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ObjectiveAlcohol misuse is present in over a quarter of trauma patients. Information in the clinical notes of the electronic health record of trauma patients may be used for phenotyping tasks with natural language processing (NLP) and supervised machine learning. The objective of this study is to train and validate an NLP classifier for identifying patients with alcohol misuse.Materials and MethodsAn observational cohort of 1422 adult patients admitted to a trauma center between April 2013 and November 2016. Linguistic processing of clinical notes was performed using the clinical Text Analysis and Knowledge Extraction System. The primary analysis was the binary classification of alcohol misuse. The Alcohol Use Disorders Identification Test served as the reference standard.ResultsThe data corpus comprised 91 045 electronic health record notes and 16 091 features. In the final machine learning classifier, 16 features were selected from the first 24 hours of notes for identifying alcohol misuse. The classifier’s performance in the validation cohort had an area under the receiver-operating characteristic curve of 0.78 (95% confidence interval [CI], 0.72 to 0.85). Sensitivity and specificity were at 56.0% (95% CI, 44.1% to 68.0%) and 88.9% (95% CI, 84.4% to 92.8%). The Hosmer-Lemeshow goodness-of-fit test demonstrates the classifier fits the data well (P = .17). A simpler rule-based keyword approach had a decrease in sensitivity when compared with the NLP classifier from 56.0% to 18.2%.ConclusionsThe NLP classifier has adequate predictive validity for identifying alcohol misuse in trauma centers. External validation is needed before its application to augment screening.

BackgroundUse of race and ethnicity is common in medical tests and procedures, even though these categories are defined by sociological, historical, and political processes, and vary considerably in their definitions over time and place. Because all societies organize themselves around these constructs in some way, they are undeniable facets of the human experience, with myriad health consequences. In the biomedical literature, they are also commonly interpreted as representing biological heterogeneity that is relevant for health and disease.ContentWe review the use of race and ethnicity in medical practice, especially in the USA, and provide 2 specific examples to represent a large number of similar instances. We then critique these uses along a number of different dimensions, including limitations in measurement, within- versus between-group variance, and implications for informativeness of risk markers for individuals, generalization from arbitrary or nonrepresentative samples, perpetuation of myths and stereotypes, instability in time and place, crowding out of more relevant risk markers, stigmatization, and the tainting of medicine with the history of oppression. We conclude with recommendations to improve practice that are technical, ethical, and pragmatic.SummaryMedicine has evolved from a mystical healing art to a mature science of human health through a rigorous process of quantification, experimentation, and evaluation. Folkloric traditions, such as race- and ethnic-specific medicine will fade from use as we become increasingly critical of outdated and irrational clinical practices and replace these with personalized, evidenced-based tests, algorithms, and procedures that privilege patients’ individual humanity over obsolete and misleading labels.

Studies have reported an association between prevalent cardiovascular disease (CVD) and risk of diabetes mellitus (DM). However, factors that may explain the association remain unclear. We examined the association of prevalent CVD with incident DM and assessed whether weight gain and medication use may explain the association.Data from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) Visit 1 (2008-2011) and Visit 2 (2014-2017) were used to compare incidence of DM among individuals with and without self-reported CVD at Visit 1. A total of 1899 individuals with self-reported CVD were matched to controls free of self-reported CVD at Visit 1 using 1:1 propensity score matching. Covariates included in the propensity model were sociodemographic characteristics, lifestyle factors, comorbid conditions, and study site. The effect of self-reported CVD on incident DM was examined using a generalized estimating equation. The mediating effects of weight gain and use of cardiovascular medications were evaluated.Covariate distributions were similar among individuals with and without self-reported CVD. The incidence of DM among persons with self-reported CVD was 15.3% vs 12.7% among those without self-reported CVD. Compared to individuals without self-reported CVD, individuals with self-reported CVD had a 24% increased risk for incident DM (odds ratio = 1.24, 95% confidence interval = 1.01, 1.51). The association between self-reported CVD and DM was mediated by the use of beta-blockers (proportion explained = 25.4%), statins (proportion explained = 18%), and diuretics (proportion explained = 8%). We found that weight gain did not explain the observed association.Prevalent cardiovascular disease was associated with a significant increased risk of incident diabetes. The observed association was partially explained by some medications used to manage CVD.背景: 已有研究报道流行的心血管疾病(CVD)与糖尿病(DM)风险之间存在关联。然而, 可能解释这种联系的因素仍不清楚。我们分析了流行的心血管疾病与糖尿病发病的关系, 并评估了体重增加和药物使用是否可以解释这种联系。 方法: 使用西班牙裔社区健康研究/拉丁裔研究(HCHS/SOL) 2008-2011及2014-2017的数据, 比较前者中有和没有自我报告心血管疾病个体的糖尿病发病率。共有1899名自我报告心血管疾病的患者, 采用1:1倾向得分匹配的方法与无自我报告心血管疾病的对照组进行配对。倾向性模型中的协变量包括社会人口学特征, 生活方式因素, 并发症情况和研究地点。使用通用的估计方程来检验自我报告的心血管疾病对糖尿病的影响。评估体重增加和心血管药物使用的中介作用。 结果: 在有和没有自我报告的心血管疾病的个体中, 协变量分布是相似的。自报心血管病患者的糖尿病发病率为15.3%, 非自报心血管病患者的糖尿病发病率为12.7%。与没有自我报告心血管疾病的个体相比, 有自我报告心血管疾病的个体发生糖尿病的风险增加24%(优势比=1.24, 95%可信区间=1.01, 1.51)。自我报告的心血管疾病和糖尿病之间的联系是通过使用β-受体阻滞剂(解释比例=25.4%), 他汀类药物(解释比例=18%)和利尿剂(解释比例=8%)来调节的。我们发现体重增加并不能解释观察到的关联。 结论: 常见的心血管疾病与糖尿病发病风险显著增加相关。一些用于治疗心血管疾病的药物部分解释了观察到的关联。.

BACKGROUND Automated and data-driven methods for screening using natural language processing (NLP) and machine learning may replace resource-intensive manual approaches in usual care of patients hospitalized with conditions related to unhealthy substance use. Rigorous evaluation of tools that use artificial intelligence (AI) is necessary to demonstrate effectiveness before system-wide implementation. OBJECTIVE To provide a study protocol to evaluate health outcomes and cost-benefit of an AI-driven automated screener compared to manual human screening for unhealthy substance use. METHODS A pre-post design to evaluate 12 months of manual screening followed by 12 months of automated screening across surgical and medical wards in a single medical center. Effectiveness in terms of patient outcomes will be determined by non-inferior rates of interventions (brief intervention/motivational interviewing, medication assisted treatment, naloxone dispensing, referral to outpatient care) in the post-period by a substance use intervention team compared to pre-period. A separate analysis will be performed to assess the cost-benefit to the health system of using automated screening. RESULTS A natural language processing tool to use routinely collected data in the electronic health record was previously validated for diagnostic accuracy in a retrospective study for screening unhealthy substance use. Our next step is a non-inferiority design incorporated into a research protocol for clinical implementation with prospective evaluation of clinical effectiveness in a large health system. The study is approved by the Institutional Review Board and registered at clinicaltrials.gov with a plan for implementation beginning in September 2022. CONCLUSIONS The use of augmented intelligence for clinical decision support is growing with an increasing number of artificial intelligence tools. We provide a research protocol for prospective evaluation of an automated NLP system for screening unhealthy substance use using a non-inferiority design to demonstrate comprehensive screening that may be as effective as manual screening but less costly via automated solutions. CLINICALTRIAL ClinicalTrials.gov NCT03833804

Recent protests by a large segment of the US population over the health and socioeconomic damages caused by structural racism highlight the long history of discrimination against Black Americans. There is a great need for a realignment of race, biomedical research and clinical practice in the US and globally.

Background and objectives Sepsis-associated AKI is a heterogeneous clinical entity. We aimed to agnostically identify sepsis-associated AKI subphenotypes using deep learning on routinely collected data in electronic health records. Design, setting, participants, & measurements We used the Medical Information Mart for Intensive Care III database, which consists of electronic health record data from intensive care units in a tertiary care hospital in the United States. We included patients ≥18 years with sepsis who developed AKI within 48 hours of intensive care unit admission. We then used deep learning to utilize all available vital signs, laboratory measurements, and comorbidities to identify subphenotypes. Outcomes were mortality 28 days after AKI and dialysis requirement. Results We identified 4001 patients with sepsis-associated AKI. We utilized 2546 combined features for K-means clustering, identifying three subphenotypes. Subphenotype 1 had 1443 patients, and subphenotype 2 had 1898 patients, whereas subphenotype 3 had 660 patients. Subphenotype 1 had the lowest proportion of liver disease and lowest Simplified Acute Physiology Score II scores compared with subphenotypes 2 and 3. The proportions of patients with CKD were similar between subphenotypes 1 and 3 (15%) but highest in subphenotype 2 (21%). Subphenotype 1 had lower median bilirubin levels, aspartate aminotransferase, and alanine aminotransferase compared with subphenotypes 2 and 3. Patients in subphenotype 1 also had lower median lactate, lactate dehydrogenase, and white blood cell count than patients in subphenotypes 2 and 3. Subphenotype 1 also had lower creatinine and BUN than subphenotypes 2 and 3. Dialysis requirement was lowest in subphenotype 1 (4% versus 7% [subphenotype 2] versus 26% [subphenotype 3]). The mortality 28 days after AKI was lowest in subphenotype 1 (23% versus 35% [subphenotype 2] versus 49% [subphenotype 3]). After adjustment, the adjusted odds ratio for mortality for subphenotype 3, with subphenotype 1 as a reference, was 1.9 (95% confidence interval, 1.5 to 2.4). Conclusions Utilizing routinely collected laboratory variables, vital signs, and comorbidities, we were able to identify three distinct subphenotypes of sepsis-associated AKI with differing outcomes.

Background Fitness epistasis, the interaction effect of genes at different loci on fitness, makes an important contribution to adaptive evolution. Although fitness interaction evidence has been observed in model organisms, it is more difficult to detect and remains poorly understood in human populations as a result of limited statistical power and experimental constraints. Fitness epistasis is inferred from non-independence between unlinked loci. We previously observed ancestral block correlation between chromosomes 4 and 6 in African Americans. The same approach fails when examining ancestral blocks on the same chromosome due to the strong confounding effect observed in a recently admixed population. Results We developed a novel approach to eliminate the bias caused by admixture linkage disequilibrium when searching for fitness epistasis on the same chromosome. We applied this approach in 16,252 unrelated African Americans and identified significant ancestral correlations in two pairs of genomic regions (P-value− 7) on chromosomes 1 and 10. The ancestral correlations were not explained by population admixture. Historical African-European crossover events are reduced between pairs of epistatic regions. We observed multiple pairs of co-expressed genes shared by the two regions on each chromosome, including ADAR being co-expressed with IFI44 in almost all tissues and DARC being co-expressed with VCAM1, S1PR1 and ELTD1 in multiple tissues in the Genotype-Tissue Expression (GTEx) data. Moreover, the co-expressed gene pairs are associated with the same diseases/traits in the GWAS Catalog, such as white blood cell count, blood pressure, lung function, inflammatory bowel disease and educational attainment. Conclusions Our analyses revealed two instances of fitness epistasis on chromosomes 1 and 10, and the findings suggest a potential approach to improving our understanding of adaptive evolution.

The current study examined the effects of chronic stress and a genetic risk score on the presence of hypertension and elevated systolic blood pressure and diastolic blood pressure among Hispanics/Latinos in the target population of Hispanic Community Health Study/Study of Latinos. Of the participants (N = 11,623) assessed during two clinic visits (Visit 1 2008–2013 & Visit 2 2014–2018), we analysed data from 7,429 adults (50.4% female), aged 18–74, who were genotyped and responded to chronic stress questionnaires. We calculated an unweighted genetic risk score using blood pressure increasing single nucleotide polymorphisms (SNPs) found to be generalisable to Hispanics/Latinos (10 SNPs). Linear and logistic regression models were used to estimate associations between chronic stress and genetic risk score and their interaction, with prevalent Visit 2 SBP or DBP, and hypertension, respectively. Models accounted for sampling weights, stratification, and cluster design. Chronic stress (adjusted OR = 1.18, 95%CI:1.15,1.22) and hypertension genetic risk score (adjusted OR = 1.04, 95%CI:1.01,1.07) were significantly associated with prevalent hypertension, but there was no significant interaction between the chronic stress and genetic risk score on hypertension (p = .49). genetic risk score (b = .32, 95%CI:.08, .55, R2 = .02) and chronic stress (b = .45, 95%CI:.19, .72, R2 = .11) were related to DBP, with no significant interaction (p = .62). Genetic risk score (b = .42, 95%CI:.08, .76, R2 = .01) and chronic stress (b = .80, 95%CI:.34,1.26, R2 = .11) were also related to SBP, with no significant interaction (p = .51). Results demonstrate the utility of a genetic risk score for blood pressure and are consistent with literature suggesting chronic stress has a strong, direct association with elevated blood pressure among U.S. Hispanics/Latinos.

Background Automated and data-driven methods for screening using natural language processing (NLP) and machine learning may replace resource-intensive manual approaches in the usual care of patients hospitalized with conditions related to unhealthy substance use. The rigorous evaluation of tools that use artificial intelligence (AI) is necessary to demonstrate effectiveness before system-wide implementation. An NLP tool to use routinely collected data in the electronic health record was previously validated for diagnostic accuracy in a retrospective study for screening unhealthy substance use. Our next step is a noninferiority design incorporated into a research protocol for clinical implementation with prospective evaluation of clinical effectiveness in a large health system. Objective This study aims to provide a study protocol to evaluate health outcomes and the costs and benefits of an AI-driven automated screener compared to manual human screening for unhealthy substance use. Methods A pre-post design is proposed to evaluate 12 months of manual screening followed by 12 months of automated screening across surgical and medical wards at a single medical center. The preintervention period consists of usual care with manual screening by nurses and social workers and referrals to a multidisciplinary Substance Use Intervention Team (SUIT). Facilitated by a NLP pipeline in the postintervention period, clinical notes from the first 24 hours of hospitalization will be processed and scored by a machine learning model, and the SUIT will be similarly alerted to patients who flagged positive for substance misuse. Flowsheets within the electronic health record have been updated to capture rates of interventions for the primary outcome (brief intervention/motivational interviewing, medication-assisted treatment, naloxone dispensing, and referral to outpatient care). Effectiveness in terms of patient outcomes will be determined by noninferior rates of interventions (primary outcome), as well as rates of readmission within 6 months, average time to consult, and discharge rates against medical advice (secondary outcomes) in the postintervention period by a SUIT compared to the preintervention period. A separate analysis will be performed to assess the costs and benefits to the health system by using automated screening. Changes from the pre- to postintervention period will be assessed in covariate-adjusted generalized linear mixed-effects models. Results The study will begin in September 2022. Monthly data monitoring and Data Safety Monitoring Board reporting are scheduled every 6 months throughout the study period. We anticipate reporting final results by June 2025. Conclusions The use of augmented intelligence for clinical decision support is growing with an increasing number of AI tools. We provide a research protocol for prospective evaluation of an automated NLP system for screening unhealthy substance use using a noninferiority design to demonstrate comprehensive screening that may be as effective as manual screening but less costly via automated solutions. Trial Registration ClinicalTrials.gov NCT03833804; https://clinicaltrials.gov/ct2/show/NCT03833804 International Registered Report Identifier (IRRID) DERR1-10.2196/42971

The burden of advanced chronic kidney disease (CKD) falls disproportionately on minorities including African Americans (AAs) and Hispanic Americans (HAs) with admixed ancestry. Even though APOL1 high-risk genotypes increase risk of kidney disease, their penetrance is incomplete, indicating that the modification of APOL1 high risk may be polygenic. For this study, we used three multi-ethnic cohorts with APOL1 high risk genotypes and calculated a multi-ethnic PRS using publicly available summary statistics. We show that CKD risk is significantly modified by a multi-ethnic polygenic risk score. Standardizing population screening for CKD by including APOL1 high-risk genotypes and polygenic risk score may improve risk stratification and outcomes.

Systolic and diastolic blood pressure (S/DBP) are highly correlated modifiable risk factors for cardiovascular disease (CVD). We report here a bidirectional Mendelian Randomization (MR) and horizontal pleiotropy analysis of S/DBP summary statistics from the UK Biobank (UKB)-International Consortium for Blood Pressure (ICBP) (UKB-ICBP) BP genome-wide association study and construct a composite genetic risk score (GRS) by including pleiotropic variants. The composite GRS captures greater (1.11-3.26 fold) heritability for BP traits and increases (1.09- and 2.01-fold) Nagelkerke's R

Nonalcoholic fatty liver disease (NAFLD) disproportionally affects Hispanic/Latino populations. However, the magnitude varies among Hispanic/Latino ethnic groups. We investigated the mechanisms of these disparities.We examined associations of NAFLD-associated genetic variants and continental ancestry with suspected NAFLD, levels of alanine aminotransferase (ALT), and liver fibrosis using data from the Hispanic Community Health Study/Study of Latinos-a population-based study of Hispanic/Latino adults in the United States. We evaluated data from 16,415 Hispanic/Latino adults in 4 cities from 2008 through 2011. Subjects suspected of having NAFLD or liver fibrosis were identified based on unexplained increases in levels of aminotransferases and FIB-4 score, respectively.Among the 9342 participants with available genetic and aminotransferase data, the PNPLA3 G allele (odds ratio [OR], 1.53; 95% CI, 1.41-1.66), TM6SF2 T allele (OR, 1.41; 95% CI, 1.20-1.67), and PPP1R3B G allele (OR, 1.16; 95% CI, 1.06-1.28) were associated with suspected NAFLD. PNPLA3 G was also associated with increased levels of ALT, except in participants with Dominican and South American backgrounds, and with liver fibrosis. The frequency of PNPLA3 G was high (41%) and TM6SF2 T (5%) was low in Hispanic/Latinos. PNPLA3 G frequency differed among Hispanic background groups with the highest proportion in Mexicans (52%) and the lowest proportion in Dominicans (23%). After adjustment for demographic, clinical, and behavioral factors, as well as PNPLA3 G, TM6SF2 T, and PPP1R3B G, American ancestry had a positive association with level of ALT (r = 6.61%; P.001), whereas African (r = -3.84%; P.001) and European (r = -4.31%; P.001) ancestry were inversely associated with level of ALT.American ancestry and PNPLA3 G are independent predictors of ALT levels in US Hispanic/Latinos and may in part explain NAFLD disparities in US Hispanic/Latinos.

Background: Over 10 years, achieving and maintaining 2017 ACC/AHA guideline goals could prevent 3.0 million (UR, 1.1–5.1 million), 0.5 million (UR, 0.2–0.7 million), and 1.4 million (UR, 0.6–2.0 million) cardiovascular disease (CVD) events compared with maintaining current blood pressure (BP) levels, achieving 2003 Seventh Joint National Committee Report goals, and achieving 2014 Eighth Joint National Committee goals, respectively. We estimated the number of cardiovascular disease events prevented and treatment-related serious adverse events incurred over 10 years among US adults with hypertension by achieving 2017 ACC/AHA guideline-recommended BP goals compared with (1) current BP levels, (2) achieving 2003 Seventh Joint National Committee Report BP goals, and (3) achieving 2014 Eighth Joint National Committee panel member report BP goals. Methods: US adults aged ≥45 years with an indication for BP treatment were grouped according to recommendations for antihypertensive drug therapy in the 2017 ACC/AHA guideline, 2003 Seventh Joint National Committee Report, and 2014 Eighth Joint National Committee. Population sizes were estimated from the 2011 to 2014 National Health and Nutrition Examination Surveys. Rates for fatal and nonfatal CVD events (stroke, coronary heart disease, or heart failure) were estimated from the REGARDS (REasons for Geographic And Racial Differences in Stroke) study, weighted to the US population. CVD risk reductions with treatment to BP goals and risk for serious adverse events were obtained from meta-analyses of BP-lowering trials. CVD events prevented and treatment-related nonfatal serious adverse events over 10 years were calculated. Uncertainty surrounding main data inputs was expressed in uncertainty ranges (UR). Results: Over ten years, achieving and maintaining 2017 ACC/AHA guideline goals compared with current BP levels, achieving 2003 Seventh Joint National Committee Report goals, or achieving 2014 Eighth Joint National Committee goals could prevent 3.0 million (UR, 1.1–5.1 million), 0.5 million (UR, 0.2–0.7 million), or 1.4 million (UR, 0.6–2.0 million) CVD events, respectively. Compared with current BP levels, achieving and maintaining 2017 goals could prevent 71.9 (UR, 26.6–122.3) CVD events per 1000 treated. Achieving 2017 guideline BP goals compared with current BP levels could also lead to nearly 3.3 million more serious adverse events over 10 years (UR, 2.2–4.4 million). Conclusions: Achieving and maintaining 2017 ACC/AHA BP goals could prevent a greater number of CVD events than achieving 2003 Seventh Joint National Committee Report or 2014 Eighth Joint National Committee BP goals but could also lead to more serious adverse events.

Systolic and diastolic blood pressure (S/DBP) are highly correlated and modifiable risk factors for cardiovascular disease (CVD). We report here a bidirectional Mendelian Randomization (MR) and GWAS pleiotropy analysis of S/DBP summary statistics from large published BP GWAS and construct a composite genetic risk score (GRS), capturing respectively 21%, 11%, and 227% more of SBP, DBP and PP heritability than achieved with the traditional GRS. The composite GRS improves the prediction of hypertension and CVD in persons of European as well as African and Asian descent. We identified and confirmed 120 novel BP pleiotropic variants that are not in linkage disequilibrium with known variants, including 17 novel BP loci. We further observed significant age-modulated genetic effects on BP, hypertension and CVD in both Europeans and Asians. Our study provides further insight into BP regulation and provides a novel way to construct a GRS for correlated traits.

Rationale & Objective Persons with end-stage kidney disease receiving in-center maintenance hemodialysis may be at high risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposure and severe outcomes with coronavirus disease 2019 (COVID-19). The objective of this study was to examine the correlation of SARS-CoV-2 positivity rate per capita and COVID-19–associated deaths with number of dialysis stations and demographics of residents within zip codes in Cook County, IL. Study Design Ecological analysis. Setting & Participants Data for SARS-CoV-2 test results and COVID-19–associated deaths during January 21 to June 15, 2020, among the 5,232,412 residents living within the 163 zip codes in Cook County, IL, were merged with demographic and income data from the US Census Bureau. The total number of positive test results in this population was 84,353 and total number of deaths was 4,007. Assessments Number of dialysis stations and stations per capita within a zip code were calculated. SARS-CoV-2–positive test results per capita were calculated as number of positive test results divided by the zip code population. COVID-19–associated deaths per capita were calculated as COVID-19 deaths among residents for a given zip code divided by the zip code population. Analytic Approach Spearman rank correlation coefficients were calculated to examine the correlation of SARS-CoV-2–positive tests per capita and COVID-19–associated deaths per capita with dialysis stations, demographics, and household poverty. To account for multiple testing, statistical significance was considered as P

Educational attainment is widely used as a surrogate for socioeconomic status (SES). Low SES is a risk factor for hypertension and high blood pressure (BP). To identify novel BP loci, we performed multi-ancestry meta-analyses accounting for gene-educational attainment interactions using two variables, "Some College" (yes/no) and "Graduated College" (yes/no). Interactions were evaluated using both a 1 degree of freedom (DF) interaction term and a 2DF joint test of genetic and interaction effects. Analyses were performed for systolic BP, diastolic BP, mean arterial pressure, and pulse pressure. We pursued genome-wide interrogation in Stage 1 studies (N = 117 438) and follow-up on promising variants in Stage 2 studies (N = 293 787) in five ancestry groups. Through combined meta-analyses of Stages 1 and 2, we identified 84 known and 18 novel BP loci at genome-wide significance level (P < 5 × 10 -8 ). Two novel loci were identified based on the 1DF test of interaction with educational attainment, while the remaining 16 loci were identified through the 2DF joint test of genetic and interaction effects. Ten novel loci were identified in individuals of African ancestry. Several novel loci show strong biological plausibility since they involve physiologic systems implicated in BP regulation. They include genes involved in the central nervous system-adrenal signaling axis (ZDHHC17, CADPS, PIK3C2G), vascular structure and function (GNB3, CDON), and renal function (HAS2 and HAS2-AS1, SLIT3). Collectively, these findings suggest a role of educational attainment or SES in further dissection of the genetic architecture of BP.

Significant disparities exist in kidney disease, with blacks facing a higher burden of CKD and kidney failure. In addition to socioeconomic/health system factors, these disparities are linked to two sequence variants (G1 and G2) in the apoL1 ( APOL1 ) gene. The high-risk APOL1 genotype (two copies

OBJECTIVE Improved blood pressure control and use of renin-angiotensin-aldosterone system blockers have altered the clinical presentation or phenotype of chronic kidney disease (CKD) in U.S. adults with diabetes. These changes may influence mortality. RESEARCH DESIGN AND METHODS Data from the National Health and Nutrition Examination Surveys (NHANES) 1988–2006 were used to examine mortality trends in adults with diabetes, defined as physician diagnosis, fasting glucose ≥126 mg/dL, HbA1c >6.5% (48 mmol/mol), or use of glucose-lowering medications. Mortality trends by CKD phenotype (estimated glomerular filtration rate [eGFR] and urine albumin-to-creatinine ratio [ACR] level) were obtained via linkage with the National Death Index through 31 December 2011 while accounting for the complex survey design. RESULTS From 1988 to 2006, adults with an eGFR CONCLUSIONS ACR values are decreasing in U.S. adults with diabetes, but optimal management strategies are needed to reduce mortality in those with a low eGFR and an ACR

While increased obesity prevalence among persons of African ancestry (AAs) compared to persons of European ancestry (EAs) is linked to social, environmental and behavioral factors, there are no gene variants that are common and significantly associated with obesity in AA populations. We sought to explore the association between ancestry specific renal risk variants in the apolipoprotein L1 (APOL1) gene with obesity related traits in AAs.We conducted a genotype-phenotype association study from 3 electronic medical record linked cohorts (BioMe Biobank, BioVU, nuGENE); randomized controlled trials (genetic testing to understand and address renal disease disparities) and prospective cohort study (Jackson Heart Study). We analyzed association of APOL1 renal risk variants with cross-sectional measures of obesity (average body mass index (BMI), and proportion of overweight and obesity) and with measures of body composition (in Jackson Heart Study).We had data on 11,930 self-reported AA adults. Across cohorts, mean age was from 42 to 49 years and percentage female from 58% to 75.3%. Individuals who have 2 APOL1 risk alleles (14% of AAs) have 30% higher obesity odds compared to others (recessive model adjusted odds ratio 1.30; 95% confidence interval 1.16-1.41; P = 2.75 × 10-6). An additive model better fit the association, in which each allele (47% of AAs) increases obesity odds by 1.13-fold (adjusted odds ratio 1.13; 95% confidence interval 1.07-1.19; P = 3.07 × 10-6) and increases BMI by 0.36 kg/m2 (∼1 kg, for 1.7 m height; P = 2 × 10-4). APOL1 alleles are not associated with refined body composition traits overall but are significantly associated with fat free mass index in women [0.30 kg/m2 increment per allele; P = .03].Thus, renal risk variants in the APOL1 gene, found in nearly half of AAs, are associated with BMI and obesity in an additive manner. These variants could, either on their own or interacting with environmental factors, explain a proportion of ethnic disparities in obesity.

OBJECTIVE This study examined the association of 25-hydroxyvitamin D [25(OH)D] levels and blood pressure above and below 25(OH)D levels of 20 ng/ml in young adults with African ancestry. METHODS This cross-sectional analysis utilized data from a pooled sample of 2242 adults with African ancestry from five different latitudes (403 in the United States, 474 in South Africa, 479 in Ghana, 448 in Jamaica, and 438 in Seychelles). Piecewise linear regression models with a single knot were fitted to determine above and below a 25(OH)D level of 20 ng/ml the slope of SBP and DBP while adjusting for covariates including calcium intake and site. RESULTS The mean age was 34.4 (6.1) years, and 46.3% were men. Mean SBP and DBP were 118.1 (15.6) and 73.2 (12.2) mmHg, respectively, and were significantly higher among the United States vs Ghana, Jamaica, and Seychelles groups (P

Although the association of vitamin D levels with cardiovascular risk profiles among Hispanics/Latinos has been studied, little is known about this association among Hispanics/Latinos with chronic conditions. This pilot study determined serum vitamin D and parathyroid hormone (PTH) levels in a sample of participants from the University of Illinois at the Chicago Cohort of Patients, Family and Friends (UIC Cohort) and examined their association with traditional cardiovascular disease risk factors. From July 2012 to June 2016, the UIC Cohort study enrolled and conducted clinical examinations on men and women ages 18 years and older, who had one or more diagnosed chronic diseases/conditions (excluding cancer). This pilot study sample included 40 participants from the six main Hispanic/Latino background groups in the United States, namely Dominican, Cuban, Puerto Rican, Mexican, Central American, and South American, and were grouped by Caribbean or mainland origin. No substantial differences were noted in the vitamin D-related measures by Hispanic/Latino background, but the PTH levels were somewhat higher in the Caribbean vs. mainland group (43.0 &plusmn, 4.6 vs. 38.6 &plusmn, 2.7 pg/mL). The associations between selected CVD risk factors (systolic and diastolic blood pressure (SBP, DBP), total cholesterol, glucose) and PTH and vitamin D-related analytes were investigated using interval-censored multivariate regression models adjusted for age, sex, percent body fat, serum albumin/calcium, and Hispanic/Latino background. A negative association between total 25[OH]D and blood pressure was corroborated (SBP: &beta, = &minus, 1.2, 95%CI = &minus, 2.0, &minus, 0.3, DBP: &beta, 0.7, 95% CI = &minus, 1.2, &minus, 0.1), whereas a positive association with total cholesterol was observed (&beta, = 1.9, 95% CI = 0.02, 3.7). Levels of 1, 25[OH]2D were not associated with CVD risk factors, whereas 24, 25[OH]2D3 was associated with blood pressure (SBP: &beta, 13.0, 95% CI = &minus, 20.7, &minus, 5.2, 6.3, 95% CI = &minus, 11.6, &minus, 1.0). Estimated free 25[OH]D was inversely associated with both SBP (&beta, 3.5, 95% CI = &minus, 6.1, &minus, 0.9) and DBP (&beta, 2.1, 95% CI = &minus, 3.8, &minus, 0.3). Similarly, calculated bioavailable 25[OH]D was inversely associated with both SBP (&beta, 9.2, 95% CI = &minus, 15.9, &minus, 2.4) and DBP(&beta, 5.3, 95% CI = &minus, 9.8, &minus, 0.8). In conclusion, a negative association between 25[OH]D with BP was observed and a positive association with lipids is suggested. Due to the small sample size, most associations did not reach statistical significance.

Elevated blood pressure (BP), a leading cause of global morbidity and mortality, is influenced by both genetic and lifestyle factors. Cigarette smoking is one such lifestyle factor. Across five ancestries, we performed a genome-wide gene–smoking interaction study of mean arterial pressure (MAP) and pulse pressure (PP) in 129 913 individuals in stage 1 and follow-up analysis in 480 178 additional individuals in stage 2. We report here 136 loci significantly associated with MAP and/or PP. Of these, 61 were previously published through main-effect analysis of BP traits, 37 were recently reported by us for systolic BP and/or diastolic BP through gene–smoking interaction analysis and 38 were newly identified (P

Introduction: Cardiovascular disease (CVD) may prevent the adoption of healthy lifestyle habits such as physical activity, and thus may lead to weight gain and increased risk for lifestyle-related conditions such as diabetes mellitus (DM). Evidence suggests that medications commonly used in the management of CVD such as diuretics, β blockers, and statins are also associated with increased risk of diabetes. We examined the association of CVD with incident DM and investigated whether this association is mediated by change in BMI or medication use. Methods: Data from the HCHS/SOL Visit 1 (2008-2011) and Visit 2 (2014-2017) examinations were used to compare incidence of DM among persons with and without CVD at Visit 1. DM was defined using the American Diabetes Association criteria, and prevalent CVD using the Framingham Heart Study definition (i.e., self-reported history of coronary heart disease, cerebrovascular events, peripheral artery disease, or heart failure). Of the 8672 participants free of DM at Visit 1 and with complete data on DM at Visit 2 and on key covariates of interest, 2191 (25.3%) had prevalent CVD at baseline. A total of 2050 participants with CVD were matched to controls free of CVD at Visit 1 using 1:1 propensity matching. Covariates included in the propensity model were age, gender, educational attainment, marital status, Hispanic background, history of hypertension, family history of diabetes, health insurance coverage, chronic kidney disease at baseline, gestational diabetes, high cholesterol, metabolic syndrome, alcohol use, cigarette pack years, physical activity level, diet quality based on alternative healthy eating index, baseline BMI, baseline prediabetes. Matched pairs were analyzed. McNemar’s test was used to compare incidence of DM among cases and controls. The mediating effects of change in BMI and medication use were examined. Results: Covariate distributions were similar among participants with and without CVD. The incidence of DM among persons with CVD was 15.7% vs. 13.6% among those without CVD (p=0.06). No natural direct effect of CVD on DM was found. The association between CVD and incidence of DM was not mediated by change in BMI. On average, BMI increased by 0.38 (SE=2.56) and 0.33 (SE=2.50) among persons with and without CVD, respectively (p=0.55). The association between CVD and DM was indirectly mediated by the use of beta-blockers (percent mediated=24.8%), statins (percent mediated=9.8%), and diuretics (percent mediated=8.9%). Conclusion: There is slight evidence that medications used to treat CVD increase risk for new onset diabetes.

Acute Respiratory Distress Syndrome (ARDS) is a syndrome of respiratory failure that may be identified using text from radiology reports. The objective of this study was to determine whether natural language processing (NLP) with machine learning performs better than a traditional keyword model for ARDS identification. Linguistic pre-processing of reports was performed and text features were inputs to machine learning classifiers tuned using 10-fold cross-validation on 80% of the sample size and tested in the remaining 20%. A cohort of 533 patients was evaluated, with a data corpus of 9,255 radiology reports. The traditional model had an accuracy of 67.3% (95% CI: 58.3-76.3) with a positive predictive value (PPV) of 41.7% (95% CI: 27.7-55.6). The best NLP model had an accuracy of 83.0% (95% CI: 75.9-90.2) with a PPV of 71.4% (95% CI: 52.1-90.8). A computable phenotype for ARDS with NLP may identify more cases than the traditional model.

After World War II, industrialized countries found themselves faced with a new epidemic of chronic disease. Stroke had long been a common cause of death, however a much more virulent form of vascular disease involving the coronary arteries was now recognized as a major public health challenge. By the late 1950s, cardiovascular diseases (CVD) accounted for almost two-thirds of deaths in the US. Within 10 years, the key causal factors underlying CVD had been fully defined, and by the mid-1960s, prevention trials, policy changes, and subsequent population-wide risk factor improvement and targeted high-risk medical therapy led to a rapid and sustained decline in both coronary heart disease (CHD) and stroke. By the turn of the century, CVD had declined over 80%, transforming health for adults and providing the main driver of lengthening life expectancy. This transformative process has now reached every country in the world. Epidemiologic, nutritional and clinical research, along with changes in social norms, public health education, smoke-free indoor air regulations, drug development, and clinical trials have led to the astounding success of the CVD control movement. The broad pattern pursued in the control of CVD provides a template for similar control efforts aimed at cancer, diabetes, renal disease, and other common chronic diseases.

High blood pressure (BP) is a major risk factor for cardiovascular disease (CVD) and is more prevalent in African Americans as compared to other US groups. Although large, population-based genome-wide association studies (GWAS) have identified over 300 common polymorphisms modulating inter-individual BP variation, largely in European ancestry subjects, most of them do not localize to regions previously identified through family-based linkage studies. This discrepancy has remained unexplained despite the statistical power differences between current GWAS and prior linkage studies. To address this issue, we performed genome-wide linkage analysis of BP traits in African-American families from the Family Blood Pressure Program (FBPP) and genotyped on the Illumina Human Exome BeadChip v1.1. We identified a genomic region on chromosome 1q31 with LOD score 3.8 for pulse pressure (PP), a region we previously implicated in DBP studies of European ancestry families. Although no reported GWAS variants map to this region, combined linkage and association analysis of PP identified 81 rare and low frequency exonic variants accounting for the linkage evidence. Replication analysis in eight independent African ancestry cohorts (N = 16,968) supports this specific association with PP (P = 0.0509). Additional association and network analyses identified multiple potential candidate genes in this region expressed in multiple tissues and with a strong biological support for a role in BP. In conclusion, multiple genes and rare variants on 1q31 contribute to PP variation. Beyond producing new insights into PP, we demonstrate how family-based linkage and association studies can implicate specific rare and low frequency variants for complex traits.

BACKGROUND: Study findings show that although palliative care decreases symptom burden, it is still underused in patients with ESKD. Little is known about disparity in use of palliative care services in such patients in the inpatient setting. METHODS: To investigate the use of palliative care consultation in patients with ESKD in the inpatient setting, we conducted a retrospective cohort study using the National Inpatient Sample from 2006 to 2014 to identify admitted patients with ESKD requiring maintenance dialysis. We compared palliative care use among minority groups (black, Hispanic, and Asian) and white patients, adjusting for patient and hospital variables. RESULTS: We identified 5,230,865 hospitalizations of such patients from 2006 through 2014, of which 76,659 (1.5%) involved palliative care. The palliative care referral rate increased significantly, from 0.24% in 2006 to 2.70% in 2014 (P

This report presents findings of an ad hoc working group assembled by the National Heart, Lung, and Blood Institute (NHLBI) to assess research needs to improve prevention, treatment, and control of hypertension among African Americans. Non-Hispanic Blacks (African American and Black will be used for US and international studies, respectively) tend to have an earlier onset, higher prevalence, and disproportionately high risk of complications for hypertension compared with non-Hispanic Whites and Mexican Americans.1 Surveys identify substantial variation in mean blood pressure (BP) among populations of African origin.2 In high-income countries, including the United States, mean BP and prevalence of hypertension are higher in adults self-described,3–6 observer reported,7,8 or otherwise identified9,10 as being black or having darker skin color.11 However, the relationship between African origin and BP is absent or only minimally apparent in reports from middle-income countries.12–14 Research to clarify reasons for this variability may contribute to understanding of hypertension-related racial disparities in the United States. In US National Health and Nutrition Examination Survey (NHANES) reports, crude and age-adjusted prevalence of hypertension (systolic BP [SBP] ≥140 mm Hg, diastolic BP ≥90 mm Hg, or taking antihypertensive medication) in adults has remained fairly constant at ≈30% since 1999 to 2000.3,4 The corresponding prevalence estimate for African Americans is ≈40% and has also remained reasonably stable. In African Americans, hypertension awareness and treatment rates are higher but control rates lower compared with non-Hispanic Whites (85.7% versus 82.7% for awareness, 77.4% versus 76.7% for treatment, and 49.5% versus 53.9% for control in NHANES 2011–2012).4 The lower prevalence of BP control is present despite use of more BP-lowering medications, including thiazide diuretics.15 This contrasts with clinical trial experience, where differences in BP control rates by race/ethnicity …