Bias in meta-analysis detected by a simple, graphical test. Prospectively identified trials could be used for comparison with meta-analyses.
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Biomedical subjects
Publications and source records attributed to P Langhorne.
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Researchers preparing systematic reviews often encounter various types of evidence, which can generally be categorized as direct or indirect. The former directly relates an exposure, diagnostic strategy, or therapeutic intervention to the occurrence of a principal health outcome. Evidence is indirect if two or more bodies of evidence are required to relate the exposure, diagnostic strategy, or intervention to the principal health outcome. Heterogeneity of data sources complicates integration of both direct and indirect evidence. Participants in different studies may have a wide spectrum of baseline risk and sociodemographic and cultural characteristics. A variety of formulations and intensities of exposures, diagnostic strategies, and interventions, as well as diversity in the selection and definition of control groups, may be encountered. Outcome measures may be different, and similar outcomes may be measured or reported differently. Heterogeneity of study designs and of methodologic features and quality within a given design may be found. The effective integration of direct and indirect evidence requires development of explicit models that serve as analytic frameworks for linking the important pieces of evidence. A model can be viewed as a series of subquestions, with each important subquestion warranting a systematic review. Several subjective and quantitative methods can then be used to integrate the evidence. Tabular displays of major findings and strength of evidence for each subquestion can help reviewers, patients, and providers to integrate the differing research findings and draw reasonable conclusions. Various quantitative techniques, such as decision analysis and the confidence profile method, are also available. No single integration approach is clearly superior, none obviates uncertainty, and all underscore the role of careful judgment in integrating evidence.
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The clinical significance of low serum vitamin B12 levels in elderly people is controversial. We aimed to document the prevalence of a low serum vitamin B12 (< 175 pmol/l) in patients referred to a geriatric medical unit, and to determine whether haemopoiesis is commonly affected in elderly patients with low serum vitamin B12. We studied prospectively 472 consecutive referrals to a geriatric medical unit; fifty-six (13%) had a low serum vitamin B12 level, of whom nineteen (34%) of the fifty-six also had evidence of Fe deficiency (serum ferritin < 45 ng/ml). Low vitamin B12 was associated with a raised mean erythrocyte volume (MCV; mean 96.0 (SD 6.7) fl), compared with a control group (91.7 (SD 6.0) fl; P = 0.001). However, only thirteen (23%) of the fifty-six patients with a low vitamin B12 had an MCV > or = 100 fl. Mean haemoglobin (Hb) levels were not significantly reduced in those with a low vitamin B12. In a subsequent study the haematological response to intramuscular hydroxocobalamin was examined in thirty-four patients with a low serum vitamin B12. Treatment resulted in a significant fall in MCV and rise in Hb; these effects could be detected both in those patients with an initially normal full blood count (change in MCV -1.2 (SD 1.2); Hb +0.5 (SD 0.6); P < 0.01) and in those with macrocytosis and/or anaemia (-9.1 (SD 11.8); +0.8 (SD 1.2); P < 0.05). A low serum vitamin B12 is common in geriatric medical patients. This is usually associated with an upset in erythropoiesis, although the abnormalities are often subtle and may not be apparent on inspection of the full blood count. Elderly patients with serum vitamin B12 < 175 pmol/l should be assumed to have vitamin deficiency even if their full blood count is normal.
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Physiotherapy is an established component of stroke rehabilitation but uncertainties remain about the most appropriate intensity of therapy input. We conducted a systematic review of the randomised trials of physiotherapy after stroke where qualitatively similar therapy regimens were provided at different levels of intensity. A heterogeneous group of seven randomised trials (597 patients) was identified. Dichotomous outcomes (death or the combined poor outcome of death or deterioration) were analysed by use of the odds ratio and 95% confidence interval. Patients subjected to more intensive physiotherapy input showed a non-significant reduction in case fatality (odds ratio 0.60; 95% CI 0.33-1.09) and a significant reduction (OR 0.54; 95% CI 0.34-0.85; p < 0.01) in the combined poor outcome of death or deterioration by the end of follow-up. Two statistical techniques were used to identify patterns within the continuous data. Firstly, impairment and disability scores were converted to a standardised measure of 0-100 and the weighted mean difference (WMD) between the scores in the intensive and conventional physiotherapy groups were then calculated. Modest improvements were observed in both the impairment (WMD+5; 95% CI-1-11) and disability scores (WMD+5; 95% CI 0-10) recorded at the initial review (median 3 months post-stroke), but not at the final review (median 1 year post-stroke). Secondly, Fisher's inverse chi-squared test was used to combine the p values from individual trials; this confirmed the above findings (p < 0.05 at initial review; p > 0.05 at final review). More intensive physiotherapy input was associated with a reduction in the combined poor outcome of death or deterioration and may enhance the rate of recovery. These observations warrant further investigation.
The recent interest in the development of services for stroke patients reflects an increasing optimism about stroke management and the recognition that properly organised care can improve outcomes after stroke. A comprehensive stroke service should provide early assessment and investigation of stroke disease in both in-patient and out-patient settings, acute care for stroke in-patients to manage their medical and surgical problems, and rehabilitation for patients with persisting functional problems. Other components may include out-patient, day hospital or domiciliary rehabilitation facilities and continuing care and support facilities for patients discharged from hospital. This article discusses the evidence to support different components of a comprehensive stroke service and emphasises the need for flexible approaches to different local conditions.
BACKGROUND AND PURPOSE: Large platelets are more reactive, produce more prothrombotic factors, and aggregate more easily. Platelet size can be readily estimated using automated analyzers, although accurate estimation depends on precise methodology. The disparate results from previous studies of mean platelet volume in cerebral ischemia may be explained by varying methodology. We have studied these variables using a precise methodology in an unselected group of stroke patients and compared them with data from age- and sex-matched control subjects. METHODS: We studied 58 stroke patients consecutively admitted to a geriatric medical unit. Platelet variables were measured in the acute (< 48 hours after stroke) and chronic (> 6 months) phases of cerebral ischemia and compared with control variables. Control patients, admitted to the same unit, were of similar age and sex and without evidence of acute vascular events. RESULTS: Mean platelet volume was higher in acute stroke (11.3 compared with 10.1 fL in control subjects; P < .001, Student's t test). In addition, platelet count was reduced in stroke patients (255 x 10(9)/L) compared with control subjects (299 x 10(9)/L; P < .01). Repeated measurements of mean platelet volume and platelet count in available survivors showed no significant change from the acute phase. Platelet changes did not relate to outcome measured at 6 months. CONCLUSIONS: With the use of more precise methodology, these findings show that an increase in mean platelet volume and a reduction in platelet count are features of both the acute and nonacute phases of cerebral ischemia. It is possible that these changes precede the vascular event, and further studies are warranted.
The optimal management of acute cerebral infarction requires consideration of the diagnosis, aetiology, identification of problems, general and specific aspects of care, and prevention of further vascular events. Stroke is a clinical diagnosis but cranial computed tomography (CT) scanning is invaluable to exclude the possibility of cerebral haemorrhage or where the diagnosis is uncertain. Good general care under a specialist multidisciplinary team can reduce mortality and the need for institutional care. Despite promising results from experimental studies, no routine drug therapies have yet shown clinical benefit in acute stroke. Several large trials are currently evaluating anticoagulant, antiplatelet, thrombolytic and neuroprotective agents. Many other proposed therapies have been subject to limited evaluation. Aspirin has a proven role in the prevention of further vascular events after a stroke or transient ischaemic attack. Warfarin, and to a lesser extent aspirin, can prevent recurrent events in patients with nonrheumatic atrial fibrillation. Concerns remain about the safety of warfarin in routine geriatric medical practice. The risk of recurrent stroke in patients with a symptomatic severe carotid artery stenosis is greatly reduced by endarterectomy.
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The management of thrombosis in stroke requires that several questions be answered concerning the diagnosis, aetiology, identification of problems, general and specific aspects of care, and prevention of further vascular events. Stroke is a clinical diagnosis, but cranial computed tomography (CT) scanning is required where there is diagnostic uncertainty or cerebral haemorrhage must be excluded. No specific medical therapies are of proven benefit in acute stroke but several large trials are currently evaluating promising antithrombotic therapies (antiplatelet, anticoagulant and thrombolytic agents). Aspirin has a proven role in the prevention of further vascular events after a stroke or transient ischaemic attack (TIA). In stroke and TIA patients with non-rheumatic atrial fibrillation, warfarin is highly effective at preventing recurrent events. The risk of recurrent stroke in patients with a symptomatic, severe carotid artery stenosis is greatly reduced by endarterectomy.
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Management of stroke patients in specialist stroke units hastens recovery but is not believed to influence mortality. We did a statistical overview of randomised controlled trials reported between 1962 and 1993 in which the management of stroke patients in a specialist unit was compared with that in general wards. We identified 10 trials, 8 of which used a strict randomisation procedure. 1586 stroke patients were included; 766 were allocated to a stroke unit and 820 to general wards. The odds ratio (stroke unit vs general wards) for mortality within the first 4 months (median follow-up 3 months) after the stroke was 0.72 (95% CI 0.56-0.92), consistent with a reduction in mortality of 28% (2p < 0.01). This reduction persisted (odds ratio 0.79, 95% CI 0.63-0.99, 2p < 0.05) when calculated for mortality during the first 12 months. The findings were not significantly altered if the analysis was limited to studies that used a formal randomisation procedure. We conclude that management of stroke patients in a stroke unit is associated with a sustained reduction in mortality.
We present a detailed Doppler evaluation of a left atrial myxoma. Doppler recordings varied considerably with the position of the patient and of the sample volume. Maximum obstruction to flow was observed in the left lateral position; but no gradient was present when sitting upright. These findings provide a haemodynamic explanation for the positional variation of murmurs characteristic of atrial myxomas.
A case of C2 deficiency presenting with disseminated gonococcal infection is described. The predisposition of C2-deficient individuals to infection in addition to the commoner problem of immune complex diseases is noted. Attention is drawn to the absence of documented cases of gonococcal infection associated with C2 deficiency. No other homozygous C2 deficient family members were identified. Lifelong penicillin prophylaxis was recommended for the patient.
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Serum cortisol concentrations were measured in juvenile Atlantic salmon (Salmo salar L.) undergoing the parr-smolt transformation in fresh water, at either 1 year (S1 population) or 2 years (S2 population) after hatching. Serum cortisol levels were generally low (less than 10 ng ml-1), but during smoltification became significantly elevated in both populations. In addition, the S2 population showed a small cortisol peak in the autumn prior to smoltification. Simultaneous measurement of gill (Na + K) ATPase activity and serum cortisol concentrations in S2 salmon juveniles revealed that both features rose during smoltification in fresh water. The rise in gill (Na + K) ATPase activity was independent of cortisol levels, and preceded the rise in cortisol titer by approximately 1 month. After seawater transfer, gill enzyme levels remained high while cortisol titers fell sharply. Serum cortisol levels, but not gill (Na + K) ATPase activities, were progressively reduced by acclimation of smolts to increasing salinities. Linear regression studies indicated that, at any one level of gill (Na + K) ATPase, cortisol titer increased with increasing surface area: volume ratio. Extracellular fluid volume (sodium space) was found to decline with increasing gill (Na + K) ATPase activity, and to increase with serum cortisol titers. These results indicate that high serum cortisol levels represent a secondary response caused by the development of hypoosmoregulatory ability while still resident in fresh water. Cortisol does not appear to directly stimulate gill (Na + K) ATPase activity in Atlantic salmon smolts.