Wildfire smoke exposure and early childhood respiratory health: a study of prescription claims data.

Wildfire smoke is associated with short-term respiratory outcomes including asthma exacerbation in children. As investigations into developmental wildfire smoke exposure on children's longer-term respiratory health are sparse, we investigated associations between developmental wildfire smoke exposure and first use of respiratory medications. Prescription claims from IBM MarketScan Commercial Claims and Encounters database were linked with wildfire smoke plume data from NASA satellites based on Metropolitan Statistical Area (MSA). A retrospective cohort of live infants (2010-2016) born into MSAs in six western states (U.S.A.), having prescription insurance, and whose birthdate was estimable from claims data was constructed (N = 184,703); of these, gestational age was estimated for 113,154 infants. The residential MSA, gestational age, and birthdate were used to estimate average weekly smoke exposure days (smoke-day) for each developmental period: three trimesters, and two sequential 12-week periods post-birth. Medications treating respiratory tract inflammation were classified using active ingredient and mode of administration into three categories:: 'upper respiratory', 'lower respiratory', 'systemic anti-inflammatory'. To evaluate associations between wildfire smoke exposure and medication usage, Cox models associating smoke-days with first observed prescription of each medication category were adjusted for infant sex, birth-season, and birthyear with a random intercept for MSA. Smoke exposure during postnatal periods was associated with earlier first use of upper respiratory medications (1-12 weeks: hazard ratio (HR) = 1.094 per 1-day increase in average weekly smoke-day, 95%CI: (1.005,1.191); 13-24 weeks: HR = 1.108, 95%CI: (1.016,1.209)). Protective associations were observed during gestational windows for both lower respiratory and systemic anti-inflammatory medications; it is possible that these associations may be a consequence of live-birth bias. These findings suggest wildfire smoke exposure during early postnatal developmental periods impact subsequent early life respiratory health.

The Burden of COVID-19 on Caregivers of Children with Suspected Genetic Conditions: A Therapeutic Odyssey.

AIMS: Children with disabilities and rare or undiagnosed conditions and their families have faced numerous hardships of living during the COVID-19 pandemic. For those with undiagnosed conditions, the diagnostic odyssey can be long, expensive, and marked by uncertainty. We, therefore, sought to understand whether and how COVID-19 impacted the trajectory of children's care. METHODS: We conducted semi-structured qualitative interviews with 25 caregivers who, prior to the pandemic, were on a diagnostic odyssey for their children. RESULTS: Most caregivers did not report any interruptions to their child's diagnostic odyssey. The greatest impact was access to therapy services, including the suspension or loss of their child's in-person therapeutic care and difficulties with virtual therapies. This therapy gap caused caregivers to fear that their children were not making progress. CONCLUSION: Although much has been written about the challenges of diagnostic odysseys for children and their families, this study illustrates the importance of expanding the focus of these studies to include therapeutic odysseys. Because therapeutic odysseys continue regardless of whether diagnoses are made, future research should investigate how to support caregivers through children's therapies within and outside of the COVID-19 context.

Adverse childhood experiences and depression among women in rural Pakistan.

BACKGROUND: Adverse Childhood Experiences (ACEs) are a common pathway to adult depression. This pathway is particularly important during the perinatal period when women are at an elevated risk for depression. However, this relationship has not been explored in South Asia. This study estimates the association between ACEs and women's (N = 889) depression at 36 months postpartum in rural Pakistan. METHOD: Data come from the Bachpan Cohort study. To capture ACEs, an adapted version of the ACE-International Questionnaire was used. Women's depression was measured using both major depressive episodes (MDE) and depressive symptom severity. To assess the relationship between ACEs and depression, log-Poisson models were used for MDE and linear regression models for symptom severity. RESULTS: The majority (58%) of women experienced at least one ACE domain, most commonly home violence (38.3%), followed by neglect (20.1%). Women experiencing four or more ACEs had the most pronounced elevation of symptom severity (ß = 3.90; 95% CL = 2.13, 5.67) and MDE (PR = 2.43; 95% CL = 1.37, 4.32). Symptom severity (ß = 2.88; 95% CL = 1.46, 4.31), and MDE (PR = 2.01; 95% CL = 1.27, 3.18) were greater for those experiencing community violence or family distress (ß = 2.04; 95%; CL = 0.83, 3.25) (PR = 1.77; 95% CL = 1.12, 2.79). CONCLUSIONS: Findings suggest that ACEs are substantively distinct and have unique relationships to depression. They signal a need to address women's ACEs as part of perinatal mental health interventions and highlight women's lifelong experiences as important factors to understanding current mental health. TRIAL REGISTRATION: NCT02111915 . Registered 11 April 2014. NCT02658994 . Registered 22 January 2016. Both trials were prospectively registered.

Maternal adverse childhood experiences on child growth and development in rural Pakistan: An observational cohort study.

Maternal adverse childhood experiences (ACEs) have significant impacts on the next generation with links to negative birth outcomes, impaired cognitive development, and increased socioemotional problems in children. However, not all types or levels of adversity are similarly deleterious and research from diverse contexts is needed to better understand why and how intergenerational transmission of adversity occurs. We examined the role of maternal ACEs on children's growth, cognitive, and socioemotional development at 36 months postpartum in rural Pakistan. We used data from 877 mother-child dyads in the Bachpan Cohort, a birth cohort study. Maternal ACEs were captured using an adapted version of the ACE-International Questionnaire. Outcomes at 36 months of age included child growth using the WHO growth z-scores, fine motor and receptive language development assessed with the Bayley Scales of Infant and Toddler Development, and socioemotional and behavioral development measured with the Ages and Stages Questionnaire: Socioemotional and Strengths and Difficulties Questionnaire. To estimate the associations between maternal ACEs and child outcomes, we used multivariable generalized linear models with inverse probability weights to account for sampling and loss to follow-up. Over half of mothers in our sample (58%) experienced at least one ACE. Emotional abuse, physical abuse, and emotional neglect were the most commonly reported ACEs. We found null relationships between the number of maternal ACEs and child growth. Maternal ACEs were associated with higher fine motor and receptive language development and worse socioemotional and behavioral outcomes. Maternal ACE domains had similarly varying relationships with child outcomes. Our findings highlight the complexity of intergenerational associations between maternal ACEs and children's growth and development. Further work is necessary to examine these relationships across cultural contexts and identify moderating factors to mitigate potential negative intergenerational effects.

Strengthening Causal Inference in Exposomics Research: Application of Genetic Data and Methods.

Advances in technologies to measure a broad set of exposures have led to a range of exposome research efforts. Yet, these efforts have insufficiently integrated methods that incorporate genetic data to strengthen causal inference, despite evidence that many exposome-associated phenotypes are heritable. Objective: We demonstrate how integration of methods and study designs that incorporate genetic data can strengthen causal inference in exposomics research by helping address six challenges: reverse causation and unmeasured confounding, comprehensive examination of phenotypic effects, low efficiency, replication, multilevel data integration, and characterization of tissue-specific effects. Examples are drawn from studies of biomarkers and health behaviors, exposure domains where the causal inference methods we describe are most often applied. Discussion: Technological, computational, and statistical advances in genotyping, imputation, and analysis, combined with broad data sharing and cross-study collaborations, offer multiple opportunities to strengthen causal inference in exposomics research. Full application of these opportunities will require an expanded understanding of genetic variants that predict exposome phenotypes as well as an appreciation that the utility of genetic variants for causal inference will vary by exposure and may depend on large sample sizes. However, several of these challenges can be addressed through international scientific collaborations that prioritize data sharing. Ultimately, we anticipate that efforts to better integrate methods that incorporate genetic data will extend the reach of exposomics research by helping address the challenges of comprehensively measuring the exposome and its health effects across studies, the life course, and in varied contexts and diverse populations. https://doi.org/10.1289/EHP9098.

Use and disparities in parathyroidectomy for symptomatic primary hyperparathyroidism in the Medicare population.

BACKGROUND: Few studies assess use of parathyroidectomy among older adults with symptomatic primary hyperparathyroidism. Our objective was to determine national usage and disparities in parathyroidectomy for symptomatic primary hyperparathyroidism among insured older adults. METHODS: We identified older adult patients with symptomatic primary hyperparathyroidism using Medicare claims (2006-2017). Primary study variables were race/ethnicity, rurality, and zip-code socioeconomic status. We calculated cumulative incidence of parathyroidectomy and used multivariable Cox proportional hazards regression models to assess the adjusted association of our study variables with parathyroidectomy. RESULTS: We included 94,803 patients. The median age at primary hyperparathyroidism diagnosis was 76 years (interquartile range 71-82). The majority of patients were female (72%), non-Hispanic White (82%), from metropolitan areas (82%), and had a Charlson Comorbidity score ≥3 (62%). Nine percent of patients (n = 8,251) underwent parathyroidectomy during follow-up. After adjustment, non-Hispanic Black patients, compared to non-Hispanic White (hazard ratio 0.80; 95% confidence interval 0.74, 0.87), and living in a low socioeconomic status neighborhood (low socioeconomic status vs highest socioeconomic status hazard ratio 0.89; 95% confidence interval 0.83, 0.95) were both associated with lower incidences of parathyroidectomy. Patients from non-metropolitan areas were more likely to undergo parathyroidectomy. CONCLUSION: Parathyroidectomy is underused for symptomatic primary hyperparathyroidism in older adults. Quality improvement efforts, rooted in equitable care, should be undertaken to increase access to parathyroidectomy for this disease.

Evaluating the clinical utility of early exome sequencing in diverse pediatric outpatient populations in the North Carolina Clinical Genomic Evaluation of Next-generation Exome Sequencing (NCGENES) 2 study: a randomized controlled trial.

BACKGROUND: Exome sequencing (ES) has probable utility for shortening the diagnostic odyssey of children with suspected genetic disorders. This report describes the design and methods of a study evaluating the potential of ES as a routine clinical tool for pediatric patients who have suspected genetic conditions and who are in the early stages of the diagnostic odyssey. METHODS: The North Carolina Clinical Genomic Evaluation by Next-generation Exome Sequencing (NCGENES) 2 study is an interdisciplinary, multi-site Phase III randomized controlled trial of two interventions: educational pre-visit preparation (PVP) and offer of first-line ES. In this full-factorial design, parent-child dyads are randomly assigned to one of four study arms (PVP + usual care, ES + usual care, PVP + ES + usual care, or usual care alone) in equal proportions. Participants are recruited from Pediatric Genetics or Neurology outpatient clinics in three North Carolina healthcare facilities. Eligible pediatric participants are < 16 years old and have a first visit to a participating clinic, a suspected genetic condition, and an eligible parent/guardian to attend the clinic visit and complete study measures. The study oversamples participants from underserved and under-represented populations. Participants assigned to the PVP arms receive an educational booklet and question prompt list before clinical interactions. Randomization to offer of first-line ES is revealed after a child's clinic visit. Parents complete measures at baseline, pre-clinic, post-clinic, and two follow-up timepoints. Study clinicians provide phenotypic data and complete measures after the clinic visit and after returning results. Reportable study-related research ES results are confirmed in a CLIA-certified clinical laboratory. Results are disclosed to the parent by the clinical team. A community consultation team contributed to the development of study materials and study implementation methods and remains engaged in the project. DISCUSSION: NCGENES 2 will contribute valuable knowledge concerning technical, clinical, psychosocial, and health economic issues associated with using early diagnostic ES to shorten the diagnostic odyssey of pediatric patients with likely genetic conditions. Results will inform efforts to engage diverse populations in genomic medicine research and generate evidence that can inform policy, practice, and future research related to the utility of first-line diagnostic ES in health care. TRIAL REGISTRATION: ClinicalTrials.gov NCT03548779 . Registered on June 07, 2018.

Engaging community stakeholders in research on best practices for clinical genomic sequencing.

Aim: Maximizing the utility and equity of genomic sequencing integration in clinical care requires engaging patients, their families, and communities. The NCGENES 2 study explores the impact of engagement between clinicians and caregivers of children with undiagnosed conditions in the context of a diagnostic genomic sequencing study. Methods: A Community Consult Team (CCT) of diverse parents and advocates for children with genetic and/or neurodevelopmental conditions was formed. Results: Early and consistent engagement with the CCT resulted in adaptations to study protocol and materials relevant to this unique study population. Discussion: This study demonstrates valuable contributions of community stakeholders to inform the implementation of translational genomics research for diverse participants.