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Loren Lipworth,1 Sergio Fazio,1,2 Edmond K Kabagambe,1 Heather M Munro,3 Victor C Nwazue,1 Robert E Tarone,3 Joseph K McLaughlin,3 William J Blot,1,3 Uchechukwu KA Sampson1,2,41Department of Medicine, Vanderbilt University Medical Center, 2Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA; 3International Epidemiology Institute, Rockville, MD, USA; 4Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN, USAPurpose: The primary objective of this study is to examine the race-specific associations between statin use and overall mortality, as well as cardiovascular and cancer mortality, among blacks and whites in the Southeastern United States (US). Little is known about these associations in blacks.Patients and methods: The Southern Community Cohort Study is an ongoing, prospective cohort study, which enrolled from 2002 through 2009 nearly 86,000 participants aged 40–79 years. We used Cox regression models to estimate race-specific hazard ratios (HRs) and 95% confidence intervals (CI) for overall and cause-specific mortality associated with statin use based on self-reported hypercholesterolemia and treatment at cohort entry. Mean age at cohort entry was 51.4 years in blacks (n=48,825) and 53.5 years in whites (n=18,560). Sixty-one percent of participants were women. Whites were more likely to have self-reported hypercholesterolemia (40% versus 27%, P0.05 for race and sex interaction). Statin use was not associated with cancer mortality overall or in subgroup analyses.Conclusion: Regardless of race or sex, self-reported statin use was linked to reduced all-cause and cardiovascular disease mortality. However, factors contributing to the modestly lower statin use and markedly lower prevalence of self-reported hypercholesterolemia among blacks remain to be determined.Keywords: statins, disparities, hypercholesteromia, undertreatment, underdiagnosis, mortality

Objective: Low BMI is a major risk factor for early mortality among HIV-infected persons starting antiretrovial therapy (ART) in sub-Saharan Africa and the common patient belief that antiretroviral medications produce distressing levels of hunger is a barrier to treatment adherence. We assessed relationships between appetite, dietary intake and treatment outcome 12 weeks after ART initiation among HIV-infected adults with advanced malnutrition and immunosuppression.Design: A prospective, observational cohort study. Dietary intake was assessed using a 24 h recall survey. The relationships of appetite, intake and treatment outcome were analysed using time-varying Cox models.Setting: A public-sector HIV clinic in Lusaka, Zambia.Subjects: One hundred and forty-two HIV-infected adults starting ART with BMI <16 kg/m2 and/or CD4+ lymphocyte count <50 cells/μl.Results: Median age, BMI and CD4+ lymphocyte count were 32 years, 16 kg/m2 and 34 cells/μl, respectively. Twenty-five participants (18%) died before 12 weeks and another thirty-three (23%) were lost to care. A 500 kJ/d higher energy intake at any time after ART initiation was associated with an approximate 16% reduction in the hazard of death (adjusted hazard ratio = 0.84; P = 0.01), but the relative contribution of carbohydrate, protein or fat to total energy was not a significant predictor of outcome. Appetite normalized gradually among survivors and hunger was rarely reported.Conclusions: Poor early ART outcomes were strikingly high in a cohort of HIV-infected adults with advanced malnutrition and mortality was predicted by lower dietary intake. Intervention trials to promote post-ART intake in this population may benefit survival and are warranted. [ABSTRACT FROM AUTHOR]

Background and Aims: The disintegrin and metalloproteinase ADAM17, also known as tumor necrosis factor alpha converting enzyme, is expressed in adipocytes. Importantly, elevated levels of ADAM17 expression have been linked to obesity and insulin resistance. Therefore, the aim of this study was to evaluate the association of six ADAM17 single nucleotide polymorphisms (SNPs) (m1254A>G, i14121C>A, i33708A>G, i48827A>C, i53440C>T, and i62781G>T) with insulin-resistance phenotypes and obesity risk, and their potential interactions with dietary polyunsaturated fatty acids (PUFA).Methods and Results: ADAM17 SNPs were genotyped in 936 subjects (448 men/488 women) who participated in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study. Anthropometrical and biochemical measurements were determined by standard procedures. PUFA intake was estimated using a validated questionnaire. G allele carriers at the ADAM17_m1254A>G polymorphism exhibited significantly higher risk of obesity (P=0.003), were shorter (P=0.017), had higher insulin (P=0.016), and lower HDL-C concentrations (P=0.027) than AA subjects. For the ADAM17_i33708A>G SNP, homozygotes for the A allele displayed higher risk of obesity (P=0.001), were heavier (P=0.011), had higher BMI (P=0.005), and higher waist measurements (P=0.023) than GG subjects. A significant gene-diet interaction was found (P=0.030), in which the deleterious association of the i33708A allele with obesity was observed in subjects with low intakes from (n-6) PUFA (P<0.001), whereas no differences in obesity risk were seen among subjects with high (n-6) PUFA intake (P>0.5)Conclusion: These findings support that ADAM17 (m1254A>G and i33708A>G) SNPs may contribute to obesity risk. For the ADAM17_i33708A>G SNP, this risk may be further modulated by (n-6) PUFA intake. [ABSTRACT FROM AUTHOR]

BACKGROUND: Several genome-wide association studies have identified novel loci (KCTD10, MVK, and MMAB) that are associated with HDL-cholesterol concentrations. Of the environmental factors that determine HDL cholesterol, high-carbohydrate diets have been shown to be associated with low concentrations. OBJECTIVE: The objective was to evaluate the associations of 8 single nucleotide polymorphisms (SNPs) located within the KCTD10, MVK, and MMAB loci with lipids and their potential interactions with dietary carbohydrates. DESIGN: KCTD10, MVK, and MMAB SNPs were genotyped in 920 subjects (441 men and 479 women) who participated in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) Study. Biochemical measurements were made by using standard procedures. Dietary intakes were estimated by using a validated questionnaire. RESULTS: For the SNPs KCTD10_i5642G-->C and MVK_S52NG-->A, homozygotes for the major alleles (G) had lower HDL-cholesterol concentrations than did carriers of the minor alleles (P = 0.005 and P = 0.019, respectively). For the SNP 12inter_108466061A-->G, homozygotes for the minor allele (G) had higher total cholesterol and LDL-cholesterol concentrations than did AG subjects (P = 0.030 and P = 0.034, respectively). Conversely, homozygotes for the major allele (G) at MMAB_3U3527G-->C had higher LDL-cholesterol concentrations than did carriers of the minor allele (P = 0.034). Significant gene-diet interactions for HDL cholesterol were found (P < 0.001-0.038), in which GG subjects at SNPs KCTD10_i5642G-->C and MMAB_3U3527G-->C and C allele carriers at SNP KCTD10_V206VT-->C had lower concentrations only if they consumed diets with a high carbohydrate content (P < 0.001-0.011). CONCLUSION: These findings suggest that the KCTD10 (V206VT-->C and i5642G-->C) and MMAB_3U3527G-->C variants may contribute to the variation in HDL-cholesterol concentrations, particularly in subjects with high carbohydrate intakes. Copyright © 2009 American Society for Nutrition [ABSTRACT FROM AUTHOR]

Objective: To examine the socio-economic and lifestyle determinants of cooking oil choice in Costa Rica during the last decade (1994-2004).Design: Cross-sectional study. Subjects (total n = 2274) belonged to the control population of a large case-control study; they were recruited yearly. Data about type of oil used for cooking, dietary intake, socio-economic and demographic characteristics were collected.Setting: A dietitian visited all subjects and conducted the interviews at their homes; all subjects lived in the Costa Rican central valley region.Subjects: Adult, free-living, rural and urban Costa Ricans with no history of myocardial infarction and physical or mental disability.Results: The odds of choosing soybean over palm oil increased significantly each year (P < 0.05) and was determined by high socio-economic status (SES) and variables that suggest health awareness (self-reported history of hypertension, high cholesterol, multivitamin use and intake of green leafy vegetables). The odds of choosing other unsaturated oils, namely corn and sunflower, over soybean oil also increased yearly (P < 0.05) and was associated with the same two factors (high SES and health awareness). Palm oil users remained in the lowest SES tertile and were more likely to live in rural areas. Across all SES tertiles, high health awareness determined the odds of choosing other unsaturated oils over palm oil, and soybean oil (P < 0.05).Conclusion: These data show that, in addition to SES, health awareness is associated with the selection of unsaturated oils over palm oil in a developing country undergoing transition. These data should be considered when targeting nutrition messages and policies that promote better dietary choices. [ABSTRACT FROM AUTHOR]

Background: Data regarding care access and outcomes in Black/Indigenous/People of Color/Hispanic (BIPOC/H) individuals is limited. This study evaluated care barriers, disease status, and outcomes among a diverse population of White/non-Hispanic (W/NH) and BIPOC/H inflammatory bowel disease (IBD) patients at a large U.S. health system., Methods: An anonymous online survey was administered to adult IBD patients at Ochsner Health treated between Aug 2019 and Dec 2021. Collected data included symptoms, the Consumer Assessment of Healthcare Providers and Systems and Barriers to Care surveys, health-related quality of life (HRQOL) via the Short Inflammatory Bowel Disease Questionnaire, the Medication Adherence Rating Scale-4, and the Beliefs about Medicines Questionnaire. Medical record data examined healthcare resource utilization. Analyses compared W/NH and BIPOC/H via chi-square and t tests., Results: Compared with their W/NH counterparts, BIPOC/H patients reported more difficulties accessing IBD specialists (26% vs 11%; P = .03), poor symptom control (35% vs 18%; P = .02), lower mean HRQOL (41 ± 14 vs 49 ± 13; P < .001), more negative impact on employment (50% vs 33%; P = .029), worse financial stability (53% vs 32%; P = .006), and more problems finding social/emotional support for IBD (64% vs 37%; P < .001). BIPOC/H patients utilized emergency department services more often (42% vs 22%; P = .004), reported higher concern scores related to IBD medication (17.1 vs 14.9; P = .001), and worried more about medication harm (19.5% vs 17.7%; P = .002). The survey response rate was 14%., Conclusions: BIPOC/H patients with IBD had worse clinical disease, lower HRQOL scores, had more medication concerns, had less access to specialists, had less social and emotional support, and used emergency department services more often than W/NH patients., (© 2023 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation.)

Background: Type 2 diabetes mellitus (T2DM) results in heavy economic and disease burdens in Louisiana. The Centers for Medicare and Medicaid Services has reimbursed non-face-to-face chronic care management (NFFCCM) for patients with two or more chronic conditions since 2015., Objective: To assess the impacts of NFFCCM on healthcare utilization and health outcomes., Design, Setting, and Participants: This retrospective cohort study included Medicare fee-for-service beneficiaries with T2DM and at least one additional chronic disease between 2014 and 2018., Exposures: At least one record of NFFCCM Current Procedural Terminology codes., Main Measures: The health outcomes in the study included major adverse cardiovascular events (MACE), all-cause mortality, and heart failure. The monthly service utilization and continuity of care index for primary care were also included. The propensity score method was used to balance the baseline differences between the two groups. Weighted multivariate regression models were developed using propensity score weights to assess the impacts of NFFCCM on outcomes., Key Results: During the 5 years of study period, 8415 patients among the 118,643 Medicare beneficiaries received at least one NFFCCM. Patients receiving any NFFCCM had reduced healthcare utilization compared with patients not receiving NFFCCM, including 0.012 (95% CI - 0.014 to - 0.011; p < 0.001) fewer monthly hospital admissions, 0.017 (95% CI - 0.019 to - 0.016; p < 0.001) fewer monthly ED visits, and 0.399 (95% CI 0.375 to 0.423; p < 0.001) more monthly outpatient encounters. Patients receiving NFFCCM services had lower MACE event rates of 7.4% (95% CI 7.1 to 7.8%; p < 0.001), all-cause mortality rate of 7.8% (95% CI 7.4 to 8.1%; p < 0.001), and heart failure rate of 0.3% (95% CI 0.2 to 0.5%; p < 0.001), respectively., Conclusions and Relevance: These findings suggest that reimbursement for NFFCCM was associated with the shifting high-cost utilization to lower-cost primary health care settings among patients with diabetes in Louisiana., (© 2024. The Author(s).)

Objective: To understand which types of Medicare patients with diabetes disproportionately used telehealth during the coronavirus disease 2019 pandemic and how their characteristics mediated their inpatient and emergency department (ED) utilization. Methods: Logistic regression analyses were used to measure the associations between patient characteristics and telehealth utilization using electronic health records among Medicare patients with diabetes ( n  = 31,654). Propensity score matching was used to examine the relative impact of telehealth use in conjunction with race, ethnicity, and age on inpatient and ED outcomes. Results: Telehealth was associated with age (75-84 vs. 65-74; odds ratio [OR] = 0.810, p < 0.01), gender (female: OR = 1.148, p < 0.01), and chronic diseases (e.g., lung disease: OR = 1.142; p < 0.01). Black patients using telehealth were less likely to visit the ED (estimate = -0.018; p  = 0.08), whereas younger beneficiaries using telehealth were less likely to experience an inpatient stay (estimate = -0.017; p  = 0.06). Conclusions: Telehealth expansion particularly benefited the clinically vulnerable but saw uneven use and uneven benefit along sociodemographic lines. Clinical Trial Registration Number: NCT03136471.

Objectives: We evaluated the impact of reimbursement for non-face-to-face chronic care management (NFFCCM) on healthcare utilization among Medicare beneficiaries with type 2 diabetes in Louisiana., Methods: We implemented group-based trajectory balancing and propensity score matching to obtain comparable treatment (with NFFCCM) and control (without NFFCCM) groups at baseline. Patients with diabetes with Medicare as their primary payer at baseline were extracted using electronic health records of 3 health systems from Research Action for Health Network, a Clinical Research Network. The study period is from 2013 to early 2020. Our outcomes include general healthcare utilization (outpatient, emergency department, and inpatient encounters) and health utilization related to diabetic complications. We tested each of these outcomes according to multiple treatment definitions and different subgroups., Results: Receiving any NFFCCM was associated with an increase in outpatient visits of 657 (95% confidence interval [CI] 626-687; P < .001) per 1000 patients per month, a decrease in inpatient admissions of 5 (95% CI 2-7; P < .001) per 1000 patients per month, and a decrease in emergency department visits of 4 (95% CI 1-7; P = .005) per 1000 patients per month after 24-month follow-up from initial NFFCCM encounter. Both complex and noncomplex NFFCCM significantly increased visits to outpatient services and inpatient admissions per month. Receiving NFFCCM has a dose-response association with increasing outpatient visits per month., Conclusions: Patients with diabetes in Louisiana who received NFFCCM had more low-cost primary healthcare and less high-cost healthcare utilization in general. The cost savings of NFFCCM in diabetes management could be further explored in the future., (Copyright © 2022. Published by Elsevier Inc.)

Aims: We evaluated the impact of reimbursement for non-face-to-face chronic care management (NFFCCM) on comprehensive metabolic risk factors among multimorbid Medicare beneficiaries with type 2 diabetes in Louisiana., Materials and Methods: We implemented a propensity score method to obtain comparable treatment (n=1501 with NFFCCM) and control (n=17,524 without NFFCCM) groups. Patients with type 2 diabetes were extracted from the electronic health records stored in REACHnet. The study period was from 2013 to February 2020. The comprehensive metabolic risk factors included the primary outcome of glycated hemoglobin (HbA1c) (as the primary outcome) and the secondary outcomes of body mass index (BMI), systolic blood pressure (BP), and low-density lipoprotein cholesterol., Results: Receiving any NFFCCM was associated with improvement in all outcomes measures: a reduction in HbA1c of 0.063% (95% CI: 0.031%-0.094%; P <0.001), a reduction in BMI of 0.155 kg/m 2 (95% CI: 0.029-0.282 kg/m 2 ; P =0.016), a reduction in systolic BP of 0.816 mm Hg (95% CI: 0.469-1.163 mm Hg; P <0.001), and a reduction in low-density lipoprotein cholesterol of 1.779 mg/dL (95% CI: 0.988 2.570 mg/dL; P <0.001). Compared with the control group, the treatment group had 1.6% more patients with HbA1c <7% (95% CI: 0.3%-2.9%; P =0.013)., Conclusions: Patients with diabetes in Louisiana receiving NFFCCM experienced better control of HbA1c, BMI, BP, and low-density lipoprotein outcomes., Competing Interests: V.F. reports and research support (to Tulane): grants from Fractyl, Jaguar Gene Therapy; honoraria for Consulting and Lectures: Takeda, Novo Nordisk, Sanofi-Aventis, Bayer Abbott, Astra-Zeneca, Intarcia, Asahi; stock options: Mellitus Health, BRAVO4Health; Stock: Amgen. E.N. reports grants from Patient Centered Outcomes Research Institute, during the conduct of the study; grants from Patient Centered Outcomes Research Institute, outside the submitted work. The remaining authors declare no conflict of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Individual inflammation biomarkers are associated with incident coronary heart disease (CHD) events. However, there is limited research on whether the risk for incident CHD is progressively higher with a higher number of inflammation biomarkers in abnormal levels., Methods: We used data from 15,758 Reasons for Geographic and Racial Differences in Stroke (REGARDS) study participants aged ≥45 years without a history of CHD at baseline in 2003-2007. Abnormal levels of baseline high-sensitivity C-reactive protein, leukocyte count and serum albumin were defined as ≥3.8 mg/L (3rd tertile), ≥6.3 x 10 9 cells/L (3rd tertile), and <4.0 g/dL (1st tertile), respectively. The outcome was a composite of incident myocardial infarction or CHD death., Results: Overall, 38.9% (n = 6,123) had 0, 36.6% (n = 5,774) had 1, 19.8% (n = 3,113) had 2 and 4.7% (n = 748) had 3 biomarkers of inflammation in abnormal levels. Over a median follow-up of 11.4 years, 954 (6.1%) participants had incident CHD. The rate of incident CHD per 1000 person-years for individuals with 0, 1, 2, and 3 biomarkers of inflammation in abnormal levels was 4.4 (95% confidence interval [CI]: 3.9-5.0), 6.3 (95% CI: 5.6-6.9), 8.8 (95% CI: 7.8-9.9), and 10.6 (95% CI: 8.1-13.1), respectively. Multi-variable adjusted hazard ratios for incident CHD associated with 1, 2 and 3 versus no inflammation biomarker in abnormal levels were 1.26 (95% CI: 1.07-1.49), 1.72 (95% CI: 1.43-2.07), and 1.84 (95% CI: 1.37-2.47), respectively (P-trend < .001)., Conclusions: The number of inflammation markers in abnormal levels was associated with increased risk of incident CHD after multi-variable adjustment., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Consistent with previous cross-sectional studies, in the Southern Community Cohort Study, the largest cohort for Black Americans conducted in a predominantly low-income population with 81,694 participants, we found that moderate alcohol drinking was associated with a significantly increased risk of mortality due to liver disease in Black Americans (hazard ratio = 2.06; 95% confidence interval: 1.08-3.94) but not in White Americans (hazard ratio = 0.87; 95% confidence interval: 0.52-1.44). We found that heavy drinking was significantly associated with an increased risk of mortality due to liver disease in both Black and White Americans. Future studies are warranted to understand the mechanism involving such racial disparity., (Copyright © 2022 by The American College of Gastroenterology.)

Background & Aims: A genome-wide significant association between anti-Helicobacter pylori (H pylori) IgG titers and Toll-like receptor (TLR1/6/10) locus on 4p14 was demonstrated for individuals of European ancestry, but not uniformly replicated. We re-investigated this association in an updated genome-wide association study (GWAS) meta-analysis for populations with low gastric cancer incidence, address potential causes of cohort heterogeneity, and explore functional implications of genetic variation at the TLR1/6/10 locus., Methods: The dichotomous GWAS (25% individuals exhibiting highest anti-H pylori IgG titers vs remaining 75%) included discovery and replication sampls of, respectively, n = 15,685 and n = 9676, all of European ancestry. Longitudinal analysis of serologic data was performed on H pylori-eradicated subjects (n = 132) and patients under surveillance for premalignant gastric lesions (n = 107). TLR1/6/10 surface expression, TLR1 mRNA, and cytokine levels were measured in leukocyte subsets of healthy subjects (n = 26) genotyped for TLR1/6/10 variants., Results: The association of the TLR1/6/10 locus with anti-H pylori IgG titers (rs12233670; β = -0.267 ± SE 0.034; P = 4.42 × 10 -15 ) presented with high heterogeneity and failed replication. Anti-H pylori IgG titers declined within 2-4 years after eradication treatment (P = 0.004), and decreased over time in patients with premalignant gastric lesions (P < 0.001). Variation at the TLR1/6/10 locus affected TLR1-mediated cytokine production and TLR1 surface expression on monocytes (P = 0.016) and neutrophils (P = 0.030), but not mRNA levels., Conclusions: The association between anti-H pylori IgG titers and TLR1/6/10 locus was not replicated across cohorts, possibly owing to dependency of anti-H pylori IgG titers on therapy, clearance, and antibody decay. H pylori-mediated immune cell activation is partly mediated via TLR1 signaling, which in turn is affected by genetic variation., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P < 5 × 10 -9 ), which were delineated to 338 distinct association signals. Fine-mapping of these signals was enhanced by the increased sample size and expanded population diversity of the multi-ancestry meta-analysis, which localized 54.4% of T2D associations to a single variant with >50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying the foundations for functional investigations. Multi-ancestry genetic risk scores enhanced transferability of T2D prediction across diverse populations. Our study provides a step toward more effective clinical translation of T2D GWAS to improve global health for all, irrespective of genetic background., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: Following the high morbidity and mortality due to Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infections in New Orleans, Louisiana, we sought to assess progress toward herd immunity., Methods: Ochsner Health employees and patients who volunteered for Abbott SARS-CoV-2 immunoglobulin G (IgG) antibody test between March 1 and May 1, 2020 were included. We estimated IgG prevalence and used logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) for variables associated with IgG test status., Results: Of the 13,343 participants with IgG test results, 78.6% were women, 70.6% were non-Hispanic White, 21.1% non-Hispanic Black, 2.9% Hispanic Americans and 5.4% belonged to other races. Overall, 7.99% (95% CI: 7.53-8.45%) of the participants tested IgG positive. In age-, sex- and body mass index (BMI)-adjusted analyses, non-Hispanic Blacks were 2.7-times more likely to test positive than non-Hispanic Whites (OR=2.72; 95% CI: 2.33-3.19). Corresponding ORs (95% CIs) were 1.29 (0.84-1.99) for Hispanic Americans and 1.22 (0.85-1.75) for Other race/ethnicities. Compared to participants in administrative occupations, physician assistants (OR=7.14; 95% CI: 1.72-29.6) and therapists (OR=4.74; 95% CI: 1.49-15.03) were significantly more likely to have IgG antibodies while the association among nurses was not significant (OR=2.35; 95% CI: 0.96-5.77). Relative to 1.40, the test threshold for positivity, our measurements indicate a strong immune response (5.38±1.69), especially among those with a higher BMI., Conclusions: SARS-COV-2 IgG antibodies were prevalent only in 8% of the participants. IgG prevalence was highest among non-Hispanic Blacks and participants with higher BMI but was lower among older participants., Competing Interests: Conflicts of Interest The authors have no financial or other conflicts of interest to disclose., (Copyright © 2021 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Data on the relation of egg consumption with risk of type 2 diabetes (T2D) and coronary heart disease (CHD) are limited and inconsistent. Few studies have controlled for overall dietary patterns in egg-T2D or egg-CHD analyses, and it is unclear whether any observed elevated risks of T2D and CHD with frequent egg consumption is real or due to confounding by dietary habits. We tested the hypothesis that frequent egg consumption is associated with a higher risk of T2D and CHD risk after adjustment for overall dietary patterns among adults., Design: We used prospective cohort design to complete time-to-event analyses., Methods: We pooled de novo, harmonized, individual-level analyses from nine US cohorts (n = 103,811). Cox regression was used to estimate hazard ratios separately in each cohort adjusting for age, ethnicity, body mass index (BMI), exercise, smoking, alcohol intake, and dietary patterns. We pooled cohort-specific results using an inverse-variance weighted method to estimate summary relative risks., Results: Median age ranged from 25 to 72 years. Median egg consumption was 1 egg per week in most of the cohorts. While egg consumption up to one per week was not associated with T2D risk, consumption of ≥2 eggs per week was associated with elevated risk [27% elevated risk of T2D comparing 7+ eggs/week with none (95% CI: 16%-37%)]. There was little evidence for heterogeneity across cohorts and we observed similar conclusions when stratified by BMI. Overall, egg consumption was not associated with the risk of CHD. However, in a sensitivity analysis, there was a 30% higher risk of CHD (95% CI: 3%-56%) restricted to older adults consuming 5-6 eggs/week., Conclusions: Our data showed an elevated risk of T2D with egg consumption of ≥2 eggs per week but not with <2 eggs/week. While there was no overall association of egg consumption with CHD risk, the elevated CHD observed with consumption of 5-6 eggs/week in older cohorts merits further investigation., Competing Interests: Disclosures Dr. Djousse received investigator-initiated grant from American Egg Board for current analyses; sponsor had no influence on design, conduct, and interpretation of the results. Other co-authors have no disclosures., (Published by Elsevier Ltd.)

Although many loci have been associated with height in European ancestry populations, very few have been identified in African ancestry individuals. Furthermore, many of the known loci have yet to be generalized to and fine-mapped within a large-scale African ancestry sample. We performed sex-combined and sex-stratified meta-analyses in up to 52,764 individuals with height and genome-wide genotyping data from the African Ancestry Anthropometry Genetics Consortium (AAAGC). We additionally combined our African ancestry meta-analysis results with published European genome-wide association study (GWAS) data. In the African ancestry analyses, we identified three novel loci (SLC4A3, NCOA2, ECD/FAM149B1) in sex-combined results and two loci (CRB1, KLF6) in women only. In the African plus European sex-combined GWAS, we identified an additional three novel loci (RCCD1, G6PC3, CEP95) which were equally driven by AAAGC and European results. Among 39 genome-wide significant signals at known loci, conditioning index SNPs from European studies identified 20 secondary signals. Two of the 20 new secondary signals and none of the 8 novel loci had minor allele frequencies (MAF) < 5%. Of 802 known European height signals, 643 displayed directionally consistent associations with height, of which 205 were nominally significant (p < 0.05) in the African ancestry sex-combined sample. Furthermore, 148 of 241 loci contained ≤20 variants in the credible sets that jointly account for 99% of the posterior probability of driving the associations. In summary, trans-ethnic meta-analyses revealed novel signals and further improved fine-mapping of putative causal variants in loci shared between African and European ancestry populations., (Copyright © 2021 American Society of Human Genetics. All rights reserved.)

Background: Non-alcoholic fatty liver disease (NAFLD) is associated with obesity and hypercholesterolemia. In addition, total fat and folate intake have been associated with NAFLD. Aims: We investigated risk factors for NAFLD among individuals of largely low socioeconomic status, and whether these associations differed by race. Methods: A nested case-control study was conducted within the Southern Community Cohort Study. Through linkage of the cohort with Centers for Medicare and Medicaid Services, International Classification of Diseases, Ninth Revision, Clinical Modification codes were used to identify incident NAFLD cases. Controls were matched 4:1 to cases on enrollment age, sex, and race. A logistic regression was used to estimate odds ratios for the associations of NAFLD with covariates of interest. Results: Neither total fat nor folate intake was significantly associated with NAFLD. Hypercholesterolemia (odds ratio 1.21) and body mass index (75th vs. 25th percentile) for blacks (odds ratio 1.96) and whites (odds ratio 2.33) were associated with an increased risk of non-alcoholic fatty liver disease. No significant interaction with race for any of the studied variables was noted. Conclusions: Both hypercholesterolemia and increasing body mass index, but not total fat and folate intake, were risk factors for NAFLD in the Southern Community Cohort Study., (Copyright © 2020 Sarkar, Lipworth, Kabagambe, Bian, Stewart, Blot, Ikizler and Hung.)

Background: Copy number variation (CNV) in the salivary amylase gene (AMY1) modulates salivary α-amylase levels and is associated with postprandial glycemic traits. Whether AMY1-CNV plays a role in age-mediated change in insulin resistance (IR) is uncertain., Methods: We measured AMY1-CNV using duplex quantitative real-time polymerase chain reaction in two studies, the Boston Puerto Rican Health Study (BPRHS, n = 749) and the Genetics of Lipid-Lowering Drug and Diet Network study (GOLDN, n = 980), and plasma metabolomic profiles in the BPRHS. We examined the interaction between AMY1-CNV and age by assessing the relationship between age with glycemic traits and type 2 diabetes (T2D) according to high or low copy numbers of the AMY1 gene. Furthermore, we investigated associations between metabolites and interacting effects of AMY1-CNV and age on T2D risk., Results: We found positive associations of IR with age among subjects with low AMY1-copy-numbers in both studies. T2D was marginally correlated with age in participants with low AMY1-copy-numbers but not with high AMY1-copy-numbers in the BPRHS. Metabolic pathway enrichment analysis identified the pentose metabolic pathway based on metabolites that were associated with both IR and the interactions between AMY1-CNV and age. Moreover, in older participants, high AMY1-copy-numbers tended to be associated with lower levels of ribonic acid, erythronic acid, and arabinonic acid, all of which were positively associated with IR., Conclusions: We found evidence supporting a role of AMY1-CNV in modifying the relationship between age and IR. Individuals with low AMY1-copy-numbers tend to have increased IR with advancing age., (Published by Oxford University Press on behalf of the American Association for Clinical Chemistry 2020. This work is written by US Government employees and is in the public domain in the US.)

Background/objectives: To identify factors associated with plasma polyunsaturated fatty acid (PUFA) levels among 3-month-old Tanzanian infants., Subjects/methods: Infants (n = 238) and mothers (n = 193) randomly selected from participants in the neonatal vitamin A supplementation randomized controlled trial. A cross-sectional study of maternal-infant pairs at 3 months postpartum., Results: All infant total, n-3, n-6, and individual PUFA levels were correlated with maternal levels. Infant plasma n-3 PUFA levels were higher when maternal n-3 PUFA levels were higher (mean difference in infant % fatty acid per unit increase in maternal levels ± standard error: 0.79 ± 0.08; P < 0.01). Infant plasma docosahexaenoic acid (DHA) levels were positively associated with maternal DHA levels (0.77 ± 0.09; P < 0.01) but were lower for twin births (-0.55 ± 0.27; P = 0.03). Greater birth weight in kilograms (1.00 ± 0.43; P = 0.02) and higher maternal n-6 PUFA levels (0.20 ± 0.07; P < 0.01) were positively associated with higher infant n-6 PUFA levels, whereas maternal mono-unsaturated fatty acid (MUFA) levels (-0.26 ± 0.08; P < 0.01), maternal mid upper arm circumference (MUAC) (-0.22 ± 0.11; P = 0.04), and male sex (-0.99 ± 0.45; P = 0.03) were associated with lower infant plasma n-6 PUFA levels. Infant plasma arachidonic acid (AA) levels were positively associated with maternal plasma AA levels (0.38 ± 0.09; P < 0.01), but inversely associated with twin births (-1.37 ± 0.67; P = 0.04)., Conclusions: Greater birth weight and higher maternal plasma PUFA levels at 3 months postpartum were significantly associated with higher infant plasma PUFA levels at 3 months age. Twin births, male sex, and higher maternal MUFA levels were associated with lower infant plasma PUFA levels. Nutrition counseling for optimal intake of PUFA-rich foods, to lactating mothers in resource-limited settings may be beneficial for improved infant health.

Introduction: The Southern Community Cohort Study is a prospective study of low socioeconomic status (SES) blacks and whites from the southeastern US, where the burden of end-stage renal disease (ESRD) and its risk factors are high. We tested whether the 2.4-fold elevated risk of ESRD we previously observed in blacks compared to whites was explained by differences in baseline kidney function., Methods: We conducted a case-cohort study of incident ESRD cases (n = 737) with stored blood and a probability sampled subcohort (n = 4238) and calculated estimated glomerular filtration rate (eGFR) from serum creatinine. 86% of participants were enrolled from community health centers in medically underserved areas and 14% from the general population in 12 states in the southeastern United States. Incident ESRD after entry into the cohort was ascertained by linkage of the cohort with the US Renal Data System (USRDS)., Results: Median (25th, 75th percentile) eGFR at baseline was 63.3 (36.0, 98.2) ml/min/1.73m 2 for ESRD cases and 103.2 (86.0, 117.9) for subcohort. Black ESRD cases had higher median (25th, 75th) eGFR [63.3 (35.9, 95.9)] compared to whites [59.1 (39.4, 99.2)]. In multivariable Cox models accounting for sampling weights, baseline eGFR was a strong predictor of ESRD risk, and an interaction with race was detected (P = 0.029). The higher ESRD risk among blacks relative to whites persisted (hazard ratio: 2.58; 95% confidence interval: 1.65, 4.03) after adjustment for eGFR., Conclusion: In this predominantly lower SES cohort, the racial disparity in ESRD risk is not explained by differences in baseline kidney function.

Objective: To compare presenting characteristics of patients with adductor spasmodic dysphonia (ADSD), ADSD with laryngeal tremor (ADSD + LT), and laryngeal tremor without ADSD (LT)., Design: Cross-sectional analysis., Methods: Patients treated for laryngeal movement disorders (1990-2016) were included. Analysis of variance and chi square tests measured differences in patient characteristics across the three disease groups. Using ADSD as the referent, multivariable logistic regression models were used to determine whether potential risk factors including patient demographics, family history, presence of potential inciting events prior to disease onset, and coprevalent movement disorders were associated with ADSD + LT or LT., Results: In all, 652 patients with ADSD (n = 377), ADSD + LT (n = 98), and LT (n = 177) were included. ADSD patients were significantly younger than those with ADSD + LT and LT (52.5 ± 13.4, 63.9 ± 11.3, and 69.3 ± 10.5 years, respectively; P < 0.001). Coprevalent movement disorders were more common in ADSD + LT (38.7%) and LT (57.1%) groups than in the ADSD group (11.5%; P < 0.001). Compared to ADSD, patients with ADSD + LT and LT were more likely to develop an additional movement disorder during follow-up. In multivariable analyses, increasing age, female gender, and having a movement disorder at presentation were associated with significantly greater odds of having ADSD + LT or LT when compared to ADSD., Conclusion: ADSD + LT patients demonstrate intermediate gender composition and age distributions between those with ADSD and LT. These findings suggest that ADSD + LT may be a distinct phenotype in the spectrum of laryngeal movement disorders., Level of Evidence: 4 Laryngoscope, 129:170-176, 2019., (© 2018 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: Intubation is an essential component of intensive care, yet it does have potential complications. Posterior glottic stenosis (PGS) is among the most severe sequela. Risk factors are poorly understood. One hypothesis is that large endotracheal tubes (ETTs) in smaller airways may increase risk. Because tracheal diameter is proportional to height, we designed a case-control study to evaluate the association between intensive care unit (ICU)-patient height (proxy for tracheal diameter) and their risk of postintubation PGS., Study Design: Retrospective case-control study METHODS: Among patients who underwent intubation in an ICU at a single tertiary care medical center between 2001 and 2015, a convenience sample of all patients with confirmed PGS (cases) were enrolled. Cases were matched 1:1 by age, sex, and race with intubated non-PGS controls chosen from the same population of ventilated patients. Data on height, weight, comorbidities, size of ETT, and duration of intubation were abstracted from the medical record. Multivariate models were used to test the association between patient height and risk of PGS development., Results: In all, 106 PGS cases (mean age 48.9 years, 50.7% female, 79.2% Caucasian) were identified; 77 met inclusion criteria. Compared to matched controls, cases were significantly shorter (mean 166 cm vs. 173 cm, P = .001). Height and PGS showed an inverse relationship in multivariate models. Specifically, odds of PGS decreased 9% (95% confidence interval: 0.01%-16%) for each centimeter increase in height., Conclusions: Shorter height is independently associated with increased odds of having PGS. Further work should consider whether height should be incorporated into ETT selection algorithms., Level of Evidence: 3b Laryngoscope, 128:2811-2814, 2018., (© 2018 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: Obesity and insulin resistance play important roles in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Mg intake is linked to a reduced risk of metabolic syndrome and insulin resistance; people with NAFLD or alcoholic liver disease are at high risk of Mg deficiency. The present study aimed to investigate whether Mg and Ca intakes were associated with risk of fatty liver disease and prediabetes by alcohol drinking status., Design: We analysed the association between Ca or Mg intake and fatty liver disease, prediabetes or both prediabetes and fatty liver disease in cross-sectional analyses., Setting: Third National Health and Nutrition Examination Survey (NHANES III) follow-up cohort of US adults., Subjects: Nationally representative sample of US adults in NHANES (n 13 489)., Results: After adjusting for potential confounders, Mg intake was associated with approximately 30 % reduced odds of fatty liver disease and prediabetes, comparing the highest intake quartile v. the lowest. Mg intake may only be related to reduced odds of fatty liver disease and prediabetes in those whose Ca intake is less than 1200 mg/d. Mg intake may also only be associated with reduced odds of fatty liver disease among alcohol drinkers., Conclusions: The study suggests that high intake of Mg may be associated with reduced risks of fatty liver disease and prediabetes. Further large studies, particularly prospective cohort studies, are warranted to confirm the findings.

Objective: To investigate race-sex associations with risk among whites and blacks in the southeastern United States. The relationship between race, sex, and kidney stone risk is poorly understood., Methods: Participants were 42,136 black and white adults enrolled in the Southern Community Cohort Study between 2002 and 2009, with no history of kidney stones and receiving Medicare or Medicaid services. Incident kidney stone diagnoses through December 2014 were determined via linkage with Centers for Medicare and Medicaid Services research files. Hazard ratios (HRs) for associations with race and sex were computed from multivariable Cox proportional hazards models adjusting for baseline characteristics, comorbid diseases, and dietary intakes., Results: During 116,931 and 270,917 person-years of follow-up for whites and blacks, respectively, age-adjusted incidence rates (95% confidence interval [CI]) were 5.98 (4.73-7.23) and 4.50 (3.86-5.14) per 1000 person-years for white men and women, respectively, while corresponding rates among blacks were 2.19 (1.71-2.67) and 2.47 (2.19-2.75) per 1000 person-years. Risk was higher among whites compared to blacks (HR = 2.23, 95% CI 1.97-2.53). Male sex was significantly associated with risk among whites (HR = 1.45, 95% CI 1.20-1.75), but not among blacks (HR = 0.90, 95% CI 0.75-1.07). Formal tests of interaction by race and sex were statistically significant for all models (P = .01 for fully adjusted model)., Conclusion: The association of incident kidney stones with sex differs between whites and blacks. White men have the highest risk, while no difference in risk is observed between black men and women., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: Dietary protein intake could have deleterious renal effects in populations at risk for chronic kidney disease. Here, we examined whether higher protein intake (≥80th percentile of energy from protein) is associated with decline in kidney function and whether this decline varies by diabetes status., Design: Observational cohort study., Subjects and Settings: Participants were African-Americans (n = 5,301), who enrolled in the Jackson Heart Study between 2000 and 2004., Methods: Dietary intake was assessed using a validated food-frequency questionnaire at baseline, and serum creatinine was measured at baseline (visit 1) and 8 years later (visit 3). Estimated glomerular filtration rates (eGFRs) at baseline and follow-up were computed using the chronic kidney disease epidemiology collaboration equation., Main Outcome Measure: The change in eGFR was computed by subtracting eGFR at visit 1 from that at visit 3., Results: Of 3,165 participants with complete data, 64% were women, 57% had hypertension, and 19% had diabetes. The median (25th, 75th percentile) percent energy intake from protein was 14.3 (12.4, 16.4), comparable to that reported for the general US population (15% of energy). During a median (25th, 75th percentile) follow-up of 8.0 (7.4, 8.3) years, eGFR declined by 10.5% from a mean (SD) of 97.4 (17.5) to 86.9 (21.3) mL/min/1.73 m 2 . In the fully adjusted model, consumption of protein as percent of energy intake in lowest and highest quintiles was associated with decline in eGFR among diabetic subjects. The analysis of variance with a robust variance estimator was used to determine whether long-term change in eGFR significantly varies by protein intake., Conclusions: Our results show that, among African-Americans with diabetes, higher protein intake as a percent of total energy intake is positively associated with greater decline in eGFR in analyses that accounted for risk factors for kidney disease., (Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Odd-numbered chain saturated fatty acids (OCSFA) have been associated with potential health benefits. Although some OCSFA (e.g., C15:0 and C17:0) are found in meats and dairy products, sources and metabolism of C19:0 and C23:0 are relatively unknown, and the influence of non-dietary determinants, including genetic factors, on circulating levels of OCSFA is not established., Objective: To elucidate the biological processes that influence circulating levels of OCSFA by investigating associations between genetic variation and OCSFA., Design: We performed a meta-analysis of genome-wide association studies (GWAS) of plasma phospholipid/erythrocyte levels of C15:0, C17:0, C19:0, and C23:0 among 11,494 individuals of European descent. We also investigated relationships between specific single nucleotide polymorphisms (SNPs) in the lactase (LCT) gene, associated with adult-onset lactase intolerance, with circulating levels of dairy-derived OCSFA, and evaluated associations of candidate sphingolipid genes with C23:0 levels., Results: We found no genome-wide significant evidence that common genetic variation is associated with circulating levels of C15:0 or C23:0. In two cohorts with available data, we identified one intronic SNP (rs13361131) in myosin X gene (MYO10) associated with C17:0 level (P = 1.37×10-8), and two intronic SNP (rs12874278 and rs17363566) in deleted in lymphocytic leukemia 1 (DLEU1) region associated with C19:0 level (P = 7.07×10-9). In contrast, when using a candidate-gene approach, we found evidence that three SNPs in LCT (rs11884924, rs16832067, and rs3816088) are associated with circulating C17:0 level (adjusted P = 4×10-2). In addition, nine SNPs in the ceramide synthase 4 (CERS4) region were associated with circulating C23:0 levels (adjusted P<5×10-2)., Conclusions: Our findings suggest that circulating levels of OCSFA may be predominantly influenced by non-genetic factors. SNPs associated with C17:0 level in the LCT gene may reflect genetic influence in dairy consumption or in metabolism of dairy foods. SNPs associated with C23:0 may reflect a role of genetic factors in the synthesis of sphingomyelin.

Background/objectives: Studies based on food frequency questionnaires suggest that folate and vitamin B12 intake could protect against hearing loss. We investigated whether erythrocyte folate and serum vitamin B12 levels are independently associated with hearing loss in humans., Subjects/methods: Participants in the 2003-2004 US National Health and Nutrition Examination Survey who had data on hearing, folate, and vitamin B12 levels were included. Pure-tone average (PTA) at 0.5, 1.0, 2.0, and 4.0 kHz was computed for each ear. We used weighted logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the relation between quartiles of folate and vitamin B12, and hearing loss (present if PTA > 25 dB in either ear and absent if PTA ≤ 25 dB in both ears)., Results: Participants (n = 1149) were 20-69 (mean 42) years old and 16.4% had hearing loss in at least one ear. Our data suggest a U-shaped relationship between folate and hearing loss. Compared to the 1st quartile, the ORs (95% CIs) for hearing loss were 0.87 (0.49-1.53), 0.70 (0.49-1.00), and 1.08 (0.61-1.94) for the 2nd, 3rd, and 4th quartile of erythrocyte folate in analyses adjusted for age, sex, vitamin B12, smoking, alcohol use, body mass index, race/ethnicity, exposure to noise, income, and education. Although we observed inverse associations between vitamin B12 and hearing loss, the associations were not statistically significant (P > 0.05)., Conclusions: Our data show a U-shaped relationship between erythrocyte folate levels and hearing loss, suggesting a need to evaluate whether optimizing blood folate levels could prevent hearing loss.

Objectives: This study examines the relationship between alcohol consumption and incident stroke among older adults and tests whether alcohol consumption contributes to observed race and sex differences in stroke., Method: Data are from a U.S. national cohort of black and white adults aged 45 and older, the REasons for Geographic And Racial Differences in Stroke (REGARDS) study. Current and past drinking levels were reported at baseline (2003-2007). Participants who had never had a stroke were followed for adjudicated stroke events through September 2015 (n = 27,265). We calculated Cox proportional hazard models for stroke, adjusting for demographic, socioeconomic, behavioral, and health characteristics., Results: Participants, mean age 64.7 years, consumed on average 2.2 drinks/week and experienced 1,140 first-time stroke events over median 9.1 years follow-up. Nondrinkers had a 12% higher risk of stroke than current drinkers; the risk of stroke among nondrinkers largely reflected high risks among past drinkers; these differences were explained by socioeconomic characteristics. Among current drinkers, light drinkers had significantly lower stroke risks than moderate drinkers after accounting for demographic, socioeconomic, behavioral, and health characteristics. Implications of alcohol did not differ between blacks and whites but did differ by sex: Especially among women, nondrinkers, and specifically past drinkers, had higher risks; these differences were largely explained by health characteristics and behaviors. Alcohol did not explain race and sex differences in stroke incidence., Discussion: Among older adults, those who used to, but no longer, drink had higher risks of stroke, especially among women; current light drinkers had the lowest risk of stroke.

Impaired hematologic status (IHS) was investigated as a determinant of immune function defined as cluster of differentiation 4 (CD4) T-helper cell count, quality of life (QOL) weight and hospitalization/mortality over 18-months among 398 adult persons living with HIV/AIDS (PLWHA) on anti-retroviral therapy. IHS was defined as having anemia at baseline (Hemoglobin: <12 g/dL for women and <13 g/dL for men), time-updated anemia or having low (<30 μg/L) or high (>200 μg/L for men and >150 μg/L for women) ferritin levels at baseline. Months-to-hospitalization/death or study-end (if no event) was calculated from enrollment. Multivariable linear-mixed models quantified associations between IHS and changes in CD4 cell-count, weight gain and QOL. Cox proportional hazards models calculated hazard ratios (HR) and corresponding 95% confidence intervals (CI) for IHS-related differences in time-to-hospitalization/death. The prevalences of anemia and high and low ferritin levels at baseline were 48.7% ( n = 194), 40.5% ( n = 161) and 17% ( n = 68), respectively. Most patients (63.4%, n = 123) remained anemic during follow-up. Weight gained (ferritin-time interaction, p < 0.01) and QOL (anemia-time interaction, p = 0.05; ferritin-time interaction, p = 0.01) were lower for PLWHA with versus without IHS. Relative to anemia-free/normal ferritin, the risk of hospitalization/death was elevated for PLWHA with anemia (HR = 2.0; 95% CI: 1.2-3.6), low or high ferritin (HR: 1.8-1.9, 95% CI: 0.9-4.1) and those that developed new/persistent/progressive anemia (HR: 2.3-6.7, 95% CI: 1.0-12.7). Among PLWHA, IHS predicted deficits in QOL, low weight gain and a high risk of hospitalization/death. Intervention to mitigate persistent IHS may be warranted among PLWHA on long-term highly active antiretroviral therapy (HAART) to improve health outcomes., Competing Interests: The authors declare no conflict of interest.

Importance: The relative outcomes of onabotulinum toxin A injections for treatment of adductor spasmodic dysphonia (ADSD), ADSD with lateral laryngeal tremor (ADSD+LT), and lateral LT without ADSD are unclear., Objective: To compare the outcomes of onabotulinum toxin A treatment on ADSD, ADSD+LT, and lateral LT without ADSD., Design, Setting, and Participants: A retrospective cohort study was conducted from January 1, 1990, to September 30, 2016, at a tertiary referral voice center. Participants included 817 patients treated with onabotulinum toxin A injections for diagnosis of ADSD, ADSD+LT, and lateral LT without ADSD., Exposure: Injection of onabotulinum toxin A into the thyroarytenoid/lateral cricoarytenoid muscle complex., Main Outcomes and Measures: Data from patient diaries were used to evaluate patient-perceived effectiveness of onabotulinum toxin A injection. Primary outcomes were (1) patient-reported good voice days (voice breaks or tremor minimized to patient satisfaction) and (2) percentage of injections in which maximal voice quality was reached (significant or complete reduction in vocal tremor or spasms during a treatment cycle). Multivariate analysis of variance tests compared differences in outcomes between groups. Subanalysis was performed to compare outcomes in patients with isolated LT with those who had mixed tremor (lateral with concomitant anterior-posterior and/or vertical components)., Results: Of 817 patients treated with onabotulinum toxin A injections for laryngeal movement disorders, 548 patients (12 771 injection sessions) met inclusion criteria (ADSD: n = 328, ADSD+LT: n = 77, lateral LT without ADSD: n = 143). Of these, 408 (80.8%) were women; mean (SD) age was 57.2 (13.7) years. Among patients with tremor, those with isolated LT had better outcomes than those with mixed tremor. In adjusted analysis, good voice days in patients with ADSD, ADSD+LT, and lateral LT without ADSD were 81.1, 75.4, and 71.3 days, respectively (partial η2, 0.05; 95% CI, 0.01-0.09). The percentage of maximally beneficial injections was 88.1% for ADSD, 83.4% for ADSD+LT, and 70.4% for LT without ADSD (partial η2, 0.12; 95% CI, 0.06-0.17)., Conclusions and Relevance: Onabotulinum toxin A injections into the thyroarytenoid/lateral cricoarytenoid muscle complex are an effective treatment for ADSD, ADSD+LT, and LT without ADSD; however, the greatest effectiveness was observed among patients with ADSD. Defining tremor directionality may help to prognosticate the effectiveness of onabotulinum toxin A injection among patients presenting with tremor components.

Background: Recent data suggest that neighborhood socioeconomic environment predicts heart failure (HF) hospital readmissions. We investigated whether neighborhood deprivation predicts risk of incident HF beyond individual socioeconomic status in a low-income population., Methods and Results: Participants were 27 078 whites and blacks recruited during 2002 to 2009 in the SCCS (Southern Community Cohort Study), who had no history of HF and were using Centers for Medicare or Medicaid Services. Incident HF diagnoses through December 31, 2010, were ascertained using International Classification of Diseases , Ninth Revision, codes 428.x via linkage with Centers for Medicare or Medicaid Services research files. Participant residential information was geocoded and census tract determined by a spatial join to the US Census Bureau TIGER/Line Shapefiles. The neighborhood deprivation index was constructed using principal components analysis based on census tract-level socioeconomic variables. Cox models with Huber-White cluster sandwich estimator of variance were used to investigate the association between neighborhood deprivation index and HF risk. The study sample was predominantly middle aged (mean, 55.5 years), black (69%), female (63%), low income (70% earned <$15 000/y), and >50% of participants lived in the most deprived neighborhoods (third neighborhood deprivation index tertile). Over median follow-up of 5.2 years, 4300 participants were diagnosed with HF. After adjustment for demographic, lifestyle, and clinical factors, a 1 interquartile increase in neighborhood deprivation index was associated with a 12% increase in risk of HF (hazard ratio, 1.12; 95% confidence interval, 1.07-1.18), and 4.8% of the variance in HF risk (intraclass correlation coefficient, 4.8; 95% confidence interval, 3.6-6.4) was explained by neighborhood deprivation., Conclusions: In this low-income population, scant neighborhood resources compound the risk of HF above and beyond individual socioeconomic status and traditional cardiovascular risk factors. Improvements in community resources may be a significant axis for curbing the burden of HF., (© 2018 American Heart Association, Inc.)

People with fatty liver disease are at high risk of magnesium deficiency. Meanwhile, low magnesium status is linked to both chronic inflammation and insulin resistance. However, no study has investigated the association between intake of magnesium and risk of mortality due to liver diseases. We evaluated the association between total magnesium intake and mortality due to liver diseases in the Third National Health and Nutrition Examination Study (NHANES III) cohort, which included 13,504 participants who completed liver ultrasound examination for hepatic steatosis. Overall magnesium intake was associated with a reduced risk of mortality due to liver disease at borderline significance (P = 0.05). In fully-adjusted analyses, every 100 mg increase in intake of magnesium was associated with a 49% reduction in the risk for mortality due to liver diseases. Although interactions between magnesium intake and alcohol use and hepatic steatosis at baseline were not significant (P > 0.05), inverse associations between magnesium intake and liver disease mortality were stronger among alcohol drinkers and those with hepatic steatosis. Our findings suggest higher intakes of magnesium may be associated with a reduced risk of mortality due to liver disease particularly among alcohol drinkers and those with hepatic steatosis. Further studies are warranted to confirm the findings.

The SLC8A1 (solute carrier family 8, member 1) gene, encoding Na + /Ca 2+ exchanger, is essential in regulating calcium reabsorption and homeostasis. Calcium homeostasis plays a key role in cell proliferation and apoptosis. We hypothesized that polymorphisms in five calcium-regulating genes (SLC8A1, ATP2B1, CALB1, CALB2, and CABP1) interact with calcium intake in relation to the risk of colorectal neoplasia. A two-phase (discovery and replication) study was conducted within the Tennessee Colorectal Polyp Study, including a total of 1275 cases and 2811 controls. In Phase I, we identified six out of 135 SNPs that significantly interacted with calcium intake in relation to adenoma risk. In Phase II, the calcium intake by rs4952490 (SLC8A1) interaction was replicated (P interaction  = 0.048). We found an inverse association between calcium intake (1000-2000 mg/day) and colorectal adenomas, particularly for multiple/advanced adenomas, among the G-allele carriers but not among homozygous carriers of the common variant (A) in rs4952490. In the joint analysis of SLC8A1, KCNJ1, and SLC12A1 SNPs, carriers of variant alleles in at least two genes and with calcium intake above the DRI (1000 mg/day) were approximately 30-57% less likely to have adenomas than those whose calcium intake was below the DRI. The association was stronger for multiple/advanced adenomas. No association was found among those who did not carry any variant alleles in these genes when calcium intake was below 2500 mg/day. These findings, if confirmed, may provide a new avenue for the personalized prevention of colorectal adenoma and cancer., (© 2017 Wiley Periodicals, Inc.)

Background: Glycated hemoglobin (HbA1c) is used to diagnose type 2 diabetes (T2D) and assess glycemic control in patients with diabetes. Previous genome-wide association studies (GWAS) have identified 18 HbA1c-associated genetic variants. These variants proved to be classifiable by their likely biological action as erythrocytic (also associated with erythrocyte traits) or glycemic (associated with other glucose-related traits). In this study, we tested the hypotheses that, in a very large scale GWAS, we would identify more genetic variants associated with HbA1c and that HbA1c variants implicated in erythrocytic biology would affect the diagnostic accuracy of HbA1c. We therefore expanded the number of HbA1c-associated loci and tested the effect of genetic risk-scores comprised of erythrocytic or glycemic variants on incident diabetes prediction and on prevalent diabetes screening performance. Throughout this multiancestry study, we kept a focus on interancestry differences in HbA1c genetics performance that might influence race-ancestry differences in health outcomes., Methods & Findings: Using genome-wide association meta-analyses in up to 159,940 individuals from 82 cohorts of European, African, East Asian, and South Asian ancestry, we identified 60 common genetic variants associated with HbA1c. We classified variants as implicated in glycemic, erythrocytic, or unclassified biology and tested whether additive genetic scores of erythrocytic variants (GS-E) or glycemic variants (GS-G) were associated with higher T2D incidence in multiethnic longitudinal cohorts (N = 33,241). Nineteen glycemic and 22 erythrocytic variants were associated with HbA1c at genome-wide significance. GS-G was associated with higher T2D risk (incidence OR = 1.05, 95% CI 1.04-1.06, per HbA1c-raising allele, p = 3 × 10-29); whereas GS-E was not (OR = 1.00, 95% CI 0.99-1.01, p = 0.60). In Europeans and Asians, erythrocytic variants in aggregate had only modest effects on the diagnostic accuracy of HbA1c. Yet, in African Americans, the X-linked G6PD G202A variant (T-allele frequency 11%) was associated with an absolute decrease in HbA1c of 0.81%-units (95% CI 0.66-0.96) per allele in hemizygous men, and 0.68%-units (95% CI 0.38-0.97) in homozygous women. The G6PD variant may cause approximately 2% (N = 0.65 million, 95% CI 0.55-0.74) of African American adults with T2D to remain undiagnosed when screened with HbA1c. Limitations include the smaller sample sizes for non-European ancestries and the inability to classify approximately one-third of the variants. Further studies in large multiethnic cohorts with HbA1c, glycemic, and erythrocytic traits are required to better determine the biological action of the unclassified variants., Conclusions: As G6PD deficiency can be clinically silent until illness strikes, we recommend investigation of the possible benefits of screening for the G6PD genotype along with using HbA1c to diagnose T2D in populations of African ancestry or groups where G6PD deficiency is common. Screening with direct glucose measurements, or genetically-informed HbA1c diagnostic thresholds in people with G6PD deficiency, may be required to avoid missed or delayed diagnoses.