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Objective The aim of the study was to examine the effects of the vitamin D (Vit-D) treatment and nontreatment on Vit-D–deficient patients without a prior history of myocardial infarction (MI). Materials and Methods This was a retrospective, observational, nested case–control study of patients (N = 20 025) with low 25-hydroxyvitamin D ([25-OH]D) levels ( Results Among the cohort of 20 025 patients, the risk of MI was significantly lower in Group C than in Group B (hazard ratio [HR] 0.65, 95% CI 0.49-0.85, P = .002) and Group A (HR 0.73, 95% CI 0.55-0.96), P = .02). There was no difference in the risk of MI between Group B and Group A (HR 1.14, 95% CI 0.91-1.42, P = 0.24). Compared with Group A, both Group B (HR 0.59, 95% CI 0.54-0.63, P Conclusions In patients with Vit-D deficiency and no prior history of MI, treatment to the (25-OH)D level of >20 ng/mL and >30 ng/mL was associated with a significantly lower risk of all-cause mortality. The lower risk of MI was observed only in individuals maintaining (25-OH)D levels ≥30 ng/mL.

Background: We have recently shown that PTSD/TBI takes an especially devastating toll on America’s veterans and their families with mental, physical and financial ramifications and poor clinical outcomes (Thakur et al. Epidemiology (Sunnyvale) 2018; 8:353). Patients with PTSD were found to have higher rates of cardiovascular symptoms, hospitalizations and mortality. Whereas electrocardiographic abnormalities, arrhythmias and ventricular dysfunction have been reported in patients with TBI. Association of PTSD/TBI with Myocardial Infarction (MI) is not well studied; the objective of this study was to examine the relationship between PTSD/TBI and MI in a large patient population. Methods: This retrospective study used national data from Veterans Administrations Informatics and Computing Infrastructure (VINCI). Propensity score analysis was performed to obtain matched pairs of (1) Non-PTSD/TBI vs. PTSD (2) Non-PTSD/TBI vs. TBI. Confounding variables used for matching were patients’ demographics and co-morbidities. Cox proportional hazard regression analysis was conducted on matched pairs to determine the relationship between PTSD, TBI and incidence of MI. Kaplan-Meier curves were plotted to compare the time to development of incident MI among the groups. Relationships between variables were examined using chi-square tests, t-tests and non-parametric tests. Results: The risk of new-onset MI was significantly higher for patients with PTSD/TBI when compared with their counterparts without PTSD/TBI. Risk of MI with TBI (HR=2.687, CI 2.546-2.835, P Conclusion: There is a significant increase in the incidence of MI in patients with a diagnosis of PTSD or TBI. Further studies are needed to formulate clinical guidelines to risk stratify and intervene to help reduce the incidence of MI in this patient population.

The high cost associated with antiviral treatment for chronic hepatitis C virus (HCV) infection mandates further investigation in the context of preventing complications such as type 2 diabetes mellitus (DM2). We determined the cumulative incidence of DM2 in subjects with chronic HCV infection who received concomitant pegylated interferon (Peg-IFN) and ribavirin. We conducted a retrospective analysis of data obtained from Veterans Administrations Informatics and Computing Infrastructure (VINCI) to identify an adult cohort of patients without diabetes with chronic HCV infection who received Peg-IFN-based therapy between October 2001 and December 2011. Patients with history of HIV, hepatitis B infection, hepatocellular cancer (HCC), non-HCC cancers, and history of transplantation were excluded. Sustained virological response (SVR) was defined as negative HCV RNA 3 months after completion of therapy. Using Cox proportional hazards regression for multivariable analysis, we determined that patients who achieved SVR were at a significantly less risk of developing DM2. Adjusted survival rates showed that the responders' group was significantly less likely to develop DM2 over time (HR 0.60, CI 0.48 to 0.74, p

The effect of normalization of serum testosterone levels with testosterone replacement therapy (TRT) in patients with a history of myocardial infarction (MI) is unknown. The objective of this study was to determine the incidence of recurrent MI and all-cause mortality in subjects with a history of MI and low total testosterone (TT) with and without TRT. We retrospectively examined 1,470 men with documented low TT levels and previous MI, categorized into Gp1: TRT with normalization of TT levels (n = 755) Gp2: TRT without normalization of TT levels (n = 542), and Gp3: no TRT (n = 173). The association of TRT with all-cause mortality and recurrent MI was compared using propensity score-weighted Cox proportional hazard models. All-cause mortality was lower in Gp1 versus Gp2 (hazard ratio [HR] 0.76, confidence interval [CI] 0.64 to 0.90, p = 0.002), and Gp1 versus Gp3 (HR 0.76, CI 0.60 to 0.98, p = 0.031). There was no significant difference in the risk of death between Gp2 versus Gp3 (HR 0.97, CI 0.76 to 1.24, p = 0.81). Adjusted regression analyses showed no significant differences in the risk of recurrent MI between groups (Gp1 vs Gp3, HR 0.79, CI 0.12 to 5.27, p = 0.8; Gp1 vs Gp2 HR 1.10, CI 0.25 to 4.77, p = 0.90; Gp2 vs Gp3 HR 0.58, CI 0.08 to 4.06, p = 0.58). In conclusion, in a large observational cohort of male veterans with previous MI, normalization of TT levels with TRT was associated with decreased all-cause mortality compared with those with non-normalized TT levels and the untreated group. Furthermore, in this high-risk population, TRT was not associated with an increased risk of recurrent MI.

Background Testosterone replacement therapy (TRT) prescriptions have increased several-fold in the last decade. There have been concerns regarding a possible increased incidence of DVT and pulmonary embolism (PE) with TRT. Few data support the association between TRT and DVT/PE. We evaluated the incidence of DVT and PE in men who were prescribed TRT for low serum total testosterone (sTT) levels. Methods This is a retrospective cohort study, conducted using data obtained from the Veterans Affairs Informatics and Computing Infrastructure. We compared the incidence of DVT/PE between those who received TRT and subsequently had normal on-treatment sTT levels (Gp1), those who received TRT but continued to have low on-treatment sTT (Gp2), and those who did not receive TRT (Gp3). Those with prior history of DVT/PE, cancer, hypercoagulable state, and chronic anticoagulation were excluded. Results The final cohort consisted of 71,407 subjects with low baseline sTT. Of these, 10,854 did not receive TRT (Gp3) and 60,553 received TRT. Of those who received TRT, 38,362 achieved normal sTT (Gp1) while 22,191 continued to have low sTT (Gp2). The incidence of DVT/PE was 0.5%, 0.4%, and 0.4% in Gp1, Gp2, and Gp3, respectively. Univariate, multivariate, and stabilized inverse probability of treatment weights analyses showed no statistically significant difference in DVT/PE-free survival between the various groups. Conclusions This study did not detect a significant association between testosterone replacement therapy and risk of DVT/PE in adult men with low sTT who were at low to moderate baseline risk of DVT/PE.

The role of vitamin D (vit-D) supplementation on the reduction of cardiovascular event and mortality remains controversial. Recent trials included patients with predominantly normal baseline 25-hydroxyvitamin D level (25-OHD) (≥20 ng/ml). Evidence in patients with low baseline levels regarding the

Objective: To examine the effect of cigarette smoking (CS) status and total testosterone (TT) levels after testosterone replacement therapy (TRT) on all-cause mortality, myocardial infarction (MI), and stroke in male smokers and nonsmokers without history of MI and stroke. Participants and Methods: Data from 18,055 males with known CS status and low TT levels who received TRT at the Veterans Health Administration between December 1, 1999, and May 31, 2014, were grouped into (1) current smokers with normalized TT, (2) current smokers with nonnormalized TT, (3) nonsmokers with normalized TT, and (4) nonsmokers with nonnormalized TT. Combined effect of CS status and TT level normalization after TRT on all-cause mortality, MI, and stroke was compared using propensity score–weighted Cox proportional hazard models. Results: Normalization of serum TT levels in nonsmokers was associated with a significant decrease in all-cause mortality (hazard ratio [HR]=0.526; 95% CI, 0.477-0.581; P

Summary Background While statins have shown antiviral effects in different studies, few data are available about their effect among different HCV genotypes. Aim To evaluate the effect of concomitant statin use on sustained virologic response (SVR) and other treatment outcomes among patients with HCV genotypes 1–3. Method Using US Department of Veterans Affairs database, multivariate (MV), propensity score matched (PSM) and repeated measures mixed model analyses were performed on patients who received combination therapy with Peg–IFN and Ribavirin for treatment of HCV genotypes 1–3 between October 2001–December 2011. Concomitant statin users were matched with non-users in each genotype and SVR rates were compared. Changes in serum ALT during treatment was assessed. Results Of 37,611 treated patients, 236 genotype 1 (GT1), 78 genotype 2 (GT2) and 23 genotype 3 (GT3) statin users and non-users were used for PSM. SVR among GT1 patients was 22.8% (overall), significantly higher among statin users (26.3% vs. 19.5% P P = 0.02 from MV). No significant impact of statin use was observed among GT2 (overall SVR – 55.8%, statin users vs. non-users – 53.9% vs. 57.7%, P = 0.32), and GT3 (overall SVR – 58.7%, statin users vs. non-users – 60.9% vs. 56.2%, P = 0.39) patients. Higher baseline LDL was positively associated with SVR while statin use reduced ALT during treatment in GT1 patients. Conclusion In view of additional benefits of statins, and the prohibitive cost of newer HCV therapies, statins could be a potential assist for hard-to-treat GT1 patients especially in resource-poor settings.

Aims There is a significant uncertainty regarding the effect of testosterone replacement therapy (TRT) on cardiovascular (CV) outcomes including myocardial infarction (MI) and stroke. The aim of this study was to examine the relationship between normalization of total testosterone (TT) after TRT and CV events as well as all-cause mortality in patients without previous history of MI and stroke. Methods and results We retrospectively examined 83 010 male veterans with documented low TT levels. The subjects were categorized into (Gp1: TRT with resulting normalization of TT levels), (Gp2: TRT without normalization of TT levels) and (Gp3: Did not receive TRT). By utilizing propensity score-weighted Cox proportional hazard models, the association of TRT with all-cause mortality, MI, stroke, and a composite endpoint was compared between these groups. The all-cause mortality [hazard ratio (HR): 0.44, confidence interval (CI) 0.42–0.46], risk of MI (HR: 0.76, CI 0.63–0.93), and stroke (HR: 0.64, CI 0.43–0.96) were significantly lower in Gp1 ( n = 43 931, median age = 66 years, mean follow-up = 6.2 years) vs. Gp3 ( n = 13 378, median age = 66 years, mean follow-up = 4.7 years) in propensity-matched cohort. Similarly, the all-cause mortality (HR: 0.53, CI 0.50–0.55), risk of MI (HR: 0.82, CI 0.71–0.95), and stroke (HR: 0.70, CI 0.51–0.96) were significantly lower in Gp1 vs. Gp2 ( n = 25 701, median age = 66 years, mean follow-up = 4.6 years). There was no difference in MI or stroke risk between Gp2 and Gp3. Conclusion In this large observational cohort with extended follow-up, normalization of TT levels after TRT was associated with a significant reduction in all-cause mortality, MI, and stroke.

Clinical studies suggest cardiovascular and renal benefits of ingesting small amounts of ethanol. Effects of ethanol, role of alcohol dehydrogenase (ADH) or of 20-hydroxyeicosatetraenoic acid (20-HETE) in podocytes of the glomerular filtration barrier have not been reported. We found that mouse podocytes at baseline generate 20-HETE and express ADH but not CYP2e1. Ethanol at high concentrations altered the actin cytoskeleton, induced CYP2e1, increased superoxide production and inhibited ADH gene expression. Ethanol at low concentrations upregulated the expression of ADH and CYP4a12a. 20-HETE, an arachidonic acid metabolite generated by CYP4a12a, blocked the ethanol-induced cytoskeletal derangement and superoxide generation. Ethanol at high concentration or ADH inhibitor increased glomerular albumin permeability in vitro. 20-HETE and its metabolite produced by ADH activity, 20-carboxy-arachidonic acid, protected the glomerular permeability barrier against an ADH inhibitor, puromycin or FSGS permeability factor. We conclude that ADH activity is required for glomerular function, 20-HETE is a physiological substrate of ADH in podocytes and that podocytes are useful biosensors to understand glomeruloprotective effects of ethanol.

Background Atrial fibrillation ( AF ) is the most common cardiac dysrhythmia associated with significant morbidity and mortality. Several small studies have reported that low serum total testosterone ( TT ) levels were associated with a higher incidence of AF . In contrast, it is also reported that anabolic steroid use is associated with an increase in the risk of AF . To date, no study has explored the effect of testosterone normalization on new incidence of AF after testosterone replacement therapy ( TRT ) in patients with low testosterone. Methods and Results Using data from the Veterans Administrations Corporate Data Warehouse, we identified a national cohort of 76 639 veterans with low TT levels and divided them into 3 groups. Group 1 had TRT resulting in normalization of TT levels (normalized TRT ), group 2 had TRT without normalization of TT levels (nonnormalized TRT ), and group 3 did not receive TRT (no TRT ). Propensity score–weighted stabilized inverse probability of treatment weighting Cox proportional hazard methods were used for analysis of the data from these groups to determine the association between post‐ TRT levels of TT and the incidence of AF . Group 1 (40 856 patients, median age 66 years) had significantly lower risk of AF than group 2 (23 939 patients, median age 65 years; hazard ratio 0.90, 95% CI 0.81–0.99, P =0.0255) and group 3 (11 853 patients, median age 67 years; hazard ratio 0.79, 95% CI 0.70–0.89, P =0.0001). There was no statistical difference between groups 2 and 3 (hazard ratio 0.89, 95% CI 0.78– 1.0009, P =0.0675) in incidence of AF . Conclusions These novel results suggest that normalization of TT levels after TRT is associated with a significant decrease in the incidence of AF .

Significant uncertainty exists surrounding adverse outcomes in patients receiving testosterone replacement therapy (TRT). We examined the incidence of recurrent myocardial infarction (MI) and all-cause mortality in patients with low total testosterone (TT) levels and a prior history of MI. We

Objective: Experiencing natural disasters such as hurricanes is associated with post-traumatic stress disorder (PTSD) and depression.We examined the role played by perceived stress and coping styles in explaining and modifying this association among pregnant women exposed to Hurricane Katrina.Design: The study comprised 192 women (133 from New Orleans and 59 from Baton Rouge) who were pregnant during Hurricane Katrina or became pregnant immediately after the hurricane. Women were interviewed regarding their hurricane experience, perceived stress, and mental health outcomes. Coping styles was assessed using the Brief COPE, PTSD symptoms using the Post-Traumatic Checklist, and depressive symptoms using the Edinburgh Depression Scale. Multivariable regression models were run to determine the effects of coping styles on mental health and the interactions among coping styles, hurricane experience, and perceived stress on mental health.Results: Apart from the positive reframing and humor coping styles, all coping styles correlated positively with PTSD or depression (p 0.05). The instrumental support, denial, venting, and behavioral disengagement coping styles were significantly associated with worsened PTSD symptoms among those who reported higher perceived stress (p 0.05). Use of a humor coping style seemed to reduce the effect of perceived stress on depressive symptoms (p = 0.02 for interaction) while use of instrumental support (p = 0.04) and behavioral disengagement (p 0.01) were both associated with more symptoms of depression among those who perceived more stress. There were no strong interactions between coping style and hurricane experience.Conclusion: Coping styles are potential moderators of the effects of stress on mental health of pregnant women.

Testosterone Replacement Therapy (TRT) prescriptions have increased 400% in the last decade. Concern over the risk of deep venous thrombosis (DVT) and pulmonary embolism (PE) with TRT has led the FDA to issue an alert. The association of TRT with DVT/PE is not clearly understood. The aim of this