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Common causal estimands include the average treatment effect, the average treatment effect of the treated, and the average treatment effect on the controls. Using augmented inverse probability weighting methods, parametric models are judiciously leveraged to yield doubly robust estimators, that is, estimators that are consistent when at least one the parametric models is correctly specified. Three sources of uncertainty are associated when we evaluate these estimators and their variances, that is, when we estimate the treatment and outcome regression models as well as the desired treatment effect. In this article, we propose methods to calculate the variance of the normalized, doubly robust average treatment effect of the treated and average treatment effect on the controls estimators and investigate their finite sample properties. We consider both the asymptotic sandwich variance estimation, the standard bootstrap as well as two wild bootstrap methods. For the asymptotic approximations, we incorporate the aforementioned uncertainties via estimating equations. Moreover, unlike the standard bootstrap procedures, the proposed wild bootstrap methods use perturbations of the influence functions of the estimators through independently distributed random variables. We conduct an extensive simulation study where we vary the heterogeneity of the treatment effect as well as the proportion of participants assigned to the active treatment group. We illustrate the methods using an observational study of critical ill patients on the use of right heart catherization.

IMPORTANCE: The effectiveness and safety of intravenous alteplase given before or concurrently with endovascular thrombectomy (EVT) is uncertain. Randomized clinical trials suggest there is little difference in outcomes but with only modest precision and insufficient power to analyze uncommon outcomes including symptomatic intracranial hemorrhage (sICH). OBJECTIVE: To determine whether 8 prespecified outcomes are different in patients with acute ischemic stroke treated in routine clinical practice with EVT with alteplase compared with patients treated with EVT alone without alteplase. It was hypothesized that alteplase would be associated with higher risk of sICH. DESIGN, SETTING, AND PARTICIPANTS: This was an observational cohort study conducted from February 1, 2019, to June 30, 2020, that included adult patients with acute ischemic stroke treated with EVT within 6 hours of time last known well, after excluding patients without information on discharge destination and patients with in-hospital stroke. Participants were recruited from Get With The Guidelines–Stroke, a large nationwide registry of patients with acute ischemic stroke from 555 hospitals in the US. EXPOSURES: Intravenous alteplase or no alteplase. MAIN OUTCOMES AND MEASURES: Prespecified outcomes were discharge destination, independent ambulation at discharge, modified Rankin score at discharge, discharge mortality, cerebral reperfusion according to modified Thrombolysis in Cerebral Infarction grade, and sICH. RESULTS: There were 15 832 patients treated with EVT (median [IQR] age, 72.0 [61.0-82.0] years; 7932 women [50.1%]); 10 548 (66.7%) received alteplase and 5284 (33.4%) did not. Patients treated with alteplase were younger, arrived via Emergency Medical Services sooner, were less likely to have certain comorbidities, including atrial fibrillation, hypertension, and diabetes, but had similar National Institutes of Health Stroke Severity (NIHSS) scores. Compared with patients who did not receive alteplase treatment, patients treated with alteplase were less likely to die (11.1% [1173 of 10 548 patients] vs 13.9% [734 of 5284 patients]; adjusted odds ratio [aOR] 0.83; 95% CI, 0.77-0.89; P

As alternatives to the time-to-first-event analysis of composite endpoints, the win statistics, that is, the net benefit, the win ratio, and the win odds have been proposed to assess treatment effects, using a hierarchy of prioritized component outcomes based on clinical relevance or severity. Whether we are using paired organs of a human body or pair-matching patients by risk profiles or propensity scores, we can leverage the level of granularity of matched win statistics to assess the treatment effect. However, inference for the matched win statistics (net benefit, win ratio, and win odds)—quantities related to proportions—is either not available or unsatisfactory, especially in samples of small to moderate size or when the proportion of wins (or losses) is near 0 or 1. In this paper, we present methods to address these limitations. First, we introduce a different statistic to test for the null hypothesis of no treatment effect and provided a sample size formula. Then, we use the method of variance estimates recovery to derive reliable, boundary-respecting confidence intervals for the matched net benefit, win ratio, and win odds. Finally, a simulation study demonstrates the performance of the proposed methods. We illustrate the proposed methods with two data examples.

Background and ObjectivesPrior regional or single-center studies have noted that 4% to 7% of eligible patients with acute ischemic stroke (AIS) decline IV tissue plasminogen activator (tPA). We sought to determine the prevalence of tPA declination in a nationwide registry of patients with AIS and to investigate differences in declination by race/ethnicity.MethodsWe used the Get With The Guidelines–Stroke registry to identify patients with AIS eligible for tPA and admitted to participating hospitals between January 1, 2016, and March 28, 2019. We compared patient demographics and admitting hospital characteristics between tPA-eligible patients who received and those who declined tPA. Using multivariable logistic regression, we determined patient and hospital factors associated with tPA declination.ResultsAmong 177,115 tPA-eligible patients with AIS at 1,976 sites, 6,545 patients (3.7%) had tPA declination as the sole documented reason for not receiving tPA. Patients declining treatment were slightly older, were more likely to be female, arrived more often at off-hours and earlier after symptom onset, and were more likely to present to Primary Stroke Centers. Compared with non-Hispanic White, non-Hispanic Black race/ethnicity was independently associated with increased (adjusted odds ratio [aOR] 1.21, 95% CI 1.11–1.31), Asian race/ethnicity with decreased (aOR 0.72, 95% CI 0.58–0.88), and Hispanic ethnicity (any race) with similar odds of tPA declination (OR 0.98, 95% CI 0.86–1.13) in multivariable analysis.DiscussionAlthough the overall prevalence of tPA declination is low, eligible non-Hispanic Black patients are more likely and Asian patients less likely to decline tPA than non-Hispanic White patients. Reducing rates of tPA declinations among non-Hispanic Black patients may be an opportunity to address disparities in stroke care.

Introduction: An increasing number of patients with acute ischemic stroke (AIS) have recently used non-vitamin K antagonist oral anticoagulants (NOACs). However, there are limited data on safety of endovascular therapy (EVT) in these patients. Methods: We performed a retrospective, observational, cohort study of patients treated with EVT within 6 hours of symptom onset in the American Heart Association’s “Get With The Guideline-Stroke Program” between October 2015 and March 2020 to compare safety and functional outcomes in patients who were or were not taking NOACs in the 7 days prior to stroke. Results: Of 33,355 patients (median age 72 years (60,81); 50.8% female), 3,727 (11.2%) were taking NOACs, and 29,628 (88.8%) were not taking any oral anticoagulants (OAC) prior to stroke. Compared with those not on OAC, patients taking NOACs were older (median age 75 vs. 71 years) and had a higher prevalence of comorbidities including cardiovascular risk factors, although stroke severity was similar between the groups (median NIHSS 18 vs. 17). After adjusting for baseline clinical factors including intravenous alteplase, patients taking NOACs were not at a significantly higher risk of sICH compared with patients not taking anticoagulants (4.9% vs 6.4%; aOR, 0.93 [95% CI, 0.75-1.14]) or in-hospital mortality (14.1% vs 13.1%; aOR, 0.90 [95% CI, 0.78-1.02]). Of the secondary discharge outcomes, 3 of 7 showed significant differences in favor of the NOAC group including ambulating independently (33.7% vs 38.7%; aOR, 1.15 [95% CI, 1.02-1.30]) and freedom from disability (modified Rankin Scale [mRS] 0-1, 13.0% vs 16.2%; aOR, 1.23 [95% CI, 1.04-1.46]) at discharge. In a subset of patients with documented time of last NOACs dose (n=213), sICH rate was 3.1% (6/196) with last dose ≤2 days and 0% (0/17) with >2 days. Conclusions: Among patients with acute ischemic stroke treated with EVT within 6 hours, use of NOACs within the preceding 7 days, compared with no use of anticoagulants, was not associated with a significantly increased risk of adverse events and was associated with better functional outcomes at discharge.

Introduction: Emergent endovascular thrombectomy (EVT) is effective in improving outcomes in patients with stroke caused by large vessel occlusion. However, there are limited data on the use of EVT in patients taking an oral vitamin K antagonist (VKA), constraining guideline development around EVT use in this vulnerable population. Methods: To address this knowledge gap, we performed a retrospective, observational, cohort study based on a population-based sample of stroke admissions in the US (the AHAs “Get With The Guidelines-Stroke" Program) between October 2015 and March 2020. We aimed to determine whether use of VKA was associated with the risk of symptomatic intracranial hemorrhage (sICH) and functional outcomes in patients undergoing EVT within 6 hours of time last known well after adjusting for pre-specified confounders. Results: Of 32,715 patients (median age 72 years; 50.7% female), 3,087 were taking a VKA and 29,628 were not on an OAC prior to stroke. Patients taking VKAs were older (median age 78 vs. 71 years) but stroke severity was similar between the groups (median NIHSS 18 vs. 17). Of patients taking a VKA, 211 (6.8%) suffered a sICH whereas 1,904 (6.4%) patients not on OAC developed a sICH. VKA was not associated with sICH (adjusted odds ratio 1.20, 95% CI: 0.96-1.49). VKA use was associated with a higher risk of life-threatening systemic hemorrhage (1.2% vs. 1.02%; aOR 1.93 (1.17-3.19)) but not with mortality/discharge to hospice (27.1% vs. 20.6%; aOR 1.02 (0.90-1.14)). Patients taking a VKA prior to EVT were more likely to be able to be ambulatory at discharge (aOR 1.24 [1.11-1.39]) and to have an mRS of 0-2 (aOR 1.23 [1.07-1.42]). Conclusions: Among patients with acute ischemic stroke on VKA, EVT appears to be well tolerated without prohibitive risks of sICH. Our results provide support for the deployment of this critical, disability-reducing therapy in this population of patients with a large vessel occlusion presenting within 6 hours of time last known well.

After the publication of the CHANCE (Clopidogrel in High Risk Patients With Acute Nondisabling Cerebrovascular Events) and POINT (Platelet-Oriented Inhibition in New Transient Ischemic Attack and Minor Ischemic Stroke) clinical trials, the American Heart Association/American Stroke Association (AHA/ASA) issued a new class 1, level of evidence A, recommendation for dual antiplatelet therapy (DAPT; aspirin plus clopidogrel) for secondary prevention in patients with minor ischemic stroke (National Institutes of Health Stroke Scale [NIHSS] score ≤3). The extent to which variations in DAPT prescribing patterns remain and the extent to which practice patterns in the US are consistent with evidence-based guidelines are unknown.To evaluate the discharge DAPT prescribing patterns after publication of the new AHA/ASA guidelines and assess the extent of hospital-level variation in the use of DAPT for secondary prevention in patients with minor stroke (NIHSS score ≤3), as indicated by guidelines, and in patients with nonminor stroke (NIHSS score3), for whom the risks and benefits of DAPT have not been fully established.This multicenter retrospective cohort study involved 132 817 patients from 1890 hospitals participating in the AHA/ASA Get With The Guidelines-Stroke program. Patients who were hospitalized for acute ischemic stroke and prescribed antiplatelet therapy at discharge between October 1, 2019, and June 30, 2020, were included.Minor ischemic stroke (NIHSS score ≤3) vs nonminor ischemic stroke (NIHSS score3).The primary outcome was DAPT prescription at discharge. The extent to which variations in DAPT use were explained at the hospital level was assessed by calculating the median odds ratio (OR), which was derived using multivariable logistic regression analysis and compared the likelihood that 2 patients with identical clinical features admitted to 2 randomly selected hospitals (1 with higher propensity and 1 with lower propensity for DAPT use) would receive DAPT at discharge. Associations between hospital-level DAPT use among patients with minor vs nonminor stroke were evaluated using Pearson ρ correlation coefficients.Among 132 817 patients (median [IQR] age, 68 [59-78] years; 68 768 men [51.8%]), 4282 (3.2%) were Asian, 11 254 (8.5%) were Hispanic, 27 221 (20.5%) were non-Hispanic Black, 84 468 (63.6%) were non-Hispanic White, and 5592 (4.2%) were of other races and/or ethnicities (including American Indian or Alaska Native, Native Hawaiian or Pacific Islander, and unable to determine). Overall, 86 551 patients (65.2%) presented with minor ischemic stroke, and 46 266 patients (34.8%) presented with nonminor ischemic stroke. After the 2019 AHA/ASA guideline updates, 40 661 patients (47.0%) with minor stroke (NIHSS median [IQR] score, 1 [0-2]) and 19 703 patients (42.6%) with nonminor stroke (NIHSS median [IQR] score, 6 [5-9]) received DAPT at discharge. Despite guideline recommendations, 45 890 patients (53.0%) with minor stroke did not receive DAPT. After accounting for patient characteristics, substantial hospital-level variations were found in the use of DAPT in those with minor stroke (median [IQR] hospital-level DAPT prescription rate, 44.8% [33.7%-57.7%]; range, 0%-91.7%; median OR, 2.03 [95% CI, 1.97-2.09]) when comparing 2 patients with identical risk factors discharged from 2 randomly selected hospitals, 1 with higher propensity and 1 with lower propensity for DAPT use. The use of DAPT in patients with nonminor stroke also varied significantly (median [IQR] hospital-level DAPT prescription rate, 41.4% [30.0%-53.8%]; range, 0%-100%; median OR, 1.90 [95% CI, 1.83-1.97]). Overall, hospitals that were more likely to prescribe DAPT for minor strokes were also more likely to prescribe DAPT for nonminor strokes (Pearson ρ = 0.72; P .001).This cohort study found that despite updated AHA/ASA guidelines, more than 50% of patients with minor acute ischemic stroke did not receive DAPT at discharge. In contrast, more than 40% of patients with nonminor stroke received DAPT despite lack of evidence in this setting. These findings suggest that enhancing adherence to evidence-based DAPT practice guidelines may be a target for quality improvement in the treatment of patients with ischemic stroke.

Background: In 2015, endovascular therapy (EVT) for large vessel occlusions became standard of care for acute ischemic stroke. Lower utilization of IV alteplase has been reported in women, but whether sex differences in EVT use in the United States exists has not been established. Methods: We identified all acute ischemic stroke discharges from Get With The Guidelines–Stroke hospitals between 2012 and 2019 who were potentially eligible for EVT, based on National Institutes of Health Stroke Scale score ≥6 and arrival Results: Of 302 965 patients potentially eligible for EVT, 42 422 (14%) received EVT. Before 2015, EVT treatment rates were 5.3% in women and 6.6% in men. From 2015 to 2019, treatment rates increased in both sexes to 16.7% in women and 18.5% in men. The adjusted odds ratio for EVT in women compared with men was 0.93 (95% CI, 0.87–0.99) before 2015, and 0.98 (95% CI, 0.96–1.01) after 2015. There were no significant sex differences in outcomes except that after 2015, women were less able to ambulate at discharge (adjusted odds ratio, 0.95 [95% CI, 0.95–0.99]) and had lower in-hospital mortality (adjusted odds ratio, 0.93 [95% CI, 0.88–0.99]). Conclusions: EVT utilization has increased dramatically in both women and men since EVT approval in 2015. Following statistical adjustment, women were less likely to receive EVT initially, but after 2015, women were as likely as men to receive EVT. After EVT, women were more likely to be disabled at discharge but less likely to experience in-hospital death compared with men.

This study reports on food insecurity (FI) amidst the COVID-19 pandemic.College students in four regions of the US completed the two-item validated Hunger Vital Sign™ screening tool on Qualtrics.FI increased significantly after March 2020 among US students (worry about food running out: 25% to 35%; food did not last: 17% to 21%) with significant regional increase in the Midwest and South. An adjusted multivariable logistic regression model indicated students that ran out of food were significantly at greater odds of experiencing hardship with paying bills (AOR: 5.59, 95% CI =3.90-8.06).The findings identified an increase in the prevalence of FI among college students during the pandemic. Suggestions of how to address FI are discussed.

Introduction: Many patients arrive beyond the guideline-recommended time window for treatment with IV alteplase. For most of these patients, few treatment options exist. There is a need to understand the characteristics, outcomes, and healthcare costs of patients in this population in order to develop new treatments options. Methods: We analyzed patients ≥65 years old with a primary diagnosis of AIS arriving within 24 hours of time last known well (LKW) but not treated with IV alteplase at Get With The Guidelines-Stroke Hospitals in the United States (Jan 2016 - Dec 2016). We report clinical characteristics, 90-day and 1-year outcomes including Medicare costs, stratified by time from LKW to arrival (≤4.5 hours, >4.5-6 hours and >6-24 hours). Results: Of 39,760 patients (80.0% White, 10.5% Black, 4.1% Hispanic, 2.2% Asian), 20,369 (51.2%) presented from 4.5 - 24 hours of LKW. Compared to patients arriving within ≤4.5 hours, patients arriving within 4.5 - 24 hours of LKW were more likely to be Black, Hispanic, or Asian (≤4.5 hours: 9.4% Black, 3.8% Hispanic, 1.9% Asian; >4.5 - 6 hours: 11.7% Black, 4.1% Hispanic, 2.4% Asian; >6 - 24 hours since LKW: 11.6% Black, 4.4% Hispanic, 2.6% Asian; p < 0.001). The most common discharge location for those arriving within ≤4.5 hours was home; for those arriving >4.5 hours since LKW the most common discharge location was inpatient rehab (IRF) or skilled nursing facility (SNF) (≤4.5 hours: 44.7% home vs 42.3% IRF or SNF; >4.5 - 6 hours: 35.4% home vs 51.7% IRF or SNF; >6 - 24 hours: 35.8% home vs 51.0% IRF or SNF). The 90-day and 1-year mortality rates were 18.9% and 30.0% in those arriving within ≤4.5 hours, 19.0% and 29.8% in those arriving between 4.5 - 6 hours, and 19.1% and 29.1% in those arriving between 6 - 24 hours. Median 90-day inpatient costs were highest among those arriving 6 - 24 hours from LKW (≤4.5 hours: $9,471 [IQR: 5,622-21,356]; >4.5 - 6 hours: $10,884 [IQR: 6,036-25,992]; 6 -24 hours: $11,162 [6,073-26,372]). Conclusions: Results show the importance of timely hospital arrival, as well as a need to address racial disparities in arrival times, reduce costs, and develop new treatment options for patients with AIS arriving after 4.5 hours from last known well time.

Background: Metformin and sulfonylureas are frequently prescribed to patients with diabetes for glycemic control. The impact of these drugs on cardiovascular outcomes among patients with heart failure (HF) and diabetes is unclear. Methods: We evaluated Medicare beneficiaries hospitalized for HF in the Get With The Guidelines-HF Registry between 2006 and 2014 who had diabetes and Part D prescription coverage (n=29,181). Patients with glomerular filtration rate 2 or prescribed metformin or sulfonylurea prior to admission were excluded. In separate analyses for metformin and sulfonylurea, patients filling new prescriptions for each therapy within 90 days of discharge were compared with patients not prescribed therapy. Multivariable models landmarked at 90 days evaluated associations between therapy and mortality and hospitalization for HF (HHF) outcomes over the following 12 months. Secondary analyses were stratified by ejection fraction (EF) ≤40% vs >40%. Results: Of 5,852 patients, 454 (7.8%) were newly prescribed metformin and 504 (8.6%) were newly prescribed sulfonylurea. After adjustment, metformin prescription was associated with reduced risk of composite mortality/HHF, but not individual components (Table) . Associations with mortality/HHF and HHF endpoints were driven by reduced risk among patients with EF>40% (all p for interaction ≤0.04). Sulfonylurea prescription was independently associated with increased risk of mortality, HHF, and the composite. Associations between sulfonylurea prescription and endpoints were consistent regardless of EF (all p for interaction >0.12). Conclusion: Among US patients hospitalized for HF with comorbid diabetes, initiation of metformin was independently associated with improved clinical outcomes, driven by improvements among patients with preserved EF. In contrast, sulfonylurea initiation was associated with adverse clinical outcomes regardless of EF.

Background Trimethoprim-sulfamethoxazole (TMP-SMX) is considered first-line therapy for Stenotrophomonas maltophilia infections based on observational data from small studies. Levofloxacin has emerged as a popular alternative due to tolerability concerns related to TMP-SMX. Data comparing levofloxacin to TMP-SMX as targeted therapy are lacking. Methods Adult inpatient encounters January 2005 through December 2017 with growth of S maltophilia in blood and/or lower respiratory cultures were identified in the Cerner Healthfacts database. Patients included received targeted therapy with either levofloxacin or TMP-SMX. Overlap weighting was used followed by downstream weighted regression. The primary outcome was adjusted odds ratio (aOR) for in-hospital mortality or discharge to hospice. The secondary outcome was number of days from index S maltophilia culture to hospital discharge. Results Among 1581 patients with S maltophilia infections, levofloxacin (n = 823) displayed statistically similar mortality risk (aOR, 0.76 [95% confidence interval {CI}, .58–1.01]; P = .06) compared to TMP-SMX (n = 758). Levofloxacin (vs TMP-SMX) use was associated with a lower aOR of death in patients with lower respiratory tract infection (n = 1452) (aOR, 0.73 [95% CI, .54–.98]; P = .03) and if initiated empirically (n = 89) (aOR, 0.16 [95% CI, .03–.95]; P = .04). The levofloxacin cohort had fewer hospital days between index culture collection and discharge (weighted median [interquartile range], 7 [4–13] vs 9 [6–16] days; P, Our findings suggest that mortality outcomes are similar comparing levofloxacin and trimethoprim-sulfamethoxazole (TMP-SMX) treatment of Stenotrophomonas maltophilialower respiratory tract and bloodstream infections. Until trial data are available, levofloxacin appears to be a reasonable alternative to TMP-SMX for these infections.

Background: Heart failure (HF) is the leading cause of morbidity and mortality in the United States. Despite considerable advancement in the management of HF, outcomes remain suboptimal, particularly among the uninsured. In 2014, the ACA expanded Medicaid eligibility, and millions of low-income, non-elderly adults gained insurance coverage in 32 states. Little is known about Medicaid expansion’s effect on quality and outcomes of inpatient care for HF. Methods: We used the American Heart Association’s Get With The Guidelines-HF registry to assess changes in inpatient care quality and outcomes among low income, non-elderly patients hospitalized for HF prior to and following Medicaid expansion, in expansion and non-expansion states. Patients were classified as low income if covered by Medicaid, uninsured, or missing insurance. We considered expansion states to be those that implemented expansions in 2014. We constructed piecewise logistic multivariable regression models to track quarterly trends over time of quality and outcome measures in the pre-expansion (1/1/2010-12/31/2013) and post-expansion (1/1/14 - 6/30/17) periods, by state expansion status. Results: The cohort included 58,804 patients hospitalized across 391 sites - 53% were covered by Medicaid, 21.3% uninsured, and 25.6% missing insurance. Among expansion states, defect-free HF care increased significantly during the pre-expansion period (aOR 1.06, 95% CI 1.03-1.08) but did not change after expansion (aOR 0.99, 95% CI 0.97-1.02). Similarly, other quality measures, such as use of aldosterone antagonists, evidence-based beta blockers, and ICD implantation significantly increased prior to expansion, but did not change following expansion (Table). In-hospital mortality rates remained similar during the pre-expansion (aOR 0.99, 95% CI 0.96-1.02) and post-expansion periods (aOR 1.00, 95% CI 0.97-1.03). Trends in quality and outcome measures for non-expansion states are also shown in the table. Conclusion: The ACA Medicaid state expansions were not associated with improvements in quality of care or in-hospital mortality in expansion states among sites participating in a national quality improvement initiative. Future investigation should evaluate the long-term impact of expansion on HF care during the post-discharge period.

Background: While 1 in 10 patients hospitalized with heart failure (HF) die within 30 days, end-of-life care for this high-risk population is not well described. Methods: We analyzed patients discharged alive from the Get With The Guidelines-HF registry between 2005-2014, linked to Medicare claims. We compared patients discharged to hospice to non-hospice “advanced HF” patients (ejection fraction ≤25% and either on inotropes, sodium ≤130, blood urea nitrogen ≥45 mg/dL, systolic blood pressure ≤90 mmHg or comfort measures) and to other GWTG-HF patients. Results: Of 121,990 US patients, hospice patients (n=4588, 2164 facility-based, 2424 home hospice) compared with advanced HF (n=4357) and others (113,045) were older (median age 86 years vs 78 years vs 81 years), more likely white race (88% vs 80% vs 82%), have intravenous loop diuretics used (74% vs 57% vs 63%), have an advanced care plan/surrogate decision maker discussed or documented (76% vs 62% vs 66%), had more dyspnea at rest (55% vs 46% vs 48%) and worse/unchanged symptoms at discharge (35% vs 2% vs 1%) (all pth , 75 th percentile: 3, 65 days) compared with advanced HF (318 days) and others (754 days); 34% of patients discharged to a hospice facility and 12% to home hospice died in Conclusion: Hospice use in patients hospitalized with HF is limited but increasing. Few hospice patients are rehospitalized and almost a quarter die within 3 days of discharge. These findings may inform interventions to improve hospice care for HF patients.

Background: Randomized data suggest that lenient rate control (resting heart rate Methods: Using data from the Get With The Guidelines-HF Program linked with Medicare data from July 1, 2011 to September 30, 2014, we identified patients with HF and AF and evaluated the association of heart rate at discharge with subsequent outcomes and the differential association by ejection fraction. Results: Of 13 981 patients with AF, 9 100 (65.0%) had strict rate control, 4 617 (33.0%) had lenient rate control, and 264 (1.9%) had poor rate control by resting heart rate on the day of discharge. After multivariable adjustment inclusive of medical therapy, compared with strict rate control, lenient rate control was associated with higher adjusted risks of all-cause death (HR 1.21, 95% CI 1.11-1.33, p Conclusions: Among patients with HF and AF, 2 out of 3 patients had a heart rate that met strict-control heart rate goals at discharge. Heart rates above 80 bpm at discharge were associated with adverse outcomes irrespective of left ventricular ejection fraction.

This study sought to evaluate and contribute to the limited data on U.S. hospital practice patterns with respect to respiratory vaccination in patients hospitalized with heart failure (HF).Respiratory infection is a major driver of morbidity in patients with HF, and many influenza and pneumococcal infections may be prevented by vaccination.This study evaluated patients hospitalized at centers participating in the Get With The Guidelines-HF (GWTG-HF) registry from October 2012 to March 2017. The proportion of patients receiving vaccination was described for influenza and pneumococcal vaccination, respectively. The association of hospital-level vaccination rates with individual GWTG-HF performance measures and defect-free care was evaluated using multivariable modeling.This study evaluated 313,761 patients discharged from 392 hospitals during the study period. The proportion of patients receiving influenza vaccination was 68% overall and declined from 70% in 2012 to 2013 to 66% in 2016 to 2017 (p 0.001), although this was not statistically significant after adjustment (odds ratio: 1.05 per flu season; 95% confidence interval [CI]: 0.94 to 1.18). The proportion of patients receiving pneumococcal vaccination was 66% overall and decreased over the study period from 71% in 2013 to 60% in 2016 (p 0.001), remaining significant after adjustment (odds ratio: 0.75 per calendar year; 95% CI: 0.67 to 0.84). Hospitals with higher vaccination rates were more likely to discharge patients with higher performance on defect-free care and individual GWTG-HF performance measures (p 0.001). In a subset of patients with linked Medicare claims, vaccinated patients had similar rates of 1-year all-cause mortality (adjusted hazard ratio: 0.96 [95% CI: 0.89 to 1.03] for influenza vaccination; adjusted hazard ratio: 0.95 [95% CI: 0.89 to 1.01] for pneumococcal vaccination) compared with those not vaccinated.Nearly 1 in 3 patients hospitalized with HF at participating hospitals were not vaccinated for influenza or pneumococcal pneumonia, and vaccination rates did not improve from 2012 to 2017. Hospitals that exhibited higher vaccination rates performed well with respect to other HF quality of care measures. Vaccination status was not associated with differences in clinical outcomes. Further randomized controlled data are needed to assess the relationship between vaccination and outcomes.

The authors sought to elucidate the true incidence of renal replacement therapy (RRT) after transcatheter aortic valve replacement (TAVR).There is a wide discrepancy in the reported rate of RRT after TAVR (1.4% to 40%). The true incidence of RRT after TAVR is unknown.The STS/ACC TVT (Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy) registry was linked to the Centers for MedicareMedicaid database to identify all patients that underwent TAVR from November 2011 through September 2015 and their outcomes. The authors compared rates of death, new RRT, and a composite of both as a function of pre-procedure glomerular filtration rate (GFR), both in stages of chronic kidney disease (CKD), as well as on a continuous scale.Pre-procedure GFR is associated with the risk of death and new RRT after TAVR when GFR is 60 ml/min/mIn both unadjusted and adjusted analysis, pre-procedural GFR was associated with the outcomes of death and new RRT. Increasing CKD stage leads to an increased risk of death and/or RRT. Continuous analysis showed significant differences in outcomes in all levels of CKD when GFR was 60 ml/min/m

Transcatheter aortic valve replacement (TAVR) has been introduced into U.S. clinical practice with efforts to optimize outcomes and minimize the learning curve.The goal of this study was to assess the degree to which increasing experience during the introduction of this procedure, separated from other outcome determinants including patient and procedural characteristics, is associated with outcomes.The authors evaluated the association of hospital TAVR volume and patient outcomes for TAVR by using data from 42,988 commercial procedures conducted at 395 hospitals submitting to the Transcatheter Valve Therapy Registry from 2011 through 2015. Outcomes assessed included adjusted and unadjusted in-hospital major adverse events.Increasing site volume was associated with lower in-hospital risk-adjusted outcomes, including mortality (p 0.02), vascular complications (p 0.003), and bleeding (p 0.001) but was not associated with stroke (p = 0.14). From the first case to the 400th case in the volume-outcome model, risk-adjusted adverse outcomes declined, including mortality (3.57% to 2.15%), bleeding (9.56% to 5.08%), vascular complications (6.11% to 4.20%), and stroke (2.03% to 1.66%). Vascular and bleeding volume-outcome associations were nonlinear with a higher risk of adverse outcomes in the first 100 cases. An association of procedure volume with risk-adjusted outcomes was also seen in the subgroup having transfemoral access.The initial adoption of TAVR into practice in the United States showed that increasing experience was associated with better outcomes. This association, whether deemed a prolonged learning curve or a manifestation of a volume-outcome relationship, suggested that concentrating experience in higher volume heart valve centers might be a means of improving outcomes. (STS/ACC Transcatheter Valve Therapy Registry [TVT Registry]; NCT01737528).

Purpose We previously reported that calcineurin, a Ca2+/calmodulin-dependent serine/threonine phosphatase, is activated and proposed that it participates in retinal ganglion cell (RGC) apoptosis in two rodent ocular hypertension models. In this study, we tested whether calcineurin activation by itself, even in the absence of ocular hypertension, is sufficient to cause RGC degeneration. Methods We compared RGC and optic nerve morphology after adeno-associated virus serotype 2 (AAV2)–mediated transduction of RGCs with constitutively active calcineurin (CaNCA) or unactivated, wild-type calcineurin (CaNwt). Retinas and optic nerves were harvested 7–16 weeks after injection of the AAV into mouse vitreous. In flatmounted retinas, the transduced RGCs were identified with immunohistochemistry. The morphology of the RGCs was revealed by immunostaining for neurofilament SMI32 or by using GFP-M transgenic mice. A modified Sholl analysis was applied to analyze the RGC dendritic morphology. Optic nerve damage was assessed with optic nerve grading according to the Morrison standard. Results CaNwt and CaNCA were highly expressed in the injected eyes. Compared to the CaNwt-expressing RGCs, the CaNCA-expressing RGCs had smaller somas, smaller dendritic field areas, shorter total dendrite lengths, and simpler dendritic branching patterns. At 16 weeks, the CaNCA-expressing eyes had greater optic nerve damage than the CaNwt-expressing eyes. Conclusions Calcineurin activation is sufficient to cause RGC dendritic degeneration and optic nerve damage. These data support the hypothesis that calcineurin activation is an important mediator of RGC degeneration, and are consistent with the hypothesis that calcineurin activation may contribute to RGC neurodegeneration in glaucoma.

Acute kidney injury (AKI) is associated with high morbidity and mortality. The lack of sensitive and specific injury biomarkers has greatly impeded the development of therapeutic strategies to improve outcomes of AKI.The unique objective of this study was to evaluate the diagnostic performance of nine urinary biomarkers of AKI-kidney injury molecule-1 (KIM-1), neutrophil gelatinase associated lipocalin (NGAL), interleukin-18 (IL-18), hepatocyte growth factor (HGF), cystatin C (Cys), N-acetyl-beta-D-glucosaminidase (NAG), vascular endothelial growth factor (VEGF), chemokine interferon-inducible protein 10 (IP-10; CXCL10), and total protein-in a cross-sectional comparison of 204 patients with or without AKI.Median urinary concentrations of each biomarker were significantly higher in patients with AKI than in those without AKI (p0.001). The area under the receiver operating characteristics curve (AUC-ROC) for the combination of biomarkers using a logic regression model [risk score of 2.93*(NGAL5.72 and HGF0.17) + 2.93*(PROTEIN0.22) -2*(KIM0.58)] was greater (0.94) than individual biomarker AUC-ROCs. Age-adjusted levels of urinary KIM-1, NAG, HGF, VEGF, and total protein were significantly higher in patients who died or required renal replacement therapy (RRT) when compared to those who survived and did not require RRT.Our results demonstrate the comparative value of multiple biomarkers in the diagnosis and prognosis of AKI.