Definitions of digital biomarkers: a systematic mapping of the biomedical literature.

BACKGROUND: Technological devices such as smartphones, wearables and virtual assistants enable health data collection, serving as digital alternatives to conventional biomarkers. We aimed to provide a systematic overview of emerging literature on 'digital biomarkers,' covering definitions, features and citations in biomedical research. METHODS: We analysed all articles in PubMed that used 'digital biomarker(s)' in title or abstract, considering any study involving humans and any review, editorial, perspective or opinion-based articles up to 8 March 2023. We systematically extracted characteristics of publications and research studies, and any definitions and features of 'digital biomarkers' mentioned. We described the most influential literature on digital biomarkers and their definitions using thematic categorisations of definitions considering the Food and Drug Administration Biomarkers, EndpointS and other Tools framework (ie, data type, data collection method, purpose of biomarker), analysing structural similarity of definitions by performing text and citation analyses. RESULTS: We identified 415 articles using 'digital biomarker' between 2014 and 2023 (median 2021). The majority (283 articles; 68%) were primary research. Notably, 287 articles (69%) did not provide a definition of digital biomarkers. Among the 128 articles with definitions, there were 127 different ones. Of these, 78 considered data collection, 56 data type, 50 purpose and 23 included all three components. Those 128 articles with a definition had a median of 6 citations, with the top 10 each presenting distinct definitions. CONCLUSIONS: The definitions of digital biomarkers vary significantly, indicating a lack of consensus in this emerging field. Our overview highlights key defining characteristics, which could guide the development of a more harmonised accepted definition.

Clinical trial evidence of quality-of-life effects of disease-modifying therapies for multiple sclerosis: a systematic analysis.

BACKGROUND: Increasingly, patients, clinicians, and regulators call for more evidence on the impact of innovative medicines on quality of life (QoL). We assessed the effects of disease-modifying therapies (DMTs) on QoL in people with multiple sclerosis (PwMS). METHODS: Randomized trials assessing approved DMTs in PwMS with results for at least one outcome referred to as "quality of life" were searched in PubMed and ClinicalTrials.gov. RESULTS: We identified 38 trials published between 1999 and 2023 with a median of 531 participants (interquartile range (IQR) 202 to 941; total 23,225). The evaluated DMTs were mostly interferon-beta (n = 10; 26%), fingolimod (n = 7; 18%), natalizumab (n = 5; 13%), and glatiramer acetate (n = 4; 11%). The 38 trials used 18 different QoL instruments, with up to 11 QoL subscale measures per trial (median 2; IQR 1-3). QoL was never the single primary outcome. We identified quantitative QoL results in 24 trials (63%), and narrative statements in 15 trials (39%). In 16 trials (42%), at least one of the multiple QoL results was statistically significant. The effect sizes of the significant quantitative QoL results were large (median Cohen's d 1.02; IQR 0.3-1.7; median Hedges' g 1.01; IQR 0.3-1.69) and ranged between d 0.14 and 2.91. CONCLUSIONS: Certain DMTs have the potential to positively impact QoL of PwMS, and the assessment and reporting of QoL is suboptimal with a multitude of diverse instruments being used. There is an urgent need that design and reporting of clinical trials reflect the critical importance of QoL for PwMS.

Nurse-led physical activity interventions for people with dementia in nursing homes: A systematic review on intervention characteristics and implementation facilitators/barriers.

BACKGROUND: Physical activities are important to maintain and promote physical functioning and activities of daily living in people with dementia. Nurses are in a key position to deliver physical activity interventions in nursing homes. However, synthesized strategies for sustainable implementation of physical activity interventions in nursing homes for people with dementia are lacking. OBJECTIVE: We aimed at synthesizing the evidence on nurse-led physical activity interventions and at identifying facilitators and barriers to sustainable implementation of physical activity interventions for people with dementia. DESIGN: Systematic review. REVIEW METHODS: We performed a comprehensive literature search combining database searches (MEDLINE, CINAHL, CENTRAL, Web of Science Core Collection; last search: September 27, 2023) and supplementary search methods (citation tracking, web searching, clinical guideline database searching). We considered studies on nurse-led physical activity interventions for people with dementia living in nursing homes for eligibility; published as journal articles and related material in English, French, German language, without restrictions on primary study design and publication year. Independently and in duplicate, we assessed the references' eligibility and the quality of the included studies. We used the Mixed Methods Appraisal Tool to appraise quality of included studies. We piloted and double-checked data extractions, and summarized the results narratively and graphically (harvest plot). We prospectively registered our review (PROSPERO CRD42021271833). RESULTS: We identified 24 studies (of which eleven were randomized trials) assessing various interventions that we categorized into physical exercise (n = 8), care-integrated physical activity (n = 6), outdoor or walking activity (n = 5), technology-supported physical exercise (n = 3), and dancing (n = 2). Types of outcomes and length of follow-up varied widely. Effects were inconclusive, except for outdoor or walking activities showing an overall positive impact on physical outcomes. For eight interventions, we identified evidence on implementation barriers (b) and facilitators (f), including staff shortage (b), staff time resources (b), or ease of implementation for staff (f) and adaptability of interventions (f) or refusal to participate of people with dementia (b). CONCLUSIONS: The results of our review provide a comprehensive overview on types, characteristics and effects of nurse-led physical activity interventions for people with dementia in nursing homes. Based on evidence from a range of study designs and sources, we came to the conclusion that all stakeholders involved considered physical activity interventions for people with dementia as useful and relevant. Outcome measures varied widely and a clear conclusion on effectiveness remains open.

[Evidence-based practice in Bachelor of Nursing programmes in Austria, Germany, and Switzerland: A survey of general conditions, teaching content and methods]. / Evidenzbasierte Praxis in Bachelor-Pflegestudiengängen in Österreich, Deutschland und der Schweiz: ein Survey zu Rahmenbedingungen, Lehrinhalten und -methoden.

BACKGROUND/AIM: Evidence-based practice (EBP) provides an important basis for improving both the quality of care and patient safety. Formulating a research question, searching the literature, and critical appraisal are crucial to developing evidence-based practice. The aim of this survey was to provide an overview of how these topics are integrated into bachelor's degree programs in nursing in Austria, Germany, and the German-speaking part of Switzerland. We also aimed to show how teachers implement these subjects and how they experience and assess the implementation. METHOD: We conducted an exploratory cross-sectional study using an online survey sent out to program directors and teaching staff of all 58 bachelor's degree programs in nursing in Austria, Germany and the German-speaking part of Switzerland. For data collection, a questionnaire was developed containing items on general teaching conditions, contents, and methods of evidence-based nursing practice, as well as on the estimated thematic interest of students. The data were analysed descriptively. RESULTS: The program directors returned 24 questionnaires (41%). Of 75 questionnaires forwarded to the faculty, 17 (23%) were received from nine programs. On average, 5.6 teaching units (SD 2.6) are used for formulating a research question, 10 teaching units (SD 4.1) for literature review, and 11.3 teaching units (SD 6.9) for critical appraisal. Half of the teaching staff indicated that linkages between education and nursing care practice have been established. The traditional teaching method of frontal teaching is used predominantly. Student interest in topics was rated as moderate by most teachers. CONCLUSIONS: Topics on evidence-based practice are an integral part of bachelor's degree programs in nursing in German-speaking countries. An increase in teaching units, active learning methods and the growing interconnection between education and practice could improve the acquisition of competencies and attitudes of students regarding EBP and further advance its implementation in practice.

Validated geographic search filters for bibliographic databases: a scoping review protocol.

OBJECTIVE: The purpose of this scoping review is to identify validated geographic search filters and report their methodology and performance measures. INTRODUCTION: Data on specific geographic areas can be required for evidence syntheses topics, such as the investigation of regional inequalities in health care or to answer context-specific epidemiological questions. Search filters are useful tools for reviewers aiming to identify publications with common characteristics in bibliographic databases. Geographic search filters limit the literature search results to a specific geographic feature (eg, a country or region). INCLUSION CRITERIA: We will include reports on validated geographic search filters that aim to identify research evidence about a defined geographic area (eg, a country/region or a group of countries/regions). METHODS: This review will be conducted in accordance with JBI methodology for scoping reviews. The literature search will be conducted in PubMed and Embase. The InterTASC Information Specialists' Sub-Group Search Filter resource and Google Scholar will also be searched. Reports published in any language, from database inception to the present, will be considered for inclusion. Two researchers will independently screen the title, abstract, and full text of the search results. A third reviewer will be consulted in the event of any disagreements. The data extraction will include study characteristics, basic characteristics of the geographical search filter (eg, country/region), and the methods used to develop and validate the search filter. The extracted data will be summarized narratively and presented in a table. REVIEW REGISTRATION: Open Science Framework https://osf.io/5czhs.

Use of pragmatic randomized trials in multiple sclerosis: A systematic overview.

BACKGROUND: Pragmatic trials are increasingly recognized for providing real-world evidence on treatment choices. OBJECTIVE: The objective of this study is to investigate the use and characteristics of pragmatic trials in multiple sclerosis (MS). METHODS: Systematic literature search and analysis of pragmatic trials on any intervention published up to 2022. The assessment of pragmatism with PRECIS-2 (PRagmatic Explanatory Continuum Indicator Summary-2) is performed. RESULTS: We identified 48 pragmatic trials published 1967-2022 that included a median of 82 participants (interquartile range (IQR) = 42-160) to assess typically supportive care interventions (n = 41; 85%). Only seven trials assessed drugs (15%). Only three trials (6%) included >500 participants. Trials were mostly from the United Kingdom (n = 18; 38%), Italy (n = 6; 13%), the United States and Denmark (each n = 5; 10%). Primary outcomes were diverse, for example, quality-of-life, physical functioning, or disease activity. Only 1 trial (2%) used routinely collected data for outcome ascertainment. No trial was very pragmatic in all design aspects, but 14 trials (29%) were widely pragmatic (i.e. PRECIS-2 score ⩾ 4/5 in all domains). CONCLUSION: Only few and mostly small pragmatic trials exist in MS which rarely assess drugs. Despite the widely available routine data infrastructures, very few trials utilize them. There is an urgent need to leverage the potential of this pioneering study design to provide useful randomized real-world evidence.

The Implementation Success of Technology-Based Counseling in Dementia Care: Scoping Review.

BACKGROUND: Implementing technology-based counseling as a complex intervention in dementia care poses challenges such as adaptation to stakeholders' needs and limited resources. While studies have examined the effectiveness of technology-based counseling, its successful implementation remains largely unexplored. OBJECTIVE: We aimed to review the knowledge about the implementation success of technology-based counseling interventions for people with dementia and their informal caregivers. METHODS: We conducted a scoping review and systematically searched CINAHL, the Cochrane Library including the Cochrane Central Register of Controlled Trials, MEDLINE, PsycINFO, and Web of Science Core Collection databases (April 2021) in combination with citation searching and web searching (November 2021). Studies reporting on technology-based counseling interventions for people with dementia or their informal caregivers were included, irrespective of the design. We used the conceptual framework for implementation outcomes to operationalize implementation success and applied the outcomes acceptability, adoption, appropriateness, feasibility, fidelity, implementation cost, penetration, and sustainability as categories to inform data extraction. We identified dimensions within the categories and synthesized results narratively and graphically. RESULTS: We included 52 publications reporting on 27 technology-based counseling interventions. The studies were conducted in 9 countries and published between 1993 and 2021. As the design of the included studies varied, the number of participants and the type of data reported varied as well. The intervention programs were heterogeneous and ranged from single counseling interventions (such as helpline services) to counseling as part of a multicomponent program. Telephone, email, videoconferencing, social media (respectively chats), and web-based platforms were used for delivering counseling. We found data on appropriateness for all interventions and data on acceptability for most interventions, describing aspects such as consumer-perceived usefulness and helpfulness of services, as well as satisfaction. Information on the other categories of adoption, feasibility, fidelity, implementation cost, penetration, and sustainability was fragmented. CONCLUSIONS: The scope and depth of information on conceptual categories of the implementation success of technology-based counseling for people with dementia and informal caregivers varied. The data only partially covered the concept of implementation success, which highlights the need for a systematic evaluation accompanying the implementation. The application of theoretical approaches for implementation and adherence to the framework for developing and evaluating complex interventions are required to promote the implementation of complex interventions and to comprehensively assess implementation success. TRIAL REGISTRATION: PROSPERO CRD42021245473; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=245473.

Inhibition of the Nogo-pathway in experimental spinal cord injury: a meta-analysis of 76 experimental treatments.

Recovery after spinal cord injury (SCI) may be propagated by plasticity-enhancing treatments. The myelin-associated nerve outgrowth inhibitor Nogo-A (Reticulon 4, RTN4) pathway has been shown to restrict neuroaxonal plasticity in experimental SCI models. Early randomized controlled trials are underway to investigate the effect of Nogo-A/Nogo-Receptor (NgR1) pathway blockers. This systematic review and meta-analysis of therapeutic approaches blocking the Nogo-A pathway interrogated the efficacy of functional locomotor recovery after experimental SCI according to a pre-registered study protocol. A total of 51 manuscripts reporting 76 experiments in 1572 animals were identified for meta-analysis. Overall, a neurobehavioral improvement by 18.9% (95% CI 14.5-23.2) was observed. Subgroup analysis (40 experiments, N = 890) revealed SCI-modelling factors associated with outcome variability. Lack of reported randomization and smaller group sizes were associated with larger effect sizes. Delayed treatment start was associated with lower effect sizes. Trim and Fill assessment as well as Egger regression suggested the presence of publication bias. Factoring in theoretically missing studies resulted in a reduced effect size [8.8% (95% CI 2.6-14.9)]. The available data indicates that inhibition of the Nogo-A/NgR1pathway alters functional recovery after SCI in animal studies although substantial differences appear for the applied injury mechanisms and other study details. Mirroring other SCI interventions assessed earlier we identify similar factors associated with outcome heterogeneity.

Exploring experiences of times without care and encounters in dementia: protocol for a living and adaptive evidence map.

INTRODUCTION: Individuals with dementia spend most of the day without care, without encounters, and usually without activity. Although this has been proven in studies, there is a knowledge gap on how individuals with dementia experience these periods of time. Such knowledge would be highly relevant for health professionals and relatives to develop adequate strategies for dealing with these periods of time. The FreiZeit study aims to reconstruct periods of time without care and encounters from the perspective of individuals with dementia and formal and informal carers. The specific objective of this review is to provide a continuously updated overview of the topical evidence that may be used to guide data synthesis and interpretation within the FreiZeit study. METHODS AND ANALYSIS: We conduct a living evidence map, based on a comprehensive systematic literature search in MEDLINE/PubMed, CINAHL, PsycINFO/Ovid and Web of Science Core Collection, citation-based searches and web searches. We include studies on times without care and encounters of individuals with dementia from the perspective of individuals with dementia themselves and formal or informal caregivers of any observational study design that were conducted in the institutional and domestic long-term care setting and published as journal article in English, French or German language without any restriction of the publication year. One reviewer screens titles, abstracts and full texts and extracts data. Key characteristics and results of the included studies are charted in a tabular format. The searches will be run and continuously updated throughout the duration of the overarching FreiZeit study (every 6 months for 2 years from 2023 to 2025). ETHICS AND DISSEMINATION: Ethics approval is not required for this evidence map. We disseminate our findings via journal articles and conference proceedings as well as other formats. REGISTRATION DETAILS: This review protocol is uploaded on Open Science Framework (OSF; DOI 10.17605/OSF.IO/GDYZ9).

(How) Do We Theorize?: A Focused Mapping Review and Synthesis of Theoretical Nursing Research in the German-Speaking Area.

There are increasing discussions on theory dynamics in nursing research. We aimed at mapping the theoretical publication output by nursing researchers from the European German-speaking area. We conducted a focused mapping review and synthesis, focusing on nursing journals articles with a theory-related aim. We identified 32 eligible publications, reflecting 2% of the nursing journal articles affiliated with researchers from our target region. Twenty-one articles involved an inductive approach. Eleven articles intended to test or revise a theory. The theoretical publication output with a theory-related aim was low. Theory-building efforts were fragmented and mostly without reference to a meta-theoretical level.

Meta-research on pragmatism of randomized trials: rationale and design of the PragMeta database.

BACKGROUND: Pragmatic trials provide decision-oriented, real-world evidence that is highly applicable and generalizable. The interest in real-world evidence is fueled by the assumption that effects in the "real-world" are different to effects obtained under artificial, controlled, research conditions as often used for traditional explanatory trials. However, it is unknown which features of pragmatism, generalizability, and applicability would be responsible for such differences. There is a need to provide empirical evidence and promote meta-research to answer these fundamental questions on the pragmatism of randomized trials and real-world evidence. Here, we describe the rationale and design of the PragMeta database which pursues this goal ( www.PragMeta.org ). METHODS: PragMeta is a non-commercial, open data platform and infrastructure to facilitate research on pragmatic trials. It collects and shares data from published randomized trials that either have a specific design feature or other characteristic related to pragmatism or they form clusters of trials addressing the same research question but having different aspects of pragmatism. This lays the foundation to determine the relationship of various features of pragmatism, generalizability, and applicability with intervention effects or other trial characteristics. The database contains trial data actively collected for PragMeta but also allows to import and link existing datasets of trials collected for other purposes, forming a large-scale meta-database. PragMeta captures data on (1) trial and design characteristics (e.g., sample size, population, intervention/comparison, outcome, longitudinal structure, blinding), (2) effects estimates, and (3) various determinants of pragmatism (e.g., the use of routinely collected data) and ratings from established tools used to determine pragmatism (e.g., the PRagmatic-Explanatory Continuum Indicator Summary 2; PRECIS-2). PragMeta is continuously provided online, inviting the meta-research community to collaborate, contribute, and/or use the database. As of April 2023, PragMeta contains data from > 700 trials, mostly with assessments on pragmatism. CONCLUSIONS: PragMeta will inform a better understanding of pragmatism and the generation and interpretation of real-world evidence.

The spinal cord injury-induced immune deficiency syndrome: results of the SCIentinel study.

Infections are prevalent after spinal cord injury (SCI), constitute the main cause of death and are a rehabilitation confounder associated with impaired recovery. We hypothesize that SCI causes an acquired lesion-dependent (neurogenic) immune suppression as an underlying mechanism to facilitate infections. The international prospective multicentre cohort study (SCIentinel; protocol registration DRKS00000122; n = 111 patients) was designed to distinguish neurogenic from general trauma-related effects on the immune system. Therefore, SCI patient groups differing by neurological level, i.e. high SCI [thoracic (Th)4 or higher]; low SCI (Th5 or lower) and severity (complete SCI; incomplete SCI), were compared with a reference group of vertebral fracture (VF) patients without SCI. The primary outcome was quantitative monocytic Human Leukocyte Antigen-DR expression (mHLA-DR, synonym MHC II), a validated marker for immune suppression in critically ill patients associated with infection susceptibility. mHLA-DR was assessed from Day 1 to 10 weeks after injury by applying standardized flow cytometry procedures. Secondary outcomes were leucocyte subpopulation counts, serum immunoglobulin levels and clinically defined infections. Linear mixed models with multiple imputation were applied to evaluate group differences of logarithmic-transformed parameters. Mean quantitative mHLA-DR [ln (antibodies/cell)] levels at the primary end point 84 h after injury indicated an immune suppressive state below the normative values of 9.62 in all groups, which further differed in its dimension by neurological level: high SCI [8.95 (98.3% confidence interval, CI: 8.63; 9.26), n = 41], low SCI [9.05 (98.3% CI: 8.73; 9.36), n = 29], and VF without SCI [9.25 (98.3% CI: 8.97; 9.53), n = 41, P = 0.003]. Post hoc analysis accounting for SCI severity revealed the strongest mHLA-DR decrease [8.79 (95% CI: 8.50; 9.08)] in the complete, high SCI group, further demonstrating delayed mHLA-DR recovery [9.08 (95% CI: 8.82; 9.38)] and showing a difference from the VF controls of -0.43 (95% CI: -0.66; -0.20) at 14 days. Complete, high SCI patients also revealed constantly lower serum immunoglobulin G [-0.27 (95% CI: -0.45; -0.10)] and immunoglobulin A [-0.25 (95% CI: -0.49; -0.01)] levels [ln (g/l × 1000)] up to 10 weeks after injury. Low mHLA-DR levels in the range of borderline immunoparalysis (below 9.21) were positively associated with the occurrence and earlier onset of infections, which is consistent with results from studies on stroke or major surgery. Spinal cord injured patients can acquire a secondary, neurogenic immune deficiency syndrome characterized by reduced mHLA-DR expression and relative hypogammaglobulinaemia (combined cellular and humoral immune deficiency). mHLA-DR expression provides a basis to stratify infection-risk in patients with SCI.

Technology-Based Counselling for People with Dementia and Their Informal Carers: A Systematic Review and Meta-Analysis.

BACKGROUND: Information technology can enhance timely and individual support for people with Alzheimer's disease and other dementias and their informal carers. OBJECTIVE: To review the effectiveness of technology-based counselling interventions for people with dementia and informal carers. METHODS: Randomized controlled trials of remote dementia counselling interventions were included. We searched CINAHL, Cochrane Library, MEDLINE, PsycINFO, and the Web of Science Core Collection (April 2021) in combination with citation tracking and free web searching (October to November 2021). We provide meta-analyses for caregiver depression, burden, and self-efficacy/mastery and structured reporting for other outcomes. The Grading of Recommendations Assessment, Development and Evaluation approach and the Risk of Bias 2 tool were applied. RESULTS: We included five randomized controlled trials involving 880 participants. Interventions were provided for carers (four studies) or dyads (one study). Carers were predominantly women and were the spouses or children of people with dementia. Counselling was delivered via telephone or videoconference with two to 23 sessions over 1 to 12 months. Control groups received educational and resource materials only, standard (helpline) services, non-directive support, or home visits. Meta-analysis for our primary outcome, depressive symptoms in carers, revealed no statistically significant effect (SMD -0.15; 95% CI -0.40 to 0.10). There were also no significant effects on burden and self-efficacy/mastery. We rated the certainty of evidence as low to very low and all outcomes at an overall high risk of bias. CONCLUSION: The effectiveness of technology-based counselling interventions for people with dementia and informal carers remains uncertain. Theory-based approaches are needed for the development and evaluation of these interventions.

Citation tracking for systematic literature searching: A scoping review.

Citation tracking (CT) collects references with citation relationships to pertinent references that are already known. This scoping review maps the benefit of and the tools and terminology used for CT in health-related systematic literature searching. We included methodological studies on evidence retrieval by CT in health-related literature searching without restrictions on study design, language, or publication date. We searched MEDLINE/Ovid, Web of Science Core Collection, CINAHL/EBSCOhost, LLISFT/EBSCOhost, LISTA/EBSCOhost, conducted web searching via Google Scholar, backward/forward CT of included studies and pertinent reviews, and contacting of experts. Two reviewers independently assessed eligibility. Data extraction and analysis were performed by one reviewer and checked by another. We screened 11,861 references and included 47 studies published between 1985 and 2021. Most studies (96%) assessed the benefit of CT either as supplementary or primary/stand-alone search method. Added value of CT for evidence retrieval was found by 96% of them. Science Citation Index and Social Sciences Citation Index were the most common citation indexes used. Application of multiple citation indexes in parallel, co-citing or co-cited references, CT iterations, or software tools was rare. CT terminology was heterogeneous and frequently ambiguous. The use of CT showed an added value in most of the identified studies; however, the benefit of CT in health-related systematic literature searching likely depends on multiple factors that could not be assessed with certainty. Application, terminology, and reporting are heterogeneous. Based on our results, we plan a Delphi study to develop recommendations for the use and reporting of CT.

Introducing the Library of Guidance for Health Scientists (LIGHTS): A Living Database for Methods Guidance.

Importance: Improving methodological quality is a priority in the health research community. Finding appropriate methods guidance can be challenging due to heterogeneous terminology, poor indexing in medical databases, and variation in formats. The Library of Guidance for Health Scientists (LIGHTS) is a new searchable database for methods guidance articles. Observations: Journal articles that aim to provide guidance for performing (including planning, design, conduct, analysis, and interpretation), reporting, and assessing the quality of health-related research involving humans or human populations (ie, excluding basic and animal research) are eligible for LIGHTS. A team of health researchers, information specialists, and methodologists continuously identifies and manually indexes eligible guidance documents. The search strategy includes focused searches of specific journals, specialized databases, and suggestions from researchers. A current limitation is that a keyword-based search of MEDLINE (and other general databases) and manual screening of records were not feasible because of the large number of hits (n = 915 523). As of September 20, 2022, LIGHTS included 1246 articles (336 reporting guidelines, 80 quality assessment tools, and 830 other methods guidance articles). The LIGHTS website provides a user-oriented search interface including filters for study type, specific methodological topic, research context, guidance type, and development process of the guidance. Automated matching of alternative methodological expressions (eg, enter loss to follow-up and find articles indexed with missing data) enhances search queries. Conclusions and Relevance: LIGHTS is a peer-supported initiative that is intended to increase access to and use of methods guidance relevant to health researchers, statisticians, methods consultants, methods developers, ethics boards, peer reviewers, journal editors, and funding bodies.

The evidence base of US Food and Drug Administration approvals of novel cancer therapies from 2000 to 2020.

Concerns have been raised that regulatory programs to accelerate approval of cancer drugs in cancer may increase uncertainty about benefits and harms for survival and quality of life (QoL). We analyzed all pivotal clinical trials and all non-pivotal randomized controlled trials (RCTs) for all cancer drugs approved for the first time by the FDA between 2000 and 2020. We report regulatory and trial characteristics. Effects on overall survival (OS), progression-free survival and tumor response were summarized in meta-analyses. Effects on QoL were qualitatively summarized. Between 2000 and 2020, the FDA approved 145 novel cancer drugs for 156 indications based on 190 clinical trials. Half of indications (49%) were approved without RCT evidence; 82% had a single clinical trial only. OS was primary endpoint in 14% of trials and QoL data were available from 25%. The median OS benefit was 2.55 months (IQR, 1.33-4.28) with a mean hazard ratio for OS of 0.75 (95%CI, 0.72-0.79, I2  = 42). Improvement for QoL was reported for 7 (4%) of 156 indications. Over time, priority review was used increasingly and the mean number of trials per indication decreased from 1.45 to 1.12. More trials reported results on QoL (19% in 2000-2005; 41% in 2016-2020). For 21 years, novel cancer drugs have typically been approved based on one single, often uncontrolled, clinical trial, measuring surrogate endpoints. This leaves cancer patients without solid evidence that novel drugs improve their survival or QoL and there is no indication towards improvement.

Challenges and care strategies associated with the admission to nursing homes in Germany: a scoping review.

BACKGROUND: The admission to a nursing home is a critical life-event for affected persons as well as their families. Admission related processes are lacking adequate participation of older people and their families. To improve transitions to nursing homes, context- and country-specific knowledge about the current practice is needed. Hence, our aim was to summarize available evidence on challenges and care strategies associated with the admission to nursing homes in Germany. METHODS: We conducted a scoping review and searched eight major international and German-specific electronic databases for journal articles and grey literature published in German or English language since 1995. Further inclusion criteria were focus on challenges or care strategies in the context of nursing home admissions of older persons and comprehensive and replicable information on methods and results. Posters, only-abstract publications and articles dealing with mixed populations including younger adults were excluded. Challenges and care strategies were identified and analysed by structured content analysis using the TRANSCIT model. RESULTS: Twelve studies of 1,384 records were finally included. Among those, seven were qualitative studies, three quantitative observational studies and two mixed methods studies. As major challenges neglected participation of older people, psychosocial burden among family caregivers, inadequate professional cooperation and a lack of shared decision-making and evidence-based practice were identified. Identified care strategies included strengthening shared decision-making and evidence-based practice, improvement in professional cooperation, introduction of specialized transitional care staff and enabling participation for older people. CONCLUSION: Although the process of nursing home admission is considered challenging and tends to neglect the needs of older people, little research is available for the German health care system. The perspective of the older people seems to be underrepresented, as most of the studies focused on caregivers and health professionals. Reported care strategies addressed important challenges, however, these were not developed and evaluated in a comprehensive and systematic way. Future research is needed to examine perspectives of all the involved groups to gain a comprehensive picture of the needs and challenges. Interventions based on existing care strategies should be systematically developed and evaluated to provide the basis of adequate support for older persons and their informal caregivers.

Robustness of reported postacute health outcomes in children with SARS-CoV-2 infection: a systematic review.

OBJECTIVE: To systematically assess the robustness of reported postacute SARS-CoV-2 infection health outcomes in children. METHODS: A search on PubMed and Web of Science was conducted to identify studies published up to 22 January 2022 that reported on postacute SARS-CoV-2 infection health outcomes in children (<18 years) with follow-up of ≥2 months since detection of infection or ≥1 month since recovery from acute illness. We assessed the consideration of confounding bias and causality, as well as the risk of bias. RESULTS: 21 studies including 81 896 children reported up to 97 symptoms with follow-up periods of 2.0-11.5 months. Fifteen studies had no control group. The reported proportion of children with post-COVID syndrome was between 0% and 66.5% in children with SARS-CoV-2 infection (n=16 986) and between 2.0% and 53.3% in children without SARS-CoV-2 infection (n=64 910). Only two studies made a clear causal interpretation of an association between SARS-CoV-2 infection and the main outcome of 'post-COVID syndrome' and provided recommendations regarding prevention measures. The robustness of all 21 studies was seriously limited due to an overall critical risk of bias. CONCLUSIONS: The robustness of reported postacute SARS-CoV-2 infection health outcomes in children is seriously limited, at least in all the published articles we could identify. None of the studies provided evidence with reasonable certainty on whether SARS-CoV-2 infection has an impact on postacute health outcomes, let alone to what extent. Children and their families urgently need much more reliable and methodologically robust evidence to address their concerns and improve care.

Clinical trial research agenda on COVID-19 - the first two years in Germany and beyond.

BACKGROUND: We have followed the COVID-19 clinical trial research agenda from the beginning using the COVID-evidence.org platform. Now, two years after the COVID-19 pandemic started, our aim was to re-examine this research agenda with the latest data to provide a global perspective on the research landscape with a focus on Germany. METHODS: We reviewed and updated previously published data on the COVID-19 clinical research agenda as of 28February 2022 focusing on randomized trials. We used the COVID-evidence.org platform including registry entries from ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform as well as publications from the Living OVerview of Evidence platform for COVID-19 (L·OVE). RESULTS: Two years on from the pandemic outbreak, there were 4,673 registered trials. The majority of these trials have remained small with a median of 120 planned participants (IQR 60-320). In the first hundred days of the pandemic most of them (50%) had been registered in China. More than two years later, the five countries with the most registered trials (alone or within a framework of international collaborations) were the USA (825 trials; 18%), Iran (619 trials; 13%), India (566 trials; 12%), China (353 trials; 8%), and Spain (309 trials; 7%). Only 119 trials were reported to have a study site in Germany (2.5% of the registered trials). Of the 4,673 trials registered, 15% (694 trials) had published their results by February 2022. The clinical research agenda has been marked by both successes, such as the large RECOVERY trial providing evidence on 10 treatments for COVID-19 including over 45,000 patients as of February 2022, and failures: worldwide only 57 randomized trials have been registered over two years that aimed to assess non-pharmaceutical interventions (e.g., face mask policies and lockdown measures) to prevent COVID-19, and only 11 of them had published results informing decisions that have an impact on the life of billions of people worldwide. CONCLUSIONS: The COVID-19 clinical research agenda has highlighted the substantial effort of the research community but also the challenges of the clinical research ecosystem. Most importantly, it has shed light on the ability to circumvent traditional barriers and to make trials more useful even under extraordinary conditions. The time to learn our lessons and apply them is now, and the time to demonstrate how we have improved the system is before the next pandemic.