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1.  Body Mass Index Categories in Observational Studies of Weight and Risk of Death 
American journal of epidemiology  2014;180(3):288-296.
The World Health Organization (Geneva, Switzerland) and the National Heart, Lung, and Blood Institute (Bethesda, Maryland) have developed standard categories of body mass index (BMI) (calculated as weight (kg)/height (m)2) of less than 18.5 (underweight), 18.5–24.9 (normal weight), 25.0–29.9 (overweight), and 30.0 or more (obesity). Nevertheless, studies of BMI and the risk of death sometimes use nonstandard BMI categories that vary across studies. In a meta-analysis of 8 large studies that used nonstandard BMI categories and were published between 1999 and 2014 and included 5.8 million participants, hazard ratios tended to be small throughout the range of overweight and normal weight. Risks were similar between subjects of high-normal weight (BMI of approximately 23.0–24.9) and those of low overweight (BMI of approximately 25.0–27.4). In an example using national survey data, minor variations in the reference category affected hazard ratios. For example, choosing high-normal weight (BMI of 23.0–24.9) instead of standard normal weight (BMI of 18.5–24.9) as the reference category produced higher nonsignificant hazard ratios (1.05 vs. 0.97 for men and 1.06 vs. 1.02 for women) for the standard overweight category (BMI of 25.0–29.9). Use of the standard BMI groupings avoids problems of ad hoc and post hoc category selection and facilitates between-study comparisons. The ways in which BMI data are categorized and reported may shape inferences about the degree of risk for various BMI categories.
PMCID: PMC4732880  PMID: 24893710
body mass index; body weight; epidemiologic methods; mortality; obesity; overweight
2.  Effects of trimming weight-for-height data on growth-chart percentiles1–3 
Before estimating smoothed percentiles of weight-for-height and BMI-for-age to construct the WHO growth charts, WHO excluded observations that were considered to represent unhealthy weights for height.
The objective was to estimate the effects of similar data trimming on empirical percentiles from the CDC growth-chart data set relative to the smoothed WHO percentiles for ages 24–59 mo.
We used the nationally representative US weight and height data from 1971 to 1994, which was the source data for the 2000 CDC growth charts. Trimming cutoffs were calculated on the basis of weight-for-height for 9722 children aged 24–71 mo. Empirical percentiles for 7315 children aged 24–59 mo were compared with the corresponding smoothed WHO percentiles.
Before trimming, the mean empirical percentiles for weight-for-height in the CDC data set were higher than the corresponding smoothed WHO percentiles. After trimming, the mean empirical 95th and 97th percentiles of weight-for-height were lower than the WHO percentiles, and the proportion of children in the CDC data set above the WHO 95th percentile decreased from 7% to 5%. The findings were similar for BMI-for-age. However, for weight-for-age, which had not been trimmed by the WHO, the empirical percentiles before trimming agreed closely with the upper percentiles from the WHO charts.
WHO data-trimming procedures may account for some of the differences between the WHO growth charts and the 2000 CDC growth charts.
PMCID: PMC4734980  PMID: 22990032
3.  Obesity Paradox in End-Stage Kidney Disease Patients 
In the general population, obesity is associated with increased cardiovascular risk and decreased survival. In patients with end-stage renal disease (ESRD), however, an “obesity paradox” or “reverse epidemiology” (to include lipid and hypertension paradoxes) has been consistently reported, i.e. a higher body mass index (BMI) is paradoxically associated with better survival. This survival advantage of large body size is relatively consistent for hemodialysis patients across racial and regional differences, although published results are mixed for peritoneal dialysis patients.. Recent data indicate that both higher skeletal muscle mass and increased total body fat are protective, although there are mixed data on visceral (intra-abdominal) fat. The obesity paradox in ESRD is unlikely to be due to residual confounding alone and has biologic plausibility. Possible causes of the obesity paradox include protein-energy wasting and inflammation, time discrepancy among competitive risk factors (undernutrition versus overnutrition), hemodynamic stability, alteration of circulatory cytokines, sequestration of uremic toxin in adipose tissue, and endotoxin-lipoprotein interaction. The obesity paradox may have significant clinical implications in the management of ESRD patients especially if obese dialysis patients are forced to lose weight upon transplant wait-listing. Well-designed studies exploring the causes and consequences of the reverse epidemiology of cardiovascular risk factors, including the obesity paradox, among ESRD patients could provide more information on mechanisms. These could include controlled trials of nutritional and pharmacologic interventions to examine whether gain in lean body mass or even body fat can improve survival and quality of life in these patients.
PMCID: PMC4733536  PMID: 24438733
Obesity paradox; Reverse epidemiology; dialysis; visceral fat
4.  Bias in calculation of attributable fractions using relative risks from non-smokers only 
Epidemiology (Cambridge, Mass.)  2014;25(6):913-916.
Studies of weight and mortality sometimes state that the mortality relative risks for obesity from non-smokers are valid estimates of the relative risks for obesity in both smokers and non-smokers. Extending this idea, several influential articles have used relative risks for obesity from non-smokers and attributable fraction methods for unadjusted risks to estimate attributable fractions of deaths in the entire population (smokers and non-smokers combined). However, stratification by smoking is a form of adjustment for confounding. Simplified examples show that the use of relative risks from only one stratum to estimate attributable fractions, without incorporating data on the stratification variable, gives incorrect results for the entire population. Even if the mortality relative risks for obesity from non-smokers are indeed valid in both smokers and non-smokers, these relative risks nonetheless need to be treated as adjusted relative risks for the purpose of calculating attributable fractions for the whole sample.
PMCID: PMC4731856  PMID: 25210928
5.  Flegal et al. Reply 
American Journal of Epidemiology  2014;180(11):1129-1130.
PMCID: PMC4271067  PMID: 25378090
6.  Perspective: Overweight, mortality and survival 
Obesity (Silver Spring, Md.)  2013;21(9):1744-1745.
PMCID: PMC3803151  PMID: 23929522
BMI; overweight; mortality; epidemiologic methods; survival; obesity paradox
8.  Childhood Obesity: Are We All Speaking the Same Language?123 
Advances in Nutrition  2011;2(2):159S-166S.
Terminology and measures used in studies of weight and adiposity in children can be complex and confusing. Differences arise in metrics, terminology, reference values, and reference levels. Most studies depend on body mass index (BMI) calculated from weight and height, rather than on more direct measures of body fatness. Definitions of overweight and obesity are generally statistical rather than risk-based and use a variety of different reference data sets for BMI. As a result, different definitions often do not give the same results. A basic problem is the lack of strong evidence for any one particular definition. Rather than formulate the question as being one of how to define obesity, it might be useful to consider what BMI cut-points best predict future health risks and how efficiently to screen for such risks. The answers may be different for different populations. In addition, rather than depending solely on BMI to make screening decisions, it is likely to be useful to also consider other factors, including not only race-ethnicity, sex and age, but also factors such as family history. Despite their limitations, BMI-based definitions of overweight and obesity provide working practical definitions that are valuable for general public health surveillance and screening.
PMCID: PMC3065752  PMID: 22332047
11.  Body mass index cut offs to define thinness in children and adolescents: international survey 
BMJ : British Medical Journal  2007;335(7612):194.
Objective To determine cut offs to define thinness in children and adolescents, based on body mass index at age 18 years.
Design International survey of six large nationally representative cross sectional studies on growth.
Setting Brazil, Great Britain, Hong Kong, the Netherlands, Singapore, and the United States.
Subjects 97 876 males and 94 851 females from birth to 25 years.
Main outcome measure Body mass index (BMI, weight/height2).
Results The World Health Organization defines grade 2 thinness in adults as BMI <17. This same cut off, applied to the six datasets at age 18 years, gave mean BMI close to a z score of −2 and 80% of the median. Thus it matches existing criteria for wasting in children based on weight for height. For each dataset, centile curves were drawn to pass through the cut off of BMI 17 at 18 years. The resulting curves were averaged to provide age and sex specific cut-off points from 2-18 years. Similar cut offs were derived based on BMI 16 and 18.5 at 18 years, together providing definitions of thinness grades 1, 2, and 3 in children and adolescents consistent with the WHO adult definitions.
Conclusions The proposed cut-off points should help to provide internationally comparable prevalence rates of thinness in children and adolescents.
PMCID: PMC1934447  PMID: 17591624
12.  Blood Lead Levels and Death from All Causes, Cardiovascular Disease, and Cancer: Results from the NHANES III Mortality Study 
Environmental Health Perspectives  2006;114(10):1538-1541.
Analyses of mortality data for participants examined in 1976–1980 in the second National Health and Nutrition Examination Survey (NHANES II) suggested an increased risk of mortality at blood lead levels > 20 μg/dL. Blood lead levels have decreased markedly since the late 1970s. In NHANES III, conducted during 1988–1994, few adults had levels > 20 μg/dL.
Our objective in this study was to determine the risk of mortality in relation to lower blood lead levels observed for adult participants of NHANES III.
We analyzed mortality information for 9,757 participants who had a blood lead measurement and who were ≥ 40 years of age at the baseline examination. Using blood lead levels categorized as < 5, 5 to < 10, and ≥ 10 μg/dL, we determined the relative risk of mortality from all causes, cancer, and cardiovascular disease through Cox proportional hazard regression analysis.
Using blood lead levels < 5 μg/dL as the referent, we determined that the relative risk of mortality from all causes was 1.24 [95% confidence interval (CI), 1.05–1.48] for those with blood levels of 5–9 μg/dL and 1.59 (95% CI, 1.28–1.98) for those with blood levels ≥ 10 μg/dL (p for trend < 0.001). The magnitude of risk was similar for deaths due to cardiovascular disease and cancer, and tests for trend were statistically significant (p < 0.01) for both causes of death.
In a nationally representative sample of the U.S. population, blood lead levels as low as 5–9 μg/dL were associated with an increased risk of death from all causes, cardiovascular disease, and cancer.
PMCID: PMC1626441  PMID: 17035139
cancer; cardiovascular disease; lead; mortality; National Health and Nutrition Examination Survey (NHANES); United States
13.  The association of blood lead level and cancer mortality among whites in the United States. 
Environmental Health Perspectives  2002;110(4):325-329.
Lead is classified as a possible carcinogen in humans. We studied the relationship of blood lead level and all cancer mortality in the general population of the United States using data from the National Health and Nutrition Examination Survey II (NHANES II) Mortality Study, 1992, consisting of a total of 203 cancer deaths (117 men and 86 women) among 3,592 whites (1,702 men and 1,890 women) with average of 13.3 years of follow-up. We used Cox proportional hazard regression models to estimate the dose-response relationship between blood lead and all cancer mortality. Log-transformed blood lead was either categorized into quartiles or treated as a continuous variable in a cubic regression spline. Relative risks (RRs) were estimated for site-specific cancers by categorizing lead above and below the median. Among men and women combined, dose-response relationship between quartile of blood lead and all cancer mortality was not significant (ptrend = 0.16), with RRs of 1.24 [95% percent confidence interval (CI), 0.66-2.33], 1.33 (95% CI, 0.57-3.09), and 1.50 (95% CI, 0.75-3.01) for the second, third, and fourth quartiles, respectively, compared with the first quartile. Spline analyses found no dose response (p = 0.29), and none of the site-specific cancer RRs were significant. Among men, no significant dose-response relationships were found for quartile or spline analyses (p trend = 0.57 and p = 0.38, respectively). Among women, no dose-response relationship was found for quartile analysis (ptrend = 0.22). However, the spline dose-response results were significant (p = 0.001), showing a threshold effect at the 94th percentile of blood lead or a lead concentration of 24 microg/dL, with an RR of 2.4 (95% CI, 1.1-5.2) compared with the risk at 12.5 percentile. Because the dose-response relationship found in women was not found in men, occurred at only the highest levels of lead, and has no clear biologic explanation, further replication of this relationship is needed before it can be considered believable. In conclusion, individuals with blood lead levels in the range of NHANES II do not appear to have increased risk of cancer mortality.
PMCID: PMC1240793  PMID: 11940448
14.  Establishing a standard definition for child overweight and obesity worldwide: international survey 
BMJ : British Medical Journal  2000;320(7244):1240.
To develop an internationally acceptable definition of child overweight and obesity, specifying the measurement, the reference population, and the age and sex specific cut off points.
International survey of six large nationally representative cross sectional growth studies.
Brazil, Great Britain, Hong Kong, the Netherlands, Singapore, and the United States.
97 876 males and 94 851 females from birth to 25 years of age.
Main outcome measure
Body mass index (weight/height2).
For each of the surveys, centile curves were drawn that at age 18 years passed through the widely used cut off points of 25 and 30 kg/m2 for adult overweight and obesity. The resulting curves were averaged to provide age and sex specific cut off points from 2-18 years.
The proposed cut off points, which are less arbitrary and more internationally based than current alternatives, should help to provide internationally comparable prevalence rates of overweight and obesity in children.
PMCID: PMC27365  PMID: 10797032

Results 1-14 (14)