External electrical and pharmacological cardioversion for atrial fibrillation, atrial flutter or atrial tachycardias: a network meta-analysis.

BACKGROUND: Atrial fibrillation (AF) is the most frequent sustained arrhythmia. Cardioversion is a rhythm control strategy to restore normal/sinus rhythm, and can be achieved through drugs (pharmacological) or a synchronised electric shock (electrical cardioversion). OBJECTIVES: To assess the efficacy and safety of pharmacological and electrical cardioversion for atrial fibrillation (AF), atrial flutter and atrial tachycardias. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, Conference Proceedings Citation Index-Science (CPCI-S) and three trials registers (ClinicalTrials.gov, WHO ICTRP and ISRCTN) on 14 February 2023. SELECTION CRITERIA: We included randomised controlled trials (RCTs) at the individual patient level. Patient populations were aged ≥ 18 years with AF of any type and duration, atrial flutter or other sustained related atrial arrhythmias, not occurring as a result of reversible causes. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodology to collect data and performed a network meta-analysis using the standard frequentist graph-theoretical approach using the netmeta package in R. We used GRADE to assess the quality of the evidence which we presented in our summary of findings with a judgement on certainty. We calculated differences using risk ratios (RR) and 95% confidence intervals (CI) as well as ranking treatments using a P value. We assessed clinical and statistical heterogeneity and split the networks for the primary outcome and acute procedural success, due to concerns about violating the transitivity assumption. MAIN RESULTS: We included 112 RCTs (139 records), from which we pooled data from 15,968 patients. The average age ranged from 47 to 72 years and the proportion of male patients ranged from 38% to 92%. Seventy-nine trials were considered to be at high risk of bias for at least one domain, 32 had no high risk of bias domains, but had at least one domain classified as uncertain risk, and one study was considered at low risk for all domains. For paroxysmal AF (35 trials), when compared to placebo, anteroapical (AA)/anteroposterior (AP) biphasic truncated exponential waveform (BTE) cardioversion (RR: 2.42; 95% CI 1.65 to 3.56), quinidine (RR: 2.23; 95% CI 1.49 to 3.34), ibutilide (RR: 2.00; 95% CI 1.28 to 3.12), propafenone (RR: 1.98; 95% CI 1.67 to 2.34), amiodarone (RR: 1.69; 95% CI 1.42 to 2.02), sotalol (RR: 1.58; 95% CI 1.08 to 2.31) and procainamide (RR: 1.49; 95% CI 1.13 to 1.97) likely result in a large increase in maintenance of sinus rhythm until hospital discharge or end of study follow-up (certainty of evidence: moderate). The effect size was larger for AA/AP incremental and was progressively smaller for the subsequent interventions. Despite low certainty of evidence, antazoline may result in a large increase (RR: 28.60; 95% CI 1.77 to 461.30) in this outcome. Similarly, low-certainty evidence suggests a large increase in this outcome for flecainide (RR: 2.17; 95% CI 1.68 to 2.79), vernakalant (RR: 2.13; 95% CI 1.52 to 2.99), and magnesium (RR: 1.73; 95% CI 0.79 to 3.79). For persistent AF (26 trials), one network was created for electrical cardioversion and showed that, when compared to AP BTE incremental energy with patches, AP BTE maximum energy with patches (RR 1.35, 95% CI 1.17 to 1.55) likely results in a large increase, and active compression AP BTE incremental energy with patches (RR: 1.14, 95% CI 1.00 to 1.131) likely results in an increase in maintenance of sinus rhythm at hospital discharge or end of study follow-up (certainty of evidence: high). Use of AP BTE incremental with paddles (RR: 1.03, 95% CI 0.98 to 1.09; certainty of evidence: low) may lead to a slight increase, and AP MDS Incremental paddles (RR: 0.95, 95% CI 0.86 to 1.05; certainty of evidence: low) may lead to a slight decrease in efficacy. On the other hand, AP MDS incremental energy using patches (RR: 0.78, 95% CI 0.70 to 0.87), AA RBW incremental energy with patches (RR: 0.76, 95% CI 0.66 to 0.88), AP RBW incremental energy with patches (RR: 0.76, 95% CI 0.68 to 0.86), AA MDS incremental energy with patches (RR: 0.76, 95% CI 0.67 to 0.86) and AA MDS incremental energy with paddles (RR: 0.68, 95% CI 0.53 to 0.83) probably result in a decrease in this outcome when compared to AP BTE incremental energy with patches (certainty of evidence: moderate). The network for pharmacological cardioversion showed that bepridil (RR: 2.29, 95% CI 1.26 to 4.17) and quindine (RR: 1.53, (95% CI 1.01 to 2.32) probably result in a large increase in maintenance of sinus rhythm at hospital discharge or end of study follow-up when compared to amiodarone (certainty of evidence: moderate). Dofetilide (RR: 0.79, 95% CI 0.56 to 1.44), sotalol (RR: 0.89, 95% CI 0.67 to 1.18), propafenone (RR: 0.79, 95% CI 0.50 to 1.25) and pilsicainide (RR: 0.39, 95% CI 0.02 to 7.01) may result in a reduction in this outcome when compared to amiodarone, but the certainty of evidence is low. For atrial flutter (14 trials), a network could be created only for antiarrhythmic drugs. Using placebo as the common comparator, ibutilide (RR: 21.45, 95% CI 4.41 to 104.37), propafenone (RR: 7.15, 95% CI 1.27 to 40.10), dofetilide (RR: 6.43, 95% CI 1.38 to 29.91), and sotalol (RR: 6.39, 95% CI 1.03 to 39.78) probably result in a large increase in the maintenance of sinus rhythm at hospital discharge or end of study follow-up (certainty of evidence: moderate), and procainamide (RR: 4.29, 95% CI 0.63 to 29.03), flecainide (RR 3.57, 95% CI 0.24 to 52.30) and vernakalant (RR: 1.18, 95% CI 0.05 to 27.37) may result in a large increase in maintenance of sinus rhythm at hospital discharge or end of study follow-up (certainty of evidence: low). All tested electrical cardioversion strategies for atrial flutter had very high efficacy (97.9% to 100%). The rate of mortality (14 deaths) and stroke or systemic embolism (3 events) at 30 days was extremely low. Data on quality of life were scarce and of uncertain clinical significance. No information was available regarding heart failure readmissions. Data on duration of hospitalisation was scarce, of low quality, and could not be pooled. AUTHORS' CONCLUSIONS: Despite the low quality of evidence, this systematic review provides important information on electrical and pharmacological strategies to help patients and physicians deal with AF and atrial flutter. In the assessment of the patient comorbidity profile, antiarrhythmic drug onset of action and side effect profile versus the need for a physician with experience in sedation, or anaesthetics support for electrical cardioversion are key aspects when choosing the cardioversion method.

Six aspects of female genital mutilation education (SAFE) model: findings from a qualitative study.

OBJECTIVES: Recent figures show that over 200 million women and girls, globally, live with the consequences of female genital mutilation (FGM). Complex debilitating physical, psychological and social problems result from the practice. Health education interventions have proven to be essential in both preventing the practice and informing support of survivors. In this study, we aimed to explore factors that affect the effectiveness of health education interventions. DESIGN: A generic qualitative approach was applied using semistructured individual and focus group interviews with women and men from communities with a history of FGM in Birmingham, UK. Framework analysis was used to group recurring themes from the data. Intersectionality was used as a theoretical lens to synthesise findings. PARTICIPANTS: Twenty-one individuals (18 women and 3 men) participated in semistructured individual and focus group interviews about their views and experiences of health and well-being intervention programmes related to FGM. RESULTS: Six themes emerged from the data and were developed into a model of issues relating to FGM education. These six themes are (1) active communication, (2) attitudes and beliefs, (3) knowledge about FGM, (4) social structures, (5) programme approach and (6) the better future. A combined discussion of all these issues was compressed into three groupings: social structures, culture and media. CONCLUSION: The results of this study depict aspects associated with FGM education that should be considered by future interventions aiming to prevent the practice and inform support services for survivors in a holistic way.

Development of a comprehensive cardiovascular disease genetic risk assessment test.

Background: Despite monogenic and polygenic contributions to cardiovascular disease (CVD), genetic testing is not widely adopted, and current tests are limited by the breadth of surveyed conditions and interpretation burden. Methods: We developed a comprehensive clinical genome CVD test with semi-automated interpretation. Monogenic conditions and risk alleles were selected based on the strength of disease association and evidence for increased disease risk, respectively. Non-CVD secondary findings genes, pharmacogenomic (PGx) variants and CVD polygenic risk scores (PRS) were assessed for inclusion. Test performance was modeled using 2,594 genomes from the 1000 Genomes Project, and further investigated in 20 previously tested individuals. Results: The CVD genome test is composed of a panel of 215 CVD gene-disease pairs, 35 non-CVD secondary findings genes, 4 risk alleles or genotypes, 10 PGx genes and a PRS for coronary artery disease. Modeling of test performance using samples from the 1000 Genomes Project revealed ~6% of individuals with a monogenic finding in a CVD-associated gene, 6% with a risk allele finding, ~1% with a non-CVD secondary finding, and 93% with CVD-associated PGx variants. Assessment of blinded clinical samples showed complete concordance with prior testing. An average of 4 variants were reviewed per case, with interpretation and reporting time ranging from 9-96 min. Conclusions: A genome sequencing based CVD genetic risk assessment can provide comprehensive genetic disease and genetic risk information to patients with CVD. The semi-automated and limited interpretation burden suggest that this testing approach could be scaled to support population-level initiatives.

Associations between Social Experiences and Psychological Health for Autistic Youth with Low IQ.

PURPOSE: Social experiences are consistently associated with psychological health among autistic individuals. However, most extant studies on this topic exclude individuals with autism who have lower IQ or are otherwise unable to self-report. The current study addresses this gap by examining associations of negative peer experiences and social participation with psychological health among autistic youth with low IQ. METHODS: An online survey was collected from 268 parents of autistic adolescents and adults ages 15-25. Negative peer experiences included measures of peer victimization and being ignored. Social participation was assessed by the amount of participation and parents' perceptions of whether their youth felt the amount of participation was meeting their needs. Psychological health was assessed by parents' report of their youth's psychological quality of life, as well as whether they felt their son/daughter was currently depressed. RESULTS: Results suggested low rates of social participation in this sample, with relatively high rates of being ignored. Regression analysis found that lower rates of peer victimization and more activities in which parents perceived that the amount of time was meeting their youth's needs was associated with higher psychological quality of life and lower likelihood that parents felt their son/daughter was depressed. CONCLUSION: Though youth with autism and low IQ are often excluded from interventions aimed at improving social experiences, these findings suggest that promoting positive social experiences and ameliorating negative ones might be an avenue to improving psychological health in this group.

Working the Edge: The Emotional Experiences of Commissioning and Funding Arrangements for Service Leaders in the Sexual Violence Voluntary Sector.

The specialist voluntary sector plays a crucial role in supporting survivors of sexual violence. However, in England, short-term funding underpins the sector's financial stability. This article examines sector leaders' ways of coping, resisting and being affected by funding practices. Using the concept of edgework, we show how funding and commissioning dynamics push individuals to the edge of service sustainability, job satisfaction, and emotional well-being. We examine how these edges are "worked," for example, by circumventing and remolding the edge. We offer an original way to theorize participants, make visible the emotional toll of service precarity and offer suggestions for support.

Variants in ZFX are associated with an X-linked neurodevelopmental disorder with recurrent facial gestalt.

Pathogenic variants in multiple genes on the X chromosome have been implicated in syndromic and non-syndromic intellectual disability disorders. ZFX on Xp22.11 encodes a transcription factor that has been linked to diverse processes including oncogenesis and development, but germline variants have not been characterized in association with disease. Here, we present clinical and molecular characterization of 18 individuals with germline ZFX variants. Exome or genome sequencing revealed 11 variants in 18 subjects (14 males and 4 females) from 16 unrelated families. Four missense variants were identified in 11 subjects, with seven truncation variants in the remaining individuals. Clinical findings included developmental delay/intellectual disability, behavioral abnormalities, hypotonia, and congenital anomalies. Overlapping and recurrent facial features were identified in all subjects, including thickening and medial broadening of eyebrows, variations in the shape of the face, external eye abnormalities, smooth and/or long philtrum, and ear abnormalities. Hyperparathyroidism was found in four families with missense variants, and enrichment of different tumor types was observed. In molecular studies, DNA-binding domain variants elicited differential expression of a small set of target genes relative to wild-type ZFX in cultured cells, suggesting a gain or loss of transcriptional activity. Additionally, a zebrafish model of ZFX loss displayed an altered behavioral phenotype, providing additional evidence for the functional significance of ZFX. Our clinical and experimental data support that variants in ZFX are associated with an X-linked intellectual disability syndrome characterized by a recurrent facial gestalt, neurocognitive and behavioral abnormalities, and an increased risk for congenital anomalies and hyperparathyroidism.

Examining the associations among knowledge, empowerment, and advocacy among parents of transition-aged youth with autism.

LAY ABSTRACT: Parents of individuals with autism face many challenges in finding appropriate services and support for their children, and they also play an important role in advocating for their children's rights and needs. Despite the increasing availability of advocacy programs, it is still uncertain how to best encourage parents to advocate for their children. This study explored the connection between parents' knowledge and sense of empowerment, and how these factors relate to three types of advocacy activities (i.e. individual, peer, and systemic). The findings reveal that feeling empowered has a greater impact on advocacy than simply having knowledge. In addition, the study found that individual advocacy correlates to more peer advocacy, which also correlates to more systemic advocacy. These results can help researchers and professionals to better develop programs to increase parent advocacy and, in turn, help improve the lives of individuals with autism.

Trajectories of Competitive Employment of Autistic Adults through Late Midlife.

Autistic adults experience challenges in maintaining employment; however, little is known about patterns of competitive employment through late midlife. This longitudinal study examined the change in hours of competitive employment for a cohort of autistic adults over a 22-year period. The study's aims were to provide a fine-grained analysis of competitive employment patterns, to determine whether there was age-related change, and to test whether trajectories differed between those with and without intellectual disability (ID). Using an accelerated longitudinal design, trajectories of hours of competitive employment were estimated from young adulthood through late midlife in a community-based cohort (n = 341; 1327 observations). Results indicated a significant curvilinear trajectory of age-related change in hours of competitive employment, with differences between those with and without ID. For those without ID, the number of competitive employment hours increased from young adulthood until early midlife, then leveled off and decreased into late midlife. For those with ID, engagement in competitive employment was low throughout. Although competitive employment is just one option for vocational engagement, it is a goal often articulated by autistic adults who seek entry into the general workforce. The present research reveals their degree of engagement in the competitive workforce across the decades of adulthood.

Perspectives on Employer-Initiated Terminations Among Young Adults on the Autism Spectrum.

Job instability is high among autistic adults, with employer-initiated terminations a common reason for job loss. The current study used qualitative methods to code reasons that autistic adults identified for their employer-initiated termination. From 315 autistic individuals ages 18-35 who completed an online survey, 93 (29.5%) reported having been terminated from a job. These individuals were asked about the reasons for their termination and responses were coded into thematic categories. Common reasons included work performance, social difficulties, attendance, and mental health challenges. Adults were more likely to attribute terminations to internal causes (related to the individual) than to external causes (environment-related). A good fit between workplace, individual preferences, skills, and abilities is likely key to promoting job continuity for autistic adults.

Associations between social activities and depressive symptoms in adolescents and young adults with autism spectrum disorder: Testing the indirect effects of loneliness.

LAY ABSTRACT: Previous studies have found that social activities and depressive symptoms in adolescents and young adults with autism spectrum disorder are related. To better understand the relationship between these issues, this study examined the frequency of various types of social activities as well as if the participants felt that the frequency of time spent in the activity met their personal needs. In addition, the role of loneliness was tested as a possible way to understand the relationship between activities and depressive symptoms. To test these ideas, 321 participants who were recruited from the Simons Foundation Powering Autism Research for Knowledge (SPARK) research match registry and completed online measures of social activities, depressive symptoms, and loneliness. While the specific pattern was different for individual activities, it was found that those who felt that their current frequency of activities did not meet their needs had higher rates of depressive symptoms than those who felt they did meet their needs. Also, loneliness helps to understand relationship between social activities and depressive symptoms. The findings were discussed in light of previous study findings, interpersonal theories of depression, and clinical implications.

Self-reported Everyday Sources of Happiness and Unhappiness in Autistic Adults.

PURPOSE: Daily mood can be influenced by a range of experiences. Identifying everyday life experiences that make autistic adults happy and unhappy holds potential to foster positive mood and tackle mental health problems amongst this group. METHODS: A total of 293 autistic adults between the ages of 18 to 35 years old (mean age of 26.51 years old (SD = 4.62); 43.3% female gender, 4.8% nonbinary) provided open-text responses regarding everyday sources of happiness and unhappiness. Using an iterative process of inductive coding, 14 happy themes and 22 unhappy themes of mood-changing life experiences were identified based on self-report qualitative data. RESULTS: Common themes across the happy and unhappy domain involved social partners, social interactions, and engagement in recreational and employment activities, with additional distinct themes specific to happy or unhappy mood. Top themes identified in the happy domain emphasizes encouraging quality relationships and positive interactions with others and cultivating supportive work/societal environments to build a sense of achievement and value. Meanwhile, emotional tolls accompanied negative relationships and interactions, underscoring the necessity to provide autistic adults with conflict resolution and coping skills to increase feelings of happiness. CONCLUSION: Overall, the wide range of sources of happy and unhappy everyday experiences highlights the importance of considering personal preferences in engagement with others and activities in treatment.

Impact of the Great Recession on Adults With Autism and Their Mothers.

Autistic individuals and their families are at risk for poor outcomes in employment and mental health and may be vulnerable to long-term effects of broader societal conditions. The aim of the current longitudinal study was to understand the impact of the Great Recession of 2007-2009 on autistic individuals and their mothers (N = 392). Hierarchical linear modeling (HLM) results indicated that problem behavior of autistic adults increased in the years following the recession. The rate at which autistic individuals moved away and lived separately from their mothers also slowed during the recession. Mothers experienced significantly higher levels of depressive symptoms postrecession, compared to prerecession. In many other respects, the autistic individuals and their mothers did not experience negative outcomes, suggesting resilience and a strong safety net. These included the physical health and vocational/employment status of the autistic adults and their mothers. Results point to specific areas of vulnerability of autistic individuals and their mothers during the economic downturn, as well as a broad pattern of resilience in these families.

Autism through midlife: trajectories of symptoms, behavioral functioning, and health.

BACKGROUND: This study describes change in autism symptoms, behavioral functioning, and health measured prospectively over 22 years. Most studies tracking developmental trajectories have focused on autism during childhood, although adulthood is the longest stage of the life course. A robust understanding of how autistic people change through midlife and into older age has yet to be obtained. METHODS: Using an accelerated longitudinal design with 9 waves of data, developmental trajectories were estimated from adolescence through midlife and into early old age in a community-based cohort (n = 406). The overall aim was to determine whether there were age-related increases or decreases, whether the change was linear or curvilinear, and whether these trajectories differed between those who have ID and those who have average or above-average intellectual functioning. Subsequently, the slopes of the trajectories were evaluated to determine if they differed depending on age when the study began, with the goal of identifying possible cohort effects. RESULTS: There were significant trajectories of age-related change for all but one of the measures, although different measures manifested different patterns. Most autism symptoms improved through adulthood, while health worsened. An inverted U-shaped curve best described change for repetitive behavior symptoms, activities of daily living, maladaptive behaviors, and social interaction. For these measures, improved functioning was evident from adolescence until midlife. Then change leveled off, with worsening functioning from later midlife into early older age. Additionally, differences between autistic individuals with and without ID were evident. Although those who have ID had poorer levels of functioning, there were some indications that those without ID had accelerating challenges in their aging years that were not evident in those with ID - increases in medications for physical health problems and worsening repetitive behaviors. CONCLUSIONS: Meeting the needs of the increasingly large population of autistic adults in midlife and old age requires a nuanced understanding of life course trajectories across the long stretch of adulthood and across multiple domains. Given the heterogeneity of autism, it will be important not to generalize across sub-groups, for example those who are minimally verbal and those who have above-average intellectual functioning.

Service evaluation of an independent domestic violence advocate post in a children's hospital.

Domestic violence and abuse (DVA) has detrimental effects on the health and well-being of children and young people exposed to it, whether they witness or experience it. The introduction of independent domestic violence advocates in UK hospitals has enhanced the safety of victims of DVA. In 2020-2021 an independent domestic violence advocate post was piloted at a children's hospital for one year, the advocate's role being to train hospital staff and support women who had experienced DVA. A service evaluation showed that the training and support provided by the independent domestic violence advocate had benefits for women, children and staff. It also confirmed that the commissioning of services for children exposed to DVA is often underfunded and overshadowed by the provision of support to adults.

Challenges and Opportunities for Clinician Implicit Bias Training: Insights from Perinatal Care Stakeholders.

Introduction: In an attempt to address health inequities, many U.S. states have considered or enacted legislation requiring antibias or implicit bias training (IBT) for health care providers. California's "Dignity in Pregnancy and Childbirth Act" requires that hospitals and alternative birthing centers provide IBT to perinatal clinicians with the goal of improving clinical outcomes for Black women and birthing people. However, there is as yet insufficient evidence to identify what IBT approaches, if any, achieve this goal. Engaging the experiences and insights of IBT stakeholders is a foundational step in informing nascent IBT policy, curricula, and implementation. Methods: We conducted a multimethod community-based participatory research study with key stakeholders of California's IBT policy to identify key challenges and recommendations for effective clinician IBT. We used focus groups, in-depth interviews, combined inductive/deductive thematic analysis, and multiple techniques to promote rigor and validity. Participants were San Francisco Bay Area-based individuals who identified as Black or African American women with a recent hospital birth (n=20), and hospital-based perinatal clinicians (n=20). Results: We identified numerous actionable challenges and recommendations regarding aspects of (1) state law; (2) IBT content and format; (3) health care facility IBT implementation; (4) health care facility environment; and (5) provider commitment and behaviors. Patient and clinician insights overlapped substantially. Many respondents felt IBT would improve outcomes only in combination with other antiracism interventions. Health Equity Implications: These stakeholder insights offer policy-makers, health system leaders, and curriculum developers crucial guidance for the future development and implementation of clinician antibias interventions.

Healthcare interventions for sex workers: protocol for a scoping review.

INTRODUCTION: Sex workers, who provide sexual or erotic acts in exchange for payment, often experience multiple disadvantages, including mental ill health and substance misuse. Mainstream healthcare services are generally not configured to facilitate engagement with sex workers and therefore, services are needed that are accessible to this population. The aim of this scoping review is to understand the evidence base for approaches, services and interventions that are aimed at addressing sex workers' health needs. METHODS AND ANALYSIS: Nine databases, CINAHL, Embase, EThOS, Google Scholar, Health Management Information Consortium, MEDLINE, ProQuest Dissertations and Theses, PsycINFO and Web of Science (Core Collection), will be searched, with results limited to English language publications and those published from 2003 onwards. De-duplication, study selection and data extraction will be conducted using Covidence software. Included studies will describe or evaluate approaches, services or interventions that address the health needs of sex workers who offer services that involve physical contact with a client. ETHICS AND DISSEMINATION: No ethical review is needed. The final report will be shared with Birmingham City Council as part of ongoing work and will be disseminated by peer-reviewed publication. STUDY REGISTRATION: Open Science Framework (doi: 10.17605/OSF.IO/N7WSX).

Improving parents' ability to advocate for services for youth with autism: A randomized clinical trial.

Youth with autism face challenges accessing services as they transition to adulthood. Improving parents' ability to advocate for services on behalf of their youth may be an effective way to improve service access and ultimately transition outcomes in this group. In this study, we tested whether participating in an advocacy intervention improved parents' ability to advocate for services for their transition-aged youth with autism. One hundred and eighty-five parents of youth with autism ages 16-26, recruited across three states in the U.S., were randomized to one of two experimental conditions. The treatment condition received the ASSIST program, a 12-week (24-h) group-based intervention. The control condition received the same written materials as the treatment condition. Primary outcomes for this report-parent advocacy ability-were collected at baseline (prior to randomization) and post-test (immediately after the treatment group finished the 12-week program) by survey. After taking ASSIST, the treatment condition had greater gains than controls in knowledge of adult services (B = -1.62, CI = -2.33 to -0.90) and perceived advocacy skills (B = -0.19, CI = -0.33 to -0.04). Participants who had less knowledge, lower perceived advocacy skills, and less active coping styles at baseline had the greatest treatment gains. Findings suggest that ASSIST is effective in improving parent advocacy ability and may be most beneficial for parents who experience greater challenges advocating for their son/daughter with autism. Future research will examine whether gains in parent advocacy ability leads to improvements in service access and post-school outcomes for transition-age youth with autism.

Exposure to Domestic Abuse and the Subsequent Development of Atopic Disease in Women.

BACKGROUND: Exposure to domestic violence and abuse (DVA) is a global public health issue associated with substantial morbidity and mortality. There are few high-quality studies that assess the impact of DVA exposure on the development of atopic disease. OBJECTIVE: To examine the association between exposure to DVA and the subsequent development of atopy. METHODS: In this population-based, retrospective, open cohort study, we identified women with no history of atopic disease between January 1, 1995 and September 30, 2019 from IQVIA Medical Research Data, an anonymized UK primary care dataset. We used clinical codes to identify exposed patients (those with a code identifying exposure to DVA; n = 13,852) and unexposed patients (n = 49,036), who were matched by age and deprivation quintile. Cox proportional hazards regression was used to calculate hazard ratios (HRs) (with 95% CIs) of developing atopic disease: asthma, atopic eczema, or allergic rhinoconjunctivitis. RESULTS: During the study period, 967 exposed women (incidence rate, 20.10/1,000 person-years) developed atopic disease, compared with 2,607 unexposed women (incidence rate, 13.24/1,000 person-years). This translated to an adjusted HR of 1.52 (95% CI, 1.41-1.64) accounting for key confounders; asthma (adjusted HR = 1.69; 95% CI, 1.44-1.99), atopic eczema (adjusted HR = 1.40; 95% CI, 1.26-1.56), and allergic rhinoconjunctivitis (adjusted HR = 1.63; 95% CI, 1.45-1.84). CONCLUSIONS: Domestic violence and abuse is a significant global public health issue. These results demonstrate a significant associated risk for developing atopic disease. Public health approaches to the prevention and detection of DVA are necessary to reduce the associated ill health burden.

Expert Panel Curation of 113 Primary Mitochondrial Disease Genes for the Leigh Syndrome Spectrum.

OBJECTIVE: Primary mitochondrial diseases (PMDs) are heterogeneous disorders caused by inherited mitochondrial dysfunction. Classically defined neuropathologically as subacute necrotizing encephalomyelopathy, Leigh syndrome spectrum (LSS) is the most frequent manifestation of PMD in children, but may also present in adults. A major challenge for accurate diagnosis of LSS in the genomic medicine era is establishing gene-disease relationships (GDRs) for this syndrome with >100 monogenic causes across both nuclear and mitochondrial genomes. METHODS: The Clinical Genome Resource (ClinGen) Mitochondrial Disease Gene Curation Expert Panel (GCEP), comprising 40 international PMD experts, met monthly for 4 years to review GDRs for LSS. The GCEP standardized gene curation for LSS by refining the phenotypic definition, modifying the ClinGen Gene-Disease Clinical Validity Curation Framework to improve interpretation for LSS, and establishing a scoring rubric for LSS. RESULTS: The GDR with LSS across the nuclear and mitochondrial genomes was classified as definitive for 31 of 114 GDRs curated (27%), moderate for 38 (33%), limited for 43 (38%), and disputed for 2 (2%). Ninety genes were associated with autosomal recessive inheritance, 16 were maternally inherited, 5 were autosomal dominant, and 3 were X-linked. INTERPRETATION: GDRs for LSS were established for genes across both nuclear and mitochondrial genomes. Establishing these GDRs will allow accurate variant interpretation, expedite genetic diagnosis of LSS, and facilitate precision medicine, multisystem organ surveillance, recurrence risk counseling, reproductive choice, natural history studies, and determination of eligibility for interventional clinical trials. ANN NEUROL 2023;94:696-712.