Co-existing mental and somatic conditions in Swedish children with the avoidant restrictive food intake disorder phenotype.

Background: Avoidant restrictive food intake disorder (ARFID) is a feeding and eating disorder, characterized by limited variety and/or quantity of food intake impacting physical health and psychosocial functioning. Children with ARFID often present with a range of psychiatric and somatic symptoms, and therefore consult various pediatric subspecialties; large-scale studies mapping comorbidities are however lacking. To characterize health care needs of people with ARFID, we systematically investigated ARFID-related mental and somatic conditions in 616 children with ARFID and >30,000 children without ARFID. Methods: In a Swedish twin cohort, we identified the ARFID phenotype in 6-12-year-old children based on parent-reports and register data. From >1,000 diagnostic ICD-codes, we specified mental and somatic conditions within/across ICD-chapters, number of distinct per-person diagnoses, and inpatient treatment days between birth and 18th birthday (90 outcomes). Hazard ratios (HR) and incidence rate ratios (IRR) were calculated. Findings: Relative risks of neurodevelopmental, gastrointestinal, endocrine/metabolic, respiratory, neurological, and allergic disorders were substantially increased in ARFID (e.g., autism HR[CI95%]=9.7[7.5-12.5], intellectual disability 10.3[7.6-13.9], gastroesophageal reflux disease 6.7[4.6-9.9], pituitary conditions 5.6[2.7-11.3], chronic lower respiratory diseases 4.9[2.4-10.1], epilepsy 5.8[4.1-8.2]). ARFID was not associated with elevated risks of autoimmune illnesses and obsessive-compulsive disorder. Children with ARFID had a significantly higher number of distinct mental diagnoses (IRR[CI95%]=4.7[4.0-5.4]) and longer duration of hospitalizations (IRR[CI95%]=5.5[1.7-17.6]) compared with children without ARFID. Children with ARFID were diagnosed earlier with a mental condition than children without ARFID. No sex-specific differences emerged. Interpretation: This study yields the broadest and most detailed evidence of co-existing mental and somatic conditions in the largest sample of children with ARFID to date. Findings suggest a complex pattern of health needs in youth with ARFID, underscoring the critical importance of attention to the illness across all pediatric specialties. Funding: Fredrik and Ingrid Thurings Foundation, Mental Health Foundation.

The national distribution of lymphatic filariasis cases in Malawi using patient mapping and geostatistical modelling.

BACKGROUND: In 2020 the World Health Organization (WHO) declared that Malawi had successfully eliminated lymphatic filariasis (LF) as a public health problem. Understanding clinical case distributions at a national and sub-national level is important, so essential care packages can be provided to individuals living with LF symptoms. This study aimed to develop a national database and map of LF clinical cases across Malawi using geostatistical modelling approaches, programme-identified clinical cases, antigenaemia prevalence and climate information. METHODOLOGY: LF clinical cases identified through programme house-to-house surveys across 90 sub-district administrative boundaries (Traditional Authority (TA)) and antigenaemia prevalence from 57 sampled villages in Malawi were used in a two-step geostatistical modelling process to predict LF clinical cases across all TAs of the country. First, we modelled antigenaemia prevalence in relation to climate covariates to predict nationwide antigenaemia prevalence. Second, we modelled clinical cases for unmapped TAs based on our antigenaemia prevalence spatial estimates. PRINCIPLE FINDINGS: The models estimated 20,938 (95% CrI 18,091 to 24,071) clinical cases in unmapped TAs (70.3%) in addition to the 8,856 (29.7%), programme-identified cases in mapped TAs. In total, the overall national number of LF clinical cases was estimated to be 29,794 (95% CrI 26,957 to 32,927). The antigenaemia prevalence and clinical case mapping and modelling found the highest burden of disease in Chikwawa and Nsanje districts in the Southern Region and Karonga district in the Northern Region of the country. CONCLUSIONS: The models presented in this study have facilitated the development of the first national LF clinical case database and map in Malawi, the first endemic country in sub-Saharan Africa. It highlights the value of using existing LF antigenaemia prevalence and clinical case data together with modelling approaches to produce estimates that may be used for the WHO dossier requirements, to help target limited resources and implement long-term health strategies.

Combinations of the azaquinazoline anti-Wolbachia agent, AWZ1066S, with benzimidazole anthelmintics synergise to mediate sub-seven-day sterilising and curative efficacies in experimental models of filariasis.

Lymphatic filariasis and onchocerciasis are two major neglected tropical diseases that are responsible for causing severe disability in 50 million people worldwide, whilst veterinary filariasis (heartworm) is a potentially lethal parasitic infection of companion animals. There is an urgent need for safe, short-course curative (macrofilaricidal) drugs to eliminate these debilitating parasite infections. We investigated combination treatments of the novel anti-Wolbachia azaquinazoline small molecule, AWZ1066S, with benzimidazole drugs (albendazole or oxfendazole) in up to four different rodent filariasis infection models: Brugia malayi-CB.17 SCID mice, B. malayi-Mongolian gerbils, B. pahangi-Mongolian gerbils, and Litomosoides sigmodontis-Mongolian gerbils. Combination treatments synergised to elicit threshold (>90%) Wolbachia depletion from female worms in 5 days of treatment, using 2-fold lower dose-exposures of AWZ1066S than monotherapy. Short-course lowered dose AWZ1066S-albendazole combination treatments also delivered partial adulticidal activities and/or long-lasting inhibition of embryogenesis, resulting in complete transmission blockade in B. pahangi and L. sigmodontis gerbil models. We determined that short-course AWZ1066S-albendazole co-treatment significantly augmented the depletion of Wolbachia populations within both germline and hypodermal tissues of B. malayi female worms and in hypodermal tissues in male worms, indicating that anti-Wolbachia synergy is not limited to targeting female embryonic tissues. Our data provides pre-clinical proof-of-concept that sub-seven-day combinations of rapid-acting novel anti-Wolbachia agents with benzimidazole anthelmintics are a promising curative and transmission-blocking drug treatment strategy for filarial diseases of medical and veterinary importance.

Sustained looking at faces at 5 months of age is associated with socio-communicative skills in the second year of life.

Efficiently processing information from faces in infancy is foundational for nonverbal communication. We studied individual differences in 5-month-old infants' (N = 517) sustained attention to faces and preference for emotional faces. We assessed the contribution of genetic and environmental influences to individual differences in these gaze behaviors, and the association between these traits and other concurrent and later phenotypes. We found an association between the mean duration of looking at a face (before looking away from it) at 5 months and socio-communicative abilities at 14 months (ß = 0.17, 95% CI: 0.08; 0.26, p < 0.001). Sustained attention to faces predicted socio-communicative abilities over and above variance captured by mean fixation duration. We also found a statistically significant but weak tendency to prefer looking at smiling faces (relative to neutral faces), but no indication that variability in this behavior was explained by genetic effects. Moderate heritability was found for sustained attention to faces (A = 0.23, CI: 0.06; 0.38), while shared environmental influences were non-significant for both phenotypes. These findings suggest that sustained looking at individual faces before looking away is a developmentally significant 'social attention' phenotype in infancy, characterized by moderate heritability and a specific relation to later socio-communicative abilities.

Elimination of lymphatic filariasis as a public health problem in Malawi.

BACKGROUND: Lymphatic filariasis (LF) is a parasitic disease transmitted by mosquitoes, causing severe pain, disfiguring, and disabling clinical conditions such as lymphoedema and hydrocoele. LF is a global public health problem affecting 72 countries, primarily in Africa and Asia. Since 2000, the World Health Organization (WHO) has led the Global Programme to Eliminate Lymphatic Filariasis (GPELF) to support all endemic regions. This paper focuses on the achievements of the Malawi LF Elimination Programme between 2000 and 2020 to eliminate LF as a public health problem, making it the second sub-Saharan country to receive validation from the WHO. METHODOLOGY/PRINCIPAL FINDINGS: The Malawi LF Programme addressed the widespread prevalence of LF infection and disease across the country, using the recommended WHO GPELF strategies and operational research initiatives in collaboration with key national and international partners. First, to stop the spread of infection (i.e., interrupt transmission) and reduce the circulating filarial antigen prevalence from as high as 74.4% to below the critical threshold of 1-2% prevalence, mass drug administration (MDA) using a two-drug regime was implemented at high coverage rates (>65%) of the total population, with supplementary interventions from other programmes (e.g., malaria vector control). The decline in prevalence was monitored and confirmed over time using several impact assessment and post-treatment surveillance tools including the standard sentinel site, spot check, and transmission assessment surveys and alternative integrated, hotspot, and easy-access group surveys. Second, to alleviate suffering of the affected populations (i.e., control morbidity) the morbidity management and disability prevention (MMDP) package of care was implemented. Specifically, clinical case estimates were obtained via house-to-house patient searching activities; health personnel and patients were trained in self-care protocols for lymphoedema and/or referrals to hospitals for hydrocoele surgery; and the readiness and quality of treatment and services were assessed with new survey tools. CONCLUSIONS: Malawi's elimination of LF will ensure that future generations are not infected and suffer from the disfiguring and disabling disease. However, it will be critical that the Malawi LF Elimination programme remains vigilant, focussing on post-elimination surveillance and MMDP implementation and integration into routine health systems to support long-term sustainability and ongoing success. SUMMARY: Lymphatic filariasis, also known as elephantiasis, is a disabling, disfiguring, and painful disease caused by a parasite that infected mosquitoes transmit to millions of people worldwide. Since 2000, the Global Programme to Eliminate Lymphatic Filariasis (GPELF) has supported endemic countries such as Malawi in south-eastern Africa, to eliminate the disease as a public health problem. The Malawi National LF Elimination Programme has worked tirelessly over the past two decades to implement the GPELF recommended strategies to interrupt the transmission with a two-drug regime, and to alleviate suffering in patients with lymphoedema and/or hydrocoele through morbidity management and disability prevention. Additionally, the LF Programme has collaborated with national and international stakeholders to implement a range of supplementary operational research projects to address outstanding knowledge gaps and programmatic barriers. In 2020, the World Health Organisation validated that Malawi had successfully eliminated LF as a public health problem, making it the second country in sub-Saharan Africa to achieve this, which is remarkable given that Malawi previously had very high infection rates. The LF Programme now remains vigilant, putting its efforts towards post-elimination surveillance and the continued implementation of care for patients with chronic conditions. Malawi's elimination of LF will ensure that future generations are not affected by this devastating disease.

Age effects on autism heritability and etiological stability of autistic traits.

BACKGROUND: Autism and autistic traits onset in childhood but persist into adulthood. Little is known about how genetic and environmental factors influence autism and autistic traits into adulthood. We aimed to determine age effects on the heritability of clinically diagnosed autism and the etiological stability of autistic traits from childhood to adulthood using twin methods. METHODS: From 23,849 twin pairs in the Swedish Twin Register born between 1959 and 2010, we identified 485 individuals (1.01%, 31.5% female) with a clinical autism diagnosis. We estimated and compared the relative contribution of genetic, shared, and nonshared environmental influences to autism in childhood and adulthood. We further used multivariate twin analysis with four measurement points among 1,348 twin pairs in the longitudinal Twin Study of Child and Adolescent Development to assess the phenotypic and etiological stability of autistic traits - measured with three scales from the Child Behavior Checklist - from childhood to adulthood. RESULTS: Autism heritability was comparable from childhood, (96% [95% CI, 76-99%]) to adulthood (87% [67-96%]). Autistic traits were moderately stable (phenotypic correlation = 0.35-0.61) from childhood to adulthood, and their heritability varied between 52 and 71%. We observed stable as well as newly emerging genetic influences on autistic traits from ages 8-9 to 19-20, and unique nonshared environmental influences at each age. CONCLUSIONS: Genetic factors are important for autism and autistic traits in adulthood and separate genetic studies in adults are warranted.

Treatment and prevention of epilepsy in onchocerciasis-endemic areas is urgently needed.

BACKGROUND: There is increasing epidemiological evidence supporting the association between onchocerciasis and seizures, reinforcing the concept of onchocerciasis-associated epilepsy (OAE). The aim of this paper is to provide an update on the new knowledge about OAE and to propose recommendations to the World Health Organization how to address this public health problem. MAIN TEXT: During the 2nd International Workshop on OAE held on 19-21 September, 2023, in Antwerp, Belgium, participants recognised OAE as a substantial yet neglected public health problem, particularly in areas of sub-Saharan Africa where onchocerciasis remains hyperendemic. Evidence from prospective population-based studies suggest that strengthening onchocerciasis elimination efforts leads to a significant reduction of OAE incidence. There is a need to validate an OAE case definition to estimate the burden of disease and identify onchocerciasis-endemic areas requiring intensification of onchocerciasis elimination programmes and integration of epilepsy care. It is expected that raising awareness about OAE will boost the population uptake of ivermectin. The implementation of a community-based epilepsy treatment programme offering free anti-seizure medications (ASMs) has shown high effectiveness in reducing the frequency of seizures and improving the overall quality of life of people with epilepsy. CONCLUSIONS: To reduce OAE burden, enhanced collaboration between onchocerciasis and mental health programmes at community, national, and international levels is required. Urgent efforts are needed to ensure the uninterrupted provision of free ASMs in onchocerciasis-endemic areas. Furthermore, OAE should be included in the quantification of the onchocerciasis disease burden.

Infants' looking preferences for social versus non-social objects reflect genetic variation.

To what extent do individual differences in infants' early preference for faces versus non-facial objects reflect genetic and environmental factors? Here in a sample of 536 5-month-old same-sex twins, we assessed attention to faces using eye tracking in two ways: initial orienting to faces at the start of the trial (thought to reflect subcortical processing) and sustained face preference throughout the trial (thought to reflect emerging attention control). Twin model fitting suggested an influence of genetic and unique environmental effects, but there was no evidence for an effect of shared environment. The heritability of face orienting and preference were 0.19 (95% confidence interval (CI) 0.04 to 0.33) and 0.46 (95% CI 0.33 to 0.57), respectively. Face preference was associated positively with later parent-reported verbal competence (ß = 0.14, 95% CI 0.03 to 0.25, P = 0.014, R2 = 0.018, N = 420). This study suggests that individual differences in young infants' selection of perceptual input-social versus non-social-are heritable, providing a developmental perspective on gene-environment interplay occurring at the level of eye movements.

The Statewide Patient Load Balancing Work of Washington State's Medical Operations Coordination Center.

OBJECTIVES: Load balancing of constrained healthcare resources has become a critical aspect of assuring access to care during periods of pandemic related surge. These impacts include patient surges, staffing shortages, and limited access to specialty resources. This research focuses on the creation and work of a novel statewide coordination center, the Washington Medical Coordination Center (WMCC), whose primary goal is the load balancing of patients across the healthcare continuum of Washington State. METHODS: This article discusses the origins, development, and operations of the WMCC including key partners, cooperative agreements, and structure necessary to create a patient load balancing system on a statewide level. RESULTS: As of April 21, 2022, the WMCC received 3821 requests from Washington State hospitals. Nearly 90% were received during the pandemic surge. Nearly 75% originated from rural hospitals that are most often limited in their ability to transfer patients when referral centers are also overwhelmed. CONCLUSIONS: The WMCC served as an effective tool to carry out patient load balancing activities during the COVID-19 pandemic surge in Washington State. It (the WMCC) has been shown to be an equity enhancing, cost effective means of managing healthcare surge events across a broad geographic region.

Mental health conditions in people affected by filarial lymphoedema in Malawi: prevalence, associated risk factors and the impact of an enhanced self-care intervention.

BACKGROUND: This study aimed to determine the key mental health indicators affecting people affected by lymphatic filariasis (LF) lymphoedema by assessing the prevalence of depressive symptoms and quality of life (QOL), identifying associated sociodemographic and clinical risk factors, and evaluating the impact of an enhanced self-care intervention for lymphoedema management. METHODS: A prospective cohort study of adults with filarial lymphoedema from two regions of Malawi was conducted over six months in 2021. Depressive symptoms and QOL were assessed using Patient Health Questionnaire (PHQ-9) and LF Specific QOL Questionnaire, respectively, at baseline (pre-intervention), 3- and 6-months (postintervention). Beta regression analysis identified risk factors, and assessed the impact of the intervention. RESULTS: Three hundred eleven affected individuals were surveyed with 23% (95% CI 18%-29%) reporting mild/moderate depressive symptoms and 31% (95% CI 26%-37%) reporting moderately low/low QOL. Higher depressive symptom scores were associated with high frequency of acute filarial attack episodes. Individuals with higher depressive symptoms (Adjusted Odds Ratios (AOR) 0.93, 95% CI 0.93-0.93) and lower QOL (AOR 0.98, 0.98-0.98) showed greatest improvement in mental health indicators over 3-months but was not sustained to the same level at 6-months. CONCLUSIONS: Sustained morbidity management and psychological support is recommended for affected persons to ensure long-term positive mental health and clinical outcomes. CONTEXTE: Cette étude vise à déterminer les principaux indicateurs de santé mentale affectant les personnes atteintes de lymphœdème dû à la filariose lymphatique (FL) en évaluant la prévalence des symptômes dépressifs et la qualité de vie (QV), en identifiant les facteurs de risque sociodémographiques et cliniques associés, et en évaluant l'impact d'une intervention améliorée d'autosoins pour la gestion du lymphœdème. MÉTHODES: Une étude de cohorte prospective d'adultes atteints de lymphoedème filaire dans deux régions du Malawi a été menée pendant six mois en 2021. Les symptômes dépressifs et la qualité de vie ont été évalués à l'aide du questionnaire sur la santé des patients (PHQ-9) et du questionnaire sur la qualité de vie spécifique au lymphœdème, respectivement, au début de l'étude (avant l'intervention), et à 3 puis 6 mois après l'intervention. Une analyse de régression beta a permis d'identifier les facteurs de risque et d'évaluer l'impact de l'intervention. RÉSULTATS: Trois cent onze personnes affectées ont été interrogées, dont 23% (95% CI 18%-29%) ont déclaré des symptômes dépressifs légers/modérés et 31% (95% CI 26%-37%) ont déclaré une qualité de vie modérément faible/faible. Des scores élevés de symptômes dépressifs ont été associés à une fréquence élevée d'épisodes de crises filariennes aiguës. Les personnes présentant des symptômes dépressifs plus élevés (rapport de cotes ajusté (RCA) 0.93, IC à 95 % 0.93-0.93) et une qualité de vie plus faible (RCA 0.98, 0.98-0.98) ont montré la plus grande amélioration des indicateurs de santé mentale au cours des trois mois, mais cette amélioration ne s'est pas maintenue au même niveau au cours des six mois suivants. CONCLUSION: Gestion de la morbidité et soutien psychologique sont des éléments clés pour garantir une santé mentale et des résultats cliniques satisfaisants de personnes atteintes sur le long terme. ANTECEDENTES: Este estudio tuvo como objetivo determinar los indicadores clave de salud mental que afectan a las personas afectadas por linfedema por filariasis linfática (FL) mediante la evaluación de la prevalencia de síntomas depresivos y calidad de vida (CdV), la identificación de factores de riesgo sociodemográficos y clínicos asociados, y la evaluación del impacto de una intervención de autocuidado mejorada para el manejo del linfedema. MÉTODOS: Se realizó un estudio prospectivo de cohortes de adultos con linfedema filarial de dos regiones de Malawi durante seis meses en 2021. Los síntomas depresivos y la calidad de vida se evaluaron mediante el Cuestionario de Salud del Paciente (PHQ-9) y el Cuestionario de Calidad de Vida específico para el LF Cuestionario, respectivamente, al inicio (preintervención) y a los 3 y 6 meses (posintervención). El análisis de regresión beta identificó los factores de riesgo y evaluó el impacto de la intervención. RESULTADOS: Se encuestó a 311 afectados, de los cuales el 23% (IC 95%, 18%-29%) presentaba síntomas depresivos leves/moderados y el 31% (IC 95%, 26%-37%) una CdV moderadamente baja/baja CdV. Las puntuaciones más altas de síntomas depresivos se asociaron con una alta frecuencia de episodios de ataques agudos de filarias. Los individuos con mayores síntomas depresivos (Odds Ratios Ajustados [ORA] 0.93; IC 95%: 0.93-0.93) y menor CdV (ORA 0.98; 0.98-0.98) mostraron la mayor mejoría en los indicadores de salud mental a los 3 meses, pero no se mantuvo al mismo nivel a los 6 meses. CONCLUSIONES: Se recomienda el manejo sostenido de la morbilidad y el apoyo psicológico a las personas afectadas para garantizar resultados clínicos y de salud mental positivos a largo plazo.

Genetic and environmental architecture of synaesthesia and its association with the autism spectrum-a twin study.

Synaesthesia is a sensory phenomenon where external stimuli, such as sounds or letters, trigger additional sensations (e.g. colours). Synaesthesia aggregates in families but its heritability is unknown. The phenomenon is more common in people on the autism spectrum compared with the general population and associated with higher autistic traits. Using classical twin design, we assessed the heritability of individual differences in self-reported synaesthesia and the genetic and environmental contributions to their association with autistic traits within a population twin cohort (n = 4262, age = 18 years). We estimated individual differences in synaesthesia to be heritable and influenced by environmental factors not shared between twins. The association between individual differences in synaesthesia and autistic traits was estimated to be predominantly under genetic influence and seemed to be mainly driven by non-social autistic traits (repetitive behaviours, restricted interests and attention to detail). Our study suggests that the link between synaesthesia and autism might reside in shared genetic causes, related to non-social autistic traits such as alterations in perception. Future studies building on these findings may attempt to identify specific groups of genes that influence both autism, synaesthesia and perception.

Psychotropic Medication Use in Children and Adolescents With Type 1 Diabetes.

Importance: Children and adolescents with type 1 diabetes (T1D) face elevated risks of psychiatric disorders. Despite their nonnegligible adverse effects, psychotropic medications are a common cost-effective approach to alleviating psychiatric symptoms, but evidence regarding their dispensation to children and adolescents with T1D remains lacking. Objective: To examine the trends and patterns of psychotropic medication dispensation among children and adolescents with T1D in Sweden between 2006 and 2019. Design, Setting, and Participants: This cohort study used data from multiple Swedish registers. The main study cohort included children and adolescents residing in Sweden from 2006 to 2019 and was followed up until the earliest of December 31, 2019, 18th birthday, emigration, or death. Data analyses were conducted from November 1, 2022, to April 30, 2023. Exposures: Type 1 diabetes. Main Outcomes and Measures: The primary outcomes were trends and patterns of psychotropic medication dispensation (including antipsychotics, antidepressants, anxiolytics, hypnotics, mood stabilizers, and medications for attention-deficit/hyperactivity disorder [ADHD]), psychotropic medication initiation, and history of neurodevelopmental and psychiatric diagnosis. Cumulative incidence curves and Cox proportional hazard models were used to estimate the aggregated incidence and hazard ratios of medication initiation after diabetes onset. Results: Of 3 723 745 children and adolescents (1 896 199 boys [50.9%]), 13 200 (0.4%; 7242 boys [54.9%]) had T1D (median [IQR] age at diagnosis, 11.1 [7.6-14.7] years). Between 2006 and 2019, psychotropic medication dispensation increased from 0.85% (95% CI, 0.65%-1.10%) to 3.84% (3.11%-4.69%) among children and from 2.72% (95% CI, 2.15%-3.39%) to 13.54% (95% CI, 12.88%-14.23%) among adolescents with T1D, consistently higher than their peers without T1D. The most commonly dispensed medications included hypnotics, ADHD medications, anxiolytics, and selective serotonin reuptake inhibitors, and all exhibited increasing trends. For those with T1D, psychiatric care was the primary prescription source, and up to 50.1% of treatments lasted more than 12 months. In addition, children and adolescents with T1D showed higher cumulative incidence and hazard ratios of medication initiation after diabetes onset than their same-age and same-sex counterparts. Conclusions and Relevance: This cohort study found an increasing trend in psychotropic medication dispensation among children and adolescents with T1D from 2006 to 2019, persistently higher than those without T1D. These findings call for further in-depth investigations into the benefits and risks of psychotropic medications within this population and highlight the importance of integrating pediatric diabetes care and mental health care for early detection of psychological needs and careful monitoring of medication use.

Association between cumulative psychosocial adversity in the family and ADHD and autism: a family-based cohort study.

Cumulative exposure to psychosocial adversity at an early age has been shown to be a risk factor for attention-deficit hyperactivity disorder (ADHD) and autism that often co-occur. However, it is not clear if this association reflects a causal effect or familial confounding. We aimed to assess whether cumulative psychosocial adversity in the family increases the risk for ADHD and autism in offspring while accounting for unmeasured familial confounding. We used a population-based cohort of 1,877,901 individuals born in Sweden between 1990 and 2009. Participants were followed from the age of 3 until 2013, with a median follow up time of 13.8 years. We created a cumulative index based on 7 psychosocial adversity factors. We used Cox regression to estimate the hazard ratios (HRs) relating neurodevelopmental conditions to cumulative psychosocial adversity. To address familial confounding, the analyses were repeated in groups of relatives of different kinship: siblings and half-siblings and cousins. A dose-response relationship was observed between cumulative exposure to psychosocial adversity and ADHD at a general population level (covariate adjusted HRs (aHRs) with 95% confidence intervals ranged from 1.55 [one adversity; 1.53-1.58] to 2.65 [ ≥ 4 adversities; 1.98-3.54]). No clear dose-response relation was seen for autism (aHRs ranged from 1.04 [.59-1.84] to 1.37 [1.30-1.45]). HRs of ADHD and autism decreased with increasing level of kinship in the analysis of relatives. Cumulative exposure to psychosocial adversity was associated with both ADHD and autism in the general population, these associations were partly explained by unmeasured familial confounding between relatives. This highlights the need for using family-based designs in studies of psychosocial adversity and ADHD and autism.

Socio-economic and environmental factors associated with high lymphatic filariasis morbidity prevalence distribution in Bangladesh.

BACKGROUND: Lymphatic filariasis (LF) is a vector-borne parasitic disease which affects 70 million people worldwide and causes life-long disabilities. In Bangladesh, there are an estimated 44,000 people suffering from clinical conditions such as lymphoedema and hydrocoele, with the greatest burden in the northern Rangpur division. To better understand the factors associated with this distribution, this study examined socio-economic and environmental factors at division, district, and sub-district levels. METHODOLOGY: A retrospective ecological study was conducted using key socio-economic (nutrition, poverty, employment, education, house infrastructure) and environmental (temperature, precipitation, elevation, waterway) factors. Characteristics at division level were summarised. Bivariate analysis using Spearman's rank correlation coefficient was conducted at district and sub-district levels, and negative binomial regression analyses were conducted across high endemic sub-districts (n = 132). Maps were produced of high endemic sub-districts to visually illustrate the socio-economic and environmental factors found to be significant. RESULTS: The highest proportion of rural population (86.8%), poverty (42.0%), tube well water (85.4%), and primary employment in agriculture (67.7%) was found in Rangpur division. Spearman's rank correlation coefficient at district and sub-district level show that LF morbidity prevalence was significantly (p<0.05) positively correlated with households without electricity (district rs = 0.818; sub-district rs = 0.559), households with tube well water (sub-district rs = 0.291), households without toilet (district rs = 0.504; sub-district rs = 0.40), mean annual precipitation (district rs = 0.695; sub-district rs = 0.503), mean precipitation of wettest quarter (district rs = 0.707; sub-district rs = 0.528), and significantly negatively correlated with severely stunted children (district rs = -0.723; sub-district rs = -0.370), mean annual temperature (district rs = -0.633.; sub-district rs = 0.353) and mean temperature (wettest quarter) ((district rs = -0.598; sub-district rs = 0.316) Negative binomial regression analyses at sub-district level found severely stunted children (p = <0.001), rural population (p = 0.002), poverty headcount (p = 0.001), primary employment in agriculture (p = 0.018), households without toilet (p = <0.001), households without electricity (p = 0.002) and mean temperature (wettest quarter) (p = 0.045) to be significant. CONCLUSIONS: This study highlights the value of using available data to identify key drivers associated with high LF morbidity prevalence, which may help national LF programmes better identify populations at risk and implement timely and targeted public health messages and intervention strategies.

A twin study of genetic and environmental contributions to attention-deficit/hyperactivity disorder over time.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is an increasingly commonly diagnosed neurodevelopmental condition. One possibility is that this reflects a genuine increase in the prevalence of ADHD due to secular environmental changes, yet this hypothesis remains untested. We therefore investigated whether the genetic and environmental variance underlying ADHD, and traits of ADHD, has changed over time. METHODS: We identified twins born from 1982 to 2008 from the Swedish Twin Registry (STR). We linked the STR with the Swedish National Patient Register and Prescribed Drug Register to identify diagnoses of ADHD and prescriptions of ADHD medication for these twins. We also utilized data collected from participants in the Child and Adolescent Twin Study in Sweden (CATSS), born from 1992 to 2008. Their parents completed a structured ADHD screening tool, which was used to measure traits of ADHD and assign broad screening diagnoses of ADHD. We used the classical twin design to test whether the degree to which variation in these measures was influenced by genetic and environmental variation changed over time. RESULTS: We included 22,678 twin pairs from the STR and 15,036 pairs from CATSS. The heritability of ADHD in the STR ranged from 66% to 86% over time, although these fluctuations were not statistically significant. We observed a modest increase in variance in ADHD traits, from 0.98 to 1.09. This was driven by small increases in the underlying genetic and environmental variance, with heritability estimated as 64%-65%. No statistically significant changes in variance in screening diagnoses were observed. CONCLUSIONS: The relative contribution of genetic and environmental factors to ADHD has remained stable over time, despite its increasing prevalence. Thus, changes in the underlying etiology of ADHD over time are unlikely to explain the increase in ADHD diagnoses.

Age-related physical health of older autistic adults in Sweden: a longitudinal, retrospective, population-based cohort study.

BACKGROUND: Research of health outcomes in older autistic adults (≥45 years) is concerningly scarce, and little is known about whether intellectual disability and sex affect the health outcomes of this population. The aim of this study was to investigate the association between autism and physical health conditions in older adults and to examine these associations by intellectual disability and sex. METHODS: We conducted a longitudinal, retrospective, population-based cohort study of the Swedish population born between Jan 1, 1932, and Dec 31, 1967, using linked data from the nationwide Total Population Register and the National Patient Register. We excluded individuals who died or emigrated before the age of 45 years, or with any chromosomal abnormalities. Follow-up started at age 45 years for all individuals, and ended at emigration, death, or Dec 31, 2013 (the latest date of available follow-up), whichever was soonest. Diagnoses of autism, intellectual disability, 39 age-related physical conditions, and five types of injury (outcomes) were obtained from the National Patient Register. For each outcome, we calculated 25-year cumulative incidence and used Cox models to estimate hazard ratios (HRs). All analyses were repeated separately by intellectual disability and sex. FINDINGS: Of 4 200 887 older adults (2 063 718 women [49·1%] and 2 137 169 men [50·9%]) in the study cohort, 5291 (0·1%) had a diagnosis of autism recorded in the National Patient Register. Older autistic adults (median follow-up 8·4 years [IQR 4·2-14·6]) had higher cumulative incidence and HRs of various physical conditions and injuries than their non-autistic counterparts (median follow-up 16·4 years [8·2-24·4]). In autistic individuals, the highest cumulative incidence was observed for bodily injuries (50·0% [95% CI 47·6-52·4]). Conditions that autistic adults were at higher risk of than were non-autistic adults included heart failure (HR 1·89 [95% CI 1·61-2·22]), cystitis (2·03 [1·66-2·49]), glucose dysregulation (2·96 [2·04-4·29]), iron deficiency anaemia (3·12 [2·65-3·68]), poisoning (4·63 [4·13-5·18]), and self-harm (7·08 [6·24-8·03]). These increased risks mainly persisted regardless of intellectual disability or sex. INTERPRETATION: Our data indicate that older autistic adults are at substantially increased risk of age-related physical conditions and injuries compared with non-autistic adults. These findings highlight the need for collaborative efforts from researchers, health services, and policy makers to provide older autistic individuals with the necessary support to attain healthy longevity and a high quality of life. FUNDING: Swedish Research Council, Servier Affaires Medicales. TRANSLATION: For the Swedish translation of the abstract see Supplementary Materials section.

Morbidity hotspot surveillance: A novel approach to detect lymphatic filariasis transmission in non-endemic areas of the Tillabéry region of Niger.

The Niger Lymphatic Filariasis (LF) Programme is making good progress towards the elimination goal and scaling up morbidity management and disability prevention (MMDP) activities. Clinical case mapping and the increased availability of services has prompted patients to come forward in both endemic and non-endemic districts. The latter included Filingué, Baleyara and Abala districts of the Tillabéry region, and in 2019, 315 patients were found during a follow-up active case finding activity, suggesting it may have low transmission. The aim of this study was to assess the endemicity status in areas reporting clinical cases, 'morbidity hotspots', in three non-endemic districts of the Tillabéry region. A cross-sectional survey was conducted in 12 villages in June 2021. Filarial antigen was detected using the rapid Filariasis Test Strip (FTS) diagnostic, and information obtained on gender, age, residency length, bed net ownership and usage, and presence of hydrocoele and/or lymphoedema. Data were summarised and mapped using QGIS software. A total of 4058 participants between 5 and 105 years old were surveyed, with 29 (0.7%) participants found to be FTS positive. Baleyara district had significantly higher FTS positive rates than the other districts. No significant differences were found by gender (male 0.8%; female 0.6%), age group (<26 years 0.7%; ≥26 years 0. 7%), and residency length (<5 years 0.7%; ≥5 years 0.7%). Three villages reported no infections; seven villages <1%, one village 1.1% and one village 4.1%, which was on the border of an endemic district. Bed net ownership (99.2%) and usage (92.6%) was very high and there was no significant difference between FTS infection rates. The results indicate that there are low levels of transmission in populations, including children, living in districts previously classified as non-endemic. This has implications for the Niger LF programme in terms of delivering targeted mass drug administration (MDA) in transmission hotspots, and MMDP services, including hydrocoele surgery to patients. The use of morbidity data may be a practical proxy to trigger mapping of ongoing transmission in low endemic areas. Continued efforts to study morbidity hotspots, post-validation transmission, cross-border and cross-district endemicity are needed to meet the WHO NTD 2030 roadmap targets.

Genetic and environmental contributions to co-occurring physical health conditions in autism spectrum condition and attention-deficit/hyperactivity disorder.

BACKGROUND: Autism spectrum condition and attention-deficit/hyperactivity disorder (ADHD) are associated with a range of physical health conditions. The aim of this study was to examine the etiological components contributing to co-occurring physical health conditions in autism and ADHD. METHODS: In this nationwide Child and Adolescent Twin Study in Sweden, we analyzed data from 10,347 twin pairs aged 9 and 12. Clinical diagnoses of autism, ADHD, and physical health conditions were identified through the Swedish National Patient Register. Subclinical phenotypes of autism and ADHD were defined by symptom thresholds on a standardized parent-interview, the Autism-Tics, ADHD, and Other Comorbidities inventory. Associations between physical health conditions and autism/ADHD phenotypes were examined using generalized estimating equations. Bivariate twin models were applied to estimate the extent to which genetic and environmental risk factors accounted for physical health comorbidities. RESULTS: Similar patterns of association with physical health conditions were found in clinical and subclinical autism/ADHD, with odds ratios ranging from 1.31 for asthma in subclinical ADHD to 8.03 for epilepsy in clinical autism. The estimated genetic correlation (ra) with epilepsy was 0.50 for clinical autism and 0.35 for subclinical autism. In addition, a modest genetic correlation was estimated between clinical autism and constipation (ra = 0.31), functional diarrhea (ra = 0.27) as well as mixed gastrointestinal disorders (ra = 0.30). Genetic effects contributed 0.86 for mixed gastrointestinal disorders in clinical ADHD (ra = 0.21). Finally, subclinical ADHD shared genetic risk factors with epilepsy, constipation, and mixed gastrointestinal disorders (ra = 0.30, 0.17, and 0.17, respectively). LIMITATIONS: Importantly, since medical records from primary care were not included in the registry data used, we probably identified only more severe rather than the full range of physical health conditions. Furthermore, it needs to be considered that the higher prevalence of physical health conditions among autistic children and children with ADHD could be associated with the increased number of medical visits. CONCLUSIONS: Shared genetic effects contribute significantly to autism and ADHD phenotypes with the co-occurring physical health conditions across different organ systems, including epilepsy and gastrointestinal disorders. The shared genetic liability with co-occurring physical health conditions was present across different levels of autism and ADHD symptom severity.

Educational Outcomes in Children and Adolescents With Type 1 Diabetes and Psychiatric Disorders.

Importance: Research shows that children and adolescents with type 1 diabetes (T1D), compared with their peers without diabetes, have a greater risk of psychiatric disorders. However, no study has comprehensively examined whether having psychiatric disorders is associated with educational outcomes in children and adolescents with T1D. Objective: To investigate educational outcomes in children and adolescents with T1D with and without psychiatric disorders. Design, Setting, and Participants: This cohort study used data from multiple Swedish registers. The main study cohort included individuals born in Sweden between January 1, 1973, and December 31, 1997, who were followed up from birth through December 31, 2013. Data analyses were conducted from March 1 to June 30, 2022. Exposures: Type 1 diabetes and psychiatric disorders (including neurodevelopmental disorders, depression, anxiety disorders, eating disorders, bipolar disorder, psychotic disorder, and substance misuse) diagnosed before 16 years of age. Main Outcomes and Measures: Achieving educational milestones (completing compulsory school [primary and lower secondary education], being eligible to and finishing upper secondary school, and starting and finishing university) and compulsory school performances. Results: Of 2 454 862 individuals (51.3% male), 13 294 (0.5%; 53.9% male) were diagnosed with T1D (median [IQR] age at diagnosis, 9.5 [6.0-12.5] years), among whom 1012 (7.6%) also had at least 1 psychiatric disorder. Compared with healthy individuals (without T1D and psychiatric disorders), individuals with T1D alone had slightly lower odds of achieving the examined educational milestones. However, those with both T1D and any psychiatric disorder had much lower odds of achieving milestones, including completing compulsory school (odds ratio [OR], 0.17; 95% CI, 0.13-0.21), being eligible for (OR, 0.25; 95% CI, 0.21-0.30) and finishing (OR, 0.19; 95% CI, 0.14-0.26) upper secondary school, and starting (OR, 0.36; 95% CI, 0.29-0.46) and finishing (OR, 0.30; 95% CI, 0.20-0.47) university. They also showed lower grade point averages for compulsory school subjects. These findings remained similar in sibling comparison analyses, suggesting independence from familial confounding. Conclusions and Relevance: In this cohort study of Swedish-born children and adolescents, those with T1D alone had minor difficulties with their educational outcomes, whereas those with both T1D and psychiatric disorders had universal long-term educational underachievement. These findings highlight the importance of identifying psychiatric disorders in pediatric patients with T1D and the need for targeted educational intervention and support to minimize the education gap between the affected children and their peers.