Patient-Reported Outcome Measures as an Intervention: A Comprehensive Overview of Systematic Reviews on the Effects of Feedback.

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.

Cost-effectiveness of prehabilitation of elderly frail or pre-frail patients prior to elective surgery (PRAEP-GO) versus usual care - Protocol for a health economic evaluation alongside a randomized controlled trial.

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 ).

Facilitators and barriers to the implementation of prehabilitation for frail patients into routine health care: a realist review.

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).

Barriers and facilitators to the implementation of prehabilitation for elderly frail patients prior to elective surgery: a qualitative study with healthcare professionals.

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).

Cost-effectiveness of prehabilitation prior to elective surgery: a systematic review of economic evaluations.

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.

Challenges and Solutions for the Benefit Assessment of Tumor-Agnostic Therapies in Germany.

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.

Utilization of innovative medical technologies in German inpatient care: does evidence matter?

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.

Restrictions and their reporting in systematic reviews of effectiveness: an observational study.

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.

Health care patterns and policies in 18 European countries during the first wave of the COVID-19 pandemic: an observational study.

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.

Perspective of potential patients on the hospital volume-outcome relationship and the minimum volume threshold for total knee arthroplasty: a qualitative focus group and interview study.

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.

Guidelines for Reporting Trial Protocols and Completed Trials Modified Due to the COVID-19 Pandemic and Other Extenuating Circumstances: The CONSERVE 2021 Statement.

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.

A descriptive analysis of the characteristics and the peer review process of systematic review protocols published in an open peer review journal from 2012 to 2017.

BACKGROUND: An a priori design is essential to reduce the risk of bias in systematic reviews (SRs). To this end, authors can register their SR with PROSPERO, and/or publish a SR protocol in an academic journal. The latter has the advantage that the manuscript for the SR protocol is usually peer-reviewed. However, since authors ought not to begin/continue the SR before their protocol has been accepted for publication, it is crucial that SR protocols are processed in a timely manner. Our main aim was to descriptively analyse the peer review process of SR protocols published in 'BMC Systematic Reviews' from 2012 to 2017. METHODS: We systematically searched MEDLINE via PubMed for all SR protocols published in 'BMC Systematic Reviews' between 2012 and 2017, except for protocols for overviews, scoping reviews or realist reviews. Data were extracted from the SR protocols and Open Peer Review reports. For each round of peer review, two researchers judged the extent of revision (minor/major) based on the reviewer reports. Their content was further investigated by two researchers in a random 10%-sample using PRISMA-P as a guideline. All data were analysed descriptively. RESULTS: We identified 544 eligible protocols published in 'BMC Systematic Reviews' between 2012 and 2017. Of those, 485 (89.2%) also registered the SR in PROSPERO, the majority (87.4%) before first submission of the manuscript for the SR protocol (median 49 days). The absolute number of published SR protocols increased from 2012 to 2017 (21 vs 145 protocols), as did the median processing time (61 vs 142 days from submission to acceptance) and the proportion of protocols requiring a major revision after first peer review (19.1% vs 52.4%). Reviewer comments most frequently addressed the PRISMA-P item 'Eligibility criteria'. Overall, 76.0% of the reviewer comments suggested more transparency. CONCLUSIONS: The number of published SR protocols increased over the years, but so did the processing time. In 2017, it took several months from submission to acceptance, which is critical from an author's perspective. New models of peer review such as post publication peer review for SR protocols should be investigated. This could probably be realized with PROSPERO.

Most systematic reviews that used the term "update" in title/abstract were not an updated version.

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.

Systematic reviewers used various approaches to data extraction and expressed several research needs: a survey.

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.

AMSTAR 2 is only partially applicable to systematic reviews of non-intervention studies: a meta-research study.

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.

Where to prospectively register a systematic review.

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.

A country-level analysis comparing hospital capacity and utilisation during the first COVID-19 wave across Europe.

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.

Prehabilitation of elderly frail or pre-frail patients prior to elective surgery (PRAEP-GO): study protocol for a randomized, controlled, outcome assessor-blinded trial.

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.

No inexplicable disagreements between real-world data-based nonrandomized controlled studies and randomized controlled trials were found.

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.

Authors should clearly report how they derived the overall rating when applying AMSTAR 2-a cross-sectional study.

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.