Representation of Patients With Chronic Kidney Disease in Clinical Trials of Cardiovascular Disease Medications: A Systematic Review.

Importance: Patients with chronic kidney disease (CKD) are at high risk for cardiovascular disease, but their systematic underrepresentation in cardiovascular randomized clinical trials (RCTs) limits the generation of appropriate evidence to guide cardiovascular risk management (CVRM). Objective: To evaluate the underrepresentation of patients with CKD in cardiovascular RCTs, and to highlight evidence gaps in CVRM medications in this population. Evidence Review: A systematic search was conducted in ClinicalTrials.gov from February 2000 through October 2021 for RCTs with full-text publications. If no full-text publications were found in ClinicalTrials.gov, MEDLINE, Embase, and Google Scholar were also searched. Eligible RCTs were those evaluating the effectiveness of antiplatelets, anticoagulants, blood pressure-lowering drugs, glucose-lowering drugs, or cholesterol-lowering drugs in adults with cardiovascular disease or cardiovascular risk factors. Trials with a sample size of fewer than 100 patients were excluded. Findings: In total, 1194 RCTs involving 2 207 677 participants (mean [SD] age, 63 [6] years; 1 343 970 males [64%]) were included. Since 2000, the percentage of cardiovascular RCTs excluding patients with CKD has increased from 66% to 79% (74% overall [884 RCTs]). In 864 RCTs (72%), more patients were excluded than anticipated on safety grounds (63% [306] of trials required no dose adjustment, and 79% [561] required dose adjustment). In total, 158 RCTs (13%) reported results for patients with CKD separately (eg, in subgroup analyses). Significant evidence gaps exist in most CVRM interventions for patients with CKD, particularly for those with CKD stages 4 to 5. Twenty-three RCTs (2%) reported results for patients with an estimated glomerular filtration rate less than 30 mL/min/1.73 m2, 15 RCTs (1%) reported for patients receiving dialysis, and 1 RCT (0.1%) reported for recipients of kidney transplant. Conclusions and Relevance: Results of this systematic review suggest that representation of patients with CKD in cardiovascular RCTs has not improved in the past 2 decades and that these RCTs excluded more patients with CKD than expected on safety grounds. Lack of reporting or underreporting of results for this patient population is associated with evidence gaps in the effectiveness of most CVRM medications in patients with all stages of CKD, particularly CKD stages 4 to 5.

Perspectives on systematic review protocol registration: a survey amongst stakeholders in the clinical research publication process.

BACKGROUND: As systematic reviews (SRs) inform healthcare decisions, it is key that they address relevant questions and use rigorous methodology. Registration of SR protocols helps researchers identify relevant topics for future reviews and aims to prevent bias and duplication of effort. However, most SRs protocols are currently not registered, despite its significance. To guide future recommendations to enhance preregistration of SRs, it is important to gain a comprehensive understanding of the perspectives within the research community. Therefore, this study aims to examine the experiences with and factors of influence (barriers and facilitators) on prospective SR registration amongst researchers, peer reviewers and journal editors. METHODS: Two different surveys were distributed to two groups: researchers and journal editors both identified from an existing sample of SRs. Researchers who indicated to have peer reviewed a SR were surveyed on their perspectives as peer reviewers as well. Survey design and analysis were informed by the Consolidated Framework for Implementation Research (CFIR). Shared and unique subthemes from the perspectives of researchers, peer reviewers and journal editors were identified and linked to the SR registration process (Innovation), to team, organisation (Inner setting) and (inter)national research community (Outer setting), and to characteristics of researchers, peer reviewers or journal editors (Individuals). RESULTS: The survey's response rates were 65/727 (9%) for researchers, of which 37 were peer reviewers, and 22/308 (7%) for journal editors. Most respondents (n = 76, 94%) were familiar with SR protocol registration and 81% of researchers had registered minimally one SR protocol. Shared SR registration process subthemes were the importance and advantages of SR protocol registration, as well as barriers such as a high administrative burden. Shared subthemes regarding the inner and outer setting centred on journal processes, external standards and time. Shared individual factors were knowledge, skills and awareness. CONCLUSIONS: The majority of the respondents were familiar with SR protocol registration and had a positive attitude towards it. This study identified suboptimal registration process, administrative burden and lack of mandatory SR protocol registration as barriers. By overcoming these barriers, SR protocol registration could contribute more effectively to the goals of open science. SYSTEMATIC REVIEW REGISTRATION: osf.io/gmv6z.

Assessing the Well-Being at Work of Nurses and Doctors in Hospitals: Protocol for a Scoping Review of Monitoring Instruments.

BACKGROUND: Well-being at work can be defined as "creating an environment to promote a state of contentment which allows an employee to flourish and achieve their full potential for the benefit of themselves and their organisation." In the health care context, well-being at work of nurses and doctors is important for good patient care. Moreover, it is strongly associated with individual- and organization-level consequences. Relevant literature presents models and concepts of physical, mental, and social well-being. This study uses the 6 elements of the job demands-resources (JD-R) model to interpret well-being at work (job demands, job resources, personal resources, leadership, well-being, and outcomes) as part of a Netherlands Federation of University Medical Hospitals program to find ways to improve and monitor health care professionals' well-being in Dutch hospitals. Many instruments exist to measure well-being at work in terms of population, setting, and other aspects. An overview of available and eligible instruments assessing and monitoring the well-being of nurses and doctors is currently missing. OBJECTIVE: We will perform a scoping review aiming to provide an overview of validated instruments assessing and monitoring the well-being of nurses and doctors at work. METHODS: We will perform a search of published literature in the following databases: Medline, Embase, and CINAHL. Studies will be eligible if they (1) assess well-being at work of nurses and doctors employed in hospitals; (2) describe an evaluation of an instrument or review an instrument; (3) measure well-being at work or aspects of well-being at work according to the elements of the JD-R model, and (4) were published in English from 2011 onwards. Title/abstract screening according to the eligibility criteria will be followed by full-text screening. Data extraction of included studies will be conducted by 3 reviewers independently. Reviewers will use standardized data extraction forms that include study characteristics, sample characteristics, measurement instrument details, and psychometric properties. The analysis will be descriptive. When synthesizing the data, a distinction will be made between comprehensive instruments and common instruments. RESULTS: This scoping review identifies instruments that have been developed and validated for monitoring the well-being of nurses and doctors at work. Studies were searched between September and December 2021 and screened between December 2021 and May 2022. A total of 739 studies were included. CONCLUSIONS: Timely screening of well-being at work may be beneficial for individual health care workers, the organization, and patients. There is often a substantial gap and mismatch between employer perceptions of well-being and well-being interventions. It is important to develop and implement suitable interventions adapted to the needs of nurses and doctors and their health or other problems. Well-being screening should be timely to gain insight into these needs and problems. Moreover, to determine the effectiveness of well-being interventions, measurement is mandatory. The results will be critical for organizations to select a monitoring instrument that best fits the needs of employees and organizations. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/43692.

Implementation and maintenance of an enhanced pulmonary rehabilitation program in a single centre: An implementation study.

BACKGROUND: Pulmonary rehabilitation (PR) has major benefits for patients with chronic obstructive pulmonary disease (COPD). An enhanced PR program was developed with a self-management education intervention. The objective of our study was to evaluate the implementation of the enhanced PR program into a single centre. METHODS: Pre-post implementation study consisted of two evaluation periods: immediately after implementation and 18 months later. Guided by the RE-AIM framework, outcomes included: Reach, Effectiveness, Adoption, Implementation and Maintenance. RESULTS: Reach: 70-75% of referred patients agreed to a PR program (n = 26). Effectiveness: Clinically important improvements occurred in some patients in functional exercise capacity (64% of the patients achieved clinical important difference in 6-min walk test in the first evaluation period and 44% in the second evaluation period), knowledge, functional status, and self-efficacy in both evaluation periods. Adoption: All healthcare professionals (HCPs) involved in PR (n = 8) participated. Implementation: Fidelity for the group education sessions ranged from 76 to 95% (first evaluation) and from 82 to 88% (second evaluation). Maintenance: The program was sustained over 18 months with minor changes. Patients and HCPs were highly satisfied with the program. CONCLUSIONS: The enhanced PR program was accepted by patients and HCPs and was implemented and maintained at a single expert center with good implementation fidelity.

Evidence for pharmacological interventions to reduce cardiovascular risk for patients with chronic kidney disease: a study protocol of an evidence map.

BACKGROUND: Patients with chronic kidney disease (CKD) require a personalised strategy for cardiovascular risk management (CVRM) to reduce their high risk of cardiovascular morbidity and mortality. Despite their high risk, patients with CKD appear to be underrepresented in randomised controlled trials (RCTs) for pharmacological CVRM interventions to reduce cardiovascular risk (pharmacological CVRM interventions). As a result, it remains unclear whether the efficacy of these interventions found in patients without CKD is similarly applicable to patients with CKD. This evidence map aims to provide an overview of the availability of the evidence from pharmacological CVRM trials for patients with CKD by assessing how often patients with reduced kidney function are specifically excluded or included from RCTs on pharmacological CVRM interventions and whether studies report efficacy estimates of interventions specifically for kidney patients. METHODS: We will perform a systematic literature search in ClinicalTrials.gov to identify relevant planned, ongoing, and completed RCTs on a broad range of CVRM medications after which we will retrieve the published protocols and papers via ClinicalTrials.gov itself, Embase, MEDLINE, or Google Scholar. We will include RCTs that investigate the efficacy of platelet inhibitors, anticoagulants, antihypertensives, glucose-lowering medication, and lipid-lowering medication on all-cause mortality, cardiovascular mortality, cardiovascular morbidity, and end-stage kidney disease in patients with a cardiovascular history or a major risk factor for cardiovascular disease. Two reviewers will independently screen trial records and their corresponding full-text publications to determine eligibility and extract data. Outcomes of interest are the exclusion of patients with reduced kidney function from RCTs and whether the study population was restricted to kidney patients or subgroup analyses were performed on kidney function. Results will be visualised in an evidence map. DISCUSSION: The availability of evidence on the efficacy and safety of pharmacological CVRM interventions in patients with CKD might be limited. Hence, we will identify knowledge gaps for future research. At the same time, the availability of evidence, or lack thereof, might warrant caution from healthcare decision-makers in making strong recommendations based on the extrapolation of results from studies to patients who were explicitly excluded from participation. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022296746.

The score after 10 years of registration of systematic review protocols.

BACKGROUND: With the exponential growth of published systematic reviews (SR), there is a high potential for overlapping and redundant duplication of work. Prospective protocol registration gives the opportunity to assess the added value of a new study or review, thereby potentially reducing research waste and simultaneously increasing transparency and research quality. The PROSPERO database for SR protocol registration was launched 10 years ago. This study aims to assess the proportion SRs of intervention studies with a protocol registration (or publication) and explore associations of SR characteristics with protocol registration status. METHODS: PubMed was searched for SRs of human intervention studies published in January 2020 and January 2021. After random-stratified sampling and eligibility screening, data extraction on publication and journal characteristics, and protocol registration status, was performed. Both descriptive and multivariable comparative statistical analyses were performed. RESULTS: A total of 357 SRs (2020: n = 163; 2021: n = 194) were included from a random sample of 1267 publications. Of the published SRs, 38% had a protocol. SRs that reported using PRISMA as a reporting guideline had higher odds of having a protocol than publications that did not report PRISMA (OR 2.71; 95% CI: 1.21 to 6.09). SRs with a higher journal impact factor had higher odds of having a protocol (OR 1.12; 95% CI 1.04 to 1.25). Publications from Asia had a lower odds of having a protocol (OR 0.43; 95% CI 0.23 to 0.80, reference category = Europe). Of the 33 SRs published in journals that endorse PROSPERO, 45% did not have a protocol. Most SR protocols were registered in PROSPERO (n = 129; 96%). CONCLUSIONS: We found that 38% of recently published SRs of interventions reported a registered or published protocol. Protocol registration was significantly associated with a higher impact factor of the journal publishing the SR and a more frequent self-reported use of the PRISMA guidelines. In some parts of the world, SR protocols are more often registered or published than others. To guide strategies to increase the uptake of SR protocol registration, further research is needed to gain understanding of the benefits and informativeness of SRs protocols among different stakeholders. SYSTEMATIC REVIEW REGISTRATION: osf.io/9kj7r/.