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Understanding the association between initial experimentation with a tobacco product and subsequent patterns of tobacco use among youth is important to informing prevention activities for youth in the US. We conducted an online survey from August to October 2017 among youth aged 13–18 years. The current analysis focused on respondents reporting initial experimentation with any tobacco product (n = 2,022). Using multinomial logistic regression, we examined the association between first tobacco product tried (cigarettes; cigars including cigarillos, little cigars, and bidis; electronic nicotine delivery systems (ENDS); smokeless and chewing tobacco; or hookah) with subsequent patterns of tobacco use while adjusting for covariates. Of the youth who experimented, 56.8% were non-current tobacco users. Of current tobacco users (n = 934), 13% were exclusive ENDS users, 5.3% exclusive combustible mono-users, 13.4% ENDS plus combustible poly-users, 3.3% combustible product only poly-users, and 8.2% other tobacco poly-users. The most common type of first tobacco product tried was ENDS (44.7%), followed by cigarettes (35.0%) and cigars (8.6%). Those who experimented with combustible tobacco products were less likely to be exclusive ENDS users [Relative Risk Ratio (RRR) = 0.46; 95% CI = 0.28, 0.73 for cigarettes; RRR = 0.32; 95% CI = 0.13, 0.81 for cigars; and RRR = 0.33; 95% CI = 0.14, 0.79 for hookah] when compared to non-current tobacco users (reference group). Tobacco product choices for initial experimentation appear to play a role in subsequent tobacco use patterns among youth. Understanding the reasons behind initial product choice may inform our understanding regarding the reasons for subsequent current tobacco product use, thus informing youth prevention efforts. [ABSTRACT FROM AUTHOR]

ContextAbnormalities in calcium metabolism may potentially contribute to the development of vascular disease. Calcium metabolism may be different in African American (AA) vs white individuals, but the effect of race on the association of serum calcium with clinical outcomes remains unclear.ObjectiveThis study sought to examine race-specific associations of serum calcium levels with mortality and with major incident cardiovascular events.Design and settingThis was a historical cohort study in the U.S. Department of Veterans Affairs health care facilities.ParticipantsParticipants included veterans (n = 1 967 622) with estimated glomerular filtration rate ≥ 60 mL/min/1.73 m2.Main outcome measuresThe association between serum calcium levels with all-cause mortality, incident coronary heart disease (CHD), and ischemic stroke incidence was examined in multivariable adjusted Cox proportional hazards models, including an interaction term for calcium and race.ResultsThe association of calcium with all-cause mortality was U-shaped in both AA and white patients, but race modified the association of calcium with all-cause mortality. Compared with white patients, AA patients experienced lower risk of mortality when calcium was ≥ 8.8 mg/dL, with a statistically significant interaction (P < .001). Conversely, AA vs white race was associated with higher mortality when calcium was < 8.8 mg/dL. Calcium showed no significant association with ischemic stroke or CHD in both races; and race did not modify these associations (P = .37 and 0.11, respectively for interaction term).ConclusionsRace modified the U-shaped association between calcium and all-cause mortality. Serum calcium is not associated with incident stroke or CHD in either AA or white patients. The race-specific difference in the association of calcium levels with mortality warrants further examination.

BackgroundIn the general population, compared wtih their White peers, African Americans suffer premature all-cause and cardiovascular (CV) deaths, attributed in part to reduced access to care and lower socioeconomic status. Prior reports indicated younger (aged 35 to 44 years) African Americans had a signficantly greater age-adjusted risk of death. Recent studies suggest that in a more egalitarian health care structure than typical United States (US) health care structures, African Americans may have similar or even better CV outcomes, but the impact of age is less well-known.MethodsWe examined age stratified all-cause mortality, and incident coronary heart disease (CHD) and ischemic stroke in 3,072,966 patients (547,441 African American and 2,525,525 White) with an estimated glomerular filtration rate (eGFR)>60 mL/min/1.73m(2) receiving care from the US Veterans Health Administration. Outcomes were examined in Cox models adjusted for demographics, comorbidities, kidney function, blood pressure, socioeconomics and indicators of the quality of health care delivery.ResultsAfrican Americans had an overall 30% lower all-cause mortality (P

The microbiome provides resistance to infection. However, the underlying mechanisms are poorly understood. We demonstrate that colonization with the intestinal bacterium Clostridium scindens protects from Entamoeba histolytica colitis via innate immunity. Introduction of C. scindens into the gut microbiota epigenetically altered and expanded bone marrow granulocyte-monocyte progenitors (GMPs) and resulted in increased intestinal neutrophils with subsequent challenge with E. histolytica. Introduction of C. scindens alone was sufficient to expand GMPs in gnotobiotic mice. Adoptive transfer of bone marrow from C. scindens-colonized mice into naive mice protected against amebic colitis and increased intestinal neutrophils. Children without E. histolytica diarrhea also had a higher abundance of Lachnoclostridia. Lachnoclostridia C. scindens can metabolize the bile salt cholate, so we measured deoxycholate and discovered that it was increased in the sera of C. scindens-colonized specific pathogen-free and gnotobiotic mice, as well as in children protected from amebiasis. Administration of deoxycholate alone increased GMPs and provided protection from amebiasis. We elucidated a mechanism by which C. scindens and the microbially metabolized bile salt deoxycholic acid alter hematopoietic precursors and provide innate protection from later infection with E. histolytica., Introduction Commensal intestinal bacteria may protect from infection (1, 2) by modulating bone marrow production of innate immune effector cells, including neutrophils and inflammatory macrophages (3-5). The host metabolome is [...]

BackgroundIn the general population, blacks experience higher mortality than their white peers, attributed in part to their lower socioeconomic status, reduced access to care, and possibly intrinsic biological factors. Patients with kidney disease are a notable exception, among whom blacks experience lower mortality. It is unclear if similar differences affecting outcomes exist in patients with no kidney disease but with equal or similar access to health care.Methods and resultsWe compared all-cause mortality, incident coronary heart disease, and incident ischemic stroke using multivariable-adjusted Cox models in a nationwide cohort of 547 441 black and 2 525 525 white patients with baseline estimated glomerular filtration rate ≥ 60 mL·min⁻¹·1.73 m⁻² receiving care from the US Veterans Health Administration. In parallel analyses, we compared outcomes in black versus white individuals in the National Health and Nutrition Examination Survey (NHANES) 1999 to 2004. After multivariable adjustments in veterans, black race was associated with 24% lower all-cause mortality (adjusted hazard ratio, 0.76; 95% confidence interval, 0.75-0.77; P

RationaleThere is a paucity of large cohort studies examining the association of obstructive sleep apnoea (OSA) with clinical outcomes including all-cause mortality, coronary heart disease (CHD), strokes and chronic kidney disease (CKD).ObjectivesWe hypothesised that a diagnosis of incident OSA is associated with higher risks of these adverse clinical outcomes.Methods, measurementsIn a nationally representative cohort of over 3 million (n=3 079 514) US veterans (93% male) with baseline estimated glomerular filtration rate (eGFR)≥60 mL/min/1.73 m(2), we examined the association between the diagnosis of incident OSA, treated and untreated with CPAP, and: (1) all-cause mortality, (2) incident CHD, (3) incident strokes, (4)incident CKD defined as eGFR

Obesity is associated with higher mortality in the general population, but this association is reversed in patients on dialysis. The nature of the relationship of obesity with adverse clinical outcomes in nondialysis-dependent CKD and the putative interaction of the severity of disease with this association are unclear. We analyzed data from a nationally representative cohort of 453,946 United States veterans with eGFR

ImportanceThe effect of strict blood pressure control on clinical outcomes in patients with chronic kidney disease (CKD) is unclear.ObjectiveTo compare the outcomes associated with a treated systolic blood pressure (SBP) of less than 120 mm Hg vs those associated with the currently recommended SBP of less than 140 mm Hg in a national CKD database of US veterans.Design, setting, and participantsHistorical cohort study using a nationwide cohort of US veterans with prevalent CKD, estimated glomerular filtration rate less than 60 mL/min/1.73 m(2), and uncontrolled hypertension, who then received 1 or more additional blood pressure medications with evidence of a decrease in SBP. Propensity scores were calculated to reflect each individual's probability for future SBP less than 120 vs 120 to 139 mm Hg.Main outcomes and measuresThe effect of SBP on all-cause mortality was evaluated by the log-rank test, and in Cox models adjusted for propensity scores.ResultsUsing a database of 651,749 patients with CKD, we identified 77,765 individuals meeting the inclusion criteria. A total of 5760 patients experienced follow-up treated SBP of less than 120 mm Hg and 72,005 patients had SBP of 120 to 139 mm Hg. During a median follow-up of 6.0 years, 19,517 patients died, with 2380 deaths in the SBP less than 120 mm Hg group (death rate, 80.9/1000 patient-years [95% CI, 77.7-84.2/1000 patient-years]) and 17,137 deaths in the SBP 120 to 139 mm Hg group (death rate, 41.8/1000 patient-years [95% CI, 41.2-42.4/1000 patient-years]; P

BackgroundIn contrast to the general population, higher body mass index (BMI) is associated with greater survival in patients receiving hemodialysis (HD; "obesity paradox"). We hypothesized that this paradoxical association between BMI and death may be modified by age and dialysis vintage.Study designRetrospective observational study using a large HD patient cohort.Setting & participants123,383 maintenance HD patients treated in DaVita dialysis clinics between July 1, 2001, and June 30, 2006, with follow-up through September 30, 2009.PredictorsAge, dialysis vintage, and time-averaged BMI. Time-averaged BMI was divided into 6 subgroups;  25kg/m(2) added no additional benefit. Based on dialysis vintage, incident HD patients had greater all-cause and cardiovascular survival benefit with a higher time-averaged BMI compared with the longer term HD patients.LimitationsCausality cannot be determined, and residual confounding cannot be excluded given the observational study design.ConclusionsHigher BMI is associated with lower death risk across all age and dialysis vintage groups. This benefit is more pronounced in incident HD patients and those younger than 65 years. Given the robustness of the survival advantage of higher BMI, examining interventions to maintain or even increase dry weight in HD patients irrespective of age and vintage are warranted.

ObjectivesThe study objective was to assess the association between angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) use and mortality in patients with chronic kidney disease (CKD).BackgroundThere is insufficient evidence about the association of ACEI or ARBs with mortality in patients with CKD.MethodsA logistic regression analysis was used to calculate the propensity of ACEI/ARB initiation in 141,413 U.S. veterans with nondialysis CKD who were previously unexposed to ACEI/ARB treatment. We examined the association of ACEI/ARB administration with all-cause mortality in patients matched by propensity scores using the Kaplan-Meier method and Cox models in "intention-to-treat" analyses and in generalized linear models with binary outcomes and inverse probability of treatment weights in "as-treated" analyses.ResultsThe age of the patients at baseline was 75 ± 10 years, 8% of patients were black, and 22% were diabetic. ACEI/ARB administration was associated with a significantly lower risk of mortality both in the intention-to-treat analysis (hazard ratio: 0.81, 95% confidence interval: 0.78 to 0.84; p < 0.001) and the as-treated analysis with inverse probability of treatment weights (odds ratio: 0.37, 95% confidence interval: 0.34 to 0.41; p < 0.001). The association of ACEI/ARB treatment with lower risk of mortality was present in all examined subgroups.ConclusionsIn this large contemporary cohort of nondialysis-dependent patients with CKD, ACEI/ARB administration was associated with greater survival.

BackgroundThe ideal blood pressure (BP) to decrease mortality rates in patients with non-dialysis-dependent chronic kidney disease (CKD) is unclear.ObjectiveTo assess the association of BP (defined as the combination of systolic BP [SBP] and diastolic BP [DBP] at the individual level) with death in patients with CKD.DesignHistorical cohort between 2005 and 2012.SettingAll U.S. Department of Veterans Affairs health care facilities.Patients651 749 U.S. veterans with CKD.MeasurementsAll possible combinations of SBP and DBP were examined in 96 categories from lowest (210/>120 mm Hg), in 10-mm Hg increments. Associations with all-cause mortality were examined in time-dependent Cox models with adjustment for relevant confounders.ResultsPatients with SBP of 130 to 159 mm Hg combined with DBP of 70 to 89 mm Hg had the lowest adjusted mortality rates, and those in whom both SBP and DBP were concomitantly very high or very low had the highest mortality rates. Patients with moderately elevated SBP combined with DBP no less than 70 mm Hg had consistently lower mortality rates than did patients with ideal SBP combined with DBP less than 70 mm Hg. Results were consistent in subgroups of patients with normal and elevated urinary microalbumin-creatinine ratios.LimitationMostly male patients, inability to establish causality, and large number of patients missing proteinuria measurement.ConclusionThe optimal BP in patients with CKD seems to be 130 to 159/70 to 89 mm Hg. It may not be advantageous to achieve ideal SBP at the expense of lower-than-ideal DBP in adults with CKD.Primary funding sourceNational Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, and U.S. Department of Veterans Affairs.

ObjectivesThis study sought to compare the association of microalbuminuria with outcomes in patients with different comorbidities.BackgroundThe risk of adverse outcomes associated with lower levels proteinuria has been found to be linearly decreasing with even low-normal levels of microalbuminuria. It is unclear whether comorbid conditions change these associations.MethodsWe examined the association of urine microalbumin-creatinine ratio (UACR) with mortality and the slopes of estimated glomerular filtration rate (eGFR) in a nationally representative cohort of 298,875 U.S. veterans. Associations of UACR with all-cause mortality overall and in subgroups of patients with and without diabetes mellitus, hypertension, cardiovascular disease, congestive heart failure, and advanced chronic kidney disease (CKD) were examined in Cox models, and with the slopes of eGFR in linear and logistic regression models.ResultsVery low levels of UACR were linearly associated with decreased mortality and less progression of CKD overall: adjusted mortality hazard ratio and estimated glomerular filtration rate slope (95% confidence interval [CI]) associated with UACR ≥200 μg/mg, compared to

BackgroundBlack dialysis patients have significantly lower mortality compared to white patients, in contradistinction to the higher mortality seen in blacks in the general population. It is unclear if a similar paradox exists in non–dialysis-dependent CKD, and if it does, what its underlying reasons are.Study DesignHistorical cohort.Setting & Participants518,406 white and 52,402 black male US veterans with non-dialysis dependent CKD stages 3–5.PredictorBlack race.Outcomes & MeasurementsWe examined overall and CKD stage-specific all-cause mortality using parametric survival models. The effect of sociodemographic characteristics, comorbidities and laboratory characteristics on the observed differences was explored in multivariable models.ResultsOver a median follow-up of 4.7 years 172,093 patients died (mortality rate, 71.0 [95% CI, 70.6–71.3] per 1000 patient-years). Black race was associated with significantly lower crude mortality (HR, 0.95; 95% CI, 0.94–0.97; p

Background and objectivesDepression is common and is associated with higher mortality in patients with ESRD or CKD (stage 5). Less information is available on earlier stages of CKD. This study aimed to determine the prevalence of depression and any association with all-cause mortality in patients with varying severity of nondialysis-dependent CKD.Design, setting, participants, & measurementsThis is a retrospective study of a national cohort of 598,153 US veterans with nondialysis-dependent CKD stages 1-5 followed for a median of 4.7 years in the US Department of Veterans Affairs Health System. Diagnosis of depression was established as a result of systematic screening and administration of antidepressants. Association of depression with all-cause mortality overall and stratified by CKD stages were examined with the Kaplan-Meier method and in Cox models.ResultsThere were 179,441 patients (30%) with a diagnosis of depression. Over median follow-up of 4.7 years, depression was associated with significantly higher age-adjusted mortality overall (hazard ratio, 1.55; 95% confidence interval, 1.54-1.57; P

BackgroundHyponatremia is common in patients with conditions such as congestive heart failure and is associated with increased mortality in hospitalized patients. Congestive heart failure is common in patients with chronic kidney disease, but the association of serum sodium concentration with mortality in such patients is not well characterized.Methods and resultsWe examined the association of serum sodium concentration with all-cause mortality in a nationally representative cohort of 655 493 US veterans with non-dialysis-dependent chronic kidney disease (95 961 [15%] of them with congestive heart failure). Associations were examined in time-dependent Cox models with adjustment for potential confounders. During a median follow-up of 5.5 years, a total of 193 956 patients died (mortality rate, 62.5/1000 patient-years; 95% confidence interval, 62.2-62.8). The association of serum sodium level with mortality was U-shaped, with the lowest mortality seen in patients with sodium level of 140 mEq/L and with both lower and higher levels showing significant associations with increased mortality. Patients with serum sodium levels of