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Objectives: Patient-reported outcome measures (PROMs) have emerged as a promising approach to involve patients in their treatment process. Beyond serving as outcome measures, PROMs can be applied to provide feedback to healthcare providers and patients, thereby offering valuable insights that can improve health outcomes and care processes. This overview offers a comprehensive synthesis of the effects of PROM feedback, contributing to the evidence-based discussion on PROMs' potential to enhance patient care., Methods: Following Cochrane Collaboration recommendations, this overview included literature reviews across diverse treatment areas, investigating the impact of PROM feedback on patient health outcomes (including quality of life, symptoms, or survival) and care process outcomes (including communication, symptom identification, or clinical practice). The methodological quality of the evidence was assessed with a modified version of A Measurement Tool to Assess Systematic Reviews 2, and the potential overlap of primary studies was quantified. Results were narratively synthesized., Results: Forty reviews grouped into 4 categories of treatment areas were included. Overall, their methodological quality was low. The overall overlap of primary studies was 2.2%, reaching up to 15.7% within specific treatment areas. The results indicate that PROM feedback may enhance the quality-of-care processes, whereas its effects on patient health outcomes remained less conclusive., Conclusions: PROM feedback positively influences the interaction between physicians and patients across the included treatment areas. Further research is needed to comprehend the trickle-down effects of PROM feedback and how to enhance its potential in yielding health benefits for patients., Competing Interests: Author Disclosures Author disclosure forms can be accessed below in the Supplemental Material section., (Copyright © 2024. Published by Elsevier Inc.)

Background: Prehabilitation aims to enhance functional capacity before surgery, minimise complications and achieve a better postoperative outcome. This can be particularly useful for older, frail patients to better tolerate surgery. The aim of this study was to identify what barriers and facilitators healthcare professionals in Germany experienced in the implementation and delivery of the multimodal prehabilitation programme "PRAEP-GO" for (pre-)frail adults aged 70 years and older to inform the implementation of prehabilitation into standard care., Methods: A nested descriptive qualitative study was conducted using semi-structured face-to-face interviews with healthcare professionals involved in the PRAEP-GO trial from the Berlin and Brandenburg region in Germany. Transcripts were analysed using Kuckartz' qualitative content analysis. Results were interpreted and synthesised using the Consolidated Framework for Implementation Research, a theoretical framework to allow their application to a more general context., Results: A total of 14 interviews were conducted. Seven therapists (physio-, ergo-, sports therapy), five physicians and two employees from other professions with mainly administrative and organisational tasks in the project. All identified barriers and facilitating factors could be assigned to the themes of organisation, prehabilitation, cooperation and communication between healthcare professionals and with patients. Much optimisation potential was found regarding organisational aspects, e.g. addressing perceived staff shortages and optimising the patient pathway. Furthermore, it became apparent that communication and cooperation between professionals but also with patients need to be improved. More evidence regarding prehabilitation should be provided to convince professionals more. Prehabilitation should be multimodal and individualised, including the programme duration. Officially introducing prehabilitation into standard care would facilitate its delivery., Discussion: These findings underscore the fact that successful implementation of prehabilitation programmes, such as PRAEP-GO, requires sufficient organisational infrastructure, human resources, access to knowledge, an adaptable and individualised programme design as well as good communication among professionals and with patients. The transferability of the findings is limited by the absence of nutritionists and resulting overrepresentation of other therapists in the sample. To further convince professionals and patients of the concept of prehabilitation, more research is needed to build a solid evidence base that will ensure greater awareness and, thus, more motivation and cooperation among professionals and patients., Trial Registration: Open Science Framework (osf.io/ksfgj)., (© 2024. The Author(s).)

Background: Prehabilitation aims to improve patients' functional capacity before surgery to reduce perioperative complications, promote recovery and decrease probability of disability. The planned economic evaluation is performed alongside a large German multi-centre pragmatic, two-arm parallel-group, randomized controlled trial on prehabilitation for frail elderly patients before elective surgery compared to standard care (PRAEP-GO RCT). The aim is to determine the cost-effectiveness and cost-utility of prehabilitation for frail elderly before an elective surgery., Methods: The planned health economic evaluation comprises cost-effectiveness, and cost-utility analyses. Analyses are conducted in the German context from different perspectives including the payer perspective, i.e. the statutory health insurance, the societal perspective and the health care provider perspective. Data on outcomes and costs, are collected alongside the ongoing PRAEP-GO RCT. The trial population includes frail or pre-frail patients aged ≥70 years with planned elective surgery. The intervention consists of frailty screening (Fried phenotype), a shared decision-making conference determining modality (physiotherapy and unsupervised physical exercises, nutrition counselling, etc.) and setting (inpatient, day care, outpatient etc.) of a 3-week individual multimodal prehabilitation prior to surgery. The control group receives standard preoperative care. Costs include the intervention costs, the costs of the index hospital stay for surgery, and health care resources consumed during a 12-month follow-up. Clinical effectiveness outcomes included in the economic evaluation are the level of care dependency, the degree of disability as measured by the WHO Disability Assessment Schedule 2.0 (WHODAS 2.0), quality-adjusted life years (QALY) derived from the EQ-5D-5L and the German utility set, and complications occurring during the index hospital stay. Each adopted perspective considers different types of costs and outcomes as outlined in the protocol. All analyses will feature Intention-To-Treat analysis. To explore methodological and parametric uncertainties, we will conduct probabilistic and deterministic sensitivity analyses. Subgroup analyses will be performed as secondary analyses., Discussion: The health economic evaluation will provide insights into the cost-effectiveness of prehabilitation in older frail populations, informing decision-making processes and contributing to the evidence base in this field. Potential limitation includes a highly heterogeneous trial population., Trial Registration: PRAEP-GO RCT: NCT04418271; economic evaluation: OSF ( https://osf.io/ecm74 )., (© 2024. The Author(s).)

Background: Despite evidence supporting the effectiveness of prehabilitation as a new preoperative care pathway to optimise perioperative outcomes, its implementation into routine health care is widely pending. Frail patients might particularly benefit from prehabilitation interventions, but facilitating and hindering factors need to be considered in the implementation process. Thus, our aim was to derive a programme theory on what prehabilitation programmes work for frail patients in what circumstances and why., Methods: Following Pawson's realist review approach, preliminary programme theories on facilitators and barriers were established. General and topic-specific databases were searched systematically for facilitators and barriers to the implementation of prehabilitation for frail patients. Articles were included if they dealt with multimodal prehabilitation programmes prior to surgery in a frail population and if they contained information on facilitators and barriers during the implementation process in the full text. Based on these articles, refined programme theories were generated., Results: From 2,609 unique titles, 34 were retained for the realist synthesis. Facilitating factors included the individualisation of prehabilitation programmes to meet the patients' needs and abilities, multimodality, adaption to the local setting and health care system, endorsement by an ambassador and sharing of responsibilities among a multidisciplinary team. Central barriers for frail patients were transportation, lack of social support, and inadequate, overwhelming information provision., Conclusions: Implementing prehabilitation as a new care pathway for frail patients requires organisational readiness and adaptability to the local setting. On an individual level, a clear understanding of responsibilities and of the intervention's goal among patients and providers are necessary. Added attention must be paid to the individualisation to fit the needs and restrictions of frail patients. This makes prehabilitation a resource-intense, but promising intervention for frail surgery patients., Trial Registration: PROSPERO (CRD42022335282)., (© 2024. The Author(s).)

Objectives: A measurement tool to assess systematic reviews 2 (AMSTAR 2) was originally developed for systematic reviews (SRs) of health-care interventions. The aim of this study was to assess the applicability of AMSTAR 2 to SRs of non-intervention studies., Study Design and Setting: This was a meta-research study. We used 20 SRs for each of the following four types of SRs: Diagnostic Test Accuracy reviews, Etiology and/or Risk reviews, Prevalence and/or Incidence reviews, and Prognostic reviews (80 in total). Three authors applied AMSTAR 2 independently to each included SRs. Then, the authors assessed the applicability of each item to that SR type and any SR type., Results: Researchers unanimously indicated that 7 of 16 AMSTAR 2 items were applicable for all four specific SR types and any SR type (items 2, 5, 6, 7, 10, 14 and 16), but 8 of 16 items for any SR type. These items could cover generic SR methods that do not depend on a specific SR type., Conclusion: AMSTAR 2 is only partially applicable for non-intervention SRs. There is a need to adapt/extend AMSTAR 2 for SRs of non-intervention studies. Our study can help to further define generic methodological aspects shared across SR types and methodological expectations for non-intervention SRs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The reimbursement of new technologies in inpatient care is not always linked to a requirement for evidence-based evaluation of patient benefit. In Germany, every new technology approved for market was until recently eligible for reimbursement in inpatient care unless explicitly excluded. The aim of this work was (1) to investigate the type of evidence that was available at the time of introduction of 25 innovative technologies and how this evidence evolved over time, and (2) to explore the relationship between clinical evidence and utilization for these technologies in German inpatient care., Methods: This study combined different methods. A systematic search for evidence published between 2003 and 2017 was conducted in four bibliographic databases, clinical trial registries, resources for clinical guidelines, and health technology assessment-databases. Information was also collected on funding mechanisms and safety notices. Utilization was measured by hospital procedures captured in claims data. The body of evidence, funding and safety notices per technology were analyzed descriptively. The relationship between utilization and evidence was explored empirically using a multilevel regression analysis., Results: The number of included publications per technology ranges from two to 498. For all technologies, non-comparative studies form the bulk of the evidence. The number of randomized controlled clinical trials per technology ranges from zero to 19. Some technologies were utilized for several years without an adequate evidence base. A relationship between evidence and utilization could be shown for several but not all technologies., Conclusions: This study reveals a mixed picture regarding the evidence available for new technologies, and the relationship between the development of evidence and the use of technologies over time. Although the influence of funding and safety notices requires further investigation, these results re-emphasize the need for strengthening market approval standards and HTA pathways as well as approaches such as coverage with evidence development., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Prehabilitation aims at enhancing patients' functional capacity and overall health status to enable them to withstand a forthcoming stressor like surgery. Our aim was to synthesise the evidence on the cost-effectiveness of prehabilitation for patients awaiting elective surgery compared with usual preoperative care., Methods: We searched PubMed, Embase, the CRD database, ClinicalTrials.gov, the WHO ICTRP and the dissertation databases OADT and DART. Studies comparing prehabilitation for patients with elective surgery to usual preoperative care were included if they reported cost outcomes. All types of economic evaluations (EEs) were included. The primary outcome of the review was cost-effectiveness based on cost-utility analyses (CUAs). The risk of bias of trial-based EEs was assessed with the Cochrane risk of bias 2 tool and the ROBINS-I tool and the credibility of model-based EEs with the ISPOR checklist. Methodological quality of full EEs was assessed using the CHEC checklist. The EEs' results were synthesised narratively using vote counting based on direction of effect., Results: We included 45 unique studies: 25 completed EEs and 20 ongoing studies. Of the completed EEs, 22 were trial-based and three model-based, corresponding to four CUAs, three cost-effectiveness analyses, two cost-benefit analyses, 12 cost-consequence analyses and four cost-minimization analyses. Three of the four trial-based CUAs (75%) found prehabilitation cost-effective, i.e. more effective and/or less costly than usual care. Overall, 16/25 (64.0%) EEs found prehabilitation cost-effective. When excluding studies of insufficient credibility/critical risk of bias, this number reduced to 14/23 (60.9%). In 8/25 (32.0%), cost-effectiveness was unclear, e.g. because prehabilitation was more effective and more costly, and in one EE prehabilitation was not cost-effective., Conclusions: We found some evidence that prehabilitation for patients awaiting elective surgery is cost-effective compared to usual preoperative care. However, we suspect a relevant risk of publication bias, and most EEs were of high risk of bias and/or low methodological quality. Furthermore, there was relevant heterogeneity depending on the population, intervention and methods. Future EEs should be performed over a longer time horizon and apply a more comprehensive perspective., Trial Registration: PROSPERO CRD42020182813., (© 2023. The Author(s).)

Objective: Data extraction is a prerequisite for analyzing, summarizing, and interpreting evidence in systematic reviews. Yet guidance is limited, and little is known about current approaches. We surveyed systematic reviewers on their current approaches to data extraction, opinions on methods, and research needs., Study Design and Setting: We developed a 29-question online survey and distributed it through relevant organizations, social media, and personal networks in 2022. Closed questions were evaluated using descriptive statistics, and open questions were analyzed using content analysis., Results: 162 reviewers participated. Use of adapted (65%) or newly developed extraction forms (62%) was common. Generic forms were rarely used (14%). Spreadsheet software was the most popular extraction tool (83%). Piloting was reported by 74% of respondents and included a variety of approaches. Independent and duplicate extraction was considered the most appropriate approach to data collection (64%). About half of respondents agreed that blank forms and/or raw data should be published. Suggested research gaps were the effects of different methods on error rates (60%) and the use of data extraction support tools (46%)., Conclusion: Systematic reviewers used varying approaches to pilot data extraction. Methods to reduce errors and use of support tools such as (semi-)automation tools are top research gaps., Competing Interests: Declaration of competing interest Andrea Tricco is Co-Editor-in-Chief of the JCE., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: Precision medicine is increasingly important in cancer treatment. Tumor-agnostic therapies are used regardless of tumor entity because they target specific biomarkers in tumors. In Germany, the benefit assessment of oncological pharmaceuticals has traditionally been entity specific. Thus, the assessment of tumor-agnostic therapies leaves stakeholders with various challenges. Our aim was to systematically identify challenges and possible solutions for the benefit assessment of therapies in tumor-agnostic indications using a 2-step sequential qualitative approach., Methods: To identify relevant challenges, we conducted qualitative interviews with different stakeholders who were involved in previous benefit assessments of tumor-agnostic therapies in Germany. To identify possible solutions for these challenges, we systematically searched MEDLINE, Embase, and the websites of European health technology assessment bodies for relevant literature., Results: We identified 9 categories of challenges of which the following were deemed particularly relevant: the absence of direct comparative studies, challenges regarding the use of basket studies and indirect comparisons, challenges in determining the appropriate comparative therapy in a tumor-agnostic indication, and challenges on the system side. Seven categories of solutions were identified, including an increased use of real-world evidence, making conditional decisions in the context of systematic reassessments, splitting the field of application, and finding (new) ways to design and analyze basket studies., Conclusion: A range of possible solutions, which can help to meet the identified challenges in Germany, have been found. Future research should investigate the acceptance and feasibility of these solutions., (Copyright © 2023. Published by Elsevier Inc.)

Objectives: To analyze whether articles labelled as systematic reviews or meta-analyses (SRs/MAs) in the title and used terms "updated" or "update" in the title or abstract are indeed a report of an updated version of a previously existing SR/MA., Study Design and Setting: We searched PubMed for SRs/MAs, using descriptors updated/update in the title/abstract published in 2018-2019. We analyzed how the articles used the term "update"/"updated" and whether the previous version of SR was referenced. We surveyed authors who indicated that the SR was an updated version, but there was no reference to the original SR., Results: Among 1,118 included articles, most (N = 716; 64%) used the term "update" only to denote that an SR includes recent data. Among 47 authors eligible for survey, 15 replied (32%). Six authors (40%) stated that their article was an updated version and gave reference to the previous version, while 9 authors (60%) stated that their SR was not an updated version of a previous SR., Conclusion: Most SRs that used the term "update" in title/abstract were not an updated version of an SR. Authors should use the descriptor "update"/"updated" in their title/abstract only to refer to a new version of an SR to avoid ambiguity., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Restrictions in systematic reviews (SRs) can lead to bias and may affect conclusions. Therefore, it is important to report whether and which restrictions were used. This study aims to examine the use of restrictions regarding language, publication period, and study type, as well as the transparency of reporting in SRs of effectiveness., Methods: A retrospective observational study was conducted with a random sample of 535 SRs of effectiveness indexed in PubMed between 2000 and 2019. The use of restrictions and their reporting were analysed using descriptive statistics., Results: Of the total 535 SRs included, four out of every ten (41.3%) lacked information on at least one of the three restrictions considered (language, publication period, or study type). Overall, 14.6% of SRs did not provide information on restrictions regarding publication period, 19.1% regarding study type, and 18.3% regarding language. Of all included SRs, language was restricted in 46.4%, and in more than half of the SRs with restricted language (130/248), it was unclear whether the restriction was applied during either the search or the screening process, or both. The restrictions were justified for publication period in 22.2% of the respective SRs (33/149), study type in 6.5% (28/433), and language in 3.2% (8/248). Differences in reporting were found between countries as well as between Cochrane and non-Cochrane reviews., Conclusions: This study suggests that there is a lack of transparency in reporting on restrictions in SRs. Authors as well as editors and reviewers should be encouraged to improve the reporting and justification of restrictions to increase the transparency of SRs., (© 2022. The Author(s).)

Background: The coronavirus disease 2019 (COVID-19) pandemic has developed into an unprecedented global challenge. Differences between countries in testing strategies, hospitalization protocols as well as ensuring and managing ICU capacities can illustrate initial responses to a major health system shock, and steer future preparedness activities., Methods: Publicly available daily data for 18 European countries were retrieved manually from official sources and documented in an Excel table (March-July 2020). The ratio of tests to cases, the share of hospitalizations out of all cases and the share of ICU admissions out of all hospitalizations were computed using 7-day rolling averages per 100 000 population. Information on country policies was collected from the COVID-19 Health System Response Monitor of the European Observatory on Health Systems and Policies. Information on health care capacities, expenditure and utilization was extracted from the Eurostat health database., Results: There was substantial variation across countries for all studied variables. In all countries, the ratio of tests to cases increased over time, albeit to varying degrees, while the shares of hospitalizations and ICU admissions stabilized, reflecting the evolution of testing strategies and the adaptation of COVID-19 health care delivery pathways, respectively. Health care patterns for COVID-19 at the outset of the pandemic did not necessarily follow the usual health service delivery pattern of each health system., Conclusions: This study enables a general understanding of how the early evolution of the pandemic influenced and was influenced by country responses and clearly demonstrates the immense potential for cross-country learning., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Public Health Association.)

Background: Frailty is expressed by a reduction in physical capacity, mobility, muscle strength, and endurance. (Pre-)frailty is present in up to 42% of the older surgical population, with an increased risk for peri- and postoperative complications. Consequently, these patients often suffer from a delayed or limited recovery, loss of autonomy and quality of life, and a decrease in functional and cognitive capacities. Since frailty is modifiable, prehabilitation may improve the physiological reserves of patients and reduce the care dependency 12 months after surgery., Methods: Patients ≥ 70 years old scheduled for elective surgery or intervention will be recruited in this multicenter, randomized controlled study, with a target of 1400 participants with an allocation ratio of 1:1. The intervention consists of (1) a shared decision-making process with the patient, relatives, and an interdisciplinary and interprofessional team and (2) a 3-week multimodal, individualized prehabilitation program including exercise therapy, nutritional intervention, mobility or balance training, and psychosocial interventions and medical assessment. The frequency of the supervised prehabilitation is 5 times/week for 3 weeks. The primary endpoint is defined as the level of care dependency 12 months after surgery or intervention., Discussion: Prehabilitation has been proven to be effective for different populations, including colorectal, transplant, and cardiac surgery patients. In contrast, evidence for prehabilitation in older, frail patients has not been clearly established. To the best of our knowledge, this is currently the largest prehabilitation study on older people with frailty undergoing general elective surgery., Trial Registration: ClinicalTrials.gov NCT04418271 . Registered on 5 June 2020. Universal Trial Number (UTN): U1111-1253-4820., (© 2022. The Author(s).)

Background: The exponential increase in SARS-CoV-2 infections during the first wave of the pandemic created an extraordinary overload and demand on hospitals, especially intensive care units (ICUs), across Europe. European countries have implemented different measures to address the surge ICU capacity, but little is known about the extent. The aim of this paper is to compare the rates of hospitalised COVID-19 patients in acute and ICU care and the levels of national surge capacity for intensive care beds across 16 European countries and Lombardy region during the first wave of the pandemic (28 February to 31 July)., Methods: For this country level analysis, we used data on SARS-CoV-2 cases, current and/or cumulative hospitalised COVID-19 patients and current and/or cumulative COVID-19 patients in ICU care. To analyse whether capacities were exceeded, we also retrieved information on the numbers of hospital beds, and on (surge) capacity of ICU beds during the first wave of the COVID-19 pandemic from the COVID-19 Health System Response Monitor (HSRM). Treatment days and mean length of hospital stay were calculated to assess hospital utilisation., Results: Hospital and ICU capacity varied widely across countries. Our results show that utilisation of acute care bed capacity by patients with COVID-19 did not exceed 38.3% in any studied country. However, the Netherlands, Sweden, and Lombardy would not have been able to treat all patients with COVID-19 requiring intensive care during the first wave without an ICU surge capacity. Indicators of hospital utilisation were not consistently related to the number of SARS-CoV-2 infections. The mean number of hospital days associated with one SARS-CoV-2 case ranged from 1.3 (Norway) to 11.8 (France)., Conclusion: In many countries, the increase in ICU capacity was important to accommodate the high demand for intensive care during the first COVID-19 wave., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Prospective registration aims to reduce bias in the conduct and reporting of research and to increase transparency. In addition, prospective registration of systematic reviews is argued to help preventing unintended duplication, thereby reducing research waste. PROSPERO was launched in 2011 as the first prospective register for systematic reviews. While it has long been the only option to prospectively register systematic reviews, recently there have been new developments. Our aim was to identify and characterize current options to prospectively register a systematic review to assist review authors in choosing a suitable register., Methods: To identify systematic review registers, we independently performed internet searches in January 2021 using keywords related to systematic reviews and prospective registration. "Registration" was defined as the process of entering information about a planned systematic review into a database before starting the systematic review process. We collected data on the characteristics of the identified registries and contacted the responsible party of each register for verification of the data related to their registry., Results: Overall, we identified five options to prospectively register a systematic review: PROSPERO, the Registry of Systematic Reviews/Meta-Analyses in Research Registry, and INPLASY, which are specific to systematic reviews, and the Open Science Framework Registries and protocols.io, which represent generic registers open to any study type. Detailed information on each register is presented in tables in the main text. Regarding the systematic-review-specific registries, authors have to trade-off between the costs of registration and the processing time of their registration record. All registers provide an option to search for systematic reviews already registered in the register. However, it is unclear how useful these search functions are., Conclusion: Authors can prospectively register their systematic review in five registries, which come with different characteristics and features. The research community should discuss fair and sustainable financing models for registers that are not operated by for-profit organizations., (© 2022. The Author(s).)

Background: Innovative medical technologies are commonly associated with positive expectations. At the time of their introduction into care, there is often little evidence available regarding their benefits and harms. Accordingly, some innovative medical technologies with a lack of evidence are used widely until or even though findings of adverse events emerge, while others with study results supporting their safety and effectiveness remain underused. This study aims at examining the diffusion patterns of innovative medical technologies in German inpatient care between 2005 and 2017 while simultaneously considering evidence development., Methods: Based on a qualitatively derived typology and a quantitative clustering of the adoption curves, a representative sample of 21 technologies was selected for further evaluation. Published scientific evidence on efficacy/effectiveness and safety of the technologies was identified and extracted in a systematic approach. Derived from a two-dimensional classification according to the degree of utilization and availability of supportive evidence, the diffusion patterns were then assigned to the categories "Success" (widespread/positive), "Hazard" (widespread/negative), "Overadoption" (widespread/limited or none), "Underadoption" (cautious/positive), "Vigilance" (cautious/negative), and "Prudence" (cautious/limited or none)., Results: Overall, we found limited evidence on the examined technologies regarding both the quantity and quality of published randomized controlled trials. Thus, the categories "Prudence" and "Overadoption" together account for nearly three-quarters of the years evaluated, followed by "Success" with 17%. Even when evidence is available, the transfer of knowledge into practice appears to be inhibited., Conclusions: The successful implementation of safe and effective innovative medical technologies into practice requires substantial further efforts by policymakers to strengthen systematic knowledge generation and translation. Creating an environment that encourages the conduct of rigorous studies, promotes knowledge translation, and rewards innovative medical technologies according to their added value is a prerequisite for the diffusion of valuable health care., (© 2021. The Author(s).)

Background: Systematic reviews (SRs) are useful tools in synthesising the available evidence, but high numbers of overlapping SRs are also discussed in the context of research waste. Although it is often claimed that the number of SRs being published is increasing steadily, there are no precise data on that. We aimed to assess trends in the epidemiology and reporting of published SRs over the last 20 years., Methods: A retrospective observational study was conducted to identify potentially eligible SRs indexed in PubMed from 2000 to 2019. From all 572,871 records retrieved, we drew a simple random sample of 4,000. The PRISMA-P definition of SRs was applied to full texts and only SRs published in English were included. Characteristics were extracted by one reviewer, with a 20% sample verified by a second person., Results: A total of 1,132 SRs published in 710 different journals were included. The estimated number of SRs indexed in 2000 was 1,432 (95% CI: 547-2,317), 5,013 (95% CI: 3,375-6,650) in 2010 and 29,073 (95% CI: 25,445-32,702) in 2019. Transparent reporting of key items increased over the years. About 7 out of 10 named their article a SR (2000-2004: 41.9% and 2015-2019: 74.4%). In 2000-2004, 32.3% of SRs were based in the UK (0% in China), in 2015-2019 24.0% were from China and 10.8% from the UK. Nearly all articles from China (94.9%) conducted a meta-analysis (overall: 58.9%). Cochrane reviews (n = 84; 7.4%) less often imposed language restrictions, but often did not report the number of records and full texts screened and did not name their article a SR (22.6% vs. 73.4%)., Conclusions: We observed a more than 20-fold increase in the number of SRs indexed over the last 20 years. In 2019, this is equivalent to 80 SRs per day. Over time, SRs got more diverse in respect to journals, type of review, and country of corresponding authors. The high proportion of meta-analyses from China needs further investigation., Study Registration: Open Science Framework (https://osf.io/pxjrv/)., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: COVID-19 frequently necessitates in-patient treatment and in-patient mortality is high. Less is known about the long-term outcomes in terms of mortality and readmissions following in-patient treatment., Aim: The aim of this paper is to provide a detailed account of hospitalized COVID-19 patients up to 180 days after their initial hospital admission., Methods: An observational study with claims data from the German Local Health Care Funds of adult patients hospitalized in Germany between February 1 and April 30, 2020, with PCR-confirmed COVID-19 and a related principal diagnosis, for whom 6-month all-cause mortality and readmission rates for 180 days after admission or until death were available. A multivariable logistic regression model identified independent risk factors for 180-day all-cause mortality in this cohort., Results: Of the 8,679 patients with a median age of 72 years, 2,161 (24.9%) died during the index hospitalization. The 30-day all-cause mortality rate was 23.9% (2,073/8,679), the 90-day rate was 27.9% (2,425/8,679), and the 180-day rate, 29.6% (2,566/8,679). The latter was 52.3% (1,472/2,817) for patients aged ≥80 years 23.6% (1,621/6,865) if not ventilated during index hospitalization, but 53.0% in case of those ventilated invasively (853/1,608). Risk factors for the 180-day all-cause mortality included coagulopathy, BMI ≥ 40, and age, while the female sex was a protective factor beyond a fewer prevalence of comorbidities. Of the 6,235 patients discharged alive, 1,668 were readmitted a total of 2,551 times within 180 days, resulting in an overall readmission rate of 26.8%., Conclusions: The 180-day follow-up data of hospitalized COVID-19 patients in a nationwide cohort representing almost one-third of the German population show significant long-term, all-cause mortality and readmission rates, especially among patients with coagulopathy, whereas women have a profoundly better and long-lasting clinical outcome compared to men., Competing Interests: RB reports grants from Berlin University Alliance, during the conduct of the study; grants from Federal Ministry of Research and Education, grants from Federal Ministry of Health, grants from Innovation Fonds of the Federal Joint Committee, grants from World Health Organization, outside the submitted work, AS reports grants from Bayer AG, outside the submitted work. CK reports personal fees from Maquet, personal fees from Xenios, personal fees from Bayer, non-financial support from Speaker of the German register of ICUs, grants from German Ministry of Research and Education, during the conduct of the study. CG, MS, TR, GS, WH, and SWC have nothing to disclose.

Importance: Extenuating circumstances can trigger unplanned changes to randomized trials and introduce methodological, ethical, feasibility, and analytical challenges that can potentially compromise the validity of findings. Numerous randomized trials have required changes in response to the COVID-19 pandemic, but guidance for reporting such modifications is incomplete., Objective: As a joint extension for the CONSORT and SPIRIT reporting guidelines, CONSERVE (CONSORT and SPIRIT Extension for RCTs Revised in Extenuating Circumstances) aims to improve reporting of trial protocols and completed trials that undergo important modifications in response to extenuating circumstances., Evidence: A panel of 37 international trial investigators, patient representatives, methodologists and statisticians, ethicists, funders, regulators, and journal editors convened to develop the guideline. The panel developed CONSERVE following an accelerated, iterative process between June 2020 and February 2021 involving (1) a rapid literature review of multiple databases (OVID Medline, OVID EMBASE, and EBSCO CINAHL) and gray literature sources from 2003 to March 2021; (2) consensus-based panelist meetings using a modified Delphi process and surveys; and (3) a global survey of trial stakeholders., Findings: The rapid review yielded 41 673 citations, of which 38 titles were relevant, including emerging guidance from regulatory and funding agencies for managing the effects of the COVID-19 pandemic on trials. However, no generalizable guidance for all circumstances in which trials and trial protocols might face unanticipated modifications were identified. The CONSERVE panel used these findings to develop a consensus reporting guidelines following 4 rounds of meetings and surveys. Responses were received from 198 professionals from 34 countries, of whom 90% (n = 178) indicated that they understood the concept definitions and 85.4% (n = 169) indicated that they understood and could use the implementation tool. Feedback from survey respondents was used to finalize the guideline and confirm that the guideline's core concepts were applicable and had utility for the trial community. CONSERVE incorporates an implementation tool and checklists tailored to trial reports and trial protocols for which extenuating circumstances have resulted in important modifications to the intended study procedures. The checklists include 4 sections capturing extenuating circumstances, important modifications, responsible parties, and interim data analyses., Conclusions and Relevance: CONSERVE offers an extension to CONSORT and SPIRIT that could improve the transparency, quality, and completeness of reporting important modifications to trials in extenuating circumstances such as COVID-19.

Background: Total knee arthroplasty (TKA) is performed to treat end-stage knee osteoarthritis. In Germany, a minimum volume threshold of 50 TKAs/hospital/year was implemented to ensure outcome quality. This study, embedded within a systematic review, aimed to investigate the perspectives of potential TKA patients on the hospital volume-outcome relationship for TKA (higher volumes associated with better outcomes)., Methods: A convenience sample of adults with knee problems and heterogeneous demographic characteristics participated in the study. Qualitative data were collected during a focus group prior to the systematic review (n = 5) and during telephone interviews, in which preliminary results of the systematic review were discussed (n = 16). The data were synthesised using content analysis., Results: All participants (n = 21) believed that a hospital volume-outcome relationship exists for TKA while recognising that patient behaviour or the surgeon could also influence outcomes. All participants would be willing to travel longer for better outcomes. Most interviewees would choose a hospital for TKA depending on reputation, recommendations, and service quality. However, some would also choose a hospital based on the results of the systematic review that showed slightly lower mortality/revision rates at higher-volume hospitals. Half of the interviewees supported raising the minimum volume threshold even if this were to increase travel time to receive TKA., Conclusions: Potential patients believe that a hospital volume-outcome relationship exists for TKA. Hospital preference is based mainly on subjective factors, although some potential patients would consider scientific evidence when making their choice. Policy makers and physicians should consider the patient perspectives when deciding on minimum volume thresholds or recommending hospitals for TKA, respectively.

Objective: To compare two strategies for requesting additional information for systematic reviews (SR) from study authors., Study Design and Setting: Randomised study within a SR of hospital volume-outcome relationships in total knee arthroplasty. We sent personalized email requests for additional information to study authors as either email text ("Email" group) or attachment with self-developed, personalised data request forms ("Attachment" group). The primary outcome was the response rate, the secondary outcomes were the data completeness rate and the reviewer time invested in author contact., Results: Of 57 study authors, 29 were randomised to the Email group and 28 to the Attachment group. The response rate was 93% for Email and 75% for Attachment (odds ratio 4.5, 95% confidence interval [0.9-24.0]). Complete data were provided by 55% (Email) vs. 36% (Attachment) of authors (odds ratio 2.2 [0.8-6.4]). The mean reviewer time was shorter in the Email (mean ± standard deviation of 20.2±14.4 minutes/author) than the Attachment group (31.8±14.4 minutes/author) with a mean difference of 11.6 [4.1-19.1] minutes/author., Conclusion: Personalised email requests elicited high response but only moderate data completeness rates regardless of the method (email text or attachment). Email requests as text took less reviewer time than creating attachments., (Copyright © 2021. Published by Elsevier Inc.)

Background: An intestinal ostomy is an artificial bowel opening created on the skin. Procedure-related mortality is extremely rare. However, the presence of an ostomy may be associated with significant morbidity. Complications negatively affect the quality of life of ostomates. Preoperative stoma site marking can reduce stoma-related complications and is recommended by several guidelines. However, there is no consensus on the procedure and recommendations are based on low-quality evidence. The objective of the systematic review will be to investigate if preoperative stoma site marking compared to no preoperative marking in patients undergoing intestinal stoma surgery reduces or prevents the rate of stoma-related complications., Methods: We will include (cluster-) randomised controlled trials and cohort studies that involve patients with intestinal ostomies comparing preoperative stoma site marking to no preoperative marking and report at least one patient-relevant outcome. For study identification, we will systematically search MEDLINE/PubMed, EMBASE, CENTRAL and CINHAL as well as Google Scholar, trial registries, conference proceedings and reference lists. Additionally, we will contact experts in the field. Two reviewers will independently perform study selection and data extraction. Outcomes will be prioritised based on findings from telephone interviews with five ostomates and five ostomy and wound nurses prior to conducting the review. Outcomes may include but are not limited to stoma-related complications (infection, parastomal abscess, hernia, mucocutaneous separation, dermatological complications, stoma necrosis, stenosis, retraction and prolapse) or other patient-relevant postoperative endpoints (quality of life, revision rate, dependence on professional care, mortality, length of stay and readmission). We will use the ROBINS-I or the Cochrane risk of bias tool to assess the risk of bias of the included studies. We will perform a meta-analysis and assess the certainty of evidence using the GRADE approach., Discussion: With the results of the systematic review, we aim to provide information for future clinical guidelines and influence clinical routine with regard to preoperative stoma site marking in patients undergoing ostomy surgery. When the evidence of our systematic review is low, it would still be a useful basis for future clinical trials by identifying data gaps., Systematic Review Registration: PROSPERO registration number: CRD42021226647.

Objectives: We assessed disagreements between nonrandomized controlled studies based on real-world data (NRCS-RWDs) and randomized controlled trials (RCTs)., Study Design and Setting: We systematically searched for studies that compared treatment effect estimates from NRCS-RWDs and RCTs on the same clinical question. We assessed the potential difference between NRCS-RWDs and RCTs related to internal and external validity. We calculated various meta-epidemiological measures to assess agreement. In case of disagreements, we tried to identify the probable causes of disagreements., Results: We included 12 studies comparing 15 treatment effect estimates of NRCS-RWDs and RCTs. There were many potential causes of disagreement. Ninety-five percent confidence intervals overlapped for 12 of 15 treatment effect estimates. Our analysis on predicted vs. observed overlap showed that there were no more disagreements than expected by chance. We observed only two substantial differences between the 15 treatment effect estimates. In both cases, we identified risk of bias in the NRCS-RWDs as the most probable cause of disagreement., Conclusion: Our findings suggest that there are clinical questions where the difference in risk of bias between a well-conducted NRCS-RWD and an RCT is negligible. In our analysis, threats to external validity appeared to have no or only a weak impact on the disagreements of treatment effect estimates., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Competing Interests: Competing interests: GCR receives funding from the NHS National Institute of Health Research (NIHR) School for Primary Care Research (SPCR), the Naji Foundation and the Rotary Foundation to study for a Doctor of Philosophy (DPhil) at the University of Oxford. GCR is a member of the EBMLive Steering Committee. SHB, ABD, CBH, BCK, TR, CW and LZJW were Doug Altman Scholars, presented at EBMLive 2019 and had their expenses reimbursed to travel to and attend the conference. CW is funded through the National Institute of Health grant number F30 CA243651-01. BCK has received funding from the NIHR Doctoral Research Fellowship program. PJG has received grant funding from the Canadian Paediatric Society, and the Canadian Institute of Health Research (CIHR) in the past 5 years. He is on the CMAJ Editorial Advisory Board and on the Institute Advisory Board for the CIHR Institute of Human Development, Child and Youth Health (IHDCYH) where he has expenses reimbursed to attend meetings. He is on the editorial board of BMJ Evidence Based Medicine. He is a member of the EBMLive Steering Committee, and he has expenses reimbursed to attend the conference.

Objectives: A measurement tool to assess systematic reviews (SRs) 2 (AMSTAR 2) allows for deriving the overall confidence in an SR. We investigated how authors derived the overall confidence rating and whether different schemes lead to different results., Study Design and Setting: We compared three different schemes (original 7-item scheme, a self-developed 5-item scheme, and the AMSTAR Web site) to derive the overall confidence in AMSTAR 2 using two distinct samples of SRs. Multiple bibliographic databases were searched for articles to analyze how AMSTAR 2 was applied by others., Results: In both samples (n = 60 and n = 58), the Friedman test revealed a significant difference between the schemes (P < 0.001). The Web site scheme was the least strict one, whereas between the 5-item and 7-item scheme, no differences were found in post hoc analyses. We included 53 publications applying AMSTAR 2 identified in our literature search. Only 37 of them (70%) used the original 7-item scheme. Less than half of them (18 of 37) reported how they derived the overall rating., Conclusion: Authors should clearly report how they have derived the overall rating when applying AMSTAR 2. Reporting should allow for reproducing the overall ratings for editors, peer reviewers, and readers., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: Preoperative functional capacity is an important predictor of postoperative outcomes. Prehabilitation aims to optimise patients' functional capacity before surgery to improve postoperative outcomes. As prolonged hospital stay and postoperative complications present an avoidable use of healthcare resources, prehabilitation might also save costs.The aim of this systematic review is to investigate the cost-effectiveness of prehabilitation programmes for patients awaiting elective surgery compared with usual preoperative care. The results will be useful to inform decisions about the implementation of prehabilitation programmes and the design of future economic evaluations of prehabilitation programmes., Methods and Analysis: We will search PubMed, Embase, the Centre for Reviews and Dissemination Database, the WHO International Clinical Trials Registry Platform and ClinicalTrials.gov for full or partial economic evaluations of preoperative prehabilitation programmes conducted in any population compared with usual preoperative care. Studies will be included regardless of the type, design and perspective of the economic evaluation, and their publication year, language or status. Initial searches were performed between 30 April and 4 May 2020.Study selection, data extraction and assessment of the included studies' risk of bias and methodological quality will initially be performed by two independent reviewers and, if agreement was sufficiently high, by one reviewer. We will extract data regarding the included studies' basic characteristics, economic evaluation methods and cost-effectiveness results.A narrative synthesis will be performed. The primary endpoint will be cost-effectiveness based on cost-utility analyses. We will discuss heterogeneity between the studies and assess the risk of publication bias. The certainty of the evidence will be determined using the Grading of Recommendations, Assessment, Development and Evaluation approach., Ethics and Dissemination: Ethics approval is not required as the systematic review will not involve human participants. We plan to present our findings at scientific conferences, pass them on to relevant stakeholder organisations and publish them in a peer-reviewed journal., Prospero Registration Number: CRD42020182813., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Surgical site infection (SSI) describes an infectious complication of surgical wounds. Although SSI is thought to be preventable, it still represents a major cause of morbidity and substantial economic burden on the health system. Wound irrigation (WI) might reduce the level of bacterial contamination, but current data on its role in reducing or preventing SSI is conflicting. Our aim was to investigate the effectiveness of WI with normal saline prior to wound closure for the reduction of SSI in patients undergoing abdominal surgery., Methods: We conducted a systematic literature search in MEDLINE, EMBASE, and CENTRAL from inception to present, and cross-checked the reference lists of all included primary studies and relevant systematic reviews. (Quasi-) randomized controlled trials (RCTs) investigating the rate of SSI when using normal saline vs. no irrigation prior to wound closure following abdominal surgery were included. Primary outcome was the rate of SSI, secondary outcome the mean length of hospital stay (LOS)., Results: Four RCTs including a total of 1194 patients were included for analysis. All studies compared wound irrigation with normal saline with no wound irrigation prior to wound closure. Their risk of bias was moderate. The relative risk of developing a SSI was lower when wound irrigation with normal saline was performed prior to wound closure although the effect was not statistically significant (risk ratio 0.73, 95%-confidence level: 0.37 to 1.43). Similarly, there was no difference in the LOS amongst both intervention arms., Conclusion: This systematic review could not identify an advantage for routine irrigation of abdominal wounds with normal saline over no irrigation prior to wound closure in preventing or reducing the rate of SSI., Systematic Review Registration: PROSPERO registry number CRD42018082287 .

In recent years there has been increasing awareness of problems that have undermined trust in medical research. This review outlines some of the most important issues including research culture, reporting biases, and statistical and methodological issues. It examines measures that have been instituted to address these problems and explores the success and limitations of these measures. The paper concludes by proposing three achievable actions which could be implemented to deliver significantly improved transparency and mitigation of bias. These measures are as follows: (1) mandatory registration of interests by those involved in research; (2) that journals support the 'registered reports' publication format; and (3) that comprehensive study documentation for all publicly funded research be made available on a World Health Organization research repository. We suggest that achieving such measures requires a broad-based campaign which mobilises public opinion. We invite readers to feedback on the proposed actions and to join us in calling for their implementation.

Objectives: This study aimed to explore views of authors of systematic reviews (SRs) registered in the International Prospective Register of Systematic Reviews (PROSPERO) toward publishing SR protocols as peer-reviewed articles., Study Design and Setting: Contact persons of all PROSPERO records for non-Cochrane SRs registered in 2018 (N = 12,531) were invited to participate in an anonymous 5-minute online survey that was administered through SurveyMonkey. The main question addressed SR authors' views toward publishing SR protocols as peer-reviewed articles. Data were analyzed descriptively., Results: In total, 4,223 (33.7%) of 12,531 invitees responded, of which 3,739 (88.5%) completed the survey. Almost half of the international respondents had published or planned to publish a protocol for the SR described in their PROSPERO record as a peer-reviewed article (1,811/4,054; 44.7%). Most respondents agreed that publishing a protocol in a peer-reviewed journal increases SR quality as reviewers get external feedback from peer reviewers (2,899/3,739; 77.5%) but at the same time agreed that it is not necessary if the SR is registered in PROSPERO (2,399/3,739; 64.2%)., Conclusion: SR authors seem to have inconsistent views toward publishing protocols as peer-reviewed articles, and many seem to consider registration in PROSPERO (without peer review) sufficient. Hence, awareness about the benefits of publishing protocols as a peer-reviewed article in addition to registration in PROSPERO should be raised., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: It is important that systematic reviews (SRs) are up-to-date, otherwise they cannot be relied upon to guide decision-making in practice and policy. Our aim was to investigate epidemiological, descriptive and reporting characteristics of a cross-section of recently published updates of SRs., Methods: A SR update was defined as a new edition of a SR, either published by the same or new authors. We searched PubMed for SR updates published from January 01, 2016 to January 22, 2018 and included a random sample of n = 100 non-Cochrane updates of SRs on interventions reported in English., Results: Most SR updates had a corresponding author from the United Kingdom, United States, or Canada (in total 48/100) and dealt with nonpharmacological interventions (63/100). The SR updates were published a median of 5 years (interquartile range [IQR] 3-7) after the previous SR and included a median of 19 (IQR 9-28) studies. 31/100 SR updates reported that the conclusion had changed since the previous version. Only 51/100 SR updates used the term "update" in the title and none reported having based the decision to update the previous SR on an existing method/decision tool. The number of newly included studies and participants and the number of studies and participants included in/from the previous SR were often not reported., Conclusions: The included non-Cochrane updates were frequently missing important information that would be expected to be present in a SR update. Thus, structured and detailed reporting guidance specific to SR updates is needed. It should focus particularly on appropriate labeling and justification of updates, and how to incorporate information regarding the previous SR., (© 2020 The Authors. Research Synthesis Methods published by John Wiley & Sons Ltd.)

Objectives: The objective of the study was to measure the level of agreement between Cochrane reviews of overlapping randomized controlled trials (RCTs) regarding risk-of-bias (RoB) judgments., Study Design and Setting: On November 5, 2017, the Cochrane Database of Systematic Reviews was searched for Cochrane reviews on tobacco. Reviews that included overlapping RCTs were included. RoB judgments were extracted from RoB tables using automated data scraping with manual verification and adjustments. Agreement between the reviews was calculated using Conger's generalized kappa coefficient (κ) and raw agreement (a)., Results: We included 53 Cochrane reviews of 376 RCTs. For the RoB domain "random sequence generation," the level of agreement between the reviews was substantial with κ = 0.63 (95% confidence interval: 0.56 to 0.71; a = 0.80). There was slight-to-moderate agreement between the reviews regarding the domains "allocation concealment": κ = 0.51 (0.41 to 0.61), a = 0.75; "blinding": κ = 0.19 (0.02 to 0.37), a = 0.52; "blinding of outcome assessment": κ = 0.43 (0.14 to 0.72) a = 0.67; and "incomplete outcome data": κ = 0.15 (-0.03 to 0.32), a = 0.64. For "blinding of participants and personnel" and "selective reporting", κ could not be calculated. The raw agreement was 0.40 and 0.42, respectively., Conclusion: The level of agreement between Cochrane reviews regarding RoB judgments ranged from slight to substantial depending on the RoB domain. Further investigations regarding reasons for variation and interventions to improve agreement are needed., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Knee osteoarthritis is a common, chronic condition and main contributor to global disability. Total knee arthroplasty (TKA) is the most successful treatment for end-stage knee osteoarthritis. It is assumed that in the field of surgery, there is a relationship between hospital volume and health outcomes and that higher hospital volume results in better health outcomes. As a consequence, minimum volume thresholds have been implemented in Germany for various procedures, including TKA (50 procedures per year). To date, it is unclear whether minimum volume thresholds truly result in better outcomes. The objective of this study will be to quantify the relationship between hospital volume and patient-relevant outcomes in patients undergoing TKA., Methods: We will include published or unpublished (cluster-) randomized controlled trials and prospective or retrospective cohort studies that involve patients with primary and/or revision TKA, report at least two different hospital volumes and report at least one patient-relevant outcome. To identify studies, we will systematically search (from inception onwards) PubMed/MEDLINE, Embase, CENTRAL, and CINAHL, as well as trial registers, conference proceedings, and reference lists. We will also contact experts in the field. Study selection and data extraction will be performed by two reviewers independently. The primary outcome will be rate of early revision. Secondary outcomes will include rate of revision > 1 year, mortality, length of stay, readmission rate, surgical complications, adverse events and health-related quality of life. We will assess the risk of bias of the included studies using ROBINS-I or the Cochrane risk of bias tool. Both a linear and a non-linear dose-response meta-analyses will be performed. We will use the GRADE approach to evaluate our confidence in the cumulative evidence. We will incorporate patients' needs, goals and preferences into our recommendations by consulting three focus groups, each consisting of eight participants., Discussion: The findings of our systematic review will probably be limited by the design of the included studies. We do not expect to identify any (cluster-) randomized controlled trials that meet our inclusion criteria. Therefore, the best available evidence included in our systematic review will most likely consist of cohort studies only. We anticipate that the results of this study will inform future health policy decisions in Germany regarding the minimum volume threshold for TKA. Systematic review registration: PROSPERO CRD42019131209.