Medicines management in children and young people: pharmacokinetics, drug calculations and off-label drug use.

Medicines management in children and young people presents specific challenges because children differ from adults in their response to medicines. The way in which medicines work inside the human body, or pharmacokinetics, varies according to age and stage of development. Accurate drug calculations for a child rely on the careful consideration of a series of factors, such as weight and height, pharmacokinetics and drug characteristics. This article focuses on three fundamental aspects: pharmacokinetics, drug calculations, and unlicensed and off-label drug use.

Parental positive affect and negative affect in same- and different-sex parent families: no associations with parental gender and caregiving role.

Positive and negative parental affect influence developing parent-child attachment relationships, especially during infancy as well as children's social-emotional, academic, and behavioral functioning later in life. Increasingly, because both mothers and fathers can play central caregiving roles, the parenting qualities of both parents demand consideration. Therefore, this study investigated whether parental gender and caregiving role were associated with mothers' and fathers' positive affect and negative affect during interactions with their 4-month-old firstborn infant, while determining whether parenting stress, infant temperament, having a singleton/twin, and living in the Netherlands, France, or the United Kingdom were related to parental positive affect and negative affect. In all, 135 different-sex, same-sex male, and same-sex female couples (113 fathers and 157 mothers, comprising 147 primary, and 123 secondary caregivers) who conceived through artificial reproductive techniques were studied. The couples were videorecorded at home while in feeding, cleaning, and playing contexts to assess the levels of positive and negative parental affect. In addition, the couples completed questionnaires about their caregiving role, parenting stress, and the infants' temperament. Mixed linear models indicated that the levels of positive and negative parental affect toward the infant in all contexts were not related to parental gender, caregiving role, the interaction between parental gender and caregiving role, parenting stress, infant temperament, or singleton/twin status. However, the target parental behaviors were related to the country of origin, suggesting differences among Dutch, French, and British parents. Overall, we found no evidence that gender or caregiving roles were associated with the levels of positive and negative affect shown by the parents.

Real-world utility of overnight oximetry for the screening of obstructive sleep apnea in children.

BACKGROUND: Obstructive sleep apnea (OSA) is a common problem in children and can result in developmental and cognitive complications if untreated. The gold-standard tool for diagnosis is polysomnography (PSG); however, it is an expensive and time-consuming test to undertake. Overnight oximetry has been suggested as a faster and cheaper initial test in comparison to PSG as it can be performed at home using limited, reusable equipment. AIM: This retrospective case control study aims to evaluate the effectiveness of a home oximetry service (implemented in response to extended waiting times for routine PSG) in reducing the time between patient referral and treatment. METHODS: Patients undergoing diagnostic sleep evaluation for suspected OSA who utilized the Queensland Children's Hospital screening home oximetry service in the first year since its inception in 2021 (n = 163) were compared to a historical group of patients who underwent PSG in 2018 (n = 311). Parameters compared between the two groups included time from sleep physician review to sleep test, ENT review, and definitive treatment in the form of adenotonsillectomy surgery (or CPAP initiation for those who had already undergone surgery). RESULTS: The time from sleep physician review and request of the sleep-related study to ENT surgical treatment was significantly reduced (187 days for the HITH oximetry group vs 359 days for the comparable PSG group; p-value <0.05), and time from sleep study request to the report of results was significantly lower for patients in the oximetry group compared to those in the PSG group (11 days vs 105 days; p-value <0.05). CONCLUSION: These results suggest that for children referred to a tertiary sleep center for possible obstructive sleep disordered breathing, a home oximetry service can be effective in assisting sleep evaluation and reducing the time to OSA treatment.

Destabilisation of T cell-dependent humoral immunity in sepsis.

Sepsis is a heterogeneous condition defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. For some, sepsis presents as a predominantly suppressive disorder, whilst others experience a pro-inflammatory condition which can culminate in a 'cytokine storm'. Frequently, patients experience signs of concurrent hyper-inflammation and immunosuppression, underpinning the difficulty in directing effective treatment. Although intensive care unit mortality rates have improved in recent years, one-third of discharged patients die within the following year. Half of post-sepsis deaths are due to exacerbation of pre-existing conditions, whilst half are due to complications arising from a deteriorated immune system. It has been suggested that the intense and dysregulated response to infection may induce irreversible metabolic reprogramming in immune cells. As a critical arm of immune protection in vertebrates, alterations to the adaptive immune system can have devastating repercussions. Indeed, a marked depletion of lymphocytes is observed in sepsis, correlating with increased rates of mortality. Such sepsis-induced lymphopenia has profound consequences on how T cells respond to infection but equally on the humoral immune response that is both elicited by B cells and supported by distinct CD4+ T follicular helper (TFH) cell subsets. The immunosuppressive state is further exacerbated by functional impairments to the remaining lymphocyte population, including the presence of cells expressing dysfunctional or exhausted phenotypes. This review will specifically focus on how sepsis destabilises the adaptive immune system, with a closer examination on how B cells and CD4+ TFH cells are affected by sepsis and the corresponding impact on humoral immunity.

A Digital Health Solution for Child Growth Monitoring at Home: Testing the Accuracy of a Novel "GrowthMonitor" Smartphone Application to Detect Abnormal Height and Body Mass Indices.

Objective: To develop and evaluate a smartphone application that accurately measures height and provides notifications when abnormalities are detected. Patients and Methods: A total of 145 (75 boys) participants with a mean age ± SD of 8.7±4.5 years (range, 1.0-17.0 years), from the Children's Hospital at Barts Health Trust, London, United Kingdom, were enrolled in the study. "GrowthMonitor" (UCL Creatives) iPhone application (GMA) measures height using augmented reality. Using population-based (UK-WHO) references, algorithms calculated height SD score (HSDS), distance from target height (THSDSDEV), and HSDS change over time (ΔHSDS). Pre-established thresholds discriminated normal/abnormal growth. The GMA and a stadiometer (Harpenden; gold standard) measured standing heights of children at routine clinic visits. A subset of parents used GMA to measure their child's height at home. Outcome targets were 95% of GMA measurements within ±0.5 SDS of the stadiometer and the correct identification of abnormal HSDS, THSDSDEV, and ΔHSDS. Results: Bland-Altman plots revealed no appreciable bias in differences between paired study team GMA and stadiometer height measurements, with a mean of the differences of 0.11 cm with 95% limits of agreement of -2.21 to 2.42 cm. There was no evidence of greater bias occurring for either shorter/younger children or taller/older children. The 2 methods of measurements were highly correlated (R=0.999). GrowthMonitor iPhone application measurements performed by parents in clinic and at home were slightly less accurate. The κ coefficient indicated reliable and consistent agreement of flag alerts for HSDS (κ=0.74) and THSDSDEV (κ=0.88) between 83 paired GMA and stadiometer measurements. GrowthMonitor iPhone application yielded a detection rate of 96% and 97% for HSDS-based and THSDSDEV-based red flags, respectively. Forty-two (18 boys) participants had GMA calculated ΔHSDS using an additional height measurement 6-16 months later, and no abnormal flag alerts were triggered for ΔHSDS values. Conclusion: GrowthMonitor iPhone application provides the potential for parents/carers and health care professionals to capture serial height measurements at home and without specialized equipment. Reliable interpretation and flagging of abnormal measurements indicate the potential of this technology to transform childhood growth monitoring.