Assessment of medication adherence and responsible use of isotretinoin and contraception through Belgian community pharmacies by using pharmacy refill data.

The aims of the study were to evaluate medication adherence and the influencing factors for isotretinoin and contraception (oral, patches, and rings) and to evaluate the concomitant use of contraception and isotretinoin. Reimbursed prescription data from January 2012 to August 2015 of all patients in Belgium were received from Pharmanet-National Institute for Health and Disability Insurance. Medication adherence was measured according to the medication possession ratio. The influence of gender and age was analyzed using the Mann-Whitney test and the Spearman coefficient correlation. The independence between adherence to contraception and adherence to isotretinoin was analyzed using the Pearson chi-square test of independence. Persistence was defined as the number of days between initiation and presumed end of treatment. The Kaplan-Meier method was used to plot the medication persistence curves, and the log-rank test was used to compare the curves. The concomitant use of contraception and isotretinoin was analyzed using descriptive statistics. The medication possession ratio was ≥0.8 for 46.1% of patients receiving isotretinoin and for 74.0% of women using contraception. For isotretinoin, this percentage decreased as the number of attempts increased (29.8% for the second attempt and 19.8% for more than two attempts). Men seemed more adherent than women, and a weak negative correlation between adherence and age was observed. The adherence data of isotretinoin and contraception were independent. The median persistence for isotretinoin treatment was 139 days (interquartile range 71-209) and was higher for men. Among women between 12 and 21 years old taking isotretinoin, 63.8% received at least one contraceptive prescription. However, 15.7% of women taking isotretinoin adhered to the use of contraception 1 month before, during, and 1 month after treatment. Medication adherence to isotretinoin and contraception and compliance with the isotretinoin safety recommendation could be improved. Health service interventions, using pharmacy refill data, should be delivered to ensure patient safety and strict adherence to contraception when under isotretinoin treatment

Research priorities in pediatric parenteral nutrition: a consensus and perspective from ESPGHAN/ESPEN/ESPR/CSPEN

Parenteral nutrition is used to treat children that cannot be fully fed by the enteral route. While the revised ESPGHAN/ESPEN/ESPR/CSPEN pediatric parenteral nutrition guidelines provide clear guidance on the use of parenteral nutrition in neonates, infants, and children based on current available evidence, they have helped to crystallize areas where research is lacking or more studies are needed in order to refine recommendations. This paper collates and discusses the research gaps identified by the authors of each section of the guidelines and considers each nutrient or group of nutrients in turn, together with aspects around delivery and organization. The 99 research priorities identified were then ranked in order of importance by clinicians and researchers working in the field using a survey methodology. The highest ranked priority was the need to understand the relationship between total energy intake, rapid catch-up growth, later metabolic function, and neurocognitive outcomes. Research into the optimal intakes of macronutrients needed in order to achieve optimal outcomes also featured prominently. Identifying research priorities in PN should enable research to be focussed on addressing key issues. Multicentre trials, better definition of exposure and outcome variables, and long-term metabolic and developmental follow-up will be key to achieving this. Impact: The recent ESPGHAN/ESPEN/ESPR/CSPEN guidelines for pediatric parenteral nutrition provided updated guidance for providing parenteral nutrition to infants and children, including recommendations for practice.However, in several areas there was a lack of evidence to guide practice, or research questions that remained unanswered. This paper summarizes the key priorities for research in pediatric parenteral nutrition, and ranks them in order of importance according to expert opinion

Intensive enteral nutrition is ineffective for individuals with severe alcoholic hepatitis treated with corticosteroids.

peer reviewedBACKGROUND & AIMS: Severe alcoholic hepatitis (AH) is a lifethreatening disease for which adequate oral nutritional support is recommended. We performed a randomized controlled trial to determine whether the combination of corticosteroid and intensive enteral nutrition therapy is more effective than corticosteroid therapy alone in patients with severe AH. METHODS: We enrolled 136 heavy consumers of alcohol (age, 18–75 y) with recent onset of jaundice and biopsy-proven severe AH in our study, performed at 18 hospitals in Belgium and 2 in France, from February 2010 through February 2013. Subjects were assigned randomly (1:1) to groups that received either intensive enteral nutrition plus methylprednisolone or conventional nutrition plus methylprednisolone (controls). In the intensive enteral nutrition group, enteral nutrition was given via feeding tube for 14 days. The primary end point was patient survival for 6 months. RESULTS: In an intention-to-treat analysis, we found no significant difference between groups in 6-month cumulative mortality: 44.4% of patients died in the intensive enteral nutrition group (95% confidence interval [CI], 32.2%–55.9%) and 52.1% of controls died (95% CI, 39.4%– 63.4%) (P ¼ .406). The enteral feeding tube was withdrawn prematurely from 48.5% of patients, and serious adverse events considered to be related to enteral nutrition occurred in 5 patients. Regardless of group, a greater proportion of patients with a daily calorie intake less than 21.5 kcal/kg/day died (65.8%; 95% CI, 48.8–78.4) than patients with a higher intake of calories (33.1%; 95% CI, 23.1%–43.4%) (P < .001). CONCLUSIONS: In a randomized trial of patients with severe AH treated with corticosteroids, we found that intensive enteral nutrition was difficult to implement and did not increase survival. However, low daily energy intake was associated with greater mortality, so adequate nutritional intake should be a main goal for treatment

Expression of Calmodulin and Myosin Light Chain Kinase during Larval Settlement of the Barnacle Balanus amphitrite

Barnacles are one of the most common organisms in intertidal areas. Their life cycle includes seven free-swimming larval stages and sessile juvenile and adult stages. The transition from the swimming to the sessile stages, referred to as larval settlement, is crucial for their survivor success and subsequent population distribution. In this study, we focused on the involvement of calmodulin (CaM) and its binding proteins in the larval settlement of the barnacle, Balanus ( = Amphibalanus) amphitrite. The full length of CaM gene was cloned from stage II nauplii of B. amphitrite (referred to as Ba-CaM), encoding 149 amino acid residues that share a high similarity with published CaMs in other organisms. Quantitative real-time PCR showed that Ba-CaM was highly expressed in cyprids, the stage at which swimming larvae are competent to attach and undergo metamorphosis. In situ hybridization revealed that the expressed Ba-CaM gene was localized in compound eyes, posterior ganglion and cement glands, all of which may have essential functions during larval settlement. Larval settlement assays showed that both the CaM inhibitor compound 48/80 and the CaM-dependent myosin light chain kinase (MLCK) inhibitor ML-7 effectively blocked barnacle larval settlement, whereas Ca2+/CaM-dependent kinase II (CaMKII) inhibitors did not show any clear effects. The subsequent real-time PCR assay showed a higher expression level of Ba-MLCK gene in larval stages than in adults, suggesting an important role of Ba-MLCK gene in larval development and competency. Overall, the results suggest that CaM and CaM-dependent MLCK function during larval settlement of B. amphitrite

A systematic review and meta-analysis to revise the Fenton growth chart for preterm infants

BACKGROUND: The aim of this study was to revise the 2003 Fenton Preterm Growth Chart, specifically to: a) harmonize the preterm growth chart with the new World Health Organization (WHO) Growth Standard, b) smooth the data between the preterm and WHO estimates, informed by the Preterm Multicentre Growth (PreM Growth) study while maintaining data integrity from 22 to 36 and at 50 weeks, and to c) re-scale the chart x-axis to actual age (rather than completed weeks) to support growth monitoring. METHODS: Systematic review, meta-analysis, and growth chart development. We systematically searched published and unpublished literature to find population-based preterm size at birth measurement (weight, length, and/or head circumference) references, from developed countries with: Corrected gestational ages through infant assessment and/or statistical correction; Data percentiles as low as 24 weeks gestational age or lower; Sample with greater than 500 infants less than 30 weeks. Growth curves for males and females were produced using cubic splines to 50 weeks post menstrual age. LMS parameters (skew, median, and standard deviation) were calculated. RESULTS: Six large population-based surveys of size at preterm birth representing 3,986,456 births (34,639 births < 30 weeks) from countries Germany, United States, Italy, Australia, Scotland, and Canada were combined in meta-analyses. Smooth growth chart curves were developed, while ensuring close agreement with the data between 24 and 36 weeks and at 50 weeks. CONCLUSIONS: The revised sex-specific actual-age growth charts are based on the recommended growth goal for preterm infants, the fetus, followed by the term infant. These preterm growth charts, with the disjunction between these datasets smoothing informed by the international PreM Growth study, may support an improved transition of preterm infant growth monitoring to the WHO growth charts