No abstract

Temporal examinations of the biological signature of stress or trauma in war-affected populations are seldom undertaken. Moreover, few studies have examined whether stress biomarkers track biological sensitivity to brief interventions targeting the improvement of psychosocial wellbeing. Our study is the first to prospectively examine, in war-affected adolescents, the associations between hair cortisol concentrations (HCC) and self-reports of stress, insecurity, posttraumatic reactions, and lifetime trauma. We conducted a randomized controlled trial to test the impact of an 8-week intervention based on profound stress attunement. We collected data for a gender-balanced sample of 733 Syrian refugee (n = 411) and Jordanian non-refugee (n = 322) adolescents (12-18 years), at three time-points. We used growth mixture models to classify cortisol trajectories, and growth models to evaluate intervention impact on stress physiology. We observed three trajectories of HCC: hypersecretion, medium secretion, and hyposecretion (9.6%, 87.5% and 2.9% of the cohort, respectively). For every one percent increase in levels of insecurity, adolescents were 0.02 times more likely to have a trajectory of hypersecretion (95% CI: 1.00, 1.03, p = 0.01). For each additional symptom of posttraumatic stress reported, they were 0.07 times less likely to show hyposecretion (95% CI: 0.89, 0.98, p = 0.01). Indeed, stronger posttraumatic stress reactions were associated with a pattern of within-individual cortisol dysregulation and medium secretion. Overall, HCC decreased by a third in response to the intervention (95% CI: -0.19, -0.03, p = 0.01). While the intervention decreased HCC for youth with hypersecretion and medium secretion, it increased HCC for youth with hyposecretion (95% CI: 0.22, 1.16, p = 0.004), relative to controls. This suggests a beneficial regularization of cortisol levels, corroborating self-reports of improved psychosocial wellbeing. We did not find evidence to suggest that gender, resilience, or posttraumatic stress disorder influenced the strength or direction of responses to the intervention. This robust impact evaluation exemplifies the utility of biomarkers for tracking physiological changes in response to interventions over time. It enhances the understanding of trajectories of endocrine response in adverse environments and patterns of stress responsivity to ecological improvement.

Adverse drug reactions (ADRs) represent a major health problem worldwide, with high morbidity and mortality rates. ADRs are classified into Type A (augmented) and Type B (bizarre) ADRs, with the former group being more common and the latter less common but often severe and clinically more problematic due to their unpredictable nature and occurrence at any dose. Pediatric populations are especially vulnerable to ADRs due to the lack of data for this age group from the drug development process and because of the wide use of off-label and unlicensed use of drugs. Children are more prone to specific types of ADRs because of the level of maturity of body systems involved in absorption, metabolism, transportation, and elimination of drugs. This state-of-the-art review provides an overview of definitions, classifications, epidemiology, and pathophysiology of ADRs and discusses the available evidence for related risk factors and causes of ADRs in the pediatric population.

Acute kidney injury (AKI) is a serious problem occurring in anywhere between 8 and 30% of children in the intensive care unit. Up to 25% of these cases are believed to be the result of pharmacotherapy. In this review we have focused on several relevant drugs and/or drug classes, which are known to cause AKI in children, including cancer chemotherapeutics, non-steroidal anti-inflammatory drugs and antimicrobials. AKI demonstrates a steady association with increased long term risk of poor outcomes including chronic kidney disease and death as determined by the extent of injury. For this reason it is important to understand the causality and implications of these drugs and drug classes. Children occupy a unique patient population, advocating the importance of understanding how they are affected dissimilarly compared with adults. While the kidney itself is likely more susceptible to injury than other organs, the inherent toxicity of these drugs also plays a major role in the resulting AKI. Mechanisms involved in the toxicity of these drugs include oxidative damage, hypersensitivity reactions, altered haemodynamics and tubule obstruction and may affect the glomerulus and/or the tubules. Understanding these mechanisms is critical in determining the most effective strategies for treatment and/or prevention, whether these strategies are less toxic versions of the same drugs or add-on agents to mitigate the toxic effect of the existing therapy.

BACKGROUND:Oral morphine for postoperative pain after minor pediatric surgery, while increasingly popular, is not supported by evidence. We evaluated whether oral morphine was superior to ibuprofen for at-home management of children's postoperative pain.