Residential mobility of pregnant women and implications for assessment of spatially-varying environmental exposures

Nature Health studies on spatially-varying exposures (e.g., air pollution) during pregnancy often estimate exposure using residence at birth, disregarding residential mobility. We investigated moving patterns in pregnant women (n = 10,116) in linked cohorts focused on Connecticut and Massachusetts, U.S., 1988–2008. Moving patterns were assessed by race/ethnicity, age, marital status, education, working status, population density, parity, income, and season of birth. In this population, 11.6% of women moved during pregnancy. Movers were more likely to be younger, unmarried, and living in urban areas with no previous children. Among movers, multiple moves were more likely for racial/ethnic minority, younger, less educated, unmarried, and lower income women. Most moves occurred later in pregnancy, with 87.4% of first moves in the second or third trimester, although not all cohort subjects enrolled in the first few weeks of pregnancy. Distance between first and second residence had a median value of 5.2 km (interquartile range 11.3 km, average 57.8 km, range 0.0–4277 km). Women moving larger distances were more likely to be white, older, married, and work during pregnancy. Findings indicate that residential mobility may impact studies of spatially-varying exposure during pregnancy and health and that subpopulations vary in probability of moving, and timing and distance of moves

Patient Engagement Programs for Recognition and Initial Treatment of Depression in Primary Care: A Randomized Trial

ImportanceEncouraging primary care patients to address depression symptoms and care with clinicians could improve outcomes but may also result in unnecessary treatment.ObjectiveTo determine whether a depression engagement video (DEV) or a tailored interactive multimedia computer program (IMCP) improves initial depression care compared with a control without increasing unnecessary antidepressant prescribing.Design, setting, and participantsRandomized clinical trial comparing DEV, IMCP, and control among 925 adult patients treated by 135 primary care clinicians (603 patients with depression and 322 patients without depression, defined by Patient Health Questionnaire-9 [PHQ-9] score) conducted from June 2010 through March 2012 at 7 primary care clinical sites in California.InterventionsDEV targeted to sex and income, an IMCP tailored to individual patient characteristics, and a sleep hygiene video (control).Main outcomes and measuresAmong depressed patients, superiority assessment of the composite measure of patient-reported antidepressant drug recommendation, mental health referral, or both (primary outcome); depression at 12-week follow-up, measured by the PHQ-8 (secondary outcome). Among nondepressed patients, noninferiority assessment of clinician- and patient-reported antidepressant drug recommendation (primary outcomes) with a noninferiority margin of 3.5%. Analyses were cluster adjusted.ResultsOf the 925 eligible patients, 867 were included in the primary analysis (depressed, 559; nondepressed, 308). Among depressed patients, rates of achieving the primary outcome were 17.5% for DEV, 26% for IMCP, and 16.3% for control (DEV vs control, 1.1 [95% CI, -6.7 to 8.9], P = .79; IMCP vs control, 9.9 [95% CI, 1.6 to 18.2], P = .02). There were no effects on PHQ-8 measured depression score at the 12-week follow-up: DEV vs control, -0.2 (95% CI, -1.2 to 0.8); IMCP vs control,  0.9 (95% CI, -0.1 to 1.9). Among nondepressed patients, clinician-reported antidepressant prescribing in the DEV and IMCP groups was noninferior to control (mean percentage point difference [PPD]: DEV vs control, -2.2 [90% CI, -8.0 to 3.49], P = .0499 for noninferiority; IMCP vs control, -3.3 [90% CI, -9.1 to 2.4], P = .02 for noninferiority); patient-reported antidepressant recommendation did not achieve noninferiority (mean PPD: DEV vs control,  0.9 [90% CI, -4.9 to 6.7], P = .23 for noninferiority; IMCP vs control,  0.3 [90% CI, -5.1 to 5.7], P = .16 for noninferiority).Conclusions and relevanceA tailored IMCP increased clinician recommendations for antidepressant drugs, a mental health referral, or both among depressed patients but had no effect on mental health at the 12-week follow-up. The possibility that the IMCP and DEV increased patient-reported clinician recommendations for an antidepressant drug among nondepressed patients could not be excluded.Trial registrationclinicaltrials.gov Identifier: NCT01144104

Evolutionary Landscape of <i>SOX</i> Genes to Inform Genotype-to-Phenotype Relationships

The SOX transcription factor family is pivotal in controlling aspects of development. To identify genotype–phenotype relationships of SOX proteins, we performed a non-biased study of SOX using 1890 open-reading frame and 6667 amino acid sequences in combination with structural dynamics to interpret 3999 gnomAD, 485 ClinVar, 1174 Geno2MP, and 4313 COSMIC human variants. We identified, within the HMG (High Mobility Group)- box, twenty-seven amino acids with changes in multiple SOX proteins annotated to clinical pathologies. These sites were screened through Geno2MP medical phenotypes, revealing novel SOX15 R104G associated with musculature abnormality and SOX8 R159G with intellectual disability. Within gnomAD, SOX18 E137K (rs201931544), found within the HMG box of ~0.8% of Latinx individuals, is associated with seizures and neurological complications, potentially through blood–brain barrier alterations. A total of 56 highly conserved variants were found at sites outside the HMG-box, including several within the SOX2 HMG-box-flanking region with neurological associations, several in the SOX9 dimerization region associated with Campomelic Dysplasia, SOX14 K88R (rs199932938) flanking the HMG box associated with cardiovascular complications within European populations, and SOX7 A379V (rs143587868) within an SOXF conserved far C-terminal domain heterozygous in 0.716% of African individuals with associated eye phenotypes. This SOX data compilation builds a robust genotype-to-phenotype association for a gene family through more robust ortholog data integration