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This study assessed the relationship between the medical home and use of health services among children with autism spectrum disorder (ASD). Data from 2016 to 2018 National Survey of Children's Health was analyzed. Outcome measures were receipt of mental and non-mental specialty care, difficulty receiving needed mental and non-mental specialty care and unmet need for mental care. Having a medical home was associated with significantly lower odds of having unmet mental health need for children with ASD ages 11-17 (OR 0.14, 95% CI 0.07-0.30) but not for those ages 3-10 (OR 0.54, 95% CI 0.21-1.43). Having a medical home was also associated with lower odds of difficulty getting needed mental health care (OR 0.38, 95% CI 0.22-0.66) as well as non-mental specialty care (OR 0.24, 95% CI 0.13-0.44).

This study assessed the relationship between the medical home and use of health services among children with autism spectrum disorder (ASD). Data from 2016 to 2018 National Survey of Children's Health was analyzed. Outcome measures were receipt of mental and non-mental specialty care, difficulty receiving needed mental and non-mental specialty care and unmet need for mental care. Having a medical home was associated with significantly lower odds of having unmet mental health need for children with ASD ages 11-17 (OR 0.14, 95% CI 0.07-0.30) but not for those ages 3-10 (OR 0.54, 95% CI 0.21-1.43). Having a medical home was also associated with lower odds of difficulty getting needed mental health care (OR 0.38, 95% CI 0.22-0.66) as well as non-mental specialty care (OR 0.24, 95% CI 0.13-0.44)., Author(s): Tobechukwu H. Ezeh [sup.1] , Brian K. Lee [sup.1] , Jessica E. Rast [sup.2] Author Affiliations: (1) grid.166341.7, 0000 0001 2181 3113, Dornsife School of Public Health, Drexel University, [...]

Background Intrahepatic cholestasis of pregnancy (ICP) is the most common obstetric liver disorder and is associated with an increased risk of iatrogenic preterm birth and adverse infant outcomes. Hence, there are several plausible pathways through which ICP could affect offspring neurodevelopment. However, to the best of our knowledge, no studies have investigated these associations. Thus, we aimed to determine whether ICP is associated with offspring neurodevelopmental conditions. Methods and findings In this Swedish register-based cohort study, we included singleton non-adopted children born in Sweden between the 1st of January 1987 and the 31st of December 2010, who were resident in Sweden >5 years, with no missing covariate information, which we followed until the 31st of December 2016. Maternal ICP diagnosis and the date of the initial diagnosis during pregnancy were obtained from the National Patient Register. Offspring diagnoses of attention deficit/hyperactivity disorder (ADHD), autism, or intellectual disability were obtained from the National Patient Register, and the dispensation of ADHD medications were obtained from the Prescribed Drug Register. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression while controlling for observed confounders and unobserved confounders shared among full siblings and maternal full cousins. A total of 2,375,856 children were included in the study; 81.6% of them were of Nordic origin, and 51.4% were male. Of these, 10,378 (0.44%) were exposed to ICP. During a median of 18 years follow-up (interquartile range 11 to 24), 143,746 (6.05%) of children were diagnosed with a neurodevelopmental condition. After adjusting for child's sex, birth year, birth month, maternal age, highest parental education level, maternal birth country, birth order, maternal psychiatric history, ICP was associated with increased odds of offspring neurodevelopmental conditions (OR 1.22, 95% CI 1.13 to 1.31), particularly among those exposed to early-onset ICP (OR 2.38, 95% CI 1.71 to 3.30) as compared to ICP diagnosed after reaching term ([greater than or equal to]37 weeks of gestation) (OR 1.08, 95% CI 0.97 to 1.20). The findings of early-onset ICP were consistent in family-based analyses. Within-family comparisons of full maternal cousins yielded an OR of 2.99 (95% CI 1.48 to 6.04), and comparisons of full siblings showed an OR of 1.92 (95% CI 0.92 to 4.02), though the latter was less precise. The findings were consistent across specific neurodevelopmental conditions and different analytical approaches. The primary limitations of this study included its observational design, the absence of data on ICP therapeutics, and the lack of bile acid measures. Conclusions In this study, we observed that exposure to ICP during gestation is associated with an increased likelihood of neurodevelopmental conditions in offspring, particularly in cases of early-onset ICP. Further studies are warranted to better understand the role of early-ICP in offspring neurodevelopment., Author(s): Shuyun Chen 1,*, Viktor H. Ahlqvist 1,*, Hugo Sjöqvist 1, Olof Stephansson 2,3, Cecilia Magnusson 1,4, Christina Dalman 1,4, Håkan Karlsson 5, Brian K. Lee 1,6,7, Renee M. Gardner [...]

Key Points: Question: Does acetaminophen use during pregnancy increase children's risk of neurodevelopmental disorders? Findings: In this population-based study, models without sibling controls identified marginally increased risks of autism and attention-deficit/hyperactivity disorder (ADHD) associated with acetaminophen use during pregnancy. However, analyses of matched full sibling pairs found no evidence of increased risk of autism (hazard ratio, 0.98), ADHD (hazard ratio, 0.98), or intellectual disability (hazard ratio, 1.01) associated with acetaminophen use. Meaning: Acetaminophen use during pregnancy was not associated with children's risk of autism, ADHD, or intellectual disability in sibling control analyses. This suggests that associations observed in other models may have been attributable to confounding. Importance: Several studies suggest that acetaminophen (paracetamol) use during pregnancy may increase risk of neurodevelopmental disorders in children. If true, this would have substantial implications for management of pain and fever during pregnancy. Objective: To examine the associations of acetaminophen use during pregnancy with children's risk of autism, attention-deficit/hyperactivity disorder (ADHD), and intellectual disability. Design, Setting, and Participants: This nationwide cohort study with sibling control analysis included a population-based sample of 2 480 797 children born in 1995 to 2019 in Sweden, with follow-up through December 31, 2021. Exposure: Use of acetaminophen during pregnancy prospectively recorded from antenatal and prescription records. Main Outcomes and Measures: Autism, ADHD, and intellectual disability based on International Classification of Diseases, Ninth Revision and International Classification of Diseases, Tenth Revision codes in health registers. Results: In total, 185 909 children (7.49%) were exposed to acetaminophen during pregnancy. Crude absolute risks at 10 years of age for those not exposed vs those exposed to acetaminophen were 1.33% vs 1.53% for autism, 2.46% vs 2.87% for ADHD, and 0.70% vs 0.82% for intellectual disability. In models without sibling control, ever-use vs no use of acetaminophen during pregnancy was associated with marginally increased risk of autism (hazard ratio [HR], 1.05 [95% CI, 1.02-1.08]; risk difference [RD] at 10 years of age, 0.09% [95% CI, −0.01% to 0.20%]), ADHD (HR, 1.07 [95% CI, 1.05-1.10]; RD, 0.21% [95% CI, 0.08%-0.34%]), and intellectual disability (HR, 1.05 [95% CI, 1.00-1.10]; RD, 0.04% [95% CI, −0.04% to 0.12%]). To address unobserved confounding, matched full sibling pairs were also analyzed. Sibling control analyses found no evidence that acetaminophen use during pregnancy was associated with autism (HR, 0.98 [95% CI, 0.93-1.04]; RD, 0.02% [95% CI, −0.14% to 0.18%]), ADHD (HR, 0.98 [95% CI, 0.94-1.02]; RD, −0.02% [95% CI, −0.21% to 0.15%]), or intellectual disability (HR, 1.01 [95% CI, 0.92-1.10]; RD, 0% [95% CI, −0.10% to 0.13%]). Similarly, there was no evidence of a dose-response pattern in sibling control analyses. For example, for autism, compared with no use of acetaminophen, persons with low (<25th percentile), medium (25th-75th percentile), and high (>75th percentile) mean daily acetaminophen use had HRs of 0.85, 0.96, and 0.88, respectively. Conclusions and Relevance: Acetaminophen use during pregnancy was not associated with children's risk of autism, ADHD, or intellectual disability in sibling control analysis. This suggests that associations observed in other models may have been attributable to familial confounding. This nationwide cohort study with sibling control analysis examines the association of acetaminophen use during pregnancy with children's risk of autism, ADHD, and intellectual disability. [ABSTRACT FROM AUTHOR]

Background Psychiatric comorbidities are common in patients with epilepsy. Reasons for the co-occurrence of psychiatric conditions and epilepsy remain poorly understood. Aim We aimed to triangulate the relationship between epilepsy and psychiatric conditions to determine the extent and possible origins of these conditions. Methods Using nationwide Swedish health registries, we quantified the lifetime prevalence of psychiatric disorders in patients with epilepsy. We then used summary data from genome-wide association studies to investigate whether the identified observational associations could be attributed to a shared underlying genetic aetiology using cross-trait linkage disequilibrium score regression. Finally, we assessed the potential bidirectional relationships using two-sample Mendelian randomisation. Results In a cohort of 7 628 495 individuals, we found that almost half of the 94 435 individuals diagnosed with epilepsy were also diagnosed with a psychiatric condition in their lifetime (adjusted lifetime prevalence, 44.09%; 95% confidence interval (CI) 43.78% to 44.39%). We found evidence for a genetic correlation between epilepsy and some neurodevelopmental and psychiatric conditions. For example, we observed a genetic correlation between epilepsy and attention-deficit/hyperactivity disorder (rg=0.18, 95% CI 0.09 to 0.27, p<0.001)--a correlation that was more pronounced in focal epilepsy (rg=0.23, 95% CI 0.09 to 0.36, p<0.001). Findings from Mendelian randomisation using common genetic variants did not support bidirectional effects between epilepsy and neurodevelopmental or psychiatric conditions. Conclusions Psychiatric comorbidities are common in patients with epilepsy. Genetic correlations may partially explain some comorbidities; however, there is little evidence of a bidirectional relationship between the genetic liability of epilepsy and psychiatric conditions. These findings highlight the need to understand the role of environmental factors or rare genetic variations in the origins of psychiatric comorbidities in epilepsy. [ABSTRACT FROM AUTHOR]

Objective: To examine antiseizure medication (ASM) prescription during pregnancy. Design: Population‐based drug utilisation study. Setting: UK primary and secondary care data, 1995–2018, from the Clinical Practice Research Datalink GOLD version. Population or Sample: 752 112 completed pregnancies among women registered for a minimum of 12 months with an 'up to standard' general practice prior to the estimated start of pregnancy and for the duration of their pregnancy. Methods: We described ASM prescription across the study period, overall and by ASM indication, examined patterns of prescription during pregnancy including continuous prescription and discontinuation, and used logistic regression to investigate factors associated with those ASM prescription patterns. Main Outcome Measures: Prescription of ASMs during pregnancy and discontinuation of ASMs before and during pregnancy. Results: ASM prescription during pregnancy increased from 0.6% of pregnancies in 1995 to 1.6% in 2018, driven largely by an increase in women with indications other than epilepsy. Epilepsy was an indication for 62.5% of pregnancies with an ASM prescription and non‐epilepsy indications were present for 66.6%. Continuous prescription of ASMs during pregnancy was more common in women with epilepsy (64.3%) than in women with other indications (25.3%). Switching ASMs was infrequent (0.8% of ASM users). Factors associated with discontinuation included age ≥35, higher social deprivation, more frequent contact with the GP and being prescribed antidepressants or antipsychotics. Conclusions: ASM prescription during pregnancy increased between 1995 and 2018 in the UK. Patterns of prescription around the pregnancy period vary by indication and are associated with several maternal characteristics. [ABSTRACT FROM AUTHOR]

While the concept of big data has emerged over the past decade as a hot topic in nearly all areas of scientific inquiry, it has rarely been discussed in the context of autism research. In this commentary we describe aspects of big data that are relevant to autism research and methodological issues such as confounding and data error that can hamper scientific investigation. Although big data studies can have transformative impact, bigger is not always better, and big data require the same methodological considerations and interdisciplinary collaboration as "small data" to extract useful scientific insight. Lay Summary: This commentary explains how big data can be used in autism research and the challenges that come with it, like confounding factors and data errors. Eventhough big data can have a big impact, it is not always better. Big data needs to be handled carefully and with collaboration from different fields to get the most out of it. [ABSTRACT FROM AUTHOR]

Mapping molecular structure to odor perception is a key challenge in olfaction. We used graph neural networks to generate a principal odor map (POM) that preserves perceptual relationships and enables odor quality prediction for previously uncharacterized odorants. The model was as reliable as a human in describing odor quality: On a prospective validation set of 400 out-of-sample odorants, the model-generated odor profile more closely matched the trained panel mean than did the median panelist. By applying simple, interpretable, theoretically rooted transformations, the POM outperformed chemoinformatic models on several other odor prediction tasks, indicating that the POM successfully encoded a generalized map of structure-odor relationships. This approach broadly enables odor prediction and paves the way toward digitizing odors. [ABSTRACT FROM AUTHOR]

Immunoglobulin A nephropathy (IgAN) is the commonest glomerulonephritis worldwide, a category that represents the third most frequent cause of end-stage kidney disease (ESKD) in the United States. Kidney transplantation remains the optimal treatment of ESKD, and yet the prospects of IgAN recurrence post-transplant dampens the enthusiasm for living kidney donation in some instances, in addition to limiting the longevity of the kidney allograft. Moreover, the lack of a standardized method for detecting IgAN recurrence, since not all centers perform protocol allograft biopsies, has led to an underestimation of the extent of the issue. The pathogenesis of de novo IgAN remains conjectural, let alone the pathways for recurrent disease, but is increasingly recognized as a multi-hit injury mechanism. Identification of recurrent disease rests mainly on clinical symptoms and signs (e.g., hematuria, proteinuria) and could only be definitively proven with histologic evidence which is invasive and prone to sampling error. Treatment had relied mainly on nonspecific goals of proteinuria reduction, and in some cases, immunosuppression for active, crescentic disease. More recently, newer targets have the potential to widen the armamentarium for directed therapies, with more studies on the horizon. This review article provides an update on recurrent IgAN post-transplant. [ABSTRACT FROM AUTHOR]

Purpose: Estimating causal effects in observational pharmacoepidemiology is a challenging task, as it is often plagued by confounding by indication. Restricting the sample to those with an indication for drug use is a commonly performed procedure; indication‐based sampling ensures that the exposed and unexposed are exchangeable on the indication—limiting the potential for confounding by indication. However, indication‐based sampling has received little scrutiny, despite the hazards of exposure‐related covariate control. Methods: Using simulations of varying levels of confounding and applied examples we describe bias amplification under indication‐based sampling. Results: We demonstrate that indication‐based sampling in the presence of unobserved confounding can give rise to bias amplification, a self‐inflicted phenomenon where one inflates pre‐existing bias through inappropriate covariate control. Additionally, we show that indication‐based sampling generally leads to a greater net bias than alternative approaches, such as regression adjustment. Finally, we expand on how bias amplification should be reasoned about when distinct clinically relevant effects on the outcome among those with an indication exist (effect‐heterogeneity). Conclusion: We conclude that studies using indication‐based sampling should have robust justification ‐ and that it should by no means be considered unbiased to adopt such approaches. As such, we suggest that future observational studies stay wary of bias amplification when considering drug indications. [ABSTRACT FROM AUTHOR]

Context and Background: The Cardiac Neurodevelopmental Outcome Collaborative has recommended using the Depression Anxiety Stress Scale (DASS) to evaluate for depression, anxiety, and stress in parents of children with congenital heart disease (CHD). There has not been a longitudinal study investigating its utility in these parents. Aims: The aim of this study was to determine the trend of depression, anxiety, and stress in parents of patients with CHD. Methods: Our center uses this self-reported survey at every visit between 6 and 36 months of age. This was a single-centered, retrospective study from January 1, 2018, to June 1,2020. Statistical Analysis: Cox regression analysis was conducted using a composite end point of having an abnormal score in any of the three domains. Results: Two hundred and seventy-three mothers and 139 fathers were included in the study. For mothers, scores in each domain were elevated at 12 and 24 months. For fathers, scores in each domain were elevated at 6 months, followed by a decrease before peaking again, with depression increasing at 36 months and anxiety and stress increasing at 30 months. Increased length of stay for the index surgery was associated with an abnormal score for mothers (B = 0.02, P < 0.01) and fathers (B = 0.01, P = 0.04). Being in a relationship with the father (B = -0.8, P < 0.01) was associated with freedom of an abnormal score for mothers. Conclusions : Scores concerning for depression, anxiety, and stress peak at different points for parents. Length of stay for the index surgery and being in a relationship are important factors in the mental health of parents. [ABSTRACT FROM AUTHOR]

Nirmatrelvir/ritonavir was recently granted emergency use authorization for mild to moderate coronavirus disease 2019. Drug–drug interactions between ritonavir and tacrolimus are underappreciated by nontransplant providers. We describe 2 solid organ transplant recipients prescribed nirmatrelvir/ritonavir for outpatient use who developed tacrolimus toxicity requiring hospitalization and were managed with rifampin for toxicity reversal. [ABSTRACT FROM AUTHOR]

In studies of vision and audition, stimuli can be chosen to span the visible or audible spectrum; in olfaction, the axes and boundaries defining the analogous odorous space are unknown. As a result, the population of olfactory space is likewise unknown, and anecdotal estimates of 10,000 odorants have endured. The journey a molecule must take to reach olfactory receptors (ORs) and produce an odor percept suggests some chemical criteria for odorants: a molecule must 1) be volatile enough to enter the air phase, 2) be nonvolatile and hydrophilic enough to sorb into the mucous layer coating the olfactory epithelium, 3) be hydrophobic enough to enter an OR binding pocket, and 4) activate at least one OR. Here, we develop a simple and interpretable quantitative model that reliably predicts whether a molecule is odorous or odorless based solely on the first three criteria. Applying our model to a database of all possible small organic molecules, we estimate that at least 40 billion possible compounds are odorous, six orders of magnitude larger than current estimates of 10,000. With this model in hand, we can define the boundaries of olfactory space in terms of molecular volatility and hydrophobicity, enabling representative sampling of olfactory stimulus space. [ABSTRACT FROM AUTHOR]

Identifying factors associated with COVID-19 vaccination acceptance among vulnerable groups, including autistic individuals, can increase vaccination rates and support public health. The purpose of this study was to determine differences among autistic adults who reported COVID-19 vaccination acceptance from those who did not. In this study we describe COVID-19 vaccination status and self-reported preferences among autistic adults and identify related factors. Vaccine accepters were more likely to report increased loneliness during COVID-19, lived in more populous counties (p = 0.02), and lived in counties won by President Biden in the 2020 US presidential election (p < 0.001). Positive correlations were found between desire to protect others, concern about contracting COVID-19, and trusting vaccine safety (p < 0.001). Concern about vaccine safety was common among the vaccine hesitant, while lack of concern about COVID-19 overall was not. Identifying health promotion strategies based on self-reported, lived experiences about COVID-19 among vulnerable groups is key for public health impact. [ABSTRACT FROM AUTHOR]