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Our purpose was to perform a meta‐analysis to evaluate the effect of Low‐level laser therapy (LLLT) on diabetic foot ulcers (DFUs). The PubMed, Cochrane, Embase, Web of Science, Chinese BioMedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), VIP and Wanfang databases were searched systematically up to August 27, 2020. Studies that met the inclusion criteria were included in the analysis. A total of 13 randomised controlled trials (RCTs) and 413 patients were analysed. Compared with the control group, LLLT significantly increased the complete healing rate (risk ratio [RR] = 2.10, 95% confidence interval [CI] 1.56‐2.83, P

Background Recruitment and retention of participants are both critical for the success of trials, yet both remain significant problems. The use of incentives to target participants and trial staff has been proposed as one solution. The effects of incentives are complex and depend upon how they are designed, but these complexities are often overlooked. In this paper, we used a scoping review to ‘map’ the literature, with two aims: to develop a checklist on the design and use of incentives to support recruitment and retention in trials; and to identify key research topics for the future. Methods The scoping review drew on the existing economic theory of incentives and a structured review of the literature on the use of incentives in three healthcare settings: trials, pay for performance, and health behaviour change. We identified the design issues that need to be considered when introducing an incentive scheme to improve recruitment and retention in trials. We then reviewed both the theoretical and empirical evidence relating to each of these design issues. We synthesised the findings into a checklist to guide the design of interventions using incentives. Results The issues to consider when designing an incentive system were summarised into an eight-question checklist. The checklist covers: the current incentives and barriers operating in the system; who the incentive should be directed towards; what the incentive should be linked to; the form of incentive; the incentive size; the structure of the incentive system; the timing and frequency of incentive payouts; and the potential unintended consequences. We concluded the section on each design aspect by highlighting the gaps in the current evidence base. Conclusions Our findings highlight how complex the design of incentive systems can be, and how crucial each design choice is to overall effectiveness. The most appropriate design choice will differ according to context, and we have aimed to provide context-specific advice. Whilst all design issues warrant further research, evidence is most needed on incentives directed at recruiters, optimal incentive size, and testing of different incentive structures, particularly exploring repeat arrangements with recruiters.

Background: Evaluations of complex interventions compared to usual care provided in palliative care are increasing. Not describing usual care may affect the interpretation of an intervention’s effectiveness, yet how it can be described remains unclear. Aim: To demonstrate the feasibility of using multi-methods to describe usual care provided in randomised controlled trials (RCTs) of complex interventions, shown within a feasibility cluster RCT. Design: Multi-method approach comprising usual care questionnaires, baseline case note review and focus groups with ward staff completed at study end. Thematic analysis of qualitative data, descriptive statistics of quantitative data, followed by methodological triangulation to appraise approach in relation to study aim. Setting/participants: Four general medical wards chosen from UK hospitals. Purposive sampling of healthcare professionals for usual care questionnaires, and focus groups. Review of 20 patients’ notes from each ward who died during admission or within 100 days of discharge. Results: Twenty-three usual care questionnaires at baseline, two focus groups comprising 20 healthcare professionals and 80 case note reviews. Triangulation of findings resulted in understanding the usual care provided to the targeted population in terms of context, structures, processes and outcomes for patients, families and healthcare professionals. Usual care was described, highlighting (1) similarities and embedded practices, (2) heterogeneity and (3) subtle changes in care during the trial within and across sites. Conclusions: We provide a feasible approach to defining usual care that can be practically adopted in different settings. Understanding usual care enhances the reliability of tested complex interventions, and informs research and policy priorities.

Background Despite careful planning, changes to some aspects of an ongoing randomised clinical trial (RCT), with a fixed design, may be warranted. We sought to elucidate the distinction between legitimate versus illegitimate changes to serve as a guide for less experienced clinical trialists and other stakeholders. Methods Using data from a large trial of statin therapy for secondary prevention, we generated a set of simulated trial datasets under the null hypothesis (H0) and a set under an alternative hypothesis (H1). Through analysis of these simulated trials, we assessed the performance of the strategy of changing aspects of the design/analysis with knowledge of treatment allocation (illegitimate) versus the strategy of making changes without knowledge of treatment allocation (legitimate). Performance was assessed using the type 1 error, as well as measures of absolute and relative bias in the treatment effect. Results Illegitimate changes led to a relative bias of 61% under H1, and a type 1 error rate under H0 of 23%—well in excess of the 5% significance level targeted. Legitimate changes produced unbiased estimates under H1 and did not inflate the type 1 error rate under H0. Conclusions Changes to pre-specified aspects of the design and analysis of an ongoing RCT may be a necessary response to unforeseen circumstances. Such changes risk introducing a bias if undertaken with knowledge of treatment allocation. Legitimate changes need to be adequately documented to provide assurance to all stakeholders of their validity.

ObjectivesA few studies on antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) treatments have shown the therapeutic efficacy of mycophenolate mofetil (MMF). However, the therapeutic efficacy of MMF compared with that of cyclophosphamide (CYC) in patients with AAV has not been established. We conducted a systematic review and meta-analysis to assess the efficacy of MMF as a remission induction therapy in patients with AAV comparing it with the efficacy of CYC.MethodsWe searched randomised controlled trials (RCTs) comparing the efficacy of MMF with that of CYC in patients with AAV on three different websites: PubMed, Cochrane Library and Google Scholar. We compared the difference in the relative risk (RR) of each outcome based on a Mantel-Haenszel random-effects model.ResultsWe analysed data from four RCTs with 300 patients for the study. The 6-month remission rate (RR 1.09, 95% CI 0.86 to 1.38, p=0.48), the 6-month ANCA negativity (RR 1.31, 95% CI 0.91 to 1.90, p=0.15) and the long-term relapse rate (RR 1.36, 95% CI 0.80 to 2.31, p=0.26) were all similar between the two treatments. The rates of death, infection and leucopenia were also similar between the two groups (RR 1.05, 95% CI 0.40 to 2.74, p=0.93; RR 1.26, 95% CI 0.79 to 2.01, p=0.33; RR 0.45, 95% CI 0.16 to 1.32, p=0.15, respectively).ConclusionsWe found no difference between the therapeutic efficacy of MMF and that of CYC in patients with AAV. MMF may be an alternative remission induction therapy in patients with non-life-threatening AAV.

Background Intervention fidelity is the degree to which interventions have been implemented as intended by their developers. Assessing fidelity is crucial for accurate interpretation of intervention effectiveness, but fidelity is often poorly addressed within trials of complex healthcare interventions. The reasons for this are unclear, and information on the use of methods to enhance and assess fidelity in trials of complex interventions remains insufficient. This study aimed to explore the knowledge, practice and attitudes towards intervention fidelity amongst researchers, triallists and healthcare professionals involved with the design and conduct of trials of complex healthcare interventions. Methods An online survey consisting of closed and open-ended questions exploring four sections (Demographics, Fidelity knowledge, Practice and Attitudes) was conducted. This was an opportunistic sample of individuals with experience of direct involvement in trials of complex healthcare interventions (e.g. design/development, conduct, evaluation). Results Data from 264 participants representing 15 countries were analysed. The majority (65.9%, n = 174) of participants identified themselves as ‘Researchers’. The majority of participants were familiar with the term “intervention fidelity” (69.7%, n = 184) and indicated that fidelity is important (89.7%, n = 236). Mean self-reported understanding of fidelity was moderate. Although 68% (n = 182) had previously used strategies to assess (e.g. audio/video-recording sessions) and enhance (e.g. training manual) fidelity in trials of complex interventions, only a limited proportion of participants indicated always reporting these strategies in subsequent publications (30.9%, n = 56). Poor knowledge or understanding was the most commonly cited barrier to addressing intervention fidelity in trials (77.4%, n = 202). Over half of respondents (52.1%, n = 137) had never completed specific fidelity training or research, and the vast majority (89.7%, n = 236) would welcome specific training in this area. Conclusion Despite good awareness of intervention fidelity and its importance, poor knowledge and understanding appears to be a key factor limiting how intervention fidelity is addressed in trials of complex interventions. Participants identified a need for further training and education in this area. Additionally, clarification of the terminology, definition and components of intervention fidelity would facilitate better understanding of the concept. A discrepancy between participants’ use of fidelity strategies and subsequent reporting raises concerns around inadequate fidelity reporting in the trials literature. Keywords DMc received a 2017 summer scholarship award from the Health Research Board Trials Methodology Research Network to complete this project under the supervision of ET. ET and KMS are funded separately by the Health Research Board Interdisciplinary Capacity Enhancement awards (ICE-2015-1026). peer-reviewed

ObjectiveTo determine in women with subclinical hypothyroidism diagnosed in pregnancy whether levothyroxine treatment compared with control, impacts important obstetrical or childhood outcomes (specifically IQ) in randomised controlled trials.DesignSystematic review and meta-analysis.Study eligibility criteriaRandomised trials which met all the following were included: (1) reported original data of women with subclinical hypothyroidism diagnosed in pregnancy (by any prespecified study definition); (2) randomised to either levothyroxine or control (placebo or no treatment); (3) reported obstetrical outcomes and/or childhood neurodevelopmental outcomes and (4) published from 1980 to January 2018 in either English or French language.Data sourcesMedline, EMBASE, CINAHL, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov.Outcome measuresObstetrical, neonatal and childhood outcomes including: miscarriage, gestational hypertension, pre-eclampsia, preterm delivery, mode of delivery, neonatal intensive care unit admission, birth weight, gestational age at delivery, childhood IQ and neurodevelopmental scores.Risk of bias assessmentCochrane Risk of Bias Tool (Modified) for Quality Assessment of Randomised Controlled TrialsResultsThree trials of low to unclear risk of bias with 1837 participants were included. Two studies were meta-analysed for maternal and neonatal outcomes and two studies for childhood IQ. No statistically significant differences were found for any clinical outcomes with levothyroxine therapy compared with control.LimitationsOnly three trials were identified for inclusion.ConclusionsThis review, based on three randomised trials in women with subclinical hypothyroidism diagnosed in pregnancy, found no evidence of benefit of levothyroxine therapy on obstetrical, neonatal, childhood IQ or neurodevelopmental outcomes. Current trial evidence does not support the treatment of subclinical hypothyroidism diagnosed in pregnancy.PROSPERO registration numberCRD4201707980.

Purpose: To evaluate the effects of a conductive education (CE) course followed by conventional practice, on gross motor function, other functional skills, quality of life, and parents’ experiences of family-centered services in young children with cerebral palsy (CP). Methods: Twenty-one children with CP, 3–6 years old, were randomized to one 3-week CE course followed by conventional practice or conventional practice on a waiting list. Outcomes were measured 4 months after baseline. A web-based log collected data on the conventional practice. Results: No additional improvements in the children’s outcome were found. However, parents in the CE group reported that they received more information than parents in the waiting list group (p = 0.01). Children in both groups performed high amount of conventional practice at home. Conclusions: A 3-week CE course did not add any improvements in the children’s functioning, possibly explained by the large amount of conventional practice reported of both groups.

Recent advances in the use of randomised control trials to evaluate the effect of development interventions promise to enhance our knowledge of what works and why. A core argument supporting randomised studies is the claim that they have high internal validity. The authors argue that this claim is weak as long as a trial registry of development interventions is not in place. Without a trial registry, the possibilities for data mining, created by analyses of multiple outcomes and subgroups, undermine internal validity. Drawing on experience from evidence-based medicine and recent examples from microfinance, they argue that a trial registry would also enhance external validity and foster innovative research.

Over the years, physical activity and exercise have been used to positively impact the health and quality of life of persons infected with HIV and, more recently, has been associated with a spectrum of body composition changes. The aim of this review was to examine the effects of various exercise interventions on body composition in HIV positive adults, using a search strategy of randomized, controlled trials (RCTs). A systematic review was performed by five independent reviewers using a predetermined protocol adapted from previous research for assessing the articles for inclusion, the extracted data, and methodological quality. Eight RCTs involving 430 (26% female) HIV positive adults performing exercise a minimum of thrice weekly for at least six weeks were finally selected: Four were progressive resistance training (PRT) studies, three were aerobic training (AT) studies, and one involved yoga. In the PRT studies, there were significant increases in three anthropometric measures, namely, body mass, sum of skinfolds and sum of limb girths. In the AT studies, significant decreases were found in seven anthropometric measures, namely, body mass index, waist-hip ratio, body mass, triceps skinfold, waist circumference and sum of skinfolds. With yoga, the changes were non-significant. Exercise contributes to improved body composition and, when applied safely, appears to be beneficial for adults living with HIV/AIDS. However, these findings should be interpreted cautiously due to the relatively few RCTs published to date. Future studies would benefit from increased attention to sample size, female participants, participant follow-up, complete statistical analysis and intention-to-treat analysis.

There are several methods in which one can assess the relationship between an intervention and an outcome. Randomized controlled trials (RCTs) are considered as the gold standard for evaluating interventions. However, for many questions of clinical importance, RCTs would be impractical or unethical. Clinicians must rely on observational studies for the best available evidence when RCTs are unavailable. This article provides an overview of observational research designs to facilitate the understanding and appraising of their validity and applicability in clinical practice. Major methodological issues of observational studies including selection bias and confounding are also discussed. In addition, strategies to minimize these problems in the design and analytical phases of a study are highlighted. Knowledge of the strengths, weaknesses and recent methodological advances in observational studies can assist clinicians to make informed decisions about whether a particular observational study would provide useful information to enhance patient care. Published literature was reviewed to identify the different observational study designs used to assess the relationship between an intervention and an outcome, the major challenges and the strategies to reduce these issues. Refereed/Peer-reviewed

The aim of this study was to test the efficacy of thermal ultrasound therapy as a treatment for severe post partum breast engorgement. A randomised double-blind, placebo-controlled trial was conducted on 197 breasts. Two ultrasound machines of identical appearance were used. One was working normally, the other had the crystal replaced with a resistor producing surface heat only. Assessment of effectiveness was subjective, using visual analogue scales for pain and hardness, and objective, using tonometry. Results indicate that both the true and sham machines were effective in reducing subjectively perceived pain and hardness. However, the results of this study show that the effect cannot be attributed to the ultrasound component.