Statin Use and Stroke Rate in Older Adults With Atrial Fibrillation: A Population-Based Cohort Study.

Background Atherosclerotic disease is an important contributor to adverse outcomes in patients with atrial fibrillation (AF). There is limited recognition of the association between statin use and stroke rates in AF. We aimed to quantify the association between statin use and stroke rate in AF. Methods and Results Using linked administrative databases in Ontario, Canada, we conducted a population-based retrospective cohort study of patients, aged ≥66 years, diagnosed with AF between 2009 and 2019. We used cause-specific hazard regression to determine the association of statin use with stroke rate. We developed a second model to further adjust for lipid levels in the subset of patients with available measurements in the year before AF diagnosis. Both models adjusted for age, sex, heart failure, hypertension, diabetes, stroke/transient ischemic attack, vascular disease, and P2Y12 inhibitors at baseline, plus anticoagulation as a time-varying covariate. We studied 261 659 qualifying patients (median age, 78 years; 49% women). Statins were used in 142 834 (54.6%) patients, and 145 673 (55.7%) had lipid measurement(s) in the preceding year. Statin use was associated with lower stroke rates, with adjusted hazard ratios of 0.83 (95% CI, 0.77-0.88; P<0.001) in the full cohort and 0.87 (95% CI, 0.78-0.97; P=0.01) when adjusting for lipid data. Stroke rates increased in a near-linear manner as low-density lipoprotein values increased >1.5 mmol/L. Conclusions Statins were associated with lower stroke rates in patients with AF, whereas higher low-density lipoprotein levels were associated with higher stroke rates, highlighting the importance of vascular risk factor treatment in AF.

Association of Neighborhood-Level Material Deprivation With Atrial Fibrillation Care in a Single-Payer Health Care System: A Population-Based Cohort Study.

BACKGROUND: There are limited data on the association of material deprivation with clinical care and outcomes after atrial fibrillation (AF) diagnosis in jurisdictions with universal health care. METHODS: This was a population-based cohort study of individuals ≥66 years of age with first diagnosis of AF between April 1, 2007, and March 31, 2019, in the Canadian province of Ontario, which provides public funding and prohibits private payment for medically necessary physician and hospital services. Prescription medications are subsidized for residents >65 years of age. The primary exposure was neighborhood material deprivation, a metric derived from Canadian census data to estimate inability to attain basic material needs. Neighborhoods were categorized by quintile from Q1 (least deprived) to Q5 (most deprived). Cause-specific hazards regression was used to study the association of material deprivation quintile with time to AF-related adverse events (death or hospitalization for stroke, heart failure, or bleeding), clinical services (physician visits, cardiac diagnostics), and interventions (anticoagulation, cardioversion, ablation) while adjusting for individual characteristics and regional cardiologist supply. RESULTS: Among 347 632 individuals with AF (median age 79 years, 48.9% female), individuals in the most deprived neighborhoods (Q5) had higher prevalence of cardiovascular disease, risk factors, and noncardiovascular comorbidity relative to residents of the least deprived neighborhoods (Q1). After adjustment, Q5 residents had higher hazards of death (hazard ratio [HR], 1.16 [95% CI, 1.13-1.20]) and hospitalization for stroke (HR, 1.16 [95% CI, 1.07-1.27]), heart failure (HR, 1.14 [95% CI, 1.11-1.18]), or bleeding (HR, 1.16 [95% CI, 1.07-1.25]) relative to Q1. There were small differences across quintiles in primary care physician visits (HR, Q5 versus Q1, 0.91 [95% CI, 0.89-0.92]), echocardiography (HR, Q5 versus Q1, 0.97 [95% CI, 0.96-0.99]), and dispensation of anticoagulation (HR, Q5 versus Q1, 0.97 [95% CI, 0.95-0.98]). There were more prominent disparities for Q5 versus Q1 in cardiologist visits (HR, 0.84 [95% CI, 0.82-0.86]), cardioversion (HR, 0.80 [95% CI, 0.76-0.84]), and ablation (HR, 0.45 [95% CI, 0.30-0.67]). CONCLUSIONS: Despite universal health care and prescription medication coverage, residents of more deprived neighborhoods were less likely to visit cardiologists or receive rhythm control interventions after AF diagnosis, even though they exhibited higher cardiovascular disease burden and higher risk of adverse outcomes.

Virtual care use during the COVID-19 pandemic and its impact on healthcare utilization in patients with chronic disease: A population-based repeated cross-sectional study.

PURPOSE: It is currently unclear how the shift towards virtual care during the 2019 novel coronavirus (COVID-19) pandemic may have impacted chronic disease management at a population level. The goals of our study were to provide a description of the levels of use of virtual care services relative to in-person care in patients with chronic disease across Ontario, Canada and to describe levels of healthcare utilization in low versus high virtual care users. METHODS: We used linked health administrative data to conduct a population-based, repeated cross-sectional study of all ambulatory patient visits in Ontario, Canada (January 1, 2018 to January 16, 2021). Further stratifications were also completed to examine patients with COPD, heart failure, asthma, hypertension, diabetes, mental illness, and angina. Patients were classified as low (max 1 virtual care visit) vs. high virtual care users. A time-series analysis was done using interventional autoregressive integrated moving average (ARIMA) modelling on weekly hospitalizations, outpatient visits, and diagnostic tests. RESULTS: The use of virtual care increased across all chronic disease patient populations. Virtual care constituted at least half of the total care in all conditions. Both low and high virtual care user groups experienced a statistically significant reduction in hospitalizations and laboratory testing at the start of the pandemic. Hospitalization volumes increased again only among the high users, while testing increased in both groups. Outpatient visits among high users remained unaffected by the pandemic but dropped in low users. CONCLUSION: The decrease of in-person care during the pandemic was accompanied by an increase in virtual care, which ultimately allowed patients with chronic disease to return to the same visit rate as they had before the onset of the pandemic. Virtual care was adopted across various chronic conditions, but the relative adoption of virtual care varied by condition with highest rates seen in mental health.

The association between anticoagulation and adverse outcomes after a positive SARS-CoV-2 test among older outpatients: A population-based cohort study.

INTRODUCTION: Anticoagulation may improve outcomes in patients with COVID-19 when started early in the course of illness. MATERIALS AND METHODS: This was a population-based cohort study using linked administrative datasets of outpatients aged ≥65 years old testing positive for SARS-CoV-2 between January 1 and December 31, 2020 in Ontario, Canada. The key exposure was anticoagulation with warfarin or direct oral anticoagulants before COVID-19 diagnosis. We calculated propensity scores and used matching weights (MWs) to reduce baseline differences between anticoagulated and non-anticoagulated patients. The primary outcome was a composite of death or hospitalization within 60 days of a positive SARS-CoV-2 test. We used the Kaplan-Meier method and cumulative incidence functions to estimate risk of the primary and component outcomes at 60 days. RESULTS: We studied 23,159 outpatients (mean age 78.5 years; 13,474 [58.2%] female), among whom 3200 (13.8%) deaths and 3183 (13.7%) hospitalizations occurred within 60 days of the SARS-CoV-2 test. After application of MWs, the 60-day risk of death or hospitalization was 29.2% (95% CI 27.4%-31.2%) for anticoagulated individuals and 32.1% (95% CI 30.7%-33.5%) without anticoagulation (absolute risk difference [ARD], -2.9%; p = 0.005). Anticoagulation was also associated with a lower risk of death: 18.6% (95% CI 17.0%-20.2%) with anticoagulation and 20.9% (95% CI 19.7%-22.2%) in non-anticoagulated patients (ARD -2.3%; p = 0.005). CONCLUSIONS: Among outpatients aged ≥65 years, oral anticoagulation at the time of a positive SARS-CoV-2 test was associated with a lower risk of a composite of death or hospitalization within 60 days.

Association of Diabetes Duration and Glycemic Control With Stroke Rate in Patients With Atrial Fibrillation and Diabetes: A Population-Based Cohort Study.

Background There are limited data on the association of diabetes duration and glycemic control with stroke risk in atrial fibrillation (AF). Our objective was to study the association of diabetes duration and glycated hemoglobin (HbA1c) with the rate of stroke in people with diabetes and newly diagnosed AF. Methods and Results This was a population-based cohort study using linked administrative data sets. We studied 37 209 individuals aged ≥66 years diagnosed with AF in Ontario between April 2009 and March 2019, who had diabetes diagnosed 1 to 16 years beforehand. The primary outcome was hospitalization for stroke at 1 year. Cause-specific hazard regression was used to model the association of diabetes duration and glycated hemoglobin (HbA1c) with the rate of stroke. Restricted cubic spline analyses showed increasing hazard ratios (HR) for stroke with longer diabetes duration that plateaued after 10 years and increasing HRs for stroke with HbA1c levels >7%. Relative to patients with <5 years diabetes duration, stroke rates were significantly higher for patients with ≥10 years duration (HR, 1.45; 95% CI, 1.16-1.82; P=0.001), while diabetes duration 5 to <10 years was not significantly different. Relative to glycated hemoglobin 6% to <7%, values ≥8% were associated with higher stroke rates (HR, 1.44; 95% CI, 1.12-1.84; P=0.004), while other HbA1c categories were not significantly different. Conclusions Longer diabetes duration and higher glycated hemoglobin were associated with significantly higher stroke rates in patients with AF and diabetes. Models for stroke risk prediction and preventive care in AF may be improved by considering patients' diabetes characteristics.

Cardiovascular Risk Associated With Ibrutinib Use in Chronic Lymphocytic Leukemia: A Population-Based Cohort Study.

PURPOSE: Ibrutinib reduces mortality in chronic lymphocytic leukemia (CLL). It increases the risk of atrial fibrillation (AF) and bleeding and there are concerns about heart failure (HF) and central nervous system ischemic events. The magnitude of these risks remains poorly quantified. METHODS: Using linked administrative databases, we conducted a population-based cohort study of Ontario patients who were treated for CLL diagnosed between 2007 and 2019. We matched ibrutinib-treated patients with controls treated with chemotherapy but unexposed to ibrutinib on prior AF, age ≥ 66 years, anticoagulant exposure, and propensity for receiving ibrutinib. Study outcomes were AF-related health care contact, hospital-diagnosed bleeding, new diagnoses of HF, and hospitalizations for stroke and acute myocardial infarction (AMI). The cumulative incidence function was used to estimate absolute risks. We used cause-specific regression to study the association of ibrutinib with bleeding rates, while adjusting for anticoagulation as a time-varying covariate. RESULTS: We matched 778 pairs of ibrutinib-treated and unexposed patients with CLL (N = 1,556). The 3-year incidence of AF-related health care contact was 22.7% (95% CI, 19.0 to 26.6) in ibrutinib-treated patients and 11.7% (95% CI, 9.0 to 14.8) in controls. The 3-year risk of hospital-diagnosed bleeding was 8.8% (95% CI, 6.5 to 11.7) in ibrutinib-treated patients and 3.1% (95% CI, 1.9 to 4.6) in controls. Ibrutinib-treated patients were more likely to start anticoagulation after the index date. After adjusting for anticoagulation as a time-varying covariate, ibrutinib remained positively associated with bleeding (HR, 2.58; 95% CI, 1.76 to 3.78). The 3-year risk of HF was 7.7% (95% CI, 5.4 to 10.6%) in ibrutinib-treated patients and 3.6% (95% CI, 2.2 to 5.4) in controls. There was no significant difference in the risk of ischemic stroke or AMI. CONCLUSION: Ibrutinib is associated with higher risk of AF, bleeding, and HF, but not AMI or stroke.

Using Administrative Data to Explore Potentially Aberrant Provision of Virtual Care During COVID-19: Retrospective Cohort Study of Ontario Provincial Data.

BACKGROUND: The COVID-19 pandemic has led to a rapid increase in virtual care use across the globe. Many health care systems have responded by creating virtual care billing codes that allow physicians to see their patients over telephone or video. This rapid liberalization of billing requirements, both in Canada and other countries, has led to concerns about potential abuse, but empirical data are limited. OBJECTIVE: The objectives of this study were to examine whether there were substantial changes in physicians' ambulatory visit volumes coinciding with the liberalization of virtual care billing rules and to describe the characteristics of physicians who significantly increased their ambulatory visit volumes during this period. We also sought to describe the relationship between visit volume changes in 2020 and the volumes of virtual care use among individual physicians and across specialties. METHODS: We conducted a population-based, retrospective cohort study using health administrative data from the Ontario Health Insurance Plan, which was linked to the ICES Physician Database. We identified a unique cohort of providers based on physicians' billings and calculated the ratio of total in-person and virtual ambulatory visits over the period from January to June 2020 (virtual predominating) relative to that over the period from January to June 2019 (in-person predominating) for each physician. Based on these ratios, we then stratified physicians into four groups: low-, same-, high-, and very high-use physicians. We then calculated various demographic and practice characteristics of physicians in each group. RESULTS: Among 28,383 eligible physicians in 2020, the mean ratio of ambulatory visits in January to June 2020:2019 was 0.99 (SD 2.53; median 0.81, IQR 0.59-1.0). Out of 28,383 physicians, only 2672 (9.4%) fell into the high-use group and only 291 (1.0%) fell into the very high-use group. High-use physicians were younger, more recent graduates, more likely female, and less likely to be international graduates. They also had, on average, lower-volume practices. There was a significant positive correlation between percent virtual care and the 2020:2019 ratio only in the group of physicians who maintained their practice (R=0.35, P<.001). There was also a significant positive correlation between the 2020:2019 ratio and the percent virtual care per specialty (R=0.59, P<.01). CONCLUSIONS: During the early stages of the pandemic, the introduction of virtual care did not lead to significant increases in visit volume. Our results provide reassuring evidence that relaxation of billing requirements early in the COVID-19 pandemic in Ontario were not associated with widespread and aberrant billing behaviors. Furthermore, the strong relationship between the ability to maintain practice volumes and the use of virtual care suggests that the introduction of virtual care allowed for continued access to care for patients.

Trends in Postpartum Opioid Prescribing: A Time Series Analysis.

Opioids are commonly prescribed following childbirth, but data are lacking on trends in postpartum opioid prescribing over time. We examined whether a highly publicized 2006 case report questioning the safety of codeine during lactation was associated with changes in postpartum opioid prescribing. We conducted a cross-sectional time series analysis of all publicly funded prescriptions for opioids to postpartum women in Ontario, Canada, from April 1, 2000, to March 31, 2017. The intervention was the publication of a case report in 2006 attributing the death of a breastfeeding neonate to maternal codeine use. The primary outcome was the rate of opioid prescribing to postpartum women. Among postpartum women eligible for prescription drug coverage, 17.5% filled an opioid prescription in the third quarter of 2006 (immediately prior to the intervention), with codeine representing 89.8% of all prescriptions. By the fourth quarter of 2010, only 12.2% of postpartum women filled an opioid prescription, representing a decline of 30% (P < 0.01), with codeine representing 71.9% of all prescriptions. During this period, we observed sizeable relative increases in the proportion of opioid prescriptions filled for morphine, hydromorphone, and oxycodone. By 2017, among women prescribed opioids post partum, 39.0% filled a prescription for codeine, while the remainder filled prescriptions for oxycodone (18.6%), morphine (25.5%), and hydromorphone (16.9%). A highly publicized case report questioning the safety of maternal codeine use during breastfeeding was associated with significant changes in opioid prescribing to postpartum women, including a decline in overall opioid prescribing and a shift from codeine to stronger opioids.

Evaluation of the Risk of Stroke Without Anticoagulation Therapy in Men and Women With Atrial Fibrillation Aged 66 to 74 Years Without Other CHA2DS2-VASc Factors.

Importance: There are limited clinical trial data and discrepant recommendations regarding use of anticoagulation therapy in patients with atrial fibrillation (AF) aged 65 to 74 years without other stroke risk factors. Objectives: To evaluate the risk of stroke without anticoagulation therapy in men and women with AF aged 66 to 74 years without other CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years, diabetes, stroke, vascular disease, age 65-74 years, female sex) risk factors and examine the association of stroke incidence with patient age. Design, Setting, and Participants: A population-based retrospective cohort study was conducted using linked administrative databases. The population included 16 351 individuals aged 66 to 74 years who were newly diagnosed with AF in Ontario, Canada, between April 1, 2007, and March 31, 2017. Exclusion criteria included long-term care residence, prior anticoagulation therapy, valvular disease, heart failure, hypertension, diabetes, stroke, and vascular disease. The cumulative incidence function was used to estimate the 1-year incidence of stroke in patients who did not receive anticoagulation therapy. Fine-Gray regression was used to study the association of patient characteristics with stroke incidence and derive estimates of stroke risk at each age. Death was treated as a competing risk and patients were censored if they initiated anticoagulation therapy. Inverse probability of censoring weights was used to account for patient censoring. Data analysis was performed from May 26, 2019, to December 9, 2020. Exposures: Atrial fibrillation and age. Main Outcomes and Measures: Hospitalizations for stroke. Results: Of the 16 351 individuals with AF (median [interquartile range] age, 70 [68-72] years), 8352 (51.1%) were men; 6314 individuals (38.6%) started anticoagulation therapy during follow-up. The overall 1-year stroke incidence among patients who did not receive anticoagulation therapy was 1.1% (95% CI, 1.0%-1.3%) and the incidence of death without stroke was 8.1% (95% CI, 7.7%-8.5%). The incidence of stroke was not significantly associated with sex. The estimated 1-year stroke risk increased with patient age from 66 years (0.7%; 95% CI, 0.5%-0.9%) to 74 years (1.7%; 95% CI, 1.3%-2.1%). Conclusions and Relevance: The risk of stroke more than doubled in this study as men and women with AF but no other CHA2DS2-VASc risk factors aged from 66 to 74 years. These data suggest that anticoagulation therapy is more likely to benefit older individuals within this group of patients, whereas younger individuals are less likely to gain net clinical benefit from anticoagulation therapy.

Rural Telemedicine Use Before and During the COVID-19 Pandemic: Repeated Cross-sectional Study.

BACKGROUND: The COVID-19 pandemic has led to a notable increase in telemedicine adoption. However, the impact of the pandemic on telemedicine use at a population level in rural and remote settings remains unclear. OBJECTIVE: This study aimed to evaluate changes in the rate of telemedicine use among rural populations and identify patient characteristics associated with telemedicine use prior to and during the pandemic. METHODS: We conducted a repeated cross-sectional study on all monthly and quarterly rural telemedicine visits from January 2012 to June 2020, using administrative data from Ontario, Canada. We compared the changes in telemedicine use among residents of rural and urban regions of Ontario prior to and during the pandemic. RESULTS: Before the pandemic, telemedicine use was steadily low in 2012-2019 for both rural and urban populations but slightly higher overall for rural patients (11 visits per 1000 patients vs 7 visits per 1000 patients in December 2019, P<.001). The rate of telemedicine visits among rural patients significantly increased to 147 visits per 1000 patients in June 2020. A similar but steeper increase (P=.15) was observed among urban patients (220 visits per 1000 urban patients). Telemedicine use increased across all age groups, with the highest rates reported among older adults aged ≥65 years (77 visits per 100 patients in 2020). The proportions of patients with at least 1 telemedicine visit were similar across the adult age groups (n=82,246/290,401, 28.3% for patients aged 18-49 years, n=79,339/290,401, 27.3% for patients aged 50-64 years, and n=80,833/290,401, 27.8% for patients aged 65-79 years), but lower among younger patients <18 years (n=23,699/290,401, 8.2%) and older patients ≥80 years (n=24,284/290,401, 8.4%) in 2020 (P<.001). There were more female users than male users of telemedicine (n=158,643/290,401, 54.6% vs n=131,758/290,401, 45.4%, respectively, in 2020; P<.001). There was a significantly higher proportion of telemedicine users residing in relatively less rural than in more rural regions (n=261,814/290,401, 90.2% vs n=28,587/290,401, 9.8%, respectively, in 2020; P<.001). CONCLUSIONS: Telemedicine adoption increased in rural and remote areas during the COVID-19 pandemic, but its use increased in urban and less rural populations. Future studies should investigate the potential barriers to telemedicine use among rural patients and the impact of rural telemedicine on patient health care utilization and outcomes.

Virtual care use before and during the COVID-19 pandemic: a repeated cross-sectional study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic is thought to have increased use of virtual care, but population-based studies are lacking. We aimed to assess the uptake of virtual care during the COVID-19 pandemic using comprehensive population-based data from Ontario. METHODS: This was a repeated cross-sectional study design. We used administrative data to evaluate changes in in-person and virtual visits among all residents of Ontario before (2012-2019) and during (January-August 2020) the COVID-19 pandemic. We included all patients who had an ambulatory care visit in Ontario. We excluded claims for patients who were not Ontario residents or had an invalid or missing health card number. We compared monthly or quarterly virtual care use across age groups, neighbourhood income quintiles and chronic disease subgroups. We also examined physician characteristics that may have been associated with virtual care use. RESULTS: Among all residents of Ontario (population 14.6 million), virtual care increased from 1.6% of total ambulatory visits in the second quarter of 2019 to 70.6% in the second quarter of 2020. The proportion of physicians who provided 1 or more virtual visits per year increased from 7.0% in the second quarter of 2019 to 85.9% in the second quarter of 2020. The proportion of Ontarians who had a virtual visit increased from 1.3% in 2019 to 29.2% in 2020. Older patients were the highest users of virtual care. The proportion of total virtual visits that were provided to patients residing in rural areas (v. urban areas) declined significantly between 2012 and 2020, reflecting a shift in virtual care to a service increasingly used in urban centres. The rates of virtual care use increased similarly across all conditions and across all income quintiles. INTERPRETATION: Our findings show that Ontario's approach to virtual care led to broad adoption across all provider groups, patient age, types of chronic diseases and neighborhood income. These findings have policy implications, including use of virtual care billing codes, for the ongoing use of virtual care during the second wave of the pandemic and beyond.

The Association Between High and Unnecessary Antibiotic Prescribing: A Cohort Study Using Family Physician Electronic Medical Records.

BACKGROUND: Approximately 25% of outpatient antibiotic prescriptions are unnecessary among family physicians in Canada. Minimizing unnecessary antibiotics is key for community antibiotic stewardship. However, unnecessary antibiotic prescribing is much harder to measure than total antibiotic prescribing. We investigated the association between total and unnecessary antibiotic use by family physicians and evaluated inter-physician variability in unnecessary antibiotic prescribing. METHODS: This was a cohort study based on electronic medical records of family physicians in Ontario, Canada, between April 2011 and March 2016. We used predefined expected antibiotic prescribing rates for 23 common primary care conditions to calculate unnecessary antibiotic prescribing rates. We used multilevel Poisson regression models to evaluate the association between total antibiotic volume (number of antibiotic prescriptions per patient visit), adjusted for multiple practice- and physician-level covariates, and unnecessary antibiotic prescribing. RESULTS: There were 499 570 physician-patient encounters resulting in 152 853 antibiotic prescriptions from 341 physicians. Substantial inter-physician variability was observed. In the fully adjusted model, we observed a significant association between total antibiotic volume and unnecessary prescribing rate (adjusted rate ratio 2.11 per 10% increase in total use; 95% CI 2.05-2.17), and none of the practice- and physician-level variables were associated with unnecessary prescribing rate. CONCLUSIONS: We demonstrated substantial inter-physician variability in unnecessary antibiotic prescribing in this cohort of family physicians. Total antibiotic use was strongly correlated with unnecessary antibiotic prescribing. Total antibiotic volume is a reasonable surrogate for unnecessary antibiotic use. These results can inform community antimicrobial stewardship efforts.

Population Trends in All-Cause Mortality and Cause Specific-Death With Incident Atrial Fibrillation.

BACKGROUND Limited studies have evaluated population-level temporal trends in mortality and cause of death in patients with contemporary managed atrial fibrillation. This study reports the temporal trends in 1-year overall and cause-specific mortality in patients with incident atrial fibrillation. METHODS AND RESULTS Patients with incident atrial fibrillation presenting to an emergency department or hospitalized in Ontario, Canada, were identified in population-level linked administrative databases that included data on vital statistics and cause of death. Temporal trends in 1-year all-cause and cause-specific mortality was determined for individuals identified between April 1, 2007 (fiscal year [FY] 2007) and March 31, 2016 (FY 2015). The study cohort consisted of 110 302 individuals, 69±15 years of age with a median congestive heart failure, hypertension, age (≥75 years), diabetes mellitus, stroke (2 points), vascular disease, age (≥65 years), sex category (female) score of 2.8. There was no significant decline in the adjusted 1-year all-cause mortality between the first and last years of the study period (adjusted mortality: FY 2007, 8.0%; FY 2015, 7.8%; P for trend=0.68). Noncardiovascular death accounted for 61% of all deaths; the adjusted 1-year noncardiovascular mortality rate rose from 4.5% in FY 2007 to 5.2% in FY 2015 (P for trend=0.007). In contrast, the 1-year cardiovascular mortality rate decreased from 3.5% in FY 2007 to 2.6% in FY 2015 (P for trend=0.01). CONCLUSIONS Overall 1-year all-cause mortality in individuals with incident atrial fibrillation has not improved despite a significant reduction in the rate of cardiovascular death. These findings highlight the importance of recognizing and managing concomitant noncardiovascular conditions in patients with atrial fibrillation.

Tamoxifen therapy in a murine model of myotubular myopathy.

Myotubular myopathy (MTM) is a severe X-linked disease without existing therapies. Here, we show that tamoxifen ameliorates MTM-related histopathological and functional abnormalities in mice, and nearly doubles survival. The beneficial effects of tamoxifen are mediated primarily via estrogen receptor signaling, as demonstrated through in vitro studies and in vivo phenotypic rescue with estradiol. RNA sequencing and protein expression analyses revealed that rescue is mediated in part through post-transcriptional reduction of dynamin-2, a known MTM modifier. These findings demonstrate an unexpected ability of tamoxifen to improve the murine MTM phenotype, providing preclinical evidence to support clinical translation.