Long-term persistence of seroprotection against measles following measles-mumps-rubella vaccination administered before and after pediatric liver transplantation.

Liver transplantation (LT) recipients are susceptible to infections, including measles. Concerns about the safety and efficacy of live-attenuated vaccines, such as the measles-mumps-rubella (MMR) vaccine, have led to hesitancy among providers in administering them to immunocompromised patients. This 9-year interventional study assessed seroprotection against measles following MMR vaccination in pediatric LT recipients. Of 119 participants enrolled, 60 (50%) were seroprotected against measles after transplantation. Among the 59 nonseroprotected participants, 56 fulfilled safety criteria and received MMR vaccination with a seroprotection rate of 90% (95% confidence interval [CI], 73%-98%) after a first dose, 95% (95% CI, 85%-99%) after primary vaccination with 1 to 3 doses, comparable to nonimmunocompromized populations. However, measles antibodies declined over time, suggesting the need for regular monitoring, and booster doses. Half of the vaccinees (26/53, 49%) subsequently lost seroprotection. Among them, 23 received additional doses of MMR, with a high seroconversion rate. At their last follow-up (median, 6.1 years; interquartile range, 3.0-8.1 after inclusion), 63% (95% CI, 49%-75%) of all vaccinees were seroprotected against measles. In conclusion, MMR vaccination in pediatric LT recipients offers seroprotection against measles, but long-term immunity should be monitored closely.

Pharmacometric in silico studies used to facilitate a national dose standardisation process in neonatology - application to amikacin.

BACKGROUND AND AIMS: Pharmacometric in silico approaches are frequently applied to guide decisions concerning dosage regimes during the development of new medicines. We aimed to demonstrate how such pharmacometric modelling and simulation can provide a scientific rationale for optimising drug doses in the context of the Swiss national dose standardisation project in paediatrics using amikacin as a case study. METHODS: Amikacin neonatal dosage is stratified by post-menstrual age (PMA) and post-natal age (PNA) in Switzerland and many other countries. Clinical concerns have been raised for the subpopulation of neonates with a post-menstrual age of 30-35 weeks and a post-natal age of 0-14 days ("subpopulation of clinical concern"), as potentially oto-/nephrotoxic trough concentrations (Ctrough >5 mg/l) were observed with a once-daily dose of 15 mg/kg. We applied a two-compartmental population pharmacokinetic model (amikacin clearance depending on birth weight and post-natal age) to real-world demographic data from 1563 neonates receiving anti-infectives (median birth weight 2.3 kg, median post-natal age six days) and performed pharmacometric dose-exposure simulations to identify extended dosing intervals that would ensure non-toxic Ctrough (Ctrough <5 mg/l) dosages in most neonates. RESULTS: In the subpopulation of clinical concern, Ctrough <5 mg/l was predicted in 59% versus 79-99% of cases in all other subpopulations following the current recommendations. Elevated Ctrough values were associated with a post-natal age of less than seven days. Simulations showed that extending the dosing interval to ≥36 h in the subpopulation of clinical concern increased the frequency of a desirable Ctrough below 5 mg/l to >80%. CONCLUSION: Pharmacometric in silico studies using high-quality real-world demographic data can provide a scientific rationale for national paediatric dose optimisation. This may increase clinical acceptance of fine-tuned standardised dosing recommendations and support their implementation, including in vulnerable subpopulations.

Prevalence of and risk factors for suicidal ideation in adolescents during the COVID-19 pandemic: a cross-sectional study.

BACKGROUND AND OBJECTIVES: Pandemic-related life changes may have had a deleterious impact on suicidal behaviours. Early detection of suicidal ideation and identification of subgroups at increased risk could help prevent suicide, one of the leading causes of death among adolescents worldwide. Here, we aimed to investigate the prevalence of and risk factors for suicidal ideation in adolescents using a population-based sample from Switzerland, two years into the pandemic. METHODS: Between December 2021 and June 2022, adolescents aged 14 to 17 years already enrolled in a population-based cohort study (State of Geneva, Switzerland) were asked about suicidal ideation over the previous year. In addition to a regression model, we conducted a network analysis of exposures which identified direct and indirect risk factors for suicidal ideation (i.e. those connected through intermediate risk factors) using mixed graphical models. RESULTS: Among 492 adolescents, 14.4% (95% CI: 11.5-17.8) declared having experienced suicidal ideation over the previous year. Using network analysis, we found that high psychological distress, low self-esteem, identifying as lesbian, gay or bisexual, suffering from bullying, extensive screen time and a severe COVID-19 pandemic impact were major risk factors for suicidal ideation, with parent-adolescent relationship having the highest centrality strength in the network. CONCLUSION: Our results show that a significant proportion of adolescents experience suicidal ideation, yet these rates are comparable with pre-pandemic results. Providing psychological support is fundamental, with a focus on improving parent-adolescent relationships.