A systematic evidence map for the evaluation of noncancer health effects and exposures to polychlorinated biphenyl mixtures.

Assessing health outcomes associated with exposure to polychlorinated biphenyls (PCBs) is important given their persistent and ubiquitous nature. PCBs are classified as a Group 1 carcinogen, but the full range of potential noncancer health effects from exposure to PCBs has not been systematically summarized and evaluated. We used systematic review methods to identify and screen the literature using combined manual review and machine learning approaches. A protocol was developed that describes the literature search strategy and Populations, Exposures, Comparators, and Outcomes (PECO) criteria used to facilitate subsequent screening and categorization of literature into a systematic evidence map of PCB exposure and noncancer health endpoints across 15 organs/systems. A comprehensive literature search yielded 62,599 records. After electronic prioritization steps, 17,037 studies were manually screened at the title and abstract level. An additional 900 studies identified by experts or supplemental searches were also included. After full-text screening of 3889 references, 1586 studies met the PECO criteria. Relevant study details such as the endpoints assessed, exposure duration, and species were extracted into literature summary tables. This review compiles and organizes the human and mammalian studies from these tables into an evidence map for noncancer health endpoints and PCB mixture exposure to identify areas of robust research as well as areas of uncertainty that would benefit from future investigation. Summary data are available online as interactive visuals with downloadable metadata. Sufficient research is available to inform PCB hazard assessments for most organs/systems, but the amount of data to inform associations with specific endpoints differs. Furthermore, despite many years of research, sparse data exist for inhalation and dermal exposures, which are highly relevant human exposure routes. This evidence map provides a foundation for future systematic reviews and noncancer hazard assessments of PCB mixtures and for strategic planning of research to inform areas of greater uncertainty.

The role of epidemiology studies in human health risk assessment of polychlorinated biphenyls.

Polychlorinated biphenyls (PCBs) are a public health concern given evidence that they persist and accumulate in the environment and can cause toxic effects in animals and humans. However, evaluating adverse effects of PCBs in epidemiologic studies is complicated by the characteristics of PCB exposure. PCBs exist as mixtures in the environment; the mixture changes over time due to degradation, and given physicochemical differences between specific PCB congeners, the mixture that an individual is exposed to (via food, air, or other sources) is likely different from that which can be measured in biological tissues. This is particularly problematic when evaluating toxicity of shorter-lived congeners that may not be measurable by the time biological samples are collected. We review these and other issues that arise when evaluating epidemiologic studies of PCBs and discuss how epidemiology data can still be used to inform both hazard identification and dose-response evaluation.

Dietary carotenoids and cognitive function among US adults, NHANES 2011-2014.

Objectives: Dietary carotenoids may limit neuronal damage from free radicals, potentially serving as a modifiable risk factor for cognitive decline. We examined intake of lutein and zeaxanthin (L and Z) in relation to cognitive performance among 2011-2014 National Health and Nutrition Examination Survey participants aged ≥60 years. Methods: L and Z intake from foods and supplements was estimated from two non-consecutive 24-hour diet recalls. Outcomes included the CERAD Word Learning sub-test score, Animal Fluency test score, and Digit Symbol Substitution test score. Regression models were adjusted for survey design variables, year, sex, age, race/ethnicity, body mass index, family income, education, alcohol, and smoking. Results: Among the 2796 participants, higher dietary intake of L and Z was associated with higher score on each test. For example, the highest quartile of L and Z intake was associated with a 2.52 point increase (SE=0.86 points, P=0.01) on the digit symbol score test, compared with the lowest quartile. There were differences by race/ethnicity, with positive associations generally stronger for Black compared to white participants. Discussion: Further research from longitudinal studies is needed, but increasing L and Z intake may help to prevent or slow cognitive decline.

Using Medicaid Data to Improve Childhood Lead Poisoning Prevention Program Outcomes and Blood Lead Surveillance.

CONTEXT: Wisconsin-specific data revealed that not all Medicaid providers were testing children appropriately for blood lead levels and not all blood lead tests were reported to the Department of Health Services, Childhood Lead Poisoning Prevention Program. The Medicaid program requires blood lead screening for all Medicaid-enrolled children at specific ages. Wisconsin state law requires reporting of all blood lead test results. Projects were implemented to encourage appropriate testing for Medicaid-enrolled children and improve blood lead surveillance. METHODS: Medicaid billing data were linked to blood lead data to identify Medicaid-enrolled children who had not received the required tests. Medicaid provider report cards were distributed annually from 2006 to 2011 to inform providers of their compliance with federal testing requirements and of the names of children within their practice who had not been tested. Blood lead tests billed to Medicaid but not in the blood lead database were identified and billing providers were contacted to obtain the test report. RESULTS: The number of children tested increased from 81 834 children per year in 2006 to 106 003 children per year in 2010. Testing of Medicaid-enrolled children increased by 31% from 2006 to 2010. The percentage of Medicaid-enrolled children receiving an age-appropriate test increased from 46% in 2004 to a high of 55% in 2010. There were 9035 blood lead tests identified in the Medicaid billing data that had not been reported from 2007 to 2015. There were 468 billing providers who had unreported tests. All sites with unreported tests were contacted, 84% of test results were obtained, and 14% of test records could not be retrieved. Outpatient clinics accounted for the majority of all unreported tests (72%) and irretrievable test records (74%). DISCUSSION: Childhood lead poisoning prevention programs can effectively utilize Medicaid data to increase testing and improve blood lead surveillance. Primary health care providers should ensure that Medicaid-enrolled children in their care receive the age-appropriate tests. Many Wisconsin health care providers lack awareness of blood lead test reporting requirements. Outpatient clinics account for the largest proportion of unreported tests and highest priority should be given working with these sites to improve reporting practices.

Perfluoroalkyl substances and fish consumption.

BACKGROUND: Perfluoroalkyl substances (PFAS) are an emerging class of contaminants. Certain PFAS are regulated or voluntarily limited due to concern about environmental persistence and adverse health effects, including thyroid disease and dyslipidemia. The major source of PFAS exposure in the general population is thought to be consumption of seafood. OBJECTIVES: In this analysis we examine PFAS levels and their determinants, as well as associations between PFAS levels and self-reported fish and shellfish consumption, using a representative sample of the U.S. METHODS: Data on PFAS levels and self-reported fish consumption over the past 30 days were collected from the 2007-2008, 2009-2010, 2011-2012, and 2013-2014 cycles of the National Health and Nutrition Examination Survey. Twelve different PFAS were measured in serum samples from participants. Ordinary least squares regression models were used to identify factors (demographic characteristics and fish consumption habits) associated with serum PFAS concentrations. Additional models were further adjusted for other potential exposures including military service and consumption of ready-to-eat and fast foods. RESULTS: Seven PFAS were detected in at least 30% of participants and were examined in subsequent analyses (PFDA, PFOA, PFOS, PFHxS, MPAH, PFNA, PFUA). The PFAS with the highest concentrations were PFOS, followed by PFOA, PFHxS and PFNA (medians of 8.3, 2.7, 1.5 and 1.0ng/mL). Fish consumption was generally low, with a median of 1.2 fish meals and 0.14 shellfish meals, reported over the past 30 days. After adjusting for demographic characteristics, total fish consumption was associated with reduced MPAH, and with elevated PFDE, PFNA and PFuDA. Shellfish consumption was associated with elevations of all PFAS examined except MPAH. Certain specific fish and shellfish types were also associated with specific PFAS. Adjustment for additional exposure variables resulted in little to no change in effect estimates for seafood variables. CONCLUSIONS: PFAS are emerging contaminants with widespread exposure, persistence, and potential for adverse health effects. In the general population, fish and shellfish consumption are associated with PFAS levels, which may indicate an avenue for education and outreach.

Comprehension of Fish Consumption Guidelines Among Older Male Anglers in Wisconsin.

Although awareness of Wisconsin's fish consumption guidelines is high among older male anglers, little is known about comprehension of guideline content, and many anglers have levels of contaminants high enough to be associated with adverse health outcomes. The Environmental Protection Agency Great Lakes Restoration Initiative supported evaluation and revision of Wisconsin's fish consumption guideline program, using a web based survey of male Wisconsin anglers over the age of 50. A total of 3740 men completed the online survey; the median age of respondents was 62 years, and nearly all had lived and fished in Wisconsin for over 10 years. Comprehension of guideline content was relatively high, although two knowledge gaps were identified, one relating to mercury exposures and fish preparation, and the other to polychlorinated biphenyl content of certain fish species. The fishing regulations booklet distributed with annual fishing licenses and warning signs posted at fishing locations were commonly reported sources of guideline information in Wisconsin. Residents of coastal counties and consumers of Great Lakes fish were more likely to report guideline knowledge and behavior changes reflective of guideline knowledge, when compared to inland residents and those not consuming Great Lakes fish, respectively. In general, Wisconsin's consumption guidelines do not appear to discourage men from eating the fish they catch; rather, the most common behavioral changes included modifying the species eaten or the water body source of their meals. Continued efforts to educate anglers about the risks and benefits of fish consumption are needed.

Lack of a protective effect of cotton dust on risk of lung cancer: evidence from two population-based case-control studies.

BACKGROUND: Lung cancer is the leading cause of cancer death in North America. Exposure to cotton dust has previously been reported to decrease the risk of lung cancer. METHODS: We used data from two large case-control studies conducted in Montreal from 1979-1986 (Study 1) and 1996-2002 (Study 2) respectively, to examine the association between occupational exposure to cotton dust and risk of lung cancer. Cases were diagnosed with incident histologically-confirmed lung cancer (857 in Study 1, 1203 in Study 2). Population controls were randomly selected from electoral lists and frequency-matched to cases by age and sex (533 in Study 1, 1513 in Study 2). Interviews for the two studies used a virtually identical questionnaire to obtain lifetime occupational and smoking history, and several lifestyle covariates. Each participant's lifetime occupational history was reviewed by experts to assess exposure to a number of occupational agents, including cotton dust. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by unconditional logistic regression, adjusting for potential confounders. RESULTS: The lifetime prevalence of exposure to cotton dust was approximately 10%-15% in both studies combined, with some variation by study and by sex. Overall there was no decreased risk of lung cancer among subjects exposed to cotton dust. Rather, among all subjects there was a suggestion of slightly increased risk associated with any lifetime exposure to cotton dust (OR = 1.2, 95% CI: 1.0-1.5). This risk appeared to be concentrated among cases of adenocarcinoma (OR = 1.6, 95% CI: 1.2-2.2), and among moderate and heavy smokers (OR = 1.3, 95% CI: 1.0-1.7). There was no association when restricting to cases of either squamous cell or small cell cancer, or among never smokers and light smokers. An analogous examination of subjects exposed to wool dust revealed neither increased nor decreased risks of lung cancer. CONCLUSIONS: There was no evidence that cotton dust exposure decreased risks of lung cancer.

A systematic review of the association between pleural plaques and changes in lung function.

OBJECTIVES: To conduct a systematic review of changes in lung function in relation to presence of pleural plaques in asbestos-exposed populations. METHODS: Database searches of PubMed and Web of Science were supplemented by review of papers' reference lists and journals' tables of contents. Methodological features (eg, consideration of potential confounding by smoking) of identified articles were reviewed by ≥ two reviewers. Meta-analyses of 20 studies estimated a summary effect of the decrements in per cent predicted (%pred) forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) associated with presence of pleural plaques. RESULTS: Among asbestos-exposed workers, the presence of pleural plaques was associated with statistically significant decrements in FVC (4.09%pred, 95% CI 2.31 to 5.86) and FEV1 (1.99%pred, 95% CI 0.22 to 3.77). Effects of similar magnitude were seen when stratifying by imaging type (X-ray or high-resolution CT) and when excluding studies with potential methodological limitations. Undetected asbestosis was considered as an unlikely explanation of the observed decrements. Several studies provided evidence of an association between size of pleural plaques and degree of pulmonary decrease, and presence of pleural plaques and increased rate or degree of pulmonary impairment. CONCLUSIONS: The presence of pleural plaques is associated with a small, but statistically significant mean difference in FVC and FEV1 in comparison to asbestos-exposed individuals without plaques or other abnormalities. From a public health perspective, small group mean decrements in lung function coupled with an increased rate of decline in lung function of the exposed population may be consequential.

Serum selenium and lipid levels: Associations observed in the National Health and Nutrition Examination Survey (NHANES) 2011-2012.

Selenium is an essential micronutrient, and due to its antioxidant activity, is hypothesized to be beneficial to cardiovascular health. However, the evidence for an association between selenium and health markers such as lipid levels has been mixed. This may be due to substantial variability in the level of selenium intake between populations and potential non-linearity of selenium-health outcome associations. We used the 2011-2012 National Health and Nutrition Examination Survey (NHANES) to examine the relationship between serum selenium and lipid levels among participants aged 12 years and older. Associations were evaluated using both linear regression models, as well as ordinal logistic regression and quantile regression models to allow for potential non-linear relationships. In all models, potential confounders of sex, age group, race/ethnicity, educational attainment and cotinine were included. Overall, 40% of participants had total cholesterol levels classified as borderline or elevated, and total cholesterol increased with increasing selenium (p=0.01). A similar pattern was seen for triglycerides (p=0.02). LDL cholesterol was also associated with selenium but not in a linear fashion; HDL cholesterol did not vary with selenium. Multivariate quantile regression showed significant associations between selenium and total cholesterol, LDL cholesterol, and triglycerides. The effect of selenium was stronger with increasing quantile for total cholesterol and for triglycerides. In contrast, for LDL cholesterol the association was positive in the 10th and 50th percentiles, but (non-significant and) negative in the 90th percentile. These results show that while selenium may impact cardiovascular health via effects on lipid levels, the associations may not be linear.

Levels of nutrients in relation to fish consumption among older male anglers in Wisconsin.

Fish is an important source of nutrients including omega-3 fatty acids, which may reduce risk of adverse health outcomes such as cardiovascular disease; however, fish may also contain significant amounts of environmental pollutants. The Wisconsin Departments of Health Services and Natural Resources developed a survey instrument, along with a strategy to collect human biological samples to assess the risks and benefits associated with long-term fish consumption among older male anglers in Wisconsin. The target population was men aged 50 years and older, who fish Wisconsin waters and live in the state of Wisconsin. Participants provided blood and hair samples and completed a detailed (paper) questionnaire, which included questions on basic demographics, health status, location of catch and species of fish caught/eaten, consumption of locally caught and commercially purchased fish, and awareness and source of information for local and statewide consumption guidelines. Biological samples were used to assess levels of docosahexaenoic acid (DHA), docosapentaenoic acid (DPA), eicosapentaenoic acid (EPA); vitamin D; and selenium in blood. Quantile regression analysis was used to investigate the associations between biomarker levels and self-reported consumption of fish from the Great Lakes and other areas of concern, other locally caught fish, and commercially purchased fish (meals per year). Respondents were largely non-Hispanic white men in their 60's with at least some college education, and about half were retired. Fish consumption was high (median of 54.5 meals per year), with most fish meals coming from locally-caught fish. Multivariate regression models showed that the effect of supplement use was much greater than that of fish consumption, on nutrient levels, although consumption of fish from the Great Lakes and areas of concern was significantly associated with higher levels of vitamin D even after controlling for supplement usage.

Generation of hazard indices for cumulative exposure to phthalates for use in cumulative risk assessment.

Exposures to multiple chemicals may contribute to increased risk of similar adverse effects. Cumulative risk may be estimated using a hazard index (HI), the sum of individual hazard quotients (HQ, ratio of exposure to the reference value). We demonstrate the HI approach for five phthalates: di(2-ethylhexyl) phthalate (DEHP), di-n-butyl phthalate (DBP), diisobutyl phthalate (DiBP), diisononyl phthalate (DiNP), and butyl benzyl phthalate (BBP). Phthalate exposure for the US general population is estimated using urine metabolite levels from NHANES, extrapolating to ingested 'dose' using the creatinine correction approach. We used two sets of reference values: European Union Tolerable Daily Intakes and Denmark Environmental Protection Agency Derived No Effect Levels. We also investigated the use of an alternate reference value for DEHP, derived from a recent study on male reproductive system development. HQs and HIs were calculated for the total population ages 6years and older, as well as for men and women of approximate reproductive age (18-39 years), and children (6-11 years). Median HQs ranged from <0.01 for BBP, to ∼0.1 (using established values) or ∼2 (using an alternate value) for DEHP. Median HIs were <0.30 (95th percentiles just >1.0), and were driven by DEHP and DBP exposures.

Risk of lung cancer associated with six types of chlorinated solvents: results from two case-control studies in Montreal, Canada.

OBJECTIVES: To determine whether exposure to various chlorinated solvents is associated with lung cancer. METHODS: Two case-control studies of occupation and lung cancer were conducted in Montreal, and included 2016 cases and 2001 population controls. Occupational exposure to a large number of agents was evaluated using a combination of subject-reported job history and expert assessment. We examined associations between lung cancer among men and six specific chlorinated solvents and two chemical families (chlorinated alkanes and alkenes). ORs were calculated using unconditional multivariate logistic regression. RESULTS: When the two studies were pooled, there were indications of an increased risk of lung cancer associated with occupational exposure to perchloroethylene (OR(any exposure) 2.5, 95% CI 1.2 to 5.6; OR(substantial exposure) 2.4, 95% CI 0.8 to 7.7) and to carbon tetrachloride (OR(any exposure) 1.2, 95% CI 0.8 to 2.1; OR(substantial exposure) 2.5, 95% CI 1.1 to 5.7). No other chlorinated solvents showed both statistically significant associations and dose-response relationships. ORs appeared to be higher among non-smokers. When the lung cancer cases were separated by histological type, there was a suggestion of differential effects by tumour type, but statistical imprecision and multiple testing preclude strong inferences in this regard. CONCLUSIONS: There were suggestive, albeit inconsistent, indications that exposure to perchloroethylene and carbon tetrachloride may increase the risk of lung cancer. Results for other solvents were compatible with absence of risk.

The risk of lung cancer related to dietary intake of flavonoids.

It has been hypothesized that flavonoids in foods and beverages may reduce cancer risk through antioxidation, inhibition of inflammation, and other antimutagenic and antiproliferative properties. We examined associations between intake of 5 flavonoid subclasses (anthocyanidins, flavan-3-ols, flavones, flavonols, and flavanones) and lung cancer risk in a population-based case-control study in Montreal, Canada (1061 cases and 1425 controls). Flavonoid intake was estimated from a food frequency questionnaire that assessed diet 2 yr prior to diagnosis (cases) or interview (controls). Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression. Overall, total flavonoid intake was not associated with lung cancer risk, the effect being similar regardless of sex and smoking level. However, low flavonoid intake from food, but not from beverages, was associated with an increased risk. The adjusted ORs (95% CIs) comparing the highest vs. the lowest quartiles of intake were 0.63 (0.47-0.85) for total flavonoids, 0.82 (0.61-1.11) for anthocyanidins, 0.67 (0.50-0.90) for flavan-3-ols, 0.68 (0.50-0.93) for flavones, 0.62 (0.45-0.84) for flavonols, and 0.70 (0.53-0.94) for flavanones. An inverse association with total flavone and flavanone intake was observed for squamous cell carcinoma but not adenocarcinoma. In conclusion, low flavonoid intake from food may increase lung cancer risk.

An evidence map of polychlorinated biphenyl exposure and health outcome studies among residents of the Akwesasne Mohawk Nation.

From the 1950s to the 1970s, three Superfund sites discharged polychlorinated biphenyl (PCB)-contaminated waste upstream of the Mohawk Nation at Akwesasne, resulting in PCB contamination of groundwater, soil, and sediment in the surrounding area. Given the persistence of PCBs in the environment and in human tissues, there are continued concerns regarding PCB exposures and the potential for adverse health effects in the community. We developed an evidence map of PCB research at Akwesasne in order to characterize the available data and to highlight potential research needs. Human health and exposure biomarker studies were identified from a literature search based on population, exposure, comparator, and outcome (PECO) criteria. Data extracted from references that met the inclusion criteria after full-text review included study characteristics (e.g., sample size, study design, sampling years), details on PCB measurements (e.g., analytical method, number of congeners analyzed, method detection limits), and results (e.g., PCB levels and summary of study conclusions). We identified 33 studies, conducted between 1986 and 2013, that examined PCB exposure characteristics and health effects in residents of the Akwesasne Mohawk Nation. Organizing this literature into an evidence map including information on study cohort, congener groupings, exposure biomarker characteristics, and health effects allowed us to identify research gaps and to suggest future research priorities for the community. We identified current PCB exposure levels and PCB source characterization as major uncertainties, both of which could be addressed by new studies of PCB concentrations in environmental media.

Epidemiology Evidence for Health Effects of 150 per- and Polyfluoroalkyl Substances: A Systematic Evidence Map.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) comprise a large class of chemicals with widespread use and persistence in the environment and in humans; however, most of the epidemiology research has focused on a small subset. OBJECTIVES: The aim of this systematic evidence map (SEM) is to summarize the epidemiology evidence on approximately 150 lesser studied PFAS prioritized by the EPA for tiered toxicity testing, facilitating interpretation of those results as well as identification of priorities for risk assessment and data gaps for future research. METHODS: The Populations, Exposure, Comparators, and Outcomes (PECO) criteria were intentionally broad to identify studies of any health effects in humans with information on associations with exposure to the identified PFAS. Systematic review methods were used to search for literature that was screened using machine-learning software and manual review. Studies meeting the PECO criteria underwent quantitative data extraction and evaluation for risk of bias and sensitivity using the Integrated Risk Information System approach. RESULTS: 193 epidemiology studies were identified, which included information on 15 of the PFAS of interest. The most commonly studied health effect categories were metabolic (n=37), endocrine (n=30), cardiovascular (30), female reproductive (n=27), developmental (n=26), immune (n=22), nervous (n=21), male reproductive (n=14), cancer (n=12), and urinary (n=11) effects. In study evaluation, 120 (62%) studies were considered High/Medium confidence for at least one outcome. DISCUSSION: Most of the PFAS in this SEM have little to no epidemiology data available to inform evaluation of potential health effects. Although exposure to the 15 PFAS that had data was fairly low in most studies, these less-studied PFAS may be used as replacements for "legacy" PFAS, leading to potentially greater exposure. It is impractical to generate epidemiology evidence to fill the existing gaps for all potentially relevant PFAS. This SEM highlights some of the important research gaps that currently exist. https://doi.org/10.1289/EHP11185.

Disparities in infectious disease hospitalizations for American Indian/ Alaska Native people.

OBJECTIVES: We described disparities in infectious disease (ID) hospitalizations for American Indian/Alaska Native (AI/AN) people. METHODS: We analyzed hospitalizations with an ID listed as the first discharge diagnosis in 1998-2006 for AI/AN people from the Indian Health Service National Patient Information Reporting System and compared them with records for the general U.S. population from the Nationwide Inpatient Survey. RESULTS: The ID hospitalization rate for AI/AN people declined during the study period. The 2004-2006 mean annual age-adjusted ID hospitalization rate for AI/AN people (1,708 per 100,000 populiation) was slightly higher than that for the U.S. population (1,610 per 100,000 population). The rate for AI/AN people was highest in the Southwest (2,314 per 100,000 population), Alaska (2,063 per 100,000 population), and Northern Plains West (1,957 per 100,000 population) regions, and among infants (9,315 per 100,000 population). ID hospitalizations accounted for approximately 22% of all AI/AN hospitalizations. Lower-respiratory-tract infections accounted for the largest proportion of ID hospitalizations among AI/AN people (35%) followed by skin and soft tissue infections (19%), and infections of the kidney, urinary tract, and bladder (11%). CONCLUSIONS: Although the ID hospitalization rate for AI/AN people has declined, it remains higher than that for the U.S. general population, and is highest in the Southwest, Northern Plains West, and Alaska regions. Lower-respiratory-tract infections; skin and soft tissue infections; and kidney, urinary tract, and bladder infections contributed most to these health disparities. Future prevention strategies should focus on high-risk regions and age groups, along with illnesses contributing to health disparities.

Prenatal exposure to multiple metals and birth outcomes: An observational study within the National Children's Study cohort.

BACKGROUND: Prenatal exposure to metals may play an important role in fetal growth. However, the epidemiologic evidence for certain metals is sparse, and most of the existing research has focused on evaluating single metals in highly exposed target populations. OBJECTIVES: We evaluated associations of cadmium, lead, manganese, selenium, and total mercury exposures during pregnancy with fetal growth using data from mother-infant pairs participating in the National Children's Study. METHODS: Prenatal metal exposures were measured using maternal blood collected from 6 to 32 weeks of gestation. Birth outcomes, including gestational age, birthweight, birth length, head circumference, and ponderal index, were ascertained through physical measurement at birth or abstraction from medical records. Regression coefficients and their 95% confidence intervals were estimated from multivariable linear regression models in the overall study population as well as among male and female infants. We further evaluated pairwise metal-metal interactions. RESULTS: Sex-specific associations were observed for lead, with inverse associations for birthweight, birth length, head circumference, and gestational age observed only among female infants. Sex-specific associations were also observed for selenium, with a positive association for birthweight observed among male infants; selenium was also positively associated with ponderal index and inversely associated with birth length among female infants. Overall, total mercury was inversely associated with birthweight and ponderal index, and the association with birthweight was stronger among female infants. No significant associations were observed with cadmium and manganese. In the metal-metal interaction analyses, we found evidence of a synergistic interaction between lead and total mercury and antagonistic interaction between selenium and total mercury with selected birth outcomes. CONCLUSIONS: Our findings suggest that prenatal exposure to metals may be related to birth outcomes, and infant sex may modify these associations.

Trends in hospitalizations for peptic ulcer disease, United States, 1998-2005.

Infection with Helicobacter pylori increases the risk for peptic ulcer disease (PUD) and its complications. To determine whether hospitalization rates for PUD have declined since antimicrobial drugs to eradicate H. pylori became available, we examined 1998-2005 hospitalization records (using the Nationwide Inpatient Sample) in which the primary discharge diagnosis was PUD. Hospitalizations for which the diagnosis was H. pylori infection were also considered. The age-adjusted hospitalization rate for PUD decreased 21% from 71.1/100,000 population (95% confidence interval [CI] 68.9-73.4) in 1998 to 56.5/100,000 in 2005 (95% CI 54.6-58.3). The hospitalization rate for PUD was highest for adults > or =65 years of age and was higher for men than for women. The age-adjusted rate was lowest for whites and declined for all racial/ethnic groups, except Hispanics. The age-adjusted H. pylori hospitalization rate also decreased. The decrease in PUD hospitalization rates suggests that the incidence of complications caused by H. pylori infection has declined.

Progressive multifocal leukoencephalopathy deaths in the USA, 1979-2005.

BACKGROUND: Progressive multifocal leukoencephalopathy (PML) is a neurological disease most often seen among immunosuppressed patients. The incidence of PML increased with an increasing incidence of HIV/AIDS. We describe recent trends and the epidemiology of PML-associated death in the era of highly active antiretroviral therapy (HAART). METHODS: National multiple-cause-of-death data for the USA were used to identify records with PML listed as a cause of death during 1979-2005. Age-adjusted PML-associated death rates were calculated overall and by sex, race, region and HIV status. RESULTS: The PML-associated death rates peaked in the mid-1990s and decreased from 2.76 deaths per 1 million persons in 1992-1995 to 0.66 in 2002-2005. This decrease was mainly due to a decreasing death rate among PML decedents with HIV diagnosis, males and those aged 20-49 years at death. A decline in death rate was also seen among PML decedents without HIV diagnosis, although this trend was not significant. Decedents in the latter time period were more often female, and older. The proportion of HIV-associated deaths from PML decreased between 1992-1995 (1.4%) and 2002-2005 (1.0%). CONCLUSION: PML mortality has decreased significantly since 1996 when HAART became the standard of care in the USA. This decline likely reflects increased survival among HIV-positive persons who receive HAART.