Objective. To determine whether multiple daily injections of PTH 1–34 are safe and effective as long-term therapy for children with hypoparathyroidism. Study design. Linear growth, bone accrual, renal function, and mineral homeostasis were studied in a long-term observational study of PTH 1–34 injection therapy in 14 children. Methods. Subjects were 14 children with hypoparathyroidism due to autoimmune polyglandular syndrome type 1 (APS-1, N=5, ages 7–12 y) or calcium receptor mutation (CaR, N=9, ages 7–16 y). Mean daily PTH 1–34 dose was 0.75 ± 0.15 μg/kg/day. Treatment duration was 6.9 ± 3.1 y (range: 1.5 – 10 y). Patients were evaluated semiannually at the NIH Clinical Center. Results. Mean height velocity and lumbar spine, whole body, and femoral neck bone accretion velocities were normal throughout the study. In the first two years, distal 1/3 radius bone accrual velocity was reduced compared with normal children (P<0.003). Serum alkaline phosphatase correlated with PTH 1–34 dose (P< 0.006) and remained normal (235.3 ± 104.8 [SD] U/L, N: 51–332 U/L). Mean serum and 24-h urine calcium levels were 2.05 ± 0.11 mmol/L (N: 2.05–2.5 mmol/L) and 6.93 ± 1.3 mmol/24h (N: 1.25–7.5 mmol/24h), respectively—with fewer high urine calcium levels vs. baseline during calcitriol and calcium treatment (P<0.001). Nephrocalcinosis progressed in 5 of 12 subjects who had repeated renal imaging althoughrenal function remained normal. Conclusions. Twice-daily or thrice-daily subcutaneous PTH 1–34 injections provided safe and effective replacement therapy for up to 10 years in children with hypoparathyroidism due to APS-1 or CaR.

Background The Centers for Medicare and Medicaid Services (CMS) implemented a core measure sepsis (SEP-1) bundle in 2015. One element was initiation of broad-spectrum antibiotics within 3 hours of diagnosis. The policy has the potential to increase antibiotic use and Clostridioides difficile infection (CDI). We evaluated the impact of SEP-1 implementation on broad-spectrum antibiotic use and CDI occurrence rates. Methods Monthly adult antibiotic data for 4 antibiotic categories (surgical prophylaxis, broad-spectrum for community-acquired infections, broad-spectrum for hospital-onset/multidrug-resistant [MDR] organisms, and anti–methicillin-resistant Staphylococcus aureus [MRSA]) from 111 hospitals participating in the Clinical Data Base Resource Manager were evaluated in periods before (October 2014–September 2015) and after (October 2015–June 2017) policy implementation. Interrupted time series analyses, using negative binomial regression, evaluated changes in antibiotic category use and CDI rates. Results At the hospital level, there was an immediate increase in the level of broad-spectrum agents for hospital-onset/MDR organisms (+2.3%, P = .0375) as well as a long-term increase in trend (+0.4% per month, P = .0273). There was also an immediate increase in level of overall antibiotic use (+1.4%, P = .0293). CDI rates unexpectedly decreased at the time of SEP-1 implementation. When analyses were limited to patients with sepsis, there was a significant level increase in use of all antibiotic categories at the time of SEP-1 implementation. Conclusions SEP-1 implementation was associated with immediate and long-term increases in broad-spectrum hospital-onset/MDR organism antibiotics. Antimicrobial stewardship programs should evaluate sepsis treatment for opportunities to de-escalate broad therapy as indicated.

Objective Total pregnancy weight gain has been associated with infant birthweight; however, most prior studies lacked repeat ultrasound measurements. Understanding of the longitudinal changes in maternal weight gain and intrauterine changes in fetal anthropometrics is limited. Study design Prospective data from 1314 Scandinavian singleton pregnancies at high-risk for delivering small-for-gestational-age (SGA) were analyzed. Women had ≥1 (median 12) antenatal weight measurements. Ultrasounds were targeted at17, 25, 33, and 37 weeks of gestation. Analyses involved a multi-step process. First, trajectories were estimated across gestation for maternal weight gain and fetal biometrics [abdominal circumference (AC, mm), biparietal diameter (BPD, mm), femur length (FL, mm), and estimated fetal weight (EFW, grams)] using linear mixed models. Second, the association between maternal weight changes (per 5kg) and corresponding fetal growth from 0–17, 17–28, and 28–37 weeks was estimated for each fetal parameter adjusting for prepregnancy body mass index, height, parity, chronic diseases, age, smoking, fetal sex, and weight gain up to the respective period as applicable. Third, the probability of fetal SGA, EFW <10th percentile, at the 3rd ultrasound was estimated across the spectrum of maternal weight gain rate by SGA status at the 2nd ultrasound. Results From 0–17 weeks, changes in maternal weight were most strongly associated with changes in BPD [β=0.51 per 5kg (95%CI 0.26, 0.76)] and FL [β=0.46 per 5kg (95%CI 0.26, 0.65)]. From 17–28 weeks, AC [β=2.92 per 5kg (95%CI 1.62, 4.22)] and EFW [β=58.7 per 5kg (95%CI 29.5, 88.0)] were more strongly associated with changes in maternal weight. Increased maternal weight gain was significantly associated with a reduced probability of intrauterine SGA; for a normal weight woman with SGA at the 2nd ultrasound, the probability of fetal SGA with a weight gain rate of 0.29kg/w (10th percentile) was 59%, compared to 38% with a rate of 0.67kg/w (90th percentile). Conclusion Among women at high-risk for SGA, maternal weight gain was associated with fetal growth throughout pregnancy, but had a differential relationship with specific biometrics across gestation. For women with fetal SGA identified mid-pregnancy, increased antenatal weight gain was associated with a decreased probability of fetal SGA approximately 7 weeks later.