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INTRODUCTION: Enterococcus species, particularly E. faecium and E. faecalis, are prominent causes of bacteraemia, posing significant clinical challenges due to antibiotic resistance. The incidence of enterococcal bacteraemia, especially vancomycin-resistant E. faecium (VREfm), has been rising in Europe. This study aims to map the trends in enterococcal bacteraemia and VREfm in the Northern Dutch-German cross-border region over a decade. METHODS: We conducted a retrospective cross-sectional study at the Dutch University Medical Center Groningen (UMCG) and German Klinikum Oldenburg (KOL) from January 1, 2013, to December 31, 2022. Data on enterococcal bacteraemia episodes, patient demographics, and antibiotic resistance were collected from blood cultures. RESULTS: A total of 1,822 episodes of enterococcal bacteraemia were identified, of which 733 at KOL and 1,089 at UMCG. VRE bacteraemia was significantly higher at KOL (67 cases) compared to UMCG (7 cases). Median ages for enterococcal bacteraemia were 67 years at KOL and 61 years at UMCG. The majority of cases were in males (68.2% at KOL, 63.4% at UMCG). Haematology/Oncology wards accounted for approximately 48% of enterococcal bacteraemia cases in both hospitals. DISCUSSION: Our findings reveal significant institutional and regional differences in the incidence and characteristics of enterococcal bacteraemia. These discrepancies highlight the need for localized surveillance for understanding the epidemiology of enterococcal bacteraemia, and tailored infection control strategies. The high burden of bacteraemia in Haematology/Oncology wards underscores the vulnerability of immunocompromised patients. Enhanced cross-border collaboration and data sharing are crucial for effective infection control in this interconnected region.

Background There are limited data on the use of angiotensin receptor neprilysin inhibitors (ARNIs) in minority populations with heart failure (HF) with reduced ejection fraction. We used data from the CHAMP-HF (Change the Management of Patients With Heart Failure) registry to evaluate ARNI initiation and associated changes in health status and clinical outcomes across different races and ethnicities. Methods and Results CHAMP-HF was a prospective, observational registry of US outpatients with chronic HF with reduced ejection fraction. We compared patients starting ARNI with patients not starting ARNI using a propensity-matched analysis. Patients were grouped as Hispanic, non-Hispanic Black, non-Hispanic White, or non-Hispanic other individuals, where "non-Hispanic other" consists of all patients who did not identify as Hispanic, Black, or White. Health status was assessed using the 12-item Kansas City Cardiomyopathy Questionnaire. Outcomes were analyzed with multivariable models that included race and ethnicity, ARNI initiation, and an interaction term between race and ethnicity and ARNI initiation. Cox proportional hazards models were used for death/HF hospitalization, and multiple regression was used for change in Kansas City Cardiomyopathy Questionnaire score. The analysis included 1516 patients, with 758 patients in each group (ARNI and no ARNI). Changes in Kansas City Cardiomyopathy Questionnaire score after ARNI initiation were similar among all race and ethnicity groups (mean [SD], non-Hispanic White individuals, 3.5 [19.0]; non-Hispanic Black individuals, 2.0 [17.0]; non-Hispanic other individuals, 5.5 [20.3]; and Hispanic individuals, 3.2 [20.1]), with no statistically significant interaction between race and ethnicity and ARNI initiation (P=0.21). There was similarly no statistically significant interaction between race and ethnicity and ARNI initiation for HF hospitalization (P=0.82) or all-cause mortality (P=0.92). Conclusions In a large registry of outpatients with HF with reduced ejection fraction, the association between ARNI initiation and outcomes did not differ by race and ethnicity. These data support the use of ARNI therapy for chronic HF with reduced ejection fraction irrespective of race and ethnicity.

Textiles are used by humans for many purposes, from clothing to technical applications such as geotextiles, agrotextiles, or medical textiles. However, in addition to their importance, textiles are also responsible for various types of environmental pollution along the entire textile chain, from production, transport and trade to daily use to their end-of-life. Here we provide a brief overview of current approaches to establishing R principles in the textile industry in order to transform the recent linear structures into a circular economy and show in which areas there is a particular need for research and action.

Background Days alive out of hospital (DAOH) is an objective and patient‐centered net benefit end point. There are no assessments of DAOH in clinical trials of interventions for atrial fibrillation (AF), and it is not known whether this end point is of clinical utility in these populations. Methods and Results ROCKET AF (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation) was an international double‐blind, double‐dummy randomized clinical trial that compared rivaroxaban with warfarin in patients with atrial fibrillation at increased risk for stroke. We assessed DAOH using investigator‐reported event data for up to 12 months after randomization in ROCKET AF. We assessed DAOH overall, by treatment group, and by subgroup, including age, sex, and comorbidities, using Poisson regression. The mean±SD number of days dead was 7.3±41.2, days hospitalized was 1.2±7.2, and mean DAOH was 350.7±56.2, with notable left skew. Patients with comorbidities had fewer DAOH overall. There were no differences in DAOH by treatment arm, with mean DAOH of 350.6±56.5 for those randomized to rivaroxaban and 350.7±55.8 for those randomized to warfarin (P=0.86). A sensitivity analysis found no difference in DAOH not disabled with rivaroxaban versus warfarin (DAOH not disabled, 349.2±59.5 days and 349.1 days±59.3 days, respectively, P=0.88). Conclusions DAOH did not identify a treatment difference between patients randomized to rivaroxaban versus warfarin. This may be driven in part by the low overall event rates in atrial fibrillation anticoagulation trials, which leads to substantial left skew in measures of DAOH.

Background Previous studies of patients with nontraumatic subarachnoid hemorrhage (SAH) suggest better outcomes at hospitals with higher case and procedural volumes, but the shape of the volume-outcome curve has not been defined. We sought to establish minimum volume criteria for SAH and aneurysm obliteration procedures that could be used for comprehensive stroke center certification. Methods and Results Data from 8512 discharges in the National Inpatient Sample (NIS) from 2010 to 2011 were analyzed using logistic regression models to evaluate the association between clinical outcomes (in-hospital mortality and the NIS-SAH Outcome Measure [NIS-SOM]) and measures of hospital annual case volume (nontraumatic SAH discharges, coiling, and clipping procedures). Sensitivity and specificity analyses for the association of desirable outcomes with different volume thresholds were performed. During 8512 SAH hospitalizations, 28.7% of cases underwent clipping and 20.1% underwent coiling with rates of 21.2% for in-hospital mortality and 38.6% for poor outcome on the NIS-SOM. The mean (range) of SAH, coiling, and clipping annual case volumes were 30.9 (1-195), 8.7 (0-94), and 6.1 (0-69), respectively. Logistic regression demonstrated improved outcomes with increasing annual case volumes of SAH discharges and procedures for aneurysm obliteration, with attenuation of the benefit beyond 35 SAH cases/year. Analysis of sensitivity and specificity using different volume thresholds confirmed these results. Analysis of previously proposed volume thresholds, including those utilized as minimum standards for comprehensive stroke center certification, showed that hospitals with more than 35 SAH cases annually had consistently superior outcomes compared with hospitals with fewer cases, although some hospitals below this threshold had similar outcomes. The adjusted odds ratio demonstrating lower risk of poor outcomes with SAH annual case volume ≥35 compared with 20 to 34 was 0.82 for the NIS-SOM (95% CI, 0.71-094; P=0.0054) and 0.80 (95% CI, 0.68-0.93; P=0.0055) for in-hospital mortality. Conclusions Outcomes for patients with SAH improve with increasing hospital case volumes and procedure volumes, with consistently better outcomes for hospitals with more than 35 SAH cases per year.

Abstract Background Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing interstitial lung disease characterised by decline in lung function. We evaluated trajectories of forced vital capacity (FVC) and diffusing capacity (DLco) in a cohort of patients with IPF. Methods Patients with IPF that was diagnosed or confirmed at the enrolling centre in the previous 6 months were enrolled into the IPF-PRO Registry between June 2014 and October 2018. Patients were followed prospectively, with lung function data collected as part of routine clinical care. Mean trajectories of FVC and DLco % predicted in all patients and in subgroups by characteristics assessed at enrolment were estimated using a joint model that accounted for factors such as disease severity and visit patterns. Results Of 1002 patients in the registry, 941 had ≥ 1 FVC and/or DLco measurement after enrolment. The median (Q1, Q3) follow-up period was 35.1 (18.9, 47.2) months. Overall, mean estimated declines in FVC and DLco % predicted were 2.8% and 2.9% per year, respectively. There was no evidence that the mean trajectories of FVC or DLco had a non-linear relationship with time at the population level. Patients who were male, white, had a family history of ILD, were using oxygen, or had prior/current use of antifibrotic therapy at enrolment had greater rates of decline in FVC % predicted. Patients who were male or white had greater rates of decline in DLco % predicted. Conclusions Data from the IPF-PRO Registry suggest a constant rate of decline in lung function over a prolonged period, supporting the inexorably progressive nature of IPF. A graphical abstract summarising the data in this manuscript is available at: https://www.usscicomms.com/respiratory/IPF-PRORegistry_LungFunctionTrajectories . Trial registration NCT01915511.

AimsThe aim of our study was to investigate heterogeneity of health status treatment response of sacubitril/valsartan in patients with heart failure with reduced ejection fraction (HFrEF).Methods and resultsWe leveraged data from CHAMP-HF, an observational registry of 140 US clinics and 5026 outpatients with chronic HFrEF, where health status was serially assessed using the Kansas City Cardiomyopathy Questionnaire (KCCQ)-12 Overall Summary Scale (range from 0 to 100; ≥20-point improvement is a very large improvement). In 334 patients newly initiated on sacubitril/valsartan, we used hierarchical multivariable logistic regression (13 patient-level characteristics as well as baseline KCCQ-12 score) to calculate the odds ratio (OR) of any characteristic being associated with a very large health status improvement. A total of 104/334 (31.1%) of patients achieved the primary endpoint, where only worse baseline health status [KCCQ-12 score of 0-60 points had an OR = 0.86/5-point higher score (CI 0.79, 0.93)], and those with a KCCQ-12 score of 60-80 points had an OR = 0.61/5-point higher score (0.45-0.82), which was associated with a very large benefit. No other patient characteristic was associated with a very large health status improvement (P > 0.05).ConclusionsWe found that, after initiation of sacubitril/valsartan, only worse baseline health status was associated with very large health status improvement. Accordingly, a trial of therapy-particularly in those with worse symptoms, function, and quality of life-and assessing treatment response are likely to be the best prospective strategy.

Two hundred and nine undergraduate students at a large public research institution were surveyed about their sense of mattering and well-being and their perceptions of the resources available to them at the university and how these affected their overall attitudes toward their educational experience. Significant relationships between well-being, mattering, and institutional resources were found as well as significant differences in well-being and mattering between some demographic groups. The results suggest that mattering, especially mattering to peers, is a unique factor influencing college student well-being. As colleges and universities work to improve their environments so that all students have quality experiences, attention to the affective aspects of education might yield positive impacts.

IntroductionPatient-reported outcomes (PROs) and satisfaction endpoints are increasingly important in clinical trials and may be associated with treatment adherence. In this post hoc substudy from ROCKET AF, we examined whether patient-reported satisfaction was associated with study drug discontinuation.MethodsROCKET AF (n = 14,264) compared rivaroxaban with warfarin for prevention of stroke and systemic embolism in patients with atrial fibrillation. We analyzed treatment satisfaction scores: the Anti-Clot Treatment Scale (ACTS) and Treatment Satisfaction Questionnaire for Medication version II (TSQM II). We compared satisfaction with study drug between the two treatment arms, and examined the association between satisfaction and patient-driven study drug discontinuation (stopping study drug due to withdrawal of consent, noncompliance, or loss to follow-up).ResultsA total of 1577 (11%) patients participated in the Patient Satisfaction substudy; 1181 (8.3%) completed both the ACTS and TSQM II 4 weeks after starting study drug. Patients receiving rivaroxaban did not experience significant differences in satisfaction compared with those receiving warfarin. During a median follow-up of 1.6 years, 448 premature study drug discontinuations occurred (213 rivaroxaban group; 235 warfarin group), of which 116 (26%) were patient-driven (52 [24%] rivaroxaban group; 64 [27%] warfarin group). No significant differences were observed between satisfaction level and rates of patient-driven study drug discontinuation.ConclusionsStudy drug satisfaction did not predict rate of study drug discontinuation. No significant difference was observed between satisfaction with warfarin and rivaroxaban, as expected given the double-blind trial design. Although these results are negative, the importance of PRO data will only increase, and these analyses may inform future studies that explore the relationship between drug-satisfaction PROs, adherence, and clinical outcomes. CLINICALTRIALS.GOV: NCT00403767.FundingThe ROCKET AF trial was funded by Johnson & Johnson and Bayer.

ObjectivesThis study sought to describe the short-term health status benefits of angiotensin-neprilysin inhibitor (ARNI) therapy in patients with heart failure and reduced ejection fraction (HFrEF).BackgroundAlthough therapy with sacubitril/valsartan, a neprilysin inhibitor, improved patients' health status (compared with enalapril) at 8 months in the PARADIGM-HF (Prospective Comparison of ARNI with ACE inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure) study, the early impact of ARNI on patients' symptoms, functions, and quality of life is unknown.MethodsHealth status was assessed by using the 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ) in 3,918 outpatients with HFrEF and left ventricular ejection fraction ≤40% across 140 U.S. centers in the CHAMP-HF (Change the Management of Patients with Heart Failure) registry. ARNI therapy was initiated in 508 patients who were matched 1:2 to 1,016 patients who were not initiated on ARNI (no-ARNI), using a nonparsimonious time-dependent propensity score (6 sociodemographic factors, 23 clinical characteristics), prior KCCQ overall summary (KCCQ-OS) score, and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker status.ResultsMultivariate linear regression demonstrated a greater mean improvement in KCCQ-OS in patients initiated on ARNI therapy (5.3 ± 19 vs. 2.5 ± 17.4, respectively; p

BackgroundWhen used in appropriately selected heart failure (HF) patients, cardiac resynchronization therapy (CRT) reduces mortality and hospitalization. It is not understood whether CRT implantation during hospitalization for HF is associated with similar benefits.HypothesisTiming of CRT implantation relative to hospitalization for HF is associated with clinical outcomes.MethodsThis analysis included patients eligible for CRT and discharged alive between January 2005 and December 2012 from 388 hospitals in Get With The Guidelines-HF. Participants were linked with Centers for Medicare and Medicaid Services data to evaluate outcomes of all-cause mortality and HF re-hospitalization based on CRT status (present on admission, placed during hospitalization, and prescribed at discharge; reference = no CRT).ResultsOf 15 619 CRT-eligible HF patients, 2408 (15%) had CRT on admission, 1269 (8%) underwent CRT implantation during hospitalization and 643 (4%) had CRT prescribed at discharge. Compared with patients without CRT, mortality was lower in those who received CRT implantation during HF hospitalization (adjusted hazard ratio [HR] 0.63; P < 0.0001) and those prescribed CRT at discharge (adjusted HR 0.78; P = 0.048). A reduction in HF re-hospitalization was observed in patients with CRT implanted during hospitalization (adjusted HR 0.64; P < 0.0001), but not in those who were prescribed CRT at discharge (adjusted HR 1.02; P = 0.77).ConclusionCRT implantation during HF hospitalization was associated with lower rates of mortality and HF re-hospitalization. These data suggest that a CRT utilization strategy that does not delay implantation to the post-discharge period may be appropriate. Randomized data are needed to definitively identify optimal timing of CRT implantation.

ImportanceThe extent to which levels of high-sensitivity C-reactive protein (hs-CRP), a known marker of increased cardiovascular risk, are elevated and are associated with standard cardiovascular risk factors in patients with a history of myocardial infarction (MI) is unknown.ObjectivesTo determine the pattern and determinants of the distribution of hs-CRP in those with a prior MI in the United States using a nationally representative sample.Design and participantsAdults with hs-CRP data in the National Health and Nutrition Examination Surveys from 1999-2010.ResultsAmong 1296 individuals in our cohort, the median age was 65 years and the median hs-CRP level was 2.69 mg/L, measured an average of 7.1 years after the MI. Among these patients, 22% had hs-CRP levels of

Abstract Background Performance benchmarks for the management of idiopathic pulmonary fibrosis (IPF) have not been established. We used data from the IPF-PRO Registry, an observational registry of patients with IPF managed at sites across the US, to examine associations between the characteristics of the enrolling sites and patient outcomes. Methods An online survey was used to collect information on the resources, operations, and self-assessment practices of IPF-PRO Registry sites that enrolled ≥ 10 patients. Site variability in 1-year event rates of clinically relevant outcomes, including death, death or lung transplant, and hospitalization, was assessed. Models were adjusted for differences in patient case mix by adjusting for known predictors of each outcome. We assessed whether site-level heterogeneity existed for each patient-level outcome, and if so, we investigated potential drivers of the heterogeneity. Results All 27 sites that enrolled ≥ 10 patients returned the questionnaire. Most sites were actively following > 100 patients with IPF (70.4%), had a lung transplant program (66.7%), and had a dedicated ILD nurse leader (77.8%). Substantial heterogeneity was observed in the event rates of clinically relevant outcomes across the sites. After controlling for patient case mix, there were no outcomes for which the site variance component was significantly different from 0, but the p-value for hospitalization was 0.052. Starting/completing an ILD-related quality improvement project in the previous 2 years was associated with a lower risk of hospitalization (HR 0.60 [95% CI 0.44, 0.82]; p = 0.001). Conclusions Analyses of data from patients with IPF managed at sites across the US found no site-specific characteristics or practices that were significantly associated with clinically relevant outcomes after adjusting for patient case mix. Trial registration ClinicalTrials.gov, NCT01915511. Registered 5 August 2013, https://clinicaltrials.gov/ct2/show/NCT01915511

The 2013 American College of Cardiology/American Heart Association cholesterol guidelines recommend high-intensity statins for patients after myocardial infarction (MI) rather than treating to a low-density lipoprotein cholesterol goal, as the previous ATP III (Adult Treatment Panel third report) guidelines had advised. To evaluate the frequency of postdischarge lipid testing and high-intensity statin use among MI patients discharged on a statin during the ATP III guidelines era, we linked ACTION (Acute Coronary Treatment and Intervention Outcomes Network) Registry data to Medicare claims for 11 046 MI patients aged ≥65 years who were discharged alive on a statin from 347 hospitals (2007-2009). Multivariable regression was used to evaluate the association between lipid testing and 1-year high-intensity statin use. Only 21% of MI patients were discharged on a high-intensity statin. By 90 days after MI, 44% of patients discharged on a statin underwent lipid testing (43% on low- or moderate-intensity statins and 49% on high-intensity statins; P=0.001). Follow-up lipid testing rates were 47% among patients with in-hospital low-density lipoprotein cholesterol ≥100 mg/dL and 47% among newly prescribed statin recipients. By 1 year, only 14% of patients were on high-intensity statins. Only 4% of patients discharged on low- or moderate-dose statin were uptitrated to high intensity; postdischarge lipid testing was associated with a slightly higher likelihood of high-intensity statin use by 1 year (5.4% versus 2.9%, adjusted odds ratio: 1.92; 95% confidence interval, 1.52-2.41). Previous guidelines recommended low-density lipoprotein cholesterol goal-directed statin therapy, but lipid testing and high-intensity statin use were infrequent after MI. The American College of Cardiology/American Heart Association guidelines may promote more intensive cardiovascular risk reduction by eliminating treatment dependence on lipid testing.

AimsPost-stroke hypertension is associated with poor short-term outcome, although the results have been conflicting. Our objective was to evaluate the association of blood pressure (BP) and in-hospital outcomes in patients with acute ischaemic stroke.Methods and resultsPatients in the Get With The Guidelines-Stroke registry with acute ischaemic stroke were included. Admission systolic and diastolic BP was used to compute mean arterial pressure (MAP) and pulse pressure (PP). The outcomes of interest were: in-hospital mortality, not discharged home, inability to ambulate independently at discharge and haemorrhagic complications due to thrombolytic therapy. A total of 309 611 patients with an ischaemic stroke were included. There was a J-shaped/U-shaped relationship between systolic BP and outcomes. Both lower and higher systolic BP values, compared with a central reference value, had higher risk of in-hospital death [e.g. adjusted odds ratio (95% confidence interval) (OR[CI]) = 1.16[1.13-1.20] for 120 vs. 150 mmHg and 1.24[1.19-1.30] for 200 vs. 150 mmHg], not discharged home (OR[CI] = 1.11[1.09-1.13] for 120 vs. 150 mmHg and 1.15[1.12-1.18] for 200 vs. 150 mmHg), inability to ambulate independently at discharge (OR[CI] = 1.16[1.13-1.18] for 120 vs. 150 mmHg and 1.09[1.06-1.11] for 200 vs. 150 mmHg). However, risk of haemorrhagic complications of thrombolytic therapy was lower with lower systolic BP (OR[CI] = 0.89[0.83-0.97] for 120 vs. 150 mmHg), while higher with higher systolic BP (OR[CI] = 1.21[1.11-1.32] for 200 vs. 150 mmHg). The results were largely similar for admission diastolic BP, MAP, and PP.ConclusionIn patients hospitalized with ischaemic stroke, J-shaped, or U-shaped relationships were observed between BP variables and short-term outcomes. However, haemorrhagic complications with thrombolytic therapy were lower with lower BP.

While hydrogen is regularly discussed as a possible option for storing regenerative energies, its low minimum ignition energy and broad range of explosive concentrations pose safety challenges regarding hydrogen storage, and there are also challenges related to hydrogen production and transport and at the point of use. A risk assessment of the whole hydrogen energy system is necessary to develop hydrogen utilization further. Here, we concentrate on the most important hydrogen storage technologies, especially high-pressure storage, liquid hydrogen in cryogenic tanks, methanol storage, and salt cavern storage. This review aims to study the most recent research results related to these storage techniques by describing typical sensors and explosion protection measures, thus allowing for a risk assessment of hydrogen storage through these technologies. [ABSTRACT FROM AUTHOR]

Background: Insulin use may be a better predictor of stroke risk and morbidity and mortality than diabetes in patients with atrial fibrillation (AF). Objectives: Determine if the increased risk of stroke observed in patients with AF and diabetes is restricted to those treated with insulin. Methods: We analyzed the association between diabetes and treatment and the occurrence of stroke/systemic embolism, myocardial infarction (MI), all-cause death, vascular death, composite outcomes, and bleeding risk in the ROCKET AF trial. Results: In a cohort of 14,264 patients, there were 40.3% (n = 5746) with diabetes, 5.9% (n = 842) on insulin, 18.9% (n = 2697) on oral medications, and 11.9% (n = 1703) diet-controlled. Compared to those without diabetes, patients with non–insulin-treated diabetes had increased risks of stroke (hazard ratio [HR] 1.33, 95% confidence interval [CI] 1.06–1.68), MI (HR 1.64, 95% CI 1.17–2.30), all-cause death (HR 1.26, 95% CI 1.08–1.46), vascular death (HR 1.33, 95% CI 1.11–1.60), and composite outcomes (HR 1.37, 95% CI 1.18–1.157). Patients with insulin-treated diabetes had a significantly higher risk of MI (HR 2.31, 95% CI 1.33–4.01) and composite outcomes (HR 1.57, 95% CI 1.19–2.08) compared to those without diabetes. There were no significant differences between insulin-treated and non–insulin-treated diabetes for any outcome. Conclusion: Among patients with AF and diabetes, there were no significant differences in outcomes in insulin-treated diabetes compared to non–insulin-treated diabetes.

Abstract Aims The aim of our study was to investigate heterogeneity of health status treatment response of sacubitril/valsartan in patients with heart failure with reduced ejection fraction (HFrEF). Methods and results We leveraged data from CHAMP‐HF, an observational registry of 140 US clinics and 5026 outpatients with chronic HFrEF, where health status was serially assessed using the Kansas City Cardiomyopathy Questionnaire (KCCQ)‐12 Overall Summary Scale (range from 0 to 100; ≥20‐point improvement is a very large improvement). In 334 patients newly initiated on sacubitril/valsartan, we used hierarchical multivariable logistic regression (13 patient‐level characteristics as well as baseline KCCQ‐12 score) to calculate the odds ratio (OR) of any characteristic being associated with a very large health status improvement. A total of 104/334 (31.1%) of patients achieved the primary endpoint, where only worse baseline health status [KCCQ‐12 score of 0–60 points had an OR = 0.86/5‐point higher score (CI 0.79, 0.93)], and those with a KCCQ‐12 score of 60–80 points had an OR = 0.61/5‐point higher score (0.45–0.82), which was associated with a very large benefit. No other patient characteristic was associated with a very large health status improvement (P > 0.05). Conclusions We found that, after initiation of sacubitril/valsartan, only worse baseline health status was associated with very large health status improvement. Accordingly, a trial of therapy—particularly in those with worse symptoms, function, and quality of life—and assessing treatment response are likely to be the best prospective strategy.

Background The WATCH‐DM (weight [body mass index], age, hypertension, creatinine, high‐density lipoprotein cholesterol, diabetes control [fasting plasma glucose], ECG QRS duration, myocardial infarction, and coronary artery bypass grafting) and TRS‐HFDM (Thrombolysis in Myocardial Infarction [TIMI] risk score for heart failure in diabetes) risk scores were developed to predict risk of heart failure (HF) among individuals with type 2 diabetes. WATCH‐DM was developed to predict incident HF, whereas TRS‐HFDM predicts HF hospitalization among patients with and without a prior HF history. We evaluated the model performance of both scores to predict incident HF events among patients with type 2 diabetes and no history of HF hospitalization across different cohorts and clinical settings with varying baseline risk. Methods and Results Incident HF risk was estimated by the integer‐based WATCH‐DM and TRS‐HFDM scores in participants with type 2 diabetes free of baseline HF from 2 randomized clinical trials (TECOS [Trial Evaluating Cardiovascular Outcomes With Sitagliptin], N=12 028; and Look AHEAD [Look Action for Health in Diabetes] trial, N=4867). The integer‐based WATCH‐DM score was also validated in electronic health record data from a single large health care system (N=7475). Model discrimination was assessed by the Harrell concordance index and calibration by the Greenwood‐Nam‐D’Agostino statistic. HF incidence rate was 7.5, 3.9, and 4.1 per 1000 person‐years in the TECOS, Look AHEAD trial, and electronic health record cohorts, respectively. Integer‐based WATCH‐DM and TRS‐HFDM scores had similar discrimination and calibration for predicting 5‐year HF risk in the Look AHEAD trial cohort (concordance indexes=0.70; Greenwood‐Nam‐D’Agostino P>0.30 for both). Both scores had lower discrimination and underpredicted HF risk in the TECOS cohort (concordance indexes=0.65 and 0.66, respectively; Greenwood‐Nam‐D’Agostino P

Background There are limited data on the use of angiotensin receptor neprilysin inhibitors (ARNIs) in minority populations with heart failure (HF) with reduced ejection fraction. We used data from the CHAMP‐HF (Change the Management of Patients With Heart Failure) registry to evaluate ARNI initiation and associated changes in health status and clinical outcomes across different races and ethnicities. Methods and Results CHAMP‐HF was a prospective, observational registry of US outpatients with chronic HF with reduced ejection fraction. We compared patients starting ARNI with patients not starting ARNI using a propensity‐matched analysis. Patients were grouped as Hispanic, non‐Hispanic Black, non‐Hispanic White, or non‐Hispanic other individuals, where “non‐Hispanic other” consists of all patients who did not identify as Hispanic, Black, or White. Health status was assessed using the 12‐item Kansas City Cardiomyopathy Questionnaire. Outcomes were analyzed with multivariable models that included race and ethnicity, ARNI initiation, and an interaction term between race and ethnicity and ARNI initiation. Cox proportional hazards models were used for death/HF hospitalization, and multiple regression was used for change in Kansas City Cardiomyopathy Questionnaire score. The analysis included 1516 patients, with 758 patients in each group (ARNI and no ARNI). Changes in Kansas City Cardiomyopathy Questionnaire score after ARNI initiation were similar among all race and ethnicity groups (mean [SD], non‐Hispanic White individuals, 3.5 [19.0]; non‐Hispanic Black individuals, 2.0 [17.0]; non‐Hispanic other individuals, 5.5 [20.3]; and Hispanic individuals, 3.2 [20.1]), with no statistically significant interaction between race and ethnicity and ARNI initiation (P=0.21). There was similarly no statistically significant interaction between race and ethnicity and ARNI initiation for HF hospitalization (P=0.82) or all‐cause mortality (P=0.92). Conclusions In a large registry of outpatients with HF with reduced ejection fraction, the association between ARNI initiation and outcomes did not differ by race and ethnicity. These data support the use of ARNI therapy for chronic HF with reduced ejection fraction irrespective of race and ethnicity.

BackgroundClinical trials of implantable cardioverter defibrillators (ICDs) for primary prevention enrolled a limited number of women. We sought to examine clinical practice data to compare survival rates among women with heart failure with or without a primary prevention ICD.Methods and resultsWe linked data from 264 US hospitals included in the Get With The Guidelines for Heart Failure registry with data from the Centers for Medicare and Medicaid Services. From these sources, we propensity score matched 430 women with heart failure who received a primary prevention ICD to 430 women who did not; we further adjusted using a Cox proportional hazards model. Median follow-up was 3.4 and 3.0 years. For comparison, we matched 859 men receiving an ICD with 859 who did not; median follow-up was 3.9 versus 2.9 years. In the matched cohorts, an ICD was associated with similarly better survival in women (hazard ratio, 0.78; 95% confidence interval, 0.66-0.92; P=0.003) and men (hazard ratio, 0.76; 95% confidence interval, 0.67-0.87 P

BackgroundDifferences in activation of emergency medical services (EMS) may contribute to racial/ethnic and sex disparities in stroke outcomes. The purpose of this study was to determine whether EMS use varied by race/ethnicity and sex among a current, diverse national sample of hospitalized acute stroke patients.Methods and resultsWe analyzed data from 398,798 stroke patients admitted to 1613 Get With The Guidelines-Stroke participating hospitals between October 2011 and March 2014. Multivariable logistic regression was used to evaluate the associations between combinations of racial/ethnic and sex groups with EMS use, adjusting for potential confounders including demographics, medical history, and stroke symptoms. Patients were 50% female, 69% white, 19% black, 8% Hispanic, 3% Asian, and 1% other, and 86% had ischemic stroke. Overall, 59% of stroke patients were transported to the hospital by EMS. White women were most likely to use EMS (62%); Hispanic men were least likely to use EMS (52%). After adjustment for patient characteristics, Hispanic and Asian men and women had 20% to 29% lower adjusted odds of using EMS versus their white counterparts; black women were less likely than white women to use EMS (odds ratio 0.75, 95% CI 0.72 to 0.77). Patients with weakness or paresis, altered level of consciousness, and/or aphasia were significantly more likely to use EMS than patients without each symptom; the observed racial/ethnic and sex differences in EMS use remained significant after adjustment for stroke symptoms.ConclusionsEMS use differed by race/ethnicity and sex. These contemporary data document suboptimal use of EMS transport among US stroke patients, especially by racial/ethnic minorities and those with less recognized stroke symptoms.

BackgroundImplantable cardioverter-defibrillator (ICD) therapy is associated with improved outcomes in patients with heart failure (HF), but whether this association holds among older patients with multiple comorbid illnesses and worse HF burden remains unclear.Methods and resultsUsing the National Cardiovascular Data Registry's ICD Registry and the Get With The Guidelines-Heart Failure (GWTG-HF) registry linked with Medicare claims, we examined outcomes associated with primary-prevention ICD versus no ICD among HF patients aged ≥65 years in clinical practice. We included patients with an ejection fraction ≤35% who received (ICD Registry) and who did not receive (GWTG-HF) an ICD. Compared with patients with an ICD, patients in the non-ICD group were older and more likely to be female and white. In matched cohorts, the 3-year adjusted mortality rate was lower in the ICD group versus the non-ICD group (46.7% versus 55.8%; adjusted hazard ratio [HR] 0.76; 95% CI 0.69 to 0.83). There was no associated difference in all-cause readmission (HR 0.99; 95% CI 0.92 to 1.08) but a lower risk of HF readmission (HR 0.88; 95% CI 0.80 to 0.97). When compared with no ICD, ICDs were also associated with better survival in patients with ≤3 comorbidities (HR 0.77; 95% CI 0.69 to 0.87) and >3 comorbidities (HR 0.77; 95% CI 0.64 to 0.93) and in patients with no hospitalization for HF (HR 0.75; 95% CI 0.65 to 0.86) and at least 1 prior HF hospitalization (HR 0.69; 95% CI 0.58 to 0.82). In subgroup analyses, there were no interactions between ICD and mortality risk for comorbidity burden (P=0.95) and for prior HF hospitalization (P=0.46).ConclusionAmong older HF patients, ICDs for primary prevention were associated with lower risk of mortality even among those with high comorbid illness burden and prior HF hospitalization.

BackgroundSudden cardiac death is the leading cause of death among end-stage kidney disease patients (ESKD) on dialysis, but the benefit of primary prevention implantable cardioverter defibrillators (ICDs) in this population is uncertain. We conducted this investigation to compare the mortality of dialysis patients receiving a primary prevention ICD with matched controls.MethodsWe used data from the National Cardiovascular Data Registry's ICD Registry to select dialysis patients who received a primary prevention ICD, and the Get with the Guidelines-Heart Failure Registry to select a comparator cohort. We matched ICD recipients and no-ICD patients using propensity score techniques to reduce confounding, and overall survival was compared between groups.ResultsWe identified 108 dialysis patients receiving primary prevention ICDs and 195 comparable dialysis patients without ICDs. One year (3-year) mortality was 42.2% (68.8%) in the ICD registry cohort compared with 38.1% (75.7%) in the control cohort. There was no significant survival advantage associated with ICD [hazard ratio (HR) 0.87, 95% confidence interval (CI) 0.66-1.13, log-rank P = 0.29]. After propensity matching, our analysis included 86 ICD patients and 86 matched controls. Comparing the propensity-matched cohorts, 1 year (3 years) mortality was 43.4% (74.0%) in the ICD cohort and 39.7% (76.6%) in the control cohort; there was no significant difference in mortality outcome between groups (HR = 0.94, 95% CI: 0.67-1.31, log-rank P = 0.71).ConclusionsWe did not observe a significant association between primary prevention ICDs and reduced mortality among ESKD patients receiving dialysis. Consideration of the potential risks and benefits of ICD implantation in these patients should be undertaken while awaiting the results of definitive clinical trials.

Background In event‐driven clinical trials, study termination is based on accrual of a target number of primary efficacy events. For noninferiority trials in which superiority is conditionally examined, the ideal cohort in which to track event accrual is unclear. We used data from the ROCKET AF (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation) trial to determine the effect of primary efficacy‐event tracking in the per‐protocol cohort during the on‐treatment period versus the intention‐to‐treat (ITT) cohort during the ITT period. Methods and Results ROCKET AF was terminated after accruing 429 primary efficacy events (stroke or systemic embolism) in the per‐protocol cohort during the on‐treatment period for noninferiority. We identified the date on which 429 events occurred in the ITT cohort during the ITT period. We performed noninferiority and superiority analyses based on hypothetical study termination on this date. ROCKET AF would have terminated 226 days earlier if events were tracked during the ITT period. Similar to the main trial findings, rivaroxaban would have met noninferiority versus warfarin for the primary efficacy end point (hazard ratio [HR], 0.77; 95% CI, 0.62–0.96; P

BackgroundRacial and ethnic minorities are under-represented in clinical trials of primary prevention implantable cardioverter-defibrillators (ICDs). This analysis investigates the association between primary prevention ICDs and mortality among Medicare, racial/ethnic minority patients.Methods and resultsData from Get With The Guidelines-Heart Failure Registry and National Cardiovascular Data Registry's ICD Registry were used to perform an adjusted comparative effectiveness analysis of primary prevention ICDs in Medicare, racial/ethnic minority patients (nonwhite race or Hispanic ethnicity). Mortality data were obtained from the Medicare denominator file. The relationship of ICD with survival was compared between minority and white non-Hispanic patients. Our analysis included 852 minority patients, 426 ICD and 426 matched non-ICD patients, and 2070 white non-Hispanic patients (1035 ICD and 1035 matched non-ICD patients). Median follow-up was 3.1 years. Median age was 73 years, and median ejection fraction was 23%. Adjusted 3-year mortality rates for minority ICD and non-ICD patients were 44.9% (95% confidence interval [CI], 44.2%-45.7%) and 54.3% (95% CI, 53.4%-55.1%), respectively (adjusted hazard ratio, 0.79; 95% CI, 0.63-0.98; P=0.034). White non-Hispanic patients receiving an ICD had lower adjusted 3-year mortality rates of 47.8% (95% CI, 47.3%-48.3%) compared with 57.3% (95% CI, 56.8%-57.9%) for those with no ICD (adjusted hazard ratio, 0.75; 95% CI, 0.67%-0.83%; P

ObjectivesThe purpose of this study was to assess the benefit of primary prevention implantable cardioverter defibrillators (ICDs) in women.BackgroundClinical trials of primary prevention ICDs enrolled a limited number of women.MethodsUsing a propensity score method, we matched 490 women ≥65 years of age who received an ICD during a hospitalization for heart failure in the National Cardiovascular Data Registry ICD Registry from January 1, 2006, through December 31, 2007, to 490 ICD-eligible women without an ICD hospitalized for heart failure in the Get With The Guidelines for Heart Failure database from January 1, 2006, through December 31, 2009. The primary endpoint was all-cause mortality obtained from the Medicare Claims Database. An identical analysis was conducted in men.ResultsMedian follow-up for patients with an ICD was 4.6 years versus 3.2 years for patients with no ICD. Compared with women with no ICD, those with an ICD were younger and less frequently white. In the matched cohorts, the survival of women with an ICD was significantly longer than that of women without an ICD (adjusted hazard ratio: 0.79, 95% confidence interval: 0.66 to 0.95; p = 0.013). Similarly, men with an ICD had longer survival than men without an ICD (adjusted hazard ratio: 0.73, 95% confidence interval: 0.65 to 0.83; p < 0.0001). There was no interaction between sex and the presence of an ICD with respect to survival (p = 0.44).ConclusionsAmong older women with left ventricular dysfunction, a primary prevention ICD was associated with a significant survival benefit that was nearly identical to that seen in men. These findings support the use of primary prevention ICDs in eligible patients regardless of sex.

ImportanceClinical trials of prophylactic implantable cardioverter-defibrillators (ICDs) have included a minority of patients with a left ventricular ejection fraction (LVEF) between 30% and 35%. Because a large number of ICDs in the United States are implanted in such patients, it is important to study survival associated with this therapy.ObjectiveTo characterize patients with LVEF between 30% and 35% and compare the survival of those with and without ICDs.Design, setting, and participantsRetrospective cohort study of Medicare beneficiaries in the National Cardiovascular Data Registry ICD registry (January 1, 2006, through December 31, 2007) with an LVEF between 30% and 35% who received an ICD during a heart failure hospitalization and similar patients in the Get With The Guidelines-Heart Failure (GWTG-HF) database (January 1, 2005, through December 31, 2009) with no ICD. The analysis was repeated in patients with an LVEF less than 30%. There were 3120 patients with an LVEF between 30% and 35% (816 in matched cohorts) and 4578 with an LVEF less than 30% (2176 in matched cohorts). Propensity score matching and Cox models were applied.Main outcomes and measuresThe primary outcome was all-cause mortality; data were obtained from Medicare claims through December 31, 2011.ResultsThere were no significant differences in the baseline characteristics of the matched groups (n = 408 for both groups). Among patients with an LVEF between 30% and 35%, there were 248 deaths in the ICD Registry group, within a median follow-up of 4.4 years (interquartile range, 2.7-4.9) and 249 deaths in the GWTG HF group, within a median follow-up of 2.9 years (interquartile range, 2.1-4.4). The risk of all-cause mortality in patients with an LVEF between 30% and 35% and an ICD was significantly lower than that in matched patients without an ICD (3-year mortality rates: 51.4% vs 55.0%; hazard ratio, 0.83 [95% CI, 0.69-0.99]; P = .04). Presence of an ICD also was associated with better survival in patients with an LVEF less than 30% (3-year mortality rates: 45.0% vs 57.6%; 634 and 660 total deaths; hazard ratio, 0.72 [95% CI, 0.65-0.81]; P