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1.  Demographic Differences and Trends of Vitamin D Insufficiency in the US Population, 1988–2004 
Archives of internal medicine  2009;169(6):626-632.
Background
Vitamin D insufficiency is associated with suboptimal health. The prevalence of vitamin D insufficiency may be rising, but population-based trends are uncertain. We sought to evaluate US population trends in vitamin D insufficiency.
Methods
We compared serum 25-hydroxyvitamin D (25[OH]D) levels from the Third National Health and Nutrition Examination Survey (NHANES III), collected during 1988 through 1994, with NHANES data collected from 2001 through 2004 (NHANES 2001–2004). Complete data were available for 18 883 participants in NHANES III and 13 369 participants in NHANES 2001–2004.
Results
The mean serum 25(OH)D level was 30 (95% confidence interval [CI], 29–30) ng/mL during NHANES III and decreased to 24 (23–25) ng/mL during NHANES 2001–2004. Accordingly, the prevalence of 25(OH)D levels of less than 10 ng/mL increased from 2% (95% CI, 2%–2%) to 6% (5%–8%), and 25(OH)D levels of 30 ng/mL or more decreased from 45% (43%–47%) to 23% (20%–26%). The prevalence of 25(OH)D levels of less than 10 ng/mL in non-Hispanic blacks rose from 9% during NHANES III to 29% during NHANES 2001–2004, with a corresponding decrease in the prevalence of levels of 30 ng/mL or more from 12% to 3%. Differences by age strata (mean serum 25[OH]D levels ranging from 28–32 ng/mL) and sex (28 ng/mL for women and 32 ng/mL for men) during NHANES III equalized during NHANES 2001–2004 (24 vs 24 ng/mL for age and 24 vs 24 ng/mL for sex).
Conclusions
National data demonstrate a marked decrease in serum 25(OH)D levels from the 1988–1994 to the 2001–2004 NHANES data collections. Racial/ethnic differences have persisted and may have important implications for known health disparities. Current recommendations for vitamin D supplementation are inadequate to address the growing epidemic of vitamin D insufficiency.
doi:10.1001/archinternmed.2008.604
PMCID: PMC3447083  PMID: 19307527
2.  Computational Toxicology of Chloroform: Reverse Dosimetry Using Bayesian Inference, Markov Chain Monte Carlo Simulation, and Human Biomonitoring Data 
Environmental Health Perspectives  2008;116(8):1040-1046.
Background
One problem of interpreting population-based biomonitoring data is the reconstruction of corresponding external exposure in cases where no such data are available.
Objectives
We demonstrate the use of a computational framework that integrates physiologically based pharmacokinetic (PBPK) modeling, Bayesian inference, and Markov chain Monte Carlo simulation to obtain a population estimate of environmental chloroform source concentrations consistent with human biomonitoring data. The biomonitoring data consist of chloroform blood concentrations measured as part of the Third National Health and Nutrition Examination Survey (NHANES III), and for which no corresponding exposure data were collected.
Methods
We used a combined PBPK and shower exposure model to consider several routes and sources of exposure: ingestion of tap water, inhalation of ambient household air, and inhalation and dermal absorption while showering. We determined posterior distributions for chloroform concentration in tap water and ambient household air using U.S. Environmental Protection Agency Total Exposure Assessment Methodology (TEAM) data as prior distributions for the Bayesian analysis.
Results
Posterior distributions for exposure indicate that 95% of the population represented by the NHANES III data had likely chloroform exposures ≤ 67 μg/L in tap water and ≤ 0.02 μg/L in ambient household air.
Conclusions
Our results demonstrate the application of computer simulation to aid in the interpretation of human biomonitoring data in the context of the exposure–health evaluation–risk assessment continuum. These results should be considered as a demonstration of the method and can be improved with the addition of more detailed data.
doi:10.1289/ehp.11079
PMCID: PMC2516557  PMID: 18709138
Bayesian; biomonitoring; chloroform; Markov chain Monte Carlo; MC; MCMC; Monte Carlo; PBPK; reverse dosimetry
3.  Impact of oral disease on quality of life in the US and Australian populations 
The US National Health and Nutrition Examination Survey (NHANES 2003–2004) evaluated oral health quality of life for the first time using a previously untested subset of seven Oral Health Impact Profile (OHIP) questions, i.e. the NHANES-OHIP.
Objectives
(i) To describe the impact of dental conditions on quality of life in the US adult population; (ii) to evaluate construct validity and adequacy of the NHANES-OHIP in NHANES 2003–2004 and a comparable Australian survey.
Methods
In the cross-sectional NHANES 2003–2004 survey of a nationally representative sample of US adults (n = 4907), prevalence was quantified as the proportion of adults who reported experiencing one or more impacts fairly often or very often within the past year. Construct validity was tested by comparing prevalence estimates across categories of sociodemographic, dental health and utilization characteristics known to vary in oral health. In 2002, Australian cross-sectional survey of a nationally representative sample of adults (n = 2644), adequacy of the NHANES-OHIP questions were tested with reference to a slightly modified version of the OHIP-14 questions.
Results
NHANES-OHIP prevalence estimates were markedly similar in the United States (15.3%) and Australia (15.7%). In the US construct, validity was evidenced by higher NHANES-OHIP scores among groups with greater levels of tooth loss, perceived treatment need and problem-oriented visiting and with lack of private dental insurance and low income. In Australia, prevalence for the NHANES-OHIP closely resembled prevalence estimates of the modified OHIP-14. Both varied to a similar degree across levels of tooth loss, perceived treatment need, problem-oriented visiting, and private dental insurance and income, demonstrating adequacy of the NHANES-OHIP as a brief independent instrument.
Conclusions
There was acceptable construct validity and adequacy of the NHANES-OHIP questionnaire. In the United States, the impact of oral disease disproportionately affected disadvantaged groups, a finding that supports application of the US Healthy People 2010 major goals of improved quality of life and reduced health disparities.
doi:10.1111/j.1600-0528.2008.00457.x
PMCID: PMC3760707  PMID: 19175659
adults; health policy; health surveys; NHANES; population groups
4.  Association between Smoking and Latent Tuberculosis in the U.S. Population: An Analysis of the National Health and Nutrition Examination Survey 
PLoS ONE  2012;7(11):e49050.
Background
Evidence of an association between cigarette smoking and latent tuberculosis infection (LTBI) is based on studies in special populations and/or from high prevalence settings. We sought to evaluate the association between LTBI and smoking in a low prevalence TB setting using population-based data from the National Health and Nutrition Examination Survey (NHANES).
Methods
In 1999–2000, NHANES assessed LTBI (defined as a tuberculin skin test measurement ≥10 mm) in participants, and those ≥20 years of age were queried regarding their tobacco use and serum cotinine was measured. We evaluated the association of LTBI with self-reported smoking history and smoking intensity in multivariable logistic regression models that adjusted for known confounders (gender, age, birthplace, race/ethnicity, poverty, education, history of BCG vaccination, and history of household exposure to tuberculosis disease).
Results
Estimated LTBI prevalence was 5.3% among those ≥20 years of age. The LTBI prevalence among never smokers, current smokers, and former smokers was 4.1%, 6.6%, and 6.2%, respectively. In a multivariable model, current smoking was associated with LTBI (OR 1.8; 95% CI, 1.1–2.9). The association between smoking and LTBI was strongest for Mexican-American and black individuals. In multivariate analysis stratified by race/ethnicity, cigarette packs per day among Mexican-American smokers and cotinine levels among black smokers, were significantly associated with LTBI.
Conclusions
In the large, representative, population-based NHANES sample, smoking was independently associated with significantly increased risks of LTBI. In certain populations, a greater risk of LTBI corresponded with increased smoking exposure.
doi:10.1371/journal.pone.0049050
PMCID: PMC3493513  PMID: 23145066
5.  Evidence for age as a modifier of genetic associations for lipid levels 
Annals of human genetics  2011;75(5):589-597.
SUMMARY
In order to identify novel genetic variants that influence plasma lipid concentrations, we performed a genome-wide association study (GWAS) comprised of 411 children under 18 years of age, ascertained at St. Jude Children’s Research Hospital, all of whom were of European, African, or Mexican-descent. Promising associations (p<10−5) were subsequently examined in 1,040 additional youths and 3,508 adults from the Third National Health and Nutrition Examination Survey (NHANES III), a diverse population-based study. Three genotype-phenotype associations replicated in NHANES III youths and three associated in NHANES III adults at p<0.05; however, no single association was significant in both youths and adults. The most significant association (p=0.009) in NHANES III youths was between low-density lipoprotein cholesterol (LDL-C) and intronic rs2429917 among participants of African-descent. Given the known age-dependency of lipid levels, we also tested for gene-age interactions in NHANES III participants across all ages. We identified a significant (p=0.024) age-dependent association between SGSM2 rs2429917 and LDL-C. This finding illustrates the utility of using children to discover novel variants associated with complex phenotypes and the importance of considering age-dependent genetic effects in association studies of lipid levels.
doi:10.1111/j.1469-1809.2011.00664.x
PMCID: PMC3155612  PMID: 21777205
6.  Impact of the population at risk of diabetes on projections of diabetes burden in the United States: an epidemic on the way 
Diabetologia  2006;50(5):934-940.
Aims/hypothesis
The aim of this study was to make projections of the future diabetes burden for the adult US population based in part on the prevalence of individuals at high risk of developing diabetes.
Materials and methods
Models were created from data in the nationally representative National Health and Nutrition Examination Survey (NHANES) II mortality survey (1976–1992), the NHANES III (1988–1994) and the NHANES 1999–2002. Population models for adults (>20 years of age) from NHANES III data were fitted to known diabetes prevalence in the NHANES 1999–2002 before making future projections. We used a multivariable diabetes risk score to estimate the likelihood of diabetes incidence in 10 years. Estimates of future diabetes (diagnosed and undiagnosed) prevalence in 2011, 2021, and 2031 were made under several assumptions.
Results
Based on the multivariable diabetes risk score, the number of adults at high risk of diabetes was 38.4 million in 1991 and 49.9 million in 2001. The total diabetes burden is anticipated to be 11.5% (25.4 million) in 2011, 13.5% (32.6 million) in 2021, and 14.5% (37.7 million) in 2031. Among individuals aged 30 to 39 years old who are not currently targeted for screening according to age, the prevalence of diabetes is expected to rise from 3.7% in 2001 to 5.2% in 2031. By 2031, 20.2% of adult Hispanic individuals are expected to have diabetes.
Conclusions/interpretation
The prevalence of diabetes is projected to rise to substantially greater levels than previously estimated. Diabetes prevalence within the Hispanic community is projected to be potentially overwhelming.
Electronic supplementary material
Supplementary material is available in the online version of this article at http://dx.doi.org/10.1007/s00125-006-0528-5 and is accessible to authorized users.
doi:10.1007/s00125-006-0528-5
PMCID: PMC1849422  PMID: 17119914
Diabetes; Epidemiology; Projection
7.  Variation in LPA Is Associated with Lp(a) Levels in Three Populations from the Third National Health and Nutrition Examination Survey 
PLoS ONE  2011;6(1):e16604.
The distribution of lipoprotein(a) [Lp(a)] levels can differ dramatically across diverse racial/ethnic populations. The extent to which genetic variation in LPA can explain these differences is not fully understood. To explore this, 19 LPA tagSNPs were genotyped in 7,159 participants from the Third National Health and Nutrition Examination Survey (NHANES III). NHANES III is a diverse population-based survey with DNA samples linked to hundreds of quantitative traits, including serum Lp(a). Tests of association between LPA variants and transformed Lp(a) levels were performed across the three different NHANES subpopulations (non-Hispanic whites, non-Hispanic blacks, and Mexican Americans). At a significance threshold of p<0.0001, 15 of the 19 SNPs tested were strongly associated with Lp(a) levels in at least one subpopulation, six in at least two subpopulations, and none in all three subpopulations. In non-Hispanic whites, three variants were associated with Lp(a) levels, including previously known rs6919246 (p = 1.18×10−30). Additionally, 12 and 6 variants had significant associations in non-Hispanic blacks and Mexican Americans, respectively. The additive effects of these associated alleles explained up to 11% of the variance observed for Lp(a) levels in the different racial/ethnic populations. The findings reported here replicate previous candidate gene and genome-wide association studies for Lp(a) levels in European-descent populations and extend these findings to other populations. While we demonstrate that LPA is an important contributor to Lp(a) levels regardless of race/ethnicity, the lack of generalization of associations across all subpopulations suggests that specific LPA variants may be contributing to the observed Lp(a) between-population variance.
doi:10.1371/journal.pone.0016604
PMCID: PMC3030597  PMID: 21305047
8.  Parenthood—A Contributing Factor to Childhood Obesity 
Prevalence of childhood obesity and its complications have increased world-wide. Parental status may be associated with children’s health outcomes including their eating habits, body weight and blood cholesterol. The National Health and Nutrition Examination Survey (NHANES) for the years 1988–1994, provided a unique opportunity for matching parents to children enabling analyses of joint demographics, racial differences and health indicators. Specifically, the NHANES III data, 1988–1994, of 219 households with single-parents and 780 dual-parent households were analyzed as predictors for primary outcome variables of children’s Body Mass Index (BMI), dietary nutrient intakes and blood cholesterol. Children of single-parent households were significantly (p < 0.01) more overweight than children of dual-parent households. Total calorie and saturated fatty acid intakes were higher among children of single-parent households than dual-parent households (p < 0.05). On average, Black children were more overweight (p < 0.04) than children of other races. The study results implied a strong relationship between single-parent status and excess weight in children. Further studies are needed to explore the dynamics of single-parent households and its influence on childhood diet and obesity. Parental involvement in the development of school- and community-based obesity prevention programs are suggested for effective health initiatives. Economic constraints and cultural preferences may be communicated directly by family involvement in these much needed public health programs.
doi:10.3390/ijerph7072800
PMCID: PMC2922726  PMID: 20717539
children’s diet; childhood obesity; NHANES; single-parent households; BMI; blood-cholesterol
9.  Have Regulatory Efforts to Reduce Organophosphorus Insecticide Exposures Been Effective? 
Environmental Health Perspectives  2012;120(4):521-525.
Background: The Food Quality Protection Act (FQPA) was signed into law in 1996 to strengthen the regulation of pesticide tolerances in food. Organophosphorus (OP) insecticides were the first group of pesticides reviewed by the U.S. Environmental Protection Agency (EPA) under the new law.
Objective: Our goal was to determine whether urinary concentrations of dialkylphosphate (DAP) metabolites of OP pesticides declined between the National Health and Nutrition Examination Survey (NHANES) III and NHANES 1999–2004.
Methods: Using mass spectrometry–based methods, we analyzed urine samples from a nationally representative sample of 2,874 adults 20–59 years of age in NHANES 1999–2004 and samples from a non-nationally representative sample of 197 adult participants for NHANES III (1988–1994) for six common DAP metabolites of OP pesticides.
Results: Median urinary DAP concentrations decreased by more than half between NHANES III and NHANES 2003–2004. Reductions of about 50%–90% were also observed for 95th percentile concentrations of five of the six metabolites. Frequencies of detection (FODs) decreased in all six metabolites (< 50% reduction). On average, median and 95th percentile concentrations and FODs showed a larger decrease in diethylphosphate metabolites than dimethylphosphate metabolites.
Conclusions: Human exposure to OP insecticides as assessed by urinary DAP concentrations has decreased since the implementation of the FQPA, although we cannot be certain that U.S. EPA actions in response to the FQPA directly caused the decrease in DAP concentrations.
doi:10.1289/ehp.1104323
PMCID: PMC3339465  PMID: 22251442
biomonitoring; dialkylphosphate metabolite; FQPA; NHANES; organophosphorus insecticide
10.  Racial and ethnic disparities in childhood asthma diagnosis: the role of clinical findings. 
OBJECTIVES: To establish rates of childhood asthma symptoms, diagnosis, and hospitalization by race, ethnicity, and income, and to ascertain if elevated reported prevalence of asthma diagnosis among African-American children could be explained by differences in clinical findings. METHODS: Estimates of each indicator were calculated based on data from the third National Health and Nutrition and Examination Survey (NHANES III). Bivariate and multivariate logistic regression models were estimated to predict parent or guardian report of current asthma diagnosis. RESULTS: African-American children aged 1 to 5 have a 2-fold higher probability of both asthma diagnosis and hospitalization during the previous year but no significant difference in wheeze prevalence compared to Mexican-American and European-American children. These differences are not explained by household income or clinical information. Children aged 6 to 16 had similar rates of diagnosis and hospitalization for all racial/ethnic groups, although African-American children reported wheeze symptoms one-third less often. CONCLUSIONS: Although younger African-American children have higher morbidity from asthma than their Mexican-American and European-American peers, clinical findings were similar and did not explain increased rates of diagnosis. Interpersonal dynamics within families and communication between families and clinicians are believed to influence both symptom reporting and diagnosis generation.
PMCID: PMC2594212  PMID: 11991334
11.  Obesity and prostate cancer detection: insights from three national surveys 
The American journal of medicine  2010;123(9):10.1016/j.amjmed.2010.05.011.
Background
Previous studies suggest that obesity is associated with higher prostate cancer progression and mortality despite an association with lower prostate cancer incidence. This study aims to better understand these apparently inconsistent relationships among obese men, by combining evidence from three nationally representative cross-sectional surveys.
Methods
We evaluated relationships between obesity and (1) testosterone concentrations in the Third National Health and Nutrition Examination Survey (NHANES III; n=845), (2) prostate-specific antigen (PSA) in NHANES 2001–2004 (n=2,458) and (3) prostate biopsy rates in the National Health Interview Survey (NHIS 2000; n=4,789) population. Mean testosterone, PSA concentrations and biopsy rates were computed for body mass index (BMI) categories.
Results
Testosterone concentrations were inversely associated with obesity (p-trend<0.0001) in NHANES III. In NHANES 2001–2004 obese (BMI >35) versus lean (BMI <25) men were less likely to have PSA concentrations that reached the biopsy threshold of >4 ng/ml (3% versus 8%; p<0.0001). Among NHIS participants all BMI groups had similar rates of PSA testing (p=0.24). However, among men who had PSA tests, 11% of men with BMI >30 versus 16% with BMI <25, achieved a PSA threshold of 4 ng/ml; p=0.01. Furthermore, biopsy rates were lower among men with BMI >30 versus BMI <25 in NHIS participants (4.6% vs. 5.8%; p=0.05).
Conclusions
Obesity was associated with lower PSA-driven biopsy rates. These data support further studies to test the hypothesis that obesity affects prostate cancer detection independent of prostate cancer risk by decreasing the PSA-driven biopsy rates.
doi:10.1016/j.amjmed.2010.05.011
PMCID: PMC3826172  PMID: 20800152
obesity; prostate cancer; prostate-specific antigen; biopsy
12.  The relationship of body mass index to diabetes mellitus, hypertension and dyslipidaemia: comparison of data from two national surveys 
The objectives of this study were to explore the relation between body mass index (BMI) and prevalence of diabetes mellitus, hypertension and dyslipidaemia; examine BMI distributions among patients with these conditions; and compare results from two national surveys. The Study to Help Improve Early evaluation and management of risk factors Leading to Diabetes (SHIELD) 2004 screening questionnaire (mailed survey) and the National Health and Nutrition Examination Surveys (NHANES) 1999–2002 (interview, clinical and laboratory data) were conducted in nationally representative samples ≥ 18 years old. Responses were received from 127,420 of 200,000 households (64%, representing 211,097 adults) for SHIELD, and 4257 participants for NHANES. Prevalence of diabetes mellitus, hypertension and dyslipidaemia was estimated within BMI categories, as was distribution of BMI levels among individuals with these diseases. Mean BMI was 27.8 kg/m2 for SHIELD and 27.9 kg/m2 for NHANES. Increased BMI was associated with increased prevalence of diabetes mellitus, hypertension and dyslipidaemia in both studies (p < 0.001). For each condition, more than 75% of patients had BMI ≥ 25 kg/m2. Estimated prevalence of diabetes mellitus and hypertension was similar in both studies, while dyslipidaemia was substantially higher in NHANES than SHIELD. In both studies, prevalence of diabetes mellitus, hypertension and dyslipidaemia occurred across all ranges of BMI, but increased with higher BMI. However, not all overweight or obese patients had these metabolic diseases and not all with these conditions were overweight or obese. Except for dyslipidaemia prevalence, SHIELD was comparable with NHANES. Consumer panel surveys may be an alternative method to collect data on the relationship of BMI and metabolic diseases.
doi:10.1111/j.1742-1241.2007.01336.x
PMCID: PMC1890993  PMID: 17493087
13.  Association of metabolic syndrome and insulin resistance with congestive heart failure: findings from the Third National Health and Nutrition Examination Survey 
Objective
Congestive heart failure (CHF) has been associated with insulin resistance, but few studies have examined its relationship with metabolic syndrome (MetS). Little is known about whether insulin resistance explains the association between MetS and CHF.
Design
Population‐based, cross‐sectional surveys.
Setting
Third National Health and Nutrition Examination Survey (NHANES III).
Participants
Data from 5549 men and non‐pregnant women aged ⩾40 years in NHANES III were analysed.
Results
About 4% of men and 3% of women had CHF between 1988 and 1994 in the US. The age‐adjusted prevalence of CHF was significantly higher in African Americans (4.1%), in Mexican Americans (8.5%) and in those of other ethnic origin (6.7%) than in white people (2.5%). People with MetS had nearly twice the likelihood of self‐reported CHF (adjusted odds ratio 1.8; 95% confidence interval 1.1 to 3.0) after adjustment for demographic and conventional risk factors such as sex, ethnicity, age, smoking, total cholesterol, left ventricular hypertrophy, and probable or possible myocardial infarction determined by electrocardiography. However, this association was attenuated after further adjustment for insulin resistance as measured by the homoeostasis model assessment (HOMA). >90% of the association between MetS and CHF was explained by the HOMA.
Conclusions
MetS was associated with about a twofold increased likelihood of self‐reported CHF and it may serve as a surrogate indicator for the association between insulin resistance and CHF.
doi:10.1136/jech.2006.048173
PMCID: PMC2465578  PMID: 17183018
14.  Generalizability of guidelines and physicians' adherence. Case study on the Sixth Joint National Commitee's guidelines on hypertension 
BMC Public Health  2003;3:24.
Background
Clinical practice guidelines (CPG) are thought to be an effective tool in improving efficiency and outcomes of clinical practice. Physicians' adherence to guidelines is reported to be poor. We evaluated the relationship between generalizability of guidelines on hypertension and physicians' adherence to guidelines' recommendations for pharmacological treatment.
Methods
We used the Sixth Joint National Committee's (JNC VI) guidelines on hypertension to evaluate our hypothesis. We evaluated the evidence from controlled clinical trials on which the JNC VI bases its recommendation, and compared the population enrolled in those trials with the American hypertensive population. Data on this population came from the National Health and Nutritional Examination Survey III.
Results
Twenty-three percent of the NHANES population had a diagnosis of hypertension, 11% had hypertension requiring drug treatment according to the JNC VI. Only half of the population requiring treatment would have been enrolled in at least two trials. Rate of adherence to CPG was 69%. We found a weak association between generalizability and physicians' adherence to guidelines. Baseline risk was the major determinant of the decision to treat.
Conclusion
JNC VI guidelines may not be generalizable to their target population. We found a relatively poor adherence rate to these guidelines. Failing of completely taking into account the clinical characteristics of the patients may be partly responsible for this lack of adherence.
doi:10.1186/1471-2458-3-24
PMCID: PMC183849  PMID: 12873353
15.  Many Americans Have Pre-Diabetes and Should Be Considered for Metformin Therapy 
Diabetes Care  2009;33(1):49-54.
OBJECTIVE
To determine the proportion of the American population who would merit metformin treatment, according to recent American Diabetes Association (ADA) consensus panel recommendations to prevent or delay the development of diabetes.
RESEARCH DESIGN AND METHODS
Risk factors were evaluated in 1,581 Screening for Impaired Glucose Tolerance (SIGT), 2,014 Third National Health and Nutrition Examination Survey (NHANES III), and 1,111 National Health and Nutrition Examination Survey 2005–2006 (NHANES 2005–2006) subjects, who were non-Hispanic white and black, without known diabetes. Criteria for consideration of metformin included the presence of both impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), with ≥1 additional diabetes risk factor: age <60 years, BMI ≥35 kg/m2, family history of diabetes, elevated triglycerides, reduced HDL cholesterol, hypertension, or A1C >6.0%.
RESULTS
Isolated IFG, isolated IGT, and IFG and IGT were found in 18.0, 7.2, and 8.2% of SIGT; 22.3, 6.4, and 9.4% of NHANES III; and 21.8, 5.0, and 9.0% of NHANES 2005–2006 subjects, respectively. In SIGT, NHANES III, and NHANES 2005–2006, criteria for metformin consideration were met in 99, 96, and 96% of those with IFG and IGT; 31, 29, and 28% of all those with IFG; and 53, 57, and 62% of all those with IGT (8.1, 9.1, and 8.7% of all subjects), respectively.
CONCLUSIONS
More than 96% of individuals with both IFG and IGT are likely to meet ADA consensus criteria for consideration of metformin. Because >28% of all those with IFG met the criteria, providers should perform oral glucose tolerance tests to find concomitant IGT in all patients with IFG. To the extent that our findings are representative of the U.S. population, ∼1 in 12 adults has a combination of pre-diabetes and risk factors that may justify consideration of metformin treatment for diabetes prevention.
doi:10.2337/dc09-0341
PMCID: PMC2797985  PMID: 19808929
16.  The Survey of the Health of Wisconsin (SHOW), a novel infrastructure for population health research: rationale and methods 
BMC Public Health  2010;10:785.
Background
Evidence-based public health requires the existence of reliable information systems for priority setting and evaluation of interventions. Existing data systems in the United States are either too crude (e.g., vital statistics), rely on administrative data (e.g., Medicare) or, because of their national scope (e.g., NHANES), lack the discriminatory power to assess specific needs and to evaluate community health activities at the state and local level. This manuscript describes the rationale and methods of the Survey of the Health of Wisconsin (SHOW), a novel infrastructure for population health research.
Methods/Design
The program consists of a series of independent annual surveys gathering health-related data on representative samples of state residents and communities. Two-stage cluster sampling is used to select households and recruit approximately 800-1,000 adult participants (21-74 years old) each year. Recruitment and initial interviews are done at the household; additional interviews and physical exams are conducted at permanent or mobile examination centers. Individual survey data include physical, mental, and oral health history, health literacy, demographics, behavioral, lifestyle, occupational, and household characteristics as well as health care access and utilization. The physical exam includes blood pressure, anthropometry, bioimpedance, spirometry, urine collection and blood draws. Serum, plasma, and buffy coats (for DNA extraction) are stored in a biorepository for future studies. Every household is geocoded for linkage with existing contextual data including community level measures of the social and physical environment; local neighborhood characteristics are also recorded using an audit tool. Participants are re-contacted bi-annually by phone for health history updates.
Discussion
SHOW generates data to assess health disparities across state communities as well as trends on prevalence of health outcomes and determinants. SHOW also serves as a platform for ancillary epidemiologic studies and for studies to evaluate the effect of community-specific interventions. It addresses key gaps in our current data resources and increases capacity for etiologic, applied and translational population health research. It is hoped that this program will serve as a model to better support evidence-based public health, facilitate intervention evaluation research, and ultimately help improve health throughout the state and nation.
doi:10.1186/1471-2458-10-785
PMCID: PMC3022857  PMID: 21182792
17.  Temporal Trends in the Prevalence of Diabetic Kidney Disease in the United States 
Context
Diabetes is the leading cause of kidney disease in the developed world. Over time, the prevalence of diabetic kidney disease (DKD) may increase due to the expanding size of the diabetes population or decrease due to the implementation of diabetes therapies.
Objective
To define temporal changes in DKD prevalence in the United States.
Design, Setting, and Participants
Cross-sectional analyses of the Third National Health and Nutrition Examination Survey (NHANES III) from 1988–1994 (N = 15 073), NHANES 1999–2004 (N = 13 045), and NHANES 2005–2008 (N=9588). Participants with diabetes were defined by levels of hemoglobin A1c of 6.5% or greater, use of glucose-lowering medications, or both (n = 1431 in NHANES III; n = 1443 in NHANES 1999–2004; n = 1280 in NHANES 2005–2008).
Main Outcome Measures
Diabetic kidney disease was defined as diabetes with albuminuria (ratio of urine albumin to creatinine >30 mg/g), impaired glomerular filtration rate (<60 mL/min/1.73 m2 estimated using the Chronic Kidney Disease Epidemiology Collaboration formula), or both. Prevalence of albuminuria was adjusted to estimate persistent albuminuria.
Results
The prevalence of DKD in the US population was 2.2% (95% confidence interval [CI], 1.8%–2.6%) in NHANES III, 2.8% (95% CI, 2.4%–3.1%) in NHANES 1999–2004, and 3.3% (95% CI, 2.8%–3.7%) in NHANES 2005–2008 (P<.001 for trend). The prevalence of DKD increased in direct proportion to the prevalence of diabetes, without a change in the prevalence of DKD among those with diabetes. Among persons with diabetes, use of glucose-lowering medications increased from 56.2% (95% CI, 52.1%–60.4%) in NHANES III to 74.2% (95% CI, 70.4%–78.0%) in NHANES 2005–2008 (P<.001); use of renin-angiotensin-aldosterone system inhibitors increased from 11.2% (95% CI, 9.0%–13.4%) to 40.6% (95% CI, 37.2%–43.9%), respectively (P<.001); the prevalence of impaired glomerular filtration rate increased from 14.9% (95% CI, 12.1%–17.8%) to 17.7% (95% CI, 15.2%–20.2%), respectively (P=.03); and the prevalence of albuminuria decreased from 27.3% (95% CI, 22.0%–32.7%) to 23.7% (95% CI, 19.3%–28.0%), respectively, but this was not statistically significant (P=.07).
Conclusions
Prevalence of DKD in the United States increased from 1988 to 2008 in proportion to the prevalence of diabetes. Among persons with diabetes, prevalence of DKD was stable despite increased use of glucose-lowering medications and renin-angiotensin-aldosterone system inhibitors.
doi:10.1001/jama.2011.861
PMCID: PMC3731378  PMID: 21693741
18.  Associations between cadmium exposure and neurocognitive test scores in a cross-sectional study of US adults 
Environmental Health  2013;12:13.
Background
Low-level environmental cadmium exposure and neurotoxicity has not been well studied in adults. Our goal was to evaluate associations between neurocognitive exam scores and a biomarker of cumulative cadmium exposure among adults in the Third National Health and Nutrition Examination Survey (NHANES III).
Methods
NHANES III is a nationally representative cross-sectional survey of the U.S. population conducted between 1988 and 1994. We analyzed data from a subset of participants, age 20–59, who participated in a computer-based neurocognitive evaluation. There were four outcome measures: the Simple Reaction Time Test (SRTT: visual motor speed), the Symbol Digit Substitution Test (SDST: attention/perception), the Serial Digit Learning Test (SDLT) trials-to-criterion, and the SDLT total-error-score (SDLT-tests: learning recall/short-term memory). We fit multivariable-adjusted models to estimate associations between urinary cadmium concentrations and test scores.
Results
5662 participants underwent neurocognitive screening, and 5572 (98%) of these had a urinary cadmium level available. Prior to multivariable-adjustment, higher urinary cadmium concentration was associated with worse performance in each of the 4 outcomes. After multivariable-adjustment most of these relationships were not significant, and age was the most influential variable in reducing the association magnitudes. However among never-smokers with no known occupational cadmium exposure the relationship between urinary cadmium and SDST score (attention/perception) was significant: a 1 μg/L increase in urinary cadmium corresponded to a 1.93% (95%CI: 0.05, 3.81) decrement in performance.
Conclusions
These results suggest that higher cumulative cadmium exposure in adults may be related to subtly decreased performance in tasks requiring attention and perception, particularly among those adults whose cadmium exposure is primarily though diet (no smoking or work based cadmium exposure). This association was observed among exposure levels that have been considered to be without adverse effects and these levels are common in U.S. adults. Thus further research into the potential neurocognitive effects of cadmium exposure is warranted. Because cumulative cadmium exposure may mediate some of the effects of age and smoking on cognition, adjusting for these variables may result in the underestimation of associations with cumulative cadmium exposure. Prospective studies that include never-smokers and non-occupationally exposed individuals are needed to clarify these issues.
doi:10.1186/1476-069X-12-13
PMCID: PMC3599125  PMID: 23379984
Cadmium; Neurocognitive; Neuropsychological; NES2; NHANES; Attention; Smoking; Metals; Aging; Cognitive
19.  A straightforward multiallelic significance test for the Hardy-Weinberg equilibrium law 
Genetics and Molecular Biology  2009;32(3):619-625.
Much forensic inference based upon DNA evidence is made assuming Hardy-Weinberg Equilibrium (HWE) for the genetic loci being used. Several statistical tests to detect and measure deviation from HWE have been devised, and their limitations become more obvious when testing for deviation within multiallelic DNA loci. The most popular methods-Chi-square and Likelihood-ratio tests-are based on asymptotic results and cannot guarantee a good performance in the presence of low frequency genotypes. Since the parameter space dimension increases at a quadratic rate on the number of alleles, some authors suggest applying sequential methods, where the multiallelic case is reformulated as a sequence of “biallelic” tests. However, in this approach it is not obvious how to assess the general evidence of the original hypothesis; nor is it clear how to establish the significance level for its acceptance/rejection. In this work, we introduce a straightforward method for the multiallelic HWE test, which overcomes the aforementioned issues of sequential methods. The core theory for the proposed method is given by the Full Bayesian Significance Test (FBST), an intuitive Bayesian approach which does not assign positive probabilities to zero measure sets when testing sharp hypotheses. We compare FBST performance to Chi-square, Likelihood-ratio and Markov chain tests, in three numerical experiments. The results suggest that FBST is a robust and high performance method for the HWE test, even in the presence of several alleles and small sample sizes.
doi:10.1590/S1415-47572009000300028
PMCID: PMC3036052  PMID: 21637528
Hardy-Weinberg equilibrium; significance tests; FBST
20.  Inflammation gene variants and susceptibility to albuminuria in the U.S. population: analysis in the Third National Health and Nutrition Examination Survey (NHANES III), 1991-1994 
BMC Medical Genetics  2010;11:155.
Background
Albuminuria, a common marker of kidney damage, serves as an important predictive factor for the progression of kidney disease and for the development of cardiovascular disease. While the underlying etiology is unclear, chronic, low-grade inflammation is a suspected key factor. Genetic variants within genes involved in inflammatory processes may, therefore, contribute to the development of albuminuria.
Methods
We evaluated 60 polymorphisms within 27 inflammatory response genes in participants from the second phase (1991-1994) of the Third National Health and Nutrition Examination Survey (NHANES III), a population-based and nationally representative survey of the United States. Albuminuria was evaluated as logarithm-transformed albumin-to-creatinine ratio (ACR), as ACR ≥ 30 mg/g, and as ACR above sex-specific thresholds. Multivariable linear regression and haplotype trend analyses were conducted to test for genetic associations in 5321 participants aged 20 years or older. Differences in allele and genotype distributions among non-Hispanic whites, non-Hispanic blacks, and Mexican Americans were tested in additive and codominant genetic models.
Results
Variants in several genes were found to be marginally associated (uncorrected P value < 0.05) with log(ACR) in at least one race/ethnic group, but none remained significant in crude or fully-adjusted models when correcting for the false-discovery rate (FDR). In analyses of sex-specific albuminuria, IL1B (rs1143623) among Mexican Americans remained significantly associated with increased odds, while IL1B (rs1143623), CRP (rs1800947) and NOS3 (rs2070744) were significantly associated with ACR ≥ 30 mg/g in this population (additive models, FDR-P < 0.05). In contrast, no variants were found to be associated with albuminuria among non-Hispanic blacks after adjustment for multiple testing. The only variant among non-Hispanic whites significantly associated with any outcome was TNF rs1800750, which failed the test for Hardy-Weinberg proportions in this population. Haplotypes within MBL2, CRP, ADRB2, IL4R, NOS3, and VDR were significantly associated (FDR-P < 0.05) with log(ACR) or albuminuria in at least one race/ethnic group.
Conclusions
Our findings suggest a small role for genetic variation within inflammation-related genes to the susceptibility to albuminuria. Additional studies are needed to further assess whether genetic variation in these, and untested, inflammation genes alter the susceptibility to kidney damage.
doi:10.1186/1471-2350-11-155
PMCID: PMC2991302  PMID: 21054877
21.  Lead-based paint health risk assessment in dependent children living in military housing. 
Public Health Reports  2002;117(5):446-452.
OBJECTIVE: In children, lead can cause serious permanent damage as a neurotoxicant. The objectives of the study were to evaluate potential exposure to lead-based paint in family housing units at a typical U.S. military installation and determine blood lead (PbB) levels in children ages 6 years or younger residing in these housing units. METHODS: The authors conducted a risk assessment of 1,723 housing units and occupants at Fort Devens in Massachusetts. Data from the military dependent cohort was compared to estimates for the U.S. national population as reported from Phase 1 of the Third National Health and Nutrition Examination Survey (NHANES III). RESULTS: A total of 1992 individuals (1,009 males and 983 females) were screened for PbB, stratified into age groups, and separated into racial/ethnic categories. Four (0.3%) dust samples and 59 (11.6%) internal and 298 (77.8%) external paint chip samples contained hazardous levels of lead. The geometric mean PbB concentration for people ages 1 year and older reported by NHANES III was 2.8 micro g/dL, compared with 1.5 microg/dL for the military installation cohort (p<0.0001). PbB levels were higher for males than for females and higher for blacks than whites 6 years of age and older. Hispanics had lower PbB concentrations for all age groups except for those ages 1-2.9 years. Prevalence of PbB levels >10 microg/dL for all age groups was 1.6% in the military cohort, compared with 4.5% for the general population. For ages 1-2.9 years, no blacks or Hispanics and 0.6% of whites had PbB levels >10 micro g/dL, compared with 21.6% of blacks, 10.1% of Hispanics, and 8.5% of whites for the general population. For ages 3-5.99 years, 0.15% of blacks, 0% of Hispanics, and 0.3% of whites had PbB levels > or = 10 microg/dL, compared with 20.0% of blacks, 6.8% of Hispanics, and 3.7% of whites for the general population. CONCLUSION: Lead exposure for occupants of on-post military housing is much less than for those residing in the civilian sector.
PMCID: PMC1497470  PMID: 12500961
22.  Gender Based Within-Household Inequality in Childhood Immunization in India: Changes over Time and across Regions 
PLoS ONE  2012;7(4):e35045.
Background and Objectives
Despite India's substantial economic growth in the past two decades, girls in India are discriminated against in access to preventive healthcare including immunizations. Surprisingly, no study has assessed the contribution of gender based within-household discrimination to the overall inequality in immunization status of Indian children. This study therefore has two objectives: to estimate the gender based within-household inequality (GWHI) in immunization status of Indian children and to examine the inter-regional and inter-temporal variations in the GWHI.
Data and Methods
The present study used households with a pair of male-female siblings (aged 1–5 years) from two rounds of National Family Health Survey (NFHS, 1992–93 and 2005–06). The overall inequality in the immunization status (after controlling for age and birth order) of children was decomposed into within-households and between-households components using Mean log deviation to obtain the GWHI component. The analysis was conducted at the all-India level as well as for six specified geographical regions and at two time points (1992–93 and 2005–06). Household fixed-effects models for immunization status of children were also estimated.
Results and Conclusions
Findings from household fixed effects analysis indicated that the immunization scores of girls were significantly lower than that of boys. The inequality decompositions revealed that, at the all-India level, the absolute level of GWHI in immunization status decreased from 0.035 in 1992–93 to 0.023 in 2005–06. However, as a percentage of total inequality, it increased marginally (15.5% to 16.5%). In absolute terms, GWHI decreased in all the regions except in the North-East. But, as a percentage of total inequality it increased in the North-Eastern, Western and Southern regions. The main conclusions are the following: GWHI contributes substantially to the overall inequality in immunization status of Indian children; and though the overall inequality in immunization status declined in all the regions, the changes in GWHI were mixed.
doi:10.1371/journal.pone.0035045
PMCID: PMC3324412  PMID: 22509379
23.  Magnesium, vitamin D status and mortality: results from US National Health and Nutrition Examination Survey (NHANES) 2001 to 2006 and NHANES III 
BMC Medicine  2013;11:187.
Background
Magnesium plays an essential role in the synthesis and metabolism of vitamin D and magnesium supplementation substantially reversed the resistance to vitamin D treatment in patients with magnesium-dependent vitamin-D-resistant rickets. We hypothesized that dietary magnesium alone, particularly its interaction with vitamin D intake, contributes to serum 25-hydroxyvitamin D (25(OH)D) levels, and the associations between serum 25(OH)D and risk of mortality may be modified by magnesium intake level.
Methods
We tested these novel hypotheses utilizing data from the National Health and Nutrition Examination Survey (NHANES) 2001 to 2006, a population-based cross-sectional study, and the NHANES III cohort, a population-based cohort study. Serum 25(OH)D was used to define vitamin D status. Mortality outcomes in the NHANES III cohort were determined by using probabilistic linkage with the National Death Index (NDI).
Results
High intake of total, dietary or supplemental magnesium was independently associated with significantly reduced risks of vitamin D deficiency and insufficiency respectively. Intake of magnesium significantly interacted with intake of vitamin D in relation to risk of both vitamin D deficiency and insufficiency. Additionally, the inverse association between total magnesium intake and vitamin D insufficiency primarily appeared among populations at high risk of vitamin D insufficiency. Furthermore, the associations of serum 25(OH)D with mortality, particularly due to cardiovascular disease (CVD) and colorectal cancer, were modified by magnesium intake, and the inverse associations were primarily present among those with magnesium intake above the median.
Conclusions
Our preliminary findings indicate it is possible that magnesium intake alone or its interaction with vitamin D intake may contribute to vitamin D status. The associations between serum 25(OH)D and risk of mortality may be modified by the intake level of magnesium. Future studies, including cohort studies and clinical trials, are necessary to confirm the findings.
doi:10.1186/1741-7015-11-187
PMCID: PMC3765911  PMID: 23981518
Magnesium intake; Serum 25-hydroxyvitamin D levels; Vitamin D insufficiency; Vitamin D deficiency; Parathyroid hormone; Mortality; Colorectal cancer; Cardiovascular diseases
24.  Gene polymorphisms in association with self-reported stroke in US adults 
Purpose
Epidemiologic studies suggest that several gene variants increase the risk of stroke, and population-based studies help provide further evidence. We identified polymorphisms associated with the prevalence of self-reported stroke in US populations using a representative sample.
Methods
Our sample comprised US adults in the Third National Health and Nutrition Examination (NHANES III) DNA bank. We examined nine candidate gene variants within ACE, F2, F5, ITGA2, MTHFR, and NOS3 for associations with self-reported stroke. We used multivariate regression and Cox proportional hazards models to test the association between these variants and history of stroke.
Results
In regression models, the rs4646994 variant of ACE (I/I and I/D genotypes) was associated with higher prevalence adjusted prevalence odds ratio [APOR] = 2.66 [1.28, 5.55] and 2.23 [1.30, 3.85], respectively) compared with the D/D genotype. The heterozygous genotype of MTHFR rs1801131 (A/C) was associated with lower prevalence of stroke (APOR = 0.48 [0.25, 0.92]) compared with A/A and C/C genotypes. For rs2070744 of NOS3, both the C/T genotype (APOR = 1.91 [1.12, 3.27]) and C/C genotype (APOR = 3.31 [1.66, 6.60]) were associated with higher prevalence of stroke compared with the T/T genotype.
Conclusion
Our findings suggest an association between the prevalence of self-reported stroke and polymorphisms in ACE, MTHFR, and NOS3 in a population-based sample.
PMCID: PMC3681161  PMID: 23776350
stroke; gene; polymorphisms; NHANES III; gene association analysis
25.  Serum phosphorus predicts incident chronic kidney disease and end-stage renal disease 
Nephrology Dialysis Transplantation  2011;26(9):2885-2890.
Background. Elevations in serum phosphorus are associated with renal decline in animal models and progression of established chronic kidney disease (CKD) in human observational studies. We examined whether serum phosphorus levels increase the risk of incident CKD or end-stage renal disease (ESRD) in two population-based prospective cohort studies.
Methods. Overall, 2269 participants free of CKD [estimated glomerular filtration rate (eGFR) <60 mL/min/1.732] from the Framingham Heart Study (FHS; mean age 42 years; 53% women) and 13 372 participants from the Third National Health and Nutrition Examination Survey (NHANES III; mean age 44.3 years, 52% women) contributed to the present study. In the FHS, we evaluated the relationship between baseline phosphorus category (<2.5 mg/dL, 2.5–3.49 mg/dL, 3.5–3.99 mg/dL and ≥4 mg/dL) and incident CKD (n = 267). In NHANES, we examined the relationship between phosphorus below and above 4 mg/dL in relation to incident ESRD (n = 65).
Results. FHS participants in the highest phosphorus category had an increased risk of CKD [odds ratio 2.14; 95% confidence interval (CI), 1.07–4.28; P = 0.03] in multivariable-adjusted models when compared to the referent group (2.5–3.49 mg/dL). Similarly, NHANES III participants with phosphorus levels ≥4 mg/dL demonstrated an increased risk of incident ESRD compared to those <4 mg/dL (relative risk 1.90; 95% CI 1.03–3.53; P = 0.04).
Conclusions. In prospective studies of the general population, serum phosphorus levels in the upper-normal range were associated with a doubling in the risk of developing incident CKD and ESRD.
doi:10.1093/ndt/gfq808
PMCID: PMC3175050  PMID: 21292817
CKD; ESRD; phosphorus

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