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Summary: Background: Infectious keratitis (IK) is the leading cause of corneal blindness globally. Deep learning (DL) is an emerging tool for medical diagnosis, though its value in IK is unclear. We aimed to assess the diagnostic accuracy of DL for IK and its comparative accuracy with ophthalmologists. Methods: In this systematic review and meta-analysis, we searched EMBASE, MEDLINE, and clinical registries for studies related to DL for IK published between 1974 and July 16, 2024. We performed meta-analyses using bivariate models to estimate summary sensitivities and specificities. This systematic review was registered with PROSPERO (CRD42022348596). Findings: Of 963 studies identified, 35 studies (136,401 corneal images from >56,011 patients) were included. Most studies had low risk of bias (68.6%) and low applicability concern (91.4%) in all domains of QUADAS-2, except the index test domain. Against the reference standard of expert consensus and/or microbiological results (seven external validation studies; 10,675 images), the summary estimates (95% CI) for sensitivity and specificity of DL for IK were 86.2% (71.6–93.9) and 96.3% (91.5–98.5). From 28 internal validation studies (16,059 images), summary estimates for sensitivity and specificity were 91.6% (86.8–94.8) and 90.7% (84.8–94.5). Based on seven studies (4007 images), DL and ophthalmologists had comparable summary sensitivity [89.2% (82.2–93.6) versus 82.2% (71.5–89.5); P = 0.20] and specificity [(93.2% (85.5–97.0) versus 89.6% (78.8–95.2); P = 0.45]. Interpretation: DL models may have good diagnostic accuracy for IK and comparable performance to ophthalmologists. These findings should be interpreted with caution due to the image-based analysis that did not account for potential correlation within individuals, relatively homogeneous population studies, lack of pre-specification of DL thresholds, and limited external validation. Future studies should improve their reporting, data diversity, external validation, transparency, and explainability to increase the reliability and generalisability of DL models for clinical deployment. Funding: NIH, Wellcome Trust, MRC, Fight for Sight, BHP, and ESCRS.

Abstract Equity and health equity are fundamental pillars in fostering a just and inclusive society. While equity underscores fairness in resource allocation and opportunity, health equity aims to eradicate avoidable health disparities among social groups. The concept of harms in interventions—undesirable consequences associated with the use of interventions—often varies across populations due to biological and social factors, necessitating a nuanced understanding. An equity lens reveals disparities in harm distribution, urging researchers and policymakers to address these differences in their decision-making processes. Furthermore, interventions, even well-intentioned ones, can inadvertently exacerbate disparities, emphasizing the need for comprehensive harm assessment. Integrating equity considerations in research practices and trial methodologies, through study design or through practices such as inclusive participant recruitment, is pivotal in advancing health equity. By prioritizing interventions that address disparities and ensuring inclusivity in research, we can foster a more equitable healthcare system.

Objective This umbrella review synthesises evidence on the methods used to recruit and retain ethnically diverse participants and report and analyse variables related to ethnic diversity in randomised controlled trials.Design Umbrella review.Data sources Ovid MEDLINE, Ovid Embase, CINAHL, PsycINFO and Cochrane and Campbell Libraries for review papers published between 1 January 2010 and 13 May 2024.Eligibility criteria English language systematic reviews focusing on inclusion and reporting of ethnicity variables. Methodological quality was assessed using the AMSTAR 2 tool.Results Sixty-two systematic reviews were included. Findings point to limited representation and reporting of ethnic diversity in trials. Recruitment strategies commonly reported by the reviews were community engagement, advertisement, face-to-face recruitment, cultural targeting, clinical referral, community presentation, use of technology, incentives and research partnership with communities. Retention strategies highlighted by the reviews included frequent follow-ups on participants to check how they are doing in the study, provision of incentives, use of tailored approaches and culturally appropriate interventions. The findings point to a limited focus on the analysis of variables relevant to ethnic diversity in trials even when they are reported in trials.Conclusion Significant improvements are required in enhancing the recruitment and retention of ethnically diverse participants in trials as well as analysis and reporting of variables relating to diversity in clinical trials.PROSPERO registration number CRD42022325241.

Abstract Background Dry eye is one of the most common ophthalmic conditions and can significantly impact quality of life. Meibomian gland dysfunction (MGD) is a major cause of evaporative dry eye. We sought to conduct a systematic review and meta-analysis to estimate the prevalence and incidence of dry eye and MGD in Central and South America and to identify factors associated with disease burden. Methods Data sources Ovid MEDLINE and Embase. Study selection A search conducted on August 16, 2021, identified studies published between January 1, 2010, and August 16, 2021, with no restrictions regarding participant age or language of publication. Case reports, case series, case–control studies, and interventional studies were excluded. Data extraction and synthesis The review was based on a protocol registered on PROSPERO (CRD42021256934). Risk of bias was assessed in duplicate using a risk of bias tool designed for the purposes of descriptive epidemiological studies. Data were extracted by one investigator and verified by another for accuracy. Prevalence of dry eye and MGD were grouped based on study participant characteristics. Main outcomes and measures Prevalence and incidence of dry eye and MGD in Central and South America. Summary estimates from meta-analysis with 95% confidence intervals (CI). Results Fourteen studies (11,594 total participants) were included. The population prevalence of dry eye was 13% (95% CI, 12%-14%) in Brazil and 41% (95% CI, 39%-44%) in Mexico based on one study each. Meta-analyses suggested that dry eye prevalence was 70% among indoor workers (95% CI, 56%-80%; I 2 , 82%; 3 studies), 71% among students (95% CI, 65%-77%; I 2 , 92%; 3 studies), and 83% in general ophthalmology clinics (95% CI, 77%-88%; I 2 , 88%; 2 studies). MGD prevalence ranged from 23% among indoor workers (95% CI, 16%-31%; 1 study) to 68% in general ophthalmology clinics (95% CI, 62%-72%; 1 study). No studies reported incidence of dry eye or MGD. Conclusions This systematic review and meta-analysis demonstrated considerable variation in the published prevalence of dry eye and MGD among the general population and subpopulations in Central and South America. Local and subpopulation estimates of dry eye disease burden may be valuable to assist needs assessments and implementation of measures to mitigate the condition.

Aim To describe the pattern of the prevalence of mental health problems during the first year of the COVID-19 pandemic and examine the impact of containment measures on these trends.Methods We identified articles published until 30 August 2021 that reported the prevalence of mental health problems in the general population at two or more time points. A crowd of 114 reviewers extracted data on prevalence, study and participant characteristics. We collected information on the number of days since the first SARS-CoV-2 infection in the study country, the stringency of containment measures and the number of cases and deaths. We synthesised changes in prevalence during the pandemic using a random-effects model. We used dose-response meta-analysis to evaluate the trajectory of the changes in mental health problems.Results We included 41 studies for 7 mental health conditions. The average odds of symptoms increased during the pandemic (mean OR ranging from 1.23 to 2.08). Heterogeneity was very large and could not be explained by differences in participants or study characteristics. Average odds of psychological distress, depression and anxiety increased during the first 2 months of the pandemic, with increased stringency of the measures, reported infections and deaths. The confidence in the evidence was low to very low.Conclusions We observed an initial increase in the average risk of psychological distress, depression-related and anxiety-related problems during the first 2 months of the pandemic. However, large heterogeneity suggests that different populations had different responses to the challenges imposed by the pandemic.

Abstract Background Prolonged facemask wearing may have negatively affected essential workers with dry eye. We conducted a mixed-methods study to examine and understand the associations of the ocular surface, periocular environment, and dry eye-related symptoms among hospital workers across the job spectrum with prolonged facemask use. Methods We recruited clinical and non-clinical hospital workers with self-reported symptoms of dry eye and prolonged facemask use. We measured symptoms using the 5-item Dry Eye Questionnaire and the Ocular Surface Disease Index (OSDI). Objective ocular signs included corneal and conjunctival staining, fluorescein tear break up time (TBUT), meibography, tear film interferometry, and periocular humidity. We compared symptoms and signs across levels of periocular humidity, dry eye severity, facemask type, and job type. Participants with moderate or severe dry eye symptoms (OSDI > = 23) were invited for a semi-structured, one-on-one interview. Results We enrolled 20 clinical and 21 non-clinical hospital workers: 27% were 40 years or older, 76% were female, 29% reported a race other than White, and 20% were Hispanic. Seventeen individuals participated in the semi-structured interviews. From the quantitative analyses, we found that 90% of participants reported worsened severity of dry eye at work due to facemasks. Although wearing facemasks resulted in higher periocular humidity levels compared with not wearing facemasks, 66% participants reported increased airflow over their eyes. Findings from the qualitative interviews supported the finding that use of facemasks worsened dry eye symptoms, especially when facemasks were not fitted around the nose. The data did not suggest that non-clinical hospital workers experienced a greater impact of dry eye than clinical workers. Conclusions Healthcare providers and patients with dry eye should be educated about the discomfort and the ocular surface health risks associated with inadequately fitted facemasks. Wearing a fitted facemask with a pliable nose wire appears to mitigate the upward airflow.

Global warming and urban heat island effects negatively impact the development of urban thermal environments, making them very uncomfortable to live in. Green space plays an essential role in controlling and improving air pollution, regulating the microclimate, and enforcing compliance with public health requirements. Therefore, this study explored the relationship between green space and thermal comfort in the historical neighborhood of Dazhalan in Beijing through questionnaires, observational interviews, and numerical simulations. The current situation of the microclimate environment in the green space of the block was observed first. Then, the microclimate environment was simulated by the ENVI-met 5.6 software. The thermal comfort of the three types of space, such as enclosed space, strip space, and corner space, was also evaluated to explore the coupling relationship between different green space elements and microclimate evaluation factors. It was found that the thermal comfort PET had a positive correlation with the sky openness SVF. The green space morphology was quantitatively measured, and it was found that the thermal comfort PET had a negative correlation with the three-dimensional green quantity of green space. The paper developed managing strategies for optimizing the layout and construction mode of the green space. The ultimate goal was to rationally match the greening planting, improve the pavement of the underlying surface of the block, and optimize the design of the internal space topography.

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.

Abstract In this commentary, we discuss ChatGPT and our perspectives on its utility to systematic reviews (SRs) through the appropriateness and applicability of its responses to SR related prompts. The advancement of artificial intelligence (AI)-assisted technologies leave many wondering about the current capabilities, limitations, and opportunities for integration AI into scientific endeavors. Large language models (LLM)—such as ChatGPT, designed by OpenAI—have recently gained widespread attention with their ability to respond to various prompts in a natural-sounding way. Systematic reviews (SRs) utilize secondary data and often require many months and substantial financial resources to complete, making them attractive grounds for developing AI-assistive technologies. On February 6, 2023, PICO Portal developers hosted a webinar to explore ChatGPT’s responses to tasks related to SR methodology. Our experience from exploring the responses of ChatGPT suggest that while ChatGPT and LLMs show some promise for aiding in SR-related tasks, the technology is in its infancy and needs much development for such applications. Furthermore, we advise that great caution should be taken by non-content experts in using these tools due to much of the output appearing, at a high level, to be valid, while much is erroneous and in need of active vetting.

Abstract Guidance for systematic reviews of interventions recommends both benefits and harms be included. Systematic reviews may reach conclusions about harms (or lack of harms) that are not true when reviews include only some relevant studies, rely on incomplete data from eligible studies, use inappropriate methods for synthesizing data, and report results selectively. Separate reviews about harms could address some of these problems, and we argue that conducting separate reviews of harms is a feasible alternative to current standards and practices. Systematic reviews of potential benefits could be organized around the use of interventions for specific health problems. Systematic reviews of potential harms could be broader, including more diverse study designs and including all people at risk of harms (who might use the same intervention to treat different health problems). Multiple reviews about benefits could refer to a single review of harms. This approach could improve the reliability, completeness, and efficiency of systematic reviews.

Objective There is no standard tool for assessing risk of bias (RoB) in prevalence studies. For the purposes of a living systematic review during the COVID-19 pandemic, we developed a tool to evaluate RoB in studies measuring the prevalence of mental health disorders (RoB-PrevMH) and tested inter-rater reliability.Methods We decided on items and signalling questions to include in RoB-PrevMH through iterative discussions. We tested the reliability of assessments by different users with two sets of prevalence studies. The first set included a random sample of 50 studies from our living systematic review. The second set included 33 studies from a systematic review of the prevalence of post-traumatic stress disorders, major depression and generalised anxiety disorder. We assessed the inter-rater agreement by calculating the proportion of agreement and Kappa statistic for each item.Results RoB-PrevMH consists of three items that address selection bias and information bias. Introductory and signalling questions guide the application of the tool to the review question. The inter-rater agreement for the three items was 83%, 90% and 93%. The weighted kappa scores were 0.63 (95% CI 0.54 to 0.73), 0.71 (95% CI 0.67 to 0.85) and 0.32 (95% CI −0.04 to 0.63), respectively.Conclusions RoB-PrevMH is a brief, user-friendly and adaptable tool for assessing RoB in studies on prevalence of mental health disorders. Initial results for inter-rater agreement were fair to substantial. The tool’s validity, reliability and applicability should be assessed in future projects.

A declaração dos Principais Itens para Relatar Revisões Sistemáticas e Meta-análises (PRISMA), publicada em 2009, foi desenvolvida para ajudar revisores sistemáticos a relatar de forma transparente por que a revisão foi feita, os métodos empregados e o que os autores encontraram. Na última década, os avanços na metodologia e terminologia de revisões sistemáticas exigiram a atualização da diretriz. A declaração PRISMA 2020 substitui a declaração de 2009 e inclui novas orientações para relato que refletem os avanços nos métodos para identificar, selecionar, avaliar e sintetizar estudos. A estrutura e apresentação dos itens foram modificadas para facilitar a implementação. Neste artigo, apresentamos a lista de checagem PRISMA 2020 de 27 itens, uma lista de checagem expandida que detalha as recomendações para relato para cada item, a lista de checagem PRISMA 2020 para resumos e os fluxogramas revisados para novas revisões e para atualização de revisões.

Introduction Infectious keratitis (IK) represents the fifth-leading cause of blindness worldwide. A delay in diagnosis is often a major factor in progression to irreversible visual impairment and/or blindness from IK. The diagnostic challenge is further compounded by low microbiological culture yield, long turnaround time, poorly differentiated clinical features and polymicrobial infections. In recent years, deep learning (DL), a subfield of artificial intelligence, has rapidly emerged as a promising tool in assisting automated medical diagnosis, clinical triage and decision-making, and improving workflow efficiency in healthcare services. Recent studies have demonstrated the potential of using DL in assisting the diagnosis of IK, though the accuracy remains to be elucidated. This systematic review and meta-analysis aims to critically examine and compare the performance of various DL models with clinical experts and/or microbiological results (the current ‘gold standard’) in diagnosing IK, with an aim to inform practice on the clinical applicability and deployment of DL-assisted diagnostic models.Methods and analysis This review will consider studies that included application of any DL models to diagnose patients with suspected IK, encompassing bacterial, fungal, protozoal and/or viral origins. We will search various electronic databases, including EMBASE and MEDLINE, and trial registries. There will be no restriction to the language and publication date. Two independent reviewers will assess the titles, abstracts and full-text articles. Extracted data will include details of each primary studies, including title, year of publication, authors, types of DL models used, populations, sample size, decision threshold and diagnostic performance. We will perform meta-analyses for the included primary studies when there are sufficient similarities in outcome reporting.Ethics and dissemination No ethical approval is required for this systematic review. We plan to disseminate our findings via presentation/publication in a peer-reviewed journal.PROSPERO registration number CRD42022348596.

BackgroundPremature ductus arteriosus constriction (DA Con) can result in right ventricular enlargement, right ventricular hypertrophy, and tricuspid regurgitation.MethodThis study retrospectively analyzed 34 singleton fetuses that underwent fetal echocardiography with a diagnosis of DA Con (16 cases with mild to moderate, and 18 cases with moderate to severe) and 45 healthy fetuses. The morphology and function parameters of cardiac, as well as the 24-Segment of ventricles, were compared between the DA Con group and controls, and between the mild to moderate and moderate to severe groups, using the fetal heart quantification (FHQ) technology.ResultsThere were no significant difference in left ventricular parameters in DA Con group when compared to controls. Moreover, fetal 4CV-GSI was significantly reduced, as well as the sphericity index (SI), fractional shortening (FS), global longitudinal strain (GS) and fractional area change (FAC) of right ventricle, especially in the basal-middle segments. Compared with the mild to moderate group, LV-FS increased and RV-FS decreased in moderate to severe group.ConclusionThe results showed that the fetal heart in the DA Con group was different from the controls in morphology and function. FHQ technology provides a comprehensive assessment for the evaluation of cardiac morphological and functional changes in DA Con fetuses.

Abstract Importance The inclusion of authors from diverse backgrounds and with different lived experiences is critical to ensuring the questions addressed in systematic reviews (SRs), as well as the subsequent conclusions and recommendations made, are representative of the global community. Objective To assess the gender and geographic diversity of authors among all Cochrane SRs in eyes and vision as compared with a random sample of non-Cochrane SRs of interventions in the field of eyes and vision. Design The Cochrane Eyes and Vision US Satellite maintains a database of SRs in the field of eyes and vision. We selected all (n = 313) eyes and vision intervention SRs published in The Cochrane Library and a random sample of 313 eyes and vision intervention SRs published elsewhere for this study. We determined gender of the first and corresponding authors (“woman,” “man,” or “unknown”) using a previously developed algorithm and their location based on institution country and the World Health Organization region. Results From the 626 reviews included in our sample, we identified 751 unique authors who comprised 887 author positions (i.e., first and/or corresponding authors). We were able to ascertain the gender of 647/751 (86%) authors: 276 women and 371 men. Among Cochrane eyes and vision SRs, the proportions of women in first and/or corresponding author positions were consistent and approximately equal to men. Among non-Cochrane eyes and vision SRs, the representation of women was markedly lower as corresponding authors than other positions. Most authors of Cochrane eyes and vision SRs were from the UK (31%) and USA (26%), whereas most authors of non-Cochrane SRs were from China (34%). Conclusions and relevance Compared with authors of non-Cochrane SRs in eyes and vision, authors of Cochrane SRs appear to have approximately equal representation of women and men among perceived important author positions and be located in European and North American countries, possibly due to the locations of the Cochrane editorial teams. Cochrane Eyes and Vision should continue to recruit authors from around the world in locations that reflect the global burden of eye disease.

Abstract Background In a randomized crossover trial, each participant is randomized to a sequence of treatments and treatment effect is estimated based on within-individual difference because each participant serves as his/her own control. This feature makes the design and reporting of randomized crossover trials different from that of parallel trials. Our objective was to characterize phase 3 crossover trials with results reported on ClinicalTrials.gov and identify issues and best practices for reporting. Methods We searched ClinicalTrials.gov for phase 3 randomized crossover trials that provided results, registered at least one primary outcome, and included at least one link to a results publication in the record by August 6, 2019. Two reviewers independently assessed the eligibility and extracted information from each record into an electronic form developed and maintained in the Systematic Review Data Repository. Results Of the 124 crossover trials analyzed, two thirds were a simple “Intervention A then B” or “Intervention B then A” (AB|BA) design. Most trials (78%, 97/124) provided enough information to understand the participant flow throughout the trial. Baseline characteristics were most often reported for all participants as a single group (52%, 65/124). Primary outcomes and adverse events were most commonly reported “per intervention” (85%, 105/124, and 80%, 99/124, respectively). Conclusions The registration and reporting of randomized crossover trials must account for the paired nature of the design. Our observations and recommendations informed the development of guidelines for good reporting practices in the registration and reporting of randomized crossover trials.

BackgroundResults from observational studies and randomized clinical trials (RCTs) have led to the consensus that hydroxychloroquine (HCQ) and chloroquine (CQ) are not effective for COVID-19 prevention or treatment. Pooling individual participant data, including unanalyzed data from trials terminated early, enables more detailed investigation of the efficacy and safety of HCQ/CQ among subgroups of hospitalized patients.MethodsWe searched ClinicalTrials.gov in May and June 2020 for US-based RCTs evaluating HCQ/CQ in hospitalized COVID-19 patients in which the outcomes defined in this study were recorded or could be extrapolated. The primary outcome was a 7-point ordinal scale measured between day 28 and 35 post enrollment; comparisons used proportional odds ratios. Harmonized de-identified data were collected via a common template spreadsheet sent to each principal investigator. The data were analyzed by fitting a prespecified Bayesian ordinal regression model and standardizing the resulting predictions.ResultsEight of 19 trials met eligibility criteria and agreed to participate. Patient-level data were available from 770 participants (412 HCQ/CQ vs 358 control). Baseline characteristics were similar between groups. We did not find evidence of a difference in COVID-19 ordinal scores between days 28 and 35 post-enrollment in the pooled patient population (odds ratio, 0.97; 95% credible interval, 0.76-1.24; higher favors HCQ/CQ), and found no convincing evidence of meaningful treatment effect heterogeneity among prespecified subgroups. Adverse event and serious adverse event rates were numerically higher with HCQ/CQ vs control (0.39 vs 0.29 and 0.13 vs 0.09 per patient, respectively).ConclusionsThe findings of this individual participant data meta-analysis reinforce those of individual RCTs that HCQ/CQ is not efficacious for treatment of COVID-19 in hospitalized patients.

Introduction Dry eye is a multifactorial chronic condition characterised by tear film insufficiency and instability, and ocular symptoms including foreign body sensation, itching, irritation, soreness and visual disturbance. The prevalence and incidence of dry eye are major determinants of the magnitude of economic and societal costs of the disease. This protocol proposes a systematic review and meta-analysis of the prevalence and incidence of dry eye in the USA.Methods and analysis Working with an information specialist, we will develop search strategies for Ovid Medline and Embase for population-based cross-sectional and cohort studies involving US-based populations that report the prevalence and/or incidence of dry eye. We will include studies involving persons of all ages from 1 January 2010 to the current date with no language restrictions. We will also hand-search references of included studies, dry eye epidemiology-related systematic reviews, clinical practice guidelines and literature provided by agencies and organisations. Two investigators will independently screen the titles and abstracts, and then full-text reports to determine eligibility. One investigator will extract study data and perform risk of bias assessments using tools designed specifically for prevalence and incidence studies. A second investigator will verify all extracted study data and risk of bias assessments. We will assess heterogeneity, qualitatively and quantitatively. When appropriate, we will meta-analyse prevalence and incidence estimates.Ethics and dissemination This review does not require approval by an ethics committee because it will use published studies. We will publish our results in a peer-reviewed journal and present at relevant conferences.PROSPERO registration number CRD42021256934.

Background: Visually impaired older adults have a greater risk of falling, making them particularly susceptible to fall-related health consequences and restricted physical activity. Unclear however, is the relationship between having falls and longitudinal changes in daily patterns of objectively measured physical activity in older adults with visual impairments. Methods: We created a three-year prospective cohort study (Falls in Glaucoma Study) of older adults with primary or suspected glaucoma at the Johns Hopkins Wilmer Eye Institute from 2013 to 2015. Cumulative incidence of falls was determined through self-reported fall calendars over 12 months. Participants were then classified into one of three groups: multiple fallers (≥2 falls), single fallers (1 fall), and non-fallers (0). Daily physical activity was measured over 1 week using a waist-bound accelerometer during baseline and three-year follow-ups. Activity fragmentation was defined as the reciprocal of the mean activity bout length, with higher fragmentation reflecting shorter, more fractured bouts of continuous activity. Multivariate linear mixed-effects models were used to assess three-year longitudinal changes in: 1) activity fragmentation, and 2) accumulation of activity across six three-hour intervals from 5 AM to 11 PM. Findings: In adjusted models accounting for visual field damage and other factors, multiple fallers demonstrated greater annual declines (per year) in daily active bouts (-1.79 bouts/day, 95% confidence interval [CI]: -3.35, -0.22), daily active minutes (-17.15 min/day, 95% CI: -26.35, -7.94), and increased fragmentation (1%, 95% CI: 0, 2%) over the three-year follow-up period as compared to non-fallers; no such changes were seen when comparing single fallers and non-fallers. In time-of-day analyses, multiple fallers experienced greater annual declines in average hourly steps over all periods of the day, though the rate of decline was only significant between 5 PM and 8 PM (-27.07 steps/hour, 95% CI: -51.15, -2.99) compared to non-fallers. Interpretation: In an older population with visual impairment, multiple falls over 12 months were associated with more transient and fragmented activity over a subsequent three-year period, and activity declines during evening hours, compared to non-fallers. These findings suggest that multiple fallers with visual impairment may be at high risk for a decline in physical capacity and endurance, warranting clinical interventions. Funding: The research was supported in part by National Institutes of Health Grant EY022976.

Abstract Background Adverse events (AEs) in clinical trials may be reported in multiple sources. Different methods for reporting adverse events across trials or across sources for a single trial may produce inconsistent information about the adverse events associated with interventions. Methods We compared the methods authors use to decide which AEs to include in a particular source (i.e., “selection criteria”), including the number of different types of AEs reported (i.e., rather than the number of events). We compared sources (e.g., journal articles, clinical study reports (CSRs)) of trials for two drug-indications—gabapentin for neuropathic pain and quetiapine for bipolar depression. Electronic searches were completed in 2015. We identified selection criteria and assessed how criteria affected AE reporting. Results We identified 21 gabapentin and 7 quetiapine trials. We found 6 gabapentin CSRs and 2 quetiapine CSRs, all written by drug manufacturers. All CSRs reported all AEs without applying selection criteria; by comparison, no other source reported all AEs, and 15/68 (22%) gabapentin sources and 19/48 (40%) quetiapine sources reported using selection criteria. Selection criteria greatly affected the number of AEs reported. For example, 67/316 (21%) AEs in one quetiapine trial met the criterion “occurring in ≥2% of participants in any treatment group,” while only 5/316 (2%) AEs met the criterion “occurring in ≥10% of quetiapine-treated patients and twice as frequent in the quetiapine group as the placebo group.” Conclusions Selection criteria for reporting AEs vary across trials and across sources for individual trials. If investigators do not pre-specify selection criteria, they might “cherry-pick” AEs based on results. Even if investigators pre-specify selection criteria, selective reporting will produce biased meta-analyses and clinical practice guidelines. Data about all AEs identified in clinical trials should be publicly available; however, sharing data will not solve all the problems identified in this study.

Abstract Background Type 2 diabetes mellitus (T2DM) is a major public health problem worldwide. It is characterized by the increased concentration of glucose in the blood and leads to damage of the body system, especially blood vessels and nerves. Lifestyle modification is often combined with anti-diabetic therapy as the standard of care for T2DM to maintain the proper blood glucose and to prevent long-term diabetic complications. The role of probiotics in improving glycemic control has been investigated in several randomized controlled trials (RCTs). Previous systematic reviews and meta-analyses, including different sets of trials have concluded an overall beneficial effect of probiotics in patients with T2DM. At least two RCTs with a longer treatment duration have been published since the publication of existing reviews. Methods We will conduct a systematic review of RCTs that evaluated the effectiveness and safety of probiotics for glycemic control in T2DM patients. Primary outcomes are fasting blood glucose and glycosylated hemoglobin (A1c). Secondary outcomes are plasma insulin, blood lipid profile, adverse events, and cost associated with the intervention and hospital visits. We will search PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, and trial registries. Two reviewers will independently screen titles and abstracts, review full texts, extract information, and assess the risk of bias. We will summarize the results both qualitatively and statistically. We will use random-effects model for meta-analysis. Discussion This systematic review aims to examine whether probiotics are effective and safe for glycemic control in T2DM patients. Evidence generated from this review will inform clinical and public health practice and future research. Systematic review registration CRD42019121682

Background: Systematic reviews underpin clinical practice and policies that guide healthcare decisions. A core component of many systematic reviews is meta-analysis, which is a statistical synthesis of results across studies. Errors in the conduct and interpretation of meta-analysis can lead to incorrect conclusions regarding the benefits and harms of interventions; and studies have shown that these errors are common. Enabling peer reviewers to better detect errors in meta-analysis through the use of a checklist provides an opportunity for these errors to be rectified before publication. To our knowledge, no such checklist exists. Objective: To develop and evaluate a checklist to detect errors in pairwise meta-analyses in systematic reviews of interventions. Methods: We will undertake a four-step process to develop the checklist. First, we will undertake a systematic review of studies that have evaluated errors in the conduct and interpretation of meta-analysis to generate a bank of items to consider for the checklist. Second, we will undertake a survey of systematic review methodologists and statisticians to seek their views on which items, of the bank of items generated in step 1, are most important to include in the checklist. Third, we will hold a virtual meeting to agree upon which items to include in the checklist. Fourth, before finalising the checklist, we will pilot with editors and peer reviewers of journals. Conclusion: The developed checklist is intended to help journal editors and peer reviewers identify errors in the application and interpretation of meta-analyses in systematic reviews. Fewer errors in the conduct and improved interpretation will lead to more accurate review findings and conclusions to inform clinical practice.

Introduction Cochrane Eyes and Vision (CEV) is an international network of individuals working to prepare, maintain and promote access to systematic reviews of interventions to treat, prevent or diagnose eye diseases or vision impairment. CEV plans to undertake a priority setting exercise to identify systematically research questions relevant to our scope, and to formally incorporate input from a wide range of stakeholders to set priorities for new and updated reviews.Methods and analysis The scope of CEV is broad and our reviews include conditions that are common and have a high global disease burden, for example, cataract and dry eye disease, and conditions that are rare but have a high impact on quality of life and high individual cost such as eye cancer. We plan to focus on conditions prioritised by WHO during the development of the Package of Eye Care Interventions. These conditions were selected based on a combination of data on disease magnitude, healthcare use and expert opinion. We will identify priority review questions systematically by summarising relevant data on research in Eyes and Vision from a range of sources, and compiling a list of 10–15 potential review questions (new and/or updates) for each condition group. We will seek the views of external and internal stakeholders on this list by conducting an online survey. Equity will be a specific consideration.Ethics and dissemination The study has been approved by the ethics committee of the London School of Hygiene & Tropical Medicine. We will disseminate the findings through Cochrane channels and prepare a summary of the work for publication in a peer-reviewed journal.

Introduction Gabapentin (Neurontin) is prescribed widely for conditions for which it has not been approved by regulators, including certain neuropathic pain conditions. There is limited evidence that gabapentin is safe and effective for the treatment of neuropathic pain. Published trial reports, and systematic reviews based on published trial reports, mislead patients and providers because information about gabapentin’s harms has been published only partly. We confirmed that trials conducted by the drug developer have been abandoned, and we plan to conduct a restoration with support from the Restoring Invisible and Abandoned Trials Support Centre (https://restoringtrials.org/).Methods and analysis In this study, we will analyse and report the harms that were observed in six trials of gabapentin, which have not been reported publicly (eg, in journal articles). We will use clinical study reports and individual participant data to identify and report the harms observed in each individual trial and to summarise the harms observed across all six trials. We will report all adverse events observed in the included trials by sharing deidentified data and summary tables on the Open Science Framework (https://osf.io/w8puv/). Additionally, we will produce a summary report that describes differences between the randomised groups in each trial and across trials for prespecified harms outcomes.Ethics and dissemination We will use secondary data. This study was determined to be exempt from Institutional Review Board (IRB) review (protocol #1910607198).

Matthew Page and co-authors describe PRISMA 2020, an updated reporting guideline for systematic reviews and meta-analyses.

Abstract Clinical trials and systematic reviews of clinical trials inform healthcare decisions. There is growing concern, however, about results from clinical trials that cannot be reproduced. Reasons for nonreproducibility include that outcomes are defined in multiple ways, results can be obtained using multiple methods of analysis, and trial findings are reported in multiple sources (“multiplicity”). Multiplicity combined with selective reporting can influence dissemination of trial findings and decision-making. In particular, users of evidence might be misled by exposure to selected sources and overly optimistic representations of intervention effects. In this commentary, drawing from our experience in the Multiple Data Sources in Systematic Reviews (MUDS) study and evidence from previous research, we offer practical recommendations to enhance the reproducibility of clinical trials and systematic reviews.

Abstract Background Systematic reviews should inform American Academy of Ophthalmology (AAO) Preferred Practice Pattern® (PPP) guidelines. The quality of systematic reviews related to the forthcoming Preferred Practice Pattern® guideline (PPP) Refractive Errors & Refractive Surgery is unknown. We sought to identify reliable systematic reviews to assist the AAO Refractive Errors & Refractive Surgery PPP. Methods Systematic reviews were eligible if they evaluated the effectiveness or safety of interventions included in the 2012 PPP Refractive Errors & Refractive Surgery. To identify potentially eligible systematic reviews, we searched the Cochrane Eyes and Vision United States Satellite database of systematic reviews. Two authors identified eligible reviews and abstracted information about the characteristics and quality of the reviews independently using the Systematic Review Data Repository. We classified systematic reviews as “reliable” when they (1) defined criteria for the selection of studies, (2) conducted comprehensive literature searches for eligible studies, (3) assessed the methodological quality (risk of bias) of the included studies, (4) used appropriate methods for meta-analyses (which we assessed only when meta-analyses were reported), (5) presented conclusions that were supported by the evidence provided in the review. Results We identified 124 systematic reviews related to refractive error; 39 met our eligibility criteria, of which we classified 11 to be reliable. Systematic reviews classified as unreliable did not define the criteria for selecting studies (5; 13%), did not assess methodological rigor (10; 26%), did not conduct comprehensive searches (17; 44%), or used inappropriate quantitative methods (3; 8%). The 11 reliable reviews were published between 2002 and 2016. They included 0 to 23 studies (median = 9) and analyzed 0 to 4696 participants (median = 666). Seven reliable reviews (64%) assessed surgical interventions. Conclusions Most systematic reviews of interventions for refractive error are low methodological quality. Following widely accepted guidance, such as Cochrane or Institute of Medicine standards for conducting systematic reviews, would contribute to improved patient care and inform future research.

Abstract Background Data abstraction, a critical systematic review step, is time-consuming and prone to errors. Current standards for approaches to data abstraction rest on a weak evidence base. We developed the Data Abstraction Assistant (DAA), a novel software application designed to facilitate the abstraction process by allowing users to (1) view study article PDFs juxtaposed to electronic data abstraction forms linked to a data abstraction system, (2) highlight (or “pin”) the location of the text in the PDF, and (3) copy relevant text from the PDF into the form. We describe the design of a randomized controlled trial (RCT) that compares the relative effectiveness of (A) DAA-facilitated single abstraction plus verification by a second person, (B) traditional (non-DAA-facilitated) single abstraction plus verification by a second person, and (C) traditional independent dual abstraction plus adjudication to ascertain the accuracy and efficiency of abstraction. Methods This is an online, randomized, three-arm, crossover trial. We will enroll 24 pairs of abstractors (i.e., sample size is 48 participants), each pair comprising one less and one more experienced abstractor. Pairs will be randomized to abstract data from six articles, two under each of the three approaches. Abstractors will complete pre-tested data abstraction forms using the Systematic Review Data Repository (SRDR), an online data abstraction system. The primary outcomes are (1) proportion of data items abstracted that constitute an error (compared with an answer key) and (2) total time taken to complete abstraction (by two abstractors in the pair, including verification and/or adjudication). Discussion The DAA trial uses a practical design to test a novel software application as a tool to help improve the accuracy and efficiency of the data abstraction process during systematic reviews. Findings from the DAA trial will provide much-needed evidence to strengthen current recommendations for data abstraction approaches. Trial registration The trial is registered at National Information Center on Health Services Research and Health Care Technology (NICHSR) under Registration # HSRP20152269: https://wwwcf.nlm.nih.gov/hsr_project/view_hsrproj_record.cfm?NLMUNIQUE_ID=20152269&SEARCH_FOR=Tianjing%20Li . All items from the World Health Organization Trial Registration Data Set are covered at various locations in this protocol. Protocol version and date: This is version 2.0 of the protocol, dated September 6, 2016. As needed, we will communicate any protocol amendments to the Institutional Review Boards (IRBs) of Johns Hopkins Bloomberg School of Public Health (JHBSPH) and Brown University. We also will make appropriate as-needed modifications to the NICHSR website in a timely fashion.

Abstract ᅟ This is a response to a Letter. Data abstraction is a time-consuming and error-prone systematic review task. Shokraneh and Adams categorize available techniques for tracking data during data abstraction into three methods: simple annotation, descriptive addressing, and Cartesian coordinate system. While we agree with the categorization of the techniques, we disagree with the authors’ statement that descriptive addressing is a PDF-independent method, i.e., any sort of descriptive addressing must reference a specific version of PDF file and not just any PDF of said report. Different versions of PDFs of the same report might place text and tables on different locations of the same page and/or on different pages. Consequently, it is our opinion that any kind of source location information should be accompanied by the source or linked by an intermediary service such as the Data Abstraction Assistant (DAA).

Abstract The correct title of the article [1] should be “Integrating multiple data sources (MUDS) for meta-analysis to improve patient-centered outcomes research: a protocol”.

The lack of adequate and standardized recording of leading risk factors for morbidity and mortality in medical records have downstream effects on research based on administrative databases. The measurement of healthcare is increasingly based on risk-adjusted outcomes derived from coded comorbidities in these databases. However inaccurate or haphazard assessment of risk factors for morbidity and mortality in medical record codes can have tremendous implications for quality improvement and healthcare reform.We aimed to compare the prevalence of obesity, overweight, tobacco use and alcohol abuse of a large administrative database with a direct data collection survey.We used the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes for four leading risk factors in the United States Nationwide Inpatient Sample (NIS) to compare them with a direct survey in the Behavioral Risk Factor Surveillance System (BRFSS) in 2011. After confirming normality of the risk factors, we calculated the national and state estimates and Pearson's correlation coefficient for obesity, overweight, tobacco use and alcohol abuse between NIS and BRFSS.Compared with direct participant questioning in BRFSS, NIS reported substantially lower prevalence of obesity (p

OBJECTIVE:To evaluate the characteristics of the design, analysis, and reporting of crossover trials for inclusion in a meta-analysis of treatment for primary open-angle glaucoma and to provide empirical evidence to inform the development of tools to assess the validity of the results from crossover trials and reporting guidelines. METHODS:We searched MEDLINE, EMBASE, and Cochrane's CENTRAL register for randomized crossover trials for a systematic review and network meta-analysis we are conducting. Two individuals independently screened the search results for eligibility and abstracted data from each included report. RESULTS:We identified 83 crossover trials eligible for inclusion. Issues affecting the risk of bias in crossover trials, such as carryover, period effects and missing data, were often ignored. Some trials failed to accommodate the within-individual differences in the analysis. For a large proportion of the trials, the authors tabulated the results as if they arose from a parallel design. Precision estimates properly accounting for the paired nature of the design were often unavailable from the study reports; consequently, to include trial findings in a meta-analysis would require further manipulation and assumptions. CONCLUSIONS:The high proportion of poorly reported analyses and results has the potential to affect whether crossover data should or can be included in a meta-analysis. There is pressing need for reporting guidelines for crossover trials.

INTRODUCTION:Choice of outcomes is critical for clinical trialists and systematic reviewers. It is currently unclear how systematic reviewers choose and pre-specify outcomes for systematic reviews. Our objective was to assess the completeness of pre-specification and comparability of outcomes in all Cochrane reviews addressing four common eye conditions. METHODS:We examined protocols for all Cochrane reviews as of June 2013 that addressed glaucoma, cataract, age-related macular degeneration (AMD), and diabetic retinopathy (DR). We assessed completeness and comparability for each outcome that was named in ≥ 25% of protocols on those topics. We defined a completely-specified outcome as including information about five elements: domain, specific measurement, specific metric, method of aggregation, and time-points. For each domain, we assessed comparability in how individual elements were specified across protocols. RESULTS:We identified 57 protocols addressing glaucoma (22), cataract (16), AMD (15), and DR (4). We assessed completeness and comparability for five outcome domains: quality-of-life, visual acuity, intraocular pressure, disease progression, and contrast sensitivity. Overall, these five outcome domains appeared 145 times (instances). Only 15/145 instances (10.3%) were completely specified (all five elements) (median = three elements per outcome). Primary outcomes were more completely specified than non-primary (median = four versus two elements). Quality-of-life was least completely specified (median = one element). Due to largely incomplete outcome pre-specification, conclusive assessment of comparability in outcome usage across the various protocols per condition was not possible. DISCUSSION:Outcome pre-specification was largely incomplete; we encourage systematic reviewers to consider all five elements. This will indicate the importance of complete specification to clinical trialists, on whose work systematic reviewers depend, and will indirectly encourage comparable outcome choice to reviewers undertaking related research questions. Complete pre-specification could improve efficiency and reduce bias in data abstraction and analysis during a systematic review. Ultimately, more completely specified and comparable outcomes could make systematic reviews more useful to decision-makers.

BACKGROUND: Details about the type of analysis (e.g., intent to treat [ITT]) and definitions (i.e., criteria for including participants in the analysis) are necessary for interpreting a clinical trial's findings. Our objective was to compare the description of types of analyses and criteria for including participants in the publication (i.e., what was reported) with descriptions in the corresponding internal company documents (i.e., what was planned and what was done). Trials were for off-label uses of gabapentin sponsored by Pfizer and Parke-Davis, and documents were obtained through litigation. METHODS AND FINDINGS: For each trial, we compared internal company documents (protocols, statistical analysis plans, and research reports, all unpublished), with publications. One author extracted data and another verified, with a third person verifying discordant items and a sample of the rest. Extracted data included the number of participants randomized and analyzed for efficacy, and types of analyses for efficacy and safety and their definitions (i.e., criteria for including participants in each type of analysis). We identified 21 trials, 11 of which were published randomized controlled trials, and that provided the documents needed for planned comparisons. For three trials, there was disagreement on the number of randomized participants between the research report and publication. Seven types of efficacy analyses were described in the protocols, statistical analysis plans, and publications, including ITT and six others. The protocol or publication described ITT using six different definitions, resulting in frequent disagreements between the two documents (i.e., different numbers of participants were included in the analyses). CONCLUSIONS: Descriptions of analyses conducted did not agree between internal company documents and what was publicly reported. Internal company documents provide extensive documentation of methods planned and used, and trial findings, and should be publicly accessible. Reporting standards for randomized controlled trials should recommend transparent descriptions and definitions of analyses performed and which study participants are excluded.