The biological embedding of social adversity: How adolescent housing insecurity impacts inflammation over time.

BACKGROUND & PURPOSE: Adolescent housing insecurity is a dynamic form of social adversity that impacts child health outcomes worldwide. However, the means by which adolescent housing insecurity may become biologically embedded to influence health outcomes over the life course remain unclear. Therefore, we aimed to utilize life course perspectives and advanced causal inference methods to evaluate the potential for inflammation to contribute to the biological embedding of adolescent housing insecurity. MATERIALS AND METHODS: Using prospective data from the Great Smoky Mountains Study, we investigated the relationship between adolescent housing insecurity and whole-blood spot samples assayed for C-reactive protein (CRP). Adolescent housing insecurity was created based on annual measures of frequent residential moves, reduced standard of living, forced separation from the home, and foster care. Annual measures of CRP ranged from 0.001 mg/L to 13.6 mg/L (median = 0.427 mg/L) and were log10 transformed to account for positively skewed values. We used g-estimation of structural nested mean models to estimate a series of conditional average causal effects of adolescent housing insecurity on CRP levels from ages 11 to 16 years and interpreted the results within life course frameworks of accumulation, recency, and sensitive periods. PRINCIPAL RESULTS: Of the 1,334 participants, 427 [44.3 %] were female. Based on the conditional average causal effect, one exposure to adolescent housing insecurity from ages 11 to 16 years led to a 6.4 % (95 % CI = 0.69 - 12.4) increase in later CRP levels. Exposure at 14 years of age led to a 27.9 % increase in CRP levels at age 15 (95 % CI = 6.5 - 53.5). Recent exposures to adolescent housing insecurity (<3 years) suggested stronger associations with CRP levels than distant exposures (>3 years), but limited statistical power prevented causal conclusions regarding recency effects at the risk of a Type II Error. MAJOR CONCLUSIONS: These findings highlight inflammation-as indicated by increased CRP levels-as one potential mechanism for the biological embedding of adolescent housing insecurity. The results also suggest that adolescent housing insecurity-particularly recent, repeated, and mid-adolescent exposures-may increase the risk of poor health outcomes and should be considered a key intervention target.

Comparing two measures of neighborhood quality and internalizing and externalizing behaviors in the adolescent brain cognitive development study.

PURPOSE: There is widespread recognition of the importance and complexity of measuring neighborhood contexts within research on child psychopathology. In this study, we assessed the cross-sectional associations between two measures of neighborhood quality and internalizing and externalizing behaviors in preadolescence. METHODS: Drawing on baseline data from the Adolescent Brain Cognitive Development Study (n = 10,577 preadolescents), we examined two multi-component assessments of neighborhood quality in relation to children's internalizing and externalizing symptoms: the Area Deprivation Index (ADI), which measures socioeconomic adversity, and the Child Opportunity Index 2.0 (COI), which measures economic, educational, and environmental opportunity. Both measures were categorized into quintiles. We then used mixed-effects linear regression models to examine bivariate and adjusted associations. RESULTS: The bivariate associations displayed strong inverse associations between the COI and ADI and externalizing symptoms, with a graded pattern of fewer externalizing behaviors with increasing neighborhood quality. Only the ADI was associated with externalizing behaviors in models adjusted for child and family characteristics. We did not observe a clear association between either measure of neighborhood quality and internalizing behaviors in bivariate or adjusted models. CONCLUSIONS: Neighborhood quality, as measured by the COI and ADI, was associated with externalizing behaviors in preadolescent children. The association using the ADI persisted after adjustment for family-level characteristics, including financial strain. Our results indicate that different assessments of neighborhood quality display distinct associations with preadolescent behavioral health. Future research is needed to assess the association between neighborhood quality and behavior trajectories and to identify place-based intervention strategies.

Culturally Tailored Anti-Smoking Messages: A Randomized Trial With U.S. Sexual Minority Young Women.

INTRODUCTION: This study evaluated effects of exposure to culturally tailored anti-smoking ads versus control ads on quitting intentions, cigarette purchase intentions, and tobacco industry perceptions among young adult, cisgender and transgender, sexual minority women (SMW). STUDY DESIGN: An online randomized controlled experiment with 1-month longitudinal follow-up was conducted. SETTING AND PARTICIPANTS: About 2,214 U.S. SMW ages 18-30 were recruited via online survey panels (The PRIDE Study and Prolific), social media ads and posts, and HER dating app ads. Data were collected in 2021-2022. INTERVENTION: Participants were randomly assigned to receive up to 20 tailored ads containing LGBTQ+ branding versus 20 control ads without LGBTQ+ branding over 4 weeks. Both conditions used identical anti-smoking statements and photographs (including several photographs of individuals who self-identified as SMW). MAIN OUTCOME MEASURES: One-month follow-up intention to purchase cigarettes, intention to quit, marketing receptivity, pro-industry attitudes, and pro-industry beliefs were measured. Analyses were conducted in 2022-2023. Linear regression models predicted outcomes at 1-month follow-up with the randomized arm, adjusted for baseline measures of each outcome and stratified by smoking status (those who currently smoked and those who did not smoke). RESULTS: Among those who smoked, follow-up intention to quit increased and intention to purchase cigarettes, marketing receptivity, pro-industry attitudes, and pro-industry beliefs decreased versus baseline in both arms. Follow-up pro-industry beliefs were significantly lower (B=-0.331, 95% CI -0.652, -0.010, p=0.043) in the tailored versus control arm, adjusted for baseline beliefs. Among those who did not smoke, marketing receptivity, pro-industry attitudes, and pro-industry beliefs decreased versus baseline in both arms. Follow-up outcomes did not differ significantly between arms. CONCLUSIONS: These findings can inform future anti-smoking campaign development to reduce cigarette smoking-related disparities among young adult, cisgender and transgender, sexual minority women and serve as the basis for developing similar ads for other LGBTQ+ audiences. TRIAL REGISTRATION: This study was registered in ClinicalTrials.gov (NCT04812795).

Prospective Associations of Childhood Housing Insecurity With Anxiety and Depression Symptoms During Childhood and Adulthood.

Importance: Childhood housing insecurity has dramatically increased in the US in recent decades, but whether an association with adverse mental health outcomes exists after adjusting for repeated measures of childhood poverty is unclear. Objective: To test whether childhood housing insecurity is associated with later anxiety and depression symptoms after adjusting for time-varying measures of childhood poverty. Design, Setting, and Participants: This prospective cohort study included individuals aged 9, 11, and 13 years at baseline from the Great Smoky Mountains Study in western North Carolina. Participants were assessed up to 11 times from January 1993 to December 2015. Data were analyzed from October 2021 to October 2022. Exposure: Participants and their parents reported social factors annually when participants were 9 to 16 years of age. A comprehensive measure of childhood housing insecurity was constructed based on frequent residential moves, reduced standard of living, forced separation from home, and foster care status. Main Outcomes and Measures: Between ages 9 and 16 years, the Child and Adolescent Psychiatric Assessment was used up to 7 times to evaluate childhood anxiety and depression symptoms. Adult anxiety and depression symptoms were assessed at ages 19, 21, 26, and 30 years using the Young Adult Psychiatric Assessment. Results: Of the 1339 participants (mean [SD] age, 11.3 [1.63] years), 739 (55.2%; 51.1% weighted) were male; 1203 individuals assessed up to 30 years of age were included in the adulthood outcome analyses. Standardized mean (SD) baseline anxiety and depression symptom scores were higher among children who experienced housing insecurity than among those who never experienced housing insecurity (anxiety: 0.49 [1.15] vs 0.22 [1.02]; depression: 0.20 [1.08] vs -0.06 [0.82]). Individuals who experienced childhood housing insecurity had higher anxiety symptom scores (fixed effects: standardized mean difference [SMD], 0.21; 95% CI, 0.12-0.30; random effects: SMD, 0.25; 95% CI, 0.15-0.35) and higher depression symptom scores (fixed effects: SMD, 0.18; 95% CI, 0.09-0.28; random effects: SMD, 0.26; 95% CI, 0.14-0.37) during childhood. In adulthood, childhood housing insecurity was associated with higher depression symptom scores (SMD, 0.11; 95% CI, 0.00-0.21). Conclusions and Relevance: In this cohort study, housing insecurity was associated with anxiety and depression during childhood and with depression during adulthood. Because housing insecurity is a modifiable, policy-relevant factor associated with psychopathology, these results suggest that social policies that support secure housing may be an important prevention strategy.

Evictions and Infant and Child Health Outcomes: A Systematic Review.

Importance: Millions of rental evictions occur in the United States each year, disproportionately affecting households with children. Increasing attention has been paid to the impact of evictions on child health outcomes. Objective: To synthesize and assess studies examining the associations of eviction exposure with infant and child health outcomes. Evidence Review: For this systematic review without meta-analysis, a database search was performed using PubMed, Web of Science, and PsycINFO, through September 25, 2022. Included studies were peer-reviewed quantitative studies examining an association between exposure to eviction and at least 1 health outcome, both before age 18 years, including prenatal exposures and perinatal outcomes. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Data were analyzed from March 3 to December 7, 2022. Findings: Database searches identified 266 studies, and 11 studies met inclusion criteria. Six studies examined associations between prenatal eviction and birth outcomes, such as gestational age, and each found that eviction was significantly associated with at least 1 adverse birth outcome. Five studies investigated other childhood outcomes, including neuropsychological test scores, parent-rated child health, lead testing rates, and body mass index, and among these 5 studies, 4 reported an association between eviction and adverse child health outcomes. Direct experience of eviction or residence in a neighborhood with more evictions was associated with adverse perinatal outcomes in 6 studies, higher neurodevelopmental risk in 2 studies, worse parent-rated child health in 2 studies, and less lead testing in 1 study. Study designs and methods were largely robust. Conclusions and Relevance: In this systematic review without meta-analysis of the association between evictions and child health outcomes, evidence demonstrated the deleterious associations of eviction with a range of developmental periods and domains. In the context of a rental housing affordability crisis, ongoing racial disparities in evictions, and continuing harm to millions of families, health care practitioners and policy makers have an integral role to play in supporting safe, stable housing for all.

Parent-child separation and cardiometabolic outcomes and risk factors in adulthood: A systematic review.

BACKGROUND: Parent-child separation has been associated with negative mental health across childhood and adulthood, yet little is known about the long-term impacts for cardiovascular health. This systematic review synthesized and evaluated the quality of the literature examining the association between exposures to parent-child separation and cardiometabolic outcomes in adulthood. METHODS: Following a registered protocol, online databases (Pubmed, PsycInfo, and Web of Science) were searched for relevant studies. Studies were included if they (a) defined the exposure before age 18 as institutionalization, foster care placement, parental incarceration, separation due to parents migrating for economic reasons, or asylum and war; and (b) quantified the association between parent-child separation and cardiometabolic events and diagnoses (e.g., coronary heart disease, diabetes) and risk factors (e.g., body mass index, fat distribution, serum-based metabolic markers, inflammatory markers in adulthood (≥ age 18). Studies lacking an unexposed comparison group were excluded. The risk for bias in each study was assessed with a modified Newcastle-Ottawa Scale. RESULTS: Of the 1938 studies identified, 13 met our inclusion criteria. Two of the four studies examining associations between parent-child separation and cardiometabolic events and diagnoses found positive associations with coronary heart disease and diabetes. Amongst the 13 studies examining associations with any type of adult cardiometabolic risk factors, eight studies reported at least one positive association. Sub-analyses considering separate reasons for parent-child separation provided clearer insights: War evacuation was associated with hypertension and high blood pressure across four studies from the same cohort; out-of home care experiences largely evidenced null results across five different studies, and two studies on parental incarceration suggested positive associations with elevated inflammation, BMI and blood pressure. CONCLUSIONS: The connections between parent-child separation and adult cardiometabolic outcomes and risk factors are currently inconsistent. The results may depend on the reason for separation, age of assessment, analytic differences and other psychosocial variables that are often unmeasured in this literature.

Longitudinal patterns of childhood homelessness and early adolescent trajectories of internalising and externalising behaviour.

BACKGROUND: Child homelessness has been associated with elevated mental health problems during early adolescence, a period of onset for psychiatric problems. Prior literature has relied on cross-sectional studies, limiting the understanding of temporality and trajectories of psychopathology. We extend prior literature by examining associations between child homelessness and internalising and externalising symptom trajectories in early adolescence, with consideration of timing and persistence of homelessness. METHODS: Using population-based longitudinal data from the Avon Longitudinal Study of Parents and Children, we used multilevel models to examine the effects of homelessness prior to age 9, the timing of homelessness (eg, early vs middle childhood) and cumulative exposure to homelessness on internalising and externalising trajectories across ages <0-9 years. We also tested for sex differences in these associations. RESULTS: Of the 8391 participants, 5.5% reported exposure to homelessness at least once before age 9. Children who experienced homelessness had elevated internalising and externalising symptoms compared with their consistently housed peers, with excess risk evident among children who first experienced homelessness in middle childhood (relative to early childhood) and children who experienced recurrent homelessness. We did not observe changes in symptom trajectories over the course of 4 years. Men who experienced homelessness displayed a more pronounced risk of internalising symptoms relative to women and men who did not experience homelessness. CONCLUSION: Childhood homelessness is associated with persistently elevated internalising and externalising symptoms across early adolescence compared with their consistently housed peers. Interventions and policies to address family homelessness may lead to better mental health among adolescents.

Covariate Selection from Data Collection Onwards: A Methodology for Neurosurgeons.

It is essential for any epidemiologic and clinical investigation to determine the appropriate covariates for which to ascertain measures and subsequently model. A number of recent articles have sought to elucidate covariate selection in the context of data analysis. Unfortunately, few articles characterize covariate selection in the context of data collection and discuss their principles under the assumption that data are measured and available for analyses. Additionally, many articles delineating the appropriate principles use jargon that may be inaccessible to the audiences that need to understand them most. Considering these gaps, this paper first seeks to put forth a simple foundational guide to primary data collection by explaining four sets of covariates for which to ascertain measures: 1) all covariates that cause both the exposure and outcome; 2) selected covariates that cause the exposure; 3) selected covariates that cause the outcome; and 4) relevant sociodemographic and baseline covariates. To the extent possible, this paper attempts to communicate these principles clearly and in the absence of advanced causal inference terminology. Finally, this paper provides a conceptual framework for covariate inclusion and exclusion with respect to data analysis and regression modeling. Specifically, this framework suggests that regression models 1) include all known common cause covariates; 2) include all sociodemographic covariates; 3) exclude any covariate that is known to be both a consequence of the exposure and cause of the outcome; and 4) generally, for every term included in the statistical model, there should be at least 10 observations in the data set.

Treatment of Refractory Anemia with Ring Sideroblasts Associated with Marked Thrombocytosis with Lenalidomide in a Patient Testing Negative for 5q Deletion and JAK2 V617F and MPL W515K/L Mutations.

Refractory anemia with ring sideroblasts associated with marked thrombocytosis (RARS-T) is a hematologic malignancy that often results in transfusion dependency and a hypercoagulable state. This rare disease currently lacks formal guidelines for treatment; however, various case reports have demonstrated efficacy in the use of lenalidomide. This immunomodulatory drug has shown promise in patients with 5q deletions, with reports of achieving transfusion independence and normalization of platelet counts. Herein we present the case of a 68-year-old African American woman with RARS-T who tested negative for 5q deletion and JAK2 V617F and MPL W515K/L mutations. Her treatment with lenalidomide therapy resulted in a five-year durable complete clinical response.

Prognostic value of complete remission with superior platelet counts in acute myeloid leukemia.

BACKGROUND: Complete remission (CR) in acute myeloid leukemia (AML) is defined as having ≤5% leukemic blast cells in the bone marrow and return of normal hematopoiesis after the first induction cycle. There is a subset of patients, however, who achieve reduction of leukemic blast cells with a subnormal platelet count, designated as CR with incomplete platelet recovery (platelet count, ≤100,000/mcL; normal, 150,000-450,000/mcL), which is associated with inferior outcomes when compared with CR. Furthermore, there is another subset of patients with CR but superior platelet counts (≥400,000/mcL) whose prognostic significance is unclear. OBJECTIVE: To establish whether CR with superior platelet counts is associated with better outcomes and can be used as a separate entity for prognostication. METHODS: A retrospective chart review of 104 cases of AML was conducted. The highest platelet count during days 25-35 from initiation of induction chemotherapy (designated as day 30 platelet count) was documented. A multivariate analysis for other factors such as age, sex, risk categories, day 14+ plasma cell count (average plasma cell percentage at days 14-21), infections, allogeneic bone marrow transplant, and remission status was done. RESULTS: Day 30 platelet count was found to be an independent predictor of survival in AML. On the multivariate analysis, the subgroup with superior platelet counts (≥400,000/mcL) was found to be associated with better outcomes. LIMITATIONS: Results need to be validated in a larger cohort. CONCLUSIONS: CR with superior platelet recovery (≥400,000/mcL) is a unique subcategory in itself and has prognostic significance. This may help better assess response to chemotherapeutic agents and aid in further decision-making regarding treatment.

Pneumatosis Intestinalis in a Patient with Acute Promyelocytic Leukemia.

Pneumatosis Intestinalis is a rare condition characterized by the presence of gas within the intestinal wall. We describe a case of a 33-year-old woman with acute promyelocytic leukemia who developed nausea and nonbloody diarrhea. CT showed intramural air in transverse and descending colon. Patient clinically improved with conservative management.