Assays of Variant Effect and Automated Patch Clamping Improve KCNH2-LQTS Variant Classification and Cardiac Event Risk Stratification.

BACKGROUND: Long QT syndrome is a lethal arrhythmia syndrome, frequently caused by rare loss-of-function variants in the potassium channel encoded by KCNH2. Variant classification is difficult, often because of lack of functional data. Moreover, variant-based risk stratification is also complicated by heterogenous clinical data and incomplete penetrance. Here we sought to test whether variant-specific information, primarily from high-throughput functional assays, could improve both classification and cardiac event risk stratification in a large, harmonized cohort of KCNH2 missense variant heterozygotes. METHODS: We quantified cell-surface trafficking of 18 796 variants in KCNH2 using a multiplexed assay of variant effect (MAVE). We recorded KCNH2 current density for 533 variants by automated patch clamping. We calibrated the strength of evidence of MAVE data according to ClinGen guidelines. We deeply phenotyped 1458 patients with KCNH2 missense variants, including QTc, cardiac event history, and mortality. We correlated variant functional data and Bayesian long QT syndrome penetrance estimates with cohort phenotypes and assessed hazard ratios for cardiac events. RESULTS: Variant MAVE trafficking scores and automated patch clamping peak tail currents were highly correlated (Spearman rank-order ρ=0.69; n=433). The MAVE data were found to provide up to pathogenic very strong evidence for severe loss-of-function variants. In the cohort, both functional assays and Bayesian long QT syndrome penetrance estimates were significantly predictive of cardiac events when independently modeled with patient sex and adjusted QT interval (QTc); however, MAVE data became nonsignificant when peak tail current and penetrance estimates were also available. The area under the receiver operator characteristic curve for 20-year event outcomes based on patient-specific sex and QTc (area under the curve, 0.80 [0.76-0.83]) was improved with prospectively available penetrance scores conditioned on MAVE (area under the curve, 0.86 [0.83-0.89]) or attainable automated patch clamping peak tail current data (area under the curve, 0.84 [0.81-0.88]). CONCLUSIONS: High-throughput KCNH2 variant MAVE data meaningfully contribute to variant classification at scale, whereas long QT syndrome penetrance estimates and automated patch clamping peak tail current measurements meaningfully contribute to risk stratification of cardiac events in patients with heterozygous KCNH2 missense variants.

Vigorous Exercise in Patients With Congenital Long QT Syndrome: Results of the Prospective, Observational, Multinational LIVE-LQTS Study.

BACKGROUND: Whether vigorous exercise increases risk of ventricular arrhythmias for individuals diagnosed and treated for congenital long QT syndrome (LQTS) remains unknown. METHODS: The National Institutes of Health-funded LIVE-LQTS study (Lifestyle and Exercise in the Long QT Syndrome) prospectively enrolled individuals 8 to 60 years of age with phenotypic and/or genotypic LQTS from 37 sites in 5 countries from May 2015 to February 2019. Participants (or parents) answered physical activity and clinical events surveys every 6 months for 3 years with follow-up completed in February 2022. Vigorous exercise was defined as ≥6 metabolic equivalents for >60 hours per year. A blinded Clinical Events Committee adjudicated the composite end point of sudden death, sudden cardiac arrest, ventricular arrhythmia treated by an implantable cardioverter defibrillator, and likely arrhythmic syncope. A National Death Index search ascertained vital status for those with incomplete follow-up. A noninferiority hypothesis (boundary of 1.5) between vigorous exercisers and others was tested with multivariable Cox regression analysis. RESULTS: Among the 1413 participants (13% <18 years of age, 35% 18-25 years of age, 67% female, 25% with implantable cardioverter defibrillators, 90% genotype positive, 49% with LQT1, 91% were treated with beta-blockers, left cardiac sympathetic denervation, and/or implantable cardioverter defibrillator), 52% participated in vigorous exercise (55% of these competitively). Thirty-seven individuals experienced the composite end point (including one sudden cardiac arrest and one sudden death in the nonvigorous group, one sudden cardiac arrest in the vigorous group) with overall event rates at 3 years of 2.6% in the vigorous and 2.7% in the nonvigorous exercise groups. The unadjusted hazard ratio for experience of events for the vigorous group compared with the nonvigorous group was 0.97 (90% CI, 0.57-1.67), with an adjusted hazard ratio of 1.17 (90% CI, 0.67-2.04). The upper 95% one-sided confidence level extended beyond the 1.5 boundary. Neither vigorous or nonvigorous exercise was found to be superior in any group or subgroup. CONCLUSIONS: Among individuals diagnosed with phenotypic and/or genotypic LQTS who were risk assessed and treated in experienced centers, LQTS-associated cardiac event rates were low and similar between those exercising vigorously and those not exercising vigorously. Consistent with the low event rate, CIs are wide, and noninferiority was not demonstrated. These data further inform shared decision-making discussions between patient and physician about exercise and competitive sports participation. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02549664.

An international multicenter cohort study on implantable cardioverter-defibrillators for the treatment of symptomatic children with catecholaminergic polymorphic ventricular tachycardia.

BACKGROUND: Catecholaminergic polymorphic ventricular tachycardia (CPVT) may cause sudden cardiac death (SCD) despite medical therapy. Therefore, implantable cardioverter-defibrillators (ICDs) are commonly advised. However, there is limited data on the outcomes of ICD use in children. OBJECTIVE: The purpose of this study was to compare the risk of arrhythmic events in pediatric patients with CPVT with and without an ICD. METHODS: We compared the risk of SCD in patients with RYR2 (ryanodine receptor 2) variants and phenotype-positive symptomatic CPVT patients with and without an ICD who were younger than 19 years and had no history of sudden cardiac arrest at phenotype diagnosis. The primary outcome was SCD; secondary outcomes were composite end points of SCD, sudden cardiac arrest, or appropriate ICD shocks with or without arrhythmic syncope. RESULTS: The study included 235 patients, 73 with an ICD (31.1%) and 162 without an ICD (68.9%). Over a median follow-up of 8.0 years (interquartile range 4.3-13.4 years), SCD occurred in 7 patients (3.0%), of whom 4 (57.1%) were noncompliant with medications and none had an ICD. Patients with ICD had a higher risk of both secondary composite outcomes (without syncope: hazard ratio 5.85; 95% confidence interval 3.40-10.09; P < .0001; with syncope: hazard ratio 2.55; 95% confidence interval 1.50-4.34; P = .0005). Thirty-one patients with ICD (42.5%) experienced appropriate shocks, 18 (24.7%) inappropriate shocks, and 21 (28.8%) device-related complications. CONCLUSION: SCD events occurred only in patients without an ICD and mostly in those not on optimal medical therapy. Patients with an ICD had a high risk of appropriate and inappropriate shocks, which may be reduced with appropriate device programming. Severe ICD complications were common, and risks vs benefits of ICDs need to be considered.

Measuring Local-Area Racial Segregation for Medicare Hospital Admissions.

Importance: Considerable racial segregation exists in US hospitals that cannot be explained by where patients live. Approaches to measuring such segregation are limited. Objective: To measure how and where sorting of older Black patients to different hospitals occurs within the same health care market. Design, Setting, and Participants: This retrospective cross-sectional study used 2019 Medicare claims data linked to geographic data. Hospital zip code markets were based on driving time. The local hospital segregation (LHS) index was defined as the difference between the racial composition of a hospital's admissions and the racial composition of the hospital's market. Assessed admissions were among US Medicare fee-for-service enrollees aged 65 or older living in the 48 contiguous states with at least 1 hospitalization in 2019 at a hospital with at least 200 hospitalizations. Data were analyzed from November 2022 to January 2024. Exposure: Degree of residential segregation, ownership status, region, teaching hospital designation, and disproportionate share hospital status. Main Outcomes and Measures: The LHS index by hospital and a regional LHS index by hospital referral region. Results: In the sample of 1991 acute care hospitals, 4 870 252 patients (mean [SD] age, 77.7 [8.3] years; 2 822 006 [56.0%] female) were treated, including 11 435 American Indian or Alaska Native patients (0.2%), 129 376 Asian patients (2.6%), 597 564 Black patients (11.9%), 395 397 Hispanic patients (7.8), and 3 818 371 White patients (75.8%). In the sample, half of hospitalizations among Black patients occurred at 235 hospitals (11.8% of all hospitals); 878 hospitals (34.4%) exhibited a negative LHS score (ie, admitted fewer Black patients relative to their market area) while 1113 hospitals (45.0%) exhibited a positive LHS (ie, admitted more Black patients relative to their market area); of all hospitals, 79.4% exhibited racial admission patterns significantly different from their market. Hospital-level LHS was positively associated with government hospital status (coefficient, 0.24; 95% CI, 0.10 to 0.38), while New York, New York; Chicago, Illinois; and Detroit, Michigan, hospital referral regions exhibited the highest regional LHS measures, with hospital referral region LHS scores of 0.12, 0.16, and 0.21, respectively. Conclusions and Relevance: In this cross-sectional study, a novel measure of LHS was developed to quantify the extent to which hospitals were admitting a representative proportion of Black patients relative to their market areas. A better understanding of hospital choice within neighborhoods would help to reduce racial inequities in health outcomes.

Public versus Private Care in the Military Health System: Evidence From Low Back Pain Patients.

INTRODUCTION: There is a longstanding debate about whether health care is more efficiently provided by the public or private sector. The debate is particularly relevant to the Military Health System (MHS), which delivers care through a combination of publicly funded federal facilities and privately contracted providers. This study compares outcomes, treatments, and costs for MHS patients obtaining care for low back pain (LBP) from public versus private providers. MATERIALS AND METHODS: A retrospective cohort study was completed using TRICARE Prime claims data from April 2015 to December 2018. The cohort was identified using International Classification of Diseases Ninth Revision and Tenth Revision diagnostic codes and then followed for 12 months after the index diagnosis to assess treatments, outcomes, and costs. Claims were classified as originating from either public or private providers. The primary outcome measure was resolution of LBP, defined as an absence of LBP diagnoses during the 6-to-12-month window following the index event. Instrumental variable models were used to assess the impact of care setting (i.e., private versus public), conditioning on the covariates. A regional measure of the fraction of private care was used as an instrument. RESULTS: Resolution of LBP was achieved for 79.7% of 144,866 patients in the cohort. No significant association was found between resolution of LBP and fraction of privately provided care. Higher fraction of private care was associated with a greater likelihood of opioid treatments (odds ratio, 1.22; 95% CI, 1.02-1.46) and a lower likelihood of benzodiazepine (odds ratio, 0.56; 95% CI, 0.45-0.70) and physical therapy (odds ratio 0.55; 95% CI, 0.42-0.74) treatments; manual therapy was not significantly associated with the fraction of private care. There was a significant negative association between the fraction of private care and cost (coefficient -0.27; 95% CI, -0.44, -0.10). CONCLUSION: This study found that privately provided care was associated with significantly higher opioid prescribing, less use of benzodiazepines and physical therapy, and lower costs. No systematic differences in outcomes (as measured by resolved cases) were identified. The findings suggest that publicly funded health care within the MHS context can attain quality comparable to privately provided care, although differences in treatment choices and costs point to possibilities for improved care within both systems.

Telehealth Trends and Hypertension Management Among Rural and Medicaid Patients After COVID-19.

Objective: Examine the associations between rurality and low income with primary care telehealth utilization and hypertension outcomes across multiple years pre- and post-COVID-19 pandemic onset. Methods: We compiled electronic health record data from the mixed rural/urban Dartmouth Health system in New Hampshire, United States, on patients with pre-existing hypertension or diabetes receiving primary care in the period before (January 2018-February 2020) and after the transition period to telehealth during the COVID-19 Pandemic (October 2020-December 2022). Stratifying by rurality and Medicaid enrollment, we examined changes in synchronous (office and telehealth visits, including audio/video use) and asynchronous (patient portal or telephone message) utilization, and control of mean systolic blood pressure (SBP) <140. Results: Analysis included 46,520 patients, of whom 8.2% were Medicaid enrollees, 42.7% urban residents. Telehealth use rates were 12% for rural versus 6.4% for urban, and 15% for Medicaid versus 8.4% non-Medicaid. The overall postpandemic telehealth visit rate was 0.29 per patient per year. Rural patients had a larger increase in telehealth use (additional 0.21 per year, 95% CI, 0.19-0.23) compared with urban, as did Medicaid (0.32, 95% CI 0.29-0.36) compared with non-Medicaid. Among the 38,437 patients with hypertension, SBP control worsened from 83% to 79% of patients across periods. In multivariable analysis, rurality corresponded to worsened control rates compared with urban (additional 2.4% decrease, 95% CI 2.1-2.8%); Medicaid and telehealth use were not associated with worsened control. Conclusions: Telehealth expansion enabled a higher shift to telehealth for rural and low-income patients without impairing hypertension management.

Genetic Testing Yield and Clinical Characteristics of Hypertrophic Cardiomyopathy in Understudied Ethnic Groups: Insights From a New Zealand National Registry.

BACKGROUND: Aotearoa/New Zealand has a multiethnic population. Patients with hypertrophic cardiomyopathy (HCM) are enrolled in the national Cardiac Inherited Diseases Registry New Zealand. Here, we report the characteristics of Cardiac Inherited Diseases Registry New Zealand HCM probands with and without pathogenic or likely pathogenic (P/LP) genetic variants for HCM, and assess genetic testing yield and variant spectrum by self-identified ethnicity. METHODS: Probands with HCM and enrolled in Cardiac Inherited Diseases Registry New Zealand who have undergone clinical genetic testing over a 17-year period were included. Clinical data, family history, and genetic test results were analyzed. RESULTS: Of 336 probands, 121 (36%) were women, 220 (66%) were European ethnicity, 41 (12%) were Maori, 26 (8%) were Pacific people, and 49 (15%) were other ethnicities. Thirteen probands (4%) presented with sudden death and 19 (6%) with cardiac arrest. A total of 134 (40%) had a P/LP variant identified; most commonly in the MYBPC3 gene (60%) followed by the MYH7 gene (24%). A P/LP variant was identified in 27% of Maori or Pacific probands versus 43% European or other ethnicity probands (P=0.022); 16% of Maori or Pacific probands had a variant of uncertain significance identified, compared with 9% of European or other ethnicity probands (P=0.092). Women more often had a P/LP variant identified than men (48% versus 35%; P=0.032), and variant-positive probands were younger at clinical diagnosis than variant of uncertain significance/variant-negative probands (39±17 versus 50±17 years; P<0.001) and more likely to have experienced cardiac arrest or sudden death events over their lifetime (P=0.002). CONCLUSIONS: Carriage of a P/LP variant in HCM probands is associated with presentation at younger age, and cardiac arrest or sudden death events. Maori or Pacific probands were less likely to have a P/LP variant identified than European or other ethnicity probands.

Multiplexed Assays of Variant Effect and Automated Patch-clamping Improve KCNH2-LQTS Variant Classification and Cardiac Event Risk Stratification.

Background: Long QT syndrome (LQTS) is a lethal arrhythmia syndrome, frequently caused by rare loss-of-function variants in the potassium channel encoded by KCNH2. Variant classification is difficult, often owing to lack of functional data. Moreover, variant-based risk stratification is also complicated by heterogenous clinical data and incomplete penetrance. Here, we sought to test whether variant-specific information, primarily from high-throughput functional assays, could improve both classification and cardiac event risk stratification in a large, harmonized cohort of KCNH2 missense variant heterozygotes. Methods: We quantified cell-surface trafficking of 18,796 variants in KCNH2 using a Multiplexed Assay of Variant Effect (MAVE). We recorded KCNH2 current density for 533 variants by automated patch clamping (APC). We calibrated the strength of evidence of MAVE data according to ClinGen guidelines. We deeply phenotyped 1,458 patients with KCNH2 missense variants, including QTc, cardiac event history, and mortality. We correlated variant functional data and Bayesian LQTS penetrance estimates with cohort phenotypes and assessed hazard ratios for cardiac events. Results: Variant MAVE trafficking scores and APC peak tail currents were highly correlated (Spearman Rank-order ρ = 0.69). The MAVE data were found to provide up to pathogenic very strong evidence for severe loss-of-function variants. In the cohort, both functional assays and Bayesian LQTS penetrance estimates were significantly predictive of cardiac events when independently modeled with patient sex and adjusted QT interval (QTc); however, MAVE data became non-significant when peak-tail current and penetrance estimates were also available. The area under the ROC for 20-year event outcomes based on patient-specific sex and QTc (AUC 0.80 [0.76-0.83]) was improved with prospectively available penetrance scores conditioned on MAVE (AUC 0.86 [0.83-0.89]) or attainable APC peak tail current data (AUC 0.84 [0.81-0.88]). Conclusion: High throughput KCNH2 variant MAVE data meaningfully contribute to variant classification at scale while LQTS penetrance estimates and APC peak tail current measurements meaningfully contribute to risk stratification of cardiac events in patients with heterozygous KCNH2 missense variants.

Ebstein's anomaly: an electrophysiological perspective.

Ebstein's anomaly of the tricuspid valve (EA) is an uncommon congenital cardiac malformation. It can present with atrioventricular tachycardia (AVRT), atrioventricular nodal re-entrant tachycardia (AVNRT), atrial arrhythmias, and rarely with ventricular tachycardia. The 12-lead electrocardiogram (ECG) is critically important and often diagnostic even prior to an electrophysiology study (EPS). Due to its complex anatomy, it poses particular challenges for mapping and ablation, even for an experienced electrophysiologist. In this review, we aim to provide insight into the electrophysiological perspective of EA and an in-depth analysis of the various arrhythmias encountered in diverse clinical scenarios.

The role of comorbidities, medications, and social determinants of health in understanding urban-rural outcome differences among patients with heart failure.

PURPOSE: There is now a 20% disparity in all-cause, excess deaths between urban and rural areas, much of which is driven by disparities in cardiovascular death. We sought to explain the sources of these disparities for Medicare beneficiaries with heart failure with reduced ejection fraction (HFrEF). METHODS: Using a sample of Medicare Parts A, B, and D, we created a cohort of 389,528 fee-for-service beneficiaries with at least 1 heart failure hospitalization from 2008 to 2017. The primary outcome was 30-day mortality after discharge; 1-year mortality, readmissions, and return emergency room (ER) admissions were secondary outcomes. We used hierarchical, logistic regression modeling to determine the contribution of comorbidities, guideline-directed medical therapy (GDMT), and social determinants of health (SDOH) to outcomes. RESULTS: Thirty-day mortality rates after hospital discharge were 6.3% in rural areas compared to 5.7% in urban regions (P < .001); after adjusting for patient health and GDMT receipt, the 30-day mortality odds ratio for rural residence was 1.201 (95% CI 1.164-1.239). Adding the SDOH measure reduced the odds ratio somewhat (1.140, 95% CI 1.103-1.178) but a gap remained. Readmission rates in rural areas were consistently lower for all model specifications, while ER admissions were consistently higher. CONCLUSIONS: Among patients with HFrEF, living in a rural area is associated with an increased risk of death and return ER visits within 30 days of discharge from HF hospitalization. Differences in SDOH appear to partially explain mortality differences but the remaining gap may be the consequence of rural-urban differences in HF treatment.

A Regional Analysis of Low Back Pain Treatments in the Military Health System.

STUDY DESIGN: Claims-based analysis of cohorts of TRICARE Prime beneficiaries. OBJECTIVE: To compare rates of utilization of 5 low back pain (LBP) treatments (physical therapy (PT), manual therapy, behavioral therapies, opioid, and benzodiazepine prescription) across catchment areas and assess their association with the resolution of LBP. SUMMARY OF BACKGROUND: Guidelines support focusing on nonpharmacologic management for LBP and reducing opioid use. Little is known about patterns of care for LBP across the Military Health System. PATIENTS AND METHODS: Incident LBP diagnoses were identified data using the International Classification of Diseases ninth revision before October 2015 and 10th revision after October 2015; beneficiaries with "red flag" diagnoses and those stationed overseas, eligible for Medicare, or having other health insurance were excluded. After exclusions, there were 159,027 patients remained in the final analytic cohort across 73 catchment areas. Treatment was defined by catchment-level rates of treatment to avoid confounding by indication at the individual level; the primary outcome was the resolution of LBP defined as an absence of administrative claims for LBP during a 6 to 12-month period after the index diagnosis. RESULTS: Adjusted rates of opioid prescribing across catchment areas ranged from 15% to 28%, physical therapy from 17% to 39%, and manual therapy from 5% to 26%. Multivariate logistic regression models showed a negative and marginally significant association between opioid prescriptions and LBP resolution (odds ratio: 0.97, 95% CI: 0.93-1.00; P = 0.051) but no significant association with physical therapy, manual therapy, benzodiazepine prescription, or behavioral therapies. When the analysis was restricted to the subset of only active-duty beneficiaries, there was a stronger negative association between opioid prescription and LBP resolution (odds ratio: 0.93, 95% CI: 0.89-0.97). CONCLUSIONS: We found substantial variability across catchment areas within TRICARE for the treatment of LBP. Higher rates of opioid prescription were associated with worse outcomes.

Flecainide Is Associated With a Lower Incidence of Arrhythmic Events in a Large Cohort of Patients With Catecholaminergic Polymorphic Ventricular Tachycardia.

BACKGROUND: In severely affected patients with catecholaminergic polymorphic ventricular tachycardia, beta-blockers are often insufficiently protective. The purpose of this study was to evaluate whether flecainide is associated with a lower incidence of arrhythmic events (AEs) when added to beta-blockers in a large cohort of patients with catecholaminergic polymorphic ventricular tachycardia. METHODS: From 2 international registries, this multicenter case cross-over study included patients with a clinical or genetic diagnosis of catecholaminergic polymorphic ventricular tachycardia in whom flecainide was added to beta-blocker therapy. The study period was defined as the period in which background therapy (ie, beta-blocker type [beta1-selective or nonselective]), left cardiac sympathetic denervation, and implantable cardioverter defibrillator treatment status, remained unchanged within individual patients and was divided into pre-flecainide and on-flecainide periods. The primary end point was AEs, defined as sudden cardiac death, sudden cardiac arrest, appropriate implantable cardioverter defibrillator shock, and arrhythmic syncope. The association of flecainide with AE rates was assessed using a generalized linear mixed model assuming negative binomial distribution and random effects for patients. RESULTS: A total of 247 patients (123 [50%] females; median age at start of flecainide, 18 years [interquartile range, 14-29]; median flecainide dose, 2.2 mg/kg per day [interquartile range, 1.7-3.1]) were included. At baseline, all patients used a beta-blocker, 70 (28%) had an implantable cardioverter defibrillator, and 21 (9%) had a left cardiac sympathetic denervation. During a median pre-flecainide follow-up of 2.1 years (interquartile range, 0.4-7.2), 41 patients (17%) experienced 58 AEs (annual event rate, 5.6%). During a median on-flecainide follow-up of 2.9 years (interquartile range, 1.0-6.0), 23 patients (9%) experienced 38 AEs (annual event rate, 4.0%). There were significantly fewer AEs after initiation of flecainide (incidence rate ratio, 0.55 [95% CI, 0.38-0.83]; P=0.007). Among patients who were symptomatic before diagnosis or during the pre-flecainide period (n=167), flecainide was associated with significantly fewer AEs (incidence rate ratio, 0.49 [95% CI, 0.31-0.77]; P=0.002). Among patients with ≥1 AE on beta-blocker therapy (n=41), adding flecainide was also associated with significantly fewer AEs (incidence rate ratio, 0.25 [95% CI, 0.14-0.45]; P<0.001). CONCLUSIONS: For patients with catecholaminergic polymorphic ventricular tachycardia, adding flecainide to beta-blocker therapy was associated with a lower incidence of AEs in the overall cohort, in symptomatic patients, and particularly in patients with breakthrough AEs while on beta-blocker therapy.

Declines in Wealth Among US Older Adults at Risk of Dementia.

This case-control study uses Health and Retirement Study data to examine the trajectories of wealth among US older adults at risk of dementia.

The diffusion of health care fraud: A bipartite network analysis.

Many studies have examined the diffusion of health care innovation but less is known about the diffusion of health care fraud. In this paper, we consider the diffusion of potentially fraudulent Medicare home health care billing in the United States during 2002-16, with a focus on the 21 hospital referral regions (HRRs) covered by local Department of Justice (DOJ) anti-fraud "strike force" offices. We hypothesize that patient-sharing across home health care agencies (HHAs) provides a mechanism for the rapid diffusion of fraudulent strategies. We measure such activity using a novel bipartite mixture (or BMIX) network index, which captures patient sharing across multiple agencies and thus conveys more information about the diffusion process than conventional unipartite network measures. Using a complete population of fee-for-service Medicare claims data, we first find a remarkable increase in home health care activity between 2002 and 2009 in many regions targeted by the DOJ; average billing per Medicare enrollee in McAllen TX and Miami increased by $2127 and $2422 compared to just an average $289 increase in other HRRs not targeted by the DOJ. Second, we establish that the HRR-level BMIX (but not other network measures) was a strong predictor of above-average home health care expenditures across HRRs. Third, within HRRs, agencies sharing more patients with other agencies were predicted to increase billing. Finally, the initial 2002 BMIX index was a strong predictor of subsequent changes in HRR-level home health billing during 2002-9. These results highlight the importance of bipartite network structure in diffusion and in infection and contagion models more generally.

Receipt of Medications for Chronic Disease During the First 2 Years of the COVID-19 Pandemic Among Enrollees in Fee-for-Service Medicare.

Importance: During the first 2 years of the COVID-19 pandemic, inpatient and ambulatory care declined dramatically. Little is known about prescription drug receipt during this period, particularly for populations with chronic illness and with high risk of adverse COVID-19 outcomes and decreased access to care. Objective: To investigate whether receipt of medications was maintained during the first 2 years of the COVID-19 pandemic among older people with chronic diseases, particularly Asian, Black, and Hispanic populations and people with dementia, who faced pandemic-related care disruptions. Design, Setting, and Participants: This cohort study used a 100% sample of US Medicare fee-for-service administrative data from 2019 to 2021 for community-dwelling beneficiaries aged 65 years or older. Population-based prescription fill rates were compared for 2020 and 2021 vs 2019. Data were analyzed from July 2022 to March 2023. Exposure: The COVID-19 pandemic. Main Outcomes and Measures: Age- and sex-adjusted monthly prescription fill rates were calculated for 5 groups of medications commonly prescribed for chronic disease : angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors (statins), oral diabetes medications, asthma and chronic obstructive pulmonary disease medications, and antidepressants. Measurements were stratified by race and ethnicity group and dementia diagnosis. Secondary analyses measured changes in the proportion of prescriptions dispensed as a 90-day or greater supply. Results: Overall, the mean monthly cohort included 18 113 000 beneficiaries (mean [SD] age, 74.5 [7.4] years; 10 520 000 females [58.1%]; 587 000 Asian [3.2%], 1 069 000 Black [5.9%], 905 000 Hispanic [5.0%], and 14 929 000 White [82.4%]); 1 970 000 individuals (10.9%) were diagnosed with dementia. Across 5 drug classifications, mean fill rates increased by 2.07% (95% CI, 2.01% to 2.12%) in 2020 and decreased by 2.61% (95% CI, -2.67% to -2.56%) in 2021 compared with 2019. Fill rates decreased by less than the mean overall decrease for Black enrollees (-1.42%; 95% CI, -1.64% to -1.20%) and Asian enrollees (-1.05%; 95% CI, -1.36% to -0.77%) and people diagnosed with dementia (-0.38%; 95% CI, -0.54% to -0.23%). The proportion of fills dispensed as 90-day or greater supplies increased during the pandemic for all groups, with an increase per 100 fills of 3.98 fills (95% CI, 3.94 to 4.03 fills) overall. Conclusions and Relevance: This study found that, in contrast to in-person health services, receipt of medications for chronic conditions was relatively stable in the first 2 years of the COVID-19 pandemic overall, across racial and ethnic groups, and for community-dwelling patients with dementia. This finding of stability may hold lessons for other outpatient services during the next pandemic.

Association Between Opening a Palliative Care Unit and Hospital Care for Patients With Serious Illness.

Background: Palliative care units (PCUs) are devoted to intensive management of symptoms and other palliative care needs. We examined the association between opening a PCU and acute care processes at a single U.S. academic medical center. Methods: We retrospectively compared acute care processes for seriously ill patients admitted before and after the opening of a PCU at a single academic medical center. Outcomes included rates of change in code status to do-not-resuscitate (DNR) and comfort measures only (CMO) status, and time to DNR and CMO. We calculated unadjusted and adjusted rates and used logistic regression to assess interaction between care period and palliative care consultation. Results: There were 16,611 patients in the pre-PCU period and 18,305 patients in the post-PCU period. The post-PCU cohort was slightly older, with a higher Charlson index (p < 0.001 for both). Post-PCU, unadjusted rates of DNR and CMO increased from 16.4% to 18.3% (p < 0.001) and 9.3% to 11.5% (p < 0.001), respectively. Post-PCU, median time to DNR was unchanged (0 days), and time to CMO decreased from 6 to 5 days. The adjusted odds ratio was 1.08 (p = 0.01) for DNR and 1.19 (p < 0.001) for CMO. Significant interaction between care period and palliative care consultation for DNR (p = 0.04) and CMO (p = 0.01) suggests an important role for palliative care engagement. Conclusions: The opening of a PCU at a single center was associated with increased rates of DNR and CMO status for seriously ill patients.

The association between beta-blockers and outcomes in patients with heart failure and concurrent Alzheimer's disease and related dementias.

BACKGROUND: Contemporary patients with heart failure with reduced ejection fraction (HFrEF) are older and have a higher prevalence of cognitive impairment than those studied in trials. The risk/benefit trade-off of routine beta-blocker (BB) use in patients with HFrEF and Alzheimer's disease and related dementias (ADRD) has not been explored. This study aimed to determine the association between BB use and outcomes among patients with HFrEF and ADRD. METHODS: Using a random 40% sample of Medicare Parts A, B, and D data we identified patients with ≥1 hospitalization for HFrEF between 2008 and 2018. Each patient was classified based on BB use prior to admission and after discharge. Outcomes include 90-day and 1-year mortality and readmission. RESULTS: Between 2008 and 2018, we identified 357,030 patients hospitalized with HFrEF; 12.7% had ADRD. Patients with HFrEF and ADRD had higher 90-day and 1-year mortality compared to patients with HFrEF-only. Among patients admitted on a BB, 60.5% of patients with HFrEF-only were continued on therapy after discharge, compared to 56.8% of patients with HFrEF and ADRD. Discontinuing BB was associated with a 2.2-fold higher risk of 90-day mortality (p < 0.001) among patients with HF-only and a 2.- fold higher risk of 90-day mortality (p < 0.001) among patients with HFrEF + ADRD. Not starting a BB was associated with a 1.8-fold higher risk of 90-day mortality (p < 0.001) among patients with HFrEF-only and a 1.7-fold higher risk of 90-day mortality (p < 0.001) among patients with HFrEF + ADRD. Similar risks were seen at 1 year. CONCLUSIONS: BB therapy is associated with significantly lower short and long-term mortality rates among all patients with HFrEF; the magnitude of these associated benefits appear at least as large in patients with HFrEF and ADRD compared to patients with HFrEF-only.

Benefits and harms of oral anticoagulants for atrial fibrillation in nursing home residents with advanced dementia.

BACKGROUND: Approximately 20% of older persons with dementia have atrial fibrillation (AF). Nearly all have stroke risks that exceed the guideline-recommended threshold for anticoagulation. Although individuals with dementia develop profound impairments and die from the disease, little evidence exists to guide anticoagulant discontinuation, and almost one-third of nursing home residents with advanced dementia and AF remain anticoagulated in the last 6 months of life. We aimed to quantify the benefits and harms of anticoagulation in this population. METHODS: Using Minimum Data Set and Medicare claims, we conducted a retrospective cohort study with 14,877 long-stay nursing home residents aged ≥66 between 2013 and 2018 who had advanced dementia and AF. We excluded individuals with venous thromboembolism and valvular heart disease. We measured anticoagulant exposure quarterly, using Medicare Part D claims. The primary outcome was all-cause mortality; secondary outcomes were ischemic stroke and serious bleeding. We performed survival analyses with multivariable adjustment and inverse probability of treatment (IPT) weighting. RESULTS: In the study sample, 72.0% were female, 82.7% were aged ≥80 years, and 13.5% were nonwhite. Mean CHA2 DS2 VASC score was 6.19 ± 1.58. In multivariable survival analysis, anticoagulation was associated with decreased risk of death (HR 0.71, 95% CI 0.67-0.75) and increased bleeding risk (HR 1.15, 95% CI 1.02-1.29); the association with stroke risk was not significant (HR 1.08, 95% CI 0.80-1.46). Results were similar in models with IPT weighting. While >50% of patients in both groups died within a year, median weighted survival was 76 days longer for anticoagulated individuals. CONCLUSION: Persons with advanced dementia and AF derive clinically modest life prolongation from anticoagulation, at the cost of elevated risk of bleeding. The relevance of this benefit is unclear in a group with high dementia-related mortality and for whom the primary goal is often comfort.