Physicians' perspectives on percutaneous left atrial appendage occlusion for patients with atrial fibrillation.

BACKGROUND: There has been an increasing uptake of transcatheter left atrial appendage occlusion (LAAO) for stroke reduction in atrial fibrillation. OBJECTIVES: To investigate the perceptions and approaches among a nationally representative sample of physicians. METHODS: Using the American Medical Association Physician Masterfile, we selected a random sample of 500 physicians from each of the specialties: general cardiologists, interventional cardiologists, electrophysiologists, and vascular neurologists. The participants received the survey by mail up to three times from November 9, 2021 to January 14, 2022. In addition to the questions about experiences, perceptions, and approaches, physicians were randomly assigned to 1 of the 4 versions of a patient vignette: white man, white woman, black man, and black woman, to investigate potential bias in decision-making. RESULTS: The top three reasons for considering LAAO were: a history of intracranial bleeding (94.3%), a history of major extracranial bleeding (91.8%), and gastrointestinal lesions (59.0%), whereas the top three reasons for withholding LAAO were: other indications for long-term oral anticoagulation (87.7%), a low bleeding risk (77.0%), and a low stroke risk (65.6%). For the reasons limiting recommendations for LAAO, 59.8% mentioned procedural risks, 42.6% mentioned "limiting efficacy data comparing LAAO to NOAC" and 32.8% mentioned "limited safety data comparing LAAO to NOAC." There was no difference in physicians' decision-making by patients' race, gender, or the concordance between patients' and physicians' race or gender. CONCLUSIONS: In the first U.S. national physician survey of LAAO, individual physicians' perspectives varied greatly, which provided information that will help customize future educational activities for different audiences. CONDENSED ABSTRACT: Although diverse practice patterns of LAAO have been documented, little is known about the reasoning or perceptions that drive these variations. Unlike prior surveys that were directed to Centers that performed LAAO, the current survey obtained insights from individual physicians, not only those who perform the procedures (interventional cardiologists and electrophysiologists) but also those who are closely involved in the decision-making and referral process (general cardiologists and vascular neurologists). The findings identify key evidence gaps and help prioritize future studies to establish a consistent and evidence-based best practice for AF stroke prevention.

Identifying treatment heterogeneity in atrial fibrillation using a novel causal machine learning method.

BACKGROUND: Lifelong oral anticoagulation is recommended in patients with atrial fibrillation (AF) to prevent stroke. Over the last decade, multiple new oral anticoagulants (OACs) have expanded the number of treatment options for these patients. While population-level effectiveness of OACs has been compared, it is unclear if there is variability in benefit and risk across patient subgroups. METHODS: We analyzed claims and medical data for 34,569 patients who initiated a nonvitamin K antagonist oral anticoagulant (non-vitamin K antagonist oral anticoagulant (NOAC); apixaban, dabigatran, and rivaroxaban) or warfarin for nonvalvular AF between 08/01/2010 and 11/29/2017 from the OptumLabs Data Warehouse. A machine learning (ML) method was applied to match different OAC groups on several baseline variables including, age, sex, race, renal function, and CHA2DS2 -VASC score. A causal ML method was then used to discover patient subgroups characterizing the head-to-head treatment effects of the OACs on a primary composite outcome of ischemic stroke, intracranial hemorrhage, and all-cause mortality. RESULTS: The mean age, number of females and white race in the entire cohort of 34,569 patients were 71.2 (SD, 10.7) years, 14,916 (43.1%), and 25,051 (72.5%) respectively. During a mean follow-up of 8.3 (SD, 9.0) months, 2,110 (6.1%) of patients experienced the composite outcome, of whom 1,675 (4.8%) died. The causal ML method identified 5 subgroups with variables favoring apixaban over dabigatran; 2 subgroups favoring apixaban over rivaroxaban; 1 subgroup favoring dabigatran over rivaroxaban; and 1 subgroup favoring rivaroxaban over dabigatran in terms of risk reduction of the primary endpoint. No subgroup favored warfarin and most dabigatran vs warfarin users favored neither drug. The variables that most influenced favoring one subgroup over another included Age, history of ischemic stroke, thromboembolism, estimated glomerular filtration rate, Race, and myocardial infarction. CONCLUSIONS: Among patients with AF treated with a NOAC or warfarin, a causal ML method identified patient subgroups with differences in outcomes associated with OAC use. The findings suggest that the effects of OACs are heterogeneous across subgroups of AF patients, which could help personalize the choice of OAC. Future prospective studies are needed to better understand the clinical impact of the subgroups with respect to OAC selection.

A prediction model for asthma exacerbations after stopping asthma biologics.

BACKGROUND: Little is known regarding the prediction of the risks of asthma exacerbation after stopping asthma biologics. OBJECTIVE: To develop and validate a predictive model for the risk of asthma exacerbations after stopping asthma biologics using machine learning models. METHODS: We identified 3057 people with asthma who stopped asthma biologics in the OptumLabs Database Warehouse and considered a wide range of demographic and clinical risk factors to predict subsequent outcomes. The primary outcome used to assess success after stopping was having no exacerbations in the 6 months after stopping the biologic. Elastic-net logistic regression (GLMnet), random forest, and gradient boosting machine models were used with 10-fold cross-validation within a development (80%) cohort and validation cohort (20%). RESULTS: The mean age of the total cohort was 47.1 (SD, 17.1) years, 1859 (60.8%) were women, 2261 (74.0%) were White, and 1475 (48.3%) were in the Southern region of the United States. The elastic-net logistic regression model yielded an area under the curve (AUC) of 0.75 (95% confidence interval [CI], 0.71-0.78) in the development and an AUC of 0.72 in the validation cohort. The random forest model yielded an AUC of 0.75 (95% CI, 0.68-0.79) in the development cohort and an AUC of 0.72 in the validation cohort. The gradient boosting machine model yielded an AUC of 0.76 (95% CI, 0.72-0.80) in the development cohort and an AUC of 0.74 in the validation cohort. CONCLUSION: Outcomes after stopping asthma biologics can be predicted with moderate accuracy using machine learning methods.

Impact of the Coronavirus Disease 2019 (COVID-19) Vaccine on Asymptomatic Infection Among Patients Undergoing Preprocedural COVID-19 Molecular Screening.

BACKGROUND: Several vaccines are now available under emergency use authorization in the United States and have demonstrated efficacy against symptomatic COVID-19. Vaccine impact on asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is largely unknown. METHODS: We conducted a retrospective cohort study of consecutive, asymptomatic adult patients (n = 39 156) within a large US healthcare system who underwent 48 333 preprocedural SARS-CoV-2 molecular screening tests between 17 December 2020 and 8 February 2021. The primary exposure of interest was vaccination with ≥1 dose of an mRNA COVID-19 vaccine. The primary outcome was relative risk (RR) of a positive SARS-CoV-2 molecular test among those asymptomatic persons who had received ≥1 dose of vaccine compared with persons who had not received vaccine during the same time period. RR was adjusted for age, sex, race/ethnicity, patient residence relative to the hospital (local vs nonlocal), healthcare system regions, and repeated screenings among patients using mixed-effects log-binomial regression. RESULTS: Positive molecular tests in asymptomatic individuals were reported in 42 (1.4%) of 3006 tests and 1436 (3.2%) of 45 327 tests performed on vaccinated and unvaccinated patients, respectively (RR, .44; 95% CI, .33-.60; P < .0001). Compared with unvaccinated patients, risk of asymptomatic SARS-CoV-2 infection was lower among those >10 days after the first dose (RR, .21; 95% CI, .12-.37; P < .0001) and >0 days after the second dose (RR, .20; 95% CI, .09-.44; P < .0001) in the adjusted analysis. CONCLUSIONS: COVID-19 vaccination with an mRNA-based vaccine showed a significant association with reduced risk of asymptomatic SARS-CoV-2 infection as measured during preprocedural molecular screening. Results of this study demonstrate the impact of the vaccines on reduction in asymptomatic infections supplementing the randomized trial results on symptomatic patients.

Comparative Risk of Serious Infections With Tumor Necrosis Factor α Antagonists vs Vedolizumab in Patients With Inflammatory Bowel Diseases.

BACKGROUND AND AIMS: We conducted a retrospective cohort study comparing the risk of serious infections between patients treated with tumor necrosis factor-a (TNFa) antagonists vs. vedolizumab in patients with inflammatory bowel diseases (IBD). METHODS: Using an administrative claims database, we identified patients with IBD who were new-users of either TNFa antagonists or vedolizumab between 2014-2018 and had insurance coverage for at least 1y before and after treatment initiation. We compared the risk of serious infections (infections requiring hospitalization) between patients treated with vedolizumab or TNFa antagonists using marginal structural Cox proportional hazard models adjusted for baseline disease characteristics, healthcare utilization, comorbidities, and time-varying use of corticosteroids, immunomodulators and opiates. RESULTS: We included 4881 patients treated with TNFa antagonists (age, 41 ± 15y, 60% with Crohn's disease [CD]) of whom 434 developed serious infections over 5786 person-year [PY] follow-up, and 1106 patients treated with vedolizumab (age, 44 ± 16y, 39% with CD) of whom 86 developed serious infections over 1040-PY follow-up. Vedolizumab was associated with 46% lower risk of serious infections as compared with TNFa antagonists in patients with ulcerative colitis (HR,0.54 [95% CI,0.35-0.83), but no significant differences were observed in patients with CD (HR,1.30 [0.80-2.11]). Vedolizumab was associated with lower risk of extra-intestinal serious infections in patients with UC, but higher risk of gastrointestinal serious infections in patients with CD. CONCLUSIONS: In an observational study of patients with IBD, vedolizumab was associated with lower risk of serious infections as compared with TNFa antagonists, in patients with UC, but not in patients with CD.

Asthma biologic trial eligibility and real-world outcomes in the United States.

OBJECTIVE: To compare the outcomes of real-world patients who would have been eligible for asthma biologics to those who would not have been eligible. METHODS: We used data from the OptumLabs Data Warehouse (OLDW) to categorize patients into eligible and ineligible groups based on clinical trials (n = 19 trials) used for Food and Drug Administration (FDA) approval. We then compared the change in the number of asthma exacerbations before and after biological initiation between the two groups. RESULTS: The percentage of people who would have been eligible for asthma biologic clinical trials ranged from 0-10.2%. The eligible group had a greater reduction in number of asthma exacerbations compared to the ineligible group based on eligibility criteria from 1 omalizumab trial (1.52, 95% CI 1.25, 1.8 in eligible vs. 0.47, 95% CI 0.43, 0.52 in ineligible) and from 1 dupilumab trial (1.6, 95% CI 0.92, 2.28 in eligible vs. 0.52, 95% CI 0.38, 0.65 ineligible). Notably, 15 of the 19 trials had fewer than 11 eligible people, limiting additional comparisons. CONCLUSIONS: Fewer than 1 in 10 people in the United States treated with asthma biologics would have been eligible to participate in the trial for the biologic they used. Where comparisons could be made, trial eligible people have a greater reduction in exacerbations.Supplemental data for this article is available online at https://doi.org/10.1080/02770903.2021.2010749 .

Risk of Malignancy with Vedolizumab Versus Tumor Necrosis Factor-α Antagonists in Patients with Inflammatory Bowel Diseases.

BACKGROUND AND AIMS: We conducted a retrospective cohort study comparing the risk of malignancy between patients treated with vedolizumab vs. tumor necrosis factor-α (TNFα) antagonists in patients with inflammatory bowel diseases (IBD). METHODS: Using an administrative claims database, we identified patients with IBD without prior malignancy who were new users of either vedolizumab or TNFα antagonists between 2014-2018, with no prior exposure to either biologic or in preceding 1 y and had insurance coverage for at least 1 y after treatment initiation. We estimated incidence rate of malignancy (solid organ, hematological or skin cancers) in patients treated with vedolizumab and TNFα antagonists, and compared risk using Cox proportional hazard analysis. RESULTS: We included 4807 patients treated with TNFα antagonists (age, 41 ± 15 y, 60% with Crohn's disease [CD]) of whom 65 developed malignancy over 7214 person-year [PY] follow-up (incidence rate [IR], 9.0 per 1000-PY), and 759 patients treated with vedolizumab (age, 46 ± 16y, 42% CD) of whom 11 developed malignancy over 950-PY follow-up (IR, 11.6). No difference was observed in the incidence of malignancy between vedolizumab versus TNFα antagonists (incidence rate ratio, 1.28; 95% CI, 0.61-2.45). After adjusting for age, sex, race, comorbidity burden, disease phenotype and concomitant use of immunomodulators, no difference was observed in time to incident malignancy between vedolizumab versus TNFα antagonists (HR, 1.15; 95% CI, 0.61-2.19). Similar results were observed on stratified analysis by age and concomitant immunomodulators, and after excluding non-melanoma skin cancers. CONCLUSIONS: In an observational study of patients with IBD, no differences were observed in the risk of incident malignancy in patients treated with vedolizumab versus TNFα antagonists.

Characterizing Patient-Clinician Communication in Secure Medical Messages: Retrospective Study.

BACKGROUND: Patient-clinician secure messaging is an important function in patient portals and enables patients and clinicians to communicate on a wide spectrum of issues in a timely manner. With its growing adoption and patient engagement, it is time to comprehensively study the secure messages and user behaviors in order to improve patient-centered care. OBJECTIVE: The aim of this paper was to analyze the secure messages sent by patients and clinicians in a large multispecialty health system at Mayo Clinic, Rochester. METHODS: We performed message-based, sender-based, and thread-based analyses of more than 5 million secure messages between 2010 and 2017. We summarized the message volumes, patient and clinician population sizes, message counts per patient or clinician, as well as the trends of message volumes and user counts over the years. In addition, we calculated the time distribution of clinician-sent messages to understand their workloads at different times of a day. We also analyzed the time delay in clinician responses to patient messages to assess their communication efficiency and the back-and-forth rounds to estimate the communication complexity. RESULTS: During 2010-2017, the patient portal at Mayo Clinic, Rochester experienced a significant growth in terms of the count of patient users and the total number of secure messages sent by patients and clinicians. Three clinician categories, namely "physician-primary care," "registered nurse-specialty," and "physician-specialty," bore the majority of message volume increase. The patient portal also demonstrated growing trends in message counts per patient and clinician. The "nurse practitioner or physician assistant-primary care" and "physician-primary care" categories had the heaviest per-clinician workload each year. Most messages by the clinicians were sent from 7 AM to 5 PM during a day. Yet, between 5 PM and 7 PM, the physicians sent 7.0% (95,785/1,377,006) of their daily messages, and the nurse practitioner or physician assistant sent 5.4% (22,121/408,526) of their daily messages. The clinicians replied to 72.2% (1,272,069/1,761,739) patient messages within 1 day and 90.6% (1,595,702/1,761,739) within 3 days. In 95.1% (1,499,316/1,576,205) of the message threads, the patients communicated with their clinicians back and forth for no more than 4 rounds. CONCLUSIONS: Our study found steady increases in patient adoption of the secure messaging system and the average workload per clinician over 8 years. However, most clinicians responded timely to meet the patients' needs. Our study also revealed differential patient-clinician communication patterns across different practice roles and care settings. These findings suggest opportunities for care teams to optimize messaging tasks and to balance the workload for optimal efficiency.

Risk of Systemic Adverse Events after Intravitreal Bevacizumab, Ranibizumab, and Aflibercept in Routine Clinical Practice.

PURPOSE: Intravitreal anti-vascular endothelial growth factor (VEGF) pharmacotherapy plays a central role in the management of neovascular age-related macular degeneration (nAMD), diabetic retinal disease (DRD), and retinal venous occlusive disease (RVO). Within clinical trials, rates of systemic serious adverse events (SAEs) after anti-VEGF treatment have been low. However, the comparative systemic safety profile of common anti-VEGF agents remains incompletely understood. The goal of this study was to compare the systemic safety of intravitreal bevacizumab, ranibizumab, and aflibercept in real-world practice. DESIGN: Retrospective cohort study. PARTICIPANTS: Using a large U.S. administrative claims database of commercially insured and Medicare Advantage enrollees, we identified adult cohorts receiving initial anti-VEGF injections for nAMD, DRD, and RVO between January 1, 2007, and June 30, 2018. We included patients with 1 year of insurance coverage before initial treatment. METHODS: We compared predefined systemic outcomes between anti-VEGF agents occurring within 180 days of treatment initiation using propensity score-weighted Cox proportional hazards models. Patients were censored upon treatment with a different anti-VEGF medication or termination of health plan coverage. MAIN OUTCOME MEASURES: Primary outcomes were acute myocardial infarction (MI), acute cerebrovascular disease (CVD), major bleeding, and all-cause hospitalization. RESULTS: A total of 87 844 patients received initial anti-VEGF injections for nAMD, DRD, and RVO between January 1, 2007, and June 30, 2018 (69 007 bevacizumab; 10 895 ranibizumab; 7942 aflibercept). Postinjection 180-day event rates per 100 patients for MI, CVD, major bleeding, and all-cause hospitalization were similar for bevacizumab (0.64, 0.59, 0.34, and 10.41, respectively), ranibizumab (0.62, 0.53, 0.40, and 9.44, respectively), and aflibercept (0.63, 0.60, 0.20, and 9.88, respectively). No differences were identified for the risk of MI, CVD, major bleeding, or all-cause hospitalization when comparing the risk-adjusted effect of treatment initiation with bevacizumab versus ranibizumab (hazard ratio [HR], 0.96 [95% confidence interval {CI}, 0.74-1.25]; HR, 1.04 [95% CI, 0.78-1.38]; HR, 0.85 [95% CI, 0.61-1.19]; HR, 1.03 [95% CI, 0.96-1.10], all P > 0.05), bevacizumab versus aflibercept (HR, 0.95 [95% CI, 0.68-1.33], HR, 0.99 [95% CI, 0.71-1.38], HR, 1.02 [95% CI, 0.60-1.74], HR, 1.01 [95% CI, 0.93-1.10], all P > 0.05), or aflibercept versus ranibizumab (HR, 0.91 [95% CI, 0.62-1.35], HR, 1.12 [95% CI, 0.74-1.69], HR, 0.96 [95% CI, 0.53-1.73], HR, 1.02 [95% CI, 0.92-1.13], all P > 0.05). CONCLUSIONS: We observed no differences in the risk of acute MI, CVD, major bleeding, or all-cause hospitalization after treatment initiation with intravitreal bevacizumab, ranibizumab, or aflibercept during routine clinical practice.

Optimizing Huddle Engagement Through Leadership and Problem Solving Within Primary Care: Results from a Cluster-Randomized Trial.

BACKGROUND: Leaders play a crucial role in implementing and sustaining changes in clinical practice, yet there is limited evidence on the strategies to engage them in team problem solving and communication. OBJECTIVE: Examine the impact of an intervention focused on facilitating leadership during daily huddles on optimizing team-based care and improving outcomes. DESIGN: Cluster-randomized trial using intention-to-treat analysis to measure the effects of the intervention (n = 13 teams) compared with routine practice (n = 16 teams). PARTICIPANTS: Twenty-nine primary care clinics affiliated with a large integrated health system in the upper Midwest; representing differing practice types and geographic settings. INTERVENTION: Full-day leadership training retreat for team leaders to facilitate of care team huddles. Biweekly coaching calls and two site visits with an assigned coach. MAIN MEASURES: Primary outcomes of team development and function were collected, pre- and post-intervention using surveys. Patient satisfaction and quality outcomes were compared pre- and post-intervention as secondary outcomes. Leadership engagement and adherence to the intervention were also assessed. KEY RESULTS: A total of 279 pre-intervention and 272 post-intervention surveys were completed. We found no impact on team development (- 0.98, 95% CI (- 3.18, 1.22)), improved team credibility (0.18, 95% CI (0.00, 0.35)), but worse psychological safety (- 0.19, 95% CI (- 0.38, 0.00)). No differences were observed in patient satisfaction; however, results were mixed among quality outcomes. Post hoc analysis within the intervention group showed higher adherence to the intervention was associated with improvement in team coordination (0.47, 95% CI (0.18, 0.76)), credibility (0.28, 95% CI (0.02, 0.53)), team learning (0.42, 95% CI (0.10, 0.74)), and knowledge creation (0.74, 95% CI (0.35, 1.13)) compared to teams that were less engaged. CONCLUSIONS: Results of this evaluation showed that leadership training and facilitation were not associated with better team functioning. Additional components to the intervention tested may be necessary to enhance team functioning. TRIAL REGISTRATION: Clinicaltrials.gov Identifier NCT03062670. Registration Date: February 23, 2017. URL: https://clinicaltrials.gov/ct2/show/NCT03062670.

Persistence of asthma biologic use in a US claims database.

BACKGROUND: Little is known on the persistence of asthma biologic use in clinical practice. OBJECTIVE: To evaluate the persistence of asthma biologic use and time to clinical response in clinical practice. METHODS: A cohort of people with asthma who used at least 1 asthma biologic was constructed using data from 2003 to 2019 in the OptumLabs Data Warehouse. Treatment persistence was defined by the length of time that a person continuously used an asthma biologic, allowing for a lapse in use up to 4 months before confirming that a person stopped. Clinical response to treatment (defined as a decline in asthma exacerbations of at least 50% compared with the 6 months before starting an asthma biologic) was described over time and in relation to biologic persistence. RESULTS: There were 9575 people who had at least 1 episode of asthma biologic use. There were 5319 people (64%, 95% confidence interval, 63%-65%) who completed 6 months or more on an asthma biologic and 3284 (45%, 95% confidence interval, 44%-46%) who completed 12 months or more. Of people with 1 or more asthma exacerbation 6 months before index biologic use, 63%, 76%, 80%, and 81% realized a 50% or more reduction in postindex asthma exacerbations in the first 6 months, 6 to 12 months, 12 to 18 months, and 18 to 24 months, respectively. CONCLUSION: Between 48% and 64% of people remained on an asthma biologic for 6 months or more after first use. Most people who achieved a reduction in asthma exacerbations did so in the first 6 months of treatment.

Drug labeling changes and pediatric hematology/oncology prescribing: Measuring the impact of U.S. legislation.

BACKGROUND/AIMS: The Pediatric Research Equity Act and Best Pharmaceuticals for Children Act are intended to promote the conduct of clinical trials that generate pediatric-specific evidence about drug safety and efficacy. This study assesses the quality of evidence generated through Pediatric Research Equity Act-mandated and Best Pharmaceuticals for Children Act-incentivized clinical trials of hematology/oncology drugs and characterizes subsequent changes in pediatric drug utilization rates. METHODS: Trial characteristics (blinding, randomization, and comparator group) were determined for clinical trials that supported pediatric label changes. Using data from OptumLabs® Data Warehouse, a de-identified administrative claims database, we calculated pediatric utilization rates for each drug. We calculated monthly utilization rates from January 2003 (or from the first month in which data were available) to December 2018. RESULTS: We identified 11 hematology/oncology drugs that underwent pediatric label changes under the Pediatric Research Equity Act Pediatric Research Equity Act and/or Best Pharmaceuticals for Children Act, and we identified 15 trials supporting these changes. Of these trials, 36% (5/14) were randomized, 31% (4/13) were blinded, and 36% (5/14) used a comparator group. A median of 49 children (interquartile range 29.5) received the drug under investigation across these trials. Pediatric label changes were not associated with subsequent changes in pediatric drug utilization. Although some drugs saw increased pediatric use after gaining new pediatric indications, this pattern was not consistently observed. In addition, there was no evidence to suggest that drugs were utilized less frequently after they failed to receive pediatric indications. CONCLUSIONS: Clinical trials of hematology/oncology drugs conducted under the Pediatric Research Equity Act Pediatric Research Equity Act and Best Pharmaceuticals for Children Act generally have low methodological rigor, and the resulting label changes are not consistently associated with changes in pediatric utilization. Alternative regulatory strategies and study designs may be necessary to maximize the impact of newly generated knowledge on drug utilization.

Impact of High Deductible Health Plans on Diabetes Care Quality and Outcomes: Systematic Review.

OBJECTIVE: To provide a review of the impact of high deductible health plans (HDHPs) on the utilizations of services required for optimal management of diabetes and subsequent health outcomes. METHODS: Systematic literature review of studies published between January 1, 2000, and May 7, 2021, was conducted that examined the impact of HDHP on diabetes monitoring (eg, recommended laboratory and surveillance testing), routine care (eg, ambulatory appointments), medication management (eg, medication initiation, adherence), and acute health care utilization (eg, emergency department visits, hospitalizations, incident complications). RESULTS: Of the 303 reviewed articles, 8 were relevant. These studies demonstrated that HDHPs lower spending at the expense of reduced high-value diabetes monitoring, routine care, and medication adherence, potentially contributing to the observed increases in acute health care utilization. Additionally, patient out-of-pocket costs for recommended screenings doubled, and total health care expenditures increased by 49.4% for HDHP enrollees compared with enrollees in traditional health plans. Reductions in disease monitoring and routine care and increases in acute health care utilization were greatest in lower-income patients. None of the studies examined the impact of HDHPs on access to diabetes self-management education, technology use, or glycemic control. CONCLUSION: Although HDHPs reduce some health care utilization and costs, they appear to do so at the expense of limiting high-value care and medication adherence. Policymakers, providers, and payers should be more cognizant of the potential for negative consequences of HDHPs on patients' health.

Uptake of evidence by physicians: De-adoption of erythropoiesis-stimulating agents after the TREAT trial.

BACKGROUND: Variation in de-adoption of ineffective or unsafe treatments is not well-understood. We examined de-adoption of erythropoiesis-stimulating agents (ESA) in anemia treatment among patients with chronic kidney disease (CKD) following new clinical evidence of harm and ineffectiveness (the TREAT trial) and the FDA's revision of its safety warning. METHOD: We used a segmented regression approach to estimate changes in use of epoetin alfa (EPO) and darbepoetin alfa (DPO) in the commercial, Medicare Advantage (MA) and Medicare fee-for-service (FFS) populations. We also examined how changes in both trends and levels of use were associated with physicians' characteristics. RESULTS: Use of DPO and EPO declined over the study period. There were no consistent changes in DPO trend across insurance groups, but the level of DPO use decreased right after the FDA revision in all groups. The decline in EPO use trend was faster after the TREAT trial for all groups. Nephrologists were largely more responsive to evidence than primary care physicians. Differences by physician's gender, and age were not consistent across insurance populations and types of ESA. CONCLUSIONS: Physician specialty has a dominant role in prescribing decision, and that specializations with higher use of treatment (nephrologists) were more responsive to new evidence of unsafety and ineffectiveness.

Outcomes for hospitalized patients with idiopathic pulmonary fibrosis treated with antifibrotic medications.

BACKGROUND: Idiopathic Pulmonary Fibrosis is a chronic, progressive interstitial lung disease for which there is no cure. However, lung function decline, hospitalizations, and mortality may be reduced with the use of the antifibrotic medications, nintedanib and pirfenidone. Historical outcomes for hospitalized patients with Idiopathic Pulmonary Fibrosis are grim; however there is a paucity of data since the approval of nintedanib and pirfenidone for treatment. In this study, we aimed to determine the effect of nintedanib and pirfenidone on mortality following respiratory-related hospitalizations, intensive care unit (ICU) admission, and mechanical ventilation. METHODS: Using a large U.S. insurance database, we created a one-to-one propensity score matched cohort of patients with idiopathic pulmonary fibrosis treated and untreated with an antifibrotic who underwent respiratory-related hospitalization between January 1, 2015 and December 31, 2018. Mortality was evaluated at 30 days and end of follow-up (up to 2 years). Subgroup analyses were performed for all patients receiving treatment in an ICU and those receiving invasive and non-invasive mechanical ventilation during the index hospitalization. RESULTS: Antifibrotics were not observed to effect utilization of mechanical ventilation or ICU treatment during the index admission or effect mortality at 30-days. If patients survived hospitalization, mortality was reduced in the treated cohort compared to the untreated cohort when followed up to two years (20.1% vs 47.8%). CONCLUSIONS: Treatment with antifibrotic medications does not appear to directly improve 30-day mortality during or after respiratory-related hospitalizations. Post-hospital discharge, however, ongoing antifibrotic treatment was associated with improved long-term survival.

Association between facility volume and mortality of patients with classic Hodgkin lymphoma.

BACKGROUND: Prior studies in oncology have shown that a higher annual facility patient volume is associated with reduced mortality. Because classic Hodgkin lymphoma is uncommon but highly curable, this study used the National Cancer Database (2003-2014) to analyze whether such a relationship exists for this disease. METHODS: The facilities were classified by quartiles, and random intercepts were used to account for clustering of patients within facilities. A Cox regression model was used to determine the volume-outcome relationship. RESULTS: There were 47,633 patients with classic Hodgkin lymphoma treated at 1310 facilities. The first quartile (Q1), which included 58.4% of the facilities, treated 3 or fewer patients per year, whereas the fourth quartile (Q4), which included 5.9% of the facilities, treated more than 9 patients per year. Compared with the patients treated at Q4 facilities, those treated at lower quartile facilities had a higher risk of death (hazard ratio for the third quartile [HR], 1.19; 95% confidence interval [CI], 1.1-1.29; HR for the second quartile, 1.28; 95% CI, 1.19-1.38; HR for Q1, 1.29; 95% CI, 1.2-1.39) after adjustments for all other factors (P < .0001). Compared with facilities treating 10 patients per year, facilities treating 40 patients per year had approximately 27% lower overall mortality rates. CONCLUSIONS: Patients with classic Hodgkin lymphoma treated at high-volume centers had lower overall mortality than those treated at lower volume centers. Because this is a highly curable malignancy, such differences may suggest a benefit from referral to higher volume facilities or the emulation of their care models.

Risk of Gastrointestinal Bleeding Increases With Combinations of Antithrombotic Agents and Patient Age.

BACKGROUND & AIMS: The safety of different antithrombotic strategies for patients with 1 or more indication for antithrombotic drugs has not been determined. We investigated the risk and time frame for gastrointestinal bleeding (GIB) in patients prescribed different antithrombotic regimens. We proposed that risk would increase over time and with combination regimens, especially among elderly patients. METHODS: We performed a retrospective analysis of nationwide claims data from privately insured and Medicare Advantage enrollees who received anticoagulant and/or antiplatelet agents from October 1, 2010, through May 31, 2017. Patients were stratified by their prescriptions (anticoagulant alone, antiplatelet alone, or a combination) and by their primary diagnosis (atrial fibrillation, ischemic heart disease, or venous thromboembolism). The 1-year GIB risk was estimated using parametric time-to-event survival models and expressed as annualized risk and number needed to harm (NNH). RESULTS: Our final analysis included 311,211 patients (mean ages, 67 years for monotherapy and 69.8 years for combination antithrombotic therapy). There was no significant difference in the proportion of patients with bleeding after anticoagulant or antiplatelet monotherapy (∼3.5%/year). Combination antithrombotic therapy increased GIB risk compared with anticoagulant (NNH, 29) or antiplatelet (NNH, 31) monotherapy, regardless of the patients' diagnosis or time point analyzed. Advancing age was associated with increasing 1-year probability of GIB. Patients prescribed combination therapy were at the greatest risk for GIB, especially after the age of 75 years (GIB occurred in 10%-17.5% of patients/y). CONCLUSIONS: In an analysis of nationwide insurance and Medicare claims data, we found GIB to occur in a higher proportion of patients prescribed combinations of anticoagulant and antiplatelet agents compared with monotherapy. Among all drug exposure categories and cardiovascular conditions, the risk of GIB increased with age, especially among patients older than 75 years.

ECG AI-Guided Screening for Low Ejection Fraction (EAGLE): Rationale and design of a pragmatic cluster randomized trial.

BACKGROUND: A deep learning algorithm to detect low ejection fraction (EF) using routine 12-lead electrocardiogram (ECG) has recently been developed and validated. The algorithm was incorporated into the electronic health record (EHR) to automatically screen for low EF, encouraging clinicians to obtain a confirmatory transthoracic echocardiogram (TTE) for previously undiagnosed patients, thereby facilitating early diagnosis and treatment. OBJECTIVES: To prospectively evaluate a novel artificial intelligence (AI) screening tool for detecting low EF in primary care practices. DESIGN: The EAGLE trial is a pragmatic two-arm cluster randomized trial (NCT04000087) that will randomize >100 clinical teams (i.e., clusters) to either intervention (access to the new AI screening tool) or control (usual care) at 48 primary care practices across Minnesota and Wisconsin. The trial is expected to involve approximately 400 clinicians and 20,000 patients. The primary endpoint is newly discovered EF ≤50%. Eligible patients will include adults who undergo ECG for any reason and have not been previously diagnosed with low EF. Data will be pulled from the EHR, and no contact will be made with patients. A positive deviance qualitative study and a post-implementation survey will be conducted among select clinicians to identify facilitators and barriers to using the new screening report. SUMMARY: This trial will examine the effectiveness of the AI-enabled ECG for detection of asymptomatic low EF in routine primary care practices and will be among the first to prospectively evaluate the value of AI in real-world practice. Its findings will inform future implementation strategies for the translation of other AI-enabled algorithms.

Response to Propoxyphene Market Withdrawal: Analgesic Substitutes, Doses, and Adverse Events.

OBJECTIVE: Experts cautioned that patients affected by the November 2010 withdrawal of the opioid analgesic propoxyphene might receive riskier prescriptions. To explore this, we compared drug receipts and outcomes among propoxyphene users before and aftermarket withdrawal. STUDY DESIGN: Using OptumLabs data, we studied 3 populations: commercial, Medicare Advantage (MA) aged (age 65+ y) and MA disabled (age below 65 y) enrollees. The exposed enrollees received propoxyphene in the 3 months before market withdrawal (n=13,622); historical controls (unexposed) received propoxyphene 1 year earlier (n=9971). Regression models estimated daily milligrams morphine equivalent (MME), daily prescription acetaminophen dose, potentially toxic acetaminophen doses, nonopioid prescription analgesics receipt, emergency room visits, and diagnosed falls, motor vehicle accidents, and hip fractures. PRINCIPAL FINDINGS: Aged MA enrollees illustrate the experience of all 3 populations examined. Following the market withdrawal, propoxyphene users in the exposed cohort experienced an abrupt decline of 69% in average daily MME, compared with a 14% decline in the unexposed. Opioids were discontinued by 34% of the exposed cohort and 18% of the unexposed. Tramadol and hydrocodone were the most common opioids substituted for propoxyphene. The proportion of each group receiving ≥4 g of prescription acetaminophen per day decreased from 12% to 2% in the exposed group but increased from 6% to 8% among the unexposed. Adverse events were rare and not significantly different in exposed versus unexposed groups. CONCLUSIONS: After propoxyphene market withdrawal, many individuals experienced abrupt discontinuation of opioids. Policymakers might consider supporting appropriate treatment transitions and monitoring responses following drug withdrawals.

Use of Potentially Nephrotoxic Medications by U.S. Adults with Chronic Kidney Disease: NHANES, 2011-2016.

BACKGROUND: People with chronic kidney disease (CKD) are at risk for adverse events and/or CKD progression with use of renally eliminated or nephrotoxic medications. OBJECTIVE: To examine the prevalence of potentially inappropriate medication (PIM) use by U.S. adults by CKD stage and self-reported CKD awareness. DESIGN: Cross-sectional analysis of National Health and Nutrition Examination Surveys, 2011-2016 PARTICIPANTS: Non-pregnant adults with stages 3a (eGFR 45-59 mL/min/1.73 m2), 3b (eGFR 30-44), or 4-5 (eGFR < 30) CKD, stratified as CKD-aware/unaware. MAIN MEASURES: PIMs were identified on the basis of KDIGO guidelines, label information, and literature review. We calculated proportions using any and individual PIMs, assessing for differences over CKD awareness within each CKD stage. Analyses were adjusted for age, sex, race/ethnicity, education, comorbidities, and insurance type. KEY RESULTS: Adjusted proportions of U.S. adults taking any PIM(s) exceeded 50% for all CKD stages and awareness categories, and were highest among CKD-unaware patients with stages 4-5 CKD: 66.6% (95% CI, 55.5-77.8). Proton pump inhibitors, opioids, metformin, sulfonylureas, and non-steroidal anti-inflammatory drugs (NSAIDs) were all used frequently across CKD stages. NSAIDs were used less frequently when CKD-aware by patients with stage 3a CKD (2.2% [95% CI, - 0.3 to 4.7] vs. 10.7% [95% CI, 7.6 to 13.8]) and stages 4-5 CKD (0.8% [95% CI, - 0.9 to 2.5] vs. 16.5% [95% CI, 4.0 to 29.0]). Metformin was used less frequently when CKD-aware by patients with stage 3b CKD (8.1% [95% CI, 0.3-15.9] vs. 26.5% [95% CI, 17.4-35.7]) and stages 4-5 CKD (none vs. 20.8% [95% CI, 1.8-39.8]). The impact of CKD awareness was statistically significant after correction for multiple comparisons only for NSAIDs in stage 3a CKD. CONCLUSIONS: PIMs are frequently used by people with CKD, with some impact of CKD awareness on NSAID and metformin use. This may lead to adverse outcomes or hasten CKD progression, reinforcing the need for improved medication management among people with CKD.