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Dapagliflozin, a sodium-glucose cotransporter-2 inhibitor, reduces cardiovascular death and worsening heart failure in patients with chronic heart failure and reduced ejection fraction. Early initiation during an acute heart failure (AHF) hospitalization may facilitate decongestion, improve natriuresis, and facilitate safe transition to a beneficial outpatient therapy for both diabetes and heart failure. The objective is to assess the efficacy and safety of initiating dapagliflozin within the first 24 hours of hospitalization in patients with AHF compared to usual care. DICTATE-AHF is a prospective, multicenter, open-label, randomized trial enrolling a planned 240 patients in the United States. Patients with type 2 diabetes hospitalized with hypervolemic AHF and an estimated glomerular filtration rate of at least 30 mL/min/1.73m2 are eligible for participation. Patients are randomly assigned 1:1 to dapagliflozin 10 mg once daily or structured usual care until day 5 or hospital discharge. Both treatment arms receive protocolized diuretic and insulin therapies. The primary endpoint is diuretic response expressed as the cumulative change in weight per cumulative loop diuretic dose in 40 mg intravenous furosemide equivalents. Secondary and exploratory endpoints include inpatient worsening AHF, 30-day hospital readmission for AHF or diabetic reasons, change in NT-proBNP, and measures of natriuresis. Safety endpoints include the incidence of hyper/hypoglycemia, ketoacidosis, worsening kidney function, hypovolemic hypotension, and inpatient mortality. The DICTATE-AHF trial will establish the efficacy and safety of early initiation of dapagliflozin during AHF across both AHF and diabetic outcomes in patients with diabetes.

We assessed trends and identified individual- and county-level factors associated with individual linkage to HIV care in Tennessee (TN). TN residents diagnosed with HIV from 2012-2016 were included in the analysis (n = 3,751). Individuals were assigned county-level factors based on county of residence at the time of diagnosis. Linkage was defined by the first CD4 or HIV RNA test date after HIV diagnosis. We used modified Poisson regression to estimate probability of 30-day linkage to care at the individual-level and the contribution of individual and county-level factors to this outcome. Both MSM (aRR 1.23, 95%CI 0.98-1.55) and women who reported heterosexual sex risk factors (aRR 1.39, 95%CI 1.18-1.65) were more likely to link to care within 30-days than heterosexual males. Non-Hispanic Black individuals had poorer linkage than White individuals (aRR 0.77, 95%CI 0.71-0.83). County-level mentally unhealthy days were negatively associated with linkage (aRR 0.63, 95%CI: 0.40-0.99). Racial disparities in linkage to care persist at both individual and county levels, even when adjusting for county-level social determinants of health. These findings suggest a need for structural interventions to address both structural racism and mental health needs to improve linkage to care and minimize racial disparities in HIV outcomes.

Background Heart failure is a major public health concern, affecting 6.7 million Americans. An estimated 16% of emergency department (ED) patients with acute heart failure (AHF) are discharged home. Our Get with the Guidelines in Emergency Department Patients with Heart Failure (GUIDED-HF) toolkit aims to improve AHF self-care and facilitate safer transitions in care for these patients. We describe implementation barriers and facilitators, and the selection and refinement of implementation strategies, to facilitate future GUIDED-HF implementation. Methods A mixed-methods cross-sectional observational study was conducted in four United States EDs in two diverse healthcare systems in the Pacific West and Midwest. Data were collected using a survey and interviews with ED providers, nurses, and leaders. The survey assessed the ED context using the context scale of the Organizational Readiness to Change Assessment (ORCA). The Consolidated Framework for Implementation Research informed interviews. Quantitative data were summarized using medians (interquartile ranges) or percentages (frequencies). Wilcoxon rank-sum tests and Kruskal–Wallis tests were used to assess differences in the healthcare system and profession. Qualitative data were analyzed and summarized using rapid qualitative analysis. Convergence of quantitative and qualitative data was used to inform specific refining of implementation strategies to the local context (e.g., who should serve as champions, how best practice alerts should be implemented). Results Participants were predominately white (76%) with median (IQR) age 37.0 (32.0, 41.0). ED leaders/administrators, providers, and nurses comprised 15%, 55%, and 29% of participants, respectively. Sites reported an ORCA context scale score of 3.7 [3.4, 4.0] (scale of 1 =  strongly disagree to 5 =  strongly agree ). Comparison of scores by profession showed a significant difference in the context score among providers (3.9 [3.5, 4.0]), leaders (3.7 [3.5, 4.0]), and nurses (3.6 [3.0, 3.9]) ( p  = 0.048). Qualitative data indicated implementation barriers (e.g., resource limitations, patient health literacy), facilitators (e.g., GUIDED-HF is patient-centric; site and intervention congruent values, norms, and goals), and site-specific needs due to contextual factors (e.g., education needs, feedback mechanisms, champions). Conclusions Specific determinants of implementation exist in ED settings and require the refining of implementation strategies to overcome site-specific barriers and enhance facilitators. Trial registration n/a.

Younger patients (18 to 65 years old) are often excluded from delirium outcome studies. We sought to determine if delirium was associated with short-term adverse outcomes in a diverse cohort of younger and older patients with acute heart failure (AHF). We conducted a multi-center prospective cohort study that included adult emergency department patients with confirmed AHF. Delirium was ascertained using the Brief Confusion Assessment Method (bCAM). The primary outcome was a composite outcome of 30-day all-cause death, 30-day all-cause rehospitalization, and prolonged index hospital length of stay. Multivariable logistic regression was performed, adjusting for demographics, cognitive impairment without delirium, and HF risk factors. Older age (≥ 65 years old)*delirium interaction was also incorporated into the model. Odds ratios (OR) with their 95% confidence intervals (95%CI) were reported. A total of 1044 patients with AHF were enrolled; 617 AHF patients were < 65 years old and 427 AHF patients were ≥ 65 years old, and 47 (7.6%) and 40 (9.4%) patients were delirious at enrollment, respectively. Delirium was significantly associated with the composite outcome (adjusted OR = 1.64, 95%CI: 1.02 to 2.64). The older age*delirium interaction p-value was 0.47. In conclusion, delirium was common in both younger and older patients with AHF and was associated with poorer short-term outcomes in both cohorts. Younger patients with acute heart failure should be included in future delirium outcome studies.

Purpose Sarcoidosis is a non-caseating granulomatous disease for which a role for infectious antigens continues to strengthen. Recent studies have reported molecular evidence of mycobacteria or propionibacteria. We assessed for immune responses against mycobacterial and propionibacterial antigens in sarcoidosis bronchoalveolar lavage (BAL) using flow cytometry, and localized signals consistent with microbial antigens with sarcoidosis specimens, using matrix-assisted laser desorption ionization imaging mass spectrometry (MALDI-IMS). Methods BAL cells from 27 sarcoidosis, 14 PPD- controls, and 9 subjects with nontuberculosis mycobacterial (NTM) infections were analyzed for production of IFN-γ after stimulation with mycobacterial ESAT-6 and Propionibacterium acnes proteins. To complement the immunological data, MALDI-IMS was performed to localize ESAT-6 and Propionibacterium acnes signals within sarcoidosis and control specimens. Results CD4+ immunologic analysis for mycobacteria was positive in 17/27 sarcoidosis subjects, compared to 2/14 PPD- subjects, and 5/9 NTM subjects ( p  = 0.008 and p  = 0.71 respectively, Fisher’s exact test). There was no significant difference for recognition of P. acnes, which occurred only in sarcoidosis subjects that also recognized ESAT-6. Similar results were also observed for the CD8+ immunologic analysis. MALDI-IMS localized signals consistent with ESAT-6 only within sites of granulomatous inflammation, whereas P. acnes signals were distributed throughout the specimen. Conclusions MALDI-IMS localizes signals consistent with ESAT-6 to sarcoidosis granulomas, whereas no specific localization of P. acnes signals is detected. Immune responses against both mycobacterial and P. acnes are present within sarcoidosis BAL, but only mycobacterial signals are distinct from disease controls. These immunologic and molecular investigations support further investigation of the microbial community within sarcoidosis granulomas.

Patients with left ventricular hypertrophy (LVH) diagnosed by electrocardiogram (ECG) have increased mortality and higher risk for life-threatening cardiovascular disease. ECGs offer an opportunity to identify patients with increased risk for potential risk-modifying therapy. We developed a novel, quick, easy to use ECG screening criterion (Seamens' Sign) for LVH. This new criterion was defined as the presence of QRS complexes touching or overlapping in two contiguous precordial leads. This study was a retrospective chart review of 2,184 patient records of patients who had an ECG performed in the emergency department and a transthoracic echocardiogram performed within 90 days. The primary outcome was whether Seamens' Sign was noninferior in confirming LVH compared to other common diagnostic criteria. Test characteristics were calculated for each of the LVH criteria. Inter-rater agreement was assessed on a random sample using Cohen's Kappa. Median age was 63, 52% of patients were male and there was a 35% prevalence of LVH by transthoracic echocardiogram (TTE). Nine percent were positive for LVH on ECG based on Seamens' Sign. Seamens' Sign had a specificity of 0.92. Tests assessing noninferiority indicated Seamens' Sign was non-inferior to all criteria (  < 0.001) except for Cornell criterion for women (  = 0.98). Seamens' Sign had 90% (0.81-1.00) inter-rater agreement, the highest of all criteria in this study. When compared to both the Sokolow-Lyon criteria and the Cornell criterion for men, Seamens' Sign is noninferior in ruling in LVH on ECG. Additionally, Seamens' Sign has higher inter-rater agreement compared to both Sokolow-Lyon criteria as well as the Cornell criteria for men and women, perhaps related to its ease of use.

Background Loop diuretics are common therapy for emergency department (ED) patients with acute heart failure (AHF). Diuretic resistance (DR) is a term used to describe blunted natriuretic response to loop diuretics. It would be important to detect DR prior to it becoming clinically apparent, so early interventions can be initiated. However, several definitions have been proposed, and it is not clear if they identify similar patients. We compared these definitions and described the clinical characteristics of patients who fulfilled them. Methods To qualify for this secondary analysis of 1033 ED patients with AHF, all patients needed to receive intravenous diuretics in the ED and have urine available within 24 h of their ED evaluation. A poor diuretic response, suggesting DR, was characterized by (1) a fractional sodium excretion (FeNa) of less than 0.2%; (2) spot urinary sodium of less than 50 meq/L; and (3) a urinary Na/K ratio <1.0. McNemar’s test was used to compare the different cohorts identified by the three definitions. Secondary analyses evaluated associations between each DR definition and hospital length of stay (LOS), ED revisits and rehospitalizations for AHF, and mortality using the Wilcoxon rank-sum tests and linear regression or Pearson chi-square test and logistic regression, as appropriate. Results The median age of the 187 patients was 64, and 50% were African-American. There were 5.9% of patients with a FeNa less than 0.2%, 17.1% had urinary sodium less than 50 meq/L, and 10.7% had a urinary Na/K ratio <1.0. The three definitions identified significantly different patients with very little overlap ( p  < 0.02 for all comparisons). There were 37 (19.8%) patients who were readmitted to the ED or hospital or died within 30 days of ED evaluation. Patients with spot urinary sodium less than 50 meq/L were more likely to be readmitted ( p  = 0.03). Conclusions The patient proportion with poor natriuresis and DR varies depending on the definition used. Early ED therapy would be impacted at different rates if clinical decisions are made based on these definitions. These findings need to be further explored in a prospective ED-based study. Trial registration ClinicalTrials.gov, NCT00508638

The emergency department (ED) is often where atrial fibrillation (AF) is first detected and acutely treated and affected patients dispositioned. We used the Nationwide Emergency Department Sample to estimate the percentage of visits resulting in hospitalization and investigate associations between patient and hospital characteristics with hospitalization at the national and regional levels. We conducted a cross-sectional study of adults with AF listed as the primary ED diagnosis in the 2007 to 2009 Nationwide Emergency Department Sample. We performed multivariate logistic regression analyses investigating the associations between prespecified patient and hospital characteristics with hospitalization. From 2007 to 2009, there were 1,320,123 weighted ED visits for AF, with 69% hospitalized nationally. Mean regional hospitalization proportions were: Northeast (74%), Midwest (68%), South (74%), and West (57%). The highest odds ratios for predicting hospitalization were heart failure (3.85, 95% confidence interval [CI] 3.66 to 4.02), chronic obstructive pulmonary disease (2.47, 95% CI 2.34 to 2.61), and coronary artery disease (1.65, 95% CI 1.58 to 1.73). After adjusting for age, privately insured (0.77, 95% CI 0.73 to 0.81) and self-pay (0.77 95% CI 0.66 to 0.90) patients had lower odds compared with Medicare recipients, whereas Medicaid (1.21, 95% CI 1.11 to 1.32) patients tended to have higher odds. Patients living in low-income zip codes (1.18, 95% CI 1.12 to 1.25) and patients treated at large metropolitan hospitals (1.75, 95% CI 1.59 to 1.93) had higher odds. In conclusion, our analysis showed considerable regional variation in the management of patients with AF in the ED and in associations between patient socioeconomic and hospital characteristics with ED disposition; adapting best practices from among these variations in management could reduce hospitalizations and health-care expenses.

Despite large-scale quality improvement initiatives, substantial proportions of patients with ST-elevation myocardial infarction (STEMI) transferred to percutaneous coronary intervention centers do not receive percutaneous coronary intervention within the recommended 120 minutes. We sought to examine the contributory role of emergency medical services (EMS) activation relative to percutaneous coronary intervention center activation in the timeliness of care for patients transferred with STEMI. We conducted a retrospective analysis of interfacility transfers from emergency departments (ED) to a single percutaneous coronary intervention center between 2011-2014. We included emergency department (ED) patients transferred to the percutaneous coronary intervention center and excluded scene transfers and those given fibrinolytics. We calculated descriptive statistics and used multivariable linear regression to model the association of variables with ED time intervals (arrival to electrocardiogram [ECG], ECG-to-EMS activation, and ECG-to-STEMI alert) adjusting for patient age, gender, mode of arrival, weekday hour presentation, facility transfers in the past year, and transferring facility distance. We identified 159 patients who met inclusion criteria. Subjects were a mean of 59 years old (standard deviation 13), 22% female, and 93% White; 59% arrived by private vehicle, and 24% presented after weekday hours. EDs transferred a median of 9 STEMIs (interquartile range [IQR] 3, 15) in the past year and a median of 65 miles (IQR 35, 90) from the percutaneous coronary intervention center. Median ED length of stay was 65 minutes (IQR 51, 85). Among component intervals, arrival to ECG was 6%, ECG-to-EMS activation 32%, and ECG-to-STEMI alert was 49% of overall ED length of stay. Only 18% of transfers had EMS activation earlier than STEMI alert. ECG-to-EMS activation was shorter in EDs achieving length of stay ≤60 minutes compared to those >60 minutes (12 vs 31 minutes, P<0.001). Multivariable modeling showed that after-hours presentation was associated with longer ECG-to-EMS activation (adjusted relative risk [RR] 1.05, P<0.001). Female gender (adjusted RR 0.81, P<0.001), prior facility transfers (adjusted RR 0.84, P<0.001), and initial ambulance presentation (adjusted RR 0.93, P = 0.02) were associated with shorter ECG-to-EMS activation. In STEMI transfers, faster EMS activation was more likely to achieve a shorter ED length of stay than a rapid, percutaneous coronary intervention center STEMI alert. Large-scale quality improvement efforts such as the American Heart Association's Mission Lifeline that were designed to regionalize STEMI have improved the timeliness of reperfusion, but major gaps, particularly in interfacility transfers, remain. While the transferring EDs are recognized as the primary source of delay during interfacility STEMI transfers, the contributions to delays at transferring EDs remain poorly understood.

AbstractObjectivesThe objective of this study was to evaluate the performance of non‐targeted hepatitis C virus (HCV) screening in emergency departments (EDs) and other healthcare settings in terms of patients identified with HCV infection and linked to HCV care. MethodsIn the Southern Appalachian region of the United States, we developed non‐targeted HCV screening and linkage‐to‐care programs in 10 institutions at different healthcare settings, including EDs, outpatient clinics, and inpatient units. Serum samples were tested for HCV antibodies, and if positive, reflexed to HCV ribonucleic acid (RNA) testing as a confirmatory test for active infection. Patients with positive RNA tests were contacted to link them to HCV care. ResultsBetween 2017 and 2019, among 195,152 patients screened for HCV infection, 16,529 (8.5%) were positive by antibody testing, 10,139 (5.2% of screened patients and 61.3% of patients positive by antibody test) were positive by RNA testing, and 5778 (3.0% of screened patients and 57.0% of patients positive by RNA test) were successfully linked to HCV care. Among 83,645 patients screened in EDs, 9060 (10.8%) were positive by HCV antibody, and 5243 (6.3%) were positive by RNA test. Among patients positive by RNA testing, linkage to care was lower for patients screened in the ED (44.1%) compared with outpatient clinics (67.6%) ( P < 0.01) and inpatient units (50.9%) ( P < 0.01). ConclusionsNon‐targeted HCV screening in acute care settings can identify large numbers of people with HCV infection. To optimize the utility of these screening programs, future work is needed to develop best practices that consistently link these patients to HCV care.