Guideline for reporting systematic reviews of outcome measurement instruments (OMIs): PRISMA-COSMIN for OMIs 2024.

PURPOSE: Although comprehensive and widespread guidelines on how to conduct systematic reviews of outcome measurement instruments (OMIs) exist, for example from the COSMIN (COnsensus-based Standards for the selection of health Measure- ment INstruments) initiative, key information is often missing in published reports. This article describes the development of an extension of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guideline: PRISMA-COSMIN for OMIs 2024. METHODS: The development process followed the Enhancing the QUAlity and Transparency Of health Research (EQUATOR) guidelines and included a literature search, expert consultations, a Delphi study, a hybrid workgroup meeting, pilot testing, and an end-of-project meeting, with integrated patient/public involvement. RESULTS: From the literature and expert consultation, 49 potentially relevant reporting items were identified. Round 1 of the Delphi study was completed by 103 panelists, whereas round 2 and 3 were completed by 78 panelists. After 3 rounds, agreement (≥ 67%) on inclusion and wording was reached for 44 items. Eleven items without consensus for inclusion and/or wording were discussed at a workgroup meeting attended by 24 participants. Agreement was reached for the inclusion and wording of 10 items, and the deletion of 1 item. Pilot testing with 65 authors of OMI systematic reviews further improved the guideline through minor changes in wording and structure, finalized during the end-of-project meeting. The final check- list to facilitate the reporting of full systematic review reports contains 54 (sub)items addressing the review's title, abstract, plain language summary, open science, introduction, methods, results, and discussion. Thirteen items pertaining to the title and abstract are also included in a separate abstract checklist, guiding authors in reporting for example conference abstracts. CONCLUSION: PRISMA-COSMIN for OMIs 2024 consists of two checklists (full reports; abstracts), their corresponding expla- nation and elaboration documents detailing the rationale and examples for each item, and a data flow diagram. PRISMA- COSMIN for OMIs 2024 can improve the reporting of systematic reviews of OMIs, fostering their reproducibility and allowing end-users to appraise the quality of OMIs and select the most appropriate OMI for a specific application.

Studying harms of interventions with an equity lens in randomized trials.

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.

A guide for social science journal editors on easing into open science.

Journal editors have a large amount of power to advance open science in their respective fields by incentivising and mandating open policies and practices at their journals. The Data PASS Journal Editors Discussion Interface (JEDI, an online community for social science journal editors: www.dpjedi.org ) has collated several resources on embedding open science in journal editing ( www.dpjedi.org/resources ). However, it can be overwhelming as an editor new to open science practices to know where to start. For this reason, we created a guide for journal editors on how to get started with open science. The guide outlines steps that editors can take to implement open policies and practices within their journal, and goes through the what, why, how, and worries of each policy and practice. This manuscript introduces and summarizes the guide (full guide: https://doi.org/10.31219/osf.io/hstcx ).

Publication of Results of Registered Trials With Published Study Protocols, 2011-2022.

Importance: Publishing study protocols might reduce research waste because of unclear methods or incomplete reporting; on the other hand, there might be few additional benefits of publishing protocols for registered trials that are never completed or published. No study has investigated the proportion of published protocols associated with published results. Objective: To estimate the proportion of published trial protocols for which there are not associated published results. Design, Setting, and Participants: This cross-sectional study used stratified random sampling to identify registered clinical trials with protocols published between January 2011 and August 2022 and indexed in PubMed Central. Ongoing studies and those within 1 year of the primary completion date on ClinicalTrials.gov were excluded. Published results were sought from August 2022 to March 2023 by searching ClinicalTrials.gov, emailing authors, and using an automated tool, as well as through incidental discovery. Main Outcomes and Measures: The primary outcome was a weighted estimate of the proportion of registered trials with published protocols that also had published main results. The proportion of trials with unpublished results was estimated using a weighted mean. Results: From 1500 citations that were screened, 308 clinical trial protocols were included, and it was found that 87 trials had not published their main results. Most included trials were investigator-initiated evaluations of nonregulated products. When published, results appeared a mean (SD) of 3.4 (2.0) years after protocol publications. With the use of a weighted mean, an estimated 4754 (95% CI, 4296-5226) eligible clinical trial protocols were published and indexed in PubMed Central between 2011 and 2022. In the weighted analysis, 1708 of those protocols (36%; 95% CI, 31%-41%) were not associated with publication of main results. In a sensitivity analysis excluding protocols published after 2019, an estimated 25% (95% CI, 20%-30%) of 3670 (95% CI, 3310-4032) protocol publications were not associated with publication of main results. Conclusions and Relevance: This cross-sectional study of clinical trial protocols published on PubMed Central between 2011 and 2022 suggests that many protocols were not associated with subsequent publication of results. The overall benefits of publishing study protocols might outweigh the research waste caused by unnecessary protocol publications.

Perturbational phenotyping of human blood cells reveals genetically determined latent traits associated with subsets of common diseases.

Although genome-wide association studies (GWAS) have successfully linked genetic risk loci to various disorders, identifying underlying cellular biological mechanisms remains challenging due to the complex nature of common diseases. We established a framework using human peripheral blood cells, physical, chemical and pharmacological perturbations, and flow cytometry-based functional readouts to reveal latent cellular processes and performed GWAS based on these evoked traits in up to 2,600 individuals. We identified 119 genomic loci implicating 96 genes associated with these cellular responses and discovered associations between evoked blood phenotypes and subsets of common diseases. We found a population of pro-inflammatory anti-apoptotic neutrophils prevalent in individuals with specific subsets of cardiometabolic disease. Multigenic models based on this trait predicted the risk of developing chronic kidney disease in type 2 diabetes patients. By expanding the phenotypic space for human genetic studies, we could identify variants associated with large effect response differences, stratify patients and efficiently characterize the underlying biology.

Harms were detected but not reported in six clinical trials of gabapentin.

OBJECTIVES: We sought to assess and report harms that were observed but not disclosed previously in clinical trials of gabapentin. STUDY DESIGN AND SETTING: We reanalyzed individual participant data from six randomized parallel trials of gabapentin for neuropathic pain, and we conducted meta-analyses. Between 1996 and 2003, adult participants were assigned to gabapentin (600 mg-3,600 mg per day) or placebo for 7-14 weeks. We calculated the proportion of participants with: one or more adverse events (AEs), one or more serious AEs, discontinued, discontinued because AEs. We also estimated effects on AEs at three levels of aggregation using COSTART, a hierarchical system for classifying AEs: body system, midlevel system, preferred term. RESULTS: We found evidence of important harms that were neither included in published trial reports nor included in systematic reviews. Aggregating related harms led to greater confidence that gabapentin might harm the nervous system and possibly the digestive, metabolic and nutritional, respiratory, sensory, and urogenital body systems. Nervous system harms were more common than previous reports suggest. CONCLUSION: Clinical trials identified harms that were not reported publicly, and journal articles overstated uncertainty about harms. Relying on journal articles to evaluate gabapentin's harms could contribute to incomplete and misleading conclusions in systematic reviews and guidelines. To prevent bias arising from the selective nonreporting of results, journal articles should describe how to access data for all harms observed in clinical trials (e.g., by sharing individual participant data).

Methodology reporting improved over time in 176,469 randomized controlled trials.

OBJECTIVES: To describe randomized controlled trial (RCT) methodology reporting over time. STUDY DESIGN AND SETTING: We used a deep learning-based sentence classification model based on the Consolidated Standards of Reporting Trials (CONSORT) statement, considered minimum requirements for reporting RCTs. We included 176,469 RCT reports published between 1966 and 2018. We analyzed the reporting trends over 5-year time periods, grouping trials from 1966 to 1990 in a single stratum. We also explored the effect of journal impact factor (JIF) and medical discipline. RESULTS: Population, Intervention, Comparator, Outcome (PICO) items were commonly reported during each period, and reporting increased over time (e.g., interventions: 79.1% during 1966-1990 to 87.5% during 2010-2018). Reporting of some methods information has increased, although there is room for improvement (e.g., sequence generation: 10.8-41.8%). Some items are reported infrequently (e.g., allocation concealment: 5.1-19.3%). The number of items reported and JIF are weakly correlated (Pearson's r (162,702) = 0.16, P < 0.001). The differences in the proportion of items reported between disciplines are small (<10%). CONCLUSION: Our analysis provides large-scale quantitative support for the hypothesis that RCT methodology reporting has improved over time. Extending these models to all CONSORT items could facilitate compliance checking during manuscript authoring and peer review, and support metaresearch.

Glioma-BioDP: database for visualization of molecular profiles to improve prognosis of brain cancer.

Cancer researchers often seek user-friendly interactive tools for validation, exploration, analysis, and visualization of molecular profiles in cancer patient samples. To aid researchers working on the both low- and high-grade gliomas, we developed Glioma-BioDP, a web tool for exploration and visualization of RNA and protein expression profiles of interest in these tumor types. Glioma-BioDP is user friendly application that include expression data from both the low- and high-grade glioma patient samples from The Cancer Genome Atlas and enabled querying by mRNA, microRNA, and protein level expression data from Illumina HiSeq and RPPA platforms respectively. Glioma-BioDP provides advance query interface and enables users to explore the association of genes, proteins, and miRNA expression with molecular and/or histological subtypes of gliomas, surgical resection status and survival. The prognostic significance and visualization of the selected expression profiles can be explored using interactive utilities provided. This tool may also enable validation and generation of new hypotheses of novel therapies impacting gliomas that aid in personalization of treatment for optimum outcomes.

Open Science Standards at Journals that Inform Evidence-Based Policy.

Evidence-based policy uses intervention research to inform consequential decisions about resource allocation. Research findings are often published in peer-reviewed journals. Because detrimental research practices associated with closed science are common, journal articles report more false-positives and exaggerated effect sizes than would be desirable. Journal implementation of standards that promote open science-such as the transparency and openness promotion (TOP) guidelines-could reduce detrimental research practices and improve the trustworthiness of research evidence on intervention effectiveness. We evaluated TOP implementation at 339 peer-reviewed journals that have been used to identify evidence-based interventions for policymaking and programmatic decisions. Each of ten open science standards in TOP was not implemented in most journals' policies (instructions to authors), procedures (manuscript submission systems), or practices (published articles). Journals implementing at least one standard typically encouraged, but did not require, an open science practice. We discuss why and how journals could improve implementation of open science standards to safeguard evidence-based policy.

Habitat and climatic associations of climate-sensitive species along a southern range boundary.

Climate change and habitat loss are recognized as important drivers of shifts in wildlife species' geographic distributions. While often considered independently, there is considerable overlap between these drivers, and understanding how they contribute to range shifts can predict future species assemblages and inform effective management. Our objective was to evaluate the impacts of habitat, climatic, and anthropogenic effects on the distributions of climate-sensitive vertebrates along a southern range boundary in Northern Michigan, USA. We combined multiple sources of occurrence data, including harvest and citizen-science data, then used hierarchical Bayesian spatial models to determine habitat and climatic associations for four climate-sensitive vertebrate species (American marten [Martes americana], snowshoe hare [Lepus americanus], ruffed grouse [Bonasa umbellus] and moose [Alces alces]). We used total basal area of at-risk forest types to represent habitat, and temperature and winter habitat indices to represent climate. Marten associated with upland spruce-fir and lowland riparian forest types, hares with lowland conifer and aspen-birch, grouse with lowland riparian hardwoods, and moose with upland spruce-fir. Species differed in climatic drivers with hares positively associated with cooler annual temperatures, moose with cooler summer temperatures and grouse with colder winter temperatures. Contrary to expectations, temperature variables outperformed winter habitat indices. Model performance varied greatly among species, as did predicted distributions along the southern edge of the Northwoods region. As multiple species were associated with lowland riparian and upland spruce-fir habitats, these results provide potential for efficient prioritization of habitat management. Both direct and indirect effects from climate change are likely to impact the distribution of climate-sensitive species in the future and the use of multiple data types and sources in the modelling of species distributions can result in more accurate predictions resulting in improved management at policy-relevant scales.

CONSORT Harms 2022 statement, explanation, and elaboration: updated guideline for the reporting of harms in randomized trials.

Randomized controlled trials remain the reference standard for healthcare research on effects of interventions, and the need to report both benefits and harms is essential. The Consolidated Standards of Reporting Trials (the main CONSORT) statement includes one item on reporting harms (i.e., all important harms or unintended effects in each group). In 2004, the CONSORT group developed the CONSORT Harms extension; however, it has not been consistently applied and needs to be updated. Here, we describe CONSORT Harms 2022, which replaces the CONSORT Harms 2004 checklist, and shows how CONSORT Harms 2022 items could be incorporated into the main CONSORT checklist. Thirteen items from the main CONSORT were modified to improve harms reporting. Three new items were added. In this article, we describe CONSORT Harms 2022 and how it was integrated into the main CONSORT checklist and elaborate on each item relevant to complete reporting of harms in randomized controlled trials. Until future work from the CONSORT group produces an updated checklist, authors, journal reviewers, and editors of randomized controlled trials should use the integrated checklist presented in this paper.

Conducting separate reviews of benefits and harms could improve systematic reviews and meta-analyses.

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.

Zinc supplementation for preventing mortality, morbidity, and growth failure in children aged 6 months to 12 years.

BACKGROUND: Zinc deficiency is prevalent in low- and middle-income countries, and is considered a significant risk factor for morbidity, mortality, and linear growth failure. The effectiveness of preventive zinc supplementation in reducing prevalence of zinc deficiency needs to be assessed. OBJECTIVES: To assess the effects of zinc supplementation for preventing mortality and morbidity, and for promoting growth, in children aged 6 months to 12 years. SEARCH METHODS: A previous version of this review was published in 2014. In this update, we searched CENTRAL, MEDLINE, Embase, five other databases, and one trials register up to February 2022, together with reference checking and contact with study authors to identify additional studies. SELECTION CRITERIA: Randomized controlled trials (RCTs) of preventive zinc supplementation in children aged 6 months to 12 years compared with no intervention, a placebo, or a waiting list control. We excluded hospitalized children and children with chronic diseases or conditions. We excluded food fortification or intake, sprinkles, and therapeutic interventions. DATA COLLECTION AND ANALYSIS: Two review authors screened studies, extracted data, and assessed the risk of bias. We contacted study authors for missing information and used GRADE to assess the certainty of evidence. The primary outcomes of this review were all-cause mortality; and cause-specific mortality, due to all-cause diarrhea, lower respiratory tract infection (LRTI, including pneumonia), and malaria. We also collected information on a number of secondary outcomes, such as those related to diarrhea and LRTI morbidity, growth outcomes and serum levels of micronutrients, and adverse events. MAIN RESULTS: We included 16 new studies in this review, resulting in a total of 96 RCTs with 219,584 eligible participants. The included studies were conducted in 34 countries; 87 of them in low- or middle-income countries. Most of the children included in this review were under five years of age. The intervention was delivered most commonly in the form of syrup as zinc sulfate, and the most common dose was between 10 mg and 15 mg daily. The median duration of follow-up was 26 weeks. We did not consider that the evidence for the key analyses of morbidity and mortality outcomes was affected by risk of bias. High-certainty evidence showed little to no difference in all-cause mortality with preventive zinc supplementation compared to no zinc (risk ratio (RR) 0.93, 95% confidence interval (CI) 0.84 to 1.03; 16 studies, 17 comparisons, 143,474 participants). Moderate-certainty evidence showed that preventive zinc supplementation compared to no zinc likely results in little to no difference in mortality due to all-cause diarrhea (RR 0.95, 95% CI 0.69 to 1.31; 4 studies, 132,321 participants); but probably reduces mortality due to LRTI (RR 0.86, 95% CI 0.64 to 1.15; 3 studies, 132,063 participants) and mortality due to malaria (RR 0.90, 95% CI 0.77 to 1.06; 2 studies, 42,818 participants); however, the confidence intervals around the summary estimates for these outcomes were wide, and we could not rule out a possibility of increased risk of mortality. Preventive zinc supplementation likely reduces the incidence of all-cause diarrhea (RR 0.91, 95% CI 0.90 to 0.93; 39 studies, 19,468 participants; moderate-certainty evidence) but results in little to no difference in morbidity due to LRTI (RR 1.01, 95% CI 0.95 to 1.08; 19 studies, 10,555 participants; high-certainty evidence) compared to no zinc. There was moderate-certainty evidence that preventive zinc supplementation likely leads to a slight increase in height (standardized mean difference (SMD) 0.12, 95% CI 0.09 to 0.14; 74 studies, 20,720 participants). Zinc supplementation was associated with an increase in the number of participants with at least one vomiting episode (RR 1.29, 95% CI 1.14 to 1.46; 5 studies, 35,192 participants; high-certainty evidence). We report a number of other outcomes, including the effect of zinc supplementation on weight and serum markers such as zinc, hemoglobin, iron, copper, etc. We also performed a number of subgroup analyses and there was a consistent finding for a number of outcomes that co-supplementation of zinc with iron decreased the beneficial effect of zinc. AUTHORS' CONCLUSIONS: Even though we included 16 new studies in this update, the overall conclusions of the review remain unchanged. Zinc supplementation might help prevent episodes of diarrhea and improve growth slightly, particularly in children aged 6 months to 12 years of age. The benefits of preventive zinc supplementation may outweigh the harms in regions where the risk of zinc deficiency is relatively high.

Evaluating the Potential Fitness Effects of Chinook Salmon (Oncorhynchus tshawytscha) Aquaculture Using Non-Invasive Population Genomic Analyses of MHC Nucleotide Substitution Spectra.

Genetic diversity plays a vital role in the adaptability of salmon to changing environmental conditions that can introduce new selective pressures on populations. Variability among local subpopulations may increase the chance that certain advantageous genes are passed down to future generations to mitigate susceptibility to novel diseases, warming oceans, loss of genetic stocks, and ocean acidification. Class I and II genes of the major histocompatibility complex (MHC) are crucial for the fitness of Chinook salmon due to the role they play in disease and pathogen resistance. The objective of this study was to assess the DNA sequence variability among wild and hatchery populations of Alaskan Chinook salmon at the class I α1 and class II ß1 exons of the MHC. We hypothesized that the 96 wild samples taken from the Deshka River would display greater levels of observed heterozygosity (Ho) relative to expected heterozygosity (He) in suggesting that individuals with similar phenotypes mate with one another more frequently than would be expected under random mating patterns. Conversely, since no mate selection occurs in the William Jack Hernandez Sport Fish hatchery, we would not expect to see this discrepancy (He = Ho) in the 96 hatchery fish tested in this study. Alternatively, we hypothesized that post-mating selection is driving higher levels of observed heterozygosity as opposed to mate selection. If this is the case, we will observe higher than expected levels of heterozygosity among hatchery salmon. Both populations displayed higher levels of observed heterozygosity than expected heterozygosity at the Class I and II loci but genetic differentiation between the spatially distinct communities was minimal. Class I sequences showed evidence of balancing selection, despite high rates of non-synonymous substitutions observed, specifically at the peptide binding regions of both MHC genes.

Exploring enablers and barriers to implementing the Transparency and Openness Promotion Guidelines: a theory-based survey of journal editors.

The Transparency and Openness Promotion (TOP) Guidelines provide a framework to help journals develop open science policies. Theories of behaviour change can guide understanding of why journals do (not) implement open science policies and the development of interventions to improve these policies. In this study, we used the Theoretical Domains Framework to survey 88 journal editors on their capability, opportunity and motivation to implement TOP. Likert-scale questions assessed editor support for TOP, and enablers and barriers to implementing TOP. A qualitative question asked editors to provide reflections on their ratings. Most participating editors supported adopting TOP at their journal (71%) and perceived other editors in their discipline to support adopting TOP (57%). Most editors (93%) agreed their roles include maintaining policies that reflect current best practices. However, most editors (74%) did not see implementing TOP as a high priority compared with other editorial responsibilities. Qualitative responses expressed structural barriers to implementing TOP (e.g. lack of time, resources and authority to implement changes) and varying support for TOP depending on study type, open science standard, and level of implementation. We discuss how these findings could inform the development of theoretically guided interventions to increase open science policies, procedures and practices.

Expanded geographic distribution and dietary strategies of the earliest Oldowan hominins and Paranthropus.

The oldest Oldowan tool sites, from around 2.6 million years ago, have previously been confined to Ethiopia's Afar Triangle. We describe sites at Nyayanga, Kenya, dated to 3.032 to 2.581 million years ago and expand this distribution by over 1300 kilometers. Furthermore, we found two hippopotamid butchery sites associated with mosaic vegetation and a C4 grazer-dominated fauna. Tool flaking proficiency was comparable with that of younger Oldowan assemblages, but pounding activities were more common. Tool use-wear and bone damage indicate plant and animal tissue processing. Paranthropus sp. teeth, the first from southwestern Kenya, possessed carbon isotopic values indicative of a diet rich in C4 foods. We argue that the earliest Oldowan was more widespread than previously known, used to process diverse foods including megafauna, and associated with Paranthropus from its onset.

Toward more rigorous and informative nutritional epidemiology: The rational space between dismissal and defense of the status quo.

To date, nutritional epidemiology has relied heavily on relatively weak methods including simple observational designs and substandard measurements. Despite low internal validity and other sources of bias, claims of causality are made commonly in this literature. Nutritional epidemiology investigations can be improved through greater scientific rigor and adherence to scientific reporting commensurate with research methods used. Some commentators advocate jettisoning nutritional epidemiology entirely, perhaps believing improvements are impossible. Still others support only normative refinements. But neither abolition nor minor tweaks are appropriate. Nutritional epidemiology, in its present state, offers utility, yet also needs marked, reformational renovation. Changing the status quo will require ongoing, unflinching scrutiny of research questions, practices, and reporting-and a willingness to admit that "good enough" is no longer good enough. As such, a workshop entitled "Toward more rigorous and informative nutritional epidemiology: the rational space between dismissal and defense of the status quo" was held from July 15 to August 14, 2020. This virtual symposium focused on: (1) Stronger Designs, (2) Stronger Measurement, (3) Stronger Analyses, and (4) Stronger Execution and Reporting. Participants from several leading academic institutions explored existing, evolving, and new better practices, tools, and techniques to collaboratively advance specific recommendations for strengthening nutritional epidemiology.