Associations between 24-h movement guidelines compliance and anxiety and depression among youth receiving special education services in the US.

BACKGROUND: Youth with disabilities are five times more likely to experience anxiety or depression than peers without disabilities. Engagement in sufficient daily physical activity (PA), adequate nightly sleep, and limited daily screen time (collectively known as 24-h movement guidelines) is associated with lower odds of anxiety and depression for peers without disabilities. Extending the investigation of these modifiable behaviors to youth with disabilities is warranted. OBJECTIVE: To estimate the association between meeting 24-h movement guidelines and anxiety and depression among a nationally representative sample of youth with disabilities. METHODS: A cross-sectional secondary analysis of the 2019-2020 NSCH was conducted and included youth 6-17 years old who were currently receiving special education services. Weighted prevalence estimates and logistic regressions were employed to estimate the association between meeting guidelines (separately and combined) and current anxiety or depression status. RESULTS: Compared to youth with disabilities who met the guideline, those not meeting the sleep or screen time guidelines, independently, had significantly higher odds of depression, or anxiety (aOR range 1.53, 2.31 respectively). Comparable odds were observed between those meeting the PA guidelines, alone or in combination, and those meeting none of the 24-h movement guidelines. CONCLUSION: Adequate nightly sleep, and limited screen time, were significantly associated with anxiety and depression among youth with disabilities, a pattern consistent to peers without disabilities. Yet, meeting more than one guideline did not further reduce odds of poor mental health, warranting further investigation of compounding benefits of the 24-h guidelines within this population.

Cytoskeletal disarray increases arrhythmogenic vulnerability during sympathetic stimulation in a model of hypertrophic cardiomyopathy.

Familial hypertrophic cardiomyopathy (FHC) patients are advised to avoid strenuous exercise due to increased risk of arrhythmias. Mice expressing the human FHC-causing mutation R403Q in the myosin heavy chain gene (MYH6) recapitulate the human phenotype, including cytoskeletal disarray and increased arrhythmia susceptibility. Following in vivo administration of isoproterenol, mutant mice exhibited tachyarrhythmias, poor recovery and fatigue. Arrhythmias were attenuated with the ß-blocker atenolol and protein kinase A inhibitor PKI. Mutant cardiac myocytes had significantly prolonged action potentials and triggered automaticity due to reduced repolarization reserve and connexin 43 expression. Isoproterenol shortened cycle length, and escalated electrical instability. Surprisingly isoproterenol did not increase CaV1.2 current. We found alterations in CaV1.2-ß1 adrenergic receptor colocalization assessed using super-resolution nanoscopy, and increased CaV1.2 phosphorylation in mutant hearts. Our results reveal for the first time that altered ion channel expression, co-localization and ß-adrenergic receptor signaling associated with myocyte disarray contribute to electrical instability in the R403Q mutant heart.

Evidence of item bias in a national flourishing measure for autistic youth.

Flourishing is a positive health indicator that aligns with strengths-based perspectives and measures within autism research. Flourishing indicators were recently included in the National Survey of Children's Health (NSCH) and have been used to evidence disparities in flourishing experienced by autistic children compared to non-autistic peers. Yet, little has been done to examine the utility of standard flourishing items for this population. This study examined the NSCH caregiver-reported flourishing items for measurement item bias. A cross-sectional, representative sample of autistic and non-autistic US children aged 6-17 years (n = 41,691) was drawn from the 2018-2019 NSCH public dataset. A confirmatory factor analysis using a multiple indicators and multiple causes model (MIMIC-CFA) was conducted to (1) test for differential item functioning (DIF; i.e., measurement bias); and (2) estimate latent mean group differences after controlling for DIF. Findings supported a 3-factor (social competence, school motivation, and behavioral control), 10-item model structure consistent with past literature, yet measurement bias was evident for 6 of the 10 items. Persistent group differences, after accounting for DIF and covariates, indicates that caregivers of autistic children perceive their children are experiencing meaningfully lower flourishing outcomes compared to caregivers of non-autistic children. However, evidence of measurement bias for items related to the social competence dimension calls into question the applicability of this measure for autistic children. Further interpretation of group differences and use of this measure should be approached with caution.

U.S. Physical Activity Para Report Card for Children and Adolescents With Disabilities.

The U.S. Report Card on Physical Activity for Children and Youth has tracked 10 physical activity (PA) indicators common to the Active Healthy Kids Global Matrix since 2014. This article expands on the U.S. report cards by presenting PA indicator assessments among children and adolescents with disabilities. Grades for indicators were assigned based on a search of peer-reviewed articles presenting nationally representative data. The Global Matrix 3.0 benchmarks and grading framework guided the process. Grades for overall PA, sedentary behaviors, organized sports, and school were F, D+, D+, and D, respectively. Insufficient evidence existed to assign grades to the remaining six indicators. There is a need in the United States for targeted PA promotion strategies that are specific to children and adolescents with disabilities. Without a commitment to this effort across sectors and settings, the low grades identified in this para report card are expected to remain.

The Frequency of Infant-Feeding Presentations at English Emergency Departments During the SARS-CoV-2 Pandemic: A Nation-Wide Electronic Health Records Study.

OBJECTIVES: To examine the frequency and distribution of infant feeding-related presentations at emergency departments (EDs) before and during the SARS-CoV-2 pandemic. SETTING: Attendances at 48 major EDs in England in two 50-week periods before and during the COVID-19 pandemic: period 1, April 2, 2019 to March 10, 2020 and period 2, April 1, 2020 to March 10, 2021. METHODS: We estimated the change in frequency of ED presentations by age group and diagnosis before and after the start of the SARS-CoV-2 pandemic in England. We compared changes in the frequency of attendances of infant-feeding related presentations by infant age, sex, ethnicity, deprivation, rurality, arrival mode, arrival time, acuity, mother's age, gravidity and mental health, birth length of stay, attendance duration, and disposal (i.e., admission or discharge). RESULTS: While total ED attendances fell by 16.7% (95% CI -16.8% to -16.6%), infant attendances increased for feeding problems (+7.5% 95% CI 2.3% to 13.0%), neonatal jaundice (+12.8%, 95% CI 3.3% to 23.3%) and gastro-esophageal reflux (+9.7%, 95% CI 4.4% to 15.2%). These increases were more pronounced amongst first babies (+22.4%, 95% CI 13.1% to 32.5%), and where the stay in hospital after birth was brief (0-1 days, +20.1%, 95% CI 14.8% to 25.7%). Our analysis suggests that many of these attendances were of low acuity. CONCLUSIONS: While ED attendances reduced dramatically and systematically with the COVID-19 pandemic, presentations for infant feeding issues increased, implying growth in the unmet needs of new mothers and infants.

24-Hour Movement Behaviors Among US Adults With Functional Disabilities.

This study aimed to quantify and compare physical activity, sitting time, and sleep behaviors among US adults with and without disabilities using the 2020 Canadian 24-hour movement framework. The weighted prevalence of 24-hour movement guideline adherence was estimated among a nationally representative sample from the 2017 to 2018 National Health and Nutrition Examination Survey of US adults (18-65 years old) with (n = 1070) and without (n = 33,370) functional disabilities in vision, hearing, mobility, cognitive, and self-care domains. The adjusted odds of single and combination guideline compliance were estimated by disability type, in reference to adults without disabilities, using separate multivariable logistic regressions. After adjusting for age, sex, and income, adults with disabilities in mobility, cognitive, or self-care domains had approximately half the odds of meeting all 3 guidelines, compared with adults without disabilities (adjusted odds range: 0.49-0.77). Significantly lower adherence was observed among adults with functional disabilities, compared with no disabilities, for sleep, and moderate to vigorous physical activity, but not sedentary guidelines. This report establishes baseline prevalence estimates for guidelines compliance among US adults with functional disabilities ages 18-65 years old. Low guideline adherence, and evidence for significant differences in physical activity and sleep, signals a need to further explore combination health behaviors among adults with disabilities.

US adults with visual impairments meeting 24-h movement guidelines: Updated national prevalence estimates.

BACKGROUND: Despite known benefits of engaging in recommended amounts of physical activity (PA), sleep, and sedentary behavior (SB), little is known about how adults with visual impairments (VIs) meet these guidelines in isolation or simultaneously. OBJECTIVE: This study estimated (a) the prevalence of US adults with VIs who are partially or fully meeting the 24-h movement guidelines, and (b) the differential contribution of work-related, leisure, and transportation to total time accrued for PA. METHODS: A cross-sectional sample of adults with VIs (n = 466) was drawn from the National Health and Nutritional Examination Survey (NHANES) 2015-2018 combined datasets. Guideline adherence was measured using self-report items for average time spent physically active, sitting and sleeping. Weighted prevalence estimates were produced for meeting guidelines separately and in combination. The average percent of PA minutes accrued across work-related, leisure and transportation were compared among those meeting PA guidelines. RESULTS: An estimated 29.6% (SE = 3.6) of US adults with VIs met all three guidelines. An estimated 59.3% (SE = 3.5) adults with VIs met PA guidelines alone or in combination with SB and sleep. Within this group, the majority of weekly PA minutes (average 63.9%) was accrued at work. CONCLUSIONS: An estimated two thirds of adults with VIs are not engaged in healthful 24-h movement behaviors. Targeted interventions for adults with VIs are warranted that may require a comprehensive approach to PA, SB, and sleep. Work emerged as an important location for adults with VIs to accrue PA, inviting future research to explore associations between employment and 24-h movements within this population.

Role of an IUCD in managing patients with post-LLETZ cervical stenosis.

Large loop excision of the transformation zone (LLETZ) is one of the fertility sparing treatments for people with high-grade cervical intraepithelial neoplasia, however, this procedure is known to increase the risk of postoperative cervical stenosis by 1.3%-5.2%. We present a case demonstrating the successful use of a copper intrauterine contraceptive device to manage a patient with cervical stenosis secondary to three LLETZ procedures for severe dyskaryosis.

Item development, internal consistency, and known-groups validity of the Self-Directed Mobility Scale.

PURPOSE: The aims of the current study include to: (1) describe the item development; and (2) begin the process of establishing the internal consistency and known-groups validity of the Self-Directed Mobility Scale. The purpose of the scale is to assess paediatric physical and occupational therapists' views towards self-directed mobility and their perceived ability and intentions to advocate for children's access to self-directed mobility. METHODS: Three individuals with expertise in kinesiology, psychology, paediatric rehabilitation, and disability studies served as the expert panel for item development. Four samples were included to determine internal consistency and known-groups validity: 350 physical therapists, 89 occupational therapists, 279 kinesiology undergraduate students, and 528 health and wellness undergraduate students. RESULTS: The internal consistency was above the acceptable level of 0.70 (range = 0.72-0.77) for all samples when two items regarding promoting other motor skills prior to powered mobility use and the temporary use of a mobility device were removed. Known-groups validity was established between all samples. CONCLUSIONS: The Self-Directed Mobility Scale appears to be a valid tool for assessing views of self-directed mobility and mobility advocacy intentions in paediatric physical and occupational therapists, as well as undergraduate students. Future work should examine the internal consistency based on study sample to ensure the (> 0.70) acceptable Cronbach's alpha level is met.Implications for rehabilitationThe Self-Directed Mobility Scale is a viable measurement tool to assess views of self-directed mobility and mobility advocacy intentions of pediatric physical and occupational therapists.In combination with other measures, the Self-Directed Mobility Scale may be used in future rehabilitation research to evaluate factors associated with provision of mobility technology to children with disabilities.

Improving documentation of prescriptions for as-required medications in hospital inpatients.

It is estimated that 1 in 10 hospital inpatients in Scotland have experienced a medication error. In our unit, an audit in 2019 identified documentation of as-required prescriptions on drug Kardexes as an important target for improvement. This project aimed to reduce the percentage of these errors to <5% in the ward in 6 months.Weekly point prevalence surveys were used to measure medication error rates over a 12-week baseline period. Errors in route, frequency of dose and maximum dose accounted for >80% of all prescribing errors. The intervention was a poster reminder about the three most common errors linked to standards for prescribing pain medication. Barriers to change were identified through inductive thematic analysis of semistructured interviews with five ward doctors and two staff nurses.In the 6 weeks after intervention, our run chart showed a shift in maximum dose errors per patient, which fell from 75% to 26%. However, route and frequency errors remained high at >70% per patient. Most of these errors were due to use of abbreviations, and qualitative interviews revealed that senior doctors and nurses believed that these abbreviations were safe. We found some evidence from national guidelines to support these beliefs.Overall, the intervention was associated with decreased prevalence of patients without a maximum dose written on their prescription, but lack of space on drug prescriptions was identified as a key barrier to further improvement in both maximum dose and abbreviation errors.

Precision Medicine in Cardiovascular Disease: Genetics and Impact on Phenotypes: JACC Focus Seminar 1/5.

Our understanding of the genetic basis of cardiovascular diseases (CVDs) has evolved rapidly. This has resulted from a combination of dedicated research in well phenotyped CVD patients, the sequencing of the human genome, and the ready accessibility and decreasing cost of next-generation sequencing technologies. This increased knowledge of the genetic basis of CVDs has heralded the era of precision medicine. This encompasses many elements including improved diagnosis, family screening, assistance with reproductive decisions, targeted therapeutics guided by both phenotype and genotype, and providing important insights into risk stratification and prognosis. Furthermore, novel insights into genetic mechanisms, clinical rollout of polygenic risk scores for common CVDs, and the promise of genome editing approaches to effectively cure disease represent some of the exciting future endeavors that will change established clinical approaches. This Part 1 of a 5-part series focuses on the underpinnings and fundamental aspects of precision medicine.

Transcriptome Sequencing of Patients With Hypertrophic Cardiomyopathy Reveals Novel Splice-Altering Variants in MYBPC3.

BACKGROUND: Transcriptome sequencing can improve genetic diagnosis of Mendelian diseases but requires access to tissue expressing disease-relevant transcripts. We explored genetic testing of hypertrophic cardiomyopathy using transcriptome sequencing of patient-specific human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs). We also explored whether antisense oligonucleotides (AOs) could inhibit aberrant mRNA splicing in hiPSC-CMs. METHODS: We derived hiPSC-CMs from patients with hypertrophic cardiomyopathy due to MYBPC3 splice-gain variants, or an unresolved genetic cause. We used transcriptome sequencing of hiPSC-CM RNA to identify pathogenic splicing and used AOs to inhibit this splicing. RESULTS: Transcriptome sequencing of hiPSC-CMs confirmed aberrant splicing in 2 people with previously identified MYBPC3 splice-gain variants (c.1090+453C>T and c.1224-52G>A). In a patient with an unresolved genetic cause of hypertrophic cardiomyopathy following genome sequencing, transcriptome sequencing of hiPSC-CMs revealed diverse cryptic exon splicing due to an MYBPC3 c.1928-569G>T variant, and this was confirmed in cardiac tissue from an affected sibling. Antisense oligonucleotide treatment demonstrated almost complete inhibition of cryptic exon splicing in one patient-specific hiPSC-CM line. CONCLUSIONS: Transcriptome sequencing of patient specific hiPSC-CMs solved a previously undiagnosed genetic cause of hypertrophic cardiomyopathy and may be a useful adjunct approach to genetic testing. Antisense oligonucleotide inhibition of cryptic exon splicing is a potential future personalized therapeutic option.

Exploring the Interaction of Disability Status and Childhood Predictors of Physical Activity and Sport Participation: An Exploratory Decision-Tree Analysis.

A secondary data analysis of 33,093 children and adolescents age 6-17 years (12% with disabilities) from a 2016-2017 National Survey of Children's Health nonrepresentative sample aimed to identify (a) unique clusters of sociodemographic characteristics and (b) the relative importance of disability status in predicting participation in daily physical activity (PA) and sports. Exploratory classification tree analyses identified hierarchical predictors of daily PA and sport participation separately. Disability status was not a primary predictor of daily PA. Instead, it emerged in the fifth level after age, sex, body mass index, and income, highlighting the dynamic intersection of disability with sociodemographic factors influencing PA levels. In comparison, disability status was a second-level predictor for sport participation, suggesting that unique factors influencing PA level are likely experienced by disabled children and adolescents. The authors employ an intersectionality lens to critically discuss implications for research in adapted PA.

Characterization of clinically relevant copy-number variants from exomes of patients with inherited heart disease and unexplained sudden cardiac death.

PURPOSE: Copy-number variant (CNV) analysis is increasingly performed in genetic diagnostics. We leveraged recent gene curation efforts and technical standards for interpretation and reporting of CNVs to characterize clinically relevant CNVs in patients with inherited heart disease and sudden cardiac death. METHODS: Exome sequencing data were analyzed for CNVs using eXome-Hidden Markov Model tool in 48 established disease genes. CNV breakpoint junctions were characterized. CNVs were classified using the American College of Medical Genetics and Genomics technical standards. RESULTS: We identified eight CNVs in 690 unrelated probands (1.2%). Characterization of breakpoint junctions revealed nonhomologous end joining was responsible for four deletions, whereas one duplication was caused by nonallelic homologous recombination between duplicated sequences in MYH6 and MYH7. Identifying the precise breakpoint junctions determined the genomic involvement and proved useful for interpreting the clinical relevance of CNVs. Three large deletions involving TTN, MYBPC3, and KCNH2 were classified as pathogenic in three patients. Haplotype analysis of a deletion in ACTN2, found in two families, suggests the deletion was caused by an ancestral event. CONCLUSION: CNVs infrequently cause inherited heart diseases and should be investigated when standard genetic testing does not reveal a genetic diagnosis.

Long term clinical outcomes associated with CMR quantified isolated left ventricular non-compaction in adults.

BACKGROUND: Left ventricular non-compaction (LVNC) is a complex clinical condition with several diagnostic criteria but no diagnostic gold standard. We aimed to evaluate our thresholding technique in a group of patients with LVNC and assess the risk of major adverse cardiovascular and cerebrovascular events (MACCE). METHODS: We retrospectively analyzed cardiac magnetic resonance (CMR) scans of patients with Petersen criteria LVNC and quantified noncompacted myocardial mass. We assessed the association of noncompacted myocardial mass, CMR derived LV volumetric parameters and late gadolinium enhancement (LGE) to MACCE including cardiac death, cardiac transplantation, sustained ventricular tachycardia/ventricular fibrillation (VT/VF) and ischemic stroke. Patients with known genetic mutations and cardiovascular disease were excluded. RESULTS: 98 patients with LVNC were included (55 males,56.7%); 17(17.3%) patients had impaired LV function and five (5.1%) had LGE. Patients with impaired LV function had more end-systolic noncompacted mass (61.9 g±22.4 vs. 38.1 g±15.8, p < 0.001) and larger end-systolic noncompacted to total myocardial mass (44%±9 vs. 36%±12, p = 0.003). At 78 months follow-up [interquartile range(IQR) 66-90], MACCE occurred in 11(11.3%) patients; nine(81.8%) had impaired LV function and two(18.2%) had LGE. Impaired LV function and LV LGE were predictors of MACCE (HR = 35.6, 95% CI = 7.65-165.21, p < 0.001 and HR = 16.2, 95% CI = 4.54-57.84, p < 0.001) whereas noncompacted mass were not. CONCLUSION: Noncompacted mass was not an independent predictor of major adverse events but in patients with impaired LV function and/or LV LGE, the risk of MACCE was high. These results highlight the importance of including LV volumetrics and scar in the assessment of patients with LV noncompaction.

Physical Activity, Medical Home, and Health Behavior Counseling Among Adolescents with Special Health Care Needs: NSCH 2016-2017.

OBJECTIVES: Aim 1 was to establish updated prevalence estimates for meeting national physical activity (PA) guidelines among adolescents with and without special healthcare needs (SHCN), 12-17 years old. To identify at-risk subgroups, our sub-aim was to compare the distribution of prevalence estimates across PA levels by SHCN subtypes, and in reference to peers without SHCN. Aim 2 was to examine the association between meeting PA guidelines, having a medical home, and receiving positive health behavior counseling in this population. METHODS: Weighted prevalence estimates for meeting the 2018 National PA Guidelines (inactive, insufficiently active, sufficiently active: guidelines met) were calculated from a secondary analysis of the National Survey of Children's Health 2016-2017 ( n = 16,171, 27% SHCN). Adjusted odds ratios and 95% CIs were estimated from logistic regression models to measure the association between PA, medical home, and postive health behavior counseling. RESULTS: Of adolescents with SHCN, 15% were reported to be meeting PA guidelines compared to 19% of peers without SHCN peers. Among adolescents with a medical home, regardless of SHCN status, those receiving positive health behavior counseling had 1.70 times the adjusted odds of meeting PA guidelines compared to peers without counseling. CONCLUSIONS FOR PRACTICE: Adolescents with and without SHCN were more likely to meet PA guidelines if they had a medical home and received positive health behavior counseling, highlighting the value of comprehensive healthcare practices for PA promotion.

Left Ventricular Non-Compaction: Review of the Current Diagnostic Challenges and Consequences in Athletes.

Left ventricular non-compaction (LVNC) is a complex clinical condition with no diagnostic gold standard. At present, there is trepidation about the accuracy of the diagnosis, the correlation to clinical outcomes and the long-term medical management. This article reviews the current imaging criteria, the limitations of echocardiography and cardiac magnetic resonance and the consequences of LV hypertrabeculation in athletes.

Genetic architecture of left ventricular noncompaction in adults.

The genetic etiology and heritability of left ventricular noncompaction (LVNC) in adults is unclear. This study sought to assess the value of genetic testing in adults with LVNC. Adults diagnosed with LVNC while undergoing screening in the context of a family history of cardiomyopathy were excluded. Clinical data for 35 unrelated patients diagnosed with LVNC at ≥18 years of age were retrospectively analyzed. Left ventricular (LV) dysfunction, electrocardiogram (ECG) abnormalities, cardiac malformations or syndromic features were identified in 25 patients; 10 patients had isolated LVNC in the absence of cardiac dysfunction or syndromic features. Exome sequencing was performed, and analysis using commercial panels targeted 193 nuclear and mitochondrial genes. Nucleotide variants in coding regions or in intron-exon boundaries with predicted impacts on splicing were assessed. Fifty-four rare variants were identified in 35 nuclear genes. Across all 35 LVNC patients, the clinically meaningful genetic diagnostic yield was 9% (3/35), with heterozygous likely pathogenic or pathogenic variants identified in the NKX2-5 and TBX5 genes encoding cardiac transcription factors. No pathogenic variants were identified in patients with isolated LVNC in the absence of cardiac dysfunction or syndromic features. In conclusion, the diagnostic yield of genetic testing in adult index patients with LVNC is low. Genetic testing is most beneficial in LVNC associated with other cardiac and syndromic features, in which it can facilitate correct diagnoses, and least useful in adults with only isolated LVNC without a family history. Cardiac transcription factors are important in the development of LVNC and should be included in genetic testing panels.