Polypharmacy in Patients with Chronic Kidney Disease.

BACKGROUND: Despite the high prevalence of polypharmacy in patients with chronic kidney disease (CKD), the extent of polypharmacy across patients with (different stages of) CKD, as well as the association with clinical outcomes remains unknown. This systematic review aimed to evaluate the prevalence of polypharmacy in (different subgroups of) patients with CKD and assess the association between polypharmacy and patient-important outcomes. METHODS: Medline, Embase, and the Cochrane Library were searched from inception until July 2022. Studies that reported the prevalence of polypharmacy, medication use, or pill burden in patients with CKD (including patients receiving dialysis and kidney transplant recipients) and their association with patient-important outcomes (i.e. mortality, kidney failure, quality of life, and medication non-adherence) were included. Two reviewers independently screened title and abstract and full texts, extracted data, and assessed risk of bias. Data were pooled in a random-effects single-arm meta-analysis. RESULTS: In total, 127 studies were included (CKD 3-5 n=39, dialysis: n=38, kidney transplant n=13, different CKD stages n=37). The pooled prevalence of polypharmacy, based on 63 studies with 484,915 patients, across all patients with CKD was 82% (95% confidence interval [CI]: 76-86%) and the pooled mean number of prescribed medications 9.7 (95%CI: 8.4-11.0). The prevalence of polypharmacy was higher in patients who received dialysis or a kidney transplant compared to patients with CKD 3-5, but did not differ between studies with regards to region, or patients' mean age or sex. In patients with CKD, polypharmacy was associated with a higher risk of all-cause mortality, kidney failure, faster eGFR decline, lower quality of life (QoL), and higher medication non-adherence, adverse drug reactions, and potentially inappropriate medications. CONCLUSIONS: The prevalence of polypharmacy in patients with CKD was over 80%, and highest in patients with a kidney transplant and those receiving dialysis. No causes of heterogeneity were identified, indicating that polypharmacy is an issue for all patients with CKD. Polypharmacy is associated with worse clinical outcomes, lower QoL, and medication-related problems in patients with CKD.

SPIN-PM: A consensus framework to evaluate the presence of spin in studies on prediction models.

OBJECTIVES: To develop a framework to identify and evaluate spin practices and its facilitators in studies on clinical prediction model, regardless of the modelling technique. STUDY DESIGN: We followed a three-phase consensus process: (1) pre-meeting literature review to generate items to be included; (2) a series of structured meetings to provide comments, discussed and exchanged viewpoints on items to be included with a panel of experienced researchers; and (3) post-meeting review on final list of items and examples to be included. Through this iterative consensus process, a framework was derived after all panel's researchers agreed. RESULTS: This consensus process involved a panel of eight researchers and resulted in SPIN-PM which consists of two categories of spin (misleading interpretation and misleading transportability), and within these categories, two forms of spin (spin practices and facilitators of spin). We provide criteria and examples. CONCLUSION: We proposed this guidance aiming to facilitate not only the accurate reporting but also an accurate interpretation and extrapolation of clinical prediction models which will likely improve the reporting quality of subsequent research, as well as reduce research waste.

Introducing re-weighted range voting in clinical practice guideline prioritization: Development and testing of the re-weighted priority-setting (REPS) tool.

We aimed to develop and test a tool based on the re-weighted range voting mechanism to prioritize items (i.e. key questions) in a priority-setting assessment for clinical practice guidelines. The secondary aim was to provide methodological context of the tool. We iteratively developed the tool and used qualitative methods (i.e. think-aloud and semi-structured interviews) to test the tool's usability and make adjustments accordingly. An observational approach was used to test the tool's outcome satisfaction in a real-world priority-setting assessment within a rare-disease guideline of a European Reference Network and under four different conditions in the tool. Four guideline methodologists tested the usability of the tool. The real-world testing was performed with a guideline panel consisting of a core working group, five expertise working groups, and a working group with patient representatives. Thirty-one panel members assigned scores in the priority-setting assessment. Seventeen panel members rated the priority-setting outcome, and sixteen panel members rated the outputs generated under the four conditions. Upon initial use, guideline methodologists found the tool to be quite overwhelming. However, with some initial effort they were able to easily identify the tool's structure. Based on observations and feedback, the tool was further refined and user guidance was developed. Guideline panel members expressed (high) satisfaction with the priority-setting outcome. They particularly preferred the condition when using mean subgroup scores as input or employing aggressive penalties in the weighting method to determine the outputs. The tool generates a ranked list of items and offers flexibility for different choices in priority-setting assessments as long as its input format requirements are met. Although it is not a consensus method, the tool assists in narrowing down a set of priority items. Additional steps in the priority-setting assessment can lead to a consensus being reached regarding the final outcome.

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.

Designing tailored maintenance strategies for systematic reviews and clinical practice guidelines using the Portfolio Maintenance by Test-Treatment (POMBYTT) framework.

BACKGROUND: Organizations face diverse contexts and requirements when updating and maintaining their portfolio, or pool, of systematic reviews or clinical practice guidelines they need to manage. We aimed to develop a comprehensive, theoretical framework that might enable the design and tailoring of maintenance strategies for portfolios containing systematic reviews and guidelines. METHODS: We employed a conceptual approach combined with a literature review. Components of the diagnostic test-treatment pathway used in clinical healthcare were transferred to develop a framework specifically for systematic review and guideline portfolio maintenance strategies. RESULTS: We developed the Portfolio Maintenance by Test-Treatment (POMBYTT) framework comprising diagnosis, staging, management, and monitoring components. To illustrate the framework's components and their elements, we provided examples from both a clinical healthcare test-treatment pathway and a clinical practice guideline maintenance scenario. Additionally, our literature review provided possible examples for the elements in the framework, such as detection variables, detection tests, and detection thresholds. We furthermore provide three example strategies using the framework, of which one was based on living recommendations strategies. CONCLUSIONS: The developed framework might support the design of maintenance strategies that could contain multiple options besides updating to manage a portfolio (e.g. withdrawing and archiving), even in the absence of the target condition. By making different choices for variables, tests, test protocols, indications, management options, and monitoring, organizations might tailor their maintenance strategy to suit specific contexts and needs. The framework's elements could potentially aid in the design by being explicit about the operational aspects of maintenance strategies. This might also be helpful for end-users and other stakeholders of systematic reviews and clinical practice guidelines.

Both clinical trial register and electronic bibliographic database searches were needed to identify randomized clinical trials for systematic reviews: an evaluation study.

OBJECTIVES: To determine whether clinical trial register (CTR) searches can accurately identify a greater number of completed randomized clinical trials (RCTs) than electronic bibliographic database (EBD) searches for systematic reviews of interventions, and to quantify the number of eligible ongoing trials. STUDY DESIGN AND SETTING: We performed an evaluation study and based our search for RCTs on the eligibility criteria of a systematic review that focused on the underrepresentation of people with chronic kidney disease in cardiovascular RCTs. We conducted a combined search of ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform through the Cochrane Central Register of Controlled Trials to identify eligible RCTs registered up to June 1, 2023. We searched Cochrane Central Register of Controlled Trials, EMBASE, and MEDLINE for publications of eligible RCTs published up to June 5, 2023. Finally, we compared the search results to determine the extent to which the two sources identified the same RCTs. RESULTS: We included 92 completed RCTs. Of these, 81 had results available. Sixty-six completed RCTs with available results were identified by both sources (81% agreement [95% CI: 71-88]). We identified seven completed RCTs with results exclusively by CTR search (9% [95% CI: 4-17]) and eight exclusively by EBD search (10% [95% CI: 5-18]). Eleven RCTs were completed but lacked results (four identified by both sources (36% [95% CI: 15-65]), one exclusively by EBD search (9% [95% CI: 1-38]), and six exclusively by CTR search (55% [95% CI: 28-79])). Also, we identified 42 eligible ongoing RCTs: 16 by both sources (38% [95% CI: 25-53]) and 26 exclusively by CTR search (62% [95% CI: 47-75]). Lastly, we identified four RCTs of unknown status by both sources. CONCLUSION: CTR searches identify a greater number of completed RCTs than EBD searches. Both searches missed some included RCTs. Based on our case study, researchers (eg, information specialists, systematic reviewers) aiming to identify all available RCTs should continue to search both sources. Once the barriers to performing CTR searches alone are targeted, CTR searches may be a suitable alternative.

Real-World Evidence to Inform Regulatory Decision Making: A Scoping Review.

Real-world evidence (RWE) is increasingly considered in regulatory decision making. When, and to which extent, RWE is considered relevant by regulators likely depends on many factors. This review aimed to identify factors that make RWE necessary or desirable to inform regulatory decision making. A scoping review was conducted using literature databases (PubMed, Embase, Emcare, Web of Science, and Cochrane Library) and websites of regulatory agencies, health technology assessment agencies, research institutes, and professional organizations involved with RWE. Articles were included if: (1) they discussed factors or contexts that impact whether RWE could be necessary or desirable in regulatory decision making; (2) focused on pharmacological or biological interventions in humans; and (3) considered decision making in Europe or North America, or without a focus on a specific region. We included 118 articles in the scoping review. Two major themes and six subthemes were identified. The first theme concerns questions addressable with RWE, with subthemes epidemiology and benefit-risk assessment. The second theme concerns contextual factors, with subthemes feasibility, ethical considerations, limitations of available evidence, and disease and treatment-specific aspects. Collectively, these themes encompassed 43 factors influencing the need for RWE in regulatory decisions. Although single factors may not make RWE fully necessary, their cumulative influence could make RWE essential and pivotal in regulatory decision making. This overview contributes to ongoing discussions emphasizing the nuanced interplay of factors influencing the necessity or desirability of RWE to inform regulatory decision making.

Increased endorsement of TRIPOD and other reporting guidelines by high impact factor journals: survey of instructions to authors.

OBJECTIVES: To assess the endorsement of reporting guidelines by high impact factor journals over the period 2017-2022, with a specific focus on the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) statement. STUDY DESIGN AND SETTING: We searched the online 'instructions to authors' of high impact factor medical journals in February 2017 and in January 2022 for any reference to reporting guidelines and TRIPOD in particular. RESULTS: In 2017, 205 out of 337 (61%) journals mentioned any reporting guideline in their instructions to authors and in 2022 this increased to 245 (73%) journals. A reference to TRIPOD was provided by 27 (8%) journals in 2017 and 67 (20%) in 2022. Of those journals mentioning TRIPOD in 2022, 22% provided a link to the TRIPOD website and 60% linked to TRIPOD information on the Enhancing the QUAlity and Transparency Of health Research (EQUATOR) Network website. Twenty-five percent of the journals required adherence to TRIPOD. CONCLUSION: About three-quarters of high-impact medical journals endorse the use of reporting guidelines and 20% endorse TRIPOD. Transparent reporting is important in enhancing the usefulness of health research and endorsement by journals plays a critical role in this.

Impact of fatigue in surgeons on performance and patient outcome: systematic review.

BACKGROUND: While fatigue is an inevitable aspect of performing surgical procedures, lack of consensus remains on its effect on surgical performance. The aim of this systematic review was to assess the effect of non-muscular fatigue on surgical outcome. METHODS: MEDLINE and Embase were searched up to 17 January 2023. Studies on students, learning, duty-hour restrictions, muscle fatigue, non-surgical or subjective outcome, the weekend effect, or time of admission were excluded. Studies were categorized based on real-life or simulated surgery. The Cochrane risk-of-bias tool was used to assess RCTs and the Newcastle-Ottawa scale was used to assess cohort studies. Due to heterogeneity among studies, data pooling was not feasible and study findings were synthesized narratively. RESULTS: From the 7251 studies identified, 134 studies (including 1 684 073 cases) were selected for analysis (110 real-life studies and 24 simulator studies). Of the simulator studies, 46% (11 studies) reported a deterioration in surgical outcome when fatigue was present, using direct measures of fatigue. In contrast, only 35.5% (39 studies) of real-life studies showed a deterioration, observed in only 12.5% of all outcome measures, specifically involving aggregated surgical outcomes. CONCLUSION: Almost half of simulator studies, along with one-third of real-life studies, consistently report negative effects of fatigue, highlighting a significant concern. The discrepancy between simulator/real-life studies may be explained by heightened motivation and effort investment in real-life studies. Currently, published fatigue and outcome measures, especially in real-life studies, are insufficient to fully define the impact of fatigue on surgical outcomes due to the absence of direct fatigue measures and crude, post-hoc outcome measures.

At some point, surgeons become tired, just like anyone else. While in other jobs, people start to perform worse as they get tired, it is not known whether this is also true for surgeons. It is important to know this because patients may be worse off if their surgeon is tired. The aim of this study was to find out if being tired affects how surgeons do their work. Medical databases were searched through for studies on tired surgeons and the impact of fatigue on their work. Some studies looked at tired surgeons during real surgery and other studies looked at tired surgeons during sessions on surgery simulators. More than 7000 studies were examined and 134 of them were selected. They included over 1.6 million surgeries. Among these studies, 110 investigated real surgeries and 24 looked at simulated surgical sessions. Interestingly, almost half of the studies looking at simulated surgeries found that being tired had a negative effect on the simulated surgery. However, in real surgeries, this happened in only one-third of studies. The difference between real surgery and simulator surgery could be because in real surgeries surgeons always try to do their best, even when fatigued, because they are dealing with real patients. Another reason could be that the tools used to check whether surgeons are tired or whether the surgery went well are not very good. To help both surgeons and patients, there is a need to find better ways to determine if surgeons are truly tired and to make sure the tests are better.

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.

Antioxidants for adults with chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) is a significant risk factor for cardiovascular disease (CVD) and death. Increased oxidative stress in people with CKD has been implicated as a potential causative factor. Antioxidant therapy decreases oxidative stress and may consequently reduce cardiovascular morbidity and death in people with CKD. This is an update of a Cochrane review first published in 2012. OBJECTIVES: To examine the benefits and harms of antioxidant therapy on death and cardiovascular and kidney endpoints in adults with CKD stages 3 to 5, patients undergoing dialysis, and kidney transplant recipients. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies until 15 November 2022 using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov. SELECTION CRITERIA: We included all randomised controlled trials investigating the use of antioxidants, compared with placebo, usual or standard care, no treatment, or other antioxidants, for adults with CKD on cardiovascular and kidney endpoints. DATA COLLECTION AND ANALYSIS: Titles and abstracts were screened independently by two authors who also performed data extraction using standardised forms. Results were pooled using random effects models and expressed as risk ratios (RR) or mean difference (MD) with 95% confidence intervals (CI). Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: We included 95 studies (10,468 randomised patients) that evaluated antioxidant therapy in adults with non-dialysis-dependent CKD (31 studies, 5342 patients), dialysis-dependent CKD (41 studies, 3444 patients) and kidney transplant recipients (21 studies, 1529 patients). Two studies enrolled dialysis and non-dialysis patients (153 patients). Twenty-one studies assessed the effects of vitamin antioxidants, and 74 assessed the effects of non-vitamin antioxidants. Overall, the quality of included studies was moderate to low or very low due to unclear or high risk of bias for randomisation, allocation concealment, blinding, and loss to follow-up. Compared with placebo, usual care, or no treatment, antioxidant therapy may have little or no effect on cardiovascular death (8 studies, 3813 patients: RR 0.94, 95% CI 0.64 to 1.40; I² = 33%; low certainty of evidence) and probably has little to no effect on death (any cause) (45 studies, 7530 patients: RR 0.95, 95% CI 0.82 to 1.11; I² = 0%; moderate certainty of evidence), CVD (16 studies, 4768 patients: RR 0.79, 95% CI 0.63 to 0.99; I² = 23%; moderate certainty of evidence), or loss of kidney transplant (graft loss) (11 studies, 1053 patients: RR 0.88, 95% CI 0.67 to 1.17; I² = 0%; moderate certainty of evidence). Compared with placebo, usual care, or no treatment, antioxidants had little to no effect on the slope of urinary albumin/creatinine ratio (change in UACR) (7 studies, 1286 patients: MD -0.04 mg/mmol, 95% CI -0.55 to 0.47; I² = 37%; very low certainty of evidence) but the evidence is very uncertain. Antioxidants probably reduced the progression to kidney failure (10 studies, 3201 patients: RR 0.65, 95% CI 0.41 to 1.02; I² = 41%; moderate certainty of evidence), may improve the slope of estimated glomerular filtration rate (change in eGFR) (28 studies, 4128 patients: MD 3.65 mL/min/1.73 m², 95% CI 2.81 to 4.50; I² = 99%; low certainty of evidence), but had uncertain effects on the slope of serum creatinine (change in SCr) (16 studies, 3180 patients: MD -13.35 µmol/L, 95% CI -23.49 to -3.23; I² = 98%; very low certainty of evidence). Possible safety concerns are an observed increase in the risk of infection (14 studies, 3697 patients: RR 1.30, 95% CI 1.14 to 1.50; I² = 3%; moderate certainty of evidence) and heart failure (6 studies, 3733 patients: RR 1.40, 95% CI 1.11 to 1.75; I² = 0; moderate certainty of evidence) among antioxidant users. Results of studies with a low risk of bias or longer follow-ups generally were comparable to the main analyses. AUTHORS' CONCLUSIONS: We found no evidence that antioxidants reduced death or improved kidney transplant outcomes or proteinuria in patients with CKD. Antioxidants likely reduce cardiovascular events and progression to kidney failure and may improve kidney function. Possible concerns are an increased risk of infections and heart failure among antioxidant users. However, most studies were of suboptimal quality and had limited follow-up, and few included people undergoing dialysis or kidney transplant recipients. Furthermore, the large heterogeneity in interventions hampers drawing conclusions on the efficacy and safety of individual agents.

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.

What are Effective Strategies to Reduce Low-Value Care? An Analysis of 121 Randomized Deimplementation Studies.

BACKGROUND: Low-value care is healthcare leading to no or little clinical benefit for the patient. The best (combinations of) interventions to reduce low-value care are unclear. PURPOSE: To provide an overview of randomized controlled trials (RCTs) evaluating deimplementation strategies, to quantify the effectiveness and describe different combinations of strategies. METHODS: Analysis of 121 RCTs (1990-2019) evaluating a strategy to reduce low-value care, identified by a systematic review. Deimplementation strategies were described and associations between strategy characteristics and effectiveness explored. RESULTS: Of 109 trials comparing deimplementation to usual care, 75 (69%) reported a significant reduction of low-value healthcare practices. Seventy-three trials included in a quantitative analysis showed a median relative reduction of 17% (IQR 7%-42%). The effectiveness of deimplementation strategies was not associated with the number and types of interventions applied. CONCLUSIONS AND IMPLICATIONS: Most deimplementation strategies achieved a considerable reduction of low-value care. We found no signs that a particular type or number of interventions works best for deimplementation. Future deimplementation studies should map relevant contextual factors, such as the workplace culture or economic factors. Interventions should be tailored to these factors and provide details regarding sustainability of the effect.

The Adoption of a COVID-19 Contact-Tracing App: Cluster Analysis.

BACKGROUND: During the COVID-19 pandemic, there was limited adoption of contact-tracing apps (CTAs). Adoption was particularly low among vulnerable people (eg, people with a low socioeconomic position or of older age), while this part of the population tends to have lesser access to information and communication technology and is more vulnerable to the COVID-19 virus. OBJECTIVE: This study aims to understand the cause of this lagged adoption of CTAs in order to facilitate adoption and find indications to make public health apps more accessible and reduce health disparities. METHODS: Because several psychosocial variables were found to be predictive of CTA adoption, data from the Dutch CTA CoronaMelder (CM) were analyzed using cluster analysis. We examined whether subgroups could be formed based on 6 psychosocial perceptions (ie, trust in the government, beliefs about personal data, social norms, perceived personal and societal benefits, risk perceptions, and self-efficacy) of (non)users concerning CM in order to examine how these clusters differ from each other and what factors are predictive of the intention to use a CTA and the adoption of a CTA. The intention to use and the adoption of CM were examined based on longitudinal data consisting of 2 time frames in October/November 2020 (N=1900) and December 2020 (N=1594). The clusters were described by demographics, intention, and adoption accordingly. Moreover, we examined whether the clusters and the variables that were found to influence the adoption of CTAs, such as health literacy, were predictive of the intention to use and the adoption of the CM app. RESULTS: The final 5-cluster solution based on the data of wave 1 contained significantly different clusters. In wave 1, respondents in the clusters with positive perceptions (ie, beneficial psychosocial variables for adoption of a CTA) about the CM app were older (P<.001), had a higher education level (P<.001), and had higher intention (P<.001) and adoption (P<.001) rates than those in the clusters with negative perceptions. In wave 2, the intention to use and adoption were predicted by the clusters. The intention to use CM in wave 2 was also predicted using the adoption measured in wave 1 (P<.001, ß=-2.904). Adoption in wave 2 was predicted by age (P=.022, exp(B)=1.171), the intention to use in wave 1 (P<.001, exp(B)=1.770), and adoption in wave 1 (P<.001, exp(B)=0.043). CONCLUSIONS: The 5 clusters, as well as age and previous behavior, were predictive of the intention to use and the adoption of the CM app. Through the distinguishable clusters, insight was gained into the profiles of CM (non)intenders and (non)adopters. TRIAL REGISTRATION: OSF Registries osf.io/cq742; https://osf.io/cq742.

Effectiveness of FeNO-guided treatment in adult asthma patients: A systematic review and meta-analysis.

OBJECTIVE: Asthma control is generally monitored by assessing symptoms and lung function. However, optimal treatment is also dependent on the type and extent of airway inflammation. Fraction of exhaled Nitric Oxide (FeNO) is a noninvasive biomarker of type 2 airway inflammation, but its effectiveness in guiding asthma treatment remains disputed. We performed a systematic review and meta-analysis to obtain summary estimates of the effectiveness of FeNO-guided asthma treatment. DESIGN: We updated a Cochrane systematic review from 2016. Cochrane Risk of Bias tool was used to assess risk of bias. Inverse-variance random-effects meta-analysis was performed. Certainty of evidence was assessed using GRADE. Subgroup analyses were performed based on asthma severity, asthma control, allergy/atopy, pregnancy and obesity. DATA SOURCES: The Cochrane Airways Group Trials Register was searched on 9 May 2023. ELIGIBILITY CRITERIA: We included randomized controlled trials (RCTs) comparing the effectiveness of a FeNO-guided treatment versus usual (symptom-guided) treatment in adult asthma patients. RESULTS: We included 12 RCTs (2,116 patients), all showing high or unclear risk of bias in at least one domain. Five RCTs reported support from a FeNO manufacturer. FeNO-guided treatment probably reduces the number of patients having ≥1 exacerbation (OR = 0.61; 95%CI 0.44 to 0.83; six RCTs; GRADE moderate certainty) and exacerbation rate (RR = 0.67; 95%CI 0.54 to 0.82; six RCTs; moderate certainty), and may slightly improve Asthma Control Questionnaire score (MD = -0.10; 95%CI -0.18 to -0.02, six RCTs; low certainty), however, this change is unlikely to be clinically important. An effect on severe exacerbations, quality of life, FEV1, treatment dosage and FeNO values could not be demonstrated. There were no indications that effectiveness is different in subgroups of patients, although evidence for subgroup analysis was limited. CONCLUSIONS: FeNO-guided asthma treatment probably results in fewer exacerbations but may not have clinically important effects on other asthma outcomes.

Diagnostic yield and safety of navigation bronchoscopy: A systematic review and meta-analysis.

BACKGROUND: Navigation bronchoscopy has seen rapid development in the past decade in terms of new navigation techniques and multi-modality approaches utilizing different techniques and tools. This systematic review analyses the diagnostic yield and safety of navigation bronchoscopy for the diagnosis of peripheral pulmonary nodules suspected of lung cancer. METHODS: An extensive search was performed in Embase, Medline and Cochrane CENTRAL in May 2022. Eligible studies used cone-beam CT-guided navigation (CBCT), electromagnetic navigation (EMN), robotic navigation (RB) or virtual bronchoscopy (VB) as the primary navigation technique. Primary outcomes were diagnostic yield and adverse events. Quality of studies was assessed using QUADAS-2. Random effects meta-analysis was performed, with subgroup analyses for different navigation techniques, newer versus older techniques, nodule size, publication year, and strictness of diagnostic yield definition. Explorative analyses of subgroups reported by studies was performed for nodule size and bronchus sign. RESULTS: A total of 95 studies (n = 10,381 patients; n = 10,682 nodules) were included. The majority (n = 63; 66.3%) had high risk of bias or applicability concerns in at least one QUADAS-2 domain. Summary diagnostic yield was 70.9% (95%-CI 68.4%-73.2%). Overall pneumothorax rate was 2.5%. Newer navigation techniques using advanced imaging and/or robotics(CBCT, RB, tomosynthesis guided EMN; n = 24 studies) had a statistically significant higher diagnostic yield compared to longer established techniques (EMN, VB; n = 82 studies): 77.5% (95%-CI 74.7%-80.1%) vs 68.8% (95%-CI 65.9%-71.6%) (p < 0.001).Explorative subgroup analyses showed that larger nodule size and bronchus sign presence were associated with a statistically significant higher diagnostic yield. Other subgroup analyses showed no significant differences. CONCLUSION: Navigation bronchoscopy is a safe procedure, with the potential for high diagnostic yield, in particular using newer techniques such as RB, CBCT and tomosynthesis-guided EMN. Studies showed a large amount of heterogeneity, making comparisons difficult. Standardized definitions for outcomes with relevant clinical context will improve future comparability.

Systematic review finds "spin" practices and poor reporting standards in studies on machine learning-based prediction models.

OBJECTIVES: We evaluated the presence and frequency of spin practices and poor reporting standards in studies that developed and/or validated clinical prediction models using supervised machine learning techniques. STUDY DESIGN AND SETTING: We systematically searched PubMed from 01/2018 to 12/2019 to identify diagnostic and prognostic prediction model studies using supervised machine learning. No restrictions were placed on data source, outcome, or clinical specialty. RESULTS: We included 152 studies: 38% reported diagnostic models and 62% prognostic models. When reported, discrimination was described without precision estimates in 53/71 abstracts (74.6% [95% CI 63.4-83.3]) and 53/81 main texts (65.4% [95% CI 54.6-74.9]). Of the 21 abstracts that recommended the model to be used in daily practice, 20 (95.2% [95% CI 77.3-99.8]) lacked any external validation of the developed models. Likewise, 74/133 (55.6% [95% CI 47.2-63.8]) studies made recommendations for clinical use in their main text without any external validation. Reporting guidelines were cited in 13/152 (8.6% [95% CI 5.1-14.1]) studies. CONCLUSION: Spin practices and poor reporting standards are also present in studies on prediction models using machine learning techniques. A tailored framework for the identification of spin will enhance the sound reporting of prediction model studies.

Overinterpretation of findings in machine learning prediction model studies in oncology: a systematic review.

OBJECTIVES: In biomedical research, spin is the overinterpretation of findings, and it is a growing concern. To date, the presence of spin has not been evaluated in prognostic model research in oncology, including studies developing and validating models for individualized risk prediction. STUDY DESIGN AND SETTING: We conducted a systematic review, searching MEDLINE and EMBASE for oncology-related studies that developed and validated a prognostic model using machine learning published between 1st January, 2019, and 5th September, 2019. We used existing spin frameworks and described areas of highly suggestive spin practices. RESULTS: We included 62 publications (including 152 developed models; 37 validated models). Reporting was inconsistent between methods and the results in 27% of studies due to additional analysis and selective reporting. Thirty-two studies (out of 36 applicable studies) reported comparisons between developed models in their discussion and predominantly used discrimination measures to support their claims (78%). Thirty-five studies (56%) used an overly strong or leading word in their title, abstract, results, discussion, or conclusion. CONCLUSION: The potential for spin needs to be considered when reading, interpreting, and using studies that developed and validated prognostic models in oncology. Researchers should carefully report their prognostic model research using words that reflect their actual results and strength of evidence.

How to conduct a systematic review and meta-analysis of prognostic model studies.

BACKGROUND: Prognostic models are typically developed to estimate the risk that an individual in a particular health state will develop a particular health outcome, to support (shared) decision making. Systematic reviews of prognostic model studies can help identify prognostic models that need to further be validated or are ready to be implemented in healthcare. OBJECTIVES: To provide a step-by-step guidance on how to conduct and read a systematic review of prognostic model studies and to provide an overview of methodology and guidance available for every step of the review progress. SOURCES: Published, peer-reviewed guidance articles. CONTENT: We describe the following steps for conducting a systematic review of prognosis studies: 1) Developing the review question using the Population, Index model, Comparator model, Outcome(s), Timing, Setting format, 2) Searching and selection of articles, 3) Data extraction using the Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies (CHARMS) checklist, 4) Quality and risk of bias assessment using the Prediction model Risk Of Bias ASsessment (PROBAST) tool, 5) Analysing data and undertaking quantitative meta-analysis, and 6) Presenting summary of findings, interpreting results, and drawing conclusions. Guidance for each step is described and illustrated using a case study on prognostic models for patients with COVID-19. IMPLICATIONS: Guidance for conducting a systematic review of prognosis studies is available, but the implications of these reviews for clinical practice and further research highly depend on complete reporting of primary studies.