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Objective: The study aimed to compare the applicability of classic lateral lamellectomy versus submucosal conchoplasty techniques in managing concha bullosa during and after functional endoscopic sinus surgery. Methods: The study randomly divided 56 patients with bilateral concha bullosa into two groups. One group of patients underwent the submucosal conchoplasty technique and the other group underwent the lateral lamellectomy technique. The study compared the intra-operative findings, including the time required for each technique, the amount of intra-operative bleeding and the post-operative endoscopic outcome of the middle meatus and middle turbinate stability. Results: Submucosal conchoplasty was significantly more time-consuming than the lateral lamellectomy technique (p = 0.001*). The difference in the intra-operative amount of bleeding was (p = 0.086*). The lateral lamellectomy group showed a higher rate of synechia formation in the middle meatus (p = 0.012*). Conclusion: Submucosal conchoplasty is a valid technique for managing concha bullosa with better post-operative endoscopic outcomes. [ABSTRACT FROM AUTHOR]

India’s clinical trial landscape has witnessed rapid growth over the period, with the recent introduction of remote trial patient monitoring utilising technologies like Artificial Intelligence (AI). The vast and diverse population, combined with well-established medical infrastructure and skilled professionals, makes India an ideal location for conducting clinical research. Many international pharmaceutical companies have chosen to outsource their operations to India as well. However, despite India emerging as a significant hub for clinical trials, recruiting participants still presents unique challenges. This review aimed to shed light on the hurdles faced in recruiting participants in Indian clinical trials and explore potential solutions to bridge this gap. It has been highlighted that overcoming the challenges in recruiting participants in Indian clinical trials requires a multi-faceted approach involving various stakeholders. Along with the powerful steps taken by the government in reforming policies and regulatory norms, certain innovative and effective strategies need to be designed to streamline the processes of participant recruitment.

India’s clinical trial landscape has witnessed rapid growth over the period, with the recent introduction of remote trial patient monitoring utilising technologies like Artificial Intelligence (AI). The vast and diverse population, combined with well-established medical infrastructure and skilled professionals, makes India an ideal location for conducting clinical research. Many international pharmaceutical companies have chosen to outsource their operations to India as well. However, despite India emerging as a significant hub for clinical trials, recruiting participants still presents unique challenges. This review aimed to shed light on the hurdles faced in recruiting participants in Indian clinical trials and explore potential solutions to bridge this gap. It has been highlighted that overcoming the challenges in recruiting participants in Indian clinical trials requires a multi-faceted approach involving various stakeholders. Along with the powerful steps taken by the government in reforming policies and regulatory norms, certain innovative and effective strategies need to be designed to streamline the processes of participant recruitment. [ABSTRACT FROM AUTHOR]

Aims Methods Results Conclusion Immune checkpoint inhibitor therapy used for lung cancer has significantly changed response and survival rates, however, the impact on patients' nutritional status remains largely unexplored. This review aims to identify common adverse events that increase nutrition risk induced in non‐small cell lung cancer patients treated with immune checkpoint inhibitor therapy and assess impact on nutritional status.PubMed, Medline and CINAHL were systematically searched in September 2023 for randomised controlled trials comparing immune checkpoint inhibitor treatment of non‐small cell lung cancer to a control group. Treatment‐related adverse events that increased nutrition impact symptoms identified in the patient‐generated subjective global assessment and clinical guidelines were extracted and qualitatively analysed. Risk of bias was assessed using Cochrane Risk of Bias tool 2.Eleven eligible randomised controlled trial studies were identified and analysed. The data demonstrated immune checkpoint inhibitor treatment was associated with a lower percentage of reported nutrition impact symptoms, for example, decreased appetite, nausea, vomiting, compared to chemotherapy treatment. Conversely, immune checkpoint inhibitor treated patients recorded a greater percentage of immune‐related adverse events that alter metabolism or nutrient absorption.Non‐small cell lung cancer patients treated with immune checkpoint inhibitors still experience nutrition impact symptoms but less frequently than patients treated with chemotherapy. This combined with unique nutrition‐related consequences from colitis and thyroid disorders induced by immune checkpoint inhibitor therapy indicates patients should be screened, assessed and interventions implemented to improve nutrition. [ABSTRACT FROM AUTHOR]

We aimed to investigate the effectiveness of n -3 fatty acids supplementation on the risk of developing depression, depressive symptoms and remission of depression. We searched PubMed, Scopus and Web of Science from inception to December 2022 to find randomised trials of n -3 fatty acids supplementation in adults. We conducted random-effects meta-analyses to estimate standardised mean differences (SMD) and 95 % CI for continuous outcomes and risk difference and 95 % CI for binary outcomes. A total of sixty-seven trials were included. Each 1 g/d n -3 fatty acids supplementation significantly improved depressive symptoms in adults with and without depression (moderate-certainty evidence), with a larger improvement in patients with existing depression. Dose–response analyses indicated a U-shaped effect in patients with existing depression, with the greatest improvement at 1·5 g/d. The analysis showed that n -3 fatty acid supplementation significantly increased depression remission by 19 more per 100 in patients with depression (low-certainty evidence). Supplementation with n -3 fatty acids did not reduce the risk of developing depression among the general population, but it did improve the severity of depression among patients with existing depression. [ABSTRACT FROM AUTHOR]

Abstract Background Although physical activity interventions are frequently reported to be effective, long-term changes are needed to generate meaningful health benefits. There are criticisms that evaluations of physical activity interventions mostly report short-term outcomes and that these are often self-reported rather than measured objectively. This study therefore aimed to assess the long-term (at least 24 month) effectiveness of behavioural interventions on objectively measured physical activity. Methods We conducted a systematic review with a meta-analysis of effects on objectively measured physical activity. We searched: Cochrane CENTRAL, EMBASE, PsychInfo, CINAHL and Pubmed up to 10th January 2022. Studies were included if they were in English and included a physical intervention that assessed physical activity in the long-term (defined as at least 24 months). Results Eight studies with 8480 participants were identified with data suitable for meta-analysis. There was a significant effect of interventions on daily steps 24 months post baseline (four studies, SMD: 0.15, 95% CI: 0.02 to 0.28) with similar results at 36 to 48 months of follow up (four studies, SMD: 0.17, 95% CI: 0.07 to 0.27). There was a significant effect of interventions on moderate-to-vigorous physical activity 24 months post baseline (four studies, SMD: 0.18 95% CI: 0.07 to 0.29) and at 36 to 48 months (three studies, SMD: 0.16 95% CI: 0.09 to 0.23). The mean effect size was small. However, the changes in moderate-to-vigorous physical activity and steps per day were clinically meaningful in the best-performing studies. Conclusion This review suggests that behavioural interventions can be effective in promoting small, but clinically meaningful increases in objectively measured physical activity for up to 48 months. There is therefore a need to develop interventions that can achieve greater increases in long-term physical activity with greater efficiency.

Introduction: The comparative efficacy of pulmonary surfactant in the treatment of respiratory distress syndrome in preterm infants remains unclear. We aimed to evaluate the effectiveness of different pulmonary surfactant in the treatment of respiratory distress syndrome in preterm infants and to provide an evidence-based reference for clinical use. Material and methods: MEDLINE, Embase, The Cochrane Library, and Clinical Trials databases were electronically searched from inception to January 2019. Two reviewers independently screened literature and extracted data, and then R and RevMan 5.3 software packages were used to perform network meta-analysis. Results: The relative risk of respiratory distress syndrome in preterm infants associated with six different pulmonary surfactant was analysed, including beractant (Survanta), surfactant A (Alveofact), calfactant (Infasurf), poractant (Curosurf), lucinactant (Surfaxin), and colfosceril (Exosurf). Patients with the following drugs appeared to have significantly reduced mortality of respiratory distress syndrome compare with beractant: surfactant A (OR = 0.53, 95% CI: 0.31-0.90), calfactant (OR = 0.91, 95% CI: 0.85-0.97), poractant (OR = 0.72, 95% CI: 0.67-0.77), lucinactant (OR = 0.80, 95% CI: 0.71- 0.90), and colfosceril (OR = 0.93, 95% CI: 0.87-0.99). The SUCRA (surface under the cumulative ranking) values for each of the drugs were: beractant (8.9%), surfactant A (93.8%), calfactant (40.3%), poractant (65.4%), lucinactant (59.8%), and colfosceril (31.6%). Conclusions: Compared with beractant, other pulmonary surfactants are more effective to reduce the mortality of respiratory distress syndrome in preterm infants. Surfactant A drugs appeared to have the best efficacy in reducing mortality of respiratory distress syndrome in preterm infants. [ABSTRACT FROM AUTHOR]

Background: Although physical activity interventions are frequently reported to be effective, long-term changes are needed to generate meaningful health benefits. There are criticisms that evaluations of physical activity interventions mostly report short-term outcomes and that these are often self-reported rather than measured objectively. This study therefore aimed to assess the long-term (at least 24 month) effectiveness of behavioural interventions on objectively measured physical activity. Methods: We conducted a systematic review with a meta-analysis of effects on objectively measured physical activity. We searched: Cochrane CENTRAL, EMBASE, PsychInfo, CINAHL and Pubmed up to 10th January 2022. Studies were included if they were in English and included a physical intervention that assessed physical activity in the long-term (defined as at least 24 months). Results: Eight studies with 8480 participants were identified with data suitable for meta-analysis. There was a significant effect of interventions on daily steps 24 months post baseline (four studies, SMD: 0.15, 95% CI: 0.02 to 0.28) with similar results at 36 to 48 months of follow up (four studies, SMD: 0.17, 95% CI: 0.07 to 0.27). There was a significant effect of interventions on moderate-to-vigorous physical activity 24 months post baseline (four studies, SMD: 0.18 95% CI: 0.07 to 0.29) and at 36 to 48 months (three studies, SMD: 0.16 95% CI: 0.09 to 0.23). The mean effect size was small. However, the changes in moderate-to-vigorous physical activity and steps per day were clinically meaningful in the best-performing studies. Conclusion: This review suggests that behavioural interventions can be effective in promoting small, but clinically meaningful increases in objectively measured physical activity for up to 48 months. There is therefore a need to develop interventions that can achieve greater increases in long-term physical activity with greater efficiency. [ABSTRACT FROM AUTHOR]

Communities' knowledge and management strategies are crucial for mitigating and controlling the threat of existing and emerging diseases. In this study, we conducted randomised control trials (RCT) to examine the impact of health education on households' knowledge and management of three Arboviral Diseases (ADs); Rift Valley fever, Chikungunya fever, and Dengue fever in Kenya. The study was based on a sample of 629 households drawn from the three of Kenya's AD hotspot counties; Baringo, Kwale, and Kilifi. Employing a difference-in-difference method, our findings indicate that health education intervention significantly improved households' understanding of ADs transmission modes, causes, and prevention strategies. However, this intervention did not sufficiently influence households' disease management behaviour. We recommend the implementation of community engagement and outreach initiatives which have the potential to drive behavioural changes at the household level, thus enhancing the management and control of ADs in Kenya. [ABSTRACT FROM AUTHOR]

ABSTRACTCommunities’ knowledge and management strategies are crucial for mitigating and controlling the threat of existing and emerging diseases. In this study, we conducted randomised control trials (RCT) to examine the impact of health education on households’ knowledge and management of three Arboviral Diseases (ADs); Rift Valley fever, Chikungunya fever, and Dengue fever in Kenya. The study was based on a sample of 629 households drawn from the three of Kenya’s AD hotspot counties; Baringo, Kwale, and Kilifi. Employing a difference-in-difference method, our findings indicate that health education intervention significantly improved households’ understanding of ADs transmission modes, causes, and prevention strategies. However, this intervention did not sufficiently influence households’ disease management behaviour. We recommend the implementation of community engagement and outreach initiatives which have the potential to drive behavioural changes at the household level, thus enhancing the management and control of ADs in Kenya.

Mental health services are placing a greater emphasis on wellbeing and recovery. The current research investigated if positive psychology interventions (PPIs) increase peoples' subjective wellbeing and reduce clinical depression. A systematic methodological review was conducted on randomized-control-trials with people attending clinical services. Five databases were searched. A hand search was then completed on the reference lists of the identified articles and the associated journals. Eleven research interventions were reviewed. PPIs were found to significantly increase wellbeing, relative to controls and there were fewer studies indicating a difference in decreasing depression. However, subsequent analysis revealed that the interventions were heterogeneous which limits the drawing of definitive systematic conclusions. A methodological evaluation also found that there were recurring issues: in delivering the interventions, measuring subjective wellbeing, and applying the design. Thus, the methodological quality of the research interventions, as measured by the current review was low. There is emerging evidence that PPIs improve peoples' mental health. However, there is scope to standardize and to improve the quality of the research interventions. [ABSTRACT FROM AUTHOR]

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 <.00001), reduced the ulcer area (standardised mean difference [SMD] = 3.52, 95% CI 1.65‐5.38, P =.0002), and shortened the mean healing time (SMD = −1.40, 95% CI −1.90 to −0.91, P <.00001) of patients with DFUs. The quality of the evidence was very low according to the GRADE system. LLLT is a promising and effective adjuvant treatment to accelerate the healing of DFUs. Further evidence from larger samples and higher quality RCTs is needed to prove the effect of LLLT and to determine the most appropriate parameters for the healing of DFUs. [ABSTRACT FROM AUTHOR]

Introduction The comparative efficacy of pulmonary surfactant in the treatment of respiratory distress syndrome in preterm infants remains unclear. We aimed to evaluate the effectiveness of different pulmonary surfactant in the treatment of respiratory distress syndrome in preterm infants and to provide an evidence-based reference for clinical use. Material and methods MEDLINE, Embase, The Cochrane Library, and Clinical Trials databases were electronically searched from inception to January 2019. Two reviewers independently screened literature and extracted data, and then R and RevMan 5.3 software packages were used to perform network meta-analysis. Results The relative risk of respiratory distress syndrome in preterm infants associated with six different pulmonary surfactant was analysed, including beractant (Survanta), surfactant A (Alveofact), calfactant (Infasurf), poractant (Curosurf), lucinactant (Surfaxin), and colfosceril (Exosurf). Patients with the following drugs appeared to have significantly reduced mortality of respiratory distress syndrome compare with beractant: surfactant A (OR = 0.53, 95% CI: 0.31–0.90), calfactant (OR = 0.91, 95% CI: 0.85–0.97), poractant (OR = 0.72, 95% CI: 0.67–0.77), lucinactant (OR = 0.80, 95% CI: 0.71–0.90), and colfosceril (OR = 0.93, 95% CI: 0.87–0.99). The SUCRA (surface under the cumulative ranking) values for each of the drugs were: beractant (8.9%), surfactant A (93.8%), calfactant (40.3%), poractant (65.4%), lucinactant (59.8%), and colfosceril (31.6%). Conclusions Compared with beractant, other pulmonary surfactants are more effective to reduce the mortality of respiratory distress syndrome in preterm infants. Surfactant A drugs appeared to have the best efficacy in reducing mortality of respiratory distress syndrome in preterm infants.

Abstract 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.

This article is a 'replication in context' of a flagship randomised control trial (RCT) conducted in Morocco on microcredit. 'Replication in context' consists in combining the quantitative replication of an RCT with a contextualised analysis of its implementation and its political economy, in the sense of the interplay between different stakeholders with divergent and potentially conflicting interests, constraints and powers. 'Replication in context' draws on quantitative and qualitative data and uses the tools of statistics, political economy and sociology of science. This method allows us to describe the entire RCT production chain, from sampling, data collection, data entry and recoding, estimates and interpretations to publication and dissemination of the results. We find that this particular RCT does not respect the key principles of randomisation (imbalanced sampling and contamination) nor those of statistics (coding and measurement problems, poor-quality data and arbitrary trimming procedures). The qualitative analysis highlights the difficulties of implementing a randomised protocol in the real world. Beyond this particular case study, our analyses call into question the supposed superiority of randomised methods, echoing the growing unease in an academic field increasingly struggling to enforce the basic rules of ethics and scientific deontology. [ABSTRACT FROM AUTHOR]

Randomised Control Trials (RCT) are both widely used in development, reaching hundreds of millions through RCT informed policy, and highly regarded, receiving a Nobel Prize in Economics. Proponents, largely academic economists, position RCTs as a scientific and ideologically neutral way to get to the heart of 'what works' in development. However, this new and radical micro-experimental approach to poverty reduction has sat uneasily within the broader development sphere, including critical geographers. We contribute to this debate by empirically examining the practical manifestation of the methodology within 'PNPM Generasi' – an innovative Indonesian cash transfer program evaluated through the largest RCT to date. Drawing primarily on field interviews, our examination finds three departures from the gold standard proclamations of the RCT methodology in practice. First, we find that randomising aid delivery breached ethical guidelines and compromised the effectiveness of the program being studied, largely as a result of RCTs being run in secret from local communities and politicians. Second, we find applying the RCT methodology on the ground was technically complex and financially costly, requiring not only an excessive use of scarce program funds, but also undermining the validity of the evaluation results. Finally, we find RCT results were not widely used in practice. We demonstrate these findings are not restricted to our specific case, but rather, reflect systemic deficiencies with RCT evaluations. Our results suggest that RCTs may have value if applied judiciously, and as part of multi-pronged approaches, but we caution against their growing monopoly influence on poverty reduction. [ABSTRACT FROM AUTHOR]

Background: Ankle fractures are the third most common fracture in the elderly. Patients over 60 years are more severely affected by these injuries than their younger counterparts and have a higher rate of complications regardless of the management strategy. Traditional management strategies for unstable ankle fractures include plaster immobilisation and open reduction and internal fixation, with newer modalities such as intramedullary fixation becoming increasingly popular. The aim of this review is to establish the best current evidence for or against different treatment strategies. Methods: A systematic review and meta-analysis of randomised controlled trials comparing treatment options for unstable ankle fractures in adults over 55 was conducted, with the primary outcome being functional assessment score at 6–12 months (Olerud and Molander Ankle Score). Secondary outcomes were adverse events including infection and re-operation. Results: The search strategies identified 426 articles. After screening and full text review, four papers met the inclusion and exclusion criteria, providing data on 754 ankle fractures. Alternative treatment groups were tibio-talo-calcaneal nail, fibular nail and casting and were compared to open reduction and internal fixation. Meta-analysis of the data showed no difference in Olerud and Molander Ankle Score between treatment modalities at 6–12 months. There was, however, a significant reduction in the incidence of adverse events (OR 0.59 (0.44, 0.81)) and wound infection (0.13 (0.05, 0.31)) in the alternative treatment groups compared to open reduction and internal fixation. Conclusion: The current evidence shows no significant difference between treatment modalities for ankle fractures in older adults in terms of functional outcome. Open reduction and internal fixation has a higher rate of adverse events and wound infection when compared to alternative treatments. Therefore, surgery should be carefully considered and if undertaken, in a select patient cohort other treatment modalities, such as intramedullary fixation should be considered. [ABSTRACT FROM AUTHOR]

Abstract 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.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Development evaluation refers to evaluating projects and programmes in development contexts. Some evaluations are too narrow. Narrow within-discipline impact evaluations are weaker than multidisciplinary, mixed-methods evaluations. A two-step process leads toward profoundly better arguments in assessing the impact of a development intervention. The first step is setting out the arena for discussion, including what the various entities are in the social, political, cultural and natural environment surrounding the chosen problem. The second step is that, once this arena has been declared, the project and triangulation of data can be brought to bear upon logical arguments with clear, transparent reasoning leading to a set of conclusions. In this second step, we do need scientific methods such as peer review, data and so on, but, crucially, the impact evaluation process must not rest upon a single data type, such as survey data. It is dangerous and undesirable to have the entire validity of the conclusions resting upon randomised control trials, or even a mixture of data types. Different contributions to knowledge exist within the evaluation process, including the interaction of people during action research, ethnography, case-study methods, process tracing and qualitative methods. The cement holding my argument together is that multiple logics are used (retroductive, deductive, and inductive, in particular). Deductive mathematics should not dominate the evaluation of an intervention, as randomised controlled trials on their own lend themselves to worrying fallacies about causality. I show this using Boolean fuzzy set logic. An indicator of high-quality development evaluation is the use of multiple logics in a transparent way. [ABSTRACT FROM AUTHOR]

Several interventions have targeted dyads to promote physical activity (PA) or reduce sedentary behaviour (SB), but the evidence has not been synthesised. Sixty-nine studies were identified from MEDLINE, PsycINFO, and Web of Science, and 59 were included in the main meta-analyses (providing 72 independent tests). Intervention details, type of dyadic goal, participant characteristics, and methodological quality were extracted and their impact on the overall effect size was examined. Sensitivity analyses tested effect robustness to (a) the effects of other statistically significant moderators; (b) outliers; (c) data included for participants who were not the main target of the intervention. Dyadic interventions had a small positive, highly heterogeneous, effect on PA g = .203, 95% CI [0.123-0.282], compared to comparison conditions including equivalent interventions targeting individuals. Shared target-oriented goals (where both dyad members hold the same PA goal for the main target of the intervention) and peer/friend dyads were associated with larger effect sizes across most analyses. Dyadic interventions produced a small homogeneous reduction in SB. Given dyadic interventions promote PA over-and-above equivalent interventions targeting individuals, these interventions should be more widespread. However, moderating factors such as the types of PA goal and dyad need to be considered to maximise effects. [ABSTRACT FROM AUTHOR]

Background: Educational interventions are often complex, and their outcomes could be due to factors not focused on in the impact evaluation. Therefore, educational evaluations using a randomised control trial (RCT) design approach need to go beyond obtaining the impact results alone. Purpose: Process evaluation is embedded in the evaluation design in order to enhance contextual understanding of the outcome results achieved from an RCT. However, in the context of evaluation studies, reporting on the fidelity to the research design protocol is also important and can be undertaken by the same process evaluation approaches as used for studying the mechanism of interventions. Research design and method: This paper reports on two RCTs in which school staff led the trials themselves in their schools - in an aggregated trial study managed and conducted at secondary school cluster-level, with expert advice from us, as independent evaluation advisors. The interventions implemented for evaluation were two highly structured programmes that targeted improvement in the literacy attainment of pupils who were at risk of failing to achieve the expected levels. Assessing the effect on literacy performance was the primary objective. However, the research design included methods for understanding the process of the interventions being implemented. Our main findings on the feasibility of aggregated trials led by schools are informed by our process evaluation, which included participant observations of the training, session observations of the interventions being implemented, and interviews with pupils, teachers and school leaders. Data on fidelity to the interventions were collected, and, using similar techniques, we also evaluated the feasibility of the research process led by school leaders and the possible barriers and challenges of RCT management by schools. We included information on randomisation procedures, perceptions of pupils and teachers involved in the study, and the programme website resources. Results: The primary outcome results of the trials showed promise from the interventions, in raising disadvantaged pupils’ reading scores during transition from primary to secondary school stage. The process evaluation revealed considerable potential benefits from involving school leaders as evaluators, and the paper describes a way forward here. However, there were some indications that there was not full compliance with the randomisation process, and this might have resulted in initial imbalance of pre-tests scores between the treatment and control groups in one trial. Conclusion: Process evaluation cannot answer research questions regarding impact outcomes, but for a general understanding of outcomes it is important to report how the impact results have been achieved. This is where rich, in-depth data of the kind we describe can assist. [ABSTRACT FROM AUTHOR]

Background: Current guidelines for the conduct of cost-effectiveness analysis (CEA) are mainly applicable to facility-based interventions in high-income settings. Differences in the unit of analysis and the high cost of data collection can make these guidelines challenging to follow within public health trials in low- and middle- income settings. Objective: This paper reflects on the challenges experienced within our own work and proposes solutions that may be useful to others attempting to collect, analyse, and compare cost data between public health research sites in low- and middle-income countries. Design: We describe the generally accepted methods (norms) for collecting and analysing cost data in a single-site trial from the provider perspective. We then describe our own experience applying these methods within eight comparable cluster randomised, controlled, trials. We describe the strategies used to maximise adherence to the norm, highlight ways in which we deviated from the norm, and reflect on the learning and limitations that resulted. Results: When the expenses incurred by a number of small research sites are used to estimate the cost-effectiveness of delivering an intervention on a national scale, then deciding which expenses constitute ‘start-up’ costs will be a nontrivial decision that may differ among sites. Similarly, the decision to include or exclude research or monitoring and evaluation costs can have a significant impact on the findings. We separated out research costs and argued that monitoring and evaluation costs should be reported as part of the total trial cost. The human resource constraints that we experienced are also likely to be common to other trials. As we did not have an economist in each site, we collaborated with key personnel at each site who were trained to use a standardised cost collection tool. This approach both accommodated our resource constraints and served as a knowledge sharing and capacity building process within the research teams. Conclusions: Given the practical reality of conducting randomised, controlled trials of public health interventions in low- and middle- income countries, it is not always possible to adhere to prescribed guidelines for the analysis of cost effectiveness. Compromises are frequently required as researchers seek a pragmatic balance between rigor and feasibility. There is no single solution to this tension but researchers are encouraged to be mindful of the limitations that accompany compromise, whilst being reassured that meaningful analyses can still be conducted with the resulting data.

Randomised control trials (RCTs) are an evidence-based research approach which has not yet been adopted and widely used in open and distance education to inform educational policy and practice. Despite the challenges entailed in their application, RCTs hold the power to robustly evaluate the effects of educational interventions in distance learning and conclude on whether (or not) these interventions should be adopted and used extensively. The aim of this paper is to spark discussions around the use of RCTs in distance learning by illustrating their benefits and drawbacks including challenges in adopting RCTs in education. To achieve this aim, a RCT was implemented to examine whether a small-scale intervention in four language modules could improve attendance at an end-of-module speaking assessment, and in consequence, performance, completion and pass rates. Results raise the need for further research in order to identify what type of interventions should be designed and put into practice to elicit a positive impact on learners. The paper concludes with a discussion on why RCTs should be brought to the forefront as a viable method for the effective evaluation of the impact of open learning analytic interventions. [ABSTRACT FROM AUTHOR]

Background and aim:Good dentofacial growth is a major goal in the treatment of unilateral cleft lip and palate (UCLP). The aim was to evaluate dental arch relationships at age 5 years after four different protocols of primary surgery for UCLP. Design:Three parallel randomised clinical trials were undertaken as an international multi-centre study by 10 cleft teams in five countries: Denmark, Finland, Sweden, Norway, and the UK. Methods:Three different surgical procedures for primary palatal repair (Arms B, C, D) were tested against a common procedure (Arm A) in the total cohort of 448 children born with non-syndromic UCLP. Study models of 418 patients (273 boys) at the mean age of 5.1 years (range = 4.8–7.0) were available. Dental arch relationships were assessed using the 5-year index by a blinded panel of 16 orthodontists. Kappa statistics were calculated to assess reliability. The trials were tested statistically witht-and Chi-square tests. Results:Good-to-very good levels of intra- and interrater reliability were obtained (0.71–0.94 and 0.70–0.87). Comparisons within each trial showed no statistically significant differences in the mean 5-year index scores or their distributions between the common method and the local team protocol. The mean index scores varied from 2.52 (Trial 2, Arm C) to 2.94 (Trial 3, Arm D). Conclusion:The results of the three trials do not provide statistical evidence that one technique is better than the others. Further analysis of the possible influence of individual surgical skill and learning curve are being pursued in this dataset. Trial registration:ISRCTN29932826. [ABSTRACT FROM AUTHOR]

Background Sexually transmitted infections (STI) are a major public health problem, with high social and economic costs. Condoms are effective for prevention of STI, but there are many barriers to successful use. Men are less likely than women to visit health professionals, and can be reluctant to discuss their sexual health with practitioners, partners or friends. An online intervention offers an alternative way to reach men at risk of STI. Digital interventions are very suitable for sexual health promotion because access can be private, anonymous and self-paced. Interventions can be targeted for specific groups (e.g. by age, gender or sexuality), and content can be tailored for individuals. Digital interventions can be expensive to develop, but offer the advantages of intervention content fidelity and the potential to reach large audiences at relatively low dissemination costs. Interventions can improve sexual behaviour as well as increasing knowledge, self-efficacy and safer sex intention, but more evidence is needed to establish effects on biological outcomes such as STI. The Men’s Safer Sex website (MenSS) is an interactive digital intervention (IDI) which provides information and tailored advice on sexual wellbeing and barriers to condom use. The website was offered to men in the waiting rooms of NHS sexual health clinics, with the aim of increasing condom use and reducing STI. Aims: To determine the feasibility and best design for a randomised controlled trial to test the effect of the Men’s Safer Sex website on condom use and STI amongst men attending sexual health clinics. Methods: Men aged 16 and over with female sexual partners and recent unprotected sex or suspected acute STI were recruited from three UK sexual health clinics (N = 159). Participants were randomised (using an automated computer algorithm) to the MenSS website in addition to usual clinic care, or to usual care only. Participants were invited via email to complete online follow-up questionnaires at 3, 6, and 12 months. The primary outcome was condom use at 3 months, with secondary outcomes of STI rates (self-reported and from clinical records). A total of £50 in online shopping vouchers was offered for completing online questionnaires. Results: Eighty-four men were allocated to receive the intervention, and 75 were randomised to the control arm. Clinical records were located for 94% of participants (for STI diagnoses over 12 months), but response rates for the online questionnaire were poor: 36% at 3 and 6 months, and 50% at 12 months. There was no detectable difference in condom use between groups, but the numbers were very small due to the low online questionnaire response rate. There were fewer clinical diagnoses of STI over one year in the intervention group who were offered the MenSS website, but the differences were non-significant (Incidence rate ratio 0.75, 95% CI 0.29 to 1.89). No harms or adverse events were identified. Conclusions The best way to assess the impact of the MenSS website was by recording STI diagnoses from clinical records. Response rates for the online questionnaire were poor despite offers of incentives. There were many challenges to conducting an online trial of a sexual health website including ethical committee concerns about email content, poor reliability of trial-related software, balancing data protection and security protocols against ease of access for participants, barriers to patient access to IT in NHS clinics, and trying to ensure that participants engage with a digital intervention for long enough. Whilst digital interventions have great potential for health promotion, we encountered significant obstacles to online research, and to implementation of an IDI in an NHS clinical setting.

Background Modern randomised controlled trials typically use composite endpoints. This is only valid if each endpoint is equally important to patients but few trials document patient preference and seek the relative importance of components of combined endpoints. If patients weigh endpoints differentially, our interpretation of trial data needs to be refined. Methods and results We derive a quantitative, structured tool to determine the relative importance of each endpoint to patients. We then apply this tool to data comparing angioplasty with drug-eluting stents to bypass surgery. The survey was administered to patients undergoing cardiac catheterisation. A meta-analysis comparing coronary artery bypass grafting (CABG) to percutaneous coronary interventuin (PCI) was then performed using (a) standard MACE and (b) patient-centred MACE. Patients considered stroke worse than death (stroke 102.3 ± 19.6%, p < 0.01), and MI and repeat revascularisation less severe than death (61.9 ± 26.8% and 41.9 ± 25.4% respectively p < 0.01 for both). 7 RCTs (5251 patients) were eligible. Meta-analysis demonstrated that standard MACE occurs more frequently with PCI than surgery (OR 1.44; 95% CI 1.10 to 1.87; p = 0.007). Re-analysis using patient-centred MACE found no significant difference between PCI and CABG (OR 1.22, 95% CI 0.97 to 1.53; p = 0.10). Conclusions Patients do not consider the constituent endpoints of MACE equal. We derive a novel patient-centred metric that recognises and quantifies the differences attributed to each endpoint. When patient preference data are applied to contemporary trial results, there is no significant difference between PCI and CABG. Responses from individual patients in clinic could be used to give individual patients a recommendation that is truly personalised. [ABSTRACT FROM AUTHOR]

The most conspicuous form of agricultural experiment is the field trial, and within the history of such trials, the arrival of the randomised control trial (RCT) is considered revolutionary. Originating with R.A. Fisher within British agricultural science in the 1920s and 1930s, the RCT has since become one of the most prodigiously used experimental techniques throughout the natural and social sciences. Philosophers of science have already scrutinised the epistemological uniqueness of RCTs, undermining their status as the 'gold standard' in experimental design. The present paper introduces a historical case study from the origins of the RCT, uncovering the initially cool reception given to this method by agricultural scientists at the University of Cambridge and the (Cambridge based) National Institute of Agricultural Botany. Rather than giving further attention to the RCT, the paper focuses instead on a competitor method-the half-drill strip-which both predated the RCT and remained in wide use for at least a decade beyond the latter's arrival. In telling this history, John Pickstone's Ways of Knowing is adopted, as the most flexible and productive way to write the history of science, particularly when sciences and scientists have to work across a number of different kinds of place. It is shown that those who resisted the RCT did so in order to preserve epistemic and social goals that randomisation would have otherwise run a tractor through. [ABSTRACT FROM AUTHOR]

Development economics has become something of an innovator within the discipline of economics, due to its adoption of experimental and statistical analysis techniques. In this paper I give examples of this new trend in development economics: randomised-control trials, natural experiments, specialist analytical techniques like pre-analysis plans, and evidence-driven policy evaluation. I explore this novel experimental development economics in conversation with current argumentation in economic/development geography about economics. I do this in order to ask whether this experimental trend responds to any of these geographical critiques. Although I find that this new development economics repeats many of the tendencies of economics that geographers find so specious, it does pose challenges to economic/development geography, which I explore. [ABSTRACT FROM AUTHOR]

Objective: Comparing outcomes of percutaneous coronary intervention (PCI) with drug eluting stent (DES) and Coronary Artery Bypass Grafting (CABG) in patients with multivessel Coronary Artery Disease (CAD) using data from randomised controlled trials (RCT). Background: PCI and CABG are established strategies for coronary revascularization in the setting of ischemic heart disease. Multiple RCT have compared outcomes of the two modalities in patients with multivessel CAD. Methods: We did a meta-analysis from six RCT in the contemporary era comparing the effectiveness of PCI with DES to at 1 year, 2 years and 5 years respectively. Results: Compared to CABG, at one year PCI was associated with a significantly higher incidence of TVR (RR= 2.31; 95% CI: [1.80 - 2.96]; P=<0.0001), lower incidence of stroke (RR= 0.35; 95% CI: [0.19 - 0.62]; P=0.0003), and no difference in death (RR= 1.02; 95% CI: [0.77 - 1.36]; P= 0.88) or MI (RR= 1.16; 95% CI: [0.72 - 1.88]; P= 0.53). At 5 years, PCI was associated with a higher incidence of death (RR= 1.3; 95% CI: [1.10 - 1.54]; P= 0.0026) and MI (RR= 2.21; 95% CI: [1.75 - 2.79]; P=<0.0001). While the higher incidence of MI with PCI was noticed in both diabetic and non-diabetics, death was increased mainly in diabetic patients. Conclusion: In patients with multi-vessel CAD, PCI with DES is associated with no significant difference in death or MI at 1 or 2 years. However at 5 years, PCI is associated with higher incidence of death and MI. [ABSTRACT FROM AUTHOR]