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Abstract Background Guideline development on testing is known to be difficult for guideline developers. It requires consideration of various aspects, such as accuracy, purpose of testing, and consequences on management and people-important outcomes. This can be outlined in a test-management pathway. We aimed to create and user-test a step-by-step guide for guideline developers for designing a test-management pathway. Methods Developmental design with a co-creative strategy. We created a draft step-by-step guide, that was user tested in a workshop with 19 experts, and by interviewing 7 guideline panel members. Results Our proposed guide consists of five blocks of signalling questions: patients/population, index test(s), current practice/comparison/control, people-important outcomes, and the link between testing and outcome(s). The user testing led to refinement of the signalling questions, the use of inclusive terminology, and addition of a test-management pathway figure with detailed explanation. Conclusions The step-by-step guide for formulating focused guideline questions regarding healthcare related testing can help in identifying relevant characteristics of the population, tests, and outcomes and to create a test management pathway. This should facilitate the formulation of evidence-based guideline recommendations about healthcare related testing.

Background Many interventions, especially those linked to open science, have been proposed to improve reproducibility in science. To what extent these propositions are based on scientific evidence from empirical evaluations is not clear. Aims The primary objective is to identify Open Science interventions that have been formally investigated regarding their influence on reproducibility and replicability. A secondary objective is to list any facilitators or barriers reported and to identify gaps in the evidence. Methods We will search broadly by using electronic bibliographic databases, broad internet search, and contacting experts in the field of reproducibility, replicability, and open science. Any study investigating interventions for their influence on the reproducibility and replicability of research will be selected, including those studies additionally investigating drivers and barriers to the implementation and effectiveness of interventions. Studies will first be selected by title and abstract (if available) and then by reading the full text by at least two independent reviewers. We will analyze existing scientific evidence using scoping review and evidence gap mapping methodologies. Results The results will be presented in interactive evidence maps, summarized in a narrative synthesis, and serve as input for subsequent research. Review registration This protocol has been pre-registered on OSF under doi https://doi.org/10.17605/OSF.IO/D65YS

There is an urgent need for biosurveillance of unregulated African meat imports at border points of entry in destination markets. This is underscored by recent pandemics linked to exotic wildlife products. Our objective was to catalog the quantity of meat that is informally transported from Africa into and through Europe often without any veterinary or sanitary checks. We searched and included peer-reviewed studies that contained data on the intercontinental movement of unregulated meat from the African continent. This was followed by an investigation of the reported contamination of such meat. We included fifteen airport studies with limited data on this topic. The references included in this review describe the quantity of meat found at border inspection posts and the presence of pathogens. Disease-causing pathogens were found to be present, and the results are organized into bacteria, virus, and parasite categories. The species of animal meat found in this review were linked to CITES-protected species some of which are known reservoir hosts for infectious diseases. This represents a potential and unquantified human health risk to populations along the supply chain, and a loss to biodiversity in supply countries. Meat samples described in this review were primarily found opportunistically by Customs officials, indicating that any estimate of the total quantities passing undetected through border checkpoints must remain tentative, and cannot rule out the possibility that it is indeed considerably higher. We propose a template for future studies regarding African meat imports at border points of entry. The result of this review illustrates a gap in knowledge and lacunae regarding the amount of unregulated African meat imports worldwide, the pathogens it may contain, and the resulting biodiversity loss that occurs from the intercontinental movement of this meat.

Background Several open science-promoting initiatives have been proposed to improve the quality of biomedical research, including initiatives for assessing researchers’ open science behaviour as criteria for promotion or tenure. Yet there is limited evidence to judge whether the interventions are effective. This review aimed to summarise the literature, identifying open science practices related to researcher assessment, and map the extent of evidence of existing interventions implemented to assess researchers and research impact. Methods A scoping review using the Joanna Briggs Institute Scoping Review Methodology was conducted. We included all study types that described any open science practice-promoting initiatives proposed or implemented to assess researchers and research impact, in health sciences, biomedicine, psychology, and economics. Data synthesis was quantitative and descriptive. Results Among 18,020 identified documents, 27 articles were selectedfor analysis. Most of the publications were in the field of health sciences (n = 10), and were indicated as research culture, perspective, commentary, essay, proceedings of a workshop, research article, world view, opinion, research note, editorial, report, and research policy articles (n = 22). The majority of studies proposed recommendations to address problems regarding threats to research rigour and reproducibility that were multi-modal (n = 20), targeting several open science practices. Some of the studies based their proposed recommendations on further evaluation or extension of previous initiatives. Most of the articles (n = 20) did not discuss implementation of their proposed intervention. Of the 27 included articles, 10 were cited in policy documents, with The Leiden Manifesto being the most cited (104 citations). Conclusion This review provides an overview of proposals to integrate open science into researcher assessment. The more promising ones need evaluation and, where appropriate, implementation. Study registration https://osf.io/ty9m7

Introduction Self-report questionnaires to screen for symptoms of common mental disorders (CMDs) are commonly used as inexpensive, easy-to-administer tools in research and clinical practice. However, their validity to detect the presence of any CMD across cultures and languages is unclear. Psychometrically sound and brief case-finding instruments are vital for the identification of individuals with mental health needs. With the increasing number of Arabic-speaking refugees in Europe, we aim to evaluate the diagnostic accuracy of Arabic-language screening instruments. Objectives The aim of this systematic review/meta-analysis is to synthesize the diagnostic accuracy of self-report questionnaires to detect depression, anxiety and posttraumatic stress disorder (PTSD) in Arabic-speaking populations. Methods Five databases were searched (inception-January 2021) (PROSPERO: CRD42018070645) for studies on the diagnostic accuracy of brief questionnaires in Arabic-speaking populations, with a clinical interview as reference standard. Data on sensitivity/specificity were extracted/calculated. Multi-threshold meta-analyses were performed (R diagmeta package). Study quality was assessed using QUADAS-2. Results We included 32 studies (N=4042 participants) reporting on questionnaires targeting depression/anxiety (14 questionnaires), distress (2 questionnaires), and PTSD (1 questionnaire). Optimal thresholds were identified for the Edinburgh Postnatal Depression Scale (EPDS; cut-off 11, sensitivity 76.9%, specificity 85.1%), Hospital Anxiety and Depression Scale (HADS) anxiety subscale (cut-off 7, sensitivity 81.9%, specificity 87.6%), depression subscale (cut-off 6, sensitivity 73.0%, specificity 88.6%), and Self-Reporting Questionnaire (SRQ-20; cut-off 8, sensitivity 86.0%, specificity 83.9%). Conclusions We present optimal thresholds that can be used by clinicians and researchers for the EPDS, HADS and SRQ-20. More research on Arabic-language questionnaires, especially those targeting PTSD, is needed. Disclosure No significant relationships.

Around 1 % of pregnancies develop Hyperemesis Gravidarum (HG), causing high physical and psychological morbidity. Reports on HG recurrence rate in subsequent pregnancies vary widely. An accurate rate of recurrence is needed for informed reproductive decision making. Our objective is to systematically review and aggregate reported rates for HG subsequent to index pregnancies affected by HG. We searched databases from inception as per the protocol registered on PROSPERO. No language restrictions were applied. Inclusion was not restricted based on how HG was defined; reports of severe NVP were included where authors defined the condition as HG. We included descriptive epidemiological, case control and cohort study designs. Eligibility screening was performed in duplo. We extracted data on populations, study methods and outcomes of significance. A panel of patients reviewed the results and provided discussion and feedback. Quality was assessed with the JBI (2017) critical appraisal tool independently by two reviewers. We performed the searches on 1st November 2019. Our search yielded 4454 unique studies, of which five (n = 40,350 HG cases) matched eligibility criteria; One longitudinal and four population-based cohort studies from five countries. Follow-up ranged from 2 to 31 years. Definition of HG and data collection methods in all the studies created heterogeneity. Quality was low; studies lacked valid and reliable exposure, and/or follow-up was insufficient. Meta-analysis was not possible due to clinical and statistical heterogeneity. This systematic review found five heterogeneous studies reporting recurrence rates from 15 to 81%. Defining HG as hospital cases may have introduced detection bias and contribute to clinical heterogeneity. A prospective longitudinal cohort study using an internationally agreed definition of HG and outcomes meaningful to patients is required to establish the true recurrence rate of HG. Keywords: Hyperemesis gravidarum, Recurrence rate, Nausea and vomiting of pregnancy, Reproductive planning

Background: Before a new test can be routinely used in your laboratory, its reliability must be established in the laboratory where it will be used. International standards demand validation and verification procedures for new tests. The International Organization for Standardization (ISO) 15189 was recently updated, and the European Commission's In Vitro Diagnostic Regulation (IVDR) came into effect. These events will likely increase the need for validation and verification procedures., Objectives: This paper aims to provide practical guidance in validating or verifying microbiology tests, including antimicrobial susceptibility tests in a clinical microbiology laboratory., Sources: It summarizes and interprets certain parts of standards such as ISO 15189:2022, and regulations, such as IVDR 2017/746 regarding validation or verification of a new test in a routine clinical microbiology laboratory., Content: The reasons for choosing a new test and the outline of the validation and verification plan are discussed. Furthermore, the following topics are touched upon: the choice of reference standard, number of samples, testing procedures, how to solve the discrepancies between results from new test and reference standard, and acceptance criteria. Arguments for selecting certain parameters (such as reference standard and sample size) and examples are given., Implications: With the expected increase in validation and verification procedures because of the implementation of IVDR, this paper may aid in planning and executing these procedures., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: To review the findings of studies that have evaluated the design and/or usability of key risk of bias (RoB) tools for the assessment of RoB in primary studies, as categorized by the Library of Assessment Tools and InsTruments Used to assess Data validity in Evidence Synthesis Network (a searchable library of RoB tools for evidence synthesis): Prediction model Risk Of Bias ASessment Tool (PROBAST) , Risk of Bias-2 (RoB2), Risk Of Bias In Non-randomised Studies of Interventions (ROBINS-I), Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2), Quality Assessment of Diagnostic Accuracy Studies-Comparative (QUADAS-C), Quality Assessment of Prognostic Accuracy Studies (QUAPAS), Risk Of Bias in Non-randomised Studies of Exposures (ROBINS-E), and the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) RoB checklist., Study Design and Setting: Systematic review of methodological studies. We conducted a forward citation search from the primary report of each tool, to identify primary studies that aimed to evaluate the design and/or usability of the tool. Two reviewers assessed studies for inclusion. We extracted tool features into Microsoft Word and used NVivo for document analysis, comprising a mix of deductive and inductive approaches. We summarized findings within each tool and explored common findings across tools., Results: We identified 13 tool evaluations meeting our inclusion criteria: PROBAST (3), RoB2 (3), ROBINS-I (4), and QUADAS-2 (3). We identified no evaluations for the other tools. Evaluations varied in clinical topic area, methodology, approach to bias assessment, and tool user background. Some had limitations affecting generalizability. We identified common findings across tools for 6/14 themes: (1) challenging items (eg, RoB2/ROBINS-I "deviations from intended interventions" domain), (2) overall RoB judgment (concerns with overall risk calculation in PROBAST/ROBINS-I), (3) tool usability (concerns about complexity), (4) time to complete tool (varying demands on time, eg, depending on number of outcomes assessed), (5) user agreement (varied across tools), and (6) recommendations for future use (eg, piloting) and development (add intermediate domain answer to QUADAS-2/PROBAST; provide clearer guidance for all tools). Of the other eight themes, seven only had findings for the QUADAS-2 tool, limiting comparison across tools, and one ("reorganization of questions") had no findings., Conclusion: Evaluations of key RoB tools have posited common challenges and recommendations for tool use and development. These findings may be helpful to people who use or develop RoB tools. Guidance is necessary to support the design and implementation of future RoB tool evaluations., Competing Interests: Declaration of competing interest Eve Tomlinson: Since working on this review, Eve has joined the QUADAS-3 steering group. Chris Cooper: None. Clare Davenport: Clare Davenport is a member of the Diagnostic test Accuracy Editorial Team and is an author on the Cochrane Handbook for Systematic Reviews of Diagnostic Test Accuracy Studies. Clare was a member of the QUADAS-2 working group and a member of the QUADAS-C steering group. She is currently a member of the QUADAS-3 steering group. Anne W.S. Rutjes: Anne is regularly hired by the Federal office of Public Health in Bern, Switzerland as a methodological consultant for Health Technology Assessment reports and receives teaching fees from the academic sector on topics related to research designs, risk of bias tools, and reporting tools. Anne was an editor for the Cochrane Dementia and Cognitive Improvement group up to March 2023 and is an author on the Cochrane Handbook for Systematic Reviews on Diagnostic Test Accuracy Studies. She was a panel member of PROBAST and various COSMIN tools, part of the steering group of QUADAS and QUADAS-2, is part of the core group developing a RoB tool for prevalence studies, and one developing a RoB and reporting tool for use in studies evaluating the incidence of adverse events detected with record review methods. Mariska Leeflang: Mariska Leeflang is an author of the following risk of bias tools: QUADAS-C, QUADAS-2, and PROBAST. Mariska is an editor of the Cochrane Diagnostic Test Accuracy Handbook. Sue Mallett: Sue Mallett is an author of the following risk of bias tools: QUADAS-C, QUADAS-2, and PROBAST. She is also on the leadership board for the LATITUDES Network. No payments are associated with this. Penny Whiting: Penny is an author on the Cochrane Handbook for Systematic Reviews on Diagnostic Test Accuracy Studies. She led the development of QUADAS and QUADAS-2, and was a steering group member for the development of PROBAST. She contributed to the development of RoB 2 and ROBINS-I. She is also on the leadership board for the LATITUDES Network., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Aim: To assess the accuracy and technical characteristics of CYP2C19 point of care tests (POCTs). Patients & methods: Systematic review of primary studies, in any population or setting, that evaluated POCTs for detecting CYP2C19 loss of function (LOF) alleles. Results: Eleven studies provided accuracy data (eight Spartan; one Genomadix Cube; one GMEX; one Genedrive). The POCTs had very high sensitivity and specificity for the alleles they tested for. Twenty-two studies reported technical characteristics: POCTs were easy to operate and provided results quickly. Limited data were reported for test failure rate and cost. Conclusion: CYP2C19 POCTs may be a useful alternative to laboratory-based testing to guide antiplatelet therapy. Further data are required on accuracy (GMEX; Genedrive), test failure and cost (all POCT).

Systematic reviews of diagnostic accuracy studies can provide the best available evidence to inform decisions regarding the use of a diagnostic test. In this guide, the authors provide a practical approach for clinicians to appraise diagnostic accuracy systematic reviews and apply their results to patient care. The first step is to identify an appropriate systematic review with a research question matching the clinical scenario. The user should evaluate the rigor of the review methods to evaluate its credibility (Did the review use clearly defined eligibility criteria, a comprehensive search strategy, structured data collection, risk of bias and applicability appraisal, and appropriate meta-analysis methods?). If the review is credible, the next step is to decide whether the diagnostic performance is adequate for clinical use (Do sensitivity and specificity estimates exceed the threshold that makes them useful in clinical practice? Are these estimates sufficiently precise? Is variability in the estimates of diagnostic accuracy across studies explained?). Diagnostic accuracy systematic reviews that are judged to be credible and provide diagnostic accuracy estimates with sufficient certainty and relevance are the most useful to inform patient care. This review discusses comparative, noncomparative, and emerging approaches to systematic reviews of diagnostic accuracy using a clinical scenario and examples based on recent publications., (© RSNA, 2023.)

Background: Biparametric (bp)-MRI and multiparametric (mp)-MRI may improve the diagnostic accuracy of renal mass histology., Purpose: To evaluate the available evidence on the diagnostic accuracy of bp-MRI and mp-MRI for solid renal masses in differentiating malignant from benign, aggressive from indolent, and clear cell renal cell carcinoma (ccRCC) from other histology., Study Type: Systematic review., Population: MEDLINE, EMBASE, and CENTRAL up to January 11, 2022 were searched., Field Strength/sequence: 1.5 or 3 Tesla., Assessment: Eligible studies evaluated the accuracy of MRI (with at least two sequences: T2, T1, dynamic contrast and diffusion-weighted imaging) for diagnosis of solid renal masses in adult patients, using histology as reference standard. Risk of bias and applicability were assessed using QUADAS-2., Statistical Tests: Meta-analysis using a bivariate logitnormal random effects model., Results: We included 10 studies (1239 masses from approximately 1200 patients). The risk of bias was high in three studies, unclear in five studies and low in two studies. The diagnostic accuracy of malignant (vs. benign) masses was assessed in five studies (64% [179/281] malignant). The summary estimate of sensitivity was 95% (95% confidence interval [CI]: 77%-99%), and specificity was 63% (95% CI: 46%-77%). No study assessed aggressive (vs. indolent) masses. The diagnostic accuracy of ccRCC (vs. other subtypes) was evaluated in six studies (47% [455/971] ccRCC): the summary estimate of sensitivity was 85% (95% CI: 77%-90%) and specificity was 77% (95% CI: 73%-81%)., Data Conclusion: Our study reveals deficits in the available evidence on MRI for diagnosis of renal mass histology. The number of studies was limited, at unclear/high risk of bias, with heterogeneous definitions of solid masses, imaging techniques, diagnostic criteria, and outcome measures., Evidence Level: 3 TECHNICAL EFFICACY: Stage 2., (© 2022 International Society for Magnetic Resonance in Medicine.)

Whereas diagnostic tests help detect the cause of signs and symptoms, prognostic tests assist in evaluating the probable course of the disease and future outcome. Studies to evaluate prognostic tests are longitudinal, which introduces sources of bias different from those for diagnostic accuracy studies. At present, systematic reviews of prognostic tests often use the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies 2) tool to assess risk of bias and applicability of included studies because no equivalent instrument exists for prognostic accuracy studies., QUAPAS (Quality Assessment of Prognostic Accuracy Studies) is an adaptation of QUADAS-2 for prognostic accuracy studies. Questions likely to identify bias were evaluated in parallel and collated from QUIPS (Quality in Prognosis Studies) and PROBAST (Prediction Model Risk of Bias Assessment Tool) and paired to the corresponding question (or domain) in QUADAS-2. A steering group conducted and reviewed 3 rounds of modifications before arriving at the final set of domains and signaling questions., QUAPAS follows the same steps as QUADAS-2: Specify the review question, tailor the tool, draw a flow diagram, judge risk of bias, and identify applicability concerns. Risk of bias is judged across the following 5 domains: participants, index test, outcome, flow and timing, and analysis. Signaling questions assist the final judgment for each domain. Applicability concerns are assessed for the first 4 domains., The authors used QUAPAS in parallel with QUADAS-2 and QUIPS in a systematic review of prognostic accuracy studies. QUAPAS improved the assessment of the flow and timing domain and flagged a study at risk of bias in the new analysis domain. Judgment of risk of bias in the analysis domain was challenging because of sparse reporting of statistical methods.

Background: Point-of-care tests could be essential in differentiating bacterial and viral acute community-acquired lower respiratory tract infections and driving antibiotic stewardship in the community., Objectives: To assess diagnostic test accuracy of point-of-care tests in community settings for acute community-acquired lower respiratory tract infections., Data Sources: Multiple databases (MEDLINE, EMBASE, Web of Science, Cochrane Library, Open Gray) from inception to 31 May 2021, without language restrictions., Study Eligibility Criteria: Diagnostic test accuracy studies involving patients at primary care, outpatient clinic, emergency department and long-term care facilities with a clinical suspicion of acute community-acquired lower respiratory tract infections. The comparator was any test used as a comparison to the index test. In order not to limit the study inclusion, the comparator was not defined a priori., Assessment of Risk of Bias: Four investigators independently extracted data, rated risk of bias, and assessed the quality using QUADAS-2., Methods of Data Synthesis: The measures of diagnostic test accuracy were calculated with 95% CI., Results: A total of 421 studies addressed at least one point-of-care test. The diagnostic performance of molecular tests was higher compared with that of rapid diagnostic tests for all the pathogens studied. The accuracy of stand-alone signs and symptoms or biomarkers was poor. Lung ultrasound showed high sensitivity and specificity (90% for both) for the diagnosis of bacterial pneumonia. Rapid antigen-based diagnostic tests for influenza, respiratory syncytial virus, human metapneumovirus, and Streptococcus pneumoniae had sub-optimal sensitivity (range 49%-84%) but high specificity (>80%)., Discussion: Physical examination and host biomarkers are not sufficiently reliable as stand-alone tests to differentiate between bacterial and viral pneumonia. Lung ultrasound shows higher accuracy than chest X-ray for bacterial pneumonia at emergency department. Rapid antigen-based diagnostic tests cannot be considered fully reliable because of high false-negative rates. Overall, molecular tests for all the pathogens considered were found to be the most accurate., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Self-report screening instruments are frequently used as scalable methods to detect common mental disorders (CMDs), but their validity across cultural and linguistic groups is unclear. We summarized the diagnostic accuracy of brief questionnaires on symptoms of depression, anxiety and posttraumatic stress disorder (PTSD) among Arabic-speaking adults., Methods: Five databases were searched from inception to 22 January 2021 (PROSPERO: CRD42018070645). Studies were included when diagnostic accuracy of brief (maximally 25 items) psychological questionnaires was assessed in Arabic-speaking populations and the reference standard was a clinical interview. Data on sensitivity/specificity, area under the curve, and data to generate 2 × 2 tables at various thresholds were extracted. Meta-analysis was performed using the diagmeta package in R. Quality of studies was assessed with QUADAS-2., Results: Thirty-two studies ( N participants = 4042) reporting on 17 questionnaires with 5-25 items targeting depression/anxiety ( n = 14), general distress ( n = 2), and PTSD ( n = 1) were included. Seventeen studies (53%) scored high risk on at least two QUADAS-2 domains. The meta-analysis identified an optimal threshold of 11 (sensitivity 76.9%, specificity 85.1%) for the Edinburgh Postnatal Depression Scale (EPDS) ( n studies = 7, n participants = 711), 7 (sensitivity 81.9%, specificity 87.6%) for the Hospital Anxiety and Depression Scale (HADS) anxiety subscale and 6 (sensitivity 73.0%, specificity 88.6%) for the depression subscale ( n studies = 4, n participants = 492), and 8 (sensitivity 86.0%, specificity 83.9%) for the Self-Reporting Questionnaire (SRQ-20) ( n studies = 4, n participants = 459)., Conclusion: We present optimal thresholds to screen for perinatal depression with the EPDS, anxiety/depression with the HADS, and CMDs with the SRQ-20. More research on Arabic-language questionnaires, especially those targeting PTSD, is needed., Competing Interests: None., (© The Author(s) 2021.)

Objective: To describe the discrimination and calibration of clinical prediction models, identify characteristics that contribute to better predictions and investigate predictors that are associated with unplanned hospital readmissions., Design: Systematic review and meta-analysis., Data Source: Medline, EMBASE, ICTPR (for study protocols) and Web of Science (for conference proceedings) were searched up to 25 August 2020., Eligibility Criteria for Selecting Studies: Studies were eligible if they reported on (1) hospitalised adult patients with acute heart disease; (2) a clinical presentation of prediction models with c-statistic; (3) unplanned hospital readmission within 6 months., Primary and Secondary Outcome Measures: Model discrimination for unplanned hospital readmission within 6 months measured using concordance (c) statistics and model calibration. Meta-regression and subgroup analyses were performed to investigate predefined sources of heterogeneity. Outcome measures from models reported in multiple independent cohorts and similarly defined risk predictors were pooled., Results: Sixty studies describing 81 models were included: 43 models were newly developed, and 38 were externally validated. Included populations were mainly patients with heart failure (HF) (n=29). The average age ranged between 56.5 and 84 years. The incidence of readmission ranged from 3% to 43%. Risk of bias (RoB) was high in almost all studies. The c-statistic was <0.7 in 72 models, between 0.7 and 0.8 in 16 models and >0.8 in 5 models. The study population, data source and number of predictors were significant moderators for the discrimination. Calibration was reported for 27 models. Only the GRACE (Global Registration of Acute Coronary Events) score had adequate discrimination in independent cohorts (0.78, 95% CI 0.63 to 0.86). Eighteen predictors were pooled., Conclusion: Some promising models require updating and validation before use in clinical practice. The lack of independent validation studies, high RoB and low consistency in measured predictors limit their applicability., Prospero Registration Number: CRD42020159839., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To estimate the effect of an intervention compared to the usual peer-review process on reducing spin in the abstract's conclusion of biomedical study reports., Study Design and Setting: We conducted a two-arm, parallel-group RCT in a sample of primary research manuscripts submitted to BMJ Open. The authors received short instructions alongside the peer reviewers' comments in the intervention group. We assessed the presence of spin (primary outcome), types of spin, and wording change in the revised abstract's conclusion. Outcome assessors were blinded to the intervention assignment., Results: Of the 184 manuscripts randomized, 108 (54 intervention, 54 control) were selected for revision and could be evaluated for the presence of spin. The proportion of manuscripts with spin was 6% lower (95% CI: 24% lower to 13% higher) in the intervention group (57%, 31/54) than in the control group (63%, 34/54). The wording of the revised abstract's conclusion was changed in 34/54 (63%) manuscripts in the intervention group and 26/54 (48%) in the control group. The four prespecified types of spin involved (i) selective reporting (12 in the intervention group vs. 8 in the control group), (ii) including information not supported by evidence (9 vs. 9), and (iii) interpretation not consistent with the study results (14 vs. 18), and (iv) unjustified recommendations for practice (5 vs. 11)., Conclusion: These short instructions to authors did not have a statistically significant effect on reducing spin in revised abstract conclusions, and based on the confidence interval, the existence of a large effect can be excluded. Other interventions to reduce spin in reports of original research should be evaluated., Study Registration: osf.io/xnuyt., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Context: In the last few decades, data acquisition and processing has seen tremendous amount of growth, thus sparking interest in machine learning (ML) within the health care system., Objective: Our aim for this review is to provide an evidence map of the current available evidence on ML in pediatrics and adolescent medicine and provide insight for future research., Data Sources: A literature search was conducted by using Medline, the Cochrane Library, the Cumulative Index to Nursing and Allied Health Literature Plus, Web of Science Library, and EBSCO Dentistry & Oral Science Source., Study Selection: Articles in which an ML model was assessed for the diagnosis, prediction, or management of any condition in children and adolescents (0-18 years) were included., Data Extraction: Data were extracted for year of publication, geographical location, age range, number of participants, disease or condition under investigation, study methodology, reference standard, type, category, and performance of ML algorithms., Results: The review included 363 studies, with subspecialties such as psychiatry, neonatology, and neurology having the most literature. A majority of the studies were from high-income (82%; n = 296) and upper middle-income countries (15%; n = 56), whereas only 3% ( n = 11) were from low middle-income countries. Neural networks and ensemble methods were most commonly tested in the 1990s, whereas deep learning and clustering emerged rapidly in the current decade., Limitations: Only studies conducted in the English language could be used in this review., Conclusions: The interest in ML has been growing across various subspecialties and countries, suggesting a potential role in health service delivery for children and adolescents in the years to come., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2021 by the American Academy of Pediatrics.)

Background: To compare the frequency of "spin" in systematic reviews of diagnostic accuracy studies in high-impact journals with the frequency a previously assessed series of reviews., Methods: Medline was searched from January 2010 to January 2019. Systematic reviews of diagnostic accuracy studies were included if they reported a meta-analysis and were published in a journal with an impact factor >5. Two investigators independently scored each included systematic review for positivity of conclusions and for actual and potential overinterpretation practices., Results: Of 137 included systematic reviews, actual overinterpretation was present in ≥1 form in the abstract in 63 (46%) and in the full-text report in 52 (38%); 108 (79%) contained a form of potential overinterpretation. Compared with the previously assessed series (reviews published 2015-2016), reviews in this series were less likely to contain ≥1 form of actual overinterpretation in the abstract and full-text report or ≥1 form of potential overinterpretation (P < 0.001 for all comparisons). The significance of these comparisons did not persist for actual overinterpretation in sensitivity analysis in which Cochrane systematic reviews were removed. Reviews published in the Cochrane Database of Systematic Reviews were less likely to contain actual overinterpretation in the abstract or the full-text report than reviews in other high-impact journals (P < 0.001 for both comparisons)., Conclusions: Reviews of diagnostic accuracy studies in high-impact journals are less likely to contain overinterpretation or spin. This difference is largely due to the reviews published in the Cochrane Database of Systematic Reviews, which contain spin less often than reviews published in other high-impact journals., (© American Association for Clinical Chemistry 2020. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: This article provides updated GRADE guidance about how authors of systematic reviews and health technology assessments and guideline developers can rate the certainty of evidence (also known as quality of the evidence or confidence in the estimates) of a body of evidence addressing test accuracy (TA) on the domains imprecision, inconsistency, publication bias, and other domains. It also provides guidance for how to present synthesized information in evidence profiles and summary of findings tables., Study Design and Setting: We present guidance for rating certainty in TA in clinical and public health and review the presentation of results of a body of evidence regarding tests., Results: Supplemented by practical examples, we describe how raters of the evidence can apply the GRADE domains inconsistency, imprecision, and publication bias to a body of evidence of TA studies., Conclusion: Using GRADE in Cochrane and other reviews as well as World Health Organization and other guidelines helped refining the GRADE approach for rating the certainty of a body of evidence from TA studies. Although several of the GRADE domains (e.g., imprecision and magnitude of the association) require further methodological research to help operationalize them, judgments need to be made on the basis of what is known so far., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: This article provides updated GRADE guidance about how authors of systematic reviews and health technology assessments and guideline developers can assess the results and the certainty of evidence (also known as quality of the evidence or confidence in the estimates) of a body of evidence addressing test accuracy (TA)., Study Design and Setting: We present an overview of the GRADE approach and guidance for rating certainty in TA in clinical and public health and review the presentation of results of a body of evidence regarding tests. Part 1 of the two parts in this 21st guidance article about how to apply GRADE focuses on understanding study design issues in test accuracy, provide an overview of the domains, and describe risk of bias and indirectness specifically., Results: Supplemented by practical examples, we describe how raters of the evidence using GRADE can evaluate study designs focusing on tests and how they apply the GRADE domains risk of bias and indirectness to a body of evidence of TA studies., Conclusion: Rating the certainty of a body of evidence using GRADE in Cochrane and other reviews and World Health Organization and other guidelines dealing with in TA studies helped refining our approach. The resulting guidance will help applying GRADE successfully for questions and recommendations focusing on tests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: CS constitutes a rare but potentially underdiagnosed and fatal disease. Its diagnosis remains difficult owing to the infrequent and indistinguishable symptoms and the lack of formal diagnostic criteria dependent upon the diagnostic techniques used. Early diagnosis and treatment, however, may help to counter its poor prognosis.We aim to characterize and compare the diagnostic accuracy of cardiac MRI, FDG-PET and myocardial biopsy for the diagnosis of cardiac sarcoidosis and to advance and compare methods for complex diagnostic test accuracy reviews and meta-analysis., Methods: Following a systematic review on DTA studies on the aforementioned topic, a four-part approach to meta-analysis will be used: (1) direct comparison of index tests with clinical reference standard, (2) indirect comparison of index tests with clinical reference standard, (3) addition of an alternative test to that indirect comparison (4) and Bayesian meta-analysis using results of part 3 as informative prior for comparisons analogous to part 1 and 2., Discussion: The most widely recognized diagnostic algorithm for cardiac sarcoidosis is considered out of date, as it precedes the introduction of imaging techniques in diagnostic pathways. These novel imaging techniques, like CMR and FDG-PET scan, have emerged as promising diagnostic tools which may fill the current diagnostic gap. Thus, a systematic review and evaluation of CS diagnosis are much needed. Such an attempt is anticipated to alter the current diagnostic guidelines for CS by shedding more light on the role of sophisticated imaging techniques on prompt CS therapy and follow-up., Trial Registration: PROSPERO, CRD42019047126., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2020.)

Background: Concerns are raised about missed, delayed and inappropriate diagnosis of Lyme Borreliosis. Quantitative descriptive studies have demonstrated non-adherence to the guidelines for testing for Lyme Borreliosis. Objectives: To gain insight into the diagnostic practices that general practitioners apply for Lyme Borreliosis, their motives for ordering tests and how they act upon test results. Methods: A qualitative study among 16 general practitioners using semi-structured interviews and thematic content analysis. Results: Five themes were distinguished: (1) recognising localised Lyme Borreliosis and symptoms of disseminated disease, (2) use of the guideline, (3) serological testing in patients with clinically suspect Lyme Borreliosis, (4) serological testing without clinical suspicion of Lyme Borreliosis, and (5) dealing with the limited accuracy of the serological tests. Whereas the national guideline recommends using serological tests for diagnosing, general practitioners also use them for ruling out disseminated Lyme Borreliosis. Reasons for non-adherence to the guideline for testing were to reassure patients with non-specific symptoms or without symptoms who feared to have Lyme disease, confirmation of localised Lyme Borreliosis and routine work-up in patients with continuing unexplained symptoms. Some general practitioners referred all patients who tested positive to medical specialists, where others struggled with the explanation of the results. Conclusion: Both diagnosis and ruling out of disseminated Lyme Borreliosis can be difficult for general practitioners. General practitioners use serological tests to reassure patients and rule out Lyme Borreliosis, thereby deviating from the national guideline. Interpretation of test results in these cases can be difficult.

Introduction: Inactivated hepatitis A (HepA) vaccines are very immunogenic in healthy individuals; however, it remains unclear how different immunosuppressive regimens affect HepA vaccine immunogenicity. Our objective was to summarise the current evidence on immunogenicity of HepA vaccination in patients using immunosuppressive drugs., Methods: We systematically searched the literature for studies on immunogenicity of inactivated HepA vaccines in adults using immunosuppressive drugs. Studies reporting seroconversion rates (SCR) 4-8 weeks after 1 and 2 doses of HepA vaccine in organ transplant recipients and patients with chronic inflammatory conditions were included in a meta-analysis., Results: We included 17 studies, comprising 1,332 individuals. In healthy controls (2 studies), SCRs were 90-94% after the first dose and 100% after the second dose. In organ transplant recipients, SCRs ranged from 0 to 67% after the first dose of vaccine and 0-97% after the second dose. In patients with chronic inflammatory conditions, SCRs ranged from 6% to 100% after the first dose and from 48 to 100% after the second dose of vaccine. Patients using a TNF-alpha inhibitor versus conventional immune-modulators (e.g. methotrexate, azathioprine, corticosteroids) were more likely to seroconvert after the first dose of vaccine (OR12.1 [2.14-68.2]) but not after the second dose of vaccine (OR 0.78 [0.21-2.92]) in a meta-analysis., Conclusion: Studies evaluating HepA vaccine immunogenicity in immunosuppressive agents are heterogeneous. Overall, there is an impaired immune response following HepA vaccination in patients using immunosuppressive drugs, especially after only one dose of vaccine and in organ transplant recipients. HepA vaccination should therefore be considered before immunosuppressive therapy. Future research should focus on alternative vaccination regimens and long-term immunogenicity., Prospero Id: CRD42018102607., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Existing high-priority target product profiles (TPPs) of the World Health Organization (WHO) establish important needs for tuberculosis (TB) diagnostic development. Building on this earlier work, this guidance series aims to provide study guidance for performing accuracy studies of novel diagnostic products that may meet the 4 high-priority WHO TPPs and thus enable adequate evidence generation to inform a WHO evidence review process. Diagnostic accuracy studies represent a fundamental step in the validation of all tests. Unfortunately, such studies often have limitations in design, execution, and reporting, leading to low certainty of the evidence about true test performance, which can delay or impede policy and scale-up decisions. This introductory paper outlines the following: (1) the purpose of this series of papers on study guidance; (2) WHO evidence needs and process for the development of policy guidelines for new TB diagnostic tests; and (3) study design considerations, ie, general diagnostic study considerations, intended use of test and role in the clinical pathway, choice of population and setting, index-test specific issues, suitable reference standard and comparators, study flow and specimen issues, and finally key issues beyond accuracy that should be considered. The other 4 papers in this series will provide more detailed guidance for each of the 4 WHO high-priority TPPs. By increasing the clarity around the clinical evaluation needs for tests that have the potential to meet the TPP specifications, we hope to support harmonized evidence generation and enable the WHO review process towards meeting the WHO End TB Strategy targets for reducing the incidence and mortality associated with TB., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Purpose: The purpose of this methodological review was to determine the extent to which comparative imaging systematic reviews of diagnostic test accuracy (DTA) use primary studies with comparative or non-comparative designs., Methods: MEDLINE was used to identify DTA systematic reviews published in imaging journals between January 2000 and May 2018., Inclusion Criteria: systematic reviews comparing at least two index tests (one of which was imaging-based); review characteristics were extracted. Study design and other characteristics of primary studies included in the systematic reviews were evaluated., Results: One hundred three comparative imaging reviews were included; 11 (11%) included only comparative studies, 12 (11%) included only non-comparative primary studies, and 80 (78%) included both comparative and non-comparative primary studies. For reviews containing both comparative and non-comparative primary studies, the median proportion of non-comparative primary studies was 81% (IQR 57-90%). Of 92 reviews that included non-comparative primary studies, 86% did not recognize this as a limitation. Furthermore, among 4182 primary studies, 3438 (82%) were non-comparative and 744 (18%) were comparative in design., Conclusion: Most primary studies included in comparative imaging reviews are non-comparative in design and awareness of the risk of bias associated with this is low. This may lead to incorrect conclusions about the relative accuracy of diagnostic tests and be counter-productive for informing guidelines and funding decisions about imaging tests., Key Points: • Few comparative accuracy imaging reviews include only primary studies with optimal comparative study designs. Among the rest, few recognize the risk of bias conferred from inclusion of primary studies with non-comparative designs. • The demand for accurate comparative accuracy data combined with minimal awareness of valid comparative study designs may lead to counter-productive research and inadequately supported clinical decisions for diagnostic tests. • Using comparative accuracy imaging reviews with a high risk of bias to inform guidelines and funding decisions may have detrimental impacts on patient care.

Objectives: This article describes the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group's framework of moving from test accuracy to patient or population-important outcomes. We focus on the common scenario when studies directly evaluating the effect of diagnostic and other tests or strategies on health outcomes are not available or are not providing the best available evidence., Study Design and Setting: Using practical examples, we explored how guideline developers and other decision makers can use information from test accuracy to develop a recommendation by linking evidence that addresses downstream consequences. Guideline panels should develop an analytic framework that summarizes the actions that follow from applying a test and the consequences., Results: We describe GRADE's current thinking about the overall certainty of the evidence (also known as quality of the evidence or confidence in the estimates) arising from consideration of the often complex pathways that involve multiple tests and management options. Each link in the evidence can-and often does-lower the overall certainty of the evidence required to formulate recommendations and make decisions about tests. The frequency with which an outcome occurs and its importance will influence whether or not a particular step in the linked evidence is critical to decision-making., Conclusions: Overall certainty may be expressed by the weakest critical step in the linked evidence. The linked approach to addressing optimal testing will often require the use of decision analytic approaches. We present an example that involves decision modeling in a GRADE Evidence to Decision framework for cervical cancer screening. However, because resources and time of guideline developers may be limited, we describe alternative, pragmatic strategies for developing recommendations addressing test use., (Copyright © 2019. Published by Elsevier Inc.)

Background: Systematic reviews are critical for obtaining accurate estimates of diagnostic test accuracy, yet these require extracting information buried in free text articles, an often laborious process., Objective: We create a dataset describing the data extraction and synthesis processes in 63 DTA systematic reviews, and demonstrate its utility by using it to replicate the data synthesis in the original reviews., Method: We construct our dataset using a custom automated extraction pipeline complemented with manual extraction, verification, and post-editing. We evaluate using manual assessment by two annotators and by comparing against data extracted from source files., Results: The constructed dataset contains 5,848 test results for 1,354 diagnostic tests from 1,738 diagnostic studies. We observe an extraction error rate of 0.06-0.3%., Conclusions: This constitutes the first dataset describing the later stages of the DTA systematic review process, and is intended to be useful for automating or evaluating the process.

Objective: To develop guidance for authors of diagnostic test accuracy (DTA) reviews to help them write a plain language summary of the results of their review., Study Design and Setting: We used a combination of focus groups, user testing, and a web-based survey. Participants included patient representatives, media representatives, and health professionals., Results: We present step-by-step guidance for authors of DTA reviews for writing a plain language summary. This guidance is illustrated with examples of reader-tested sentences, explanations, and a figure., Conclusion: We hope this guidance will allow reviewers to present the findings of DTA reviews so that it is easier for readers to understand the results and conclusions. This will increase the accessibility of these reviews for various audiences., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: In comparative systematic reviews of diagnostic accuracy, inconsistencies between direct and indirect comparisons may lead to bias. We investigated whether using individual patient data (IPD) can adjust for this form of bias., Study Design and Setting: We included IPD of 3 ovarian reserve tests from 32 studies. Inconsistency was defined as a statistically significant difference in relative accuracy or different comparative results between the direct and indirect evidence. We adjusted for the effect of threshold and reference standard, as well as for patient-specific variables., Results: Anti-Müllerian hormone (AMH) and follicle stimulation hormone (FSH) differed significantly in sensitivity (-0.1563, P = 0.04). AMH and antral follicle count (AFC) differed significantly in sensitivity (0.1465, P < 0.01). AMH and AFC differed significantly in specificity (-0.0607, P = 0.02). The area under the curve (AUC) differed significantly between AFC and FSH (0.0948, P < 0.01) in the direct comparison but not (0.0678, P = 0.09) in the indirect comparison. The AUCs of AFC and AMH differed significantly (-0.0830, P < 0.01) in the indirect comparison but not (-0.0176, P = 0.29) in the direct comparison. These differences remained after adjusting for indirectness., Conclusion: Estimates of comparative accuracy obtained through indirect comparisons are not always consistent with those obtained through direct comparisons. Using IPD to adjust for indirectness did not successfully remove the bias in this case study., (Copyright © 2015 Elsevier Inc. All rights reserved.)