The effect on income of providing near vision correction to workers in Bangladesh: The THRIVE (Tradespeople and Hand-workers Rural Initiative for a Vision-enhanced Economy) randomized controlled trial.

INTRODUCTION: Presbyopia, the leading cause of vision impairment globally, is common during working years. However, no trials have assessed presbyopia's impact on income. METHODS: In April 2017, we conducted a census among 59 Bangladesh villages to identify persons aged 35 to 65 years with presbyopia (presenting distance vision > = 6/12 bilaterally and correctable inability to see 6/13 at 40 cm with both eyes), who never had owned glasses. Participants were randomized (1:1) to receive immediate free reading glasses (intervention) or glasses delivered 8 months later (control). Visual demand of different jobs was stratified into three levels. Outcomes were between-group differences in the 8 month change in: self-reported monthly income (primary) and Near Vision Related Quality of Life (NVRQOL, secondary). RESULTS: Among 10,884 census participants, 3,655 (33.6%) met vision criteria and 863 (23.6%) comprised a sample enriched for near vision-intensive jobs, but 39 (4.52%) could not be reached. All participants allocated to intervention (n = 423, 51.3%) and control (n = 401, 48.7%) received the appropriate intervention, and follow-up was available for 93.4% and 96.8% respectively. Groups were similar at baseline in all characteristics: mean age was 47 years, 50% were male, 35% literate, and about half engaged in "most near vision-intensive" occupations. Glasses wear at 8-month follow-up was 88.3% and 7.81% in intervention and control respectively. At baseline, both the intervention and control groups had a self-reported median monthly income of US$35.3. At endline, the median income for the intervention group was US$47.1 compared with US$35.3 for control, a difference of 33.4%. Predictors of greater income increase in multivariate models included intervention group allocation (OR 1.45, 95% CI 1.12, 1.88, P = 0.005), male sex (OR 2.41, 95% CI 1.84, 3.16, P <0.001), and not engaging in income-producing work at baseline (OR 2.35, 95% CI 1.69, 3.26, P<0.001). CONCLUSION: Provision of reading glasses increases income in near vision-intensive occupations, and may facilitate return to work for those currently unemployed.

A survey of experts to identify methods to detect problematic studies: Stage 1 of the INSPECT-SR Project.

Background: Randomised controlled trials (RCTs) inform healthcare decisions. Unfortunately, some published RCTs contain false data, and some appear to have been entirely fabricated. Systematic reviews are performed to identify and synthesise all RCTs which have been conducted on a given topic. This means that any of these 'problematic studies' are likely to be included, but there are no agreed methods for identifying them. The INSPECT-SR project is developing a tool to identify problematic RCTs in systematic reviews of healthcare-related interventions. The tool will guide the user through a series of 'checks' to determine a study's authenticity. The first objective in the development process is to assemble a comprehensive list of checks to consider for inclusion. Methods: We assembled an initial list of checks for assessing the authenticity of research studies, with no restriction to RCTs, and categorised these into five domains: Inspecting results in the paper; Inspecting the research team; Inspecting conduct, governance, and transparency; Inspecting text and publication details; Inspecting the individual participant data. We implemented this list as an online survey, and invited people with expertise and experience of assessing potentially problematic studies to participate through professional networks and online forums. Participants were invited to provide feedback on the checks on the list, and were asked to describe any additional checks they knew of, which were not featured in the list. Results: Extensive feedback on an initial list of 102 checks was provided by 71 participants based in 16 countries across five continents. Fourteen new checks were proposed across the five domains, and suggestions were made to reword checks on the initial list. An updated list of checks was constructed, comprising 116 checks. Many participants expressed a lack of familiarity with statistical checks, and emphasized the importance of feasibility of the tool. Conclusions: A comprehensive list of trustworthiness checks has been produced. The checks will be evaluated to determine which should be included in the INSPECT-SR tool.

Admission avoidance hospital at home.

BACKGROUND: Admission avoidance hospital at home provides active treatment by healthcare professionals in the patient's home for a condition that would otherwise require acute hospital inpatient care, and always for a limited time period. This is the fourth update of this review. OBJECTIVES: To determine the effectiveness and cost of managing patients with admission avoidance hospital at home compared with inpatient hospital care. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and CINAHL on 24 February 2022, and checked the reference lists of eligible articles. We sought ongoing and unpublished studies by searching ClinicalTrials.gov and WHO ICTRP, and by contacting providers and researchers involved in the field. SELECTION CRITERIA: Randomised controlled trials recruiting participants aged 18 years and over. Studies comparing admission avoidance hospital at home with acute hospital inpatient care. DATA COLLECTION AND ANALYSIS: We followed the standard methodological procedures expected by Cochrane and the Effective Practice and Organisation of Care (EPOC) Group. We performed meta-analysis for trials that compared similar interventions, reported comparable outcomes with sufficient data, and used individual patient data when available. We used the GRADE approach to assess the certainty of the body of evidence for the most important outcomes. MAIN RESULTS: We included 20 randomised controlled trials with a total of 3100 participants; four trials recruited participants with chronic obstructive pulmonary disease; two trials recruited participants recovering from a stroke; seven trials recruited participants with an acute medical condition who were mainly older; and the remaining trials recruited participants with a mix of conditions. We assessed the majority of the included studies as at low risk of selection, detection, and attrition bias, and unclear for selective reporting and performance bias. For an older population, admission avoidance hospital at home probably makes little or no difference on mortality at six months' follow-up (risk ratio (RR) 0.88, 95% confidence interval (CI) 0.68 to 1.13; P = 0.30; I2 = 0%; 5 trials, 1502 participants; moderate-certainty evidence); little or no difference on the likelihood of being readmitted to hospital after discharge from hospital at home or inpatient care within 3 to 12 months' follow-up (RR 1.14, 95% CI 0.97 to 1.34; P = 0.11; I2 = 41%; 8 trials, 1757 participants; moderate-certainty evidence); and probably reduces the likelihood of living in residential care at six months' follow-up (RR 0.53, 95% CI 0.41 to 0.69; P < 0.001; I2 = 67%; 4 trials, 1271 participants; moderate-certainty evidence). Hospital at home probably results in little to no difference in patient's self-reported health status (2006 patients; moderate-certainty evidence). Satisfaction with health care received may be improved with admission avoidance hospital at home (1812 participants; low-certainty evidence); few studies reported the effect on caregivers. Hospital at home reduced the initial average hospital length of stay (2036 participants; low-certainty evidence), which ranged from 4.1 to 18.5 days in the hospital group and 1.2 to 5.1 days in the hospital at home group. Hospital at home length of stay ranged from an average of 3 to 20.7 days (hospital at home group only). Admission avoidance hospital at home probably reduces costs to the health service compared with hospital admission (2148 participants; moderate-certainty evidence), though by a range of different amounts and using different methods to cost resource use, and there is some evidence that it decreases overall societal costs to six months' follow-up. AUTHORS' CONCLUSIONS: Admission avoidance hospital at home, with the option of transfer to hospital, may provide an effective alternative to inpatient care for a select group of older people who have been referred for hospital admission. The intervention probably makes little or no difference to patient health outcomes; may improve satisfaction; probably reduces the likelihood of relocating to residential care; and probably decreases costs.

Early switch from intravenous to oral antibiotic therapy in patients with cancer who have low-risk neutropenic sepsis: the EASI-SWITCH RCT.

Background: Neutropenic sepsis is a common complication of systemic anticancer treatment. There is variation in practice in timing of switch to oral antibiotics after commencement of empirical intravenous antibiotic therapy. Objectives: To establish the clinical and cost effectiveness of early switch to oral antibiotics in patients with neutropenic sepsis at low risk of infective complications. Design: A randomised, multicentre, open-label, allocation concealed, non-inferiority trial to establish the clinical and cost effectiveness of early oral switch in comparison to standard care. Setting: Nineteen UK oncology centres. Participants: Patients aged 16 years and over receiving systemic anticancer therapy with fever (≥ 38°C), or symptoms and signs of sepsis, and neutropenia (≤ 1.0 × 109/l) within 24 hours of randomisation, with a Multinational Association for Supportive Care in Cancer score of ≥ 21 and receiving intravenous piperacillin/tazobactam or meropenem for < 24 hours were eligible. Patients with acute leukaemia or stem cell transplant were excluded. Intervention: Early switch to oral ciprofloxacin (750 mg twice daily) and co-amoxiclav (625 mg three times daily) within 12-24 hours of starting intravenous antibiotics to complete 5 days treatment in total. Control was standard care, that is, continuation of intravenous antibiotics for at least 48 hours with ongoing treatment at physician discretion. Main outcome measures: Treatment failure, a composite measure assessed at day 14 based on the following criteria: fever persistence or recurrence within 72 hours of starting intravenous antibiotics; escalation from protocolised antibiotics; critical care support or death. Results: The study was closed early due to under-recruitment with 129 patients recruited; hence, a definitive conclusion regarding non-inferiority cannot be made. Sixty-five patients were randomised to the early switch arm and 64 to the standard care arm with subsequent intention-to-treat and per-protocol analyses including 125 (intervention n = 61 and control n = 64) and 113 (intervention n = 53 and control n = 60) patients, respectively. In the intention-to-treat population the treatment failure rates were 14.1% in the control group and 24.6% in the intervention group, difference = 10.5% (95% confidence interval 0.11 to 0.22). In the per-protocol population the treatment failure rates were 13.3% and 17.7% in control and intervention groups, respectively; difference = 3.7% (95% confidence interval 0.04 to 0.148). Treatment failure predominantly consisted of persistence or recurrence of fever and/or physician-directed escalation from protocolised antibiotics with no critical care admissions or deaths. The median length of stay was shorter in the intervention group and adverse events reported were similar in both groups. Patients, particularly those with care-giving responsibilities, expressed a preference for early switch. However, differences in health-related quality of life and health resource use were small and not statistically significant. Conclusions: Non-inferiority for early oral switch could not be proven due to trial under-recruitment. The findings suggest this may be an acceptable treatment strategy for some patients who can adhere to such a treatment regimen and would prefer a potentially reduced duration of hospitalisation while accepting increased risk of treatment failure resulting in re-admission. Further research should explore tools for patient stratification for low-risk de-escalation or ambulatory pathways including use of biomarkers and/or point-of-care rapid microbiological testing as an adjunct to clinical decision-making tools. This could include application to shorter-duration antimicrobial therapy in line with other antimicrobial stewardship studies. Trial registration: This trial is registered as ISRCTN84288963. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 13/140/05) and is published in full in Health Technology Assessment; Vol. 28, No. 14. See the NIHR Funding and Awards website for further award information.

Neutropenic sepsis, or infection with a low white blood cell count, can occur following cancer treatment. Usually patients receive treatment with intravenous antibiotics (antibiotics delivered into a vein) for two or more days. Patients at low risk of complications from their infection may be able to have a shorter period of intravenous antibiotics benefitting both patients and the NHS. The trial compared whether changing from intravenous to oral antibiotics (antibiotics taken by mouth as tablets or liquid) 12­24 hours after starting antibiotic treatment ('early switch') is as effective as usual care. Patients could take part if they had started intravenous antibiotics for low-risk neutropenic sepsis. Patients were randomly allocated to 'early switch' or to usual care. The main outcome measured was treatment failure. Treatment failure happened if fever persisted or recurred despite antibiotics, if patients needed to change antibiotics, if they needed to be re-admitted to hospital or needed to be admitted to intensive care within 14 days or died. We had originally intended that 628 patients would take part, but after review of the design of the study the number needed to take part was revised to 230. We were not able to complete the trial as planned as unfortunately only 129 patients took part. As the trial was smaller than expected we were not able to draw conclusions as to whether 'early switch' is no less effective than usual care. Our findings suggest that 'early switch' might result in a shorter time in hospital initially; however, treatment failure was more likely to occur, meaning some patients had to return to hospital for further antibiotics. There were no differences in side effects and no serious complications from treatment or treatment failure (such as intensive care admission or death) among the 65 patients in the 'early switch' group. Patients were satisfied with 'early switch'. Early switch may be a treatment option for some patients with low-risk neutropenic sepsis who would prefer a shorter duration of hospital admission but accept a risk of needing hospital re-admission.

Protocol for the development of a tool (INSPECT-SR) to identify problematic randomised controlled trials in systematic reviews of health interventions.

INTRODUCTION: Randomised controlled trials (RCTs) inform healthcare decisions. It is now apparent that some published RCTs contain false data and some appear to have been entirely fabricated. Systematic reviews are performed to identify and synthesise all RCTs that have been conducted on a given topic. While it is usual to assess methodological features of the RCTs in the process of undertaking a systematic review, it is not usual to consider whether the RCTs contain false data. Studies containing false data therefore go unnoticed and contribute to systematic review conclusions. The INveStigating ProblEmatic Clinical Trials in Systematic Reviews (INSPECT-SR) project will develop a tool to assess the trustworthiness of RCTs in systematic reviews of healthcare-related interventions. METHODS AND ANALYSIS: The INSPECT-SR tool will be developed using expert consensus in combination with empirical evidence, over five stages: (1) a survey of experts to assemble a comprehensive list of checks for detecting problematic RCTs, (2) an evaluation of the feasibility and impact of applying the checks to systematic reviews, (3) a Delphi survey to determine which of the checks are supported by expert consensus, culminating in, (4) a consensus meeting to select checks to be included in a draft tool and to determine its format and (5) prospective testing of the draft tool in the production of new health systematic reviews, to allow refinement based on user feedback. We anticipate that the INSPECT-SR tool will help researchers to identify problematic studies and will help patients by protecting them from the influence of false data on their healthcare. ETHICS AND DISSEMINATION: The University of Manchester ethics decision tool was used, and this returned the result that ethical approval was not required for this project (30 September 2022), which incorporates secondary research and surveys of professionals about subjects relating to their expertise. Informed consent will be obtained from all survey participants. All results will be published as open-access articles. The final tool will be made freely available.

Using behavioral science to increase core outcome set use in trials.

OBJECTIVES: Core outcome sets (COS) are agreed sets of outcomes for use in clinical trials, which can increase standardization and reduce heterogeneity of outcomes in research. Using a COS, or not, is a behavior that can potentially be increased using behavioral strategies. The aim of this study was to identify behavioral intervention components to potentially increase use of COS in trials. METHODS: This project was informed by the Behavior Change Wheel framework. Two reviewers extracted barriers and facilitators to COS use from four recently published studies examining COS use in trials. Barriers and facilitators were coded to the Capability, Opportunity, Motivation-Behavior (COM-B) model, which forms part of the Behavior Change Wheel. COM-B findings were mapped to intervention functions by two reviewers, and then mapped to behavior change techniques (BCTs). Full-team Affordability, Practicability, Effectiveness/Cost-effectiveness, Acceptability, Side effects/Safety, Equity ratings were used to reach consensus on intervention functions and BCTs. BCTs were operationalized using examples of tangible potential applications and were categorized based on similarity. RESULTS: Barriers and facilitators were identified for all capability, opportunity and motivation aspects of the COM-B model. Five intervention functions (education, training, enablement, persuasion, and modeling) and 15 BCTs were identified. Thirty-six BCT examples were developed, including providing information on benefits of COS for health research, and information choosing COS. BCT examples are categorized by approaches related to "workshops," "guidance," "audio/visual resources," and "other resources." CONCLUSION: Study findings represent diverse ways to potentially increase COS use in trials. Future work is needed to examine effects of these behavioral intervention components on COS use. If effective, increased use of COS can improve outcome reporting and minimize outcome heterogeneity and research waste.

An international consensus study to identify "what" outcomes should be included in a core outcome set for endodontic treatments (COSET) for utilization in clinical practice and research.

BACKGROUND: Development of a standardized set of topic-specific outcomes known as a Core Outcome Set (COS) is important to address issues of heterogeneity in reporting research findings in order to streamline evidence synthesis and clinical decision making. AIM: The aim of the current international consensus study is to identify "what" outcomes to include in the Core Outcome Set for Endodontic Treatments (COSET). Outcomes of various endodontic treatments (non-surgical root canal treatment, surgical endodontics, vital pulp treatment and revitalization procedures) performed on permanent teeth were considered. METHODS: A standard validated methodology for COS development and reporting was adopted. The process involved identification of existing outcomes through four published scoping reviews. This enabled creation of a list of outcomes to be prioritized via semi-structured patient interviews, e-Delphi process and a consensus meeting with a range of relevant global stakeholders. Outcomes were prioritized using a 1-9 Likert scale, with outcomes rated 7-9 considered critical, 4-6 are important and 1-3 are less important. Outcomes rated 7-9 by ≥70% and 1-3 by <15% of participants were considered to achieve consensus for inclusion in the COS. The outcomes that did not achieve consensus in the first round were considered for further prioritization in the second Delphi round and consensus meeting. Final decisions about the outcomes to include in COSET were made by voting during the consensus panel meeting using the Zoom Poll function. RESULTS: A total of 95 participants including patients contributed to the COS development process. The consensus panel recommended, with strong consensus, eight outcomes shared across all treatment modalities for inclusion in COSET: pain; signs of infection (swelling, sinus tract); further intervention/exacerbation; tenderness to percussion/palpation; radiographic evidence of disease progression/healing; function; tooth survival; and patient satisfaction. Additional treatment specific outcomes were also recommended. DISCUSSION: Many of the outcomes included in COSET are patient reported. All should be included in future outcomes studies. CONCLUSION: COSET identified outcomes that are important for patients and clinicians and validated these using a rigorous methodology. Further work is ongoing to determine "how" and "when" these outcomes should be measured.

Methods proposed for monitoring the implementation of evidence-based research: a cross-sectional study.

OBJECTIVES: Evidence-based research (EBR) is the systematic and transparent use of prior research to inform a new study so that it answers questions that matter in a valid, efficient, and accessible manner. This study surveyed experts about existing (e.g., citation analysis) and new methods for monitoring EBR and collected ideas about implementing these methods. STUDY DESIGN AND SETTING: We conducted a cross-sectional study via an online survey between November 2022 and March 2023. Participants were experts from the fields of evidence synthesis and research methodology in health research. Open-ended questions were coded by recurring themes; descriptive statistics were used for quantitative questions. RESULTS: Twenty-eight expert participants suggested that citation analysis should be supplemented with content evaluation (not just what is cited but also in which context), content expert involvement, and assessment of the quality of cited systematic reviews. They also suggested that citation analysis could be facilitated with automation tools. They emphasized that EBR monitoring should be conducted by ethics committees and funding bodies before the research starts. Challenges identified for EBR implementation monitoring were resource constraints and clarity on responsibility for EBR monitoring. CONCLUSION: Ideas proposed in this study for monitoring the implementation of EBR can be used to refine methods and define responsibility but should be further explored in terms of feasibility and acceptability. Different methods may be needed to determine if the use of EBR is improving over time.

Exploring trial publication and research waste in COVID-19 randomised trials of hydroxychloroquine, corticosteroids, and vitamin D: a meta-epidemiological cohort study.

BACKGROUND: The global research response to the COVID-19 pandemic was impressive, but also led to an infodemic and considerable research waste. Registered, but unpublished trials added to this noise. We aimed to determine the proportion of registered randomised trials of common COVID-19 treatments that were published and to describe the characteristics of these trials to examine the association between trial characteristics, publication status and research waste. METHODS: This meta-epidemiological cohort study used a sample of randomised trials of corticosteroids, hydroxychloroquine or vitamin D as treatments for COVID-19, registered between 1 November 2019 and 31 December 2021 and available via the WHO ICTRP portal. We searched for the trials' published results up to 20 October 2022. We extracted the trial characteristics, analysing with descriptive statistics. We performed univariate logistic regression to examine the association between trials' characteristics and publication status, followed by multiple logistic regression using significant characteristics to assess the association between trial characteristics and publication status. RESULTS: We identified 357 eligible trials on ICTRP. Of these, 107 (30%) had published or made their results available publicly by 20 October 2022, while 250 (70%) had not been published or shared their results publicly. Multiple logistic regression analysis showed that a larger target sample size was a significant positive predictor of publication with target sample sizes above 300 almost tripling the odds of publication (aOR: 2.75, 95% CI: 1.35 to 5.62). CONCLUSIONS: Less than one third of registered trials made their results public and our findings identified that many trialists had not updated their trial registry entry with the trial status, results or both. Failure to share trial results publicly is a disservice to patients, clinicians and policy makers and adds to research waste.

Early switch to oral antibiotic therapy in patients with low-risk neutropenic sepsis (EASI-SWITCH): a randomized non-inferiority trial.

OBJECTIVES: To determine whether early switch to oral antibiotic treatment in adults with neutropenic sepsis at low risk of complications is non-inferior to switching later. METHODS: This non-inferiority, parallel-group, randomized, open-label clinical trial enrolled UK adults hospitalized with neutropenic sepsis. Participants were randomly assigned to either switch to oral ciprofloxacin plus co-amoxiclav within 12-24 hours or to continue intravenous treatment for at least 48 hours. The primary outcome was a composite measure of treatment failure, 14 days after randomization. The non-inferiority margin was 15%. RESULTS: There were 129 participants from 16 centres and 125 were assessed for the primary outcome. Of these, 113 patients completed protocolized treatment and comprised the per-protocol population. In total, 9 (14.1%) of 64 patients in the standard care arm met the primary end point, compared with 15 (24.6%) of 61 in the early switch arm, giving a risk difference of 10.5% (1-sided 95% CI, -∞% to 22%; p 0.14). In the per-protocol population, 8 (13.3%) of the 60 patients in the standard care arm met the primary end point, compared with 9 (17%) of 53 in the intervention arm giving a risk difference of 3.7% (one-sided 95% CI, -∞% to 14.8%; p 0.59). Duration of hospital stay was shorter in the intervention arm (median 2 [inter-quartile range (IQR) 2-3] vs. 3 days [IQR 2-4]; p 0.002). DISCUSSION: Although non-inferiority of early oral switch was found in the per-protocol population, the intervention was not non-inferior in the intent-to-treat population.

Impact of Vision Impairment and Ocular Morbidity and Their Treatment on Quality of Life in Children: A Systematic Review.

TOPIC: This review summarizes existing evidence of the impact of vision impairment and ocular morbidity and their treatment on children's quality of life (QoL). CLINICAL RELEVANCE: Myopia and strabismus are associated with reduced QoL among children. Surgical treatment of strabismus significantly improves affected children's QoL. METHODS: We conducted a systematic review and meta-analysis by screening articles in any language in 9 databases published from inception through August 22, 2022, addressing the impact of vision impairment, ocular morbidity, and their treatment on QoL in children. We reported pooled standardized mean differences (SMDs) using random-effects meta-analysis models. Quality appraisal was performed using Joanna Briggs Institute and National Institutes of Health tools. This study was registered with the International Prospective Register of Systematic Reviews (identifier, CRD42021233323). RESULTS: Our search identified 29 118 articles, 44 studies (0.15%) of which were included for analysis that included 32 318 participants from 14 countries between 2005 and 2022. Seventeen observational and 4 interventional studies concerned vision impairment, whereas 10 observational and 13 interventional studies described strabismus and other ocular morbidities. Twenty-one studies were included in the meta-analysis. The QoL scores did not differ between children with and without vision impairment (SMD, -1.04; 95% confidence interval [CI], -2.11 to 0.03; P = 0.06; 9 studies). Myopic children demonstrated significantly lower QoL scores than those with normal vision (SMD, -0.60; 95% CI, -1.09 to -0.11; P = 0.02; 7 studies). Children with strabismus showed a significantly lower QoL score compared with those without (SMD, -1.19; 95% CI, -1.66 to -0.73; P < 0.001; 7 studies). Strabismus surgery significantly improved QoL in children (SMD, 1.36; 95% CI, 0.48-2.23; P < 0.001; 7 studies). No randomized controlled trials (RCTs) concerning refractive error and QoL were identified. Among all included studies, 35 (79.5%) were scored as low to moderate quality; the remaining met all quality appraisal tools criteria. DISCUSSION: Reduced QoL was identified in children with myopia and strabismus. Surgical correction of strabismus improves the QoL of affected children, which supports insurance coverage of strabismus surgery. Further studies, especially RCTs, investigating the impact of correction of myopia on QoL are needed. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Correction: Guidelines, Consensus Statements, and Standards for the Use of Artificial Intelligence in Medicine: Systematic Review.

[This corrects the article DOI: 10.2196/46089.].

Methods to increase response to postal and electronic questionnaires.

BACKGROUND: Self-administered questionnaires are widely used to collect data in epidemiological research, but non-response reduces the effective sample size and can introduce bias. Finding ways to increase response to postal and electronic questionnaires would improve the quality of epidemiological research. OBJECTIVES: To identify effective strategies to increase response to postal and electronic questionnaires. SEARCH METHODS: We searched 14 electronic databases up to December 2021 and manually searched the reference lists of relevant trials and reviews. We contacted the authors of all trials or reviews to ask about unpublished trials; where necessary, we also contacted authors to confirm the methods of allocation used and to clarify results presented. SELECTION CRITERIA: Randomised trials of methods to increase response to postal or electronic questionnaires. We assessed the eligibility of each trial using pre-defined criteria. DATA COLLECTION AND ANALYSIS: We extracted data on the trial participants, the intervention, the number randomised to intervention and comparison groups and allocation concealment. For each strategy, we estimated pooled odds ratios (OR) and 95% confidence intervals (CI) in a random-effects model. We assessed evidence for selection bias using Egger's weighted regression method and Begg's rank correlation test and funnel plot. We assessed heterogeneity amongst trial odds ratios using a Chi2 test and quantified the degree of inconsistency between trial results using the I2 statistic. MAIN RESULTS: Postal We found 670 eligible trials that evaluated over 100 different strategies of increasing response to postal questionnaires. We found substantial heterogeneity amongst trial results in half of the strategies. The odds of response almost doubled when: using monetary incentives (odds ratio (OR) 1.86; 95% confidence interval (CI) 1.73 to 1.99; heterogeneity I2 = 85%); using a telephone reminder (OR 1.96; 95% CI 1.03 to 3.74); and when clinical outcome questions were placed last (OR 2.05; 95% CI 1.00 to 4.24). The odds of response increased by about half when: using a shorter questionnaire (OR 1.58; 95% CI 1.40 to 1.78); contacting participants before sending questionnaires (OR 1.36; 95% CI 1.23 to 1.51; I2 = 87%); incentives were given with questionnaires (i.e. unconditional) rather than when given only after participants had returned their questionnaire (i.e. conditional on response) (OR 1.53; 95% CI 1.35 to 1.74); using personalised SMS reminders (OR 1.53; 95% CI 0.97 to 2.42); using a special (recorded) delivery service (OR 1.68; 95% CI 1.36 to 2.08; I2 = 87%); using electronic reminders (OR 1.60; 95% CI 1.10 to 2.33); using intensive follow-up (OR 1.69; 95% CI 0.93 to 3.06); using a more interesting/salient questionnaire (OR 1.73; 95% CI 1.12 to 2.66); and when mentioning an obligation to respond (OR 1.61; 95% CI 1.16 to 2.22). The odds of response also increased with: non-monetary incentives (OR 1.16; 95% CI 1.11 to 1.21; I2 = 80%); a larger monetary incentive (OR 1.24; 95% CI 1.15 to 1.33); a larger non-monetary incentive (OR 1.15; 95% CI 1.00 to 1.33); when a pen was included (OR 1.44; 95% CI 1.38 to 1.50); using personalised materials (OR 1.15; 95% CI 1.09 to 1.21; I2 = 57%); using a single-sided rather than a double-sided questionnaire (OR 1.13; 95% CI 1.02 to 1.25); using stamped return envelopes rather than franked return envelopes (OR 1.23; 95% CI 1.13 to 1.33; I2 = 69%), assuring confidentiality (OR 1.33; 95% CI 1.24 to 1.42); using first-class outward mailing (OR 1.11; 95% CI 1.02 to 1.21); and when questionnaires originated from a university (OR 1.32; 95% CI 1.13 to 1.54). The odds of response were reduced when the questionnaire included questions of a sensitive nature (OR 0.94; 95% CI 0.88 to 1.00). Electronic We found 88 eligible trials that evaluated over 30 different ways of increasing response to electronic questionnaires. We found substantial heterogeneity amongst trial results in half of the strategies. The odds of response tripled when: using a brief letter rather than a detailed letter (OR 3.26; 95% CI 1.79 to 5.94); and when a picture was included in an email (OR 3.05; 95% CI 1.84 to 5.06; I2 = 19%). The odds of response almost doubled when: using monetary incentives (OR 1.88; 95% CI 1.31 to 2.71; I2 = 79%); and using a more interesting topic (OR 1.85; 95% CI 1.52 to 2.26). The odds of response increased by half when: using non-monetary incentives (OR 1.60; 95% CI 1.25 to 2.05); using shorter e-questionnaires (OR 1.51; 95% CI 1.06 to 2.16; I2 = 94%); and using a more interesting e-questionnaire (OR 1.85; 95% CI 1.52 to 2.26). The odds of response increased by a third when: offering survey results as an incentive (OR 1.36; 95% CI 1.16 to 1.59); using a white background (OR 1.31; 95% CI 1.10 to 1.56); and when stressing the benefits to society of response (OR 1.38; 95% CI 1.07 to 1.78; I2 = 41%). The odds of response also increased with: personalised e-questionnaires (OR 1.24; 95% CI 1.17 to 1.32; I2 = 41%); using a simple header (OR 1.23; 95% CI 1.03 to 1.48); giving a deadline (OR 1.18; 95% CI 1.03 to 1.34); and by giving a longer time estimate for completion (OR 1.25; 95% CI 0.96 to 1.64). The odds of response were reduced when: "Survey" was mentioned in the e-mail subject (OR 0.81; 95% CI 0.67 to 0.97); when the email or the e-questionnaire was from a male investigator, or it included a male signature (OR 0.55; 95% CI 0.38 to 0.80); and by using university sponsorship (OR 0.84; 95%CI 0.69 to 1.01). The odds of response using a postal questionnaire were over twice those using an e-questionnaire (OR 2.33; 95% CI 2.25 to 2.42; I2 = 98%). Response also increased when: providing a choice of response mode (electronic or postal) rather than electronic only (OR 1.76 95% CI 1.67 to 1.85; I2 = 97%); and when administering the e-questionnaire by computer rather than by smartphone (OR 1.62 95% CI 1.36 to 1.94). AUTHORS' CONCLUSIONS: Researchers using postal and electronic questionnaires can increase response using the strategies shown to be effective in this Cochrane review.

Delivery of a novel intervention to facilitate liberation from mechanical ventilation in paediatric intensive care: A process evaluation.

BACKGROUND: Prolonged mechanical ventilation increases the risk of mortality and morbidity. Optimising sedation and early testing for possible liberation from invasive mechanical ventilation (IMV) has been shown to reduce time on the ventilator. Alongside a multicentre trial of sedation and ventilation weaning, we conducted a mixed method process evaluation to understand how the intervention content and delivery was linked to trial outcomes. METHODS: 10,495 children admitted to 18 paediatric intensive care units (ICUs) in the United Kingdom participated in a stepped-wedge, cluster randomised controlled trial, with 1955 clinical staff trained to deliver the intervention. The intervention comprised assessment and optimisation of sedation levels, and bedside screening of respiratory parameters to indicate readiness for a spontaneous breathing trial prior to liberation from ventilation. 193 clinical staff were interviewed towards the end of the trial. Interview data were thematically analysed, and quantitative adherence data were analysed using descriptive statistics. RESULTS: The intervention led to a reduced duration of IMV (adjusted median difference- 7.1 hours, 95% CI -9.6 to -5.3, p = 0.01). Overall intervention adherence was 75% (range 59-85%). Ease and flexibility of the intervention promoted it use; designated responsibilities, explicit pathways of decision-making and a shared language for communication fostered proactivity and consistency towards extubation. Delivery of the intervention was hindered by established hospital and unit organisational and patient care routines, clinician preference and absence of clinical leadership. CONCLUSIONS: The SANDWICH trial showed a significant, although small, reduction in duration of IMV. Findings suggest that greater direction in decision-making pathways, robust embedment of new practice in unit routine, and capitalising on the skills of Advanced Nurse Practitioners and physiotherapists would have contributed to greater intervention effect. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN16998143.

Guidelines, Consensus Statements, and Standards for the Use of Artificial Intelligence in Medicine: Systematic Review.

BACKGROUND: The application of artificial intelligence (AI) in the delivery of health care is a promising area, and guidelines, consensus statements, and standards on AI regarding various topics have been developed. OBJECTIVE: We performed this study to assess the quality of guidelines, consensus statements, and standards in the field of AI for medicine and to provide a foundation for recommendations about the future development of AI guidelines. METHODS: We searched 7 electronic databases from database establishment to April 6, 2022, and screened articles involving AI guidelines, consensus statements, and standards for eligibility. The AGREE II (Appraisal of Guidelines for Research & Evaluation II) and RIGHT (Reporting Items for Practice Guidelines in Healthcare) tools were used to assess the methodological and reporting quality of the included articles. RESULTS: This systematic review included 19 guideline articles, 14 consensus statement articles, and 3 standard articles published between 2019 and 2022. Their content involved disease screening, diagnosis, and treatment; AI intervention trial reporting; AI imaging development and collaboration; AI data application; and AI ethics governance and applications. Our quality assessment revealed that the average overall AGREE II score was 4.0 (range 2.2-5.5; 7-point Likert scale) and the mean overall reporting rate of the RIGHT tool was 49.4% (range 25.7%-77.1%). CONCLUSIONS: The results indicated important differences in the quality of different AI guidelines, consensus statements, and standards. We made recommendations for improving their methodological and reporting quality. TRIAL REGISTRATION: PROSPERO International Prospective Register of Systematic Reviews (CRD42022321360); https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=321360.

Protocol for the development of a tool (INSPECT-SR) to identify problematic randomised controlled trials in systematic reviews of health interventions.

Introduction: Randomised controlled trials (RCTs) inform healthcare decisions. It is now apparent that some published RCTs contain false data and some appear to have been entirely fabricated. Systematic reviews are performed to identify and synthesise all RCTs that have been conducted on a given topic. While it is usual to assess methodological features of the RCTs in the process of undertaking a systematic review, it is not usual to consider whether the RCTs contain false data. Studies containing false data therefore go unnoticed and contribute to systematic review conclusions. The INSPECT-SR project will develop a tool to assess the trustworthiness of RCTs in systematic reviews of healthcare related interventions. Methods and analysis: The INSPECT-SR tool will be developed using expert consensus in combination with empirical evidence, over five stages: 1) a survey of experts to assemble a comprehensive list of checks for detecting problematic RCTs, 2) an evaluation of the feasibility and impact of applying the checks to systematic reviews, 3) a Delphi survey to determine which of the checks are supported by expert consensus, culminating in 4) a consensus meeting to select checks to be included in a draft tool and to determine its format, 5) prospective testing of the draft tool in the production of new health systematic reviews, to allow refinement based on user feedback. We anticipate that the INSPECT-SR tool will help researchers to identify problematic studies, and will help patients by protecting them from the influence of false data on their healthcare.

Clinical trials of pneumonia management assess heterogeneous outcomes and measurement instruments.

OBJECTIVES: To inform clinical practice guidelines, randomized controlled trials (RCTs) of the management of pneumonia need to address the outcomes that are most important to patients and health professionals using consistent instruments, to enable results to be compared, contrasted, and combined as appropriate. This systematic review describes the outcomes reported in clinical trials of pneumonia management and the instruments used to measure these outcomes. STUDY DESIGN AND SETTING: Based on a prospective protocol, we searched MEDLINE/PubMed, Cochrane CENTRAL and clinical trial registries for ongoing or completed clinical trials evaluating pneumonia management in adults in any clinical setting. We grouped reported outcomes thematically and classified them following the COMET Initiative's taxonomy. We describe instruments used for assessing each outcome. RESULTS: We found 280 eligible RCTs of which 115 (41.1%) enrolled critically ill patients and 165 (58.9%) predominantly noncritically ill patients. We identified 43 distinct outcomes and 108 measurement instruments, excluding nonvalidated scores and questionnaires. Almost all trials reported clinical/physiological outcomes (97.5%). Safety (63.2%), mortality (56.4%), resource use (48.6%) and life impact (11.8%) outcomes were less frequently addressed. The most frequently reported outcomes were treatment success (60.7%), mortality (56.4%) and adverse events (41.1%). There was significant variation in the selection of measurement instruments, with approximately two-thirds used in less than 10 of the 280 RCTs. None of the patient-reported outcomes were used in 10 or more RCTs. CONCLUSION: This review reveals significant variation in outcomes and measurement instruments reported in clinical trials of pneumonia management. Outcomes that are important to patients and health professionals are often omitted. Our findings support the need for a rigorous core outcome set, such as that being developed by the European Respiratory Society.

School-based relationship and sexuality education intervention engaging adolescent boys for the reductions of teenage pregnancy: the JACK cluster RCT.

Background: The need to engage boys in gender-transformative relationships and sexuality education (RSE) to reduce adolescent pregnancy is endorsed by the World Health Organization and the United Nations Educational, Scientific and Cultural Organization. Objectives: To evaluate the effects of If I Were Jack on the avoidance of unprotected sex and other sexual health outcomes. Design: A cluster randomised trial, incorporating health economics and process evaluations. Setting: Sixty-six schools across the four nations of the UK. Participants: Students aged 13-14 years. Intervention: A school-based, teacher-delivered, gender-transformative RSE intervention (If I Were Jack) versus standard RSE. Main outcome measures: Self-reported avoidance of unprotected sex (sexual abstinence or reliable contraceptive use at last sex) after 12-14 months. Secondary outcomes included knowledge, attitudes, skills, intentions and sexual behaviours. Results: The analysis population comprised 6556 students: 86.6% of students in the intervention group avoided unprotected sex, compared with 86.4% in the control group {adjusted odds ratio 0.85 [95% confidence interval (CI) 0.58 to 1.26], p = 0.42}. An exploratory post hoc analysis showed no difference for sexual abstinence [78.30% intervention group vs. 78.25% control group; adjusted odds ratio 0.85 (95% CI 0.58 to 1.24), p = 0.39], but more intervention group students than control group students used reliable contraception at last sex [39.62% vs. 26.36%; adjusted odds ratio 0.52 (95% CI 0.29 to 0.920), p = 0.025]. Students in schools allocated to receive the intervention had significantly higher scores on knowledge [adjusted mean difference 0.18 (95% CI 0.024 to 0.34), p = 0.02], gender-equitable attitudes and intentions to avoid unintended pregnancy [adjusted mean difference 0.61 (95% CI 0.16 to 1.07), p = 0.01] than students in schools allocated to receive the control. There were positive but non-significant differences in sexual self-efficacy and communication skills. The total mean incremental cost of the intervention compared with standard RSE was £2.83 (95% CI -£2.64 to £8.29) per student. Over a 20-year time horizon, the intervention is likely to be cost-effective owing to its impact on unprotected sex because it would result in 379 (95% CI 231 to 477) fewer unintended pregnancies, 680 (95% CI 189 to 1467) fewer sexually transmitted infections and a gain of 10 (95% CI 5 to 16) quality-adjusted life-years per 100,000 students for a cost saving of £9.89 (95% CI -£15.60 to -£3.83). Limitations: The trial is underpowered to detect some effects because four schools withdrew and the intraclass correlation coefficient (0.12) was larger than that in sample size calculation (0.01). Conclusions: We present, to our knowledge, the first evidence from a randomised trial that a school-based, male engagement gender-transformative RSE intervention, although not effective in increasing avoidance of unprotected sex (defined as sexual abstinence or use of reliable contraception at last sex) among all students, did increase the use of reliable contraception at last sex among students who were, or became, sexually active by 12-14 months after the intervention. The trial demonstrated that engaging all adolescents early through RSE is important so that, as they become sexually active, rates of unprotected sex are reduced, and that doing so is likely to be cost-effective. Future work: Future studies should consider the longer-term effects of gender-transformative RSE as students become sexually active. Gender-transformative RSE could be adapted to address broader sexual health and other settings. Trial registration: This trial is registered as ISRCTN10751359. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Public Health Research programme (PHR 15/181/01) and will be published in full in Public Health Research; Vol. 11, No. 8. See the NIHR Journals Library website for further project information.

Adolescent pregnancy is often thought to be an issue for young women alone, but it is important to engage young men to tackle the problem and find solutions. The If I Were Jack intervention was especially designed to engage with boys as well as girls aged 14 years and to promote positive masculinity and gender equality to prevent adolescent pregnancy and promote positive sexual health. It uses tailored interactive films and resources, made with the help of students and teachers, to make it relevant to each of the four UK nations. This relationship and sexuality education intervention encourages adolescents to avoid unprotected sex by delaying sexual activity until they feel ready and to use reliable contraception once sexually active. It also promotes knowledge, attitudes (such as beliefs about gender and masculinities), skills and intentions for safe and pleasurable relationships. In this trial, we compared students in 33 schools randomly allocated to deliver the intervention with students in 33 schools that continued with their usual relationship and sexuality education practices. Four schools withdrew, two because of COVID-19 school closures. This left a total of 6556 students who completed questionnaires at the start of the study and 12­14 months later. Responses from all these students showed that If I Were Jack had a positive impact on knowledge, attitudes and intentions required for safe and pleasurable relationships, but did not have a significant effect on overall avoidance of unprotected sex. This was because the intervention had no effect on delaying sexual activity. However, we found that the intervention was effective in increasing the use of reliable contraception as students became sexually active, as well as for those who already were sexually active prior to receiving the intervention. We also found that If I Were Jack was likely to provide value for money by reducing unintended pregnancies and improving sexual health.