Although treatment of hepatitis C has improved,up to 50% do not respond to standard therapy with interferonregimes or cannot tolerate the treatment due to side effects.The purpose of the present investigation was to evaluate thesafety and effectiveness of the antiviral drug amantadine forthe treatment of hepatitis C in those who had either previouslyfailed interferon therapy or were not candidates for interferon.

A Randomized Double-blind Placebo-controlled Trial

OBJECTIVES: To consider methods and related evidence for evaluating bias in non-randomised intervention studies. DATA SOURCES: Systematic reviews and methodological papers were identified from a search of electronic databases; handsearches of key medical journals and contact with experts working in the field. New empirical studies were conducted using data from two large randomised clinical trials. METHODS: Three systematic reviews and new empirical investigations were conducted. The reviews considered, in regard to non-randomised studies, (1) the existing evidence of bias, (2) the content of quality assessment tools, (3) the ways that study quality has been assessed and addressed. (4) The empirical investigations were conducted generating non-randomised studies from two large, multicentre randomised controlled trials (RCTs) and selectively resampling trial participants according to allocated treatment, centre and period. RESULTS: In the systematic reviews, eight studies compared results of randomised and non-randomised studies across multiple interventions using meta-epidemiological techniques. A total of 194 tools were identified that could be or had been used to assess non-randomised studies. Sixty tools covered at least five of six pre-specified internal validity domains. Fourteen tools covered three of four core items of particular importance for non-randomised studies. Six tools were thought suitable for use in systematic reviews. Of 511 systematic reviews that included non-randomised studies, only 169 (33%) assessed study quality. Sixty-nine reviews investigated the impact of quality on study results in a quantitative manner. The new empirical studies estimated the bias associated with non-random allocation and found that the bias could lead to consistent over- or underestimations of treatment effects, also the bias increased variation in results for both historical and concurrent controls, owing to haphazard differences in case-mix between groups. The biases were large enough to lead studies falsely to conclude significant findings of benefit or harm. Four strategies for case-mix adjustment were evaluated: none adequately adjusted for bias in historically and concurrently controlled studies. Logistic regression on average increased bias. Propensity score methods performed better, but were not satisfactory in most situations. Detailed investigation revealed that adequate adjustment can only be achieved in the unrealistic situation when selection depends on a single factor. CONCLUSIONS: Results of non-randomised studies sometimes, but not always, differ from results of randomised studies of the same intervention. Non-randomised studies may still give seriously misleading results when treated and control groups appear similar in key prognostic factors. Standard methods of case-mix adjustment do not guarantee removal of bias. Residual confounding may be high even when good prognostic data are available, and in some situations adjusted results may appear more biased than unadjusted results. Although many quality assessment tools exist and have been used for appraising non-randomised studies, most omit key quality domains. Healthcare policies based upon non-randomised studies or systematic reviews of non-randomised studies may need re-evaluation if the uncertainty in the true evidence base was not fully appreciated when policies were made. The inability of case-mix adjustment methods to compensate for selection bias and our inability to identify non-randomised studies that are free of selection bias indicate that non-randomised studies should only be undertaken when RCTs are infeasible or unethical. Recommendations for further research include: applying the resampling methodology in other clinical areas to ascertain whether the biases described are typical; developing or refining existing quality assessment tools for non-randomised studies; investigating how quality assessments of non-randomised studies can be incorporated into reviews and the implications of individual quality features for interpretation of a review's results; examination of the reasons for the apparent failure of case-mix adjustment methods; and further evaluation of the role of the propensity score.

/pdf/evaluating-non-randomised-intervention-studies-2k25cz7x6r.pdf

Evaluating non-randomised intervention studies.

Loss of functional movement is a common consequence of stroke for which a wide range of interventions has been developed. In this Review, we aimed to provide an overview of the available evidence on interventions for motor recovery after stroke through the evaluation of systematic reviews, supplemented by recent randomised controlled trials. Most trials were small and had some design limitations. Improvements in recovery of arm function were seen for constraint-induced movement therapy, electromyographic biofeedback, mental practice with motor imagery, and robotics. Improvements in transfer ability or balance were seen with repetitive task training, biofeedback, and training with a moving platform. Physical fitness training, high-intensity therapy (usually physiotherapy), and repetitive task training improved walking speed. Although the existing evidence is limited by poor trial designs, some treatments do show promise for improving motor recovery, particularly those that have focused on high-intensity and repetitive task-specific practice.

https://www.thelancet.com/pdfs/journals/laneur/PIIS1474-4422(09)70150-4.pdf

Motor recovery after stroke: a systematic review

Stroke Care 2: Stroke rehabilitation

This book discusses the most important techniques available for longitudinal data analysis, from simple techniques such as the paired t-test and summary statistics, to more sophisticated ones such as generalized estimating of equations and mixed model analysis A distinction is made between longitudinal analysis with continuous, dichotomous and categorical outcome variables The emphasis of the discussion lies in the interpretation and comparison of the results of the different techniques The second edition includes new chapters on the role of the time variable and presents new features of longitudinal data analysis Explanations have been clarified where necessary and several chapters have been completely rewritten The analysis of data from experimental studies and the problem of missing data in longitudinal studies are discussed Finally, an extensive overview and comparison of different software packages is provided This practical guide is essential for non-statisticians and researchers working with longitudinal data from epidemiological and clinical studies

Applied Longitudinal Data Analysis for Epidemiology: A Practical Guide

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(98)09477-X.pdf

Intensity of leg and arm training after primary middle-cerebral-artery stroke: a randomised trial

Background and Purpose A research synthesis was performed to (1) critically review controlled studies evaluating effects of different intensities of stroke rehabilitation in terms of disabilities and impairments and (2) quantify patterns by calculating summary effect sizes. The influences of organizational setting of rehabilitation management, blind recording, and amount of rehabilitation on the summary effect sizes were calculated. Methods A Medline literature search was performed for a critical review of the literature. The internal and external validity of the studies was evaluated. In addition, a meta-analysis was performed by applying the fixed (Hedges’s g) effects model. Results The effects of different intensities of rehabilitation were studied in nine controlled studies involving 1051 patients. Analysis of the methodological quality revealed scores varying from 14% to 47% of the maximum feasible score. Meta-analysis demonstrated a statistically significant summary effect size for activities of dai...

Effects of intensity of rehabilitation after stroke. A research synthesis.

Cladribine treatment of multiple sclerosis.

To the Editor. —A number of studies have shown that pulsed therapy with high-dose intravenously administered methylprednisolone is usually effective during multiple sclerosis (MS) relapses. It has been hypothesized that a regimen of repeated pulses of intravenous methylprednisolone, not restricted to relapses but given at regular intervals during the years of disease activity, might be effective in preventing progression of the disease. It can, however, reliably be predicted that under these circumstances the frequency of adverse effects will rise and, therefore, the importance of assessing the exact benefits and risks of such a regimen has been stressed in a number of leading articles. 1-3 We recently performed a small, open, pilot study in which monthly pulses of methylprednisolone (500 mg intravenously) were given to patients with progressive MS. Ten patients with definite MS according to the Poser criteria were selected for the study. During the 12 months before entry into

Johan C. Koetsier

Papers

Intensity of leg and arm training after primary middle-cerebral-artery stroke: a randomised trial

Effects of intensity of rehabilitation after stroke. A research synthesis.

Cladribine treatment of multiple sclerosis.

A commentary on steroid treatment in multiple sclerosis.