Impact of social complexity on outcomes in cystic fibrosis after transfer to adult care

Objective This study evaluates the roles of medical and social complexity in health care use outcomes in cystic fibrosis (CF) after transfer from pediatric to adult care. Methods Retrospective cohort design included patients with CF who were transitioned into adult care at Indiana University from 2005 to 2015. Predictor variables included demographic and comorbidity data, age at transition, treatment complexity score (TCS), and an objective scoring measure of their social complexity (Bob's Level of Social Support, BLSS). Outcome variables included outpatient visit rates and hospitalization rates. Pearson's correlations and linear regression were used to analyze the data. Results The median age of the patients (N = 133) at the time of transition was 20 (IQR 19‐23) years. The mean FEV1 % predicted at transition was 69 ± 24%. TCS correlated with outpatient visit rates (r = 0.3, P = 0.003), as well as hospitalization rates (r = 0.4, P < 0.001); while the BLSS only correlated with hospitalization rates (r = 0.7, P < 0.001). After adjusting for covariates, the strongest predictors of post‐transfer hospitalizations are BLSS (P < 0.0001) and pre‐transfer hospitalization rate (P < 0.0001). Conclusion Greater treatment complexity is associated with greater healthcare utilization overall, while greater social complexity is associated with increased hospitalizations (but not outpatient visits). Screening young adults for social complexity may identify high‐risk subpopulations and allow for patient centered interventions to support them and prevent avoidable health care use

Analysis of shared heritability in common disorders of the brain

ience, this issue p. eaap8757 Structured Abstract INTRODUCTION Brain disorders may exhibit shared symptoms and substantial epidemiological comorbidity, inciting debate about their etiologic overlap. However, detailed study of phenotypes with different ages of onset, severity, and presentation poses a considerable challenge. Recently developed heritability methods allow us to accurately measure correlation of genome-wide common variant risk between two phenotypes from pools of different individuals and assess how connected they, or at least their genetic risks, are on the genomic level. We used genome-wide association data for 265,218 patients and 784,643 control participants, as well as 17 phenotypes from a total of 1,191,588 individuals, to quantify the degree of overlap for genetic risk factors of 25 common brain disorders. RATIONALE Over the past century, the classification of brain disorders has evolved to reflect the medical and scientific communities' assessments of the presumed root causes of clinical phenomena such as behavioral change, loss of motor function, or alterations of consciousness. Directly observable phenomena (such as the presence of emboli, protein tangles, or unusual electrical activity patterns) generally define and separate neurological disorders from psychiatric disorders. Understanding the genetic underpinnings and categorical distinctions for brain disorders and related phenotypes may inform the search for their biological mechanisms. RESULTS Common variant risk for psychiatric disorders was shown to correlate significantly, especially among attention deficit hyperactivity disorder (ADHD), bipolar disorder, major depressive disorder (MDD), and schizophrenia. By contrast, neurological disorders appear more distinct from one another and from the psychiatric disorders, except for migraine, which was significantly correlated to ADHD, MDD, and Tourette syndrome. We demonstrate that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine. We also identify significant genetic sharing between disorders and early life cognitive measures (e.g., years of education and college attainment) in the general population, demonstrating positive correlation with several psychiatric disorders (e.g., anorexia nervosa and bipolar disorder) and negative correlation with several neurological phenotypes (e.g., Alzheimer's disease and ischemic stroke), even though the latter are considered to result from specific processes that occur later in life. Extensive simulations were also performed to inform how statistical power, diagnostic misclassification, and phenotypic heterogeneity influence genetic correlations. CONCLUSION The high degree of genetic correlation among many of the psychiatric disorders adds further evidence that their current clinical boundaries do not reflect distinct underlying pathogenic processes, at least on the genetic level. This suggests a deeply interconnected nature for psychiatric disorders, in contrast to neurological disorders, and underscores the need to refine psychiatric diagnostics. Genetically informed analyses may provide important "scaffolding" to support such restructuring of psychiatric nosology, which likely requires incorporating many levels of information. By contrast, we find limited evidence for widespread common genetic risk sharing among neurological disorders or across neurological and psychiatric disorders. We show that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures. Further study is needed to evaluate whether overlapping genetic contributions to psychiatric pathology may influence treatment choices. Ultimately, such developments may pave the way toward reduced heterogeneity and improved diagnosis and treatment of psychiatric disorders

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

Schizophrenia-associated somatic copy-number variants from 12,834 cases reveal recurrent NRXN1 and ABCB11 disruptions

While germline copy-number variants (CNVs) contribute to schizophrenia (SCZ) risk, the contribution of somatic CNVs (sCNVs)—present in some but not all cells—remains unknown. We identified sCNVs using blood-derived genotype arrays from 12,834 SCZ cases and 11,648 controls, filtering sCNVs at loci recurrently mutated in clonal blood disorders. Likely early-developmental sCNVs were more common in cases (0.91%) than controls (0.51%, p = 2.68e−4), with recurrent somatic deletions of exons 1–5 of the NRXN1 gene in five SCZ cases. Hi-C maps revealed ectopic, allele-specific loops forming between a potential cryptic promoter and non-coding cis-regulatory elements upon 5′ deletions in NRXN1. We also observed recurrent intragenic deletions of ABCB11, encoding a transporter implicated in anti-psychotic response, in five treatment-resistant SCZ cases and showed that ABCB11 is specifically enriched in neurons forming mesocortical and mesolimbic dopaminergic projections. Our results indicate potential roles of sCNVs in SCZ risk

Implementation and evaluation of STOPP/START criteria to address polypharmacy in older adults in an inpatient psychiatric setting

Background: There is a scarcity of research in applying the Screening Tool of Older Person's Prescriptions/Screening Tool to Alert to Right Treatment (STOPP/START) criteria to older adults admitted to a psychiatric hospital. Objectives: The primary aim of this study was to determine the extent of polypharmacy in older adults admitted to a psychiatric hospital and to assess the number of STOPP/START triggers detected and recommended by pharmacists. Secondary objectives include evaluating if the STOPP/START criteria is a useful tool to improve prescribing in this setting by assessing the implementation rates of STOPP/START triggers. Methods: This was a prospective, longitudinal study in a psychiatry inpatient setting. Data were collected over a 7-week period. Explicit informed consent was obtained from participants. Medication reconciliation was completed and participants' medications were reviewed using STOPP/START criteria. The number of STOPP/START triggers detected, recommended and implemented was recorded. Results: Sixty-two patients were included in the study. Ninety-four percent were prescribed ≥5 medications and 55% were prescribed ≥10 medications on admission. The mean number of medications prescribed per patient increased from 10 on admission to 12 at follow-up. Of 174 Potential Inappropriate Medications (PIMs) detected, 41% were recommended for review and, of these only 31% were implemented. 27% of the 77 Potential Prescribing Omissions (PPOs) detected were recommended for review and only 23% of those were implemented. Conclusion: STOPP/START did not reduce the prevalence of polypharmacy in this setting. The implementation rates observed in this study were much lower than those observed in non-psychiatric settings

Maturation and Sex Differences in Neuromuscular Characteristics of Youth Athletes

Understanding how neuromuscular factors that are associated with lower extremity injury risk, such as landing kinematics, muscle strength, and flexibility, change as children mature may enhance age-specific recommendations for injury prevention programs. The purpose of this study was to compare these factors in prepubertal, pubertal, and postpubertal male and female athletes. Subjects were classified on maturation stage (prepubertal: 16 males, 15 females, age: 9 ± 1 years; pubertal: 13 males, 12 females, age: 12 ± 3 years; postpubertal: 30 males, 27 females, age: 16 ± 2 years). Researchers measured lower extremity isometric muscle strength and flexibility and evaluated kinematics and vertical ground reaction forces (VGRFs) during a jump-landing task. Three-dimensional kinematics at initial contact (IC), joint displacements, and peak VGRF were calculated. Separate multivariate analyses of variance were performed to evaluate sex and maturation differences (α ≤ 0.05). Postpubertal females landed with less knee flexion at IC (p 0.006) and demonstrated lower knee extension strength (p 0.01) than prepubertal and pubertal females. Postpubertal males landed with less hip adduction displacement (postpubertal males 12.53 ± 6.15°, prepubertal males 18.84 ± 7.47°; p 0.04) and less peak VGRF (postpubertal males 1.53 ± 0.27% body weight [BW], prepubertal males 1.99 ± 0.32% BW; p 0.03) compared with prepubertal males. These findings suggest encouraging sagittal plane absorption and decreasing frontal plane motion at the hip, whereas maintaining quadriceps strength may be important for reducing injury risk in postpubertal athletes

Maturation and sex differences in neuromuscular characteristics of youth athletes

Understanding how neuromuscular factors that are associated with lower extremity injury risk, such as landing kinematics, muscle strength, and flexibility, change as children mature may enhance age-specific recommendations for injury prevention programs. The purpose of this study was to compare these factors in prepubertal, pubertal, and postpubertal male and female athletes. Subjects were classified on maturation stage (prepubertal: 16 males, 15 females, age: 9 ± 1 years; pubertal: 13 males, 12 females, age: 12 ± 3 years; postpubertal: 30 males, 27 females, age: 16 ± 2 years). Researchers measured lower extremity isometric muscle strength and flexibility and evaluated kinematics and vertical ground reaction forces (VGRFs) during a jump-landing task. Three-dimensional kinematics at initial contact (IC), joint displacements, and peak VGRF were calculated. Separate multivariate analyses of variance were performed to evaluate sex and maturation differences (α ≤ 0.05). Postpubertal females landed with less knee flexion at IC (p 0.006) and demonstrated lower knee extension strength (p 0.01) than prepubertal and pubertal females. Postpubertal males landed with less hip adduction displacement (postpubertal males 12.53 ± 6.15°, prepubertal males 18.84 ± 7.47°; p 0.04) and less peak VGRF (postpubertal males 1.53 ± 0.27% body weight [BW], prepubertal males 1.99 ± 0.32% BW; p 0.03) compared with prepubertal males. These findings suggest encouraging sagittal plane absorption and decreasing frontal plane motion at the hip, whereas maintaining quadriceps strength may be important for reducing injury risk in postpubertal athletes

Pillars of Cloud‐Based Earth Observation Science Education

Abstract Earth observation (EO) is undergoing a paradigm shift with the development of cloud‐based analytical platforms supporting EO data collection and access, parallel processing, easier communication of results, and expanded accessibility. As the global community of users and the diversity of applications grow, there is a clear need for expanded educational capacity to leverage these developments and increase the impact of EO research and teaching. Drawing upon extensive conversations between educators, practitioners, and researchers, we propose three pillars that must be prioritized to prepare students, researchers, and professionals to take full advantage of the cloud‐based EO paradigm and guide future growth

\u3ci\u3eDrosophila\u3c/i\u3e Muller F Elements Maintain a Distinct Set of Genomic Properties Over 40 Million Years of Evolution

The Muller F element (4.2 Mb, ~80 protein-coding genes) is an unusual autosome of Drosophila melanogaster; it is mostly heterochromatic with a low recombination rate. To investigate how these properties impact the evolution of repeats and genes, we manually improved the sequence and annotated the genes on the D. erecta, D. mojavensis, and D. grimshawi F elements and euchromatic domains from the Muller D element. We find that F elements have greater transposon density (25–50%) than euchromatic reference regions (3–11%). Among the F elements, D. grimshawi has the lowest transposon density (particularly DINE-1: 2% vs. 11–27%). F element genes have larger coding spans, more coding exons, larger introns, and lower codon bias. Comparison of the Effective Number of Codons with the Codon Adaptation Index shows that, in contrast to the other species, codon bias in D. grimshawi F element genes can be attributed primarily to selection instead of mutational biases, suggesting that density and types of transposons affect the degree of local heterochromatin formation. F element genes have lower estimated DNA melting temperatures than D element genes, potentially facilitating transcription through heterochromatin. Most F element genes (~90%) have remained on that element, but the F element has smaller syntenic blocks than genome averages (3.4–3.6 vs. 8.4–8.8 genes per block), indicating greater rates of inversion despite lower rates of recombination. Overall, the F element has maintained characteristics that are distinct from other autosomes in the Drosophila lineage, illuminating the constraints imposed by a heterochromatic milieu

Effect of Noninvasive Respiratory Strategies on Intubation or Mortality Among Patients With Acute Hypoxemic Respiratory Failure and COVID-19: The RECOVERY-RS Randomized Clinical Trial.

Importance Continuous positive airway pressure (CPAP) and high-flow nasal oxygen (HFNO) have been recommended for acute hypoxemic respiratory failure in patients with COVID-19. Uncertainty exists regarding the effectiveness and safety of these noninvasive respiratory strategies. Objective To determine whether either CPAP or HFNO, compared with conventional oxygen therapy, improves clinical outcomes in hospitalized patients with COVID-19-related acute hypoxemic respiratory failure. Design, Setting, and Participants A parallel group, adaptive, randomized clinical trial of 1273 hospitalized adults with COVID-19-related acute hypoxemic respiratory failure. The trial was conducted between April 6, 2020, and May 3, 2021, across 48 acute care hospitals in the UK and Jersey. Final follow-up occurred on June 20, 2021. Interventions Adult patients were randomized to receive CPAP (n = 380), HFNO (n = 418), or conventional oxygen therapy (n = 475). Main Outcomes and Measures The primary outcome was a composite of tracheal intubation or mortality within 30 days. Results The trial was stopped prematurely due to declining COVID-19 case numbers in the UK and the end of the funded recruitment period. Of the 1273 randomized patients (mean age, 57.4 [95% CI, 56.7 to 58.1] years; 66% male; 65% White race), primary outcome data were available for 1260. Crossover between interventions occurred in 17.1% of participants (15.3% in the CPAP group, 11.5% in the HFNO group, and 23.6% in the conventional oxygen therapy group). The requirement for tracheal intubation or mortality within 30 days was significantly lower with CPAP (36.3%; 137 of 377 participants) vs conventional oxygen therapy (44.4%; 158 of 356 participants) (absolute difference, -8% [95% CI, -15% to -1%], P = .03), but was not significantly different with HFNO (44.3%; 184 of 415 participants) vs conventional oxygen therapy (45.1%; 166 of 368 participants) (absolute difference, -1% [95% CI, -8% to 6%], P = .83). Adverse events occurred in 34.2% (130/380) of participants in the CPAP group, 20.6% (86/418) in the HFNO group, and 13.9% (66/475) in the conventional oxygen therapy group. Conclusions and Relevance Among patients with acute hypoxemic respiratory failure due to COVID-19, an initial strategy of CPAP significantly reduced the risk of tracheal intubation or mortality compared with conventional oxygen therapy, but there was no significant difference between an initial strategy of HFNO compared with conventional oxygen therapy. The study may have been underpowered for the comparison of HFNO vs conventional oxygen therapy, and early study termination and crossover among the groups should be considered when interpreting the findings. Trial Registration isrctn.org Identifier: ISRCTN16912075