Impact of randomly assigned "pay-as-you-go" liquefied petroleum gas prices on energy use for cooking: Experimental pilot evidence from rural Rwanda.

The disease burden related to air pollution from traditional solid-fuel cooking practices in low- and middle-income countries impacts millions of people globally. Although the use of liquefied petroleum gas (LPG) fuel for cooking can meaningfully reduce household air pollution concentrations, major barriers, including affordability and accessibility, have limited widespread adoption. Using a randomized controlled trial, our objective was to evaluate the association between the cost and use of LPG among 23 rural Rwandan households. We provided a 2-burner LPG stove with accessories and incorporated a "pay-as-you-go" (PAYG) LPG service model that included fuel delivery. PAYG services remove the large up-front cost of cylinder refills by integrating "smart meter" technology that allows participants to pay in incremental amounts, as needed. We assigned three randomized discounted prices for LPG to each household at ~4-week intervals over a 12-week period. We modeled the relationship between randomized PAYG LPG price and use (standardized to monthly periods), analyzing effect modification by relative household wealth. A 1000 Rwandan Franc (about 1 USD at the time of the study) increase in LPG price/kg was associated with a 4.1 kg/month decrease in use (95% confidence interval [CI]: -6.7, -1.6; n=69 observations). Wealth modified this association; we observed a 9.7 kg/month reduction (95% CI: -14.8, -4.5) among wealthier households and a 2.5 kg/month reduction (95% CI: -5.3, 0.3) among lower-wealth households (p-interaction=0.01). The difference in price sensitivity was driven by higher LPG use among wealthier households at more heavily discounted prices; from an 80% to 10% discount, wealthy households used 17.5 to 5.3 kg/month and less wealthy households used 6.2 to 3.1 kg/month. Our pilot-level experimental evidence of PAYG LPG in a rural low-resource setting suggests that further exploration of subsidized pricing varied by household wealth is needed to ensure future policy initiatives can achieve targets without exacerbating inequities.

Food Insecurity and Hypoglycemia among Older Patients with Type 2 Diabetes Treated with Insulin or Sulfonylureas: The Diabetes & Aging Study.

BACKGROUND: Severe hypoglycemia is a serious adverse drug event associated with hypoglycemia-prone medications; older patients with diabetes are particularly at high risk. Economic food insecurity (food insecurity due to financial limitations) is a known risk factor for hypoglycemia; however, less is known about physical food insecurity (due to difficulty cooking or shopping for food), which may increase with age, and its association with hypoglycemia. OBJECTIVE: Study associations between food insecurity and severe hypoglycemia. DESIGN: Survey based cross-sectional study. PARTICIPANTS: Survey responses were collected in 2019 from 1,164 older (≥ 65 years) patients with type 2 diabetes treated with insulin or sulfonylureas. MAIN MEASURES: Risk ratios (RR) for economic and physical food insecurity associated with self-reported severe hypoglycemia (low blood glucose requiring assistance) adjusted for age, financial strain, HbA1c, Charlson comorbidity score and frailty. Self-reported reasons for hypoglycemia endorsed by respondents. KEY RESULTS: Food insecurity was reported by 12.3% of the respondents; of whom 38.4% reported economic food insecurity only, 21.1% physical food insecurity only and 40.5% both. Economic food insecurity and physical food insecurity were strongly associated with severe hypoglycemia (RR = 4.3; p = 0.02 and RR = 4.4; p = 0.002, respectively). Missed meals ("skipped meals, not eating enough or waiting too long to eat") was the dominant reason (77.5%) given for hypoglycemia. CONCLUSIONS: Hypoglycemia prevention efforts among older patients with diabetes using hypoglycemia-prone medications should address food insecurity. Standard food insecurity questions, which are used to identify economic food insecurity, will fail to identify patients who have physical food insecurity only.

Standardizing Fidelity to Evidence-Based Practice in the Early Psychosis Intervention Network.

OBJECTIVE: This study investigated variations in the measurement of fidelity to coordinated specialty care (CSC) within the Early Psychosis Intervention Network (EPINET), a learning health system that consists of 101 CSC programs within eight hubs. The study investigated the degree to which five fidelity scales could be mapped onto a standard scale. METHODS: The investigators identified six fidelity scales in use by EPINET participants; examined their item content, scoring, and data sources; and mapped five scales onto the First Episode Psychosis Services Fidelity Scale (FEPS-FS), which is the most widely used scale. RESULTS: Mapping five fidelity scales onto the FEPS-FS showed that the percentage of FEPS-FS components successfully mapped ranged from 42% to 81%. CONCLUSIONS: Mapping five scales onto one that uses dichotomous scoring identified the degree of variation in measures and reduced the amount and quality of usable fidelity data. Identifying variations in fidelity measurement is a core function of a learning health system.

Digital health and medical technology for perioperative sarcopenia optimisation and prehabilitation - Where to go from here?

Sarcopenia has been shown to cause poorer outcomes in surgical oncology. With the advancement of artificial intelligence technology, body composition analysis can be obtained with ease. Given the lead time between cancer diagnosis and surgery, selected patients at risk of complications secondary to sarcopenia may be amenable to prehabilitation. The COVID-19 pandemic has led to the rapid adaptation of digital health and medical technology. Our perspective piece will review the current available evidence and propose innovative ways to incorporate technology into physical and nutritional prehabilitation.

Assessing the Evidence Base for School-Based Promotion and Prevention Interventions: Introduction to the Series.

Schools are an important component in the mental health system of care for youths. Teachers and other school staff have unique opportunities to promote emotional wellness and prevent mental health conditions. Although numerous programs are available, identifying evidence-based and effective options is a significant challenge. This introduction lays out the rationale and methodology of the Assessing the Evidence Base (AEB) Series, a collection of systematic reviews of school-based mental health promotion and prevention approaches recommended by the National Academies of Sciences, Engineering, and Medicine for students in kindergarten through grade 12. Authors of the current AEB Series used the rating criteria derived from the 2014 AEB Series, which provided systematic reviews of a wide spectrum of interventions for mental and substance use disorders. Like its predecessor, the current series upholds a high standard of scientific rigor while ensuring that the information is easily accessible to various stakeholders in education, behavioral health, and communities. It describes the universal features included in each systematic review, such as a rating of the level of evidence for interventions, intervention program components, identification of interventions that have yielded positive outcomes for students from underserved populations, and a review of cost data. The AEB systematic reviews will serve as an important tool for decision makers involved in managing limited resources for various programs in school-based mental health services by synthesizing large bodies of research for use by leaders in education and behavioral health.

Resf1 is a compound G4 quadruplex-associated tumor suppressor for triple negative breast cancer.

Patients with ER-negative breast cancer have the worst prognosis of all breast cancer subtypes, often experiencing rapid recurrence or progression to metastatic disease shortly after diagnosis. Given that metastasis is the primary cause of mortality in most solid tumors, understanding metastatic biology is crucial for effective intervention. Using a mouse systems genetics approach, we previously identified 12 genes associated with metastatic susceptibility. Here, we extend those studies to identify Resf1, a poorly characterized gene, as a novel metastasis susceptibility gene in ER- breast cancer. Resf1 is a large, unstructured protein with an evolutionarily conserved intron-exon structure, but with poor amino acid conservation. CRISPR or gene trap mouse models crossed to the Polyoma Middle-T antigen genetically engineered mouse model (MMTV-PyMT) demonstrated that reduction of Resf1 resulted in a significant increase in tumor growth, a shortened overall survival time, and increased incidence and number of lung metastases, consistent with patient data. Furthermore, an analysis of matched tail and primary tissues revealed loss of the wildtype copy in tumor tissue, consistent with Resf1 being a tumor suppressor. Mechanistic analysis revealed a potential role of Resf1 in transcriptional control through association with compound G4 quadruplexes in expressed sequences, particularly those associated with ribosomal biogenesis. These results suggest that loss of Resf1 enhances tumor progression in ER- breast cancer through multiple alterations in both transcriptional and translational control.

Protein phosphatase 6 activates NF-κB to confer sensitivity to MAPK pathway inhibitors in KRAS- and BRAF-mutant cancer cells.

The Ras-mitogen-activated protein kinase (MAPK) pathway is a major target for cancer treatment. To better understand the genetic pathways that modulate cancer cell sensitivity to MAPK pathway inhibitors, we performed a CRISPR knockout screen with MAPK pathway inhibitors on a colorectal cancer (CRC) cell line carrying mutant KRAS. Genetic deletion of the catalytic subunit of protein phosphatase 6 (PP6), encoded by PPP6C, rendered KRAS- and BRAF-mutant CRC and BRAF-mutant melanoma cells more resistant to these inhibitors. In the absence of MAPK pathway inhibition, PPP6C deletion in CRC cells decreased cell proliferation in two-dimensional (2D) adherent cultures but accelerated the growth of tumor spheroids in 3D culture and tumor xenografts in vivo. PPP6C deletion enhanced the activation of nuclear factor κB (NF-κB) signaling in CRC and melanoma cells and circumvented the cell cycle arrest and decreased cyclin D1 abundance induced by MAPK pathway blockade in CRC cells. Inhibiting NF-κB activity by genetic and pharmacological means restored the sensitivity of PPP6C-deficient cells to MAPK pathway inhibition in CRC and melanoma cells in vitro and in CRC cells in vivo. Furthermore, a R264 point mutation in PPP6C conferred loss of function in CRC cells, phenocopying the enhanced NF-κB activation and resistance to MAPK pathway inhibition observed for PPP6C deletion. These findings demonstrate that PP6 constrains the growth of KRAS- and BRAF-mutant cancer cells, implicates the PP6-NF-κB axis as a modulator of MAPK pathway output, and presents a rationale for cotargeting the NF-κB pathway in PPP6C-mutant cancer cells.

Protocol for a seamless phase 2A-phase 2B randomized double-blind placebo-controlled trial to evaluate the safety and efficacy of benfotiamine in patients with early Alzheimer's disease (BenfoTeam).

BACKGROUND: Benfotiamine provides an important novel therapeutic direction in Alzheimer's disease (AD) with possible additive or synergistic effects to amyloid targeting therapeutic approaches. OBJECTIVE: To conduct a seamless phase 2A-2B proof of concept trial investigating tolerability, safety, and efficacy of benfotiamine, a prodrug of thiamine, as a first-in-class small molecule oral treatment for early AD. METHODS: This is the protocol for a randomized, double-blind, placebo-controlled 72-week clinical trial of benfotiamine in 406 participants with early AD. Phase 2A determines the highest safe and well-tolerated dose of benfotiamine to be carried forward to phase 2B. During phase 2A, real-time monitoring of pre-defined safety stopping criteria in the first approximately 150 enrollees will help determine which dose (600 mg or 1200 mg) will be carried forward into phase 2B. The phase 2A primary analysis will test whether the rate of tolerability events (TEs) is unacceptably high in the high-dose arm compared to placebo. The primary safety endpoint in phase 2A is the rate of TEs compared between active and placebo arms, at each dose. The completion of phase 2A will seamlessly transition to phase 2B without pausing or stopping the trial. Phase 2B will assess efficacy and longer-term safety of benfotiamine in a larger group of participants through 72 weeks of treatment, at the selected dose. The co-primary efficacy endpoints in phase 2B are CDR-Sum of Boxes and ADAS-Cog13. Secondary endpoints include safety and tolerability measures; pharmacokinetic measures of thiamine and its esters, erythrocyte transketolase activity as blood markers of efficacy of drug delivery; ADCS-ADL-MCI; and MoCA. CONCLUSION: The BenfoTeam trial utilizes an innovative seamless phase 2A-2B design to achieve proof of concept. It includes an adaptive dose decision rule, thus optimizing exposure to the highest and best-tolerated dose. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT06223360, registered on January 25, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT06223360.

Preterm and Early-Term Delivery After Heat Waves in 50 US Metropolitan Areas.

Importance: Heat waves are increasing in frequency, intensity, and duration and may be acutely associated with pregnancy outcomes. Objective: To examine changes in daily rates of preterm and early-term birth after heat waves in a 25-year nationwide study. Design, Setting, and Participants: This cohort study of singleton births used birth records from 1993 to 2017 from the 50 most populous US metropolitan statistical areas (MSAs). The study included 53 million births, covering 52.8% of US births over the period. Data were analyzed between October 2022 and March 2023 at the National Center for Health Statistics. Exposures: Daily temperature data from Daymet at 1-km2 resolution were averaged over each MSA using population weighting. Heat waves were defined in the 4 days (lag, 0-3 days) or 7 days (lag, 0-6 days) preceding birth. Main Outcomes and Measures: Daily counts of preterm birth (28 to <37 weeks), early-term birth (37 to <39 weeks), and ongoing pregnancies in each gestational week on each day were enumerated in each MSA. Rate ratios for heat wave metrics were obtained from time-series models restricted to the warm season (May to September) adjusting for MSA, year, day of season, and day of week, and offset by pregnancies at risk. Results: There were 53 154 816 eligible births in the 50 MSAs from 1993 to 2017; 2 153 609 preterm births and 5 795 313 early-term births occurring in the warm season were analyzed. A total of 30.0% of mothers were younger than 25 years, 53.8% were 25 to 34 years, and 16.3% were 35 years or older. Heat waves were positively associated with daily rates of preterm and early-term births, showing a dose-response association with heat wave duration and temperatures and stronger associations in the more acute 4-day window. After 4 consecutive days of mean temperatures exceeding the local 97.5th percentile, the rate ratio for preterm birth was 1.02 (95% CI, 1.00-1.03), and the rate ratio for early-term birth was 1.01 (95% CI, 1.01-1.02). For the same exposure, among those who were 29 years of age or younger, had a high school education or less, and belonged to a racial or ethnic minority group, the rate ratios were 1.04 (95% CI, 1.02-1.06) for preterm birth and 1.03 (95% CI, 1.02-1.05) for early-term birth. Results were robust to alternative heat wave definitions, excluding medically induced deliveries, and alternative statistical model specifications. Conclusions and Relevance: In this cohort study, preterm and early-term birth rates increased after heat waves, particularly among socioeconomically disadvantaged subgroups. Extreme heat events have implications for perinatal health.

Associations of pollen and cardiovascular disease morbidity in Atlanta during 1993-2018.

Background: Pollen exposure is associated with substantial respiratory morbidity, but its potential impact on cardiovascular disease (CVD) remains less understood. This study aimed to investigate the associations between daily levels of 13 pollen types and emergency department (ED) visits for eight CVD outcomes over a 26-year period in Atlanta, GA. Methods: We acquired pollen data from Atlanta Allergy & Asthma, a nationally certified pollen counting station, and ED visit data from individual hospitals and the Georgia Hospital Association. We performed time-series analyses using quasi-Poisson distributed lag models, with primary analyses assessing 3-day (lag 0-2 days) pollen levels. Models controlled for temporally varying covariates, including air pollutants. Results: During 1993-2018, there were 1,573,968 CVD ED visits. Most pairwise models of the 13 pollen types and eight CVD outcomes showed no association, with a few exceptions potentially due to chance. Conclusion: We found limited evidence of the impact of pollen on cardiovascular morbidity in Atlanta. Further study on pollen exposures in different climactic zones and exploration of pollen-pollution mixture effects is warranted.

A multicenter, randomized, double-blind, placebo-controlled ascending dose study to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamic (PD) effects of Posiphen in subjects with Early Alzheimer's Disease.

Background: Amyloid beta protein (Aß) is a treatment target in Alzheimer's Disease (AD). Lowering production of its parent protein, APP, has benefits in preclinical models. Posiphen binds to an iron-responsive element in APP mRNA and decreases translation of APP and Aß. To augment human data for Posiphen, we evaluated safety, tolerability and pharmacokinetic and pharmacodynamic (PD) effects on Aß metabolism using Stable Isotope Labeling Kinetic (SILK) analysis. Methods: Double-blind phase 1b randomized ascending dose clinical trial, at five sites, under an IRB-approved protocol. Participants with mild cognitive impairment or mild AD (Early AD) with positive CSF biomarkers were randomized (within each dose arm) to Posiphen or placebo. Pretreatment assessment included lumbar puncture for CSF. Participants took Posiphen or placebo for 21-23 days, then underwent CSF catheter placement, intravenous infusion of 13C6-leucine, and CSF sampling for 36 hours. Safety and tolerability were assessed through participant reports, EKG and laboratory tests. CSF SILK analysis measured Aß40, 38 and 42 with immunoprecipitation-mass spectrometry. Baseline and day 21 CSF APP, Aß and other biomarkers were measured with immunoassays. The Mini-Mental State Exam and ADAS-cog12 were given at baseline and day 21. Results: From June 2017 to December 2021, 19 participants were enrolled, in dose cohorts (6 active: 2 placebo) of 60 mg once/day and 60 mg twice/day; 1 participant was enrolled and completed 60 mg three times/day. 10 active drug and 5 placebo participants completed all study procedures. Posiphen was safe and well-tolerated. 8 participants had headaches related to CSF catheterization; 5 needed blood patches. Prespecified SILK analyses of Fractional Synthesis Rate (FSR) for CSF Aß40 showed no significant overall or dose-dependent effects of Posiphen vs. placebo. Comprehensive multiparameter modeling of APP kinetics supported dose-dependent lowering of APP production by Posiphen. Cognitive measures and CSF biomarkers did not change significantly from baseline to 21 days in Posiphen vs placebo groups. Conclusions: Posiphen was safe and well-tolerated in Early AD. A multicenter SILK study was feasible. Findings are limited by small sample size but provide additional supportive safety and PK data. Comprehensive modeling of biomarker dynamics using SILK data may reveal subtle drug effects. Trial registration: NCT02925650 on clinicaltrials.gov.

Joint effects of prenatal exposure to indoor air pollution and psychosocial factors on early life inflammation.

It is hypothesized that air pollution and stress impact the central nervous system through neuroinflammatory pathways Despite this, the association between prenatal exposure to indoor air pollution and psychosocial factors on inflammatory markers in infancy has been underexplored in epidemiology studies. This study investigates the individual and joint effects of prenatal exposure to indoor air pollution and psychosocial factors on early life inflammation (interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α)). We analyzed data from the South African Drakenstein Child Health Study (N = 225). Indoor air pollution and psychosocial factor measurements were taken in the 2nd trimester of pregnancy. Circulating inflammatory markers (IL-1ß, Il-6, and TNF-α) were measured in serum in the infants at 6 weeks postnatal. Linear regression models were used to investigate associations between individual exposures and inflammatory markers. To investigate joint effects of environmental and psychosocial factors, Self-Organizing Maps (SOM) were used to create exposure profile clusters. These clusters were added to linear regression models to investigate the associations between exposure profiles and inflammatory markers. All models were adjusted for maternal age, maternal HIV status, and ancestry to control for confounding. Most indoor air pollutants were positively associated with inflammatory markers, particularly benzene and TNF-α in single pollutant models. No consistent patterns were found for psychosocial factors in single-exposure linear regression models. In joint effects analyses, the SOM profile with high indoor air pollution, low SES, and high maternal depressive symptoms were associated with higher inflammation. Indoor air pollutants were consistently associated with increased inflammation in both individual and joint effects models, particularly in combination with low SES and maternal depressive symptoms. The trend for individual psychosocial factors was not as clear, with mainly null associations. As we have observed pro- and anti-inflammatory effects, future research should investigate joint effects of these exposures on inflammation and their health effects.

Person-centered hospital discharge data: Essential existing infrastructure to enhance public health surveillance of maternal substance use disorders in the midst of a national maternal overdose crisis.

OBJECTIVES: As crises of drug-related maternal harms escalate, US public health surveillance capacity remains suboptimal for drug-related maternal morbidities. Most state hospital discharge databases (HDDs) are encounter-based, and thus limit ascertainment of morbidities to delivery visits and ignoring those occurring during the 21 months spanning pregnancy and postpartum year. This study analyzes data from a state that curates person-centered HDD to compare patterns of substance use disorder (SUD) diagnoses at delivery vs. the full 21 pregnancy/postpartum months, overall and by maternal social position. METHODS: Among people who experienced an in-hospital birth in New York State between 9/1/2016 and 1/1/2018 (N = 330,872), we estimated SUD diagnosis (e.g., opioids, stimulants, benzodiazepines, cannabis) prevalence at delivery; across the full 9 months of pregnancy and 12 postpartum months; and by trimester and postpartum quarter. Risk ratio and risk difference estimated disparities by race/ethnicity, age, rurality, and payor. RESULTS: The 21-month SUD prevalence rate per 100,000 was 2671 (95% CI 2616-2726), with 31% (29.5%-31.5%) missing SUD indication when ascertained at delivery only (1866; 95% CI 1820-1912). Quarterly rates followed a roughly J-shaped trajectory. Structurally marginalized individuals suffered the highest 21-month SUD prevalence (e.g., Black:White risk ratio=1.80 [CI:1.73-1.88]). CONCLUSION: By spanning the full 21 months of pregnancy/postpartum, person-centered HDD reveal than the maternal SUD crisis is far greater than encounter-based delivery estimates had revealed. Generating person-centered HDD will improve efforts to tailor interventions to help people who use drugs survive while pregnant and postpartum, and eliminate inequities.

Clinical value of Alzheimer's disease biomarker testing.

INTRODUCTION: In the Investigating the Impact of Alzheimer's Disease Diagnostics in British Columbia (IMPACT-AD BC) study, we aimed to understand how Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarker testing-used in medical care-impacted medical decision-making (medical utility), personal decision-making (personal utility), and health system economics. METHODS: The study was designed as an observational, longitudinal cohort study. A total of 149 patients were enrolled between February 2019 and July 2021. Patients referred to memory clinics were approached to participate if their dementia specialist ordered AD CSF biomarker testing as part of their routine medical care, and the clinical scenario met the appropriate use criteria for lumbar puncture and AD CSF biomarker testing. For the medical utility pillar, detailed clinical management plans were collected via physician questionnaires pre- and post-biomarker disclosure. RESULTS: Patients with completed management questionnaires (n = 142) had a median age of 64 (interquartile range: 59-69) years, 48% were female, and 60% had CSF biomarker profiles on the AD continuum. Clinical management changed in 89.4% of cases. AD biomarker testing was associated with decreased need for other diagnostic procedures, including brain imaging (-52.0%) and detailed neuropsychological assessments (-63.2%), increased referrals and counseling (57.0%), and guided AD-related drug prescriptions (+88.4% and -50.0% in biomarker-positive and -negative cases, respectively). DISCUSSION: AD biomarker testing was associated with significant and positive changes in clinical management, including decreased health care resource use, therapy optimization, and increased patient and family member counseling. While certain changes in management were linked to the AD biomarker profile (e.g., referral to clinical trials), the majority of changes were independent of baseline clinical presentation and level of cognitive impairment, demonstrating a broad value for AD biomarker testing in individuals meeting the appropriate use criteria for testing.

Personal value of Alzheimer's disease biomarker testing and result disclosure from the patient and care partner perspective.

INTRODUCTION: We described patients' and care partners' experiences with Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarker testing and result disclosure in routine care. METHODS: IMPACT-AD BC is an observational study of clinic patients who underwent AD CSF biomarker testing as part of their routine medical care (n = 142). In the personal utility arm of the study, semi-structured phone interviews were conducted with a subset of patients (n = 34), and separately with their care partners (n = 31). Post-disclosure interviews were conducted ∼1 month and ∼6 months after biomarker result disclosure and investigated the patients' decision-making process around testing, impact of receiving results, wellness and lifestyle changes, and future planning. RESULTS: A majority of patients (90%) rated their decision to undergo testing as "easy." Post-disclosure, the majority (82%) reported overall positive feelings from having greater certainty and the ability to plan ahead, and results spurred them to adopt/continue healthy behaviors such as exercise (84%) and cognitive activities (54%). Care partners expressed relief from having more diagnostic certainty, increased appreciation of future caregiving responsibilities, and a desire to connect with support resources. DISCUSSION: Perspectives of persons with lived experience in dementia provide new insight into the value of biomarker testing and should be included as part of evidence-guided considerations for pre-test counseling and result disclosure. Moreover, study findings identify an interval when patients and care partners are highly receptive to positive lifestyle and medical interventions.

Joint Effects of Indoor Air Pollution and Maternal Psychosocial Factors During Pregnancy on Trajectories of Early Childhood Psychopathology.

BACKGROUND: Prenatal indoor air pollution and maternal psychosocial factors have been associated with adverse psychopathology. We used environmental exposure mixture methodology to investigate joint effects of both exposure classes on child behavior trajectories. METHODS: For 360 children from the South African Drakenstein Child Health Study, we created trajectories of Child Behavior Checklist scores (24, 42, 60 months) using latent class linear mixed effects models. Indoor air pollutants and psychosocial factors were measured during pregnancy (2nd trimester). After adjusting for confounding, single-exposure effects (per natural log-1 unit increase) were assessed using polytomous logistic regression models; joint effects using self-organizing maps (SOM), and principal component (PC) analysis. RESULTS: Three trajectories were chosen for both internalizing and externalizing problems, with "high" (externalizing) or "increasing" (internalizing) being the most adverse trajectories. High externalizing trajectory was associated with increased particulate matter (PM10) exposure (OR [95%-CI]: 1.25 [1.01,1.55]) and SOM exposure profile most associated with smoking (2.67 [1.14,6.27]). Medium internalizing trajectory was associated with increased emotional intimate partner violence (2.66 [1.17,5.57]), increasing trajectory with increased benzene (1.24 [1.02,1.51]) and toluene (1.21 [1.02,1.44]) and the PC most correlated with benzene and toluene (1.25 [1.02, 1.54]). CONCLUSIONS: Prenatal exposure to environmental pollutants and psychosocial factors was associated with internalizing and externalizing child behavior trajectories. Understanding joint effects of adverse exposure mixtures will facilitate targeted interventions to prevent childhood psychopathology.

A scalar-on-quantile-function approach for estimating short-term health effects of environmental exposures.

Environmental epidemiologic studies routinely utilize aggregate health outcomes to estimate effects of short-term (eg, daily) exposures that are available at increasingly fine spatial resolutions. However, areal averages are typically used to derive population-level exposure, which cannot capture the spatial variation and individual heterogeneity in exposures that may occur within the spatial and temporal unit of interest (eg, within a day or ZIP code). We propose a general modeling approach to incorporate within-unit exposure heterogeneity in health analyses via exposure quantile functions. Furthermore, by viewing the exposure quantile function as a functional covariate, our approach provides additional flexibility in characterizing associations at different quantile levels. We apply the proposed approach to an analysis of air pollution and emergency department (ED) visits in Atlanta over 4 years. The analysis utilizes daily ZIP code-level distributions of personal exposures to 4 traffic-related ambient air pollutants simulated from the Stochastic Human Exposure and Dose Simulator. Our analyses find that effects of carbon monoxide on respiratory and cardiovascular disease ED visits are more pronounced with changes in lower quantiles of the population's exposure. Software for implement is provided in the R package nbRegQF.

Developing the Healthy Actions and Lifestyles to Avoid Dementia or Hispanos y el ALTo a la Demencia program.

INTRODUCTION: With Alzheimer's disease and related dementias (ADRD) representing an enormous public health challenge, there is a need to support individuals in learning about and addressing their modifiable risk factors (e.g., diet, sleep, and physical activity) to prevent or delay dementia onset. However, there is limited availability for evidence-informed tools that deliver both quality education and support for positive behavior change such as by increasing self-efficacy and personalizing goal setting. Tools that address the needs of Latino/a, at higher risk for ADRD, are even more scarce. METHODS: We established a multidisciplinary team to develop the Healthy Actions and Lifestyles to Avoid Dementia or Hispanos y el ALTo a la Demencia (HALT-AD) program, a bilingual online personalized platform to educate and motivate participants to modify their risk factors for dementia. Grounded in social cognitive theory and following a cultural adaptation framework with guidance from a community advisory board, we developed HALT-AD iteratively through several cycles of rapid prototype development, user-centered evaluation through pilot testing and community feedback, and refinement. RESULTS: Using this iterative approach allowed for more than 100 improvements in the content, features, and design of HALT-AD to improve the program's usability and alignment with the interests and educational/behavior change support needs of its target audience. Illustrative examples of how pilot data and community feedback informed improvements are provided. DISCUSSION: Developing HALT-AD iteratively required learning through trial and error and flexibility in workflows, contrary to traditional program development methods that rely on rigid, pre-set requirements. In addition to efficacy trials, studies are needed to identify mechanisms for effective behavior change, which might be culturally specific. Flexible and personalized educational offerings are likely to be important in modifying risk trajectories in ADRD.