Notes

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Posaconazole exhibits broad-spectrum antifungal activity. An IV formulation became available in 2014. Few studies describing the use of this formulation exist in patients under the age of 18 years. This study describes our experience using IV posaconazole in paediatric and young adult cancer patients.

This single-centre retrospective chart review evaluated patients who received IV posaconazole and had at least one posaconazole plasma concentration obtained after five or more days with a consistent dosage. Relationships between doses required to achieve a plasma concentration of ≥1 µg/mL and patient age, weight and body surface area (BSA) were evaluated. The clinical record was reviewed to identify descriptions of any adverse events.

Twenty-five patients were analysed, with a median age of 10.5 years (range 1.9-22.9 years; 92% were <18 years). All patients were able to achieve a posaconazole plasma concentration ≥1 µg/mL during their treatment course. The daily mg/kg/day dose required to achieve the target concentration decreased significantly with increasing age of the patient (P = 0.018). Assessment of dosage based on BSA suggested a requirement of 225 mg/m2/day across all age groups <18 years. Adverse events documented in the clinical record were consistent with those described with the oral formulations. No CNS toxicities were observed with use of IV posaconazole.

Concentrations ≥1 µg/mL are achievable and a BSA-based dosing approach may allow a consistent empirical dose for patients <18 years of age. Therapeutic drug monitoring is recommended to ensure patients achieve therapeutic concentrations.
Concentrations ≥1 µg/mL are achievable and a BSA-based dosing approach may allow a consistent empirical dose for patients less then 18 years of age. Therapeutic drug monitoring is recommended to ensure patients achieve therapeutic concentrations.
An increased focus on biological age, 'frailty', is important in an ageing population including those undergoing cardiac surgery. None of the existing surgery risk scores European System for Cardiac Operative Risk Evaluation II or Society of Thoracic Surgeons score incorporates frailty. Therefore, there is a need for an additional risk score model including frailty and not simply the chronological age. The aim of this study was to evaluate the impact of frailty assessment on 1-year mortality and morbidity for patients undergoing cardiac surgery.

A total of 604 patients aged ≥65 years undergoing non-acute cardiac surgery were included in this single-centre prospective observational study. We compared 1-year mortality and morbidity in frail versus non-frail patients. The Comprehensive Assessment of Frailty (CAF) score was used This is a score of 1-35 determined via minor physical tests. A CAF score ≥11 indicates frailty.

The median age was 73 years and 79% were men. Twenty-five percent were deemed frail. Frail patients had four-fold, odds ratios 4.63, 95% confidence interval (CI) 2.21-9.69; P < 0.001 increased 1-year mortality and increased risk of postoperative complications, i.e. surgical wound infections and prolonged hospital length of stay. A univariable Cox proportional hazards regression showed that an increased CAF score was a risk factor of mortality at any time after undergoing cardiac surgery (hazards ratios 1.11, 95% CI 1.07-1.14; P < 0.001).

CAF score identified frail patients undergoing cardiac surgery and was a good predictor of 1-year mortality.

NCT02992587.
NCT02992587.The COVID-19 pandemic has presented unique circumstances that have the potential to both positively and negatively affect pediatric adherence and self-management in youth with chronic medical conditions. The following paper discusses how these circumstances (e.g., stay-at-home orders, school closures, changes in pediatric healthcare delivery) impact disease management at the individual, family, community, and healthcare system levels. We also discuss how barriers to pediatric adherence and self-management exacerbated by the pandemic may disproportionately affect underserved and vulnerable populations, potentially resulting in greater health disparities. Given the potential for widespread challenges to pediatric disease management during the pandemic, ongoing monitoring and promotion of adherence and self-management is critical. Technology offers several opportunities for this via telemedicine, electronic monitoring, and mobile apps. Moreover, pediatric psychologists are uniquely equipped to develop and implement adherence-promotion efforts to support youth and their families in achieving and sustaining optimal disease management as the current public health situation continues to evolve. Research efforts addressing the short- and long-term impact of the pandemic on pediatric adherence and self-management are needed to identify both risk and resilience factors affecting disease management and subsequent health outcomes during this unprecedented time.Maternal hyperoxygenation is a feasible, noninvasive method to treat fetal diseases, such as heart hypoplasia, but effects of maternal hyperoxygenation on the developing brain remain poorly understood. Previous studies showed that short-term maternal hyperoxygenation during midneurogenic phase (E14-E16) but not in earlier development (E10-E12) increases oxygen tension and enhances neurogenesis in the developing mouse cortex. click here We investigated effects of early chronic maternal hyperoxygenation (CMH) as a potential clinical treatment. Pregnant C57BL/6J mice were housed in a chamber at 75% atmospheric oxygen and the brains of E16 fetuses were analyzed using immunohistochemistry. The mitosis marker phH3 showed a significant reduction of proliferation in the dorsolateral cortices of CMH-treated E16 fetuses. Numbers of Tbr2-positive intermediate progenitor cells were unaffected whereas numbers of Pax6-positive apical progenitor cells were significantly reduced in CMH-treated mice. This resulted in altered cortical plate development with fewer Satb2-positive upper layer neurons but more Tbr1-positive neurons corresponding to the deeper layer 6. Thus, maternal hyperoxygenation affects the developing cortex depending on timing and length of applied oxygen. Early CMH causes a severe reduction of neuroprogenitor proliferation likely affecting cortical development. Further studies are needed to investigate the mechanisms underlying these findings and to assess the clinical and neurodevelopmental outcomes of the pups.
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