Estimated cytomegalovirus seroprevalence in the general population of the United States and Canada.

Seroprevalence data for cytomegalovirus (CMV), a widespread virus causing lifelong infection, vary widely, and contemporary data from the United States (US) and Canada are limited. Utilizing a modeling approach based on a literature review (conducted August, 2022) of data published since 2005, we determine age-, sex-, and country-specific CMV seroprevalence in the general US and Canadian populations. Sex-specific data were extracted by age categories, and a random-effects meta-regression model was used to fit the reported data (incorporating splines for the US). Seven studies reported US CMV seroprevalence (both sexes, aged 1‒89 years); all used National Health and Nutrition Examination Survey data. Due to limited population-based studies, Canadian estimates were modeled using other limited country data. In both countries, modeled seroprevalence estimates increased with age and were higher in females versus males (US: 49.0% vs. 41.6% at 18‒19 years; 61.5% vs. 50.0% at 38‒39 years; Canada: 23.7% vs. 13.7% at 18‒19 years; 32.6% vs. 22.6% at 38‒39 years). Notably, by young adulthood, one-half of US and one-quarter of Canadian females have acquired CMV. The observed differences in CMV seroprevalence in the US and Canada may partially reflect variations in general population characteristics.

Prevalence of self-inflicted injuries among transgender and gender diverse adolescents and young adults compared to their peers: an examination of interaction with mental health morbidity.

PURPOSE: Compare occurrence of self-inflicted injuries among transgender and gender diverse (TGD) youth to that of their cisgender peers while accounting for mental health diagnoses. METHODS: Review of electronic health records from three integrated health care systems identified 1087 transfeminine and 1431 transmasculine adolescents and young adults. Poisson regression was used to calculate prevalence ratios comparing the proportion of TGD participants with at least one self-inflicted injury (a surrogate for suicide attempt) before index date (first evidence of TGD status) to the corresponding proportions in presumed cisgender male and female referents matched on age, race/ethnicity, and health plan. Interactions between gender identities and mental health diagnoses were assessed on multiplicative and additive scales. RESULTS: TGD adolescents and young adults were more likely to have a self-inflicted injury, various mental health diagnoses, and multiple mental health diagnoses than their cisgender peers. The prevalence of self-inflicted injuries among TGD adolescents and young adults was high even in the absence of mental health diagnoses. Results were consistent with positive additive interaction and negative multiplicative interaction. CONCLUSIONS: Universal suicide prevention efforts for all youth, including those with no mental health diagnoses, and more intensive suicide prevention efforts for TGD adolescents and young adults and those with at least one mental health diagnosis are warranted.

Medicaid expansion, health insurance coverage, and cost barriers to care among low-income adults with asthma: the Adult Asthma Call-Back Survey.

OBJECTIVE: To examine Medicaid expansion (ME) effects on health insurance coverage (HIC) and cost barriers to medical care among people with asthma. METHOD: We analyzed 2012-2013 and 2015-2016 data from low-income adults with current asthma aged 18-64 years in the Behavioral Risk Factor Surveillance System Asthma Call-Back Survey (state-level telephone survey). We calculated weighted percentages and 95% confidence intervals from ME and non-ME jurisdictions (according to 2014 ME status). Outcomes were HIC and cost barriers to buying asthma medication (MED), seeing a health care provider for asthma (HCP), or any asthma care (AAC). Using SUDAAN, we performed survey-weighted difference-in-differences analyses, adjusting for demographics. Subgroup analyses were stratified by demographics. RESULTS: Our study population included 6445 participants from 25 states plus Puerto Rico. In 2015-2016 compared to 2012-2013, HIC was more common in ME jurisdictions (P < 0.001) but unchanged in non-ME jurisdictions. Adjusted difference-in-differences analyses showed ME was associated with a statistically significant 13.36 percentage-point increase in HIC (standard error = 0.053). Cost barriers to MED, HCP, and AAC did not change significantly for either group in descriptive and difference-in-differences analyses. In subgroup analyses, we noted variation in outcomes by demographics and 2014 ME status. CONCLUSIONS: We found ME significantly affected HIC among low-income adults with asthma, but not cost barriers to asthma-related health care. Strategies to reduce cost barriers to asthma care could further improve health care access among low-income adults with asthma in ME jurisdictions.

A definition of the causal effect of a political party's nominee on the U.S. general presidential election using counterfactual response types.

The electability of the candidates for the 2020 Democratic U.S. presidential nomination was frequently debated. Arguments regarding a candidate's electability often claimed that they would affect the general election by changing the behavior of a certain subset of eligible voters. For example, is it more important electorally that a candidate drive turnout or swing voting? As lay consumers of political opinion, we were having difficulty weighing these questions from a strategic standpoint. Although candidate electability is a nebulous term that might be interpreted in various ways, one interpretation of the term is a population-based causal question: What would the effect of the Democratic nominee be on the presidential election result? Population-based causal questions are commonly studied in epidemiology. To aid interpretation of electability arguments, we frame the question through a counterfactual model used in epidemiology. Specifically, we define the causal effect by characterizing the population of eligible voters into nine counterfactual response types. The definition clarifies our ability to interpret arguments regarding the electability of the candidates. For example, the causal effect can be subdivided into three parts: the effect of the nominee on (1) Democratic turnout, (2) Republican turnout, and (3) swing voting. We show using notation that the third part has twice the weight as the other two. The definition follows intuition. However, we hope its formalization using counterfactual response types may foster interdisciplinary communication.

Prenatal exposure to organochlorine pesticides and early childhood communication development in British girls.

BACKGROUND: The developing brain is susceptible to exposure to neurodevelopmental toxicants such as pesticides. AIMS: We explored associations of prenatal serum concentrations of hexachlorobenzene (HCB), beta-Hexachlorocyclohexane (ß-HCH), 2,2-Bis(4-chlorophenyl)-1,1-dichloroethene (p,p'-DDE) and 2,2-Bis(4-chlorophenyl-1,1,1-trichloroethane (p,p'-DDT) with maternal-reported measures of verbal and non-verbal communication in young girls. STUDY DESIGN AND METHODS: We studied a sample of 400 singleton girls and their mothers participating in the Avon Longitudinal Study of Parents and Children (ALSPAC) using multivariable linear regression models adjusting for parity, Home Observation Measurement of the Environment (HOME) score, maternal age and education status, and maternal tobacco use during the first trimester of pregnancy. EXPOSURE AND OUTCOME MEASURES: Maternal serum samples (collected at median 15 wks. gestation [IQR 10, 28]) were assessed for selected organochlorine pesticide levels. Communication was assessed at 15 and 38 months, using adapted versions of the MacArthur Bates Communicative Development Inventories for Infants and Toddlers (MCDI). RESULTS: At 15 months, girls born to mothers with prenatal concentrations of HCB in the highest tertile had vocabulary comprehension and production scores approximately 16% (p = 0.007) lower than girls born to mothers with concentrations in the lowest tertile. This association varied by maternal parity in that the evidence was stronger for daughters of nulliparous mothers. At 38 months, girls born to mothers with prenatal concentrations of HCB in the highest tertile had mean adjusted intelligibility scores that were 3% (p = 0.03) lower than those born to mothers with concentrations in the lowest tertile; however, results did not vary significantly by parity. Maternal concentrations of ß-HCH and p,p'-DDE were not significantly associated with MCDI scores at 15 or 36 months. p,p'-DDT had an inconsistent pattern of association; a significant positive association was observed between p,p'-DDT with verbal comprehension scores at 15 months; however, at 38 months a significant inverse association was observed for p,p'-DDT with communicative scores. This inverse association for p,p'-DDT among older girls tended to be stronger among daughters of mothers who had lower depression scores. CONCLUSIONS: Organochlorine pesticide exposure in utero may affect communication development.

Oxidative balance score and oxidative stress biomarkers in a study of Whites, African Americans, and African immigrants.

CONTEXT: Oxidative balance score (OBS) is a composite measure of multiple pro- and antioxidant exposures. OBJECTIVE: To investigate associations of OBS with F2-isoprostanes (FIP), mitochondrial DNA copy number (mtDNA), and fluorescent oxidative products (FOP), and assess inter-relationships among the biomarkers. METHODS: In a cross-sectional study, associations of a thirteen-component OBS with biomarker levels were assessed using multivariable regression models. RESULTS: Association of OBS with FIP, but not with FOP, was in the hypothesized direction. The results for mtDNA were unstable and analysis-dependent. The three biomarkers were not inter-correlated. CONCLUSIONS: Different biomarkers of oxidative stress may reflect different biological processes.

Exposure to traffic pollution, acute inflammation and autonomic response in a panel of car commuters.

BACKGROUND: Exposure to traffic pollution has been linked to numerous adverse health endpoints. Despite this, limited data examining traffic exposures during realistic commutes and acute response exists. OBJECTIVES: We conducted the Atlanta Commuters Exposures (ACE-1) Study, an extensive panel-based exposure and health study, to measure chemically-resolved in-vehicle exposures and corresponding changes in acute oxidative stress, lipid peroxidation, pulmonary and systemic inflammation and autonomic response. METHODS: We recruited 42 adults (21 with and 21 without asthma) to conduct two 2-h scripted highway commutes during morning rush hour in the metropolitan Atlanta area. A suite of in-vehicle particulate components were measured in the subjects' private vehicles. Biomarker measurements were conducted before, during, and immediately after the commutes and in 3 hourly intervals after commutes. RESULTS: At measurement time points within 3h after the commute, we observed mild to pronounced elevations relative to baseline in exhaled nitric oxide, C-reactive-protein, and exhaled malondialdehyde, indicative of pulmonary and systemic inflammation and oxidative stress initiation, as well as decreases relative to baseline levels in the time-domain heart-rate variability parameters, SDNN and rMSSD, indicative of autonomic dysfunction. We did not observe any detectable changes in lung function measurements (FEV1, FVC), the frequency-domain heart-rate variability parameter or other systemic biomarkers of vascular injury. Water soluble organic carbon was associated with changes in eNO at all post-commute time-points (p<0.0001). CONCLUSIONS: Our results point to measureable changes in pulmonary and autonomic biomarkers following a scripted 2-h highway commute.

Pregnancy termination following prenatal diagnosis of anencephaly or spina bifida: a systematic review of the literature.

BACKGROUND: In regions where prenatal screening for anencephaly and spina bifida is widespread, many cases of these defects are diagnosed prenatally. The purpose of this study was to estimate the frequency of termination of pregnancy (TOP) following prenatal diagnosis of anencephaly or spina bifida and to investigate factors associated with TOP that might lead to selection bias in epidemiologic studies. METHODS: We included articles indexed in Medline or Embase between 1990 and May 2012 reporting the frequency of TOP following prenatal diagnosis of anencephaly or spina bifida with English-language abstracts, 20 or more prenatally diagnosed cases, and at least half of the study years in 1990 or later. We summarized the frequency of TOP across studies using random-effects metaanalysis and stratified results by fetal and study characteristics. RESULTS: Among the 17 studies identified, 9 included anencephaly and 15 included spina bifida. Nine were from Europe, six were from North America, and one each was from South America and Asia. The overall frequency of TOP following prenatal diagnosis was 83% for anencephaly (range, 59-100%) and 63% for spina bifida (range, 31-97%). There were insufficient data to stratify the results for anencephaly; TOP for spina bifida was more common when the prenatal diagnosis occurred at less than 24 weeks' gestation, with defects of greater severity, and in Europe versus North America. CONCLUSIONS: Because underascertainment of birth defects might be more likely when the pregnancy ends in TOP and TOP is associated with fetal characteristics, selection bias is possible in epidemiologic studies of anencephaly or spina bifida.

Risk factors for elevated blood lead levels among African refugee children in New Hampshire, 2004.

OBJECTIVES: Surveillance blood lead screening of refugee children resettled in Manchester, NH, in 2004 revealed that 39 (42%) of 92 children had elevated levels (>or=10 microg/dL) after resettlement. Furthermore, 27/92 children (29%) had nonelevated screening blood lead levels on arrival (BLL1) but had elevated follow-up blood lead levels 3-6 months after settlement (BLL2). The main objective was to identify risk factors for increasing lead levels among refugee children after resettlement in Manchester in 2004. PATIENTS AND METHODS: We conducted a cohort study, with completion of household interviews and home assessments for refugee families who had resettled in 2004 in Manchester, NH. Blood lead level (BLL) data were abstracted from the New Hampshire (NH) Childhood Lead Poisoning Prevention Program. To assess acute and chronic malnutrition among refugees, we used anthropometric data from International Organization of Migration documents to calculate nutritional indices. RESULTS AND DISCUSSION: Of the 93 African refugee children in 42 families who participated, 60 (65%) had been born in a refugee camp. Median age was 5.5 years at the time of BLL2 measurement. Thirty-six (39%) of the refugee children had BLL2 >or= 10 microg/dL. Liberians and those born in refugee camps had higher geometric mean BLL2 than those not Liberian or not born in camps. Younger children and children with nutritional wasting before immigrating to the United States had a greater increase in geometric mean from BLL1 to BLL2, compared to older children and those without nutritional wasting. Follow-up blood lead testing of refugee children, particularly those resettled in areas with older housing stock, as in Manchester, is important for identifying lead exposure occurring after resettlement. Increased attention to improve nutritional status of children in refugee camps and after arrival in the United States and awareness of children who were born in refugee camps should be incorporated into lead-poisoning prevention strategies.

Study design options in evaluating gene-environment interactions: practical considerations for a planned case-control study of pediatric leukemia.

BACKGROUND: We compare methodological approaches for evaluating gene-environment interaction using a planned study of pediatric leukemia as a practical example. We considered three design options: a full case-control study (Option I), a case-only study (Option II), and a partial case-control study (Option III), in which information on controls is limited to environmental exposure only. PROCEDURE: For each design option we determined its ability to measure the main effects of environmental factor E and genetic factor G, and the interaction between E and G. Using the leukemia study example, we calculated sample sizes required to detect and odds ratio (OR) of 2.0 for E alone, an OR of 10 for G alone and an interaction G x E of 3. RESULTS: Option I allows measuring both main effects and interaction, but requires a total sample size of 1,500 cases and 1,500 controls. Option II allows measuring only interaction, but requires just 121 cases. Option III allows calculating the main effect of E, and interaction, but not the main effect of G, and requires a total of 156 cases and 133 controls. CONCLUSIONS: In this case, the partial case-control study (Option III) appears to be more efficient with respect to its ability to answer the research questions for the amount of resources required. The design options considered in this example are not limited to observational epidemiology and may be applicable in studies of pharmacogenomics, survivorship, and other areas of pediatric ALL research.

Inference for case-control studies when exposure status is both informatively missing and misclassified.

In case-control studies, it is common for a categorical exposure variable to be misclassified. It is also common for exposure status to be informatively missing for some individuals, in that the probability of missingness may be related to exposure. Procedures for addressing the bias due to misclassification via validation data have been extensively studied, and related methods have been proposed for dealing with informative missingness based on supplemental sampling of some of those with missing data. In this paper, we introduce study designs and analytic procedures for dealing with both problems simultaneously in a 2x2 analysis. Results based on convergence in probability illustrate that the combined effects of missingness and misclassification, even when the latter is non-differential, can lead to naïve exposure odds ratio estimates that are inflated or on the wrong side of the null. The motivating example comes from a case-control study of the association between low birth weight and the diagnosis of breast cancer later in life, where self-reported birth weight for some women is supplemented by accurate information from birth certificates.

An epidemiologic assessment of genomic profiling for measuring susceptibility to common diseases and targeting interventions.

PURPOSE: The current clinical value of genomic profiling (testing for genotypes at multiple loci) for assessing susceptibility to common diseases and targeting behavioral and medical interventions is questionable. As common diseases result from many gene-environment interactions, epidemiologic studies should be used to examine the value of genomic profiling in terms of clinical validity (future disease positive and negative predictive value stratified by exposure), clinical utility (targeted interventions to reduce disease risk among persons with the profile) and public health utility (comparing reduction of disease burden in the population based on genomic profiling to population-wide interventions). METHODS: We investigate these parameters for a hypothetical common disease (5% lifetime risk), for which 3 genetic variants at different loci and one environmental exposure are risk factors. RESULTS: We show that even for modest effects of each variant alone (risk ratios from 1.5-3.0) and modest interactions between the exposure and the genes, the disease predictive value for people with 2 or more variants (especially 3) can be quite high (50-100%) in the presence of a modifiable exposure. Individual risks can then be reduced by targeted exposure intervention among persons with the genotype. However, the predictive value for multiple genotypes is much lower for rarer diseases (< 1 per 1000). Also, with increasing number of genes in a profile, the population impact of disease reduction for targeted intervention based on genotype will be smaller, especially for rare genotypes, weak associations, and weak interactions. CONCLUSION: To assess the value of genomic profiling, well-designed epidemiologic studies are needed to quantify disease risks, in addition to costs, benefits, and risks for testing and interventions.

Case-control studies of genotypic relative risks using children of cases as controls.

The use of a child as a case's control in a case-control study of genetic factors may be advantageous in some situations. We describe three methods of analysing such data. A method based upon the unconditional likelihood using case/child pairings apparently is the most efficient method. However, a conditional likelihood method using case/child pairs is more robust in that it allows for heterogeneity of the genetic trait among subpopulations as long as matings occur only within the same subpopulation. We argue that the child can be considered a genetic surrogate for the missing spouse and hence such designs are as valid as are those using spouses.