Variation in Urinary Flow Rates According to Demographic Characteristics and Body Mass Index in NHANES: Potential Confounding of Associations between Health Outcomes and Urinary Biomarker Concentrations

Background:

Urinary analyte concentrations are affected both by exposure level and by urinary flow rate (UFR). Systematic variations in UFR with demographic characteristics or body mass index (BMI) could confound assessment of associations between health outcomes and biomarker concentrations.

Objectives:

We assessed patterns of UFR (milliliters per hour) and body weight–adjusted UFR (UFRBW; milliliters per kilogram per hour) across age, sex, race/ethnicity, and BMI category in the NHANES (National Health and Nutrition Examination Survey) 2009–2012 data sets.

Methods:

Geometric mean (GM) UFR and UFRBW were compared across age-stratified (6–11, 12–19, 20–39, 40–59, and ≥ 60 years) subgroups (sex, race/ethnicity, and BMI category). Patterns of analyte urinary concentration or mass excretion rates (nanograms per hour and nanograms per kilogram per hour BW) were assessed in sample age groups for case study chemicals bisphenol A and 2,5-dichlorophenol.

Results:

UFR increased from ages 6 to 60 years and then declined with increasing age. UFRBW varied inversely with age. UFR, but not UFRBW, differed significantly by sex (males > females after age 12 years). Differences in both metrics were observed among categories of race/ethnicity. UFRBW, but not UFR, varied inversely with BMI category and waist circumference in all age groups. Urinary osmolality increased with increasing BMI. Case studies demonstrated different exposure–outcome relationships depending on exposure metric. Conventional hydration status adjustments did not fully address the effect of flow rate variations.

Conclusions:

UFR and UFRBW exhibit systematic variations with age, sex, race/ethnicity, and BMI category. These variations can confound assessments of potential exposure–health outcome associations based on urinary concentration. Analyte excretion rates are valuable exposure metrics in such assessments.

Citation:

Hays SM, Aylward LL, Blount BC. 2015. Variation in urinary flow rates according to demographic characteristics and body mass index in NHANES: potential confounding of associations between health outcomes and urinary biomarker concentrations. Environ Health Perspect 123:293–300; http://dx.doi.org/10.1289/ehp.1408944     

Drinking habits among older persons: findings from the NHANES I Epidemiologic Followup Study (1982-84). National Health and Nutrition Examination Survey

OBJECTIVES: To describe alcohol use and its sociodemographic correlates among persons aged 65 years and older in a US probability sample. DESIGN: Cross-sectional analysis of a national probability sample-based cohort study. SETTING: Multiple sites throughout the United States. PARTICIPANTS: A total of 3448 persons aged 65 and older who participated in the first wave of the NHANES I Epidemiologic Followup Study (1982-84). MEASUREMENTS: We describe the alcohol use behaviors and demographic characteristics of 3448 persons aged 65 and older. Least squares regression models were used to assess associations between older persons' sociodemographic characteristics and alcohol use. RESULTS: Sixty percent of the sample reported having 12 or more drinks of alcohol in at least 1 year of their lives. Seventy-nine percent of these older drinkers were currently drinking. Twenty-five percent of all drinkers drank daily (31% men, 19% women). Using gender-specific definitions (men >2 drinks/day; women >1 drink/day), 16% of men drinking alcohol and 15% of women drinking alcohol were heavy drinkers. Younger age, male gender, and higher income were associated with greater alcohol use. CONCLUSIONS: Most older persons who ever drank alcohol in their lifetimes were currently drinking. In addition, a substantial number of older persons were drinking currently at levels that may place them at risk of adverse health consequences.     

The alcohol-related problems survey: identifying hazardous and harmful drinking in older primary care patients

OBJECTIVES: Older adults can incur problems at low levels of alcohol consumption because of age-related physiological changes, declining health and functional status, and medication use. We have developed and tested a screening measure specifically for older people, the Alcohol-Related Problems Survey (ARPS), to identify older adults with these risks. DESIGN: Survey. SETTING: Academic and community primary care clinics. PARTICIPANTS: Five hundred forty-nine current drinkers aged 65 and older, mostly white with high school or more education. MEASURES: Alcohol use was classified as harmful, hazardous, or nonhazardous depending upon consumption alone or combined with selected comorbidities and medication use. Harmful drinking (including alcohol abuse or dependence) means the presence of problems (e.g., hypertension, adverse drug events, legal problems) due to drinking. Hazardous drinking means risks for problems are likely. Nonhazardous drinking poses no known risks for problems. RESULTS: Eleven percent of subjects were harmful drinkers and 35% were hazardous drinkers. Harmful drinking was more common in men than women and in persons younger than 75 than those aged 75 and older. Similar proportions of men and women and younger and older age groups were hazardous drinkers. Most harmful drinkers were identified by their use of alcohol with their comorbidity, whereas most hazardous drinkers were identified by their use of alcohol with medications. Test-retest reliability was substantial (kappa = 0.65). CONCLUSION: Physicians are urged to screen for alcohol-related problems in older persons. The ARPS reliably identifies harmful, hazardous, and nonhazardous drinking in older adults resulting most often from the interaction between alcohol and disease and medication use.     

Detection of genomic deletions of PKP2 in arrhythmogenic right ventricular cardiomyopathy

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited myocardial disease that predominantly affects the right ventricle and is associated with ventricular arrhythmias that may lead to sudden cardiac death. Mutations within at least seven separate genes have been identified to cause ARVC, however a genetic culprit remains elusive in approximately 50% of cases. Although negative genetic testing may be secondary to pathogenic mutations within undiscovered genes, an alternative explanation may be the presence of large deletions or duplications involving known genes. These large copy number variants may not be detected with standard clinical genetic testing which is presently limited to direct DNA sequencing. We describe two cases of ARVC possessing large deletions involving plakophilin‐2 (PKP2) identified with microarray analysis and/or multiplex ligation‐dependent probe amplification (MLPA) that would have been classified as genotype negative with standard clinical genetic testing. A deletion of the entire coding region of PKP2 excluding exon 1 was identified in patient 1 and his son. In patient 2, MLPA analysis of PKP2 revealed deletion of the entire gene with subsequent microarray analysis demonstrating a de novo 7.9 Mb deletion of chromosome 12p12.1p11.1. These findings support screening for large copy number variants in clinically suspected ARVC cases without clear disease causing mutations following initial sequencing analysis.     

Effects on the buoyant density of rabbit platelets of ADP and agents that increase the concentration of cyclic AMP

Rabbit platelets were aggregated by adenosine diphosphate (ADP), allowed to deaggregate and then separated into density subpopulations by centrifugation through discontinuous Stractan density gradients. Although ADP causes little or no release of the contents of the amine storage granules of rabbit platelets, ADP caused a decrease in platelet density as compared with control platelets subjected to the same procedures except for exposure to ADP. The density change persisted for at least four hours. The apparent size of platelets stimulated with ADP increased initially, but returned to control values during a one-hour period. A similar decrease in platelet density was observed with an albumin density gradient. Under conditions in which aggregation did not occur in response to ADP with ethylenediaminetetraacetic acid (EDTA) in the medium, little or no decrease in platelet density was observed. Agglutination with polylysine did not change platelet density. Thus, not only agents such as thrombin and plasmin that cause the release of the contents of the platelet granules decrease platelet density, but ADP also has this effect. Platelets would be exposed to all of these stimuli during thromboembolic processes, and their effect on platelets may account for the decrease in platelet density observed previously in experiments with rabbits with indwelling aortic catheters. Agents that increase the concentration of cyclic AMP (cAMP) in platelets (PGE1, adenosine, dibutyryl cAMP, forskolin, and papaverine) also decreased platelet density. This effect persisted when the platelets were washed and resuspended in fresh medium and was also demonstrable in plasma. Platelet size was gradually increased by prostaglandin E1 (PGE1) which maintains platelets in a disc shape and does not cause the release of granule contents, indicating that the decrease in platelet density caused by PGE1 may be attributable to platelet swelling.     

Response patterns of purified myeloma cells to hematopoietic growth factors

Tumor cells were isolated from the bone marrow of seven patients with multiple myeloma and from the peripheral blood of three patients with plasma cell leukemia using Ficoll-Hypaque (FH) density sedimentation followed by immune rosette depletion of T, myeloid, monocytoid, and natural killer (NK) cells. Enrichment to greater than or equal to 93% plasma cells was confirmed with Wright's-Giemsa staining, with intracytoplasmic immunoglobulin staining, and with staining using monoclonal antibodies (MoAbs) directed at B, T, myeloid, monocytoid, and myeloma antigens in indirect immunofluorescence assays. Myeloma cells neither proliferated nor secreted Ig in response to G/M-CSF, G- CSF, M-CSF, interleukin-1 alpha (IL-1 alpha), interleukin-1 beta (IL-1 beta), interleukin-2 (IL-2), or interleukin-4 (IL-4). Significant proliferation (SI greater than or equal to 3.0) was induced by interleukin-6 (IL-6) in six of ten patients (SI of 31 and 43 in two cases); and to interleukin-3 (IL-3) and interleukin-5 (IL-5), independently, in two patients each. Peak proliferation to IL-5 or IL-6 and to IL-3 occurred in cells pulsed with 3[H] thymidine at 24 and 48 hours, respectively; and proliferation to combinations of factors did not exceed that noted to IL-6 alone; Ig secretion was not documented under any culture conditions. Three myeloma-derived cell lines similarly studied demonstrated variable responses. The heterogeneity in the in vitro responses of myeloma cells and derived cell lines to exogenous growth factors enhances our understanding of abnormal plasma cell growth and may yield insight into the pathophysiology of plasma cell dyscrasias.     

Longitudinal correlations between MRE,MRI-PDFF,and liver histology in patients with non-alcoholic steatohepatitis: Analysis of data from a phase II trial of selonsertib

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