Decreasing Bilirubin Serum Tests in Healthy Newborns During Birth Hospitalization.

OBJECTIVES: Substantial variability exists in hyperbilirubinemia screening and monitoring leading to unnecessary total serum bilirubin (TSB) testing in healthy newborns. We aimed to assess the impact of value-care interventions to decrease the monthly TSB testing rate per 100 patient-days among healthy newborns in our Mother-Baby Unit by 30% by June 2022. METHODS: We formed a multidisciplinary team to review the current practice for ordering TSB among housestaff in our Mother-Baby Unit. We identified several themes: variation in clinical practice, fear of hyperbilirubinemia, and desire to act for high-intermediate risk bilirubin levels. The interventions consisted of obtaining faculty buy-in, redesigning the hyperbilirubinemia pathway, educating staff on high value-care, producing an instructional video, and prompting staff to incorporate a bilirubin risk assessment via smart phrases in our electronic health record. The primary outcome was the monthly TSB testing rate per 100 patient-days. Universal predischarge bilirubin screening, length of stay, phototherapy rates, and readmission rates were chosen as balancing measures. RESULTS: The monthly rate of TSB testing was reduced from 51 to 26.3 TSB per 100 patient-days, representing a 48% reduction. This improvement was sustained for 12 months. The percentage of infants with at least 1 TSB measurement during birth hospitalization decreased from 48% to 30%. Predischarge bilirubin screening, length of stay, and readmission rates were unchanged. CONCLUSIONS: Our quality improvement initiative led to a significant reduction in the monthly TSB testing per 100 patient-days in healthy newborns without evidence of harm.

Osteopontin Promotes Left Ventricular Diastolic Dysfunction Through a Mitochondrial Pathway.

BACKGROUND: Patients with chronic kidney disease (CKD) and coincident heart failure with preserved ejection fraction (HFpEF) may constitute a distinct HFpEF phenotype. Osteopontin (OPN) is a biomarker of HFpEF and predictive of disease outcome. We recently reported that OPN blockade reversed hypertension, mitochondrial dysfunction, and kidney failure in Col4a3-/- mice, a model of human Alport syndrome. OBJECTIVES: The purpose of this study was to identify potential OPN targets in biopsies of HF patients, healthy control subjects, and human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs), and to characterize the cardiac phenotype of Col4a3-/- mice, relate this to HFpEF, and investigate possible causative roles for OPN in driving the cardiomyopathy. METHODS: OGDHL mRNA and protein were quantified in myocardial samples from patients with HFpEF, heart failure with reduced ejection fraction, and donor control subjects. OGDHL expression was quantified in hiPS-CMs treated with or without anti-OPN antibody. Cardiac parameters were evaluated in Col4a3-/- mice with and without global OPN knockout or AAV9-mediated delivery of 2-oxoglutarate dehydrogenase-like (Ogdhl) to the heart. RESULTS: OGDHL mRNA and protein displayed abnormal abundances in cardiac biopsies of HFpEF (n = 17) compared with donor control subjects (n = 12; p < 0.01) or heart failure with reduced ejection fraction patients (n = 12; p < 0.05). Blockade of OPN in hiPS-CMs conferred increased OGDHL expression. Col4a3-/- mice demonstrated cardiomyopathy with similarities to HFpEF, including diastolic dysfunction, cardiac hypertrophy and fibrosis, pulmonary edema, and impaired mitochondrial function. The cardiomyopathy was ameliorated by Opn-/- coincident with improved renal function and increased expression of Ogdhl. Heart-specific overexpression of Ogdhl in Col4a3-/- mice also improved cardiac function and cardiomyocyte energy state. CONCLUSIONS: Col4a3-/- mice present a model of HFpEF secondary to CKD wherein OPN and OGDHL are intermediates, and possibly therapeutic targets.