Project description:The American Heart Association's Strategically Focused Children's Research Network started in July 2017 with 4 unique programs at Children's National Hospital in Washington, DC; Duke University in Durham, North Carolina; University of Utah in Salt Lake City, Utah; and Lurie Children's Hospital/Northwestern University in Chicago, Illinois. The overarching goal of the Children's National center was to develop evidence-based strategies to strengthen the health system response to rheumatic heart disease through synergistic basic, clinical, and population science research. The overall goals of the Duke center were to determine risk factors for obesity and response to treatment including those that might work on a larger scale in communities across the country. The integrating theme of the Utah center focused on leveraging big data-science approaches to improve the quality of care and outcomes for children with congenital heart defects, within the context of the patient and their family. The overarching hypothesis of the Northwestern center is that the early course of change in cardiovascular health, from birth onward, reflects factors that result in either subsequent development of cardiovascular risk or preservation of lifetime favorable cardiovascular health. All 4 centers exceeded the original goals of research productivity, fellow training, and collaboration. This article describes details of these accomplishments and highlights challenges, especially around the COVID-19 pandemic.
Project description:OBJECTIVES:The main objectives of this study were to describe in-hospital acute respiratory compromise among children (< 18 yr old), and its association with cardiac arrest and in-hospital mortality. DESIGN:Observational study using prospectively collected data. SETTING:U.S. hospitals reporting data to the "Get With The Guidelines-Resuscitation" registry. PATIENTS:Pediatric patients (< 18 yr old) with acute respiratory compromise. Acute respiratory compromise was defined as absent, agonal, or inadequate respiration that required emergency assisted ventilation and elicited a hospital-wide or unit-based emergency response. INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:The primary outcome was in-hospital mortality. Cardiac arrest during the event was a secondary outcome. To assess the association between patient, event, and hospital characteristics and the outcomes, we created multivariable logistic regressions models accounting for within-hospital clustering. One thousand nine hundred fifty-two patients from 151 hospitals were included. Forty percent of the events occurred on the wards, 19% in the emergency department, 25% in the ICU, and 16% in other locations. Two hundred eighty patients (14.6%) died before hospital discharge. Preexisting hypotension (odds ratio, 3.26 [95% CI, 1.89-5.62]; p < 0.001) and septicemia (odds ratio, 2.46 [95% CI, 1.52-3.97]; p < 0.001) were associated with increased mortality. The acute respiratory compromise event was temporally associated with a cardiac arrest in 182 patients (9.3%), among whom 46.2% died. One thousand two hundred eight patients (62%) required tracheal intubation during the event. In-hospital mortality among patients requiring tracheal intubation during the event was 18.6%. CONCLUSIONS:In this large, multicenter study of acute respiratory compromise, 40% occurred in ward settings, 9.3% had an associated cardiac arrest, and overall in-hospital mortality was 14.6%. Preevent hypotension and septicemia were associated with increased mortality rate.
Project description:BackgroundBecause randomized trials of sustained dietary changes are sometimes impractical for long-term outcomes, the explicit emulation of a (hypothetical) target trial using observational data may be an important tool for nutritional epidemiology.ObjectivesWe describe a methodological approach that aims to emulate a target trial of dietary interventions sustained over many years using data from observational cohort studies.MethodsWe estimated the 20-y risk of all-cause mortality under the sustained implementation of the food-based goals of the American Heart Association (AHA) 2020 using data from 3 prospective observational studies of US men [Health Professionals Follow-up Study (HPFS)] and women [Nurses' Health Study (NHS) and Nurses' Health Study II (NHS II)]. We applied the parametric g-formula to estimate the 20-y mortality risk under a dietary intervention and under no dietary intervention.ResultsThere were 165,411 participants who met the eligibility criteria. The mean age at baseline was 57.4 y (range, 43-82 y) in the HPFS, 52.4 y (range, 39-66 y) in the NHS, and 40.2 y (range, 30-50 y) in the NHS II. During 20 y of follow-up, 13,241 participants died. The estimated 20-y mortality risks under a dietary intervention versus no intervention were 21.9% compared with 25.8%, respectively, in the HPFS (risk difference, -3.9%; 95% CI: -4.9% to -3.2%); 10.0% compared with 12.6%, respectively, in the NHS (risk difference, -2.6%; 95% CI: -3.1% to -1.8%); and 2.1% compared with 2.5%, respectively, in the NHS II (risk difference, -0.35%; 95% CI: -0.56% to -0.09%). The corresponding risk ratios were 0.85 (95% CI: 0.81-0.88) in the HPFS, 0.79 (95% CI: 0.75-0.85) in the NHS, and 0.86 (95% CI: 0.78-0.96) in the NHS II.ConclusionsWe estimated that adherence to the food-based AHA 2020 Dietary Goals starting in midlife may reduce the 20-y risk of mortality.
Project description:BackgroundPneumonia is the leading infectious cause of death. Early deterioration and death commonly result from progressive sepsis, shock, respiratory failure, and cardiac complications. Recent data suggest that cardiac arrest may also be common, yet few previous studies have addressed this. Accordingly, we sought to characterize early cardiac arrest in patients who are hospitalized with coexisting pneumonia.MethodsWe performed a retrospective analysis of a multicenter cardiac arrest database, with data from > 500 North American hospitals. We included in-hospital cardiac arrest events that occurred in community-dwelling adults with pneumonia within the first 72 h after hospital admission. We compared patient and event characteristics for patients with and without pneumonia. For patients with pneumonia, we also compared events according to event location.ResultsWe identified 4,453 episodes of early cardiac arrest in patients who were hospitalized with pneumonia. Among patients with preexisting pneumonia, only 36.5% were receiving mechanical ventilation and only 33.3% were receiving infusions of vasoactive drugs prior to cardiac arrest. Only 52.3% of patients on the ward were receiving ECG monitoring prior to cardiac arrest. Shockable rhythms were uncommon in all patients with pneumonia (ventricular tachycardia or fibrillation, 14.8%). Patients on the ward were significantly older than patients in the ICU.ConclusionsIn patients with preexisting pneumonia, cardiac arrest may occur in the absence of preceding shock or respiratory failure. Physicians should be alert to the possibility of abrupt cardiopulmonary collapse, and future studies should address this possibility. The mechanism may involve myocardial ischemia, a maladaptive response to hypoxia, sepsis-related cardiomyopathy, or other phenomena.
Project description:OBJECTIVES:To describe the clinical characteristics and outcomes of a large, multicenter cohort of pediatric medical emergency team (MET) events occurring in US hospitals reported to the American Heart Association's Get With the Guidelines-Resuscitation registry. METHODS:We analyzed consecutive pediatric (<18 years) MET events reported to the registry from January 2006 to February 2012. RESULTS:We identified 3647 MET events from 151 US hospitals: 3080 (84%) ward and 567 (16%) telemetry/step-down unit events; median age 3.0 years (interquartile range: 0.0-11.0); 54% male; median duration 29 minutes (interquartile range: 18-49). Triggers included decreased oxygen saturation (32%), difficulty breathing (26%), and staff concern (24%). Thirty-seven percent (1137/3059) were admitted within 24 hours before MET event. Within 24 hours before the MET event, 16% were transferred from a PICU, 24% from an emergency department, and 7% from a pediatric anesthesia care unit. Fifty-three percent of MET events resulted in transfer to a PICU; 3251 (89%) received nonpharmacologic interventions, 2135 (59%) received pharmacologic interventions, 223 (6.1%) progressed to an acute respiratory compromise event, and 17 events (0.5%) escalated to cardiopulmonary arrest during the event. Survival to hospital discharge was 93.3% (n=3299/3536). CONCLUSIONS:Few pediatric MET events progress to respiratory or cardiac arrest, but most require nonpharmacologic and pharmacologic intervention. Median duration of MET event was 29 minutes (interquartile range: 18-49), and 53% required transfer to a PICU. Events often occurred within 24 hours after hospital admission or transfer from the PICU, emergency department, or pediatric anesthesia care unit and may represent an opportunity to improve triage and other systems of care.
Project description:BackgroundMany people may underappreciate the role of lifestyle in avoiding heart failure. We estimated whether greater adherence in middle age to American Heart Association's Life's Simple 7 guidelines—on smoking, body mass, physical activity, diet, cholesterol, blood pressure, and glucose—is associated with lower lifetime risk of heart failure and greater preservation of cardiac structure and function in old age.MethodsWe studied the population-based Atherosclerosis Risk in Communities Study cohort of 13,462 adults ages 45-64 years in 1987-1989. From the 1987-1989 risk factor measurements, we created a Life's Simple 7 score (range 0-14, giving 2 points for ideal, 1 point for intermediate, and 0 points for poor components). We identified 2218 incident heart failure events using surveillance of hospital discharge and death codes through 2011. In addition, in 4855 participants free of clinical cardiovascular disease in 2011-2013, we performed echocardiography from which we quantified left ventricular hypertrophy and diastolic dysfunction.ResultsOne in four participants (25.5%) developed heart failure through age 85 years. Yet, this lifetime heart failure risk was 14.4% for those with a middle-age Life's Simple 7 score of 10-14 (optimal), 26.8% for a score of 5-9 (average), and 48.6% for a score of 0-4 (inadequate). Among those with no clinical cardiovascular event, the prevalence of left ventricular hypertrophy in late life was approximately 40% as common, and diastolic dysfunction was approximately 60% as common, among those with an optimal middle-age Life's Simple 7 score, compared with an inadequate score.ConclusionsGreater achievement of American Heart Association's Life's Simple 7 in middle age is associated with a lower lifetime occurrence of heart failure and greater preservation of cardiac structure and function.
Project description:LCAT converts free cholesterol to cholesteryl esters in the process of reverse cholesterol transport. Familial LCAT deficiency (FLD) is a genetic disease that was first described by Kaare R. Norum and Egil Gjone in 1967. This report is a summary from a 2017 symposium where Dr. Norum recounted the history of FLD and leading experts on LCAT shared their results. The Tesmer laboratory shared structural findings on LCAT and the close homolog, lysosomal phospholipase A2. Results from studies of FLD patients in Finland, Brazil, Norway, and Italy were presented, as well as the status of a patient registry. Drs. Kuivenhoven and Calabresi presented data from carriers of genetic mutations suggesting that FLD does not necessarily accelerate atherosclerosis. Dr. Ng shared that LCAT-null mice were protected from diet-induced obesity, insulin resistance, and nonalcoholic fatty liver disease. Dr. Zhou presented multiple innovations for increasing LCAT activity for therapeutic purposes, whereas Dr. Remaley showed results from treatment of an FLD patient with recombinant human LCAT (rhLCAT). Dr. Karathanasis showed that rhLCAT infusion in mice stimulates cholesterol efflux and suggested that it could also enhance cholesterol efflux from macrophages. While the role of LCAT in atherosclerosis remains elusive, the consensus is that a continued study of both the enzyme and disease will lead toward better treatments for patients with heart disease and FLD.