Using the Translating Research into Practice framework to develop a diabetes prevention intervention in primary care: a mixed-methods study.

BACKGROUND: Pre-diabetes affects one-third of US adults and increases the risk of type 2 diabetes. Effective evidence-based interventions, such as the Diabetes Prevention Program, are available, but a gap remains in effectively translating and increasing uptake of these interventions into routine care. METHODS: We applied the Translating Research into Practice (TRiP) framework to guide three phases of intervention design and development for diabetes prevention: (1) summarise the evidence, (2) identify local barriers to implementation and (3) measure performance. In phase 1, we conducted a retrospective cohort analysis of linked electronic health record claims data to evaluate current practices in the management of pre-diabetes. In phase 2, we conducted in-depth interviews of 16 primary care physicians, 7 payor leaders and 31 patients to elicit common barriers and facilitators for diabetes prevention. In phase 3, using findings from phases 1 and 2, we developed the core elements of the intervention and performance measures to evaluate intervention uptake. RESULTS: In phase 1 (retrospective cohort analysis), we found few patients with pre-diabetes received diabetes prevention interventions. In phase 2 (stakeholder engagement), we identified common barriers to include a lack of knowledge about pre-diabetes among patients and about the Diabetes Prevention Program among clinicians. In phase 3 (intervention development), we developed the START Diabetes Prevention Clinical Pathway as a systematic change package to address barriers and facilitators identified in phases 1 and 2, performance measures and a toolkit of resources to support the intervention components. CONCLUSIONS: The TRiP framework supported the identification of evidence-based care practices for pre-diabetes and the development of a well-fitted, actionable intervention and implementation plan designed to increase treatment uptake for pre-diabetes in primary care settings. Our change package can be adapted and used by other health systems or clinics to target prevention of diabetes or other related chronic conditions.

Randomized Experiments to Reduce Overuse of Health Care: A Scoping Review.

OBJECTIVE: Health care overuse is pervasive in countries with advanced health care delivery systems. We hypothesize that effective interventions to reduce low-value care that targets patients or clinicians are mediated by psychological and cognitive processes that change behaviors and that interventions targeting these processes are varied. Thus, we performed a scoping review of experimental studies of interventions, including the interventions' objectives and characteristics, to reduce low-value care that targeted psychological and cognitive processes. METHODS: We systematically searched databases for experimental studies of interventions to change cognitive orientations and affective states in the setting of health care overuse. Outcomes included observed overuse or a stated intention to use services. We used existing frameworks for behavior change and mechanisms of change to categorize the interventions and the mediating processes. RESULTS: Twenty-seven articles met the inclusion criteria. Sixteen studied the provision of information to patients or clinicians, with most providing cost information. Six studies used educational interventions, including the provision of feedback about individual practice. Studies rarely used counseling, behavioral nudges, persuasion, and rewards. Mechanisms for behavior change included gain in knowledge or confidence and motivation by social norms. CONCLUSIONS: In this scoping review, we found few experiments testing interventions that directly target the psychological and cognitive processes of patients or clinicians to reduce low-value care. Most studies provided information to patients or clinicians without measuring or considering mediating factors toward behavior change. These findings highlight the need for process-driven experimental designs, including trials of behavioral nudges and persuasive language involving a trusting patient-clinician relationship, to identify effective interventions to reduce low-value care.

Patient, provider, and system-level factors associated with preoperative cardiac testing: A systematic review.

BACKGROUND: Overuse of preoperative cardiac testing contributes to high healthcare costs and delayed surgeries. A large body of research has evaluated factors associated with variation in preoperative cardiac testing. However, patient, provider, and system-level factors associated with variation in testing have not been systematically studied. OBJECTIVE: To conduct a systematic review to better delineate the patient, provider, and system-level factors associated with variation in preoperative cardiac testing. METHODS: We included studies of an adult US population evaluating a patient, provider, or system-level factor associated with variation in preoperative cardiac testing for noncardiac surgery since 2012. Our search strategy used terms related to preoperative testing, diagnostic cardiac tests, and care variation with Ovid MEDLINE and Embase from inception through January 2023. We extracted study characteristics and factors associated with variation and qualitatively analyzed them. We assessed risk of bias using the Newcastle-Ottawa Scale and Evidence Project Risk of Bias tool. RESULTS: Twenty-eight articles met inclusion criteria. Older age and higher comorbidity were strongly associated with higher-intensity testing. The evidence for provider and system-level covariates was weaker. However, there was strong evidence that a focus on primary care and away from preoperative clinic and cardiac consultations was associated with less testing and that interventions to reduce low-value testing can be successful. CONCLUSIONS: There is significant interprovider and interhospital variation in preoperative cardiac testing, the correlates of which are not well-defined. Further work should aim to better understand these factors.

Assessing Heterogeneity of Treatment Effect in Real-World Data.

Increasing availability of real-world data (RWD) generated from patient care enables the generation of evidence to inform clinical decisions for subpopulations of patients and perhaps even individuals. There is growing opportunity to identify important heterogeneity of treatment effects (HTE) in these subgroups. Thus, HTE is relevant to all with interest in patients' responses to interventions, including regulators who must make decisions about products when signals of harms arise postapproval and payers who make coverage decisions based on expected net benefit to their beneficiaries. Prior work discussed HTE in randomized studies. Here, we address methodological considerations when investigating HTE in observational studies. We propose 4 primary goals of HTE analyses and the corresponding approaches in the context of RWD: to confirm subgroup effects, to describe the magnitude of HTE, to discover clinically important subgroups, and to predict individual effects. We discuss other possible goals including exploring prognostic score- and propensity score-based treatment effects, and testing the transportability of trial results to populations different from trial participants. Finally, we outline methodological needs for enhancing real-world HTE analysis.

Comparative effectiveness of omalizumab, mepolizumab, and dupilumab in asthma: A target trial emulation.

BACKGROUND: Multiple mAbs are currently approved for the treatment of asthma. However, there is limited evidence on their comparative effectiveness. OBJECTIVE: Our aim was to compare the effectiveness of omalizumab, mepolizumab, and dupilumab in individuals with moderate-to-severe asthma. METHODS: We emulated a hypothetical randomized trial using electronic health records from a large US-based academic health care system. Participants aged 18 years or older with baseline IgE levels between 30 and 700 IU/mL and peripheral eosinophil counts of at least 150 cells/µL were eligible for study inclusion. The study period extended from March 2016 to August 2021. Outcomes included the incidence of asthma-related exacerbations and change in baseline FEV1 value over 12 months of follow-up. RESULTS: In all, 68 individuals receiving dupilumab, 68 receiving omalizumab, and 65 receiving mepolizumab met the inclusion criteria. Over 12 months of follow-up, 31 exacerbations occurred over 68 person years (0.46 exacerbations per person year) in the dupilumab group, 63 over 68 person years (0.93 per person year) in the omalizumab group, and 86 over 65 person years (1.32 per person year) in the mepolizumab group (adjusted incidence rate ratios: dupilumab vs mepolizumab, 0.28 [95% CI = 0.09-0.84]; dupilumab vs omalizumab, 0.36 [95% CI = 0.12-1.09]; and omalizumab vs mepolizumab, 0.78 [95% CI = 0.32-1.91]). The differences in the change in FEV1 comparing patients who received the different biologics were as follows: 0.11 L (95% CI = -0.003 to 0.222 L) for dupilumab versus mepolizumab, 0.082 L (95% CI -0.040 to 0.204 L) for dupilumab versus omalizumab, and 0.026 L (95% CI -0.083 to 0.140 L) for omalizumab versus mepolizumab. CONCLUSIONS: Among patients with asthma and eosinophil counts of at least 150 cells/µL and IgE levels of 30 to 700 kU/L, dupilumab was associated with greater improvements in exacerbation and FEV1 value than omalizumab and mepolizumab.

Reducing Overuse by Healthcare Systems: A Positive Deviance Analysis.

BACKGROUND: Healthcare in the USA is increasingly delivered by large healthcare systems that include one or more hospitals and associated outpatient practices. It is unclear what role healthcare systems play in driving or preventing overutilization of healthcare services in the USA. OBJECTIVE: To learn how high-value healthcare systems avoid overuse of services DESIGN: We identified "positive deviant" health systems using a previously constructed Overuse Index. These systems have much lower-than-average overuse of healthcare services. We confirmed that these health systems also delivered high-quality care. We conducted semi-structured interviews with executive leaders of these systems to validate a published framework for understanding drivers of overuse. PARTICIPANTS: Leaders at select healthcare systems in the USA. INTERVENTIONS: None APPROACH: We developed an interview guide and conducted semi-structured interviews. We iteratively developed a code book. Paired reviewers coded and reconciled each interview. We analyzed the interviews by applying constant comparative techniques. We mapped the emergent themes to provide the first empirical data to support a previously developed theoretical framework. KEY RESULTS: We interviewed 15 leaders from 10 diverse healthcare systems. Consistent with important domains from the overuse framework, themes from our study support the role of clinicians and patients in avoiding overuse. The leaders described how they create a culture of professional practice and how they modify clinicians' attitudes to facilitate high-value practices. They also described how their patients view healthcare consumption and the characteristics of their patient populations allowed them to practice high-value medicine. They described the role of quality metrics, insurance plan ownership, and alternative payment model participation as encouraging avoidance of overuse. CONCLUSIONS: Our qualitative analysis of positive deviant health systems supports the framework that is in the published literature, although health system leaders also described their financial structures as another important factor for reducing overuse and encouraging high-value care delivery.

Healthcare utilization differences between an apixaban-based and warfarin-based strategy for acute venous thromboembolism in patients with end-stage kidney disease.

INTRODUCTION: Evidence suggests that an apixaban-based strategy to treat acute venous thromboembolism (VTE) in patients with End-Stage Kidney Disease (ESKD) may be safer than a warfarin-based strategy. Apixaban has an additional advantage of not requiring bridging with heparin which often necessitates long hospitalizations for patients with ESKD. We sought to determine if an apixaban-based strategy is associated with less healthcare utilization than a warfarin-based strategy. MATERIAL AND METHODS: We employed a new-user, active-comparator retrospective cohort study using inverse probability of treatment weights (IPTW) to adjust for confounding demographic and clinical variables. Patients with ESKD newly initiated on either apixaban or warfarin for an acute VTE between 2014 and 2018 in the United States Renal Data System were included. Outcomes were presence of index hospitalization, length of index hospitalization, total hospital days, total hospital days excluding index hospitalization, total emergency department (ED) visits that did not result in hospitalization, and total skilled nursing facility days. RESULTS: At six months, patients who received apixaban were less likely to have an index hospitalization, had a shorter index hospitalization (median of 4.0 vs 8.0 days, p < 0.001), and had fewer total hospital days. The IPTW and index year-adjusted incidence rate ratios of total hospital days at one, three, and six months were 0.83 (95 % confidence intervals (CI) 0.79-0.86), 0.84 (95 % CI 0.81-0.88), and 0.88 (95 % CI 0.83-0.92) for apixaban compared to warfarin. CONCLUSION: Among patients with ESKD and VTE, resource utilization for an apixaban-based strategy appears to be lower than for a warfarin-based strategy.

Hydroxychloroquine lowers Alzheimer's disease and related dementias risk and rescues molecular phenotypes related to Alzheimer's disease.

We recently nominated cytokine signaling through the Janus-kinase-signal transducer and activator of transcription (JAK/STAT) pathway as a potential AD drug target. As hydroxychloroquine (HCQ) has recently been shown to inactivate STAT3, we hypothesized that it may impact AD pathogenesis and risk. Among 109,124 rheumatoid arthritis patients from routine clinical care, HCQ initiation was associated with a lower risk of incident AD compared to methotrexate initiation across 4 alternative analyses schemes addressing specific types of biases including informative censoring, reverse causality, and outcome misclassification (hazard ratio [95% confidence interval] of 0.92 [0.83-1.00], 0.87 [0.81-0.93], 0.84 [0.76-0.93], and 0.87 [0.75-1.01]). We additionally show that HCQ exerts dose-dependent effects on late long-term potentiation (LTP) and rescues impaired hippocampal synaptic plasticity prior to significant accumulation of amyloid plaques and neurodegeneration in APP/PS1 mice. Additionally, HCQ treatment enhances microglial clearance of Aß1-42, lowers neuroinflammation, and reduces tau phosphorylation in cell culture-based phenotypic assays. Finally, we show that HCQ inactivates STAT3 in microglia, neurons, and astrocytes suggesting a plausible mechanism associated with its observed effects on AD pathogenesis. HCQ, a relatively safe and inexpensive drug in current use may be a promising disease-modifying AD treatment. This hypothesis merits testing through adequately powered clinical trials in at-risk individuals during preclinical stages of disease progression.

Comparative Effectiveness and Safety of Direct Oral Anticoagulants Versus Warfarin Among Adults With Cancer and Atrial Fibrillation.

BACKGROUND: While clinical guidelines recommend direct-acting oral anticoagulants (DOAC) over warfarin to treat isolated nonvalvular atrial fibrillation, guidelines are silent regarding nonvalvular atrial fibrillation treatment among individuals with cancer, reflecting the paucity of evidence in this setting. We quantified relative risk of ischemic stroke or systemic embolism and major bleeding (primary outcomes), and all-cause and cardiovascular death (secondary outcomes) among older individuals with cancer and nonvalvular atrial fibrillation comparing DOACs and warfarin. METHODS: This retrospective cohort study used Surveillance, Epidemiology, and End Results cancer registry and linked US Medicare data from 2010 through 2016, and included individuals diagnosed with cancer and nonvalvular atrial fibrillation who newly initiated DOAC or warfarin. We used inverse probability of treatment weighting to control confounding. We used competing risk regression for primary outcomes and cardiovascular death, and Cox proportional hazard regression for all-cause death. RESULTS: Among 7675 individuals included in the cohort, 4244 (55.3%) received DOACs and 3431 (44.7%) warfarin. In the inverse probability of treatment weighting analysis, there was no statistically significant difference among DOAC and warfarin users in the risk of ischemic stroke or systemic embolism (1.24 versus 1.19 events per 100 person-years, adjusted hazard ratio 1.41 [95% CI, 0.92-2.14]), major bleeding (3.08 versus 4.49 events per 100 person-years, adjusted hazard ratio 0.90 [95% CI, 0.70-1.17]), and cardiovascular death (1.88 versus 3.14 per 100 person-years, adjusted hazard ratio 0.82 [95% CI, 0.59-0.1.13]). DOAC users had significantly lower risk of all-cause death (7.09 versus 13.3 per 100 person-years, adjusted hazard ratio 0.81 [95% CI, 0.69-0.94]) compared to warfarin users. CONCLUSIONS: Older adults with cancer and atrial fibrillation exposed to DOACs had similar risks of stroke and systemic embolism and major bleeding as those exposed to warfarin. Relative to warfarin, DOAC use was associated with a similar risk of cardiovascular death and a lower risk of all-cause death.

No association between initiation of phosphodiesterase-5 inhibitors and risk of incident Alzheimer's disease and related dementia: results from the Drug Repurposing for Effective Alzheimer's Medicines study.

We evaluated the hypothesis that phosphodiesterase-5 inhibitors, including sildenafil and tadalafil, may be associated with reduced incidence of Alzheimer's disease and related dementia using a patient-level cohort study of Medicare claims and cell culture-based phenotypic assays. We compared incidence of Alzheimer's disease and related dementia after phosphodiesterase-5 inhibitor initiation versus endothelin receptor antagonist initiation among patients with pulmonary hypertension after controlling for 76 confounding variables through propensity score matching. Across four separate analytic approaches designed to address specific types of biases including informative censoring, reverse causality, and outcome misclassification, we observed no evidence for a reduced risk of Alzheimer's disease and related dementia with phosphodiesterase-5 inhibitors;hazard ratio (95% confidence interval): 0.99 (0.69-1.43), 1.00 (0.71-1.42), 0.67 (0.43-1.06), and 1.15 (0.57-2.34). We also did not observe evidence that sildenafil ameliorated molecular abnormalities relevant to Alzheimer's disease in most cell culture-based phenotypic assays. These results do not provide support to the hypothesis that phosphodiesterase-5 inhibitors are promising repurposing candidates for Alzheimer's disease and related dementia.

Development and Validation of the Summary Elixhauser Comorbidity Score for Use With ICD-10-CM-Coded Data Among Older Adults.

BACKGROUND: Older adults have many comorbidities contributing to mortality. OBJECTIVE: To develop a summary Elixhauser (S-Elixhauser) comorbidity score to predict 30-day, in-hospital, and 1-year mortality in older adults using the 38 comorbidities operationalized by the Agency for Healthcare Research and Quality (AHRQ). DESIGN: Retrospective cohort study. SETTING: Medicare beneficiaries from 2017 to 2019. PATIENTS: Persons hospitalized in 2018 (n = 899 844) and 3 disease-specific hospitalized cohorts. MEASUREMENTS: Weights were derived for 38 comorbidities to predict 30-day, in-hospital, and 1-year mortality. The S-Elixhauser score was internally validated and calibrated. Individual Elixhauser comorbidity indicators (38 comorbidities), the modified application of the AHRQ-derived Elixhauser summary score, the Charlson comorbidity indicators (17 comorbidities), and the Charlson summary score were externally validated. The c-statistic was used to evaluate discrimination of a comorbidity score model. RESULTS: The S-Elixhauser score was well calibrated and internally validated, with a c-statistic of 0.705 (95% CI, 0.703 to 0.707) in predicting 30-day mortality, 0.654 (CI, 0.651 to 0.657) for in-hospital mortality, and 0.743 (CI, 0.741 to 0.744) for 1-year mortality. In external validation of other comorbidity indices for 30-day mortality, the c-statistic was 0.711 (CI, 0.709 to 0.713) for the individual Elixhauser comorbidity indicators, 0.688 (CI, 0.686 to 0.690) for the AHRQ Elixhauser score, 0.696 (CI, 0.694 to 0.698) for the Charlson comorbidity indicators, and 0.690 (CI, 0.688 to 0.693) for the Charlson summary score. In 3 disease-specific populations, the discrimination of the S-Elixhauser score in predicting 30-day mortality ranged from 0.657 to 0.732. LIMITATION: Validation of the S-Elixhauser comorbidity score and head-to-head comparison with other comorbidity scores in an external population are needed to evaluate comparative performance. CONCLUSION: The S-Elixhauser comorbidity score is well calibrated and internally validated but its advantage over the AHRQ Elixhauser and Charlson summary scores is unclear. PRIMARY FUNDING SOURCE: National Institute on Aging.

Factors Associated With Overuse of Health Care Within US Health Systems: A Cross-sectional Analysis of Medicare Beneficiaries From 2016 to 2018.

Importance: Overuse of health care is a pervasive threat to patients that requires measurement to inform the development of interventions. Objective: To measure low-value health care use within health systems in the US and explore features of the health systems associated with low-value care delivery. Design Setting and Participants: In this cross-sectional analysis, we identified occurrences of 17 low-value services in 3745 hospitals and affiliated outpatient sites. Hospitals were linked to 676 health systems in the US using the Agency for Healthcare Research and Quality (AHRQ) Compendium of Health Systems. The participants were 100% of Medicare beneficiaries with claims from 2016 to 2018. Exposures: We identified occurrences of 17 low-value services in 3839 hospitals and affiliated outpatient sites. Main Outcomes and Measures: Hospitals were linked to health systems using AHRQ's Compendium of Health Systems. Between March and August 2021, we modeled overuse occurrences with a negative binomial regression model including the year-quarter, procedure indicator, and a health system indicator. The model included random effects for hospital and beneficiary age, sex, and comorbidity count specific to each indicator, hospital, and quarter. The beta coefficients associated with the health system term, normalized, reflect the tendency of that system to use low-value services relative to all other systems. With ordinary least squares regression, we explored health system characteristics associated with the Overuse Index (OI), expressed as a standard deviation where the mean across all health systems is 0. Results: There were 676 unique health systems assessed in our study that included from 1 to 163 hospitals (median of 2). The mean age of eligible beneficiaries was 75.5 years and 76% were women. Relative to the lowest tertile, health systems in the upper tertile of medical groups count and bed count had an OI that was higher by 0.38 standard deviations (SD) and 0.44 SD, respectively. Health systems that were primarily investor owned had an OI that was 0.56 SD higher than those that were not investor owned. Relative to the lowest tertile, health systems in the upper tertile of primary care physicians, upper tertile of teaching intensity, and upper quartile of uncompensated care had an OI that was lower by 0.59 SD, 0.45 SD, and 0.47 SD, respectively. Conclusions and Relevance: In this cross-sectional study of US health systems, higher amounts of overuse among health systems were associated with investor ownership and fewer primary care physicians. The OI is a valuable tool for identifying potentially modifiable drivers of overuse and is adaptable to other levels of investigation, such as the state or region, which might be affected by local policies affecting payment or system consolidation.

Safety and effectiveness of apixaban versus warfarin for acute venous thromboembolism in patients with end-stage kidney disease: A national cohort study.

BACKGROUND: Patients with end-stage kidney disease (ESKD) are at significantly increased risk for both thrombosis and bleeding relative to those with normal renal function. The optimal therapy of venous thromboembolism (VTE) in patients with ESKD is unknown. OBJECTIVE: To compare the safety and effectiveness of apixaban relative to warfarin in patients with ESKD and acute VTE. DESIGN, SETTING AND PARTICIPANTS: New-user, active-comparator retrospective United States population-based cohort with inverse probability of treatment weighting, using the United States Renal Data System data from 2014 to 2018. We included adults with ESKD on hemodialysis or peritoneal dialysis who were newly initiated on apixaban or warfarin for an acute VTE. MAIN OUTCOME AND MEASURES: The coprimary outcomes were major bleeding, recurrent VTE, and all-cause mortality within 6 months of anticoagulant initiation. Secondary outcomes were intracranial hemorrhage and gastrointestinal bleeding. The primary analyses were based on intent-to-treat defined by the first drug received and accounted for competing risks of death. Sensitivity analyses included varied follow-up time, as-treated analyses, and dose-specific apixaban subgroups. RESULTS: The apixaban and warfarin cohorts included 2302 and 9263 patients, respectively. Apixaban was associated with a lower risk of major bleeding (hazard ratio [HR] 0.81, 95% confidence interval [CI]: 0.70-0.94), intracranial bleeding (HR 0.69, 95% CI 0.48-0.98), and gastrointestinal bleeding (HR 0.82, 95% CI 0.69-0.96). Recurrent VTE and all-cause mortality were not significantly different between the groups. CONCLUSION: Apixaban was associated with a lower risk of bleeding relative to warfarin when used to treat acute VTE in patients with ESKD on dialysis.

Telemedicine in Primary Care: Qualitative Work Towards a Framework for Appropriate Use.

INTRODUCTION: Telemedicine has been implemented in many health systems by necessity, yet evidence is sparse about its appropriate use for the delivery of primary care. We sought to understand what clinicians and patients consider to be appropriate use of telemedicine in primary care to inform future development of a framework that should be valuable to diverse stakeholders. METHODS: We conducted in-depth, structured interviews of patients, clinicians who deliver primary care, and other select informants. They were asked to discuss optimal, acceptable, and suboptimal uses of telemedicine for delivering care relative to in-person care delivery. Audio was transcribed and paired reviewers analyzed the content to identify the key concepts that motivated the informants. The reviewers did thematic analysis to organize the concepts into unifying themes. RESULTS: Our 18 key informants generated 103 unique concepts. The unique concepts aggregated into themes suggesting the clinical situations in which telemedicine is appropriately used in primary care and clinical situations in which it should be avoided. We also learned of motivators toward expanded, or at least continued, use of telemedicine and motivators away from telemedicine's continued use. The informants expressed their expectations regarding decision making about telemedicine use and who should make these decisions. DISCUSSION: These key concepts and themes are expected to be a valuable starting point for the development of a framework to inform appropriate use of telemedicine in primary care.

Working Framework for Appropriate Use of Virtual Care in Primary Care.

BACKGROUND: Given the absence of guidelines for use of virtual visits for primary care delivery, a framework is needed to inform the most appropriate use of virtual visits. METHODS: We conducted in-depth, structured interviews of 18 patients, primary care clinicians, and other select informants. They were asked to discuss optimal, acceptable, and suboptimal uses of telemedicine for delivering care relative to in-person care delivery. The concepts expressed informed our development of a framework about appropriate use of virtual visits. RESULTS: The 103 concepts supported 5 main themes that emerged as a framework: clinical situations which are optimal for in-person care; situations optimal for virtual visits; situations that might be exchangeable between sites; contextual factors favoring in-person care; and contextual factors favoring virtual visits. CONCLUSIONS: After further validation, we expect that this framework may guide future research and practice: it may be valuable for clinical practice redesign, for designing evaluations of the outcomes of virtual visits, for outcomes research, for patient education, for triage, and possibly for reimbursement considerations.

Use of oral anticoagulants among individuals with cancer and atrial fibrillation in the United States, 2010-2016.

BACKGROUND: Anticoagulation among patients with cancer and atrial fibrillation is challenging due to elevated risk of bleeding and stroke. We characterized use of oral anticoagulants among patients with cancer and non-valvular atrial fibrillation (NVAF). METHODS: We used Surveillance, Epidemiology, and End Results (SEER)-Medicare data and included patients with cancer aged ≥66 years with an incident diagnosis of NVAF from 2010 to 2016. We used a Cox proportional hazard model and multivariable logistic regression to identify factors associated with anticoagulant use versus no use and direct oral anticoagulants (DOACs) versus warfarin use, respectively. RESULTS: Of 27,702 patients with cancer and NVAF, 4469 (16.1%) used DOACs and 3577 (12.9%) used warfarin. Among 8046 anticoagulant users, DOACs use increased from 21.8% in 2011 to 76.2% in 2016, with a corresponding decline in warfarin use from 78.2% to 23.8%. Nearly 7 out of 10 patients with cancer and NVAF did not initiate anticoagulation in 2016. Anticoagulant use was more likely among those with higher CHA2DS2-VASc scores (hazard ratio [HR] 1.55, 95% confidence interval [CI] 1.27-1.90 for score ≥6 vs. 1) or with lower HAS-BLED scores (HR 1.96, 95% CI 1.67-2.30 for score 1 vs. ≥6). Among anticoagulant users, DOAC use was less likely than warfarin in those with higher CHA2DS2-VASc scores (odds ratio [OR] 0.53, 95% CI 0.33-0.84 for score ≥6 vs. 1). CONCLUSIONS: Nearly 7 out of 10 patients with cancer and NVAF did not receive anticoagulation. Use of DOACs increased from 2010 to 2016, with a corresponding decline in warfarin use. DOACs are used less than warfarin among those at higher risk of stroke.

Clinical Care Among Individuals with Prediabetes in Primary Care: a Retrospective Cohort Study.

BACKGROUND: The incidence of diabetes in the general US population (6.7 per 1000 adults in 2018) has not changed significantly since 2000, suggesting that individuals with prediabetes are not connecting to evidence-based interventions. OBJECTIVE: We sought to describe the clinical care of individuals with prediabetes, determine patient factors associated with this care, and evaluate risk for diabetes development. DESIGN: Retrospective cohort study using linked claims and electronic health record data. PARTICIPANTS: We created a cohort of adults with prediabetes based on laboratory measures. We excluded patients with a prior history of diabetes, pregnancy in prior 6 months, or recent steroid use. MAIN MEASURES: We measured ordering and completion of clinical services targeting prediabetes management and diabetes incidence within 12 months following cohort entry. We tested the strength of the association between individuals' characteristics and outcomes of interest using bivariate and multiple logistic regression. RESULTS: Our cohort included 3888 patients with a laboratory diagnosis of prediabetes (incident or prevalent prediabetes). Within 12 months, 63.4% had repeat glycemic testing, yet only 10.4% had coded diagnoses of prediabetes, 1.0% were referred for nutrition services, and 5.4% were prescribed metformin. Most patients completed labs and nutrition visits when referred and filled metformin when prescribed. Individuals with a higher glycemic level or BMI were more likely to receive prediabetes clinical care. Six percent of individuals developed diabetes within 12 months of cohort entry and had higher glycemic levels and BMI ≥ 30 kg/m2. In the adjusted model, Black individuals had 1.4 times higher odds of developing diabetes than White individuals. CONCLUSIONS: Rates of prediabetes clinical care activities are low and have not improved. Strategies are urgently needed to improve prediabetes care delivery thereby preventing or delaying incident diabetes.

Long-term use of immunosuppressive medicines and in-hospital COVID-19 outcomes: a retrospective cohort study using data from the National COVID Cohort Collaborative.

BACKGROUND: Many individuals take long-term immunosuppressive medications. We evaluated whether these individuals have worse outcomes when hospitalised with COVID-19 compared with non-immunosuppressed individuals. METHODS: We conducted a retrospective cohort study using data from the National COVID Cohort Collaborative (N3C), the largest longitudinal electronic health record repository of patients in hospital with confirmed or suspected COVID-19 in the USA, between Jan 1, 2020, and June 11, 2021, within 42 health systems. We compared adults with immunosuppressive medications used before admission to adults without long-term immunosuppression. We considered immunosuppression overall, as well as by 15 classes of medication and three broad indications for immunosuppressive medicines. We used Fine and Gray's proportional subdistribution hazards models to estimate the hazard ratio (HR) for the risk of invasive mechanical ventilation, with the competing risk of death. We used Cox proportional hazards models to estimate HRs for in-hospital death. Models were adjusted using doubly robust propensity score methodology. FINDINGS: Among 231 830 potentially eligible adults in the N3C repository who were admitted to hospital with confirmed or suspected COVID-19 during the study period, 222 575 met the inclusion criteria (mean age 59 years [SD 19]; 111 269 [50%] male). The most common comorbidities were diabetes (23%), pulmonary disease (17%), and renal disease (13%). 16 494 (7%) patients had long-term immunosuppression with medications for diverse conditions, including rheumatological disease (33%), solid organ transplant (26%), or cancer (22%). In the propensity score matched cohort (including 12 841 immunosuppressed patients and 29 386 non-immunosuppressed patients), immunosuppression was associated with a reduced risk of invasive ventilation (HR 0·89, 95% CI 0·83-0·96) and there was no overall association between long-term immunosuppression and the risk of in-hospital death. None of the 15 medication classes examined were associated with an increased risk of invasive mechanical ventilation. Although there was no statistically significant association between most drugs and in-hospital death, increases were found with rituximab for rheumatological disease (1·72, 1·10-2·69) and for cancer (2·57, 1·86-3·56). Results were generally consistent across subgroup analyses that considered race and ethnicity or sex, as well as across sensitivity analyses that varied exposure, covariate, and outcome definitions. INTERPRETATION: Among this cohort, with the exception of rituximab, there was no increased risk of mechanical ventilation or in-hospital death for the rheumatological, antineoplastic, or antimetabolite therapies examined. FUNDING: None.