Explore the vast range of titles available.

Background Dopamine antagonists are the main pharmacological options to treat gastroparesis. The aim of this study was to conduct a systematic literature review (SLR) to evaluate the profile of adverse events (AEs) of dopamine antagonists used in the treatment of children and adults with gastroparesis. Methods We searched EMBASE and MEDLINE up to March 25, 2021, for relevant clinical trials and observational studies. We conducted a proportional meta-analysis to estimate the pooled occurrence of AEs (%), with 95% confidence interval (CI), from arm-level data across studies and the comparative occurrence of AEs from placebo-controlled clinical trials (odds ratio [OR] with 95% CI). Results We identified 28 studies assessing AEs experienced by patients treated for gastroparesis with domperidone and metoclopramide; 22 studies contributed data to the meta-analyses. Cardiovascular, neurological, and endocrine AEs were commonly observed, with point incidences varying from 1 to > 50%. Clinically important AEs, such as QTc prolongation, occurred in 5% of patients treated with domperidone (95% CI: 3.32–8.62). Restlessness, an extrapyramidal AE, occurred in 15% of patients (95% CI: 7.48–26.61) treated with metoclopramide, with a 7-fold increase compared with patients receiving placebo (OR: 7.72; 95% CI: 1.27–47.05). Variation in terminology to describe extrapyramidal events precluded further pooled analyses. Additional meta-analyses were not feasible due to discrepancies in the assessment and reporting of the AEs. Conclusions The evidence confirms concerns of cardiovascular, extrapyramidal, and endocrine AEs in patients with gastroparesis treated with domperidone and metoclopramide. Imprecise AE reporting limits firm interpretation and conclusions. Registration PROSPERO international prospective register of systematic reviews (registration number: CRD42021248888).

Objective To examine whether delivery by caesarean section is a risk factor for childhood obesity. Design Prospective prebirth cohort study (Project Viva). Setting Eight outpatient multi-specialty practices based in the Boston, Massachusetts area. Participants We recruited women during early pregnancy between 1999 and 2002, and followed their children after birth. We included 1255 children with body composition measured at 3 years of age. Main outcome measures BMI score, obesity (BMI for age and sex ≥95th percentile), and sum of triceps plus subscapular skinfold thicknesses at 3 years of age. Results 284 children (22.6%) were delivered by caesarean section. At age 3, 15.7% of children delivered by caesarean section were obese compared with 7.5% of children born vaginally. In multivariable logistic and linear regression models adjusting for maternal prepregnancy BMI, birth weight, and other covariates, birth by caesarean section was associated with a higher odds of obesity at age 3 (OR 2.10, 95% CI 1.36 to 3.23), higher mean BMI z-score (0.20 units, 95% CI 0.07 to 0.33), and higher sum of triceps plus subscapular skinfold thicknesses (0.94 mm, 95% CI 0.36 to 1.51). Conclusions Infants delivered by caesarean section may be at increased risk of childhood obesity. Further studies are needed to confirm our findings and to explore mechanisms underlying this association.

Screening for drug-induced hyperprolactinaemia, a condition characterised by higher-than-normal levels of serum prolactin induced by drug treatments, requires a comprehensive understanding of the clinical presentations and long-term complications of the condition. Using two databases, Embase and MEDLINE, we summarised the available evidence on the clinical presentations and long-term complications of drug-induced hyperprolactinaemia. Clinical and observational studies reporting on drug treatments known or suspected to induce hyperprolactinaemia were included. Database searches were limited to the English language; no date or geographic restrictions were applied. Fifty studies were identified for inclusion, comprising a variety of study designs and patient populations. Most data were reported in patients treated with antipsychotics, but symptoms were also described among patients receiving other drugs, such as prokinetic drugs and antidepressants. Notably, the diagnosis of drug-induced hyperprolactinaemia varied across studies since a standard definition of elevated prolactin levels was not consistently applied. Frequent clinical presentations of hyperprolactinaemia were menstrual cycle bleeding, breast or lactation disorders, and sexual dysfunctions, described in 80% (40/50), 74% (37/50), and 42% (21/50) of the included studies, respectively. In the few studies reporting such symptoms, the prevalence of vaginal dryness impacted up to 53% of females, and infertility in both sexes ranged from 15 to 31%. Clinicians should be aware of these symptoms related to drug-induced hyperprolactinaemia when treating patients with drugs that can alter prolactin levels. Future research should explore the long-term complications of drug-induced hyperprolactinaemia and apply accepted thresholds of elevated prolactin levels (i.e., 20 ng/mL for males and 25 ng/mL for females) to diagnose hyperprolactinaemia as a drug-induced adverse event. Trial Registration PROSPERO International Prospective Register Of Systematic Reviews (CRD42021245259).

Vitamin D deficiency is highly prevalent among children and adolescents worldwide. The high rates of vitamin D deficiency during childhood are of major public health relevance, given the growing evidence that vitamin D deficiency may play a key role in the pathophysiology of many chronic diseases beyond rickets, including autoimmune conditions, cardiovascular diseases, and cancer. Identification, treatment, and prevention of vitamin D deficiency in childhood may therefore have profound health effects throughout the life span. In this review, we discuss the definitions, epidemiology, clinical implications, and treatment of vitamin D deficiency in children and adolescents.

Trazpiroben is a dopamine D2/D3 receptor antagonist under development for the treatment of gastroparesis. This phase I, open‐label, randomized, two‐way crossover study (NCT04121078) evaluated the effect of single‐dose intravenous rifampin, a potent inhibitor of the organic anion transporting polypeptides (OATPs) 1B1 and 1B3, on the pharmacokinetics and safety of trazpiroben in healthy adults. The utility of coproporphyrin (CP) I and CPIII as biomarkers of OATP inhibition was also assessed. Overall, 12 participants were enrolled and randomized (1:1) into one of two treatment sequences (AB and BA). Participants received either a single oral dose of trazpiroben 25 mg (treatment A) or a single oral dose of trazpiroben 25 mg immediately after a single 30‐min intravenous infusion of rifampin 600 mg (treatment B). After a washout period of at least 7 days, participants received the other treatment. Geometric mean area under the curve from time 0 extrapolated to infinity (AUC∞) and maximum serum concentration (Cmax) of plasma trazpiroben were higher in participants receiving treatment B than those receiving treatment A (AUC∞, 168.5 vs. 32.68 ng*h/ml; Cmax, 89.62 vs. 14.37 ng/ml); corresponding geometric mean ratios (90% confidence interval) showed 5.16 (4.25–6.25) and 6.24 (4.62–8.42)‐fold increases in these parameters, respectively. In this study, trazpiroben was confirmed as a substrate of OATP1B1/1B3, and therefore co‐administration of trazpiroben with moderate to strong inhibitors of OATP1B1/1B3 is not recommended. This is also the first assessment of the utility of CPI and CPIII as endogenous biomarkers of OATP1B1/1B3 inhibition after a single intravenous dose of rifampin.

Growth failure is prevalent among infants with CHD. A Standardized Clinical Assessment and Management Plan was introduced at Boston Children's Hospital's cardiac medical ward to identify patients with growth failure, evaluate relevant contributing conditions, and recommend a management plan including collaboration with nutrition physicians. The objective of this study was to determine whether enrolled patients had improved growth compared with historical controls. A total of 29 patients were enrolled in the period July, 2013-June, 2014. In all, 42 historical controls who met eligibility criteria for enrolment were selected for comparison from patients admitted to the same ward in the period June, 2010-June, 2011. Patients with CHD aged <1 year , with growth failure defined as weight-for-age z-score <-2, or failure to sustain adequate weight gain were eligible for participation. Primary outcome was change in weight-for-age z-score from enrolment to most recent weight measurement among patients with at least 6 months of follow-up. Control patients were older at baseline admission weight (118 versus 95 days, p=0.33), and had a higher weight-for-age z-score, -2.9 (-3.1, -2.6) versus -3.7 (-4.3, -3.0) (p=0.02), compared with enrolled patients. Enrolled patients had greater gain in weight-for-age z-score, 2.7 (2.0, 3.4) versus 1.8 (1.5, 2.2) (p=0.03), from baseline to most recent follow-up. Patients enrolled in a nutrition-focused protocol had greater weight improvement than historical controls. Identification of growth failure and collaboration with a nutrition support team was associated with improved weight gain among CHD patients experiencing growth failure. CHD programmes should consider a structural approach, including nutrition expertise to address growth failure.

Trazpiroben, a dopamine D2/D3 receptor antagonist under development to treat gastroparesis, displays decreasing solubility with increasing pH. This single‐sequence, open‐label, two‐period, crossover study evaluated the effect of esomeprazole, a proton pump inhibitor that raises gastric pH, on the single‐dose pharmacokinetics, safety, and tolerability of trazpiroben in healthy adults (NCT03849690). In total, 12 participants were enrolled and entered period 1 (days 1–3), receiving a single oral dose of trazpiroben 25 mg on day 1. After a 4‐day washout, participants then entered period 2 (days 8–13) and received esomeprazole 40 mg once daily on days 8–12, with a single oral dose of trazpiroben 25 mg co‐administered 1 h post esomeprazole dosing on day 11. Geometric mean area under the curve from time 0 extrapolated to infinity (AUC∞) and maximum plasma concentration (Cmax) values were generally similar when trazpiroben was administered alone versus alongside esomeprazole (AUC∞, 44.03 vs. 38.85 ng h/ml; Cmax, 19.76 vs. 17.24 ng/ml). Additionally, the associated geometric mean ratio (GMR; co‐administration: administration alone) 90% confidence intervals (CIs) suggested no clinically meaningful difference between treatment groups (AUC∞, GMR 0.88, 90% CI 0.78–1.00; Cmax, 0.87, 90% CI 0.70–1.09). Mean apparent first‐order terminal elimination half‐life values were similar between treatments, illustrating co‐administration with esomeprazole had minimal effect on trazpiroben elimination. Trazpiroben was well‐tolerated in healthy adults following administration alone and alongside esomeprazole, with no clinically relevant adverse events reported. The lack of evidence of any clinically meaningful drug–drug interaction supports the co‐administration of esomeprazole with trazpiroben.

Objective:Decrease time to enteral feeding initiation and advancement.Study Design:In our all-referral neonatal intensive care unit, we developed an evidence-based guideline addressing feeding initiation and advancement. During 6 months before and 7 months after guideline implementation, we measured time to initiate feeding, time to 100 ml/kg/day of feeding, gastric residual measurement frequency, and incidence of necrotizing enterocolitis (balancing measure).Result:Two hundred twenty-three infants were studied. Time from admission to feeding initiation was shorter after guideline implementation (mean 0.5 days [95% CI: 0.4–0.7] vs. 1.1 days [95% CI: 0.7–1.5], p = 0.01). Time from admission to 100 ml/kg/day feeding was also shorter (3.6 days [95% CI: 2.8–4.4] vs. 6.2 days [95% CI: 4.4–8.1], p = 0.01). After guideline implementation, routine gastric residual measurements were discontinued.Conclusion:After implementation of an enteral feeding guideline, which included discontinuation of routine gastric residual assessment, we observed a faster initiation of enteral feeding and shorter time to reach 100 ml/kg/day.