Assessment of serum total 25-hydroxyvitamin D assays for Vitamin D External Quality Assessment Scheme (DEQAS) materials distributed at ambient and frozen conditions.

The Vitamin D External Quality Assessment Scheme (DEQAS) distributes human serum samples four times per year to over 1000 participants worldwide for the determination of total serum 25-hydroxyvitamin D [25(OH)D)]. These samples are stored at -40 °C prior to distribution and the participants are instructed to store the samples frozen at -20 °C or lower after receipt; however, the samples are shipped to participants at ambient conditions (i.e., no temperature control). To address the question of whether shipment at ambient conditions is sufficient for reliable performance of various 25(OH)D assays, the equivalence of DEQAS human serum samples shipped under frozen and ambient conditions was assessed. As part of a Vitamin D Standardization Program (VDSP) commutability study, two sets of the same nine DEQAS samples were shipped to participants at ambient temperature and frozen on dry ice. Twenty-eight laboratories participated in this study and provided 34 sets of results for the measurement of 25(OH)D using 20 ligand binding assays and 14 liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods. Equivalence of the assay response for the frozen versus ambient DEQAS samples for each assay was evaluated using multi-level modeling, paired t-tests including a false discovery rate (FDR) approach, and ordinary least squares linear regression analysis of frozen versus ambient results. Using the paired t-test and confirmed by FDR testing, differences in the results for the ambient and frozen samples were found to be statistically significant at p < 0.05 for four assays (DiaSorin, DIAsource, Siemens, and SNIBE prototype). For all 14 LC-MS/MS assays, the differences in the results for the ambient- and frozen-shipped samples were not found to be significant at p < 0.05 indicating that these analytes were stable during shipment at ambient conditions. Even though assay results have been shown to vary considerably among different 25(OH)D assays in other studies, the results of this study also indicate that sample handling/transport conditions may influence 25(OH)D assay response for several assays.

Age and sex disparities in hypertension control: The multi-ethnic study of atherosclerosis (MESA).

OBJECTIVE: Determine sex differences in hypertension control by age group in a diverse cohort of adults age 45-84 years at baseline followed for an average of 12 years. METHODS: The Multi-Ethnic Study of Atherosclerosis enrolled 3213 men and 3601 women from six communities in the U.S. during years 2000-2002 with follow-up exams completed approximately every two years. At each exam, resting blood pressure (BP) was measured in triplicate, and the last two values were averaged. Hypertension was defined as a BP ≥ 140/90 mmHg and/or use of antihypertensive medications. Hypertension control was defined as a BP < 140/90 mmHg and in separate analyses as < 130/90 mmHg. Generalized linear mixed effects models with a binomial function were used to calculate the odds of hypertension control by age group (45-64,75-74, 75+) at a given exam and by sex, while accounting for the intra-individual correlation, and adjustment for demographics, co-morbidities, smoking, alcohol use, education and site among participants with hypertension at any of the first five exams. RESULTS: At baseline, mean age was 64.1 (9.1 [SD]) years, 48.0% were men, and race/ethnicity was Non-Hispanic white in 34.1%, 10.1% Chinese, 35.1% Non-Hispanic Black and 20.7% Hispanic. Average SBP was lower while average DBP was higher among men vs. women at each exam. Adjusted odds ratios of hypertension control defined as BP < 140/90 mmHg among men vs. women was 0.89 (95% CI 0.67, 1.19) for age 45-64 years, 1.37 (95% CI 1.04, 1.81) for age 65-74 years and 2.08 (95% CI 1.43, 3.02) for age 75+ years. When defined as < 130/80 mmHg, adjusted odds of hypertension control among men vs. women was 0.60 (OR 0.60; 95% CI 0.46, 0.79) at age 45-64 years, 1.01 (OR 1.01; 95% CI 0.77, 1.31) at age 65-74 years and 1.71 (95% CI 1.19, 2.45) at age 75+ years. CONCLUSION: Sex disparities in hypertension control increase with advancing age and are greatest among adults age 75+ years.

Association of Subjective Social Status With Life's Simple 7s Cardiovascular Health Index Among Hispanic/Latino People: Results From the HCHS/SOL.

Background Evidence suggests that subjective (perceived) social status (SSS) may predict health outcomes more strongly than objective social status, but little is known about the relationship between SSS and cardiovascular health (CVH). This study focuses on this relationship among diverse Hispanic/Latino adults because while poor CVH profiles are prevalent in this population, immigration complicates attempts to measure their social status. Methods and Results We analyzed baseline HCHS/SOL (Hispanic Community Health Study/Study of Latinos) data on 15 374 Hispanic/Latino adults aged 18 to 74 years in 2008 to 2011. SSS was assessed using the McArthur Scale, a 10-rung "social ladder." CVH was based on levels of 7 metrics defined by the American Heart Association. Linear and logistic regressions were used to examine cross-sectional associations of SSS with CVH (overall and single metrics) after adjusting for objective social status, demographic, and health factors. Less than half of the population (46%) had Ideal scores in ≥4 metrics of CVH. In multivariable-adjusted models, an increase in SSS was associated with a higher overall CVH score (ß=0.04; 95% CI, 0.01-0.06) and greater likelihood of Ideal levels of body mass index, physical activity, and fasting blood glucose levels. Nativity and time in the United States modified the association between SSS and Ideal smoking. Conclusions Subjective measures of social status can enhance an understanding of CVH among Hispanic/Latino people. Future studies should explore the stability of SSS over time in comparison with objective social status and the mechanisms through which SSS may influence CVH.

Assessment of serum total 25-hydroxyvitamin D assay commutability of Standard Reference Materials and College of American Pathologists Accuracy-Based Vitamin D (ABVD) Scheme and Vitamin D External Quality Assessment Scheme (DEQAS) materials: Vitamin D Standardization Program (VDSP) Commutability Study 2.

An interlaboratory study was conducted through the Vitamin D Standardization Program (VDSP) to assess commutability of Standard Reference Materials® (SRMs) and proficiency testing/external quality assessment (PT/EQA) samples for determination of serum total 25-hydroxyvitamin D [25(OH)D] using ligand binding assays and liquid chromatography-tandem mass spectrometry (LC-MS/MS). A set of 50 single-donor serum samples were assigned target values for 25-hydroxyvitamin D2 [25(OH)D2] and 25-hydroxyvitamin D3 [25(OH)D3] using reference measurement procedures (RMPs). SRM and PT/EQA samples evaluated included SRM 972a (four levels), SRM 2973, six College of American Pathologists (CAP) Accuracy-Based Vitamin D (ABVD) samples, and nine Vitamin D External Quality Assessment Scheme (DEQAS) samples. Results were received from 28 different laboratories using 20 ligand binding assays and 14 LC-MS/MS methods. Using the test assay results for total serum 25(OH)D (i.e., the sum of 25(OH)D2 and 25(OH)D3) determined for the single-donor samples and the RMP target values, the linear regression and 95% prediction intervals (PIs) were calculated. Using a subset of 42 samples that had concentrations of 25(OH)D2 below 30 nmol/L, one or more of the SRM and PT/EQA samples with high concentrations of 25(OH)D2 were deemed non-commutable using 5 of 11 unique ligand binding assays. SRM 972a (level 4), which has high exogenous concentration of 3-epi-25(OH)D3, was deemed non-commutable for 50% of the LC-MS/MS assays.

Vitamin D Standardization Program (VDSP) intralaboratory study for the assessment of 25-hydroxyvitamin D assay variability and bias.

An intralaboratory study assessing assay variability and bias for determination of serum total 25-hydroxyvitamin D [25(OH)D] was conducted by the Vitamin D Standardization Program (VDSP). Thirteen assays for serum total 25(OH)D were evaluated in a single laboratory including 11 unique immunoassays and one liquid chromatography - tandem mass spectrometry (LC-MS/MS) assay. Fifty single-donor serum samples, including eight samples with high concentrations of 25(OH)D2 (> 30 nmol/L), were assigned target values for 25(OH)D2 and 25(OH)D3 using reference measurement procedures (RMP). Using four replicate measurements for each sample, the mean total percent coefficient of variation (%CV) and mean % bias from the target values were determined for each assay using the 50 single-donor samples and a 42-sample subset, which excluded 8 high 25(OH)D2 concentration samples, and compared with VDSP performance criteria of ≤ 10 % CV and ≤ ±5 % mean bias. All 12 assays achieved the performance criterion for % CV, and 9 of the 12 assays were within ≤ ±5 % mean bias. The Fujirebio Inc. assay exhibited the lowest %CV and highest percentage of individual measurements within ≤ ±5 % mean bias. Ten immunoassays exhibited changes in response due to the high 25(OH)D2 samples with Abbott, Biomérieux, DiaSorin, DIAsource, and IDS-iSYS assays having the largest deviations. The Fujirebio Inc. and Beckman Coulter assays were only minimally affected by the presence of the high 25(OH)D2 samples. Samples with high concentrations of 25(OH)D2 provided a critical performance test for immunoassays indicating that some assays may not have equal response or recovery for 25(OH)D2 and 25(OH)D3.

A Web-Based Positive Psychological Intervention to Improve Blood Pressure Control in Spanish-Speaking Hispanic/Latino Adults With Uncontrolled Hypertension: Protocol and Design for the ¡Alégrate! Randomized Controlled Trial.

BACKGROUND: Growing evidence links psychological well-being and resilience with superior cardiac health, but there remains a critical scientific gap about whether (or how) interventions that aim to cultivate psychological well-being reduce cardiac risk. Hispanic/Latino people in the United States have high cardiovascular disease risk and poorly controlled blood pressure (BP) compared with their peers of European ancestry, and they represent a population in need of new and innovative therapeutic approaches. As such, a focused intervention to boost psychological well-being holds promise as a novel therapeutic target for hypertension in Hispanic/Latino adults; to date, however, no research has explored whether a causal link is evident. OBJECTIVE: The aim of this paper is to detail the protocol for the ¡Alégrate! (Be Happy!) intervention, a Phase II randomized controlled trial testing initial efficacy in improving BP of a web-based positive psychological intervention designed to boost psychological well-being in Spanish-speaking Hispanic/Latino people with hypertension. METHODS: A total of 70 Hispanic/Latino people aged ≥18 years, fluent in Spanish, and with elevated BP (≥140/90 mm Hg) will be recruited in person from a single Federally Qualified Health Center in Chicago. Enrollees will be randomly assigned to 1 of 2 trial arms: (1) web-based positive psychological intervention or (2) an active control condition (eg, 3 times weekly emotion reporting). Our 5-week Spanish-language ¡Alégrate! intervention is web-based and delivers curricular content via didactic instruction, journaling, and assigned at-home practice-all accessed via our website using investigator-purchased tablet computers, with a unique username and password assigned to each enrollee. Targeted skills include noting daily positive events, positive reappraisal of stressful events, effective expression of gratitude, performing acts of kindness, and regular practice of mindfulness and meditation. The primary outcome is improvement in BP, both sitting values and 24-hour ambulatory readings, as measured at baseline and 5 and 12 weeks from baseline. Secondary outcomes include psychological well-being, engagement in healthy behaviors, and circulating levels of inflammatory markers. The outcomes of interest are collected by trained research staff through in-person interviews using the REDCap software. RESULTS: Activities of the ¡Alégrate! intervention were funded in August 2017, and data collection is ongoing. We expect to submit trial results for peer-reviewed publications in 2021, soon after recruitment has been concluded and statistical analyses are finalized. CONCLUSIONS: Findings will provide evidence on whether interventions to boost psychological well-being and resilience have downstream effects on BP control and cardiovascular health, particularly as they are deployed in the Spanish language with cultural tailoring and via a web-based platform. If effective, we will have an easily disseminatable application that can positively impact well-being profiles and BP control in Hispanic/Latino people, with the possibility of addressing health disparities of this US racial/ethnic minority group. TRIAL REGISTRATION: ClinicalTrials.gov NCT03892057; https://clinicaltrials.gov/ct2/show/NCT03892057. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/17721.

Trends, Cost, and Mortality From Sepsis After Trauma in the United States: An Evaluation of the National Inpatient Sample of Hospitalizations, 2012-2016.

OBJECTIVES: Identification and outcomes in patients with sepsis have improved over the years, but little data are available in patients with trauma who develop sepsis. We aimed to examine the cost and epidemiology of sepsis in patients hospitalized after trauma. DESIGN: Retrospective cohort study. PATIENTS: National Inpatient Sample. INTERVENTIONS: Sepsis was identified between 2012 and 2016 using implicit and explicit International Classification of Diseases, Ninth and Tenth Revision codes. Analyses were stratified by injury severity score greater than or equal to 15. Annual trends were modeled using generalized linear models. Survey-adjusted logistic regression was used to compare the odds for in-hospital mortality, and the average marginal effects were calculated to compare the cost of hospitalization with and without sepsis. MEASUREMENTS AND MAIN RESULTS: There were 320,450 (SE = 3,642) traumatic injury discharges from U.S. hospitals with sepsis between 2012 and 2016, representing 6.0% (95% CI, 5.9-6.0%) of the total trauma population (n = 5,329,714; SE = 47,447). In-hospital mortality associated with sepsis after trauma did not change over the study period (p > 0.40). In adjusted analysis, severe (injury severity score ≥ 15) and nonsevere injured septic patients had an odds ratio of 1.39 (95% CI, 1.31-1.47) and 4.32 (95% CI, 4.06-4.59) for in-hospital mortality, respectively. The adjusted marginal cost for sepsis compared with nonsepsis was $16,646 (95% CI, $16,294-$16,997), and it was greater than the marginal cost for severe injury compared with nonsevere injury $8,851 (95% CI, $8,366-$8,796). CONCLUSIONS: While national trends for sepsis mortality have improved over the years, our analysis of National Inpatient Sample did not support this trend in the trauma population. The odds risk for death after sepsis and the cost of care remained high regardless of severity of injury. More rigor is needed in tracking sepsis after trauma and evaluating the effectiveness of hospital mandates and policies to improve sepsis care in patients after trauma.

Patient Outcomes and Cost-Effectiveness of a Sepsis Care Quality Improvement Program in a Health System.

OBJECTIVES: Assess patient outcomes in patients with suspected infection and the cost-effectiveness of implementing a quality improvement program. DESIGN, SETTING, AND PARTICIPANTS: We conducted an observational single-center study of 13,877 adults with suspected infection between March 1, 2014, and July 31, 2017. The 18-month period before and after the effective date for mandated reporting of the sepsis bundle was examined. The Sequential Organ Failure Assessment score and culture and antibiotic orders were used to identify patients meeting Sepsis-3 criteria from the electronic health record. INTERVENTIONS: The following interventions were performed as follows: 1) multidisciplinary sepsis committee with sepsis coordinator and data abstractor; 2) education campaign; 3) electronic health record tools; and 4) a Modified Early Warning System. MAIN OUTCOMES AND MEASURES: Primary health outcomes were in-hospital death and length of stay. The incremental cost-effectiveness ratio was calculated and the empirical 95% CI for the incremental cost-effectiveness ratio was estimated from 5,000 bootstrap samples. RESULTS: In multivariable analysis, the odds ratio for in-hospital death in the post- versus pre-implementation periods was 0.70 (95% CI, 0.57-0.86) in those with suspected infection, and the hazard ratio for time to discharge was 1.25 (95% CI, 1.20-1.29). Similarly, a decrease in the odds for in-hospital death and an increase in the speed to discharge was observed for the subset that met Sepsis-3 criteria. The program was cost saving in patients with suspected infection (-$272,645.7; 95% CI, -$757,970.3 to -$79,667.7). Cost savings were also observed in the Sepsis-3 group. CONCLUSIONS AND RELEVANCE: Our health system's program designed to adhere to the sepsis bundle metrics led to decreased mortality and length of stay in a cost-effective manner in a much larger catchment than just the cohort meeting the Centers for Medicare and Medicaid Services measures. Our single-center model of interventions may serve as a practice-based benchmark for hospitalized patients with suspected infection.

Perceived discrimination and physical health-related quality of life: The Hispanic Community Health Study/Study of Latinos (HCHS/SOL) Sociocultural Ancillary Study.

RATIONALE: The aim of this study was to examine the direct associations of perceived personal and group discrimination with physical health-related quality of life (HRQoL) among Latinx adults. We also tested whether ethnic identity and depression symptoms sequentially mediate these associations. METHOD: This population-based study included 5313 Latinx adults, ages 18-74 years, from the Hispanic Community Health Study/Study of Latinos (2008-11) and its Sociocultural Ancillary Study (2010-11). Participants were recruited from the Bronx; NY; Chicago, IL; Miami, FL; and San Diego, CA. Self-reported perceived personal and group discrimination, ethnic identity, depression symptoms, and physical HRQoL were ascertained through interviewer-administered surveys. Survey-weighted path analysis was used to examine direct and indirect effects simultaneously in one analytic model controlling for demographic covariates. RESULTS: Path analysis indicated that higher perceived personal discrimination was directly associated with poorer physical HRQoL and this association was only mediated by depression symptoms. In contrast, perceived group discrimination was not directly associated with physical HRQoL. However, each of the direct paths linking perceived group discrimination to physical HRQoL were statistically significant: perceived group discrimination was positively associated with ethnic identity, and ethnic identity was negatively associated with depression symptoms, and, in turn, depression symptoms were negatively associated with physical HRQoL. Our model accounted for 18% of the variance of physical HRQoL. CONCLUSIONS: Perceived personal and group discrimination are differently associated with physical HRQoL. Results highlight the importance of considering self-perceptions of different discrimination forms when evaluating its impact on the physical HRQoL of Latinx adults.

A hypertension emergency department intervention aimed at decreasing disparities: Design of a randomized clinical trial.

Effective interventions to identify and treat uncontrolled hypertension (HTN), particularly in underrepresented populations that use the emergency department (ED) for primary care, are critically needed. Uncontrolled HTN contributes significantly to cardiovascular morbidity and mortality and is more frequently encountered among patients presenting to the ED as compared to the primary care setting. EDs serve as the point of entry into the health care system for high-risk patient populations, including minority and low-income patients. Previous studies have demonstrated that the prevalence of uncontrolled/undiagnosed HTN in patients presenting to the ED is alarmingly high. Thus ED engagement and early risk assessment/stratification is a feasible innovation to help close health disparity gaps in HTN. A Hypertension Emergency Department Intervention Aimed at Decreasing Disparities (AHEAD2) trial, funded by the National Heart, Lung, and Blood Institute (NHLBI) is a three-arm single site randomized clinical pilot trial of adults presenting to the ED with Stage 2 hypertension (blood pressure [BP]>160/100) comparing (1) an ED-initiated Screening, Brief Intervention, and Referral for Treatment (SBIRT) focused on HTN, (2) the same ED-initiated SBIRT coupled with a Post-Acute Care Hypertension Transition Consultation by ED Clinical Pharmacists, and (3) usual care. The primary outcome is mean BP differences between study arms. Secondary outcomes are proportion of participants with BP control (BP<140/90mmHg), and improvements in HTN knowledge and medication adherence scores between study arms. The objective of this report is to describe the development of the AHEAD2 trial, including the methods, research infrastructure, and other features of the randomized clinical trial design.

Baseline Assessment of 25-Hydroxyvitamin D Reference Material and Proficiency Testing/External Quality Assurance Material Commutability: A Vitamin D Standardization Program Study.

The Vitamin D Standardization Program (VDSP) coordinated a study in 2012 to assess the commutability of reference materials and proficiency testing/external quality assurance materials for total 25-hydroxyvitamin D [25(OH)D] in human serum, the primary indicator of vitamin D status. A set of 50 single-donor serum samples as well as 17 reference and proficiency testing/external quality assessment materials were analyzed by participating laboratories that used either immunoassay or LC-MS methods for total 25(OH)D. The commutability test materials included National Institute of Standards and Technology Standard Reference Material 972a Vitamin D Metabolites in Human Serum as well as materials from the College of American Pathologists and the Vitamin D External Quality Assessment Scheme. Study protocols and data analysis procedures were in accordance with Clinical and Laboratory Standards Institute guidelines. The majority of the test materials were found to be commutable with the methods used in this commutability study. These results provide guidance for laboratories needing to choose appropriate reference materials and select proficiency or external quality assessment programs and will serve as a foundation for additional VDSP studies.

Baseline Assessment of 25-Hydroxyvitamin D Assay Performance: A Vitamin D Standardization Program (VDSP) Interlaboratory Comparison Study.

The Vitamin D Standardization Program (VDSP) coordinated an interlaboratory study to assess the comparability of measurements of total 25-hydroxyvitamin D [25(OH)D] in human serum, which is the primary marker of vitamin D status. A set of 50 individual donor samples were analyzed by 15 different laboratories representing national nutrition surveys, assay manufacturers, and clinical and/or research laboratories to provide results for total 25(OH)D using both immunoassays (IAs) and LC tandem MS (MS/MS). The results were evaluated relative to bias compared with the target values assigned based on a combination of measurements at Ghent University (Belgium) and the U.S. National Institute of Standards and Technology using reference measurement procedures for the determination of 25(OH)D2 and 25(OH)D3. CV and mean bias for each laboratory and assay platform were assessed and compared with previously established VDSP performance criteria, namely CV ≤ 10% and mean bias ≤ 5%. Nearly all LC-MS/MS results achieved VDSP criteria, whereas only 50% of IAs met the criterion for a ≤10% CV and only three of eight IAs achieved the ≤5% bias. These results establish a benchmark for the evaluation of 25(OH)D assay performance and standardization activities in the future.

Cardiovascular risk status of Afro-origin populations across the spectrum of economic development: findings from the Modeling the Epidemiologic Transition Study.

BACKGROUND: Cardiovascular risk factors are increasing in most developing countries. To date, however, very little standardized data has been collected on the primary risk factors across the spectrum of economic development. Data are particularly sparse from Africa. METHODS: In the Modeling the Epidemiologic Transition Study (METS) we examined population-based samples of men and women, ages 25-45 of African ancestry in metropolitan Chicago, Kingston, Jamaica, rural Ghana, Cape Town, South Africa, and the Seychelles. Key measures of cardiovascular disease risk are described. RESULTS: The risk factor profile varied widely in both total summary estimates of cardiovascular risk and in the magnitude of component factors. Hypertension ranged from 7% in women from Ghana to 35% in US men. Total cholesterol was well under 200 mg/dl for all groups, with a mean of 155 mg/dl among men in Ghana, South Africa and Jamaica. Among women total cholesterol values varied relatively little by country, following between 160 and 178 mg/dl for all 5 groups. Levels of HDL-C were virtually identical in men and women from all study sites. Obesity ranged from 64% among women in the US to 2% among Ghanaian men, with a roughly corresponding trend in diabetes. Based on the Framingham risk score a clear trend toward higher total risk in association with socioeconomic development was observed among men, while among women there was considerable overlap, with the US participants having only a modestly higher risk score. CONCLUSIONS: These data provide a comprehensive estimate of cardiovascular risk across a range of countries at differing stages of social and economic development and demonstrate the heterogeneity in the character and degree of emerging cardiovascular risk. Severe hypercholesterolemia, as characteristic in the US and much of Western Europe at the onset of the coronary epidemic, is unlikely to be a feature of the cardiovascular risk profile in these countries in the foreseeable future, suggesting that stroke may remain the dominant cardiovascular event.

Seasonal Changes in Vitamin D-Effective UVB Availability in Europe and Associations with Population Serum 25-Hydroxyvitamin D.

Low vitamin D status is common in Europe. The major source of vitamin D in humans is ultraviolet B (UVB)-induced dermal synthesis of cholecalciferol, whereas food sources are believed to play a lesser role. Our objectives were to assess UVB availability (Jm(-2)) across several European locations ranging from 35° N to 69° N, and compare these UVB data with representative population serum 25-hydroxyvitamin D (25(OH)D) data from Ireland (51-54° N), Iceland (64° N) and Norway (69° N), as exemplars. Vitamin D-effective UVB availability was modelled for nine European countries/regions using a validated UV irradiance model. Standardized serum 25(OH)D data was accessed from the EC-funded ODIN project. The results showed that UVB availability decreased with increasing latitude (from 35° N to 69° N), while all locations exhibited significant seasonal variation in UVB. The UVB data suggested that the duration of vitamin D winters ranged from none (at 35° N) to eight months (at 69° N). The large seasonal fluctuations in serum 25(OH)D in Irish adults was much dampened in Norwegian and Icelandic adults, despite considerably lower UVB availability at these northern latitudes but with much higher vitamin D intakes. In conclusion, increasing the vitamin D intake can ameliorate the impact of low UVB availability on serum 25(OH)D status in Europe.

Comparison of Two ELISA Methods and Mass Spectrometry for Measurement of Vitamin D-Binding Protein: Implications for the Assessment of Bioavailable Vitamin D Concentrations Across Genotypes.

Studies using vitamin D-binding protein (DBP) concentrations to estimate free and bioavailable vitamin D have increased dramatically in recent years. Combinations of two single-nucleotide polymorphisms (SNPs) produce three major DBP isoforms (Gc1f, Gc1s, and Gc2). A recent study showed that DBP concentrations quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) did not differ by race, whereas a widely used monoclonal enzyme-linked immunosorbent assay (ELISA) quantified DBP differentially by isoform, yielding significantly lower DBP concentrations in black versus white individuals. We compared measurements of serum DBP using a monoclonal ELISA, a polyclonal ELISA, and LC-MS/MS in 125 participants in the Chronic Renal Insufficiency Cohort (CRIC). Serum free and bioavailable 25OHD were calculated based on DBP concentrations from these three assays in homozygous participants, and race differences were compared. We confirmed that the monoclonal ELISA quantifies DBP differentially by isoform and showed that the polyclonal ELISA is not subject to this bias. Whereas ≤9% of the variability in DBP concentrations quantified using either LC-MS/MS or the polyclonal ELISA was explained by genotype, 85% of the variability in the monoclonal ELISA-based measures was explained by genotype. DBP concentrations measured by the monoclonal ELISA were disproportionately lower than LC-MS/MS-based results for Gc1f homozygotes (median difference -67%; interquartile range [IQR] -71%, -64%), 95% of whom were black. In contrast, the polyclonal ELISA yielded consistently and similarly higher measurements of DBP than LC-MS/MS, irrespective of genotype, with a median percent difference of +50% (IQR +33%, +65%). Contrary to findings using the monoclonal ELISA, DBP concentrations did not differ by race, and free and bioavailable 25OHD were significantly lower in black versus white participants based on both the polyclonal ELISA and LC-MS/MS, consistent with their lower total 25OHD. Future studies of DBP and free or bioavailable vitamin D metabolites should employ DBP assays that are not biased by DBP genotype. © 2016 American Society for Bone and Mineral Research.

Fibroblast Growth Factor-23 (FGF-23) Levels Differ Across Populations by Degree of Industrialization.

CONTEXT: Compensatory increases in fibroblast growth factor 23 (FGF23) with increasing phosphate intake may adversely impact health. However, population and clinical studies examining the link between phosphate intake and FGF23 levels have focused mainly on populations living in highly industrialized societies in which phosphate exposure may be homogenous. OBJECTIVE: The objective of the study was to contrast dietary phosphate intake, urinary measures of phosphate excretion, and FGF23 levels across populations that differ by the level of industrialization. DESIGN: This was a cross-sectional analysis of three populations. SETTING: The study was conducted in Maywood, Illinois; Mahé Island, Seychelles; and Kumasi, Ghana. PARTICIPANTS: Adults with African ancestry aged 25-45 years participated in the study. MAIN OUTCOME: FGF23 levels were measured. RESULTS: The mean age was 35.1 (6.3) years and 47.9% were male. Mean phosphate intake and fractional excretion of phosphate were significantly higher in the United States vs Ghana, whereas no significant difference in phosphate intake or fractional excretion of phosphate was noted between the United States and Seychelles for men or women. Overall, median FGF23 values were 57.41 RU/mL (interquartile range [IQR] 43.42, 75.09) in the United States, 42.49 RU/mL (IQR 33.06, 55.39) in Seychelles, and 33.32 RU/mL (IQR 24.83, 47.36) in Ghana. In the pooled sample, FGF23 levels were significantly and positively correlated with dietary phosphate intake (r = 0.11; P < .001) and the fractional excretion of phosphate (r = 0.13; P < .001) but not with plasma phosphate levels (r = -0.001; P = .8). Dietary phosphate intake was significantly and positively associated with the fractional excretion of phosphate (r = 0.23; P < .001). CONCLUSION: The distribution of FGF23 levels in a given population may be influenced by the level of industrialization, likely due to differences in access to foods preserved with phosphate additives.

Constrained Total Energy Expenditure and Metabolic Adaptation to Physical Activity in Adult Humans.

Current obesity prevention strategies recommend increasing daily physical activity, assuming that increased activity will lead to corresponding increases in total energy expenditure and prevent or reverse energy imbalance and weight gain [1-3]. Such Additive total energy expenditure models are supported by exercise intervention and accelerometry studies reporting positive correlations between physical activity and total energy expenditure [4] but are challenged by ecological studies in humans and other species showing that more active populations do not have higher total energy expenditure [5-8]. Here we tested a Constrained total energy expenditure model, in which total energy expenditure increases with physical activity at low activity levels but plateaus at higher activity levels as the body adapts to maintain total energy expenditure within a narrow range. We compared total energy expenditure, measured using doubly labeled water, against physical activity, measured using accelerometry, for a large (n = 332) sample of adults living in five populations [9]. After adjusting for body size and composition, total energy expenditure was positively correlated with physical activity, but the relationship was markedly stronger over the lower range of physical activity. For subjects in the upper range of physical activity, total energy expenditure plateaued, supporting a Constrained total energy expenditure model. Body fat percentage and activity intensity appear to modulate the metabolic response to physical activity. Models of energy balance employed in public health [1-3] should be revised to better reflect the constrained nature of total energy expenditure and the complex effects of physical activity on metabolic physiology.

Daily activity patterns of 2316 men and women from five countries differing in socioeconomic development.

Daily rhythmicity in the locomotor activity of laboratory animals has been studied in great detail for many decades, but the daily pattern of locomotor activity has not received as much attention in humans. We collected waist-worn accelerometer data from more than 2000 individuals from five countries differing in socioeconomic development and conducted a detailed analysis of human locomotor activity. Body mass index (BMI) was computed from height and weight. Individual activity records lasting 7 days were subjected to cosinor analysis to determine the parameters of the daily activity rhythm: mesor (mean level), amplitude (half the range of excursion), acrophase (time of the peak) and robustness (rhythm strength). The activity records of all individual participants exhibited statistically significant 24-h rhythmicity, with activity increasing noticeably a few hours after sunrise and dropping off around the time of sunset, with a peak at 1:42 pm on average. The acrophase of the daily rhythm was comparable in men and women in each country but varied by as much as 3 h from country to country. Quantification of the socioeconomic stages of the five countries yielded suggestive evidence that more developed countries have more obese residents, who are less active, and who are active later in the day than residents from less developed countries. These results provide a detailed characterization of the daily activity pattern of individual human beings and reveal similarities and differences among people from five countries differing in socioeconomic development.

Depression in the US population during the time periods surrounding the great recession.

OBJECTIVE: To determine whether the time periods surrounding the 2008 US economic downturn were accompanied by an increase in prevalence of depression in the US adult population. METHOD: We used data from the 24,182 adults aged ≥ 18 years who participated in the National Health and Nutrition Examination Survey during 2005-2012. A cross-sectional analysis was performed at each time period to determine prevalence of major and other depression as assessed by standardized questionnaires based on 9 criteria for major depressive episodes defined by DSM-IV. RESULTS: The demographic characteristics of the US population were similar across time periods except for the percentage of adults living in poverty, which increased from 26.43% during 2005-2006 to 33.46% during 2011-2012. The prevalence of major depression increased from 2.33% (95% CI, 1.64%-3.01%) during 2005-2006 to 3.49% (95% CI, 2.84%-4.03%) in 2009-2010 to 3.79% (95% CI, 3.01%-4.57%) in 2011-2012. Prevalence of other depression increased from 4.10% (95% CI, 3.37%-4.88%) in 2005-2006 to 4.79% (95% CI, 4.10%-5.44%) in the 2009-2010 period but then declined to 3.68% (95% CI, 2.84%-4.48%) in the 2011-2012 time period (P = .4). After adjustment for the distribution of age, sex, race/ethnicity, education, insurance status, and poverty status in the US adult noninstitutionalized population, each 2-year period after the 2005-2006 time period was associated with a 0.4% increase in major depression prevalence (P < .001). No significant differences in other depression prevalence were noted by time period (P = .6). CONCLUSIONS: The time periods surrounding the recent economic recession were accompanied by a significant and sustained increase in major depression prevalence in the US population. It is plausible that the recession, given its strong, persistent, and negative effects on employment, job and housing security, and stock investments, contributed to the sustained increase in prevalence of major depression in the US population, but other factors associated with the recession time period could have played a role. The impact of the economic downturn on depression prevalence should be considered when formulating future policies and programs to promote and maintain the health of the US population.