Effect of systematic tuberculosis detection on mortality in young children with severe pneumonia in countries with high incidence of tuberculosis: a stepped-wedge cluster-randomised trial.

Background: Tuberculosis diagnosis might be delayed or missed in children with severe pneumonia because this diagnosis is usually only considered in cases of prolonged symptoms or antibiotic failure. Systematic tuberculosis detection at hospital admission could increase case detection and reduce mortality.

Methods: We did a stepped-wedge cluster-randomised trial in 16 hospitals from six countries (Cambodia, Cameroon, Côte d'Ivoire, Mozambique, Uganda, and Zambia) with high incidence of tuberculosis.

Tissue mosaicism, FMR1 expression and intellectual functioning in males with fragile X syndrome.

Fragile X syndrome (FXS) is caused by hypermethylation of the FMR1 promoter due to the full mutation expansion (full mutation [FM]: CGG ≥ 200 repeats) and silencing of FMR1. Assessment of mosaicism for active-unmethylated alleles has prognostic utility. This study examined relationships between FMR1 methylation in different tissues with FMR1 messenger ribonucleic acid (mRNA) and intellectual functioning in 87 males with FXS (1.

Global estimates and determinants of antituberculosis drug pharmacokinetics in children and adolescents: a systematic review and individual patient data meta-analysis.

Background: Suboptimal exposure to antituberculosis (anti-TB) drugs has been associated with unfavourable treatment outcomes. We aimed to investigate estimates and determinants of first-line anti-TB drug pharmacokinetics in children and adolescents at a global level.

Methods: We systematically searched MEDLINE, Embase and Web of Science (1990-2021) for pharmacokinetic studies of first-line anti-TB drugs in children and adolescents.

Neurodevelopmental and Epilepsy Phenotypes in Individuals With Missense Variants in the Voltage-Sensing and Pore Domains of .

Background And Objectives: encodes the voltage-gated potassium channel EAG2/Kv10.2. We aimed to delineate the neurodevelopmental and epilepsy phenotypic spectrum associated with de novo variants.

Key lessons from the COVID-19 public health response in Australia.

Australia avoided the worst effects of the COVID-19 pandemic, but still experienced many negative impacts. Reflecting on lessons from Australia's public health response, an Australian expert panel composed of relevant discipline experts identified the following key lessons: 1) movement restrictions were effective, but their implementation requires careful consideration of adverse impacts, 2) disease modelling was valuable, but its limitations should be acknowledged, 3) the absence of timely national data requires re-assessment of national surveillance structures, 4) the utility of advanced pathogen genomics and novel vaccine technology was clearly demonstrated, 5) decision-making that is evidence informed and consultative is essential to maintain trust, 6) major system weaknesses in the residential aged-care sector require fixing, 7) adequate infection prevention and control frameworks are critically important, 8) the interests and needs of young people should not be compromised, 9) epidemics should be recognised as a 'standing threat', 10) regional and global solidarity is important. It should be acknowledged that we were unable to capture all relevant nuances and context specific differences.

Sex-specific transcriptomic and epitranscriptomic signatures of PTSD-like fear acquisition.

Our understanding of the molecular pathology of posttraumatic stress disorder (PTSD) is evolving due to advances in sequencing technologies. With the recent emergence of Oxford Nanopore direct RNA-seq (dRNA-seq), it is now also possible to interrogate diverse RNA modifications, collectively known as the "epitranscriptome.".

Current practice in diagnostic genetic testing of the epilepsies.

Epilepsy genetics is a rapidly developing field, in which novel disease-associated genes, novel mechanisms associated with epilepsy, and precision medicine approaches are continuously being identified. In the past decade, advances in genomic knowledge and analysis platforms have begun to make clinical genetic testing accessible for, in principle, people of all ages with epilepsy. For this reason, the Genetics Commission of the International League Against Epilepsy (ILAE) presents this update on clinical genetic testing practice, including current techniques, indications, yield of genetic testing, recommendations for pre- and post-test counseling, and follow-up after genetic testing is completed.

Unclassified white matter disorders: A diagnostic journey requiring close collaboration between clinical and laboratory services.

Background: Next generation sequencing studies have revealed an ever-increasing number of causes for genetic disorders of central nervous system white matter. A substantial number of disorders are identifiable from their specific pattern of biochemical and/or imaging findings for which single gene testing may be indicated. Beyond this group, the causes of genetic white matter disorders are unclear and a broader approach to genomic testing is recommended.

Performance of Xpert MTB/RIF and Mycobacterial Culture on Multiple Specimen Types for Diagnosis of Tuberculosis Disease in Young Children and Clinical Characterization According to Standardized Research Case Definitions.

Background: Tuberculosis (TB) is a leading cause of illness and death in children globally. Improved bacteriologic and clinical diagnostic approaches in children are urgently needed.

Methods: In a prospective cohort study, a consecutive series of young (<5 years) children presenting with symptoms suggestive of TB and parenchymal abnormality on chest radiograph in inpatient and outpatient settings in Kisumu County, Kenya from October 2013 to August 2015 were evaluated at baseline and over 6 months.

The role of common genetic variation in presumed monogenic epilepsies.

Background: The developmental and epileptic encephalopathies (DEEs) are the most severe group of epilepsies which co-present with developmental delay and intellectual disability (ID). DEEs usually occur in people without a family history of epilepsy and have emerged as primarily monogenic, with damaging rare mutations found in 50% of patients. Little is known about the genetic architecture of patients with DEEs in whom no pathogenic variant is identified.

Implications of providing wrist-hand orthoses for children with cerebral palsy: evidence from a randomised controlled trial.

Purpose: To investigate the effects of providing rigid wrist-hand orthoses plus usual multidisciplinary care, on reducing hand impairments in children with cerebral palsy.

Methods: A pragmatic, multicentre, assessor-blinded randomised controlled trial aimed to enrol 194 children aged 5-15 years, with wrist flexor Modified Ashworth Scale score ≥1. Randomisation with concealed allocation was stratified by study site and passive wrist range.

Common risk variants for epilepsy are enriched in families previously targeted for rare monogenic variant discovery.

Background: The epilepsies are highly heritable conditions that commonly follow complex inheritance. While monogenic causes have been identified in rare familial epilepsies, most familial epilepsies remain unsolved. We aimed to determine (1) whether common genetic variation contributes to familial epilepsy risk, and (2) whether that genetic risk is enriched in familial compared with non-familial (sporadic) epilepsies.

Rapid deployment of support for a mental health crisis: 10 priorities framing Australia’s COVID-19 pandemic response.

The COVID-19 pandemic has challenged the mental health of communities worldwide, with the triple pressures of financial insecurity, lockdowns, and worry about the infection. Australia rapidly deployed resources to protect the mental wellbeing of the community through supplementing existing services, supporting at-risk groups, investing in social supports, embracing technology, and supporting the health workforce. This paper describes the Australian Government's investment in mental health during the COVID-19 pandemic in relation to the 10 priority areas identified in Australia's National Mental Health Pandemic Response Plan.

Evolution and spread of a highly drug resistant strain of Mycobacterium tuberculosis in Papua New Guinea.

Background: Molecular mechanisms determining the transmission and prevalence of drug resistant tuberculosis (DR-TB) in Papua New Guinea (PNG) are poorly understood. We used genomic and drug susceptibility data to explore the evolutionary history, temporal acquisition of resistance and transmission dynamics of DR-TB across PNG.

Methods: We performed whole genome sequencing on isolates from Central Public Health Laboratory, PNG, collected 2017-2019.

International League Against Epilepsy classification and definition of epilepsy syndromes with onset at a variable age: position statement by the ILAE Task Force on Nosology and Definitions.

The goal of this paper is to provide updated diagnostic criteria for the epilepsy syndromes that have a variable age of onset, based on expert consensus of the International League Against Epilepsy Nosology and Definitions Taskforce (2017-2021). We use language consistent with current accepted epilepsy and seizure classifications and incorporate knowledge from advances in genetics, electroencephalography, and imaging. Our aim in delineating the epilepsy syndromes that present at a variable age is to aid diagnosis and to guide investigations for etiology and treatments for these patients.

Nasal High-Flow Therapy during Neonatal Endotracheal Intubation.

Background: Neonatal endotracheal intubation often involves more than one attempt, and oxygen desaturation is common. It is unclear whether nasal high-flow therapy, which extends the time to desaturation during elective intubation in children and adults receiving general anesthesia, can improve the likelihood of successful neonatal intubation on the first attempt.

Methods: We performed a randomized, controlled trial to compare nasal high-flow therapy with standard care (no nasal high-flow therapy or supplemental oxygen) in neonates undergoing oral endotracheal intubation at two Australian tertiary neonatal intensive care units.

Child and caregiver perspectives on access to psychosocial and educational support in pediatric chronic kidney disease: a focus group study.

Background: Children with chronic kidney disease (CKD) generally have worse educational and psychosocial outcomes compared with their healthy peers. This can impair their ability to manage their treatment, which in turn can have long-term health consequences through to adulthood. We attempted to capture the experiences of children with CKD and to describe the perspectives of their parents and caregivers on access to educational and psychosocial support.

Tuberculosis in Children and Adolescents: Progress and Perseverance.

Although it is an ancient pathogen, tuberculosis (TB) remains a major infectious cause of death globally, transiently displaced by COVID-19 [...