Causal inference in the absence of positivity: The role of overlap weights.

How to analyze data when there is violation of the positivity assumption? Several possible solutions exist in the literature. In this paper, we consider propensity score (PS) methods that are commonly used in observational studies to assess causal treatment effects in the context where the positivity assumption is violated. We focus on and examine four specific alternative solutions to the inverse probability weighting (IPW) trimming and truncation: matching weight (MW), Shannon's entropy weight (EW), overlap weight (OW), and beta weight (BW) estimators. We first specify their target population, the population of patients for whom clinical equipoise, that is, where we have sufficient PS overlap. Then, we establish the nexus among the different corresponding weights (and estimators); this allows us to highlight the shared properties and theoretical implications of these estimators. Finally, we introduce their augmented estimators that take advantage of estimating both the propensity score and outcome regression models to enhance the treatment effect estimators in terms of bias and efficiency. We also elucidate the role of the OW estimator as the flagship of all these methods that target the overlap population. Our analytic results demonstrate that OW, MW, and EW are preferable to IPW and some cases of BW when there is a moderate or extreme (stochastic or structural) violation of the positivity assumption. We then evaluate, compare, and confirm the finite-sample performance of the aforementioned estimators via Monte Carlo simulations. Finally, we illustrate these methods using two real-world data examples marked by violations of the positivity assumption.

Recent Vitamin K Antagonist Use and Intracranial Hemorrhage After Endovascular Thrombectomy for Acute Ischemic Stroke.

Importance: Use of oral vitamin K antagonists (VKAs) may place patients undergoing endovascular thrombectomy (EVT) for acute ischemic stroke caused by large vessel occlusion at increased risk of complications. Objective: To determine the association between recent use of a VKA and outcomes among patients selected to undergo EVT in clinical practice. Design, Setting, and Participants: Retrospective, observational cohort study based on the American Heart Association's Get With the Guidelines-Stroke Program between October 2015 and March 2020. From 594 participating hospitals in the US, 32 715 patients with acute ischemic stroke selected to undergo EVT within 6 hours of time last known to be well were included. Exposure: VKA use within the 7 days prior to hospital arrival. Main Outcome and Measures: The primary end point was symptomatic intracranial hemorrhage (sICH). Secondary end points included life-threatening systemic hemorrhage, another serious complication, any complications of reperfusion therapy, in-hospital mortality, and in-hospital mortality or discharge to hospice. Results: Of 32 715 patients (median age, 72 years; 50.7% female), 3087 (9.4%) had used a VKA (median international normalized ratio [INR], 1.5 [IQR, 1.2-1.9]) and 29 628 had not used a VKA prior to hospital presentation. Overall, prior VKA use was not significantly associated with an increased risk of sICH (211/3087 patients [6.8%] taking a VKA compared with 1904/29 628 patients [6.4%] not taking a VKA; adjusted odds ratio [OR], 1.12 [95% CI, 0.94-1.35]; adjusted risk difference, 0.69% [95% CI, -0.39% to 1.77%]). Among 830 patients taking a VKA with an INR greater than 1.7, sICH risk was significantly higher than in those not taking a VKA (8.3% vs 6.4%; adjusted OR, 1.88 [95% CI, 1.33-2.65]; adjusted risk difference, 4.03% [95% CI, 1.53%-6.53%]), while those with an INR of 1.7 or lower (n = 1585) had no significant difference in the risk of sICH (6.7% vs 6.4%; adjusted OR, 1.24 [95% CI, 0.87-1.76]; adjusted risk difference, 1.13% [95% CI, -0.79% to 3.04%]). Of 5 prespecified secondary end points, none showed a significant difference across VKA-exposed vs VKA-unexposed groups. Conclusions and Relevance: Among patients with acute ischemic stroke selected to receive EVT, VKA use within the preceding 7 days was not associated with a significantly increased risk of sICH overall. However, recent VKA use with a presenting INR greater than 1.7 was associated with a significantly increased risk of sICH compared with no use of anticoagulants.

Racial and Ethnic Differences in Presentation and Outcomes for Patients Hospitalized With COVID-19: Findings From the American Heart Association's COVID-19 Cardiovascular Disease Registry.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has exposed longstanding racial and ethnic inequities in health risks and outcomes in the United States. We aimed to identify racial and ethnic differences in presentation and outcomes for patients hospitalized with COVID-19. METHODS: The American Heart Association COVID-19 Cardiovascular Disease Registry is a retrospective observational registry capturing consecutive patients hospitalized with COVID-19. We present data on the first 7868 patients by race/ethnicity treated at 88 hospitals across the United States between January 17, 2020, and July 22, 2020. The primary outcome was in-hospital mortality. Secondary outcomes included major adverse cardiovascular events (death, myocardial infarction, stroke, heart failure) and COVID-19 cardiorespiratory ordinal severity score (worst to best: death, cardiac arrest, mechanical ventilation with mechanical circulatory support, mechanical ventilation with vasopressors/inotrope support, mechanical ventilation without hemodynamic support, and hospitalization alone. Multivariable logistic regression analyses were performed to assess the relationship between race/ethnicity and each outcome adjusting for differences in sociodemographic, clinical, and presentation features, and accounting for clustering by hospital. RESULTS: Among 7868 patients hospitalized with COVID-19, 33.0% were Hispanic, 25.5% were non-Hispanic Black, 6.3% were Asian, and 35.2% were non-Hispanic White. Hispanic and Black patients were younger than non-Hispanic White and Asian patients and were more likely to be uninsured. Black patients had the highest prevalence of obesity, hypertension, and diabetes. Black patients also had the highest rates of mechanical ventilation (23.2%) and renal replacement therapy (6.6%) but the lowest rates of remdesivir use (6.1%). Overall mortality was 18.4% with 53% of all deaths occurring in Black and Hispanic patients. The adjusted odds ratios for mortality were 0.93 (95% CI, 0.76-1.14) for Black patients, 0.90 (95% CI, 0.73-1.11) for Hispanic patients, and 1.31 (95% CI, 0.96-1.80) for Asian patients compared with non-Hispanic White patients. The median odds ratio across hospitals was 1.99 (95% CI, 1.74-2.48). Results were similar for major adverse cardiovascular events. Asian patients had the highest COVID-19 cardiorespiratory severity at presentation (adjusted odds ratio, 1.48 [95% CI, 1.16-1.90]). CONCLUSIONS: Although in-hospital mortality and major adverse cardiovascular events did not differ by race/ethnicity after adjustment, Black and Hispanic patients bore a greater burden of mortality and morbidity because of their disproportionate representation among COVID-19 hospitalizations.

US Surveillance of Acute Ischemic Stroke Patient Characteristics, Care Quality, and Outcomes for 2019.

BACKGROUND: The United States lacks a timely and accurate nationwide surveillance system for acute ischemic stroke (AIS). We use the Get With The Guidelines-Stroke registry to apply poststratification survey weights to generate national assessment of AIS epidemiology, hospital care quality, and in-hospital outcomes. METHODS: Clinical data from the Get With The Guidelines-Stroke registry were weighted using a Bayesian interpolation method anchored to observations from the national inpatient sample. To generate a US stroke forecast for 2019, we linearized time trend estimates from the national inpatient sample to project anticipated AIS hospital volume, distribution, and race/ethnicity characteristics for the year 2019. Primary measures of AIS epidemiology and clinical care included patient and hospital characteristics, stroke severity, vital and laboratory measures, treatment interventions, performance measures, disposition, and clinical outcomes at discharge. RESULTS: We estimate 552 476 patients with AIS were admitted in 2019 to US hospitals. Median age was 71 (interquartile range, 60-81), 48.8% female. Atrial fibrillation was diagnosed in 22.6%, 30.2% had prior stroke/transient ischemic attack, and 36.4% had diabetes. At baseline, 46.4% of patients with AIS were taking antiplatelet agents, 19.2% anticoagulants, and 46.3% cholesterol-reducers. Mortality was 4.4%, and only 52.3% were able to ambulate independently at discharge. Performance nationally on AIS achievement measures were generally higher than 95% for all measures but the use of thrombolytics within 3 hours of early stroke presentations (81.9%). Additional quality measures had lower rates of receipt: dysphagia screening (84.9%), early thrombolytics by 4.5 hours (79.7%), and statin therapy (80.6%). CONCLUSIONS: We provide timely, reliable, and actionable US national AIS surveillance using Bayesian interpolation poststratification weights. These data may facilitate more targeted quality improvement efforts, resource allocation, and national policies to improve AIS care and outcomes.

Association of readmission penalty amount with subsequent 30-day risk standardized readmission and mortality rates among patients hospitalized with heart failure: An analysis of get with the guidelines - heart failure participating centers.

BACKGROUND: The Hospital Readmissions Reduction Program penalizes hospitals with excess 30-day risk-standardized readmission rates (RSRR) for heart failure (HF). The association of financial penalty amount with subsequent short-term clinical outcomes is unknown. METHODS: Patients admitted to American Heart Association Get With The Guidelines-HF registry participating centers from October 1, 2012 through December 1, 2015 who had Medicare-linked data were included. October 2012 hospital-specific penalty amounts were calculated based on diagnosis-related group payments and excess readmission ratios. Adjusted Cox models were created to evaluate the association of penalty amount categories (non-penalized: 0%; low-penalized: >0%-<0.50%; mid-penalized ≥0.50%-<0.99%; high-penalized ≥0.99%) with subsequent 30-day RSRR and risk-standardized mortality rates (RSMR). Trends in post-discharge 30-day RSRR and RSMR from 2012 to 2015 were analyzed across hospitals stratified by penalty amount categories. RESULTS: The present study included 61,329 patients who were admitted across 262 hospitals. Compared with patients admitted to non-penalized hospitals (36.3%), those admitted to increasingly penalized hospitals were more likely to have higher 30-day RSRR (low-penalized [43.9%]: HR, 1.10 [95% CI, 1.04-1.16]; mid-penalized [12.0%]: HR, 1.07 [95% CI, 0.99-1.16]; high-penalized [7.9%]: HR, 1.23 [95% CI, 1.12-1.35]) but not 30-day RSMR. Over time, 30-day RSRR and RSMR did not meaningfully change across penalized versus non-penalized hospitals. CONCLUSIONS: Financial penalties based on 30-day RSRR are not associated with declines in 30-day RSRR or RSMR from 2012 to 2015 among patients hospitalized with HF. Financially penalizing hospitals based on current Hospital Readmissions Reduction Program metrics may not incentivize improvements in short-term clinical outcomes for HF.

Is the affordable care act medicaid expansion associated with receipt of heart failure guideline-directed medical therapy by race and ethnicity?

BACKGROUND: Uninsurance is a known contributor to racial/ethnic health inequities. Insurance is often needed for prescriptions and follow-up appointments. Therefore, we determined whether the Affordable Care Act(ACA) Medicaid Expansion was associated with increased receipt of guideline-directed medical treatment(GDMT) at discharge among patients hospitalized with heart failure(HF) by race/ethnicity. METHODS: Using Get With The Guidelines-HF registry, logistic regression was used to assess odds of receiving GDMT(HF medications; education; follow-up appointment) in early vs non-adopter states before(2012 - 2013) and after ACA Medicaid Expansion(2014 - 2019) within each race/ethnicity, accounting for patient-level covariates and within-hospital clustering. We tested for an interaction(p-int) between GDMT and pre/post Medicaid Expansion time periods. RESULTS: Among 271,606 patients(57.5% early adopter, 42.5% non-adopter), 65.5% were White, 22.8% African American, 8.9% Hispanic, and 2.9% Asian race/ethnicity. Independent of ACA timing, Hispanic patients were more likely to receive all GDMT for residing in early adopter states compared to non-adopter states (P <.0001). In fully-adjusted analyses, ACA Medicaid Expansion was associated with higher odds of receipt of ACEI/ARB/ARNI in Hispanic patients [before ACA:OR 0.40(95%CI:0.13,1.23); after ACA:OR 2.46(1.10,5.51); P-int = .0002], but this occurred in the setting of an immediate decline in prescribing patterns, particularly among non-adopter states, followed by an increase that remained lowest in non-adopter states. The ACA was not associated with receipt of GDMT for other racial/ethnic groups. CONCLUSIONS: Among GWTG-HF hospitals, Hispanic patients were more likely to receive all GDMT if they resided in early adopter states rather than non-adopter states, independent of ACA Medicaid Expansion timing. ACA implementation was only associated with higher odds of receipt of ACEI/ARB/ARNI in Hispanic patients. Additional steps are needed for improved GDMT delivery for all.

Achievement and quality measure attainment in patients hospitalized with atrial fibrillation: Results from The Get With The Guidelines - Atrial Fibrillation (GWTG-AFIB) registry.

BACKGROUND: The Get With The Guidelines - Atrial Fibrillation (GWTG-AFIB) Registry uses achievement and quality measures to improve the care of patients with atrial fibrillation (AF). We sought to evaluate overall and site-level variation in attainment of these measures among sites participating in the GWTG-AFIB Registry. METHODS: From the GWTG-AFIB registry, we included patients with AF admitted between 1/3/2013 and 6/30/2019. We described patient-level attainment and variation in attainment across sites of 6 achievement measures with 1) defect-free scores (percent of patients with all eligible measures attained), and 2) composite opportunity scores (percent of all eligible patient measures attained). We also described attainment of 11 quality measures at the patient-level. RESULTS: Among 80,951 patients hospitalized for AF (age 70±13 years, 47.0% female; CHA2DS2-VASc 3.6±1.8) at 132 sites. Site-level defect-free scores ranged from 4.7% to 85.8% (25th, 50th, 75th percentile: 32.7%, 52.1%, 64.4%). Composite opportunity scores ranged from 39.4% to 97.5% (25th, 50th, 75th: 68.1%, 80.3%, 87.1%). Attainment was notably low for the following quality measures: 1) aldosterone antagonist prescription when ejection fraction ≤35% (29% of those eligible); and 2) avoidance of antiplatelet therapy with OAC in patients without coronary/peripheral artery disease (81% of those eligible). CONCLUSIONS: Despite high overall attainment of care measures across GWTG-AFIB registry sites, large site variation was present with meaningful opportunities to improve AF care beyond OAC prescription, including but not limited to prescription of aldosterone antagonists in those with AF and systolic dysfunction and avoidance of non-indicated adjunctive antiplatelet therapy.

Association of Recent Use of Non-Vitamin K Antagonist Oral Anticoagulants With Intracranial Hemorrhage Among Patients With Acute Ischemic Stroke Treated With Alteplase.

Importance: Current guidelines recommend against use of intravenous alteplase in patients with acute ischemic stroke who are taking non-vitamin K antagonist oral anticoagulants (NOACs). Objective: To evaluate the safety and functional outcomes of intravenous alteplase among patients who were taking NOACs prior to stroke and compare outcomes with patients who were not taking long-term anticoagulants. Design, Setting, and Participants: A retrospective cohort study of 163 038 patients with acute ischemic stroke either taking NOACs or not taking anticoagulants prior to stroke and treated with intravenous alteplase within 4.5 hours of symptom onset at 1752 US hospitals participating in the Get With The Guidelines-Stroke program between April 2015 and March 2020, with complementary data from the Addressing Real-world Anticoagulant Management Issues in Stroke registry. Exposures: Prestroke treatment with NOACs within 7 days prior to alteplase treatment. Main Outcomes and Measures: The primary outcome was symptomatic intracranial hemorrhage occurring within 36 hours after intravenous alteplase administration. There were 4 secondary safety outcomes, including inpatient mortality, and 7 secondary functional outcomes assessed at hospital discharge, including the proportion of patients discharged home. Results: Of 163 038 patients treated with intravenous alteplase (median age, 70 [IQR, 59 to 81] years; 49.1% women), 2207 (1.4%) were taking NOACs and 160 831 (98.6%) were not taking anticoagulants prior to their stroke. Patients taking NOACs were older (median age, 75 [IQR, 64 to 82] years vs 70 [IQR, 58 to 81] years for those not taking anticoagulants), had a higher prevalence of cardiovascular comorbidities, and experienced more severe strokes (median National Institutes of Health Stroke Scale score, 10 [IQR, 5 to 17] vs 7 [IQR, 4 to 14]) (all standardized differences >10). The unadjusted rate of symptomatic intracranial hemorrhage was 3.7% (95% CI, 2.9% to 4.5%) for patients taking NOACs vs 3.2% (95% CI, 3.1% to 3.3%) for patients not taking anticoagulants. After adjusting for baseline clinical factors, the risk of symptomatic intracranial hemorrhage was not significantly different between groups (adjusted odds ratio [OR], 0.88 [95% CI, 0.70 to 1.10]; adjusted risk difference [RD], -0.51% [95% CI, -1.36% to 0.34%]). There were no significant differences in the secondary safety outcomes, including inpatient mortality (6.3% for patients taking NOACs vs 4.9% for patients not taking anticoagulants; adjusted OR, 0.84 [95% CI, 0.69 to 1.01]; adjusted RD, -1.20% [95% CI, -2.39% to -0%]). Of the secondary functional outcomes, 4 of 7 showed significant differences in favor of the NOAC group after adjustment, including the proportion of patients discharged home (45.9% vs 53.6% for patients not taking anticoagulants; adjusted OR, 1.17 [95% CI, 1.06 to 1.29]; adjusted RD, 3.84% [95% CI, 1.46% to 6.22%]). Conclusions and Relevance: Among patients with acute ischemic stroke treated with intravenous alteplase, use of NOACs within the preceding 7 days, compared with no use of anticoagulants, was not associated with a significantly increased risk of intracranial hemorrhage.

Patient characteristics, care patterns, and outcomes of atrial fibrillation associated hospitalizations in patients with chronic kidney disease and end-stage renal disease.

BACKGROUND: Chronic Kidney Disease (CKD) and end-stage renal disease (ESRD) are associated with poor outcomes in patients with cardiovascular disease. There is a paucity of contemporary data on in-hospital outcomes and care patterns of atrial fibrillation (AF) associated hospitalizations CKD and ESRD. METHODS: Outcomes and care patterns were evaluated in GWTG-AFIB database (Jan 2013-Dec 2018), including in-hospital mortality, use of a rhythm control strategy, and oral anticoagulation (OAC) prescription at discharge among eligible patients. Generalized logistic regression models with generalized estimating equations were used to ascertain differences in outcomes. Hospital-level variation in OAC prescription and rhythm control was also evaluated. RESULTS: Among 50,154 patients from 105 hospitals the median age was 70 years (interquartile range 61-79) and 47.3% were women. The prevalence of CKD was 36.0% while that of ESRD was 1.6%. Among eligible patients, discharge OAC prescription rates were 93.6% for CKD and 89.1% for ESRD. After adjustment, CKD and ESRD were associated with higher in-hospital mortality (odds ratio [OR] 3.08, 95% confidence interval [CI] 1.57-6.03 for ESRD and OR 2.02, 95% CI 1.52-2.67 for CKD), lower odds of OAC prescription at discharge (OR 0.59, 95% CI 0.44-0.79 for ESRD and OR 0.84, 95% CI 0.75-0.94 for CKD) compared with normal renal function. CKD was associated with lower utilization of rhythm control strategy (OR 0.92, 95% CI 0.87-0.98) with no significant difference between ESRD and normal renal function (OR 1.32, 95% CI 0.79-1.11). There was large hospital-level variation in OAC prescription at discharge (MOR 2.34, 95% CI 2.05-2.76) and utilization of a rhythm control strategy (MOR 2.69, 95% CI 2.34-3.21). CONCLUSIONS: CKD/ESRD is associated with higher in-hospital mortality, less frequent rhythm control, and less OAC prescription among patients hospitalized for AF. There is wide hospital-level variation in utilization of a rhythm control strategy and OAC prescription at discharge highlighting potential opportunities to improve care and outcomes for these patients, and better define standards of care in this patient population.

Temporal trends in risk profiles among patients hospitalized for heart failure.

BACKGROUND: Postdischarge mortality following hospitalization for heart failure with reduced ejection fraction (HFrEF) has remained high and unchanged over the past 2 decades, despite effective therapies for HFrEF. We aimed to explore whether these patterns could in part be explained by changes in longitudinal risk profile and HF severity over time. METHODS: Among patients hospitalized for HF in the GWTG-HF registry from January 2005 to December 2018 with available data, we evaluated GWTG-HF and ADHERE risk scores, observing in-hospital mortality per-year. The risk profiles and outcomes were described overall and by subgroups based on ejection fraction (EF), diabetes mellitus (DM), sex, and age. RESULTS: Overall, 335,735 patients were included (50% HFrEF, 46% DM, 48% female, mean age 74 years). In-hospital mortality increased by 2.0% per year from 2005 to 2018. There was no significant change in mean GWTG-HF risk score overall or when stratified by EF groups (P = 0.46 HFrEF, p = 0.26 HF mid-range EF [HFmrEF], and P = 0.72 HF preserved EF [HFpEF]), age, sex, or presence of DM. The observed/expected ratio based on the GWTG-HF risk score was 0.93 (0.91-0.96), 0.83 (0.77-0.90), 0.92 (0.89-95) for HFrEF, HFmrEF, and HFpEF, respectively. Similar findings were seen when risk was assessed using ADHERE risk score. CONCLUSIONS: There were no significant changes in average risk profiles among hospitalized HF patients over the study duration. These data do not support the notion that worsening risk profile explains the lack of improved outcomes despite therapeutic advances, underscoring the importance of aggressive implementation of guideline-recommended therapies and investigation of novel treatments.

Profile of Patients Hospitalized for Heart Failure Who Leave Against Medical Advice.

BACKGROUND: There is a paucity of information on patients hospitalized with heart failure (HF) who leave against medical advice (AMA). We sought to identify patient and hospital characteristics and outcomes of patients with HF who left AMA compared with those conventionally discharged to home. METHODS AND RESULTS: Using the Get With The Guidelines-Heart Failure registry, data were analyzed from January 2010 to June 2019. In addition, outcomes were examined from a subset of hospitalizations with Medicare-linked claims between January 2010 and November 2015. The fully eligible population included 561,823 patients and the Medicare-linked subset included 74,502 patients. In total, 8747 patients (1.56%) left AMA. The proportion of patients leaving AMA increased from 1.1% to 2.1% over the years of study. Patients leaving a HF hospitalization AMA, compared with patients conventionally discharged to home, were more likely younger, minorities, Medicaid covered, or uninsured. The Medicare-linked subset of patients who left AMA had substantially higher 30-day and 12-month readmission rates and higher mortality at each assessment point over 12 months compared with patients who were conventionally discharged to home. After risk adjustments, the hazard ratio of mortality in the Medicare-linked subset AMA group compared with the conventionally discharged to home group was 1.25 (95% confidence interval, 1.03-1.51; P = .005). CONCLUSIONS: One in 64 hospitalized patients with HF left AMA. An AMA discharge status was associated with higher risk for adverse 30-day and 12-month outcomes compared with being conventionally discharged home. Strategies that identify patients at risk of leaving AMA and policies to direct interventional strategies are warranted.

National surveillance of stroke quality of care and outcomes by applying post-stratification survey weights on the Get With The Guidelines-Stroke patient registry.

BACKGROUND: The U.S. lacks a stroke surveillance system. This study develops a method to transform an existing registry into a nationally representative database to evaluate acute ischemic stroke care quality. METHODS: Two statistical approaches are used to develop post-stratification weights for the Get With The Guidelines-Stroke registry by anchoring population estimates to the National Inpatient Sample. Post-stratification survey weights are estimated using a raking procedure and Bayesian interpolation methods. Weighting methods are adjusted to limit the dispersion of weights and make reasonable epidemiologic estimates of patient characteristics, quality of hospital care, and clinical outcomes. Standardized differences in national estimates are reported between the two post-stratification methods for anchored and non-anchored patient characteristics to evaluate estimation quality. Primary measures evaluated are patient and hospital characteristics, stroke severity, vital and laboratory measures, disposition, and clinical outcomes at discharge. RESULTS: A total of 1,388,296 acute ischemic strokes occurred between 2012 and 2014. Raking and Bayesian estimates of clinical data not available in administrative data are estimated within 5 to 10% of margin for expected values. Median weight for the raking method is 1.386 and the weights at the 99th percentile is 6.881 with a maximum weight of 30.775. Median Bayesian weight is 1.329 and the 99th percentile weights is 11.201 with a maximum weight of 515.689. CONCLUSIONS: Leveraging existing databases with patient registries to develop post-stratification weights is a reliable approach to estimate acute ischemic stroke epidemiology and monitoring for stroke quality of care nationally. These methods may be applied to other diseases or settings to better monitor population health.

Adherence to Guideline-Directed Stroke Prevention Therapy for Atrial Fibrillation Is Achievable.

BACKGROUND: Efforts to improve prescription of oral anticoagulation (OAC) drugs in patients with atrial fibrillation have had limited success in improving guideline adherence. METHODS: We evaluated adherence to the American College of Cardiology/American Heart Association performance measures for OAC in eligible patients with a CHA2DS2-VASc score ≥2 and trends in prescription over time in the American Heart Association's Get With The Guidelines-AFIB (atrial fibrillation) registry. Adjusted associations with in-hospital outcomes were also determined. The cohort included 33 235 patients with a CHA2DS2-VASc score ≥2 who were admitted for atrial fibrillation and were enrolled at 115 sites between January 1, 2013, and September 31, 2017. RESULTS: The median (25th, 75th percentile) age was 73 years (65, 81 years); 51% were female; and the median (25th, 75th percentile) CHA2DS2-VASc score was 4 (3, 5). At admission, 16 206 (59.5%) of 27 221 patients with a previous diagnosis of atrial fibrillation were taking OAC agents, and OAC drug use at admission was associated with a lower adjusted odds of in-hospital ischemic stroke (odds ratio, 0.38; 95% CI, 0.24-0.59; P<0.0001). At discharge, prescription of OAC in eligible patients (no contraindications) was 93.5% (n=25 499 of 27 270). In a sensitivity analysis, when excluding only strict contraindications (4.6%, n=1497 of 32 806), OAC prescription at discharge was 80.3%. OAC prescription at discharge was higher in those aged ≤75 years, men, those with heart failure, those with previous atrial fibrillation ablation, and those with rhythm control ( P<0.0001 for all). OAC use was lowest in Hispanic patients (90.2%, P<0.0001). Prescription of OAC at discharge in eligible patients improved over time from 79.9% to 96.6% ( P<0.0001). CONCLUSIONS: Among hospitals participating in the GWTG-AFIB quality improvement program, OAC prescription at discharge in eligible guideline-indicated patients increased significantly and improved consistently over time. These data confirm that high-level adherence to guideline-recommended stroke prevention is achievable.

Outcomes and cost among Medicare beneficiaries hospitalized for heart failure assigned to accountable care organizations.

Little is known about the impact of accountable care organizations (ACO) on hospitalized heart failure (HF) patients, a high-cost and high-risk population. OBJECTIVE: We linked Medicare fee-for-service claims from 2013 to 2015 with data from American Heart Association Get With The Guidelines-HF registry to compare HF care, post-discharge outcomes, and total annual Medicare spending by ACO status at discharge. METHODS: Using adjusted Cox models and accounting for competing risks of death, we compared all-cause mortality and readmission at 1 year by ACO status with reporting of hazard ratios (HR) and 99% confidence intervals (CI). RESULTS: The study included 45,259 HF patients from 300 hospitals, with 21.1% assigned to an ACO. Patient characteristics were similar between the two groups with a few exceptions. The ACO patients lived in geographic areas with higher median income ($54400 [IQR $48600-65900] vs $52300 [$45900-61200], P < .0001). Compliance with four HF-specific quality measures was modestly higher in the ACO group (80% vs 76%, P < .0001). In adjusted analysis, ACO status was associated with similar all-cause readmission (HR: 1.03; 99% CI: 0.99, 1.07) but lower risk of 1-year mortality (HR: 0.85; 99% CI: 0.85, 0.90) compared with non-ACO status. Median Medicare spending in the calendar year of hospitalization was similar (ACO $42,737 [IQR $23,011-72,667] vs non-ACO $42,586 [$22,896-72,518], P = 0.06). CONCLUSIONS: Among Medicare patients hospitalized for HF, participation in an ACO was associated with similar rates of all-cause readmission and no associated cost reductions compared with non-ACO status. There was a lower risk of 1-year mortality associated with ACO participation, which warrants further evaluation.

Regression with a right-censored predictor using inverse probability weighting methods.

In a longitudinal study, measures of key variables might be incomplete or partially recorded due to drop-out, loss to follow-up, or early termination of the study occurring before the advent of the event of interest. In this paper, we focus primarily on the implementation of a regression model with a randomly censored predictor. We examine, particularly, the use of inverse probability weighting methods in a generalized linear model (GLM), when the predictor of interest is right-censored, to adjust for censoring. To improve the performance of the complete-case analysis and prevent selection bias, we consider three different weighting schemes: inverse censoring probability weights, Kaplan-Meier weights, and Cox proportional hazards weights. We use Monte Carlo simulation studies to evaluate and compare the empirical properties of different weighting estimation methods. Finally, we apply these methods to the Framingham Heart Study data as an illustrative example to estimate the relationship between age of onset of a clinically diagnosed cardiovascular event and low-density lipoprotein among cigarette smokers.

Association Between Thrombolytic Door-to-Needle Time and 1-Year Mortality and Readmission in Patients With Acute Ischemic Stroke.

Importance: Earlier administration of intravenous tissue plasminogen activator (tPA) in acute ischemic stroke is associated with reduced mortality by the time of hospital discharge and better functional outcomes at 3 months. However, it remains unclear whether shorter door-to-needle times translate into better long-term outcomes. Objective: To examine whether shorter door-to-needle times with intravenous tPA for acute ischemic stroke are associated with improved long-term outcomes. Design, Setting, and Participants: This retrospective cohort study included Medicare beneficiaries aged 65 years or older who were treated for acute ischemic stroke with intravenous tPA within 4.5 hours from the time they were last known to be well at Get With The Guidelines-Stroke participating hospitals between January 1, 2006, and December 31, 2016, with 1-year follow-up through December 31, 2017. Exposures: Door-to-needle times for intravenous tPA. Main Outcomes and Measures: The primary outcomes were 1-year all-cause mortality, all-cause readmission, and the composite of all-cause mortality or readmission. Results: Among the 61 426 patients treated with tPA within 4.5 hours, the median age was 80 years and 43.5% were male. The median door-to-needle time was 65 minutes (interquartile range, 49-88 minutes). The 48 666 patients (79.2%) who were treated with tPA and had door-to-needle times of longer than 45 minutes, compared with those treated within 45 minutes, had significantly higher all-cause mortality (35.0% vs 30.8%, respectively; adjusted HR, 1.13 [95% CI, 1.09-1.18]), higher all-cause readmission (40.8% vs 38.4%; adjusted HR, 1.08 [95% CI, 1.05-1.12]), and higher all-cause mortality or readmission (56.0% vs 52.1%; adjusted HR, 1.09 [95% CI, 1.06-1.12]). The 34 367 patients (55.9%) who were treated with tPA and had door-to-needle times of longer than 60 minutes, compared with those treated within 60 minutes, had significantly higher all-cause mortality (35.8% vs 32.1%, respectively; adjusted hazard ratio [HR], 1.11 [95% CI, 1.07-1.14]), higher all-cause readmission (41.3% vs 39.1%; adjusted HR, 1.07 [95% CI, 1.04-1.10]), and higher all-cause mortality or readmission (56.8% vs 53.1%; adjusted HR, 1.08 [95% CI, 1.05-1.10]). Every 15-minute increase in door-to-needle times was significantly associated with higher all-cause mortality (adjusted HR, 1.04 [95% CI, 1.02-1.05]) within 90 minutes after hospital arrival, but not after 90 minutes (adjusted HR, 1.01 [95% CI, 0.99-1.03]), higher all-cause readmission (adjusted HR, 1.02; 95% CI, 1.01-1.03), and higher all-cause mortality or readmission (adjusted HR, 1.02 [95% CI, 1.01-1.03]). Conclusions and Relevance: Among patients aged 65 years or older with acute ischemic stroke who were treated with tissue plasminogen activator, shorter door-to-needle times were associated with lower all-cause mortality and lower all-cause readmission at 1 year. These findings support efforts to shorten time to thrombolytic therapy.

Association of post-discharge specialty outpatient visits with readmissions and mortality in high-risk heart failure patients.

Heart failure (HF) outcomes are especially poor in high-risk patients with certain comorbidities including diabetes mellitus (DM), chronic kidney disease (CKD), and chronic obstructive pulmonary disease (COPD). Whether early specialty or primary care provider (PCP) follow-up after HF discharge affects outcomes in high-risk patients is unknown. METHODS: We analyzed patients discharged from a Get With The Guidelines HF-participating hospital from 2007-2012 with linked Medicare claims to investigate the association of medical specialist visit within 14 days of discharge stratified by comorbidity with the primary outcome of 90-day HF readmission. Secondary outcomes included 90-day and 1-year all-cause mortality. RESULTS: Out of 33,243 patients, 39.4% had DM, 19.8% had CKD, 30.0% had COPD, and 36.3% had no key comorbidity. Nephrologist visit in patients with CKD was associated with a 35% reduction in 90-day HF readmission (hazard ratio [HR] 0.65, 95% confidence interval [CI] 0.49-0.85). Pulmonologist visit in patients with COPD was associated with a 29% reduction in 90-day HF readmission (HR 0.71, 95% CI 0.55-0.91). In patients with no key comorbidity, PCP and Cardiologist visits were associated with decreased 90-day mortality (HR for PCP 0.79, 95% CI 0.66-0.94; HR for Cardiologist 0.78, 95% CI 0.63-0.96). In patients with DM, Endocrinologist visit was associated with a 42% reduction of 90-day mortality (HR 0.58, 95% CI 0.34-0.99). CONCLUSIONS: Specialist and PCP visit in the immediate post-discharge period may improve 90-day HF readmission and mortality in certain high-risk groups of patients with HF.

Long-term outcomes for heart failure patients with and without diabetes: From the Get With The Guidelines-Heart Failure Registry.

BACKGROUND: Diabetes mellitus is an increasingly prevalent condition among heart failure (HF) patients. The long-term morbidity and mortality among patients with and without diabetes with HF with reduced (HFrEF), borderline (HFbEF), and preserved ejection fraction (HFpEF) are not well described. METHODS: Using the Get With The Guidelines (GWTG)-HF Registry linked to Centers for Medicare & Medicaid Services claims data, we evaluated differences between HF patients with and without diabetes. Adjusted Cox proportional-hazard models controlling for patient and hospital characteristics were used to evaluate mortality and readmission outcomes. RESULTS: A cohort of 86,659 HF patients aged ≥65 years was followed for 3 years from discharge. Unadjusted all-cause mortality was between 4.4% and 5.5% and all-cause hospitalization was between 19.4% and 22.6% for all groups at 30 days. For all-cause mortality at 3 years from hospital discharge, diabetes was associated with an adjusted hazard ratio of 1.27 (95% CI 1.07-1.49, P = .0051) for HFrEF, 0.95 (95% CI 0.55-1.65, P = .8536) for HFbEF, 1.02 (95% CI 0.87-1.19, P = .8551) for HFpEF. For all-cause readmission, diabetes was associated with an adjusted hazard ratio of 1.06 (95% CI 0.87-1.29, P = .5585) for HFrEF, 1.48 (95% CI 1.15-1.90, P = .0023) for HFbEF, and 1.06 (95% CI 0.91-1.22, P = .4747) for HFpEF. CONCLUSIONS: HFrEF and HFbEF patients with diabetes are at increased risk for mortality and rehospitalization after hospitalization for HF, independent of other patient and hospital characteristics. Among HFpEF patients, diabetes does not appear to be independently associated with significant additional risks.

A Study of Practice Behavior for Endotracheal Intubation Site for Children With Congenital Heart Disease Undergoing Surgery: Impact of Endotracheal Intubation Site on Perioperative Outcomes-An Analysis of the Society of Thoracic Surgeons Congenital Cardiac Anesthesia Society Database.

BACKGROUND: In adults undergoing cardiopulmonary bypass surgery, oral intubation is typically preferred over nasal intubation due to reduced risk of sinusitis and infection. In children, nasal intubation is more common and sometimes preferred due to perceived benefits of less postoperative sedation and a lower risk for accidental extubation. This study sought to describe the practice of nasal intubation in the pediatric population undergoing cardiopulmonary bypass surgery and assess the risks/benefits of a nasal route against an oral one. METHODS: Patients <18 years of age in the Society of Thoracic Surgeons Congenital Heart Surgery Database between January 2010 and December 2015 were included. Patients with a preoperative endotracheal tube, tracheostomy, or known airway anomalies were excluded. Multivariable modeling was used to assess the association between route of tracheal intubation and a composite measure of infection risk (wound infection, mediastinitis, septicemia, pneumonia, and endocarditis). Covariates were included to adjust for important patient characteristics (eg, weight, age, comorbidities), case complexity, and center effects. Secondary outcomes included length of intubation, hospital length of stay, and airway complications including accidental extubations. We also performed a subanalysis in children <12 months of age in high-volume centers (>100 cases/y) examining how infection risk may change with age at the time of surgery. RESULTS: Nasal intubation was used in 41% of operations in neonates, 38% in infants, 15% in school-aged children, and 2% in adolescents. Nasal intubation appeared protective for accidental extubation only in neonates (P = .02). Multivariable analysis in infants and neonates showed that the nasal route of intubation was not associated with the infection composite (relative risk [RR], 0.84; 95% CI, 0.59-1.18) or a shorter length of stay (RR, 0.992; 95% CI, 0.947-1.039), but was associated with a shorter intubation length (RR, 0.929; 95% CI, 0.869-0.992). Restricting to high-volume centers showed a significant interaction between age and intubation route with a risk change for infection occurring between approximately 6-12 months of age (P = .003). CONCLUSIONS: While older children undergoing nasal intubation trend similar to the adult population with an increased risk of infection, nasal intubation in neonates and infants does not appear to carry a similar risk. Nasal intubation in neonates and infants may also be associated with a shorter intubation length but not a shorter length of stay. Prospective studies are required to better understand these complex associations.

Diabetes and long-term outcomes of ischaemic stroke: findings from Get With The Guidelines-Stroke.

Aims: There is a paucity of data on the influence of diabetes on long-term outcomes after ischaemic stroke (IS). We assessed whether outcomes after IS differ between patients with and without diabetes. Methods and results: Patients aged ≥65 years (n = 409 060) in Get With The Guidelines-Stroke (nationwide registry of stroke patients from 1690 sites in the USA) were followed for 3 years post-discharge. The outcomes of interest were mortality, cardiovascular and non-cardiovascular hospitalizations, heart failure (HF), and recurrence of IS/transient ischaemic attack (TIA). Patients with diabetes (29.6%) were younger and had more comorbidities. At 3 years post-discharge after IS, diabetes was associated with higher risks of adverse outcomes: all-cause mortality [cumulative incidence 46.0% vs. 44.2%, absolute difference (AD) 1.8%; adjusted hazard ratio (aHR) 1.24, 95% confidence interval 1.23-1.25], all-cause readmission (71.3% vs. 63.7%, AD 7.6%; aHR 1.22, 1.21-1.23), composite of mortality and all-cause readmission (84.1% vs. 79.3%, AD 4.8%; aHR 1.21, 1.20-1.22), composite of mortality and cardiovascular readmission (69.5% vs. 64.3%, AD 5.2%; aHR 1.19, 1.18-1.20), IS/TIA readmission (15.9% vs. 13.3%, AD 2.6%; aHR 1.18, 1.16-1.20), HF readmission (10.3% vs. 6.4%, AD 3.9%; aHR 1.60, 1.56-1.64), non-cardiovascular readmission (58.3% vs. 50.3%, AD 8.0%; aHR 1.28, 1.26-1.29), and non-IS/TIA readmission (67.6% vs. 59.7%, AD 7.9%; aHR 1.23, 1.22-1.25). Accounting for the initial severity of stroke using the National Institute of Health Stroke Scale as well as using propensity score matching method as a sensitivity analysis, did not modify the results. Conclusion: Among older IS patients diabetes was associated with increased risks of death, cardiovascular and non-cardiovascular hospitalizations, HF, and IS/TIA recurrence.