Effectiveness of behavioural and psychological interventions for managing obesity in children and adolescents: A systematic review and meta-analysis framed using minimal important difference estimates based on GRADE guidance to inform a clinical practice guideline.

Objective: Conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) of behavioural and psychological interventions for managing paediatric obesity.

Methods: Eligible studies, published between 1985 and 2022, included 0 to 18 year olds with outcomes reported ≥3 months post-baseline, including patient-reported outcome measures (PROMs), cardiometabolic and anthropometric outcomes, and adverse events (AEs). We pooled data using a random effects model and assessed certainty of evidence (CoE) related to minimally important difference estimates for outcomes using GRADE.

Maralixibat Reduces Serum Bile Acids and Improves Cholestatic Pruritus in Adolescents With Alagille Syndrome.

Background: Alagille syndrome (ALGS) is a multisystem cholestatic disorder. Maralixibat is approved for the treatment of cholestatic pruritus in ALGS with limited data in adults.

Methods: Participants were included if they received ≥ 2 doses of maralixibat at age ≥ 16 years in one of the three previously published maralixibat ALGS clinical trials.

Reduction of elevated Gli3 does not alter the progression of autosomal recessive polycystic kidney disease.

Polycystic kidney diseases (PKD) are genetic disorders which disrupt kidney architecture and function. Autosomal recessive PKD (ARPKD) is a rare form of PKD, caused by mutations in PKHD1, and clinically more severe than the more common autosomal dominant PKD (ADPKD). Prior studies have implicated Hedgehog (Hh) signaling in ADPKD, with increased levels of Hh components in experimental ADPKD and reduced cystogenesis following pharmacological Hh inhibition.

Mental Practice to Maintain Procedural Competency of Faculty with Decreased Opportunities.

Background: Physicians practicing in pediatric critical care medicine (PCCM) should maintain procedural skills competency. Faculty practicing in academic centers face challenges that may affect their procedural skills maintenance. The overall clinical opportunities are decreasing in PCCM.

Outcomes of Cyclosporine Treatment in Pediatric Drug Reaction with Eosinophilia and Systemic Symptoms (DReSS): A Retrospective Cohort Analysis.

Drug Reaction with Eosinophilia and Systemic Symptoms (DReSS) is a rare but severe hypersensitivity reaction. This retrospective cohort study compared the efficacy of systemic corticosteroids, the current first-line therapy, with cyclosporine, an emerging alternative therapy, in pediatric DReSS patients. We analyzed 14 cases of pediatric patients (<18 years) admitted to The Hospital for Sick Children between January 2016 and September 2023.

Pediatric erythromelalgia from multidisciplinary perspectives: a scoping review.

Erythromelalgia is a rare, chronic pain disorder characterized by the triad of intense burning sensation, warmth, and redness, primarily involving the hands and feet, and usually alleviated by cold and worsened by heat. The objective of this scoping review was to: 1) map the existing literature on erythromelalgia in youth, 2) identify knowledge gaps, and 3) inform directions for future research in pediatric erythromelalgia. One hundred and sixty-seven studies reporting 411 cases of childhood-onset erythromelalgia were identified.

Methods and Practical Considerations for Conducting Budget Impact Analysis for Non-Pharmaceutical Interventions.

Background: Health technology assessment (HTA) can be conducted at the national, provincial, or hospital level. Although provincial and hospital-based HTAs often focus on non-pharmaceutical interventions, budget impact analysis (BIA) methods for non-pharmaceutical interventions have received less attention in the literature.

Methods: We reviewed HTAs of non-pharmaceutical interventions published since 2015 by a Canadian provincial HTA agency, evaluating the characteristics and challenges of conducting a BIA.

Postnatal management of preterm infants with congenital diaphragmatic hernia.

Introduction: Congenital diaphragmatic hernia (CDH) in the preterm population is increasingly common in the current era of fetal endoluminal tracheal occlusion (FETO) therapy. There remains a lack of clinical guidance for clinicians and surgeons regarding optimal management strategies for such infants. We aimed to describe our experience in managing preterm CDH in a single quaternary neonatal intensive care unit (NICU).

Frequency and Impact of Constitutional Mismatch Repair Deficiency in Patients With High-Grade Glioma, a Retrospective Analysis of 7 Years in Pakistan: an IRRDC Study.

Purpose: Constitutional mismatch repair deficiency (CMMRD) is a genetic cancer predisposition syndrome among children and young adults. This study aimed to evaluate the frequency of CMMRD among patients with pediatric high-grade glioma (pHGG) in a single tertiary care center in Pakistan, a country with high consanguinity rates.

Patients And Methods: We reviewed the data of patients age <18 years with pHGG, anaplastic astrocytoma, and diffuse midline glioma (DMG) with CMMRD testing between 2016 and 2023.

Mapping TcdB interactions with host cell-surface and intracellular factors using proximity-dependent biotinylation labeling.

Many bacterial toxins exert their cytotoxic effects by enzymatically inactivating one or more cytosolic targets in host cells. To reach their intracellular targets, these toxins possess functional domains or subdomains that interact with and exploit various host factors and biological processes. Despite great progress in identifying many of the key host factors involved in the uptake of toxins, significant knowledge gaps remain as to how partially characterized and newly discovered microbial toxins exploit host factors or processes to intoxicate target cells.

Target-agnostic identification of human antibodies to sexual forms reveals cross-stage recognition of glutamate-rich repeats.

Circulating sexual stages of ) can be transmitted from humans to mosquitoes, thereby furthering the spread of malaria in the population. It is well established that antibodies can efficiently block parasite transmission. In search for naturally acquired antibodies targets on sexual stages, we established an efficient method for target-agnostic single B cell activation followed by high-throughput selection of human monoclonal antibodies (mAbs) reactive to sexual stages of in the form of gametes and gametocyte extracts.

Global Disparities in Outcomes of Pregnant Individuals With Rheumatic Heart Disease: A Scoping Review.

Background: Rheumatic heart disease (RHD) remains as 1 of the major contributors to indirect pregnancy-related mortality and morbidity worldwide and disproportionately affects marginalized populations.

Objectives: In this scoping review, the authors sought to explore the socioeconomic, cultural, and health care access-related causes of global disparities in outcomes of pregnancy among individuals with RHD.

Methods: We performed a literature search of all studies published between January 1, 1990, and January 1, 2022, that investigated causes for disparate outcomes in pregnant individuals with RHD.

Systemic Sirolimus Therapy Is Associated With Reduced Intervention Frequency in Pulmonary Vein Stenosis.

Background: Early clinical outcomes data for adjunctive systemic sirolimus therapy (SST) for moderate to severe pediatric pulmonary vein stenosis (PVS) are promising but limited.

Objectives: The authors aimed to characterize a cohort of patients treated with SST to determine if SST was associated with a reduction in frequency of PVS interventions.

Methods: Medical records of 45 patients with PVS treated with SST for ≥1 month from 2015 to 2022 were retrospectively reviewed.

Parental use of routines, setting limits, and child screen use during COVID-19: findings from a large Canadian cohort study.

Background: An increase in child screen time has been observed throughout the COVID-19 pandemic. Home environment and parenting practices have been associated with child screen time. The purpose of this study was to examine associations between parental use of routines, limit setting, and child screen time during the (COVID-19) pandemic to inform harm-reducing strategies to limit the potential harms ensued by excessive screen use.

Metabolomic in severe traumatic brain injury: exploring primary, secondary injuries, diagnosis, and severity.

Background: Traumatic brain injury (TBI) is a major public health concern worldwide, contributing to high rates of injury-related death and disability. Severe traumatic brain injury (sTBI), although it accounts for only 10% of all TBI cases, results in a mortality rate of 30-40% and a significant burden of disability in those that survive. This study explored the potential of metabolomics in the diagnosis of sTBI and explored the potential of metabolomics to examine probable primary and secondary brain injury in sTBI.

Combining theory and usability testing to inform optimization and implementation of an online primary care depression management tool.

Background: The 'Ottawa Depression Algorithm' is an evidence-based online tool developed to support primary care professionals care for adults with depression. Uptake of such tools require provider behaviour change. Identifying issues which may impact use of an innovation in routine practice (i.

Consensus outcomes between health professionals and parents for oral corticosteroids in treating preschool wheeze: a multi-national survey and nominal group technique study.

Objective: To obtain priority consensus for outcome measures of oral corticosteroid treatment of preschool wheeze that represent stakeholder groups.

Design: (1) A systematic review to identify a set of outcome measures; (2) an international survey for healthcare professionals (HCPs) and a nominal group meeting with parents; (3) a final consensus nominal group meeting with key HCPs (trial investigators and paediatric emergency medicine clinicians) and the same parent group.

Main Outcome Measures: Consensus priority of treatment outcome measures, outcome minimal clinically important differences (MCIDs) and level of concerns about adverse effects.

Effect of Characteristic Inflammatory and Structural Pelvic Magnetic Resonance Imaging Lesions on Expert Assessment of Axial Juvenile Spondyloarthritis.

Objective: To evaluate the influence of pelvic magnetic resonance imaging (MRI) findings on axial disease assessment in juvenile spondyloarthritis (JSpA).

Methods: This was a cross-sectional study of patients with JSpA with suspected axial disease. Three experts reviewed each case and rated their confidence (-3 to +3) in the presence of axial disease, first with clinical data and second with clinical and MRI data.

Child Neurology: Severe -Related Congenital Muscular Dystrophy With Rapidly Progressive Encephalopathy Leading to Infantile Death.

Pathogenic variants in cause congenital muscular dystrophy through hypoglycosylation of alpha-dystroglycan (OMIM #615350). The established phenotypic spectrum of GMPPB-related disorders includes recurrent rhabdomyolysis, limb-girdle muscular dystrophy, neuromuscular transmission abnormalities, and congenital muscular dystrophy with variable brain and eye anomalies. We report a 9-month-old male infant with congenital muscular dystrophy, infantile spasms, and compound heterozygous pathogenic variants (c.

regulates melanocortin 4 receptor transcription and energy homeostasis.

Disruption of hypothalamic melanocortin 4 receptors (MC4Rs) causes obesity in mice and humans. Here, we investigated the transcriptional regulation of in the hypothalamus. In mice, we show that the homeodomain transcription factor Orthopedia (OTP) is enriched in MC4R neurons in the paraventricular nucleus (PVN) of the hypothalamus and directly regulates transcription.

Mutations disrupting the kinase domain of IKKα lead to immunodeficiency and immune dysregulation in humans.

IKKα, encoded by CHUK, is crucial in the non-canonical NF-κB pathway and part of the IKK complex activating the canonical pathway alongside IKKβ. The absence of IKKα causes fetal encasement syndrome in humans, fatal in utero, while an impaired IKKα-NIK interaction was reported in a single patient and causes combined immunodeficiency. Here, we describe compound heterozygous variants in the kinase domain of IKKα in a female patient with hypogammaglobulinemia, recurrent lung infections, and Hay-Wells syndrome-like features.

Prevalence of pathogenic variants of inborn errors of immunity in critically ill children admitted to the pediatric intensive care unit for sepsis: A Moroccan cohort study.

Introduction: Pediatric sepsis remains a leading cause of morbidity and mortality in Africa. Nearly half of pediatric sepsis deaths occur in previously healthy children. The role of inborn errors of immunity (IEI) in susceptibility to sepsis is yet to be identified and their prevalence amongst previously healthy children admitted to the pediatric intensive care unit (PICU) is unclear.

Utilities Associated with the Treatment of Growth Hormone Deficiency (GHD): A Time Trade-off (TTO) Study in the UK and Canada.

Purpose: Growth hormone deficiency (GHD) causes decreased growth rate in children, resulting in short stature in childhood and adulthood. Daily subcutaneous injections with growth hormone (GH) have been standard treatment. Newer weekly GH formulations now exist.

Visual Acuity, Full-field Stimulus Thresholds, and Electroretinography for 4 Years in The Rate of Progression of USH2A-related Retinal Degeneration (RUSH2A) Study.

Purpose: To describe progression of best-corrected visual acuity (BCVA), full-field stimulus thresholds (FST), and electroretinography (ERG) over 4 years in the -related Retinal Degeneration study and to assess their suitability as clinical trial endpoints.

Design: Prospective natural history study.

Participants: Participants (n = 105) with biallelic disease-causing sequence variants in USH2A and BCVA letter scores of ≥54 were included.

Neonatal Encephalopathy: Novel Phenotypes and Genotypes Identified by Genome Sequencing.

Background And Objectives: Neonatal encephalopathy (NE) is characterized by an abnormal level of consciousness with or without seizures in the neonatal period. It affects 1-6/1,000 live term newborns. We applied genome sequencing (GS) in term newborns with NE to investigate the underlying genetic causes.