Circulating biomarkers might improve the prediction of outcomes in patients with traumatic brain injury (TBI) beyond current approaches. Robust and up-to-date evidence is required to support their clinical utility and integration into medical practice to guide decision-making. Our objective was to critically appraise the existing evidence for six core blood-based TBI biomarkers (S100 calcium-binding protein B, glial fibrillary acidic protein [GFAP], neuron-specific enolase, ubiquitin C-terminal hydrolase-L1 [UCH-L1], tau and neurofilament proteins), in predicting outcome after TBI. Electronic databases, including Medline and Embase, were searched for articles published from their inception to October 2023. Studies were included if they evaluated the accuracy of blood biomarker concentrations at hospital presentation for outcome prediction in adult patients with TBI. Outcomes assessed were mortality, Glasgow Outcome Scale (GOS)/GOS extended (GOS-E), or the Rivermead Post-Concussion Symptoms Questionnaire (RPQ). Study selection, data extraction, and quality assessment using the modified Quality Assessment of Prognostic Accuracy Studies tool were performed by two authors independently, with disagreements being resolved through discussion or arbitration. If appropriate, a meta-analysis was conducted by calculating the weighted summary area under the curve (AUC) and using a bivariate regression model. Of 12,792 retrieved records, 32 articles, including 7481 patients with TBI, were selected as relevant. Two biomarkers showed strong associations with in-hospital and 6-month mortality: GFAP (unadjusted pooled AUC 0.81 [95% confidence interval [CI] 0.75-0.87] and 0.82 [0.80-0.85], respectively) and UCH-L1 (0.80 [0.74-0.85] and 0.83 [0.77-0.88]). Their addition to models that included established risk factors consistently improved the predictive value, though models and performance varied substantially across studies. In four studies measuring both markers, UCH-L1 outperformed GFAP in improving risk stratification when added to established prediction models. At ∼1.5 ng/mL (five studies), the summary sensitivity of GFAP for predicting mortality was 78% (95% CI 67-85%), and the summary specificity was 79% (95% CI 64-89%). The other assessed biomarkers had fair to good performance in mortality prediction with unclear added benefits. Neurofilament light (NfL) (three studies) demonstrated the strongest association in predicting a 6-month poor outcome (GOS-E ≤4; GOS ≤3) (unadjusted pooled AUC 0.81 [95% CI 0.75-0.87]), whereas the other assessed biomarkers had a fair performance with unclear or irrelevant added value. All core biomarkers had only marginal or no association with incomplete recovery and post-concussion symptoms/syndrome, as assessed by RPQ. Serious problems were found in the design and analysis of many of the studies. We conclude that admission measurements of core blood TBI biomarkers, in particular GFAP and UCH-L1, are strongly associated with mortality. There remains little evidence that any of these markers are ready for clinical implementation for prognostic purposes. Future work focused on the intended use and applying unbiased rigorous analysis methods is necessary to demonstrate that the biomarker test results are "prognostically actionable."

Previous studies have shown contradictory results between early application of antiplatelet therapy and intravenous thrombolysis (IVT) for mild acute ischaemic stroke (AIS), with National Institutes of Health Stroke Scale score 0-5.

To compare the benefits and risks of antiplatelet therapy and IVT in patients with mild AIS.

A systematic search of MEDLINE, Embase and Cochrane Library was conducted from database inception until July 2023, without language restriction. Randomised clinical trials (RCTs) or observational studies were selected. The primary outcomes were 90-day functional outcomes, measured by the modified Rankin Scale (mRS) score. The protocol has been registered before data collection.

Two RCTs and four observational studies with relatively low risk of bias that enrolled 3975 patients were analysed (2454 in antiplatelet therapy and 1521 in IVT therapy). There were no significant differences between antiplatelet therapy and IVT in 90-day functional outcomes (mRS 0-1, OR 1.08 (95% CI 0.73 to 1.58); mRS 0-2, OR, 1.04 (95% CI 0.63 to 1.73)), death (OR, 0.64 (95% CI 0.19 to 2.13)) and stroke recurrence (OR, 0.71 (95% CI 0.28 to 1.79)). Antiplatelet therapy was associated with a reduced risk of symptomatic intracranial haemorrhage (sICH) compared with IVT (OR, 0.20 (95% CI 0.06 to 0.69)).

Among patients with mild AIS, compared with IVT, early application of antiplatelet therapy was not significantly associated with improved functional outcomes, reduced death or stroke recurrence, but was significantly associated with a reduced risk of sICH.

CRD42023447862.

To develop a living systematic review to deliver continuous, real-time evidence synthesis in the context of a rapidly evolving landscape of studies on potential therapeutic interventions during the COVID-19 pandemic.

The living systematic review was conducted using the COVID-19 Living Overview of Evidence platform, which aggregates studies from more than 40 sources, including electronic databases and preprint servers. Daily searches identified randomized controlled trials assessing pharmacological interventions for COVID-19. Meta-analytical pooling was applied to derive precise effect estimates, and the GRADE framework was used to assess certainty. The iterative process ensured the continuous integration of new evidence and rapid updates to the review.

The review evaluated 305 interventions across 924 randomized controlled trials and included 48 updates from its launch in April 2020. This dynamic process allowed the team to respond promptly to decision-maker queries and deliver reliable information on intervention effectiveness and safety. The outputs of the review supported the development of therapeutic guidelines and informed decision-makers, playing a pivotal role in shaping clinical practices and public health strategies during the pandemic.

The living systematic review approach demonstrated how dynamic evidence synthesis can meet the demands of a rapidly evolving global health crisis. By providing decision-makers with timely, high-quality evidence, the process underscored the importance of integrating living reviews into preparedness strategies for future public health emergencies or rapidly evolving fields where new evidence emerges quickly.

Delays in translating new medical evidence into clinical practice hinder patient access to the best available treatments. Our data reveals an average delay of nine years from the initiation of human research to its adoption in clinical guidelines, with 1.7-3.0 years lost between trial publication and guideline updates. A substantial part of these delays stems from slow, manual processes in updating clinical guidelines, which rely on time-intensive evidence synthesis workflows. The Next Generation Evidence (NGE) system addresses this challenge by harnessing state-of-the-art biomedical Natural Language Processing (NLP) methods. This novel system integrates diverse evidence sources, such as clinical trial reports and digital guidelines, enabling automated, data-driven analyses of the time it takes for research findings to inform clinical practice. Moreover, the NGE system provides precision-focused literature search filters tailored specifically for guideline maintenance. In benchmarking against two German oncology guidelines, these filters demonstrate exceptional precision in identifying pivotal publications for guideline updates.

Chikungunya virus significantly impacts public health, primarily affecting regions in Africa and the Americas (predominantly Latin America and the Caribbean). Despite the global spread of the virus and its clinical manifestations and complications in vulnerable populations such as children and pregnant persons, no widely available vaccine is currently available. With recent advancements in vaccine development, there is a need to systematically evaluate the emerging evidence on the safety, immunogenicity, and efficacy of chikungunya vaccine candidates. This protocol outlines a living systematic review designed to continuously assess the growing research on chikungunya vaccines, focusing on diverse populations, including children and pregnant persons. We aim to provide up-to-date evidence to inform public health decisions and vaccine recommendations as new data is available.

Our objective is to carry out a living systematic review and meta-analysis through biweekly searches in medical databases and clinical trial registries, aiming to identify relevant chikungunya vaccines studies on pregnant individuals, children, and adolescents. Pairs of reviewers will independently screen studies, extract data, and assess the risk of bias. Clinical trials, quasi-experimental studies, and observational studies, including case reports, will be considered for inclusion. Main outcomes will include the safety, efficacy, and effectiveness of chikungunya vaccines in pregnant individuals (including neonatal outcomes), as well as in children and adolescents. Reactogenicity and immunogenicity will be considered as secondary outcomes. Paired meta-analyses, incorporating predefined subgroup and sensitivity analyses, will be performed. Evidence certainty will be assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach.

This living systematic review and meta-analysis will continuously assess the safety, immunogenicity, and effectiveness of chikungunya vaccines in pregnant persons, children, and adolescents. Given the significant disease burden and potential complications in these populations, synthesizing emerging evidence is crucial for guiding immunization policies and clinical recommendations. By maintaining an updated analysis, this review will provide timely insights for public health agencies, researchers, and clinicians involved in vaccine implementation and maternal-child health.

Two protocols were registered in the International Prospective Register of Systematic Reviews database, CRD42024514513 and CRD42024516754.

Lassa fever (LF), caused by the Lassa virus (LASV), is a zoonotic viral hemorrhagic disease endemic to West Africa, primarily transmitted through rodent excreta and infected bodily fluids. It poses significant public health challenges due to its high morbidity and mortality rates, particularly among at-risk populations like pregnant persons and children. Despite decades of research, vaccine development has been hindered by the virus's genetic diversity and complex epidemiology. While several vaccine candidates have been developed, none have received regulatory approval. Given the rapidly evolving vaccine landscape, a living systematic review (LSR) was selected to enable real-time evidence synthesis. This protocol outlines a living systematic review (LSR) to evaluate the safety, efficacy, effectiveness, and immunogenicity of LASV vaccines, providing evidence to guide public health interventions and vaccine recommendations.

We will conduct a biweekly updated LSR and meta-analysis, systematically searching databases (e.g., MEDLINE, EMBASE, CENTRAL) and clinical trial registries from January 2014 onward to identify studies of LASV vaccines in pregnant persons, children, and adolescents. All study designs, including randomized trials, cohort studies, case-control studies, and case reports, will be eligible. Pairs of reviewers will independently assess eligibility, extract data, and evaluate the risk of bias. Primary outcomes include vaccine safety, efficacy, and effectiveness in pregnant persons (including neonatal outcomes), children, and adolescents, while secondary outcomes assess immunogenicity and reactogenicity. Data on adult populations will also be included, and results on this group will be reported as available. We will conduct paired meta-analyses, including prespecified subgroup and sensitivity analyses. We will use the grading of recommendations assessment, development, and evaluation approach to evaluate the certainty of evidence.

This LSR offers a dynamic framework to generate timely evidence on LASV vaccines for vulnerable populations. By integrating findings into an interactive Microsoft Power BI dashboard, stakeholders can access and utilize real-time updates to inform public health strategies. Despite challenges like study heterogeneity and vaccine platform variability, subgroup and sensitivity analyses will mitigate these issues. This review aims to support clinical trial designs, guide policy, and improve health outcomes in Lassa fever-endemic regions.

Two protocols were registered in the International Prospective Register of Systematic Reviews (PROSPERO) database: CRD42024514513 and CRD42024516754.

The synthesis of evidence in health care is essential for informed decision-making and policy development. This study aims to validate The Umbrella Collaboration (TU), an innovative, semiautomatic tertiary evidence synthesis methodology, by comparing it with Traditional Umbrella Reviews (TUR), which are currently the gold standard.

This study aimed to evaluate whether TU, an artificial intelligence-assisted, software-driven system for tertiary evidence synthesis, can achieve comparable effectiveness to TURs, while offering a more timely, efficient, and comprehensive approach. In addition, as a secondary objective, the study aims to assess the accessibility and comprehensibility of TU's outputs to ensure its usability and practical applicability for health care professionals.

This protocol outlines a comparative study divided into 2 main parts. The first part involves a quantitative comparison of results obtained using TU and TURs in geriatrics. We will evaluate the identification, size effect, direction, statistical significance, and certainty of outcomes, as well as the time and resources required for each methodology. Data for TURs will be sourced from Medline (via PubMed), while TU will use artificial intelligence-assisted informatics to replicate the research questions of the selected TURs. The second part of the study assesses the ease of use and comprehension of TU through an online survey directed at health professionals, using interactive features and detailed data access.

Expected results include the assessment of concordance in identifying outcomes, the size effect, direction and significance of these outcomes, and the certainty of evidence. In addition, we will measure the operational efficiency of each methodology by evaluating the time taken to complete projects. User perceptions of the ease of use and comprehension of TU will be gathered through detailed surveys. The implementation of new methodologies in evidence synthesis requires validation. This study will determine whether TU can match the accuracy and comprehensiveness of TURs while offering benefits in terms of efficiency and user accessibility. The comparative study is designed to address the inherent challenges in validating a new methodology against established standards.

If TU proves as effective as TURs but more time-efficient, accessible, and easily updatable, it could significantly enhance the process of evidence synthesis, facilitating informed decision-making and improving health care. This study represents a step toward integrating innovative technologies into routine evidence synthesis practice, potentially transforming health research.

PRR1-10.2196/67248.

Stem cells are specialised precursor cells that can replace aged or damaged cells and thereby maintain healthy tissue function. Stem cell therapy is increasingly used as a treatment for knee osteoarthritis, despite the lack of clarity around the mechanism by which stem cell therapy may slow down disease progression in osteoarthritis, and uncertainty regarding its benefits and harms.

To assess the benefits and harms of stem cell injections for people with osteoarthritis of the knee. A secondary objective is to maintain the currency of the evidence, using a living systematic review approach.

We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and Embase on 15 September 2023, unrestricted by date or language of publication. We also searched ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) for relevant trial protocols and ongoing trials.

We included randomised controlled trials (RCTs), or trials using quasi-randomised methods of participant allocation, comparing stem cell injection with placebo injection, no treatment or usual care, glucocorticoid injection, other injections, exercise, drug therapy, surgical interventions, and supplements and complementary therapies in people with knee osteoarthritis.

Two review authors selected studies for inclusion, extracted trial characteristics and outcome data, assessed risk of bias and assessed the certainty of evidence using the GRADE approach. The primary comparison was stem cell injection compared with placebo injection. The primary time point for pain, function and quality of life was three to six months, and the end of the trial period for participant-reported success, joint structure changes and adverse event outcomes. Major outcomes were pain, function, quality of life, global assessment of success, radiographic joint progression, withdrawals due to adverse events and serious adverse events.

We found 25 randomised trials (1341 participants) comparing stem cell injections with placebo injection (eight trials), no treatment or usual care (analgesia, weight loss and exercise) (two trials), glucocorticoid injection (one trial), hyaluronic acid injection (seven trials), platelet-rich plasma injections (two trials), oral acetaminophen (paracetamol) (one trial), non-steroidal anti-inflammatory drugs plus physical therapy plus hyaluronic acid injection (one trial) and stem cell injection plus intra-articular co-intervention versus co-intervention alone (three trials) in people with osteoarthritis of the knee. Trials were predominantly small, with sample sizes ranging from 6 to 252 participants, with only two trials having more than 100 participants. The average age of participants across trials ranged from 51 to 66 years, and symptom duration varied from one to 10 years. Placebo-controlled trials were largely free from bias, while most trials without a placebo control were susceptible to performance and detection biases. Here, we limit reporting to the main comparison, stem cell injection versus placebo injection. Compared with placebo injection, stem cell injection may slightly improve pain and function up to six months after treatment. Mean pain (0 to 10 scale, 0 no pain) was 4.5 out of 10 points with placebo injection and 1.2 points better (2.5 points better to 0 points better) with stem cell injection (I2 = 80%; 7 studies, 445 participants). Mean function (0 to 100 scale, 0 best function) was 46.3 points with placebo injection and 14.2 points better (25.3 points better to 3.1 points better) with stem cell injection (I2 = 82%; 7 studies, 432 participants). We are uncertain whether stem cell injections improve quality of life or increase the number of people who report treatment success compared to placebo injection, because the certainty of the evidence was very low. Mean quality of life was 45.3 points with placebo injection and 22.8 points better (18.0 points worse to 63.7 points better) with stem cell injection (I2 = 96%; 2 studies, 288 participants) at up to six months follow-up. At the end of follow-up, 89/168 participants (530 per 1000) in the placebo injection group reported treatment success compared with 126/180 participants (683 per 1000) in the stem cell injection group (risk ratio (RR) 1.29, 95% CI 1.10 to 1.53; I2 = 0%; 4 trials, 348 participants). We downgraded the evidence to low certainty for pain and function due to indirectness (as the source, method of preparation and dose of stem cells varied across studies), and suspected publication bias (up to three larger RCTs have been conducted but withdrawn prior to reporting of results). For quality of life and treatment success, we further downgraded the evidence to very low certainty due to imprecision in addition to indirectness and suspected publication bias. We are uncertain of the potential harms associated with stem cell injection, as there were very low event rates for serious adverse events. At the end of follow-up, 5/219 participants (23 per 1000) in the placebo injection group experienced serious adverse events compared with 4/242 participants (16 per 1000) in the stem cell injection group (RR 0.72, 95% CI 0.20 to 2.64; I2 = 0%; 7 trials, 461 participants) and there were no reported withdrawals due to adverse events. We downgraded the evidence to very low certainty due to indirectness, suspected publication bias and imprecision. Radiographic progression was not assessed in any of the included studies.

Compared with placebo injections and based upon low-certainty evidence, stem cell injections for people with knee osteoarthritis may slightly improve pain and function. We are uncertain of the effects of stem cell injections on quality of life or the number who report treatment success. Although the putative benefits of stem cell therapies for osteoarthritis include potential regenerative effects on damaged tissues, particularly articular cartilage, we remain uncertain of the effect of stem cell injections on structural progression in the knee (measured by radiographic appearance). There is also uncertainty regarding the safety of stem cell injections. Serious adverse events were infrequently reported, although all invasive joint procedures (including injections) carry a small risk of septic arthritis. The risk of other important harms, including potential concerns related to the use of a therapy with the theoretical capacity to promote cell growth, or to the use of allogeneic cells, remains unknown.

Trace amine-associated receptor 1 (TAAR1) agonists offer a new approach, but there is uncertainty regarding their effects, exact mechanism of action and potential role in treating psychosis.

To evaluate the available evidence on TAAR1 agonists in psychosis, using triangulation of the output of living systematic reviews (LSRs) of animal and human studies, and provide recommendations for future research prioritisation.

This study is part of GALENOS (Global Alliance for Living Evidence on aNxiety, depressiOn and pSychosis). In the triangulation process, a multidisciplinary group of experts, including those with lived experience, met and appraised the first co-produced living systematic reviews from GALENOS, on TAAR1 agonists.

The animal data suggested a potential antipsychotic effect, as TAAR1 agonists reduced locomotor activity induced by pro-psychotic drug treatment. Human studies showed few differences for ulotaront and ralmitaront compared with placebo in improving overall symptoms in adults with acute schizophrenia (four studies, n = 1291 participants, standardised mean difference (SMD) 0.15, 95% CI -0.05 to 0.34). Large placebo responses were seen in ulotaront phase three trials. Ralmitaront was less efficacious than risperidone (one study, n = 156 participants, SMD = -0.53, 95% CI -0.86 to -0.20). The side-effect profile of TAAR1 agonists was favourable compared with existing antipsychotics. Priorities for future studies included (a) using different animal models of psychosis with greater translational validity; (b) animal and human studies with wider outcomes including cognitive and affective symptoms and (c) mechanistic studies and investigations of other potential applications, such as adjunctive treatments and long-term outcomes. Recommendations for future iterations of the LSRs included (a) meta-analysis of individual human participant data, (b) including studies that used different methodologies and (c) assessing other disorders and symptoms.

This co-produced, international triangulation examined the available evidence and developed recommendations for future research and clinical applications for TAAR1 agonists in psychosis. Broader challenges included difficulties in assessing the risk of bias, reproducibility, translation and interpretability of animal models to clinical outcomes, and a lack of individual and clinical characteristics in the human data. The research will inform a separate, independent prioritisation process, led by lived experience experts, to prioritise directions for future research.

The objective of this scoping review is to describe existing guidance documents or studies reporting on the conduct of meta-analyses in updated systematic reviews (USRs) or living systematic reviews (LSRs).

The rapid increase in the medical literature poses a substantial challenge in keeping systematic reviews up to date. In LSRs, a review is updated with a pre-specified frequency or when some other signalling criterion is triggered. While the LSR framework is well-established, there is uncertainty regarding the most appropriate methods for conducting repeated meta-analyses over time, which may result in sub-optimal decision-making.

Studies of any design (including commentaries, books, manuals) providing guidance on conducting meta-analysis in USRs or LSRs.

This review will use the JBI methodology for scoping reviews. We will search multiple medical bibliographic databases (Cochrane Library, Embase, ERIC, MEDLINE, JBI Evidence Synthesis , and PsycINFO), statistical and mathematics databases (COBRA, Current Index to Statistics, MathSciNet, Project Euclid Complete, and zbMATH), pre print archives (Arvix, BioRxiv, and MedRxiv), and unpublished (or gray) literature sources. Two reviewers will independently screen titles, abstracts, and full-text documents, and extract data. Characteristics of recommendations for meta-analysis in USRs and LSRs will be presented using descriptive statistics and categorized concepts.

Open Science Framework https://osf.io/9c27g.

The objective of this review was to identify and map the available information related to the definition, structure, and core methodological components of evidence summaries, as well as to identify any indicators of quality.

Evidence summaries offer a practical solution to overcoming some of the barriers present in evidence-based health care, such as lack of access to evidence at the point of care, and the knowledge and expertise to evaluate the quality and translate the evidence into clinical decision-making. However, lack of transparency in reporting and inconsistencies in the methodology of evidence summary development have previously been cited and pose problems for end users (eg, clinicians, policymakers).

Any English-language resource that described the methodological development or appraisal of an evidence summary was included.

PubMed, Embase, and CINAHL (EBSCOhost) were systematically searched in November 2019, with no limits on the search. The search was updated in June 2021 and January 2023. Gray literature searches and pearling of references of included sources were also conducted at the same time as the database searches. All resources (ie, articles, papers, books, dissertations, reports, and websites) were eligible for inclusion in the review if they evaluated or described the development or appraisal of an evidence summary methodology within a point-of-care context and were published in English. Literature reviews (eg, systematic reviews, rapid reviews)-including summaries of evidence on interventions or health care activities that measure effects, a phenomenon of interest, or where the objective was the development, description, or evaluation of methods without a clear point-of-care target-were excluded from the review.

A total of 76 resources (n = 56 articles from databases and n = 20 reports from gray literature sources) were included in the review. The most common type/name of resource included critically appraised topic (n = 18) and evidence summary (n = 17). A total of 25 resources provided a definition of an evidence summary: commonalities included a clinical question; a structured, systematic literature search; a description of literature selection; and appraisal of evidence. Of these 25 resources, 16 included descriptors such as brief, concise, rapid, short, succinct , and snapshot . The reported methodological components closely reflected the definition results, with the most reported methodological components being a systematic, multi-database search, and critical appraisal. Evidence summary examples were mostly presented as narrative summaries and usually included a reference list, background or clinical context, and recommendations or implications for practice or policy. Four quality assessment tools and a systematic review of tools were included.

The findings of this review highlight the wide variability in the definition, language, methodological components, and structure used for point-of-care resources that met our definition of an evidence summary. This scoping review is one of the first stjpg aimed at improving the credibility and transparency of evidence summaries in evidence-based health care, with further research required to standardize the definitions and methodologies associated with point-of-care resources and accepted tools for quality assessment.

A Chinese-language version of the abstract of this review is available at http://links.lww.com/SRX/A79 ; a list of studies ineligible following full-text review is available at http://links.lww.com/SRX/A60 .

Trial sequential analysis (TSA) is an increasingly used tool in systematic reviews to monitor synthesized evidence. However, the current practice of TSAs often overlooks the order of same-year studies, which are typically ordered alphabetically based on the last names of the studies' authors by default in the widely used TSA software application. This practice is inappropriate and contrary to the TSA's definition. This issue is particularly concerning in systematic reviews on time-sensitive topics, such as COVID-19, where reviews include many studies within a short period. In this article, we use a case study to illustrate the impact of the order of same-year studies on TSA conclusions. It shows dramatically different patterns of evidence accumulation when same-year studies are ordered alphabetically vs in their actual temporal order. This article offers suggestions for authors to pay attention to study ordering in future TSAs.

The amount of scientific data on liver surgery is exploding. There is a critical unmet need to develop tools that will facilitate navigating the literature and offer easy, fast and accurate access to data with a high level of evidence. Evidence maps (EM) combining living systematic reviews (SR) and user-friendly synthesis with graphs and figures were developed for this purpose in other medical fields and showed promising results but remain yet unavailable in liver surgery. The present study protocol aims to generate an EM in liver surgery, gathering randomised clinical trials (RCT) and SR.

A systematic search will be conducted in the Cochrane Central Register of Controlled Trials, Web of Science, Embase and Medline to identify all RCT and SR concerning liver surgery. RCT and SR will be classified in research topics. Selected endpoints will be extracted and meta-analysed. Results will be freely available for patients, clinicians and researchers via a web-based evidence map platform. EM and meta-analyses (MA) will be updated at regular intervals.

Including publicly available data, this type of study design did not require ethical committee approval. EM displays the required properties to facilitate literature search and to get a rapid overview of the current evidence, an unavailable tool in liver surgery, to date. Generating such an aid may considerably help patients, clinicians and researchers in many aspects: accessing accurate data, helping in decision-making and identifying gaps in the field. On completion of the project, results will be published, freely available via www.evidencemap.surgery and permanently updated.

CRD42023489201 (https://www.crd.york.ac.uk/prospero/).

Transcatheter aortic valve replacement (TAVR) has emerged as a critical innovation for managing severe aortic stenosis, prompting the development of numerous clinical practice guidelines worldwide. This study systematically evaluates the guideline development methodologies of major international TAVR guidelines using the AGREE II and AGREE-REX instruments, aiming to enhance understanding of current development processes.

A comprehensive search was conducted in PubMed, Embase, Web of Science, and specialized guideline repositories. Twenty-four TAVR-specific guidelines were independently evaluated by four reviewers using the AGREE II and AGREE-REX instruments. The guidelines were categorized as evidence- or consensus-based, and statistical analysis was performed using SPSS to standardize scores and assess inter-rater reliability.

Systematic assessment revealed significant methodological variations across guidelines. The AGREE II evaluation showed the highest performance in scope and purpose (83.9 ± 10.0%) but lower scores in rigor of development (43.5 ± 29.0%) and applicability (42.4 ± 26.8%). The AGREE-REX analysis demonstrated stronger performance in implementability (78.6 ± 14.5%) while identifying gaps in the integration of values and preferences (35.7 ± 17.2%). Evidence-based guidelines consistently outperformed consensus-based ones across multiple domains, particularly in terms of methodological rigor and implementation planning.

This evaluation highlights key areas for improving guideline development methodology, including standardized evidence evaluation processes, systematic stakeholder engagement, and structured implementation planning. The considerable variability in methodological quality underscores the need for more standardized approaches.

Current TAVR guidelines exhibit significant heterogeneity in methodological quality, with evidence-based guidelines demonstrating superior performance in development rigor and implementation planning. Systematic approaches to evidence synthesis and stakeholder engagement are crucial for high-quality guideline development.

Up to 15% of survivors of COVID-19 infection experience long-term health effects, including fatigue, myalgia and impaired cognitive function, termed post-COVID-19 condition or long COVID. Several trials that study the benefits and harms of various interventions to manage long COVID have been published and hundreds more are planned or are ongoing. Trustworthy systematic reviews that clarify the benefits and harms of interventions are critical to promote evidence-based practice.

To create and maintain a living systematic review and network meta-analysis addressing the benefits and harms of pharmacologic and non-pharmacologic interventions for the treatment and management of long COVID.

Eligible trials will randomise adults with long COVID to pharmacologic or non-pharmacologic interventions, placebo, sham or usual care. We will identify eligible studies by searching MEDLINE, EMBASE, CINAHL, PsycINFO, AMED and CENTRAL from inception, without language restrictions.Reviewers will work independently and in duplicate to screen search records, collect data from eligible trials, including trial and patient characteristics and outcomes of interest and assess risk of bias. Our outcomes of interest will include patient-reported fatigue, pain, postexertional malaise, changes in education or employment status, cognitive function, mental health, dyspnoea, quality of life, physical function, recovery and serious adverse events.For each outcome, when possible, we will perform a frequentist random-effects network meta-analysis. When there are compelling reasons to suspect that certain interventions are only applicable or effective for a subtype of long COVID, we will perform separate network meta-analyses. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach will guide our assessment of the certainty of evidence.We will update our living review biannually, on the publication of a seminal trial, or when new evidence emerges that may change clinical practice.

This living systematic review and network meta-analysis will provide comprehensive, trustworthy and up-to-date summaries of the evidence addressing the benefits and harms of interventions for the treatment and management of long COVID. We will make our findings available publicly and work with guideline-producing organisations to inform their recommendations.

The study describes the protocol for a systematic review that uses data from published trial reports. Therefore, the study is exempt from ethics review. We intend to deposit all data in a public repository and publish each iteration of the living review online.

Neuromodulation has been a staple of treatment for moderate-to-severe chronic refractory pain since the introduction of the first spinal cord stimulator by Norman Shealy in 1967. Appreciating the dynamic nature of electrical modulation of the nervous system from the epidural space, the goal has been consistent, reliable, and therapeutic neural activation of the spinal cord. This has proven to be extremely difficult. Recently, the Food and Drug Administration (FDA) released a guidance on physiologic closed loop controlled (PCLC) devices, highlighting the potential for these therapies to deliver accurate, consistent, real-time therapy, enhancing medical care and reducing variability. Because of the growing neuromodulation market focus on PCLC strategies, the American Society of Pain and Neuroscience (ASPN) sought to develop guidance on safety and efficacy, along with a taxonomy surrounding PCLC systems (PCLCSs) and to develop an evidence-based best practice review.

A librarian-assisted literature search was performed to identify manuscripts relevant to the topic of PCLC stimulation for management of chronic pain. Initial literature search was performed utilizing MEDLINE, EMBASE, Cochrane database, BioMed Central, and Web of Science. Included manuscripts encompassed meta-analyses, systematic reviews, randomized controlled trials (RCTs), prospective or retrospective studies with follow-up to 12 months, limited to the English language. MESH terms utilized included "closed-loop", "physiologic closed loop controlled", "spinal cord stimulation", "closed loop feedback", "feedback controlled", "neuromodulation", "pain", "persistent pain", "neuropathic pain", and "chronic pain". The modified USPSTF evidence and recommendation grading strategy previously utilized was again employed.

Four studies were identified for review, 2 prospective, one retrospective, and one randomized controlled study with at least 12-month follow-up.

PCLC neuromodulation is an innovation that requires a responsible introduction. As commercial access grows, there is a responsibility that requires consistency with definition, evidence generation, focused on safety and efficacy.

Living evidence involves continuous evidence surveillance to incorporate new relevant evidence into systematic reviews and clinical practice guideline recommendations as soon as it becomes available. Thus, living evidence may improve the timeliness of recommendation updates and reduce the knowledge-to-practice gap. When considering a living evidence model, several processes and practical aspects need to be explored. Some of these include identifying the need for a living evidence model, funding, governance structure, time, team skills and capabilities, frequency of updates, approval and endorsement, and publication and dissemination.

Since 2015, the Complex Reviews Synthesis Unit (CRSU) has developed a suite of web-based applications (apps) that conduct complex evidence synthesis meta-analyses through point-and-click interfaces. This has been achieved in the R programming language by combining existing R packages that conduct meta-analysis with the shiny web-application package. The CRSU apps have evolved from two short-term student projects into a suite of eight apps that are used for more than 3,000 h per month.

Here, we present our experience of developing production grade web-apps from the point-of-view of individuals trained primarily as statisticians rather than software developers in the hopes of encouraging and inspiring other groups to develop valuable open-source statistical software whilst also learning from our experiences.

We discuss how we have addressed challenges to research software development such as responding to feedback from our real-world users to improve the CRSU apps, the implementation of software engineering principles into our app development process and gaining recognition for non-traditional research work within the academic environment.

The CRSU continues to seek funding opportunities both to maintain and further develop our shiny apps. We aim to increase our user base by implementing new features within the apps and building links with other groups developing complementary evidence synthesis tools.

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To determine the benefits and harms of dose reduction or discontinuation of biologic disease-modifying anti-rheumatic drugs or targeted synthetic disease-modifying anti-rheumatic drugs in adults with psoriatic arthritis who are in remission or a low disease activity state.

A range of school-based interventions are effective in improving student diet and physical activity (e.g. school food policy interventions and classroom physical activity interventions), and reducing obesity, tobacco use and/or alcohol use (e.g. tobacco control programmes and alcohol education programmes). However, schools are frequently unsuccessful in implementing such evidence-based interventions.

The primary review objective is to evaluate the effectiveness of strategies aiming to improve school implementation of interventions to address students' (aged 5 to 18 years) diet, physical activity, obesity, tobacco use and/or alcohol use. The secondary objectives are to: 1. determine whether the effects are different based on the characteristics of the intervention including school type and the health behaviour or risk factor targeted by the intervention; 2. describe any unintended consequences and adverse effects of strategies on schools, school staff or students; and 3. describe the cost or cost-effectiveness of strategies.

We searched CENTRAL, MEDLINE (Ovid), Embase (Ovid), five additional databases, the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), and the US National Institutes of Health registry (clinicaltrials.gov). The latest search was between 1 May 2021 and 30 June 2023 to identify any relevant trials published since the last published review.

We defined 'implementation' as the use of strategies to adopt and integrate evidence-based health interventions and to change practice patterns within specific settings. We included any randomised controlled trial (RCT) or cluster-RCT conducted on any scale, in a school setting, with a parallel control group that compared a strategy to improve the implementation of policies or practices to address diet, physical activity, obesity, tobacco use and/or alcohol use by students (aged 5 to 18 years) to no active implementation strategy (i.e. no intervention, inclusive of usual practice, minimal support) or a different implementation strategy.

We used standard Cochrane methods. Given the large number of outcomes reported, we selected and included the effects of a single outcome measure for each trial for the primary outcome using a decision hierarchy (i.e. continuous over dichotomous, most valid, total score over subscore). Where possible, we calculated standardised mean differences (SMDs) to account for variable outcome measures with 95% confidence intervals (CI). We conducted meta-analyses using a random-effects model. Where we could not combine data in meta-analysis, we followed recommended Cochrane methods and reported results in accordance with 'Synthesis without meta-analysis' (SWiM) guidelines. We conducted assessments of risk of bias and evaluated the certainty of evidence (GRADE approach) using Cochrane procedures.

We included an additional 14 trials in this update, bringing the total number of included trials in the review to 39 trials with 83 trial arms and 6489 participants. Of these, the majority were conducted in Australia and the USA (n = 15 each). Nine were RCTs and 30 were cluster-RCTs. Twelve trials tested strategies to implement healthy eating practices; 17 physical activity, two tobacco, one alcohol, and seven a combination of risk factors. All trials used multiple implementation strategies, the most common being educational materials, educational meetings, and education outreach visits, or academic detailing. Of the 39 included trials, we judged 26 as having high risks of bias, 11 as having some concerns, and two as having low risk of bias across all domains. Pooled analyses found, relative to a control (no active implementation strategy), the use of implementation strategies probably results in a large increase in the implementation of interventions in schools (SMD 0.95, 95% CI 0.71, 1.19; I2 = 78%; 30 trials, 4912 participants; moderate-certainty evidence). This is equivalent to a 0.76 increase in the implementation of seven physical activity intervention components when the SMD is re-expressed using an implementation measure from a selected included trial. Subgroup analyses by school type and targeted health behaviour or risk factor did not identify any differential effects, and only one study was included that was implemented at scale. Compared to a control (no active implementation strategy), no unintended consequences or adverse effects of interventions were identified in the 11 trials that reported assessing them (1595 participants; moderate-certainty evidence). Nine trials compared costs between groups with and without an implementation strategy and the results of these comparisons were mixed (2136 participants; low-certainty evidence). A lack of consistent terminology describing implementation strategies was an important limitation of the review.

We found the use of implementation strategies probably results in large increases in implementation of interventions targeting healthy eating, physical activity, tobacco and/or alcohol use. While the effectiveness of individual implementation strategies could not be determined, such examination will likely be possible in future updates as data from new trials can be synthesised. Such research will further guide efforts to facilitate the translation of evidence into practice in this setting. The review will be maintained as a living systematic review.

Trastuzumab therapy for HER2-positive cancers is associated with cardiotoxicity. This umbrella review synthesizes evidence from systematic reviews and meta-analyses on cardioprotective interventions during trastuzumab treatment.

A comprehensive search was conducted in PubMed, Embase, Cochrane Library, and Web of Science. Systematic reviews and meta-analyses examining cardioprotective interventions in patients receiving trastuzumab were included. The methodological quality was assessed using the AMSTAR-2 tool. Data on cardiac events, treatment interruptions, left ventricular ejection fraction (LVEF) changes, and exercise interventions were synthesized.

Ten systematic reviews met the inclusion criteria. Statins demonstrated the strongest cardioprotective effect (RR = 0.47, 95% CI: 0.26-0.84), potentially preventing more than half of cardiac events during trastuzumab therapy, followed by beta-blockers (RR = 0.61, 95% CI: 0.39-0.93). Beta-blockers and ACEIs effectively reduced treatment interruptions, enabling approximately 40% more patients to maintain treatment continuity (RR = 0.63, 95% CI: 0.47-0.86). Among non-pharmacological interventions, structured exercise programs showed significant benefits in preserving cardiac function, demonstrating meaningful improvements in resting LVEF (WMD = -3.27%, 95% CI: -5.86 to -0.68).

This review demonstrates that cardioprotective interventions, particularly statins and beta-blockers, significantly reduce the risk of cardiac complications during trastuzumab therapy. The positive impact on cardiac events and treatment interruptions suggests these interventions may enhance overall treatment efficacy by allowing more patients to complete their prescribed course.

Evidence strongly supports the systematic implementation of cardioprotective strategies in clinical practice, particularly statins and beta-blockers, as part of routine care protocols for patients receiving trastuzumab therapy. These interventions demonstrate significant potential in preventing cardiac complications and maintaining treatment continuity. Further research should focus on optimizing personalized approaches and evaluating long-term outcomes.

The COVID-19 pandemic resulted in a rapid accumulation of novel vaccine research evidence. As a means to monitor this evidence, the Public Health Agency of Canada (PHAC) created the Evidence eXtraction Team for Research Analysis (EXTRA), which contributed to situational awareness in Canada through a bibliographic repository used to support decision-making by the National Advisory Committee on Immunization. We describe the process by which this literature was identified and catalogued, and provide an overview of characteristics in the identified literature.

To expedite the process, PHAC leveraged an artificial intelligence (AI) tool to assist in the screening and selection of relevant articles. Literature search results were initially screened by AI, then manually reviewed for relevance. Relevant articles were tagged using controlled vocabulary and stored in a bibliographic repository. This repository was analyzed to identify trends in vaccine research over time according to several key characteristics.

As of December 31, 2023, EXTRA's repository contained 19,050 articles relevant to PHAC's immunization mandate. The majority of these articles (63.9 %) were identified between August 2021 and January 2023, with an average of 20 relevant articles added daily during this period. Nearly 14,000 articles reported on mRNA vaccines. Safety outcomes were most frequently reported (n = 8,289), followed by immunogenicity (n = 7,269) and efficacy/effectiveness (n = 3,246). COVID-19 vaccine literature output started to decrease in mid-2023, two years after the initial dramatic increase in mid-2021.

This hybrid (AI and human) approach was critical for PHAC situational awareness and the development of timely vaccine guidance in Canada during the COVID-19 pandemic. Given the volume of data and analyses required, the AI-augmented processes made this massive undertaking manageable. Analysis of COVID-19 vaccine research patterns supports projections of research volume, type, and rate that will help predict resourcing and information needs to plan future emergency vaccine guidance activities.

Using reports of randomised trials of smoking cessation interventions as a test case, this study aimed to develop and evaluate machine learning (ML) algorithms for extracting information from study reports and predicting outcomes as part of the Human Behaviour-Change Project. It is the first of two linked papers, with the second paper reporting on further development of a prediction system.

Researchers manually annotated 70 items of information ('entities') in 512 reports of randomised trials of smoking cessation interventions covering intervention content and delivery, population, setting, outcome and study methodology using the Behaviour Change Intervention Ontology. These entities were used to train ML algorithms to extract the information automatically. The information extraction ML algorithm involved a named-entity recognition system using the 'FLAIR' framework. The manually annotated intervention, population, setting and study entities were used to develop a deep-learning algorithm using multiple layers of long-short-term-memory (LSTM) components to predict smoking cessation outcomes.

The F1 evaluation score, derived from the false positive and false negative rates (range 0-1), for the information extraction algorithm averaged 0.42 across different types of entity (SD=0.22, range 0.05-0.88) compared with an average human annotator's score of 0.75 (SD=0.15, range 0.38-1.00). The algorithm for assigning entities to study arms ( e.g., intervention or control) was not successful. This initial ML outcome prediction algorithm did not outperform prediction based just on the mean outcome value or a linear regression model.

While some success was achieved in using ML to extract information from reports of randomised trials of smoking cessation interventions, we identified major challenges that could be addressed by greater standardisation in the way that studies are reported. Outcome prediction from smoking cessation studies may benefit from development of novel algorithms, e.g., using ontological information to inform ML (as reported in the linked paper 1).

One-third of adults aged 65+ fall annually. Injuries from falls can be devastating for individuals and account for 1.5% of annual healthcare spending. With the growing ageing population, falls place increased strain on scarce health resources. Prevention strategies that target individuals at high risk for falls demonstrate the best value for money; however, limited efficiency (ie, cost-effectiveness) information for fall prevention interventions hinders the implementation of effective falls prevention programmes. Living systematic reviews provide a timely up-to-date evidence-based resource to inform clinical guidelines and health policy decisions. This protocol details the methodology for a living systematic review of the efficiency (ie, cost-effectiveness) of fall prevention interventions for older adults in three settings: community-dwelling, aged care and hospitals.

This protocol used the reporting guidelines from the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocol. Peer-reviewed economic evaluations of controlled clinical trials or health state models will be included. Reports will be obtained through monthly systematic searches of CENTRAL (Ovid), CINAHL (EBSCO), Embase (Ovid), MEDLINE (Ovid), SCOPUS (Elsevier) and Web of Science (Clarivate) alongside snowballing and handsearching EconLit and the Tufts Cost Effectivness Analysis Registry. Screening, data extraction, quality assessment and risk of bias will be assessed by multiple reviewers. The primary outcomes will be the incremental cost-effectiveness (ie, incremental cost per fall prevented), incremental cost-utility (ie, incremental cost per quality-adjusted life year gained) or cost-benefit ratio. Additional outcomes will include falls and cost-related measures. All economic outcomes will be reported in a common year and currency. Results will be reported as a narrative synthesis; meta-analysis will be considered based on data quality, suitability and availability.

Ethical approval is not required as primary human data will not be collected. Results will be disseminated through peer-reviewed publications and a dedicated website.

CRD42024532485.

To improve outcomes for youth who do not respond optimally to existing treatments, we need to identify robust predictors, moderators, and mediators that are ideal targets for personalisation in mental health care. We propose a solution to leverage the Individual Patient Data Meta-analysis (IPDMA) approach to allow broader access to individual-level data while maintaining methodological rigour. Such a resource has the potential to answer questions that are unable to be addressed by single studies, reduce researcher burden, and enable the application of newer statistical techniques, all to provide data-driven strategies for clinical decision-making. Using childhood anxiety as the worked example, the editorial perspective outlines the rationale for leveraging IPDMA methodology to build a data repository, the Platform for Anxiety Disorder Data in Youth. We also include recommendations to address the methods and challenges inherent in this endeavour.

Several AI-aided screening tools have emerged to tackle the ever-expanding body of literature. These tools employ active learning, where algorithms sort abstracts based on human feedback. However, researchers using these tools face a crucial dilemma: When should they stop screening without knowing the proportion of relevant studies? Although numerous stopping rules have been proposed to guide users in this decision, they have yet to undergo comprehensive evaluation. In this study, we evaluated the performance of three stopping rules: the knee method, a data-driven heuristic, and a prevalence estimation technique. We measured performance via sensitivity, specificity, and screening cost and explored the influence of the prevalence of relevant studies and the choice of the learning algorithm. We curated a dataset of abstract collections from meta-analyses across five psychological research domains. Our findings revealed performance differences between stopping rules regarding all performance measures and variations in the performance of stopping rules across different prevalence ratios. Moreover, despite the relatively minor impact of the learning algorithm, we found that specific combinations of stopping rules and learning algorithms were most effective for certain prevalence ratios of relevant abstracts. Based on these results, we derived practical recommendations for users of AI-aided screening tools. Furthermore, we discuss possible implications and offer suggestions for future research.

Journals have experienced a significant rise in submissions of systematic reviews and other types of reviews that often fall short of acceptable quality standards. These shortcomings typically stem from insufficient rigor in their methodology, reporting, or critical appraisal. As a result, these submissions are frequently rejected raising concerns about the standards authors are following when preparing such work. This growing trend of low-quality reviews not only places a burden on editorial teams but also poses a risk to the scientific community by potentially disseminating flawed or unreliable conclusions. Ensuring that articles maintain high standards is crucial for preserving the integrity of the scientific literature and facilitating evidence-based decision-making. In an effort to address this problem, this viewpoint editorial aims to offer concepts and recommendations on available tools for future authors to improve the quality of their reviews, as well as to guide readers and potential journal reviewers on how to critically interpret these articles.

Pregnant persons are susceptible to significant complications following COVID-19, even death. However, worldwide COVID-19 vaccination coverage during pregnancy remains suboptimal.

This study assessed the safety and effectiveness of COVID-19 vaccines administered to pregnant persons and shared this evidence via an interactive online website.

We followed Cochrane methods to conduct this living systematic review. We included studies assessing the effects of COVID-19 vaccines in pregnant persons. We conducted searches every other week for studies until October 2023, without restrictions on language or publication status, in ten databases, guidelines, preprint servers, and COVID-19 websites. The reference lists of eligible studies were hand searched to identify additional relevant studies. Pairs of review authors independently selected eligible studies using the web-based software COVIDENCE. Data extraction and risk of bias assessment were performed independently by pairs of authors. Disagreements were resolved by consensus. We performed random-effects meta-analyses of adjusted relative effects for relevant confounders of comparative studies and proportional meta-analyses to summarize frequencies from one-sample studies using R statistical software. We present the GRADE certainty of evidence from comparative studies. Findings are available on an interactive living systematic review webpage, including an updated evidence map and real-time meta-analyses customizable by subgroups and filters.

We included 177 studies involving 638,791 participants from 41 countries. Among the 11 types of COVID-19 vaccines identified, the most frequently used platforms were mRNA (154 studies), viral vector (51), and inactivated virus vaccines (17). Low to very low-certainty evidence suggests that vaccination may result in minimal to no important differences compared to no vaccination in all assessed maternal and infant safety outcomes from 26 fewer to 17 more events per 1000 pregnant persons, and 13 fewer to 9 more events per 1000 neonates, respectively. We found statistically significant reductions in emergency cesarean deliveries (9%) with mRNA vaccines, and in stillbirth (75-83%) with mRNA/viral vector vaccines. Low to very low-certainty evidence suggests that vaccination during pregnancy with mRNA vaccines may reduce severe cases or hospitalizations in pregnant persons with COVID-19 (72%; 95% confidence interval [CI] 42-86), symptomatic COVID-19 (78%; 95% CI 21-94), and virologically confirmed SARS-CoV-2 infection (82%; 95% CI 39-95). Reductions were lower with other vaccine types and during Omicron variant dominance than Alpha and Delta dominance. Infants also presented with fewer severe cases or hospitalizations due to COVID-19 and laboratory-confirmed SARS-CoV-2 infection (64%; 95% CI 37-80 and 66%; 95% CI 37-81, respectively).

We found a large body of evidence supporting the safety and effectiveness of COVID-19 vaccines during pregnancy. While the certainty of evidence is not high, it stands as the most reliable option available, given the current absence of pregnant individuals in clinical trials. Results are shared in near real time in an accessible and interactive format for scientists, decision makers, clinicians, and the general public. This living systematic review highlights the relevance of continuous vaccine safety and effectiveness monitoring, particularly in at-risk populations for COVID-19 impact such as pregnant persons, during the introduction of new vaccines.

PROSPERO: CRD42021281290.

Depression and dementia represent significant health challenges in older adults. Despite guidelines recommending antidepressants, their efficacy in depressed patients with dementia remains undetermined.

This review, in following a living systematic review approach, primarily aims to determine the effect of any-type antidepressant on the level of depressive symptoms in older adults with dementia and secondly if there is an effect of any-type antidepressants on cognitive state, quality of life, and functionality in the old-age population with dementia.

Systematic review and meta-analysis of RCTs from Medline, Embase, and Cochrane Register. Participants were ≥65 years, with both depression and any type of dementia. Certainty-of-Evidence was assessed through the Cochrane Risk-of-Bias tool and GRADE. Analysis involved standardized mean difference, with 95 % confidence-intervals (CIs).

Of the 27,771 screened articles, 8 studies (617 participants), treated with SSRI, SSNRI, atypical, and tricyclic antidepressants were retained for quantitative synthesis. No evidence for an effect was found (SMD -0.10 [-0.26, 0.07]), nor when subgrouped based on depression severity or dementia level, nor for secondary outcomes.

This review did not find evidence of a clinical effect of antidepressants for treating depression in older adults with dementia. Methodological challenges might contribute to this finding.

Chronic diseases are a considerable burden to health systems, communities, and patients. Much of this burden, however, could be prevented if interventions effective in reducing chronic disease risks were routinely implemented.

The aim of this paper is to discuss the role of public health agencies in preventing chronic disease through the application of learning health system (LHS) approaches to improve the implementation of evidence-based interventions.

We draw on the literature and our experience operating a local LHS in Australia that has achieved rapid improvements in the implementation of chronic disease prevention interventions.

The proposed LHS framework has been adapted to be both implementation and chronic disease prevention focused. The framework describes both broad improvement processes, and the infrastructure and other support (pillars) recommended to support its core functions.

The framework serves as a basis for further exploration of the potentially transformative role LHS's may have in addressing the chronic disease health crisis.

Systematic reviews (SR) are regularly updated to reflect new evidence. However, updates are time-consuming and costly, and therefore should ideally be informed by new high-quality research. The purpose of this study is to assess trends in the quantity, quality, and recency of evidence intervening updates of orthodontic SR.

SR relevant to orthodontics with at least two versions were identified from the Cochrane Database. The number, risk of bias, and year of publication of included trials were recorded for each update. Multivariate regression was conducted to assess factors affecting the risk of bias in trials, and the proportions within SR.

Forty-five SR inclusive of updates were included. The median number of trials was three per review and this increased across subsequent versions. Seven reviews (15.6%) included no evidence, and 40.74% of updates included no new evidence. Most of the primary research was considered high risk of bias (57.3%), although this was reduced marginally across updates. The proportion of studies considered low risk did not improve significantly between updates. There was no impact of publication year of clinical trials on the risk of bias (P = 0.349). However, average age of trials included in a systematic review significantly affected the proportion of low risk-of-bias studies (P = 0.039).

SR are frequently updated without including new evidence. New evidence that is included is commonly deemed to be at high risk of bias. Targeted strategies to improve the efficient use of resources and improve research quality should be considered.