Methodological criteria for the assessment of moderators in systematic reviews of randomised controlled trials: a consensus study.

BACKGROUND: Current methodological guidelines provide advice about the assessment of sub-group analysis within RCTs, but do not specify explicit criteria for assessment. Our objective was to provide researchers with a set of criteria that will facilitate the grading of evidence for moderators, in systematic reviews. METHOD: We developed a set of criteria from methodological manuscripts (n = 18) using snowballing technique, and electronic database searches. Criteria were reviewed by an international Delphi panel (n = 21), comprising authors who have published methodological papers in this area, and researchers who have been active in the study of sub-group analysis in RCTs. We used the Research ANd Development/University of California Los Angeles appropriateness method to assess consensus on the quantitative data. Free responses were coded for consensus and disagreement. In a subsequent round additional criteria were extracted from the Cochrane Reviewers' Handbook, and the process was repeated. RESULTS: The recommendations are that meta-analysts report both confirmatory and exploratory findings for sub-groups analysis. Confirmatory findings must only come from studies in which a specific theory/evidence based a-priori statement is made. Exploratory findings may be used to inform future/subsequent trials. However, for inclusion in the meta-analysis of moderators, the following additional criteria should be applied to each study: Baseline factors should be measured prior to randomisation, measurement of baseline factors should be of adequate reliability and validity, and a specific test of the interaction between baseline factors and interventions must be presented. CONCLUSIONS: There is consensus from a group of 21 international experts that methodological criteria to assess moderators within systematic reviews of RCTs is both timely and necessary. The consensus from the experts resulted in five criteria divided into two groups when synthesising evidence: confirmatory findings to support hypotheses about moderators and exploratory findings to inform future research. These recommendations are discussed in reference to previous recommendations for evaluating and reporting moderator studies.

Manual therapy for unsettled, distressed and excessively crying infants: a systematic review and meta-analyses.

OBJECTIVE: To conduct a systematic review and meta-analyses to assess the effect of manual therapy interventions for healthy but unsettled, distressed and excessively crying infants and to provide information to help clinicians and parents inform decisions about care. METHODS: We reviewed published peer-reviewed primary research articles in the last 26 years from nine databases (Medline Ovid, Embase, Web of Science, Physiotherapy Evidence Database, Osteopathic Medicine Digital Repository , Cochrane (all databases), Index of Chiropractic Literature, Open Access Theses and Dissertations and Cumulative Index to Nursing and Allied Health Literature). Our inclusion criteria were: manual therapy (by regulated or registered professionals) of unsettled, distressed and excessively crying infants who were otherwise healthy and treated in a primary care setting. Outcomes of interest were: crying, feeding, sleep, parent-child relations, parent experience/satisfaction and parent-reported global change. RESULTS: Nineteen studies were selected for full review: seven randomised controlled trials, seven case series, three cohort studies, one service evaluation study and one qualitative study.We found moderate strength evidence for the effectiveness of manual therapy on: reduction in crying time (favourable: -1.27 hours per day (95% CI -2.19 to -0.36)), sleep (inconclusive), parent-child relations (inconclusive) and global improvement (no effect). The risk of reported adverse events was low: seven non-serious events per 1000 infants exposed to manual therapy (n=1308) and 110 per 1000 in those not exposed. CONCLUSIONS: Some small benefits were found, but whether these are meaningful to parents remains unclear as does the mechanisms of action. Manual therapy appears relatively safe. PROSPERO REGISTRATION NUMBER: CRD42016037353.

Driving impairment and crash risk in Parkinson disease: A systematic review and meta-analysis.

OBJECTIVES: To provide the best possible evidence base for guiding driving decisions in Parkinson disease (PD), we performed a meta-analysis comparing patients with PD to healthy controls (HCs) on naturalistic, on-the-road, and simulator driving outcomes. METHODS: Seven major databases were systematically searched (to January 2018) for studies comparing patients with PD to HCs on overall driving performance, with data analyzed using random-effects meta-analysis. RESULTS: Fifty studies comprising 5,410 participants (PD = 1,955, HC = 3,455) met eligibility criteria. Analysis found the odds of on-the-road test failure were 6.16 (95% confidence interval [CI] 3.79-10.03) times higher and the odds of simulator crashes 2.63 (95% CI 1.64-4.22) times higher for people with PD, with poorer overall driving ratings also observed (standardized mean differences from 0.50 to 0.67). However, self-reported real-life crash involvement did not differ between people with PD and HCs (odds ratio = 0.84, 95% CI 0.57-1.23, p = 0.38). Findings remained unchanged after accounting for any differences in age, sex, and driving exposure, and no moderating influence of disease severity was found. CONCLUSIONS: Our findings provide persuasive evidence for substantive driving impairment in PD, but offer little support for mandated PD-specific relicensure based on self-reported crash data alone, and highlight the need for objective measures of crash involvement.

Barriers and facilitators of effective self-management in asthma: systematic review and thematic synthesis of patient and healthcare professional views.

Self-management is an established, effective approach to controlling asthma, recommended in guidelines. However, promotion, uptake and use among patients and health-care professionals remain low. Many barriers and facilitators to effective self-management have been reported, and views and beliefs of patients and health care professionals have been explored in qualitative studies. We conducted a systematic review and thematic synthesis of qualitative research into self-management in patients, carers and health care professionals regarding self-management of asthma, to identify perceived barriers and facilitators associated with reduced effectiveness of asthma self-management interventions. Electronic databases and guidelines were searched systematically for qualitative literature that explored factors relevant to facilitators and barriers to uptake, adherence, or outcomes of self-management in patients with asthma. Thematic synthesis of the 56 included studies identified 11 themes: (1) partnership between patient and health care professional; (2) issues around medication; (3) education about asthma and its management; (4) health beliefs; (5) self-management interventions; (6) co-morbidities (7) mood disorders and anxiety; (8) social support; (9) non-pharmacological methods; (10) access to healthcare; (11) professional factors. From this, perceived barriers and facilitators were identified at the level of individuals with asthma (and carers), and health-care professionals. Future work addressing the concerns and beliefs of adults, adolescents and children (and carers) with asthma, effective communication and partnership, tailored support and education (including for ethnic minorities and at risk groups), and telehealthcare may improve how self-management is recommended by professionals and used by patients. Ultimately, this may achieve better outcomes for people with asthma.

Effective delivery styles and content for self-management interventions for chronic musculoskeletal pain: a systematic literature review.

OBJECTIVES: The objective of the study was to report the evidence for effectiveness of different self-management course characteristics and components for chronic musculoskeletal pain. METHODS: We searched 9 relevant electronic databases for randomized, controlled trials (RCTs). Two reviewers selected studies against inclusion criteria and assessed their quality. We classified RCTs according to type of course delivery (group, individual, mixed or remote), tutor (healthcare professional, lay or mixed), setting (medical, community or occupational), duration (more or less than 8 weeks), and the number and type of components (psychological, lifestyle, pain education, mind body therapies, and physical activity). We extracted data on pain intensity, physical function, self-efficacy, global health, and depression and compared these outcomes for self-management and usual care or waiting list control. We used random effects standardized mean difference meta-analysis. We looked for patterns of clinically important and statistically significant beneficial effects for courses with different delivery characteristics and the presence or absence of components across outcomes over 3 follow-up intervals. RESULTS: We included 46 RCTs (N=8539). Group-delivered courses that had healthcare professional input showed more beneficial effects. Longer courses did not necessarily give better outcomes. There was mixed evidence of effectiveness for components of courses, but data for courses with a psychological component showed slightly more consistent beneficial effects over each follow-up period. DISCUSSION: Serious consideration should be given to the development of short (<8 weeks) group and healthcare professional-delivered interventions but more research is required to establish the most effective and cost-effective course components.

Measuring pain self-efficacy.

BACKGROUND: It is likely that people with chronic pain who have low self-efficacy have a worse prognosis. A standard, high-quality measure of self-efficacy in such populations would improve evidence, by allowing meaningful comparisons amongst subgroups and between treatments, and by facilitating pooling across studies in systematic reviews. OBJECTIVES: To identify self-administered pain-related self-efficacy measures used in people with chronic pain and to evaluate the clinimetric evidence of the most commonly used scales systematically. METHODS: We searched 2 databases to identify self-efficacy questionnaires. We evaluated questionnaires identified against previously developed criteria for clinimetric assessment. RESULTS: We identified 13 relevant measurements assessing self-efficacy, and clinimetrically assessed 5 of these. These questionnaires were the Arthritis Self-Efficacy Scale, the Chronic Disease Self-Efficacy Scale, the Pain Self-Efficacy Questionnaire, the Chronic Pain Self-Efficacy Scale, and the Self-Efficacy Scale. None of the questionnaires showed satisfactory results for all properties. All scales were easily scored and dimensionality was assessed in 2 of 6 of the scales. Internal consistency was acceptable for all questionnaires. There was positive evidence for construct validity in 4 of 6 of the questionnaires. None of the studies used the most up-to-date method of test-retest reliability or responsiveness. Information on interpretability of the scores was minimal in all questionnaires. DISCUSSION: Further research should focus on assessing responsiveness and interpretability of these questionnaires. Researchers should select questionnaires that are most appropriate for their study aims and population and contribute to further validation of these scales. Future research should measure outcome expectancy alongside self-efficacy to best predict future behavior.

Can we identify how programmes aimed at promoting self-management in musculoskeletal pain work and who benefits? A systematic review of sub-group analysis within RCTs.

BACKGROUND: There are now several systematic reviews of RCTs testing self-management for those with chronic musculoskeletal pain. Evidence for the effectiveness of self-management interventions in chronic musculoskeletal pain is equivocal and it is not clear for which sub-groups of patients SM is optimally effective. AIMS: To systematically review randomized controlled trials of self-management for chronic musculoskeletal pain that reported predictors, i.e., 'baseline factors that predict outcome independent of any treatment effect'; moderators, i.e., 'baseline factors which predict benefit from a particular treatment'; or mediators i.e., 'factors measured during treatment that impact on outcome' of outcome. METHOD: We searched relevant electronic databases. We assessed the evidence according to the methodological strengths of the studies. We did meta-regression analyses for age and gender, as potential moderators. RESULTS: Although the methodological quality of primary trials was good, there were few relevant studies; most were compromised by lack of power for moderator and mediator analyses. We found strong evidence that self-efficacy and depression at baseline predict outcome and strong evidence that pain catastrophizing and physical activity can mediate outcome from self-management. There was insufficient data on moderators of treatment. CONCLUSIONS: The current evidence suggests four factors that relate to outcome as predictors/mediators, but there is no evidence for effect moderators. Future studies of mediation and moderation should be designed with 'a priori' hypotheses and adequate statistical power.

Estrogen treatment effects on cognition, memory and mood in male-to-female transsexuals.

Gonadal hormones, particularly estrogens, have been suggested to influence memory and cognitive tasks that show sex differences. Previously, we reported that male-to-female (M-F) transsexuals undergoing estrogen treatment for sex re-assignment scored higher on verbal Paired Associate Learning (PAL) than a transsexual control group awaiting estrogen treatment. The present study used a more robust design to examine further associations between estrogen and cognition. We assessed additional aspects of memory, including visual, spatial, object and location memory, other cognitive abilities that show reliable sex differences, including verbal and visual-spatial abilities, and mood variables that could mediate associations between estrogen and cognition. In addition to comparing groups of individuals on and off estrogen, we used two repeated measures designs (AB and BA). The AB group was tested prior to hormone treatment and then again after treatment had begun; the BA group was tested while on estrogen treatment and then again when hormones had been withdrawn prior to surgery. Few changes in memory or cognition were observed, and changes that were observed were not consistent across study designs. The lack of significant effects did not relate to mood changes or to the sexual orientation of participants. These findings suggest that estrogen treatment associated with sex change for M-F transsexuals has little or no influence on sex-typed aspects of cognition or memory.