Recent Single-Family Home Buyer Knowledge, Attitudes, and Behaviors Related to Lead and Radon Exposure Prevention.

CONTEXT: Federal law requires property owners to disclose the presence of known lead-based paint and/or lead hazards to potential home buyers and renters in homes built before 1978. OBJECTIVE: Using 2015-2016 randomized survey data, we measured lead and radon knowledge, awareness, and exposure avoidance practices. SETTING: Home buyers from 4 US states (Illinois, Minnesota, North Carolina, and Ohio). PARTICIPANTS: 477 recent, single-family pre-1978 dwelling home buyers. MAIN OUTCOME MEASURE(S): Predictors of the home buyer decision to purchase the home during the entire home buying experience based on their understanding of health issues related to lead-based paint and radon exposure. RESULTS: Personal networks (22%) and real estate agents (21%) were the most common sources of health-related lead information. Many home buyers (77%) reported that their awareness of lead did not affect their purchasing decision, and 78% could not confirm that their homes were tested for lead. Respondents who understood lead-related health effects were 5.4 times more likely (95% CI, 1.7-17.5) to have their decision to buy a home affected when their real estate agent discussed lead-based paint issues. Many home buyers reported either they did not remember (37%) or did not sign (20%) the federal law requirement that property owners reveal known lead paint hazards to prospective buyers before a property is sold. Home buyers with awareness of health issues caused by radon were 1.7 times (95% CI, 1.4-2.1) more likely than those who understood lead-related health issues to have their decision to buy the home affected. CONCLUSION: Real estate agents play an important role to increase awareness of potential lead-based paint health issues when people buy older homes. Home buyer knowledge, awareness, and practice of radon exposure prevention was greater compared to lead exposure prevention. More than half of home buyers did not sign or remember signing lead disclosure paperwork.

Test-Retest Reproducibility of Adult-Reported High School Diet Varies among Racially and Ethnically Diverse US Men and Women.

Background: Adolescent diet is thought to play an important role in future chronic disease risk. However, few studies have examined the reproducibility of adult-reported adolescent diet, and evidence for possible differences in reproducibility by demographic characteristics is limited. Objective: We assessed the ability of adults to consistently report past high school diet over a 1-y period and examined differences in reproducibility by selected demographic characteristics. Methods: By using age-adjusted partial Spearman (ρ) or Pearson (r) correlations, we assessed 1-y reproducibility for 33 line items, 20 food groups, and 2 dietary patterns of high school diet reported in adulthood via a questionnaire completed by 742 participants in the Cancer Prevention Study 3 (CPS-3) Diet Substudy. Results: Participants' median age was 53 y (range: 31-70 y), 65.2% were women, 59.8% were non-Hispanic white, 24.8% were non-Hispanic black, and 15.4% were Hispanic. The mean Spearman correlation assessing reproducibility across the 33 line items was 0.60 and ranged from 0.44 to 0.72, with no differences in mean correlations by age, sex, race/ethnicity, education, or body mass index (BMI). Reproducibility was similar across food groups (ρ = 0.62; range: 0.44-0.68), with differences by sex, ethnicity, age, or BMI observed for some food groups (e.g., sugar-sweetened beverages). Pearson correlations for the reproducibility of 2 major eating patterns, "fast food" and "whole food," were 0.73 and 0.72, respectively. Conclusion: These results show good 1-y reproducibility of assessed high school diet, as reported from memory in adulthood, by line item, food group, and dietary pattern, with noted differences by demographic characteristics.

The Effect of a Regimen of Antifungal Cream Use on Episodes of Acute Adenolymphangitis (ADL) among Lymphedema Patients: An Application Using Marginal Structural Models.

Episodes of adenolymphangitis (ADL) are a recurrent clinical aspect of lymphatic filariasis (LF) and a risk factor for progression of lymphedema. Inter-digital entry lesions, often found on the web spaces between the toes of those suffering from lymphedema, have been shown to contribute to the occurrence of ADL episodes. Use of antifungal cream on lesions is often promoted as a critical component of lymphedema management. Our objective was to estimate the observed effect of antifungal cream use on ADL episodes according to treatment regimen among a cohort of lymphedema patients enrolled in a morbidity management program. We estimated this effect using marginal structural models for time varying confounding. In this longitudinal study, we estimate that for every one-unit increase in the number of times one was compliant to cream use through 12 months, there was a 23% (RR = 0.77 (0.62, 0.96)) decrease in the number of ADL episodes at 18 months, however the RR's were not statistically significant at other study time points. Traditionally adjusted models produced a non-significant RR closer to the null at all time points. This is the first study to estimate the effect of a regimen of antifungal cream on the frequency of ADL episodes. This study also highlights the importance of the consideration and proper handling of time-varying confounders in longitudinal observational studies.

Cancer deaths and cases attributable to lifestyle factors and infections in China, 2013.

BACKGROUND: The burden of cancer in China is high, and it is expected to further increase. Information on cancers attributable to potentially modifiable risk factors is essential in planning preventive measures against cancer. We estimated the number and proportion of cancer deaths and cases attributable to ever-smoking, second-hand smoking, alcohol drinking, low fruit/vegetable intake, excess body weight, physical inactivity, and infections in China, using contemporary data from nationally representative surveys and cancer registries. METHODS: The number of cancer deaths and cases in 2013 were obtained from the National Central Cancer Registry of China and data on most exposures were obtained from the China National Nutrition and Health Survey 2002 or 2006 and Global Adult Tobacco Smoking 2010. We used a bootstrap simulation method to calculate the number and proportion of cancer deaths and cases attributable to risk factors and their corresponding 95% confidence intervals (CIs), allowing for uncertainty in data. RESULTS: Approximately 718 000 (95% CI 702 100-732 200) cancer deaths in men and 283 100 (278 800-288 800) cancer deaths in women were attributable to the studied risk factors, accounting for 52% of all cancer deaths in men and 35% in women. The numbers for incident cancer cases were 952 500 (95% CI 934 200-971 400) in men and 442 700 (437 200-447 900) in women, accounting for 47% of all incident cases in men and 28% in women. The greatest proportions of cancer deaths attributable to risk factors were for smoking (26%), HBV infection (12%), and low fruit/vegetable intake (7%) in men and HBV infection (7%), low fruit/vegetable intake (6%), and second-hand smoking (5%) in women. CONCLUSIONS: Effective public health interventions to eliminate or reduce exposure from these risk factors, notably tobacco control and vaccinations against carcinogenic infections, can have considerable impact on reducing the cancer burden in China.

Norovirus in symptomatic and asymptomatic individuals: cytokines and viral shedding.

Noroviruses (NoV) are the most common cause of epidemic gastroenteritis world-wide. NoV infections are often asymptomatic, although individuals still shed large amounts of NoV in their stool. Understanding the differences between asymptomatic and symptomatic individuals would help in elucidating mechanisms of NoV pathogenesis. Our goal was to compare the serum cytokine responses and faecal viral RNA titres of asymptomatic and symptomatic NoV-infected individuals. We tested serum samples from infected subjects (n = 26; 19 symptomatic, seven asymptomatic) from two human challenge studies of GI.1 NoV for 16 cytokines. Samples from prechallenge and days 1-4 post-challenge were tested for these cytokines. Cytokine levels were compared to stool NoV RNA titres quantified previously by reverse transcription-polymerase chain reaction (RT-qPCR). While both symptomatic and asymptomatic groups had similar patterns of cytokine responses, the symptomatic group generally exhibited a greater elevation of T helper type 1 (Th1) and Th2 cytokines and IL-8 post-challenge compared to the asymptomatic group (all P < 0·01). Daily viral RNA titre was associated positively with daily IL-6 concentration and negatively with daily IL-12p40 concentration (all P < 0·05). Symptoms were not associated significantly with daily viral RNA titre, duration of viral shedding or cumulative shedding. Symptomatic individuals, compared to asymptomatic, have greater immune system activation, as measured by serum cytokines, but they do not have greater viral burden, as measured by titre and shedding, suggesting that symptoms may be immune-mediated in NoV infection.

Human norovirus infection and the acute serum cytokine response.

Noroviruses (NoV) are the most common cause of epidemic gastroenteritis worldwide. The acute immune response to NoV in humans is poorly understood, hindering research on prevention and treatment. To elucidate the acute immune response and test for cytokine predictors of susceptibility to infection, serum samples from two human NoV challenge studies were tested for 16 cytokines. Subjects who became infected (n = 26) were age-matched with subjects who remained uninfected following NoV challenge (n = 26). Samples were tested from prechallenge and days 1-4 post-challenge. Cytokine responses were compared between infected and uninfected groups. Overall, infected individuals exhibited an elevation in T helper type 1 (Th1) and Th2 cytokines, as well as chemokines interleukin (IL)-8 and monocyte chemoattractant protein (MCP-1), compared to uninfected individuals (all P < 0.05). Most cytokines peaked on day 2 post-challenge in infected subjects, and tumour necrosis factor (TNF)-α, IL-8, and IL-10 remained elevated to day 3. The only cytokine elevated significantly among infected subjects to day 4 post-challenge was IL-10 (P = 0.021). Prechallenge cytokine concentrations were not predictive of infection status post-challenge. There were no significant changes in serum cytokines among NoV-challenged subjects who remained uninfected. These results suggest that NoV infection elicits a Th1-type response, with some Th2 activation. Persistent elevation of IL-10 among infected subjects is consistent with activation of adaptive immune responses, such as B cell expansion, as well as down-regulation of Th1 cytokines. This study presents the first comprehensive description of the acute cytokine response to GI.1 NoV in humans.

Characterizing concentrations of diethylene glycol and suspected metabolites in human serum, urine, and cerebrospinal fluid samples from the Panama DEG mass poisoning.

CONTEXT: Diethylene glycol (DEG) mass poisoning is a persistent public health problem. Unfortunately, there are no human biological data on DEG and its suspected metabolites in poisoning. If present and associated with poisoning, the evidence for use of traditional therapies such as fomepizole and/or hemodialysis would be much stronger. OBJECTIVE: To characterize DEG and its metabolites in stored serum, urine, and cerebrospinal fluid (CSF) specimens obtained from human DEG poisoning victims enrolled in a 2006 case-control study. METHODS: In the 2006 study, biological samples from persons enrolled in a case-control study (42 cases with new-onset, unexplained AKI and 140 age-, sex-, and admission date-matched controls without AKI) were collected and shipped to the Centers for Disease Control and Prevention (CDC) in Atlanta for various analyses and were then frozen in storage. For this study, when sufficient volume of the original specimen remained, the following analytes were quantitatively measured in serum, urine, and CSF: DEG, 2-hydroxyethoxyacetic acid (HEAA), diglycolic acid, ethylene glycol, glycolic acid, and oxalic acid. Analytes were measured using low resolution GC/MS, descriptive statistics calculated and case results compared with controls when appropriate. Specimens were de-identified so previously collected demographic, exposure, and health data were not available. The Wilcoxon Rank Sum test (with exact p-values) and bivariable exact logistic regression were used in SAS v9.2 for data analysis. RESULTS: The following samples were analyzed: serum, 20 case, and 20 controls; urine, 11 case and 22 controls; and CSF, 11 samples from 10 cases and no controls. Diglycolic acid was detected in all case serum samples (median, 40.7 mcg/mL; range, 22.6-75.2) and no controls, and in all case urine samples (median, 28.7 mcg/mL; range, 14-118.4) and only five (23%) controls (median, < Lower Limit of Quantitation (LLQ); range, < LLQ-43.3 mcg/mL). Significant differences and associations were identified between case status and the following: 1) serum oxalic acid and serum HEAA (both OR = 14.6; 95% C I = 2.8-100.9); 2) serum diglycolic acid and urine diglycolic acid (both OR > 999; exact p < 0.0001); and 3) urinary glycolic acid (OR = 0.057; 95% C I = 0.001-0.55). Two CSF sample results were excluded and two from the same case were averaged, yielding eight samples from eight cases. Diglycolic acid was detected in seven (88%) of case CSF samples (median, 2.03 mcg/mL; range, < LLQ, 7.47). DISCUSSION: Significantly elevated HEAA (serum) and diglycolic acid (serum and urine) concentrations were identified among cases, which is consistent with animal data. Low urinary glycolic acid concentrations in cases may have been due to concurrent AKI. Although serum glycolic concentrations among cases may have initially increased, further metabolism to oxalic acid may have occurred thereby explaining the similar glycolic acid concentrations in cases and controls. The increased serum oxalic acid concentration results in cases versus controls are consistent with this hypothesis. CONCLUSION: Diglycolic acid is associated with human DEG poisoning and may be a biomarker for poisoning. These findings add to animal data suggesting a possible role for traditional antidotal therapies. The detection of HEAA and diglycolic acid in the CSF of cases suggests a possible association with signs and symptoms of DEG-associated neurotoxicity. Further work characterizing the pathophysiology of DEG-associated neurotoxicity and the role of traditional toxic alcohol therapies such as fomepizole and hemodialysis is needed.

Physical activity and cardiovascular risk factors at menopause: the Nord-Trøndelag health study.

BACKGROUND: Lowered physical activity levels may partially explain changes in metabolic risk factors in women after menopause. OBJECTIVES: To evaluate the association between physical activity and metabolic risk factors at baseline and after 11 years, as well as the change in that association over time in women who were premenopausal and ≥ 40 years at baseline. METHODS: Subjects in a Norwegian population-based health survey answered questionnaires and had body and serum measurements during 1995-1997 (HUNT 2) and in a follow-up study during 2006-2008 (HUNT 3). Repeated-measures analyses were used to estimate the association between physical activity and metabolic factors, adjusting for age, smoking status, education, alcohol intake, and parity. Adjustment for hormonal treatment and medication was made, as appropriate. RESULTS: In women remaining premenopausal, a higher physical activity score in HUNT 3 was associated with lower weight (p < 0.01) and waist-hip ratio (p < 0.01) and higher high density lipoprotein (HDL) cholesterol in HUNT 3 (p < 0.01). In women that were postmenopausal by the time of follow-up, a higher physical activity score in HUNT 3 was associated with lower weight (p < 0.01), waist-hip ratio (p < 0.01), triglycerides (p < 0.01), and higher total cholesterol (p < 0.05), HDL cholesterol (p < 0.01), and diastolic blood pressure (p < 0.05) in HUNT 3. The association of total physical activity score with weight and waist-hip ratio was stronger in HUNT 3 than in HUNT 2 (p < 0.01). CONCLUSION: Increased physical activity may reduce the risk of adverse outcomes and use of pharmacological management in women of menopausal age.

Physical activity and age at menopause: the Nord-Trøndelag population-based health study.

BACKGROUND: Age at menopause may affect women's subsequent morbidity and mortality. In contrast to numerous other health outcomes, little is known about the possible effects of physical activity on age at menopause. OBJECTIVES: To assess the relationship between leisure-time physical activity and age at menopause. METHODS: Premenopausal women participating in a population-based health survey (HUNT 2) conducted in the county of Nord-Trøndelag, Norway reported their physical activity in the period of 1995-1997. Age at menopause was reported during 2006-2008 (HUNT 3). Cox proportional hazards models were used to estimate hazard ratios for menopause and logistic regression to estimate odds ratios for early menopause, with 95% confidence intervals, adjusting for age at menarche, parity, use of oral contraceptives prior to the 6 months preceding participation in HUNT 2, symptoms of depression, smoking status, and education. RESULTS: Women aged 40-49 years at baseline had lower hazard ratios for menopause when participating in any light leisure-time physical activity compared with no activity (p < 0.05) and similar results were observed in 19-39-year-olds. In 50-59-year-old women, the results varied greatly and did not reach statistical significance. CONCLUSIONS: The effects of leisure-time physical activity on age at menopause may be age-dependent. We found indications of earlier menopause for the least active women aged 19-49 years at baseline.

Comparison of emergency department and hospital admissions data for air pollution time-series studies.

BACKGROUND: Emergency department (ED) visit and hospital admissions (HA) data have been an indispensible resource for assessing acute morbidity impacts of air pollution. ED visits and HAs are types of health care visits with similarities, but also potentially important differences. Little previous information is available regarding the impact of health care visit type on observed acute air pollution-health associations from studies conducted for the same location, time period, outcome definitions and model specifications. METHODS: As part of a broader study of air pollution and health in St. Louis, individual-level ED and HA data were obtained for a 6.5 year period for acute care hospitals in the eight Missouri counties of the St. Louis metropolitan area. Patient demographic characteristics and diagnostic code distributions were compared for four visit types including ED visits, HAs, HAs that came through the ED, and non-elective HAs. Time-series analyses of the relationship between daily ambient ozone and PM2.5 and selected cardiorespiratory outcomes were conducted for each visit type. RESULTS: Our results indicate that, compared with ED patients, HA patients tended to be older, had evidence of greater severity for some outcomes, and had a different mix of specific outcomes. Consideration of 'HA through ED' appeared to more effectively select acute visits than consideration of 'non-elective HA'. While outcomes with the strongest observed temporal associations with air pollutants tended to show strong associations for all visit types, we found some differences in observed associations for ED visits and HAs. For example, risk ratios for the respiratory disease-ozone association were 1.020 for ED visits and 1.004 for 'HA through ED'; risk ratios for the asthma/wheeze-ozone association were 1.069 for ED visits and 1.106 for 'HA through ED'. Several factors (e.g. age) were identified that may be responsible, in part, for the differences in observed associations. CONCLUSIONS: Demographic and diagnostic differences between visit types may lead to preference for one visit type over another for some questions and populations. The strengths of observed associations with air pollutants sometimes varied between different health care visit types, but the relative strengths of association generally were specific to the pollutant-outcome combination.

Residential carbon monoxide alarm prevalence and ordinance awareness.

OBJECTIVE: Unintentional carbon monoxide (CO) poisoning is a leading cause of poisoning in the United States. Most poisoning cases occur in residential settings and a working CO alarm may prevent many of these events. The use of a CO alarm is mandated in many parts of the country; however, little is known about the compliance and adoption of such ordinances at the population level. This study determined the prevalence of residential CO alarm and awareness of a 2001 CO alarm ordinance in Mecklenburg County, North Carolina in 2009. METHODS: A random sample of households stratified by housing type (eg, single-family homes, multifamily homes) was included in a cross-sectional survey conducted. One adult respondent from each household was administered a questionnaire that included information on sociodemographic and household characteristics, presence of a CO alarm, and CO alarm ordinance awareness. Data were analyzed using multivariate stratified conditional logistic regression. RESULTS: Among 214 participating households (response rate, 23.4%), 145 (67.8%) reported having a working CO alarm and 79 (36.9%) of the respondents were aware of the CO alarm ordinance. Respondents who were aware of the ordinance had 9 times higher odds (95% confidence interval, 3.3-25.9) of having a CO alarm than those who were unaware. Also, households with an attached garage had more than 2 times higher odds (95% confidence interval, 1.0-6.2) of having a CO alarm than those without an attached garage. Awareness of the CO alarm ordinance was not associated with any sociodemographic (eg, age, sex, race, education, income) or household (eg, home ownership, home construction year) characteristics. CONCLUSIONS: Carbon monoxide alarm prevalence in Mecklenburg County households was higher than the national average and was associated with CO alarm ordinance awareness. Public health efforts might benefit from regulations aimed at population-level adoption of preventive health behaviors.

Race, neighbourhood characteristics and disparities in chemotherapy for colorectal cancer.

BACKGROUND: Studies have found significant race/ethnic and age differences in receipt of adjuvant chemotherapy for stages III colon and II/III rectal cancers. Little is known about the role of neighbourhood factors in these disparities. METHODS: The 4748 Black and White patients from the Georgia Comprehensive Cancer Registry were diagnosed with stages III colon and II/III rectal cancers between 2000 and 2004. Neighbourhood poverty, segregation (% Black residents) and rurality were linked to each patient using census tract identifiers. Multilevel analyses explored the role of neighbourhood characteristics and the nested association of patient race within categories of neighbourhoods in receipt of chemotherapy. RESULTS: Odds of receiving chemotherapy for urban and suburban patients were 38% (95% CI 1.09 to 1.74) and 53% (95% CI 1.20 to 1.94) higher than for rural patients. However, odds of receiving chemotherapy for urban Black patients were 24% (95% CI 0.62 to 0.94) lower than for their White counterparts. Receipt of chemotherapy did not significantly differ between Blacks and Whites residing in suburban or rural areas. CONCLUSION: Black-White disparities in receipt of chemotherapy among Georgia colorectal cancer patients were confined to urban patients. Disparities in receipt of this treatment for rural patients were found irrespective of patient race. Our findings highlight geographic areas where targeted interventions might be needed.

Physical activity and fertility in women: the North-Trøndelag Health Study.

BACKGROUND: Changes in the state of energy balance owing to changes in physical activity may affect the reproductive system. We evaluated the association between physical activity (PA) and fertility and parity in healthy women. METHODS: A population-based health survey (HUNT 1) was conducted during 1984-1986 in Nord-Trøndelag county, Norway, with follow-up from 1995 to 1997 (HUNT 2). The study included 3887 women, <45 years old in HUNT 2. PA was assessed by baseline questionnaire, and fertility and parity by questionnaire at follow-up. Data focused on overall occurrence of infertility in the population (without biological confirmation). RESULTS: Increased frequency, duration and intensity of PA were associated with increased subfertility, and frequency of PA was associated with voluntary childlessness (P < 0.01). After adjusting for age, parity, smoking, and marital status, women who were active on most days were 3.2 times more likely to have fertility problems than inactive women. Exercising to exhaustion was associated with 2.3 times the odds of fertility problems versus low intensity. Women with highest intensity of PA at baseline had the lowest frequency of continuing nulliparity and highest frequency of having three or more children during follow-up (P < 0.05). Sensitivity analysis including body mass index as confounder did not alter the results. No associations were found between lower activity levels and fertility or parity. CONCLUSION: Increased risk of infertility was only found for the small group of women reporting the highest levels of intensity and frequency of PA. Awareness of the possible risks of infertility should be highlighted among non-athletic women who exercise vigorously.

The issue of confounding in epidemiological studies of ambient air pollution and pregnancy outcomes.

BACKGROUND: Relationships between ambient air pollution levels during pregnancy and adverse pregnancy outcomes have been investigated using one of three analytic approaches: ambient pollution levels have been contrasted over space, time or both space and time. Although the three approaches share a common goal, to estimate the causal effects of pollution on pregnancy outcomes, they face different challenges with respect to confounding. METHODS: A framework based on counterfactual effect definitions to examine issues related to confounding in spatial, temporal, and spatial-temporal analyses of air pollution and pregnancy outcomes is presented, and their implications for inference are discussed. RESULTS: In spatial analyses, risk factors that are spatially correlated with pollution levels are confounders; the primary challenges relate to the availability and validity of risk factor measurements. In temporal analyses, where smooth functions of time are commonly used to control for confounding, concerns relate to the adequacy of control and the possibility that abrupt changes in risk might be systematically related to pollution levels. Spatial-temporal approaches are subject to challenges faced in both spatial and temporal analyses. CONCLUSION: Each approach faces different challenges with respect to the likely sources of confounding and the ability to control for that confounding because of differences in the type, availability, and quality of information required. Thoughtful consideration of these differences should help investigators select the analytic approach that best promotes the validity of their research.

Adjusting for reverse causality in the relationship between obesity and mortality.

Reverse causality, in which obesity-induced disease leads to both weight loss and higher mortality, may bias observed associations between body mass index (BMI) and mortality, but the magnitude of that bias is unknown. The authors examined the impact of reverse causality and the exclusion of various diseases on the observed age-specific mortality ratios for BMI by using a state space model and sensitivity analyses. They found that reverse causality may decrease the ratios and induce a J-shaped curve on a graph. The authors further found that the net effect of excluding various diseases becomes a balance of competing forces, some tending to increase observed mortality ratios, where as others, such as selection based on common effects, may decrease them. Instead of studying just the change in observed mortality ratios, which can be misleading, investigators need to consider causal relationships and evaluate the conceptual and theoretical impact of any analytic maneuver. Analyses should be balanced with sensitivity approaches as well as with alternative analytic approaches such as the use of structural models, G-estimation, simulations and ancillary data from animal studies.

Maternal plasma cytokines in early- and mid-gestation of normal human pregnancy and their association with maternal factors.

Few studies have assessed longitudinal changes in circulating cytokine levels during normal pregnancy. We have examined the natural history of maternal plasma cytokines from early- to mid-pregnancy in a large, longitudinal cohort. Multiplex flow cytometry was used to measure interleukin (IL)-2, IL-6, IL-12, tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma and granulocyte-macrophage colony-stimulating factor (GM-CSF) in early- (median [IQR]: 8.5 weeks [7.1, 10.0]) and mid-pregnancy (25.0 [24.1, 26.1]) from 1274 Danish women delivering singleton term infants. GM-CSF decreased from early- to mid-pregnancy (median percent change [95% CI]: -51.3% [-59.1%, -41.8%]), while increases were observed in IL-6 (24.3% [4.6%, 43.9%]), IL-12 (21.3% [8.9%, 35.7%]) and IFN-gamma (131.7% [100.2%, 171.6%]); IL-2 (-2.8% [-11.5%, 0.0%]) and TNF-alpha (0% [-5.9%, 25.6%]) remained stable. Positive correlations were found between all cytokines, both in early- and mid-pregnancy (all p<0.001). Early- and mid-pregnancy levels were rank-correlated for IL-2, IL-12, TNF-alpha and GM-CSF, but not IL-6 and IFN-gamma; these correlations were generally weaker than correlations between different cytokines at a single time point in pregnancy. Women with a pre-pregnancy BMI <18.5 had reduced levels of IFN-gamma and GM-CSF compared to women in other BMI categories, while women aged >or=35 years had elevated IL-2, IL-6, TNF-alpha and IFN-gamma. Early-pregnancy levels of TNF-alpha were higher in women with a prior preterm delivery. Cytokine levels were not associated with gravidity. In conclusion, cytokines were detected in plasma during early- and mid-pregnancy, with IL-6, IL-12, IFN-gamma and GM-CSF concentrations varying over pregnancy. Concentrations may depend on BMI, maternal age and prior preterm delivery.

Blood lead levels and risk factors for lead poisoning in children and caregivers in Chuuk State, Micronesia.

Lead poisoning is a preventable environmental disease. Children and developing fetuses are especially vulnerable; even low blood lead levels (BLLs) are linked with learning and behavioral problems. We assessed children's and their caregivers' BLLs and risk factors for lead exposure in Chuuk State, Federated States of Micronesia. Children aged 2-6 years were randomly selected within 20 randomly selected villages. Children and caregivers provided venous blood, and caregivers offered information about possible risk factors for lead exposure. Mean BLLs were 39 microg/l for children and 16 microg/l for caregivers. Children with BLLs of > or = 100 microg/l (elevated) were 22.9 (95% CI: 4.5-116.0) times more likely to have a caregiver with an elevated BLL, 6.2 (95% CI: 1.4-27.3) times more likely to live on an outer island, and 3.4 (95% CI: 1.7-6.9) times more likely to have a family member who made lead fishing weights than did other children even after controlling for age and sex. For children, 61% of elevated BLLs could be attributed to making fishing weights. Caregivers with elevated BLLs were 5.9 (95% CI: 1.5-23.7) times more likely to live in a household that melted batteries than other caregivers even after controlling for age and education. For caregivers, 37% of the elevated BLLs could be attributed to melting batteries. The association of elevated BLLs in children and their caregiver suggests a common environmental exposure. Melting batteries to make fishing sinkers is a preventable source of lead exposure for children and their caregivers in Chuuk. Published by Elsevier GmbH.

Tests of trait-haplotype association when linkage phase is ambiguous, appropriate for matched case-control and cohort studies with competing risks.

The impact of competing risks on tests of association between disease and haplotypes has been largely ignored. We consider situations in which linkage phase is ambiguous and show that tests for disease-haplotype association can lead to rejection of the null hypothesis, even when true, with more than the nominal 5 per cent frequency. This problem tends to occur if a haplotype is associated with overall mortality, even if the haplotype is not associated with disease risk. A small simulation study illustrates the magnitude of bias (high type I error rate) in the context of a cohort study in which a modest number of disease cases (about 350) occur over time. The bias remains even if the score test is based on a logistic model that includes age as a covariate. For cohort studies, we propose a new test based on a modification of the proportional hazards model and for case-control studies, a test based on a conditional likelihood that have the correct size under the null even in the presence of competing risks, and that can be used when haplotype is ambiguous.

Is readmission to hospital an indicator of poor process of care for patients with heart failure?

BACKGROUND: Controversy exists about the appropriateness of using readmission as an indicator of the quality of care. A study was undertaken to measure the validity and predictive ability of readmission in this context. METHODS: An evaluation study was performed in patients discharged alive with heart failure from three Swiss academic medical centres. Process quality indicators were derived from evidence based guidelines for the management and treatment of heart failure. Readmissions were calculated from hospital administrative data. The predictive ability of readmissions was evaluated using bivariate and multivariate analyses, and validity by calculating sensitivity, specificity, positive and negative predictive value, using process indicators as the "gold standard". RESULTS: Of 1055 eligible patients discharged alive, 139 (13.2%) were readmitted within 30 days. The adjusted odds ratio (OR) for absence of measurement of left ventricular function was 0.70 (95% CI 0.45 to 1.08) for readmissions. In patients with left ventricular systolic dysfunction, three dose categories of angiotensin converting enzyme inhibitor were examined using ordinal logistic regression. The adjusted OR for these categories was 1.07 (95% CI 0.56 to 2.06) for readmissions. When using process indicators as the gold standard to assess the validity of readmissions, sensitivity ranged from 0.08 to 0.17 and specificity from 0.86 to 0.93. CONCLUSIONS: Readmission did not predict and was not a valid indicator of the quality of care for patients with heart failure admitted to three Swiss university hospitals.