Assessing the robustness of positive vascular surgery randomized controlled trials using their fragility index.

OBJECTIVE: The fragility index (FI) measures the robustness of statistically significant findings in randomized controlled trials (RCTs) by quantifying the minimum number of event conversions required to reverse a dichotomous outcome's statistical significance. In vascular surgery, many clinical guidelines and critical decision-making points are informed by a handful of key RCTs, especially regarding open surgical versus endovascular treatment. The objective of this study is to evaluate the FI of RCTs with statistically significant primary outcomes that compared open vs endovascular surgery in vascular surgery. METHODS: In this meta-epidemiological study and systematic review, MEDLINE, Embase, and CENTRAL were searched for RCTs comparing open versus endovascular treatments for abdominal aortic aneurysms, carotid artery stenosis, and peripheral arterial disease to December 2022. RCTs with statistically significant primary outcomes were included. Data screening and extraction were conducted in duplicate. The FI was calculated by adding an event to the group with the smaller number of events while subtracting a nonevent to the same group until Fisher's exact test produced a nonstatistically significant result. The primary outcome was the FI and proportion of outcomes where the loss to follow-up was greater than the FI. The secondary outcomes assessed the relationship of the FI to disease state, presence of commercial funding, and study design. RESULTS: Overall, 5133 articles were captured in the initial search with 21 RCTs reporting 23 different primary outcomes being included in the final analysis. The median FI (first quartile, third quartile) was 3 (3, 20) with 16 outcomes (70%) reporting a loss to follow-up greater than its FI. Mann-Whitney U test revealed that commercially funded RCTs and composite outcomes had greater FIs (median, 20.0 [5.5, 24.5] vs median, 3.0 [2.0, 5.5], P = .035; median, 21 [8, 38] vs median, 3.0 [2.0, 8.5], P = .01, respectively). The FI did not vary between disease states (P = .285) or between index and follow-up trials (P = .147). There were significant correlations between the FI and P values (Pearson r = 0.90; 95% confidence interval, 0.77-0.96), and the number of events (r = 0.82; 95% confidence interval, 0.48-0.97). CONCLUSIONS: A small number of event conversions (median, 3) are needed to alter the statistical significance of primary outcomes in vascular surgery RCTs evaluating open surgical and endovascular treatments. Most studies had loss to follow-up greater than its FI, which can call into question trial results, and commercially funded studies had a greater FI. The FI and these findings should be considered in future trial design in vascular surgery.

Association of a Heart Failure Management Incentive in Primary Care With Clinical Outcomes: A Retrospective Cohort Study.

BACKGROUND: We aim to examine the association between primary care physicians' billing of Q050A, a pay-for-performance heart failure (HF) management incentive fee code, and the composite outcome of mortality, hospitalization, and emergency department visits. METHODS AND RESULTS: This population-based cohort study linked administrative health databases in Ontario, Canada, for patients with HF aged >66 years between January 1, 2008, and March 31, 2020. Cases were patients with HF who had a Q050A fee code billed. Cases and controls were matched 1:1 on age, sex, patient status on being rostered to a primary care physician, cardiologist, or internist visit in the 6 months before study enrollment, Johns Hopkins Adjusted Clinical Group resource use bands, days between HF diagnosis and study enrollment (±2 years), and the logit of the propensity score. A Cox proportional hazards model assessed the association of Q050A with the outcome. A total of 59 664 cases had a Q050A billed, whereas 244 883 patients did not. Before matching, patients who had a Q050A billed were more likely to be men (52% versus 49%), were rostered to a primary care physician (100% versus 96%), had a higher Charlson Comorbidity Index, and had higher health care costs. The mean follow-up was 481 days for cases and 530 days for controls. The composite outcome (hazard ratio, 1.11 [95% CI, 1.09-1.12]) was significantly higher for cases than controls. CONCLUSIONS: The Q050A incentive improved financial compensation for primary care physicians managing patients with HF but was not associated with improvements in the outcome. Research on promoting evidence-based HF management is warranted.

Integration of the social determinants of health into quality indicators for colorectal cancer surgery: a scoping review protocol.

INTRODUCTION: Quality monitoring is a critical component of high-performing cancer care systems. Quality indicators (QIs) are standardised, evidence-based measures of healthcare quality that allow healthcare systems to track performance, identify gaps in healthcare delivery and inform areas of priority for strategic planning. Social structures and economic systems that allow for unequal access to power and resources that shape health and health inequities can be described through the social determinants of health (SDoH) framework. Therefore, granular analysis of healthcare quality through SDoH frameworks is required to identify patient subgroups who may experience health inequity. Given the high burden of disease of colorectal cancer (CRC) and well-defined cancer care pathways, CRC is often the first disease site targeted by health systems for quality improvement. The objective of this review is to examine how SDoH have been integrated into QIs for CRC surgery. This review aims to address three primary questions: (1) Have SDoH been integrated into the development, reporting and assessment of CRC surgery QIs? (2) When integrated, what measures and statistical methods have been applied? (3) In which direction do individual SDoH influence QIs outputs? METHODS: This review will follow Arksey and O'Malley frameworks for scoping reviews. We will search MEDLINE, EMBASE, HealthSTAR databases for papers that examine QIs for CRC surgery applicable to healthcare systems from database inception until January 2023. Interventional trials, prospective and retrospective observational studies, reviews, case series and qualitative study designs will be included. Two authors will independently review all titles, abstracts and full texts to determine which studies meet the inclusion criteria. ETHICS & DISSEMINATION: No ethics approval is required for this review. Results will be disseminated through scientific presentation and relevant conferences targeted for researchers examining healthcare quality and equity in cancer care. REGISTRATION DETAILS: osf.io/vfzd3-Open Science Framework.

Global Comparison of Readmission Rates for Patients With Heart Failure.

BACKGROUND: Heart failure (HF) readmission rates are low in some jurisdictions. However, international comparisons are lacking and could serve as a foundation for identifying regional patient management strategies that could be shared to improve outcomes. OBJECTIVES: This study sought to summarize 30-day and 1-year all-cause readmission and mortality rates of hospitalized HF patients across countries and to explore potential differences in rates globally. METHODS: We performed a systematic review and meta-analysis using MEDLINE, Embase, and CENTRAL for observational reports on hospitalized adult HF patients at risk for readmission or mortality published between January 2010 and March 2021. We conducted a meta-analysis of proportions using a random-effects model, and sources of heterogeneity were evaluated with meta-regression. RESULTS: In total, 24 papers reporting on 30-day and 23 papers on 1-year readmission were included. Of the 1.5 million individuals at risk, 13.2% (95% CI: 10.5%-16.1%) were readmitted within 30 days and 35.7% (95% CI: 27.1%-44.9%) within 1 year. A total of 33 papers reported on 30-day and 45 papers on 1-year mortality. Of the 1.5 million individuals hospitalized for HF, 7.6% (95% CI: 6.1%-9.3%) died within 30 days and 23.3% (95% CI: 20.8%-25.9%) died within 1 year. Substantial variation in risk across countries was unexplained by countries' gross domestic product, proportion of gross domestic product spent on health care, and Gini coefficient. CONCLUSIONS: Globally, hospitalized HF patients exhibit high rates of readmission and mortality, and the variability in readmission rates was not explained by health care expenditure, risk of mortality, or comorbidities.

Derivation and validation of predictors of oral anticoagulant-related adverse events in seniors transitioning from hospital to home.

INTRODUCTION: Oral anticoagulant (OAC)-related adverse events are high post-hospitalization. We planned to develop and validate a prediction model for OAC-related harm within 30 days of hospitalization. METHODS: We undertook a population-based study of adults aged ≥66 years who were discharged from hospital on an OAC from September 2010 to March 2015 in Ontario, Canada. The primary outcome was a composite of time to first hospitalization or emergency department visit for a hemorrhagic or thromboembolic event, or mortality within 30 days of hospital discharge. Cox proportional hazards regression was used to build the model. RESULTS: We included 120,721 patients of which 5423 experienced the outcome. Most patients were aged ≥75 years (59.5%) and were female (55.6%). Sixty percent of the cohort had a follow-up visit with a healthcare provider within 7 days of discharge. Patients discharged on a direct acting OAC versus warfarin (apixaban: Hazard Ratio [HR] 0.82, 95% confidence interval [CI] 0.71-0.94; dabigatran: HR 0.73, 95% CI 0.63-0.84; rivaroxaban: HR 0.79, 95% CI 0.71-0.88), were prevalent users of the dispensed OAC versus incident users (HR 0.82, 95% CI 0.69-0.96), had a joint replacement in the past 35 days (HR 0.40, 95% CI 0.33-0.50) or major surgery during index hospital stay (HR 0.69, 95% CI 0.60-0.80) had a lower risk for the outcome. The Cox model was stable with acceptable discrimination but poor goodness-of-fit. CONCLUSIONS: A model for OAC-related harm in the early post-discharge period was developed. External validation studies are required to understand the model's poor calibration.

Adverse event rates associated with oral anticoagulant treatment early versus later after hospital discharge in older adults: a retrospective population-based cohort study.

BACKGROUND: Oral anticoagulants are commonly used high-risk medications, but little is known about their safety in transition from hospital to home. Our objective was to measure the rates of hemorrhage and thromboembolic events among older adults receiving oral anticoagulant treatment early after hospital discharge compared to later. METHODS: We conducted a retrospective population-based cohort study among Ontario residents aged 66 years or more who started, continued or resumed oral anticoagulant therapy at hospital discharge between September 2010 and March 2015. We calculated the rates of hemorrhage and thromboembolic events requiring hospital admission or an emergency department visit over a 1-year follow-up period, stratified by the first 30 days after discharge and the remainder of the year. We used multivariable regression models, adjusting for covariates, to estimate the effect of sex, prevalent versus incident use, and switching anticoagulants on events. RESULTS: A total of 123 139 patients (68 408 women [55.6%]; mean age 78.2 yr) were included. About one-quarter (32 563 [26.4%]) had a Charlson Comorbidity Index score of 2 or higher. The rates of hemorrhage and thromboembolic events per 100 person-years were highest during the first 30 days after hospital discharge (25.8, 95% CI 24.8-26.8 and 19.3, 95% CI 18.4-20.2, respectively), falling to 15.7 (95% CI 15.3-16.1) and 6.9 (95% CI 6.6-7.1), respectively, during the subsequent 11 months. Multivariable analysis showed that patients whose anticoagulant was switched in hospital and men had more hemorrhages and thromboembolic events in follow-up. INTERPRETATION: The first few weeks following hospital discharge represent a very high-risk period for adverse events related to oral anticoagulant treatment among older adults. The results support an intervention trial addressing anticoagulation management in the early postdischarge period.

Drug-drug interactions with warfarin: A systematic review and meta-analysis.

AIMS: The objective of this paper is to systematically review the literature on drug-drug interactions with warfarin, with a focus on patient-important clinical outcomes. METHODS: MEDLINE, EMBASE and the International Pharmaceutical Abstract (IPA) databases were searched from January 2004 to August 2019. We included studies describing drug-drug interactions between warfarin and other drugs. Screening and data extraction were conducted independently and in duplicate. We synthesized pooled odds ratios (OR) with 95% confidence intervals (CIs), comparing warfarin plus another medication to warfarin alone. We assessed the risk of bias at the study level and evaluated the overall certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: Of 42 013 citations identified, a total of 72 studies reporting on 3 735 775 patients were considered eligible, including 11 randomized clinical trials and 61 observational studies. Increased risk of clinically relevant bleeding when added to warfarin therapy was observed for antiplatelet (AP) regimens (OR = 1.74; 95% CI 1.56-1.94), many antimicrobials (OR = 1.63; 95% CI 1.45-1.83), NSAIDs including COX-2 NSAIDs (OR = 1.83; 95% CI 1.29-2.59), SSRIs (OR = 1.62; 95% CI 1.42-1.85), mirtazapine (OR = 1.75; 95% CI 1.30-2.36), loop diuretics (OR = 1.92; 95% CI 1.29-2.86) among others. We found a protective effect of proton pump inhibitors (PPIs) against warfarin-related gastrointestinal (GI) bleeding (OR = 0.69; 95% CI 0.64-0.73). No significant effect on thromboembolic events or mortality of any drug group used with warfarin was found, including single or dual AP regimens. CONCLUSIONS: This review found low to moderate certainty evidence supporting the interaction between warfarin and a small group of medications, which result in increased bleeding risk. PPIs are associated with reduced hospitalization for upper GI bleeding for patients taking warfarin. Further studies are required to better understand drug-drug interactions leading to thromboembolic outcomes or death.

Uptake of the Heart Failure Management Incentive Billing Code by Family Physicians in Ontario, Canada: A Retrospective Cohort Study.

In 2008, the Ontario Ministry of Health and Long-Term Care (MOHLTC) implemented an incentive payment, Q050A billing code, to family physicians for provision of comprehensive guideline-based care for patients with heart failure in the community. Our objective was to report on the uptake of this program from fiscal years 2008-2014. We determined the numbers of claims billed per year and the proportion of eligible patients with congestive heart failure (CHF) for whom a physician billed. The code was billed by 10.4% of all family physicians in 2008-2009, which increased to 15.1% in 2014-2015. The code was claimed for 4.1% of all identified patients with CHF in 2008-2009 and 5.9% of patients with CHF in 2014-2015. Given these findings, it is estimated that MOHLTC paid an additional CAD$10,118,514 to family physicians managing patients with CHF. This is the first study to examine the uptake of a CHF-specific incentive program, which will help to inform health policy makers in implementing such programs in Ontario.

Predictors of oral anticoagulant-associated adverse events in seniors transitioning from hospital to home: a retrospective cohort study protocol.

INTRODUCTION: Oral anticoagulants (OACs) are widely prescribed in older adults. High OAC-related adverse event rates in the early period following hospital discharge argue for an analysis to identify predictors. Our objective is to identify and validate clinical and continuity of care variables among seniors discharged from hospital on an OAC, which are independently associated with OAC-related adverse events within 30 days. METHODS AND ANALYSIS: We propose a population-based retrospective cohort study of all adults aged 66 years or older who were discharged from hospital on an OAC from September 2010 to March 2015 in Ontario, Canada. The primary outcome is a composite of the first hospitalisation or emergency department visit for a haemorrhage or thromboembolic event or mortality within 30 days of hospital discharge. A Cox proportional hazards model will be used to determine the association between the composite outcome and a set of prespecified covariates. A split sample method will be adopted to validate the variables associated with OAC-related adverse events. ETHICS AND DISSEMINATION: The use of data in this project was authorised under section 45 of Ontario's Personal Health Information Protection Act, which does not require review by a research ethics board. Results will be disseminated via peer-reviewed publications and presentations at conferences and will determine intervention targets to improve OAC management in upcoming randomised trials. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT02777047; Pre-results.