Hair cortisol analysis: An update on methodological considerations and clinical applications.

BACKGROUND: Hair cortisol analysis is increasingly being appreciated and applied in both research and medicine, aiding endocrinologists with diagnosis. CONTENT: We provide an overview of hair cortisol research in general and an update on methodological considerations including the incorporation of cortisol into hair, hair growth rates, and sampling procedures, mincing vs. grinding of samples during preparation for extraction, various extraction protocols, and quantification techniques. We compare the clinical utility and application of hair cortisol with traditional methods of measurement while acknowledging the limitations of analysis including variations in hair growth parameters. We explore the value of hair cortisol in cases of Cushing syndrome (particularly Cyclical Cushing), Adrenal insufficiency (including Addison's disease), therapy monitoring, cardiovascular disease, stress, and mental illness. SUMMARY: Hair cortisol provides a unique objective biomarker for the analysis of endogenous cortisol levels for not only clinical diagnostic purposes but also in research. The use of hair cortisol has great potential for advancing patient care.

Hair cortisol concentrations in war-affected adolescents: A prospective intervention trial.

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.

Oral morphine versus ibuprofen administered at home for postoperative orthopedic pain in children: a randomized controlled trial.

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. METHODS: We conducted a randomized superiority trial comparing oral morphine (0.5 mg/kg) with ibuprofen (10 mg/kg) in children 5 to 17 years of age who had undergone minor outpatient orthopedic surgery (June 2013 to September 2016). Participants took up to 8 doses of the intervention drug every 6 hours as needed for pain at home. The primary outcome was pain, according to the Faces Pain Scale - Revised, for the first dose. Secondary outcomes included additional analgesic requirements, adverse effects, unplanned health care visits and pain scores for doses 2 to 8. RESULTS: We analyzed data for 77 participants in each of the morphine and ibuprofen groups. Both interventions decreased pain scores with no difference in efficacy. The median difference in pain score before and after the first dose of medication was 1 (interquartile range 0-1) for both morphine and ibuprofen (p = 0.2). For doses 2 to 8, the median differences in pain score before and after the dose were not significantly different between groups. Significantly more participants taking morphine reported adverse effects (45/65 [69%] v. 26/67 [39%], p < 0.001), most commonly drowsiness (31/65 [48%] v. 15/67 [22%] in the morphine and ibuprofen groups, respectively; p = 0.003). INTERPRETATION: Morphine was not superior to ibuprofen, and both drugs decreased pain with no apparent difference in efficacy. Morphine was associated with significantly more adverse effects, which suggests that ibuprofen is a better first-line option after minor surgery. TRIAL REGISTRATION: ClinicalTrials.gov, no. NCT01686802.

Drug-induced acute kidney injury in children.

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.