Social-ecological considerations informing a universal screening strategy for sleep health in the community

“Poor sleep health” (PSH), defined as reduced amount of sleep and non-restorative sleep, affects cognitive, social and emotional development. Evidence suggests an association of sleep deprivation and mental health problems; however, there are no universal concepts allowing a first-tier screening of PSH at a community level. The focus of this narrative review is to highlight the cultural context of the current medicalized approach to PSH and to suggest social ecological strategies informing new and holistic community-based screening concepts. We present two conceptual screening frameworks; a “medical” and a merged “social emotional wellbeing framework” and combine them utilizing the concept of “ecologies.” The first framework proposes the incorporation of “sleep” in the interpretation of “vigilance” and “inappropriate” labeled behaviors. In the first framework, we provide a logic model for screening the myriad of presentations and possible root causes of sleep disturbances as a tool to assess daytime behaviors in context with PSH. In the second framework, we provide evidence that informs screening for “social emotional wellbeing” in the context of predictive factors, perpetuating factors and predispositions through different cultural perspectives. The distinct goals of both frameworks are to overcome training-biased unidirectional thinking and a priori medicalization of challenging, disruptive and/or disobedient behaviors. The latter has been explicitly informed by the critical discourse on colonization and its consequences, spearheaded by First Nations. Our “transcultural, transdisciplinary and transdiagnostic screening framework” may serve as a starting point from which adaptations of medical models could be developed to suit the purposes of holistic screening, diagnosis, and treatment of complex childhood presentations in different cultural contexts

Claudin-11 in health and disease: implications for myelin disorders, hearing, and fertility

Claudin-11 plays a critical role in multiple physiological processes, including myelination, auditory function, and spermatogenesis. Recently, stop-loss mutations in CLDN11 have been identified as a novel cause of hypomyelinating leukodystrophy (HLD22). Understanding the multifaceted roles of claudin-11 and the potential pathogenic mechanisms in HLD22 is crucial for devising targeted therapeutic strategies. This review outlines the biological roles of claudin-11 and the implications of claudin-11 loss in the context of the Cldn11 null mouse model. Additionally, HLD22 and proposed pathogenic mechanisms, such as endoplasmic reticulum stress, will be discussed

Editorial: Sleep, vigilance & disruptive behaviors

The Frontiers in Psychiatry Research Theme of Sleep, vigilance, and disruptive behaviors has two aims: first, to promote the understanding of the connections between vigilance and disruptive daytime behavior in the context of sleep deprivation and, second, to explore how naturalistic observations and pattern recognition can play a role in furthering our understanding of these connections. . .

Sleep Health Issues for Children with FASD: Clinical Considerations

This article describes the combined clinical experience of a multidisciplinary group of professionals on the sleep disturbances of children with fetal alcohol spectrum disorders (FASD) focusing on sleep hygiene interventions. Such practical and comprehensive information is not available in the literature. Severe, persistent sleep difficulties are frequently associated with this condition but few health professionals are familiar with both FASD and sleep disorders. The sleep promotion techniques used for typical children are less suitable for children with FASD who need individually designed interventions. The types, causes, and adverse effects of sleep disorders, the modification of environment, scheduling and preparation for sleep, and sleep health for their caregivers are discussed. It is our hope that parents and also researchers, who are interested in the sleep disorders of children with FASD, will benefit from this presentation and that this discussion will stimulate much needed evidence-based research

Changes in healthcare costs following genome-wide sequencing for children with developmental disorders and early onset seizures in England and Canada

Importance Etiologic diagnoses for rare diseases can involve a diagnostic odyssey, with repeated health care interactions and inconclusive diagnostics. Prior studies reported cost savings associated with genome-wide sequencing (GWS) compared with cytogenetic or molecular testing through rapid genetic diagnosis, but there is limited evidence on whether diagnosis from GWS is associated with reduced health care costs. Objective To measure changes in health care costs after diagnosis from GWS for Canadian and English children with suspected rare diseases. Design, Setting, and Participants This cohort study was a quasiexperimental retrospective analysis across 3 distinct English and Canadian cohorts, completed in 2023. Mixed-effects generalized linear regression was used to estimate associations between GWS and costs in the 2 years before and after GWS. Difference-in-differences regression was used to estimate associations of genetic diagnosis and costs. Costs are in 2019 US dollars. GWS was conducted in a research setting (Genomics England 100 000 Genomes Project [100KGP] and Clinical Assessment of the Utility of Sequencing and Evaluation as a Service [CAUSES] Research Clinic) or clinical outpatient setting (publicly reimbursed GWS in British Columbia [BC], Canada). Participants were children with developmental disorders, seizure disorders, or both undergoing GWS between 2014 and 2019. Data were analyzed from April 2021 to September 2023. Exposures GWS and genetic diagnosis. Main Outcomes and Measures Annual health care costs and diagnostic costs per child. Results Study cohorts included 7775 patients in 100KGP, among whom 788 children had epilepsy (mean [SD] age at GWS, 11.6 [11.1] years; 400 female [50.8%]) and 6987 children had an intellectual disability (mean [SD] age at GWS, 8.2 [8.4] years; 2750 female [39.4%]); 77 patients in CAUSES (mean [SD] age at GWS, 8.5 [4.4] years; 33 female [42.9%]); and 118 publicly reimbursed GWS recipients from BC (mean [SD] age at GWS, 5.5 [5.2] years; 58 female [49.2%]). GWS diagnostic yield was 143 children (18.1%) for those with epilepsy and 1323 children (18.9%) for those with an intellectual disability in 100KGP, 47 children (39.8%) in the BC publicly reimbursed setting, and 42 children (54.5%) in CAUSES. Mean annual per-patient spending over the study period was $5283 (95$5121-$5427) for epilepsy and$3373 (95% CI, $3322-$3424) for intellectual disability in the 100KGP, $724 (95$563-$886) in CAUSES, and$1573 (95% CI, $1372-$1773) in the BC reimbursed setting. Receiving a genetic diagnosis from GWS was not associated with changed costs in any cohort. Conclusions and Relevance In this study, receiving a genetic diagnosis was not associated with cost savings. This finding suggests that patient benefit and cost-effectiveness should instead drive GWS implementation

Iron Deficiency and Sleep/Wake Behaviors: A Scoping Review of Clinical Practice Guidelines-How to Overcome the Current Conundrum?

Current evidence suggests that iron deficiency (ID) plays a key role in the pathogenesis of conditions presenting with restlessness such as attention deficit hyperactivity disorder (ADHD) and restless legs syndrome (RLS). In clinical practice, ID and iron supplementation are not routinely considered in the diagnostic work-up and/or as a treatment option in such conditions. Therefore, we conducted a scoping literature review of ID guidelines. Of the 58 guidelines included, only 9 included RLS, and 3 included ADHD. Ferritin was the most frequently cited biomarker, though cutoff values varied between guidelines and depending on additional factors such as age, sex, and comorbidities. Recommendations surrounding measurable iron biomarkers and cutoff values varied between guidelines; moreover, despite capturing the role of inflammation as a concept, most guidelines often did not include recommendations for how to assess this. This lack of harmonization on the interpretation of iron and inflammation biomarkers raises questions about the applicability of current guidelines in clinical practice. Further, the majority of ID guidelines in this review did not include the ID-associated disorders, ADHD and RLS. As ID can be associated with altered movement patterns, a novel consensus is needed for investigating and interpreting iron status in the context of different clinical phenotypes

Iron Deficiency and Sleep/Wake Behaviors: A Scoping Review of Clinical Practice Guidelines—How to Overcome the Current Conundrum?

Current evidence suggests that iron deficiency (ID) plays a key role in the pathogenesis of conditions presenting with restlessness such as attention deficit hyperactivity disorder (ADHD) and restless legs syndrome (RLS). In clinical practice, ID and iron supplementation are not routinely considered in the diagnostic work-up and/or as a treatment option in such conditions. Therefore, we conducted a scoping literature review of ID guidelines. Of the 58 guidelines included, only 9 included RLS, and 3 included ADHD. Ferritin was the most frequently cited biomarker, though cutoff values varied between guidelines and depending on additional factors such as age, sex, and comorbidities. Recommendations surrounding measurable iron biomarkers and cutoff values varied between guidelines; moreover, despite capturing the role of inflammation as a concept, most guidelines often did not include recommendations for how to assess this. This lack of harmonization on the interpretation of iron and inflammation biomarkers raises questions about the applicability of current guidelines in clinical practice. Further, the majority of ID guidelines in this review did not include the ID-associated disorders, ADHD and RLS. As ID can be associated with altered movement patterns, a novel consensus is needed for investigating and interpreting iron status in the context of different clinical phenotypes

Arginine:glycine amidinotransferase (AGAT) deficiency: Clinical features and long term outcomes in 16 patients diagnosed worldwide

Abstract Background Arginine:glycine aminotransferase (AGAT) (GATM) deficiency is an autosomal recessive inborn error of creative synthesis. Objective We performed an international survey among physicians known to treat patients with AGAT deficiency, to assess clinical characteristics and long-term outcomes of this ultra-rare condition. Results 16 patients from 8 families of 8 different ethnic backgrounds were included. 1 patient was asymptomatic when diagnosed at age 3 weeks. 15 patients diagnosed between 16 months and 25 years of life had intellectual disability/developmental delay (IDD). 8 patients also had myopathy/proximal muscle weakness. Common biochemical denominators were low/undetectable guanidinoacetate (GAA) concentrations in urine and plasma, and low/undetectable cerebral creatine levels. 3 families had protein truncation/null mutations. The rest had missense and splice mutations. Treatment with creatine monohydrate (100–800 mg/kg/day) resulted in almost complete restoration of brain creatine levels and significant improvement of myopathy. The 2 patients treated since age 4 and 16 months had normal cognitive and behavioral development at age 10 and 11 years. Late treated patients had limited improvement of cognitive functions. Conclusion AGAT deficiency is a treatable intellectual disability. Early diagnosis may prevent IDD and myopathy. Patients with unexplained IDD with and without myopathy should be assessed for AGAT deficiency by determination of urine/plasma GAA and cerebral creatine levels (via brain MRS), and by GATM gene sequencing

Morquio-like dysostosis multiplex presenting with neuronopathic features is a distinct GLB1-related phenotype

Background Morquio B disease (MBD) is a distinct GLB1-related dysostosis multiplex presenting a mild phenocopy of GALNS-related Morquio A disease. Previously reported cases from European countries carry the W273L variant on at least one GLB1 allele and exhibit a pure skeletal phenotype (pure MBD). Only a minority of MBD cases have been described with additional neuronopathic findings (MBD plus). Objectives and Methods With the aim to further describe patterns of MBD-related dysostosis multiplex, we analyzed clinical, biochemical, and genetic features in 17 cases with GLB1-related dysostosis multiplex living and diagnosed in Brazil. Results About 14 of the 17 individuals had three or more skeletal findings characteristic of Morquio syndrome. Two had no additional neuronopathic features (pure MBD) and 12 exhibited additional neuronopathic features (MBD plus). Three of the 17 cases had mild dysostosis without distinct features of MBD. Seven of the 12 MBD plus patients had signs of spinal cord compression (SCC), as a result of progressive spinal vertebral dysostosis. There was an age-dependent increase in the number of skeletal findings and in the severity of growth impairment. GLB1 mutation analysis was completed in 10 of the 14 MBD patients. T500A occurred in compound heterozygosity in 8 of the 19 alleles. Conclusion Our study extends the phenotypic spectrum of GLB1-related conditions by describing a cohort of patients with MBD and GM1-gangliosidosis (MBD plus). Targeting the progressive nature of the skeletal manifestations in the development of new therapies for GLB1-related conditions is warranted

Children\u27s Sleep during COVID-19: How Sleep Influences Surviving and Thriving in Families

Objective The COVID-19 pandemic has the potential to disrupt the lives of families and may have implications for children with existing sleep problems. As such, we aimed to: (1) characterize sleep changes during the COVID-19 pandemic in children who had previously been identified as having sleep problems, (2) identify factors contributing to sleep changes due to COVID-19 safety measures, and (3) understand parents and children s needs to support sleep during the pandemic. Methods Eighty-five Canadian parents with children aged 4 14 years participated in this explanatory sequential, mixed-methods study using an online survey of children s and parents sleep, with a subset of 16 parents, selected based on changes in their children s sleep, participating in semi-structured interviews. Families had previously participated in the Better Nights, Better Days (BNBD) randomized controlled trial. Results While some parents perceived their child s sleep quality improved during the COVID-19 pandemic (14.1%, n 12), many parents perceived their child s sleep had worsened (40.0%, n 34). Parents attributed children s worsened sleep to increased screen time, anxiety, and decreased exercise. Findings from semi-structured interviews highlighted the effect of disrupted routines on sleep and stress, and that stress reciprocally influenced children s and parents sleep. Conclusions The sleep of many Canadian children was affected by the first wave of the COVID-19 pandemic, with the disruption of routines influencing children s sleep. eHealth interventions, such as BNBD with modifications that address the COVID-19 context, could help families address these challenges