contralesional posterior and horizontal semicircular canals. The average traces of slow phase velocity for all four subjects (fig 4) showed a similar pattern. In fig 4 the nystagmus axes of all patients are normalised (see Methods) and presented as if the lesion was generally on the left side. All axes were aligned between the PC and HC of the contralesional side. Figure 4 Rotation axes of spontaneous nystagmus (all patients). The slow phase axes of the spontaneous nystagmus of all subjects (#1–#4) are presented as if all the lesions were located on the left side. The mean normalised rotation axes of the slow phases of the contralesional eye (closed circles) and the ipsilesional eye (open squares) are shown in three different projections (A–C). A schematic of the appropriate projection is indicated below (x, torsional coordinate axis; y, vertical coordinate axis; z, horizontal coordinate axis). For comparison, the predicted movement axes of contralesional (right) semicircular canal stimulation are plotted (solid line; AC, anterior semicircular canal; HC, horizontal semicircular canal; PC, posterior semicircular canal; c, contralesional). To test if the 3-D axes orientation of the slow phase is related to the semicircular canals, we calculated the 3-D deviation (in degrees) of the nystagmus slow phase axes from the expected axes as obtained by individual semicircular canal stimulation (fig 5).11 Large deviations were found in all subjects if the slow phase axes were compared to the expected axes of single contralesional (fig 5A–