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Sample records for 28-day all-cause mortality

  1. Structural pluralism and all-cause mortality.

    PubMed Central

    Young, F W; Lyson, T A

    2001-01-01

    OBJECTIVES: This study tested the hypothesis that "structural pluralism" reduces age-standardized mortality rates. Structural pluralism is defined as the potential for political competition in communities. METHODS: US counties were the units of analysis. Multiple regression techniques were used to test the hypothesis. RESULTS: Structural pluralism is a stronger determinant of lower mortality than any of the other variables examined--specifically, income, education, and medical facilities. CONCLUSIONS: These findings support the case for a new structural variable, pluralism, as a possible cause of lower mortality, and they indirectly support the significance of comparable ecologic dimensions, such as social trust. PMID:11189808

  2. Association Between Interstitial Lung Abnormalities and All-Cause Mortality

    PubMed Central

    Putman, Rachel K.; Hatabu, Hiroto; Araki, Tetsuro; Gudmundsson, Gunnar; Gao, Wei; Nishino, Mizuki; Okajima, Yuka; Dupuis, Josée; Latourelle, Jeanne C.; Cho, Michael H.; El-Chemaly, Souheil; Coxson, Harvey O.; Celli, Bartolome R.; Fernandez, Isis E.; Zazueta, Oscar E.; Ross, James C.; Harmouche, Rola; Estépar, Raúl San José; Diaz, Alejandro A.; Sigurdsson, Sigurdur; Gudmundsson, Elías F.; Eiríksdottír, Gudny; Aspelund, Thor; Budoff, Matthew J.; Kinney, Gregory L.; Hokanson, John E.; Williams, Michelle C; Murchison, John T.; MacNee, William; Hoffmann, Udo; O’Donnell, Christopher J.; Launer, Lenore J.; Harrris, Tamara B.; Gudnason, Vilmundur; Silverman, Edwin K.; O’Connor, George T.; Washko, George R.; Rosas, Ivan O.; Hunninghake, Gary M.

    2016-01-01

    IMPORTANCE Interstitial lung abnormalities have been associated with decreased six-minute walk distance, diffusion capacity for carbon monoxide and total lung capacity; however to our knowledge, an association with mortality has not been previously investigated. OBJECTIVE To investigate whether interstitial lung abnormalities are associated with increased mortality. DESIGN, SETTING, POPULATION Prospective cohort studies of 2633 participants from the Framingham Heart Study (FHS) (CT scans obtained 9/08–3/11), 5320 from the Age Gene/Environment Susceptibility (AGES)-Reykjavik (recruited 1/02–2/06), 2068 from COPDGene (recruited 11/07–4/10), and 1670 from the Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE) (between 12/05–12/06). EXPOSURES Interstitial lung abnormality status as determined by chest CT evaluation. MAIN OUTCOMES AND MEASURES All cause mortality over approximately 3 to 9 year median follow up time. Cause-of-death information was also examined in the AGES-Reykjavik cohort. RESULTS Interstitial lung abnormalities were present in 177 (7%) of the participants from FHS, 378 (7%) from AGES-Reykjavik, 156 (8%) from COPDGene, and in 157 (9%) from ECLIPSE. Over median follow-up times of ~3–9 years there were more deaths (and a greater absolute rate of mortality) among those with interstitial lung abnormalities compared to those without interstitial lung abnormalities in each cohort; 7% compared to 1% in FHS (6% difference, 95% confidence interval [CI] 2%, 10%), 56% compared to 33% in AGES-Reykjavik (23% difference, 95% CI 18%, 28%), 16% compared to 11% in COPDGene (5% difference, 95% CI −1%, 11%) and 11% compared to 5% in ECLIPSE (6% difference, 95% CI 1%, 11%). After adjustment for covariates, interstitial lung abnormalities were associated with an increase in the risk of death in the FHS (HR=2.7, 95% CI, 1.1–65, P=0.030), AGES-Reykjavik (HR 1.3, 95% CI 1.2–1.4, P<0.001), COPDGene (HR=1.8, 95% CI, 1.1, 2

  3. Adverse childhood experiences and premature all-cause mortality.

    PubMed

    Kelly-Irving, Michelle; Lepage, Benoit; Dedieu, Dominique; Bartley, Mel; Blane, David; Grosclaude, Pascale; Lang, Thierry; Delpierre, Cyrille

    2013-09-01

    Events causing stress responses during sensitive periods of rapid neurological development in childhood may be early determinants of all-cause premature mortality. Using a British birth cohort study of individuals born in 1958, the relationship between adverse childhood experiences (ACE) and mortality≤50 year was examined for men (n=7,816) and women (n=7,405) separately. ACE were measured using prospectively collected reports from parents and the school: no adversities (70%); one adversity (22%), two or more adversities (8%). A Cox regression model was carried out controlling for early life variables and for characteristics at 23 years. In men the risk of death was 57% higher among those who had experienced 2+ ACE compared to those with none (HR 1.57, 95% CI 1.13, 2.18, p=0.007). In women, a graded relationship was observed between ACE and mortality, the risk increasing as ACE accumulated. Women with one ACE had a 66% increased risk of death (HR 1.66, 95% CI 1.19, 2.33, p=0.003) and those with ≥2 ACE had an 80% increased risk (HR 1.80, 95% CI 1.10, 2.95, p=0.020) versus those with no ACE. Given the small impact of adult life style factors on the association between ACE and premature mortality, biological embedding during sensitive periods in early development is a plausible explanatory mechanism.

  4. The Gamma Gap and All-Cause Mortality

    PubMed Central

    Juraschek, Stephen P.; Moliterno, Alison R.; Checkley, William; Miller, Edgar R.

    2015-01-01

    Background The difference between total serum protein and albumin, i.e. the gamma gap, is a frequently used clinical screening measure for both latent infection and malignancy. However, there are no studies defining a positive gamma gap. Further, whether it is an independent risk factor of mortality is unknown. Methods and Findings This study examined the association between gamma gap, all-cause mortality, and specific causes of death (cardiovascular, cancer, pulmonary, or other) in 12,260 participants of the National Health and Nutrition Examination Survey (NHANES) from 1999–2004. Participants had a comprehensive metabolic panel measured, which was linked with vital status data from the National Death Index. Cause of death was based on ICD10 codes from death certificates. Analyses were performed with Cox proportional hazards models adjusted for mortality risk factors. The mean (SE) age was 46 (0.3) years and the mean gamma gap was 3.0 (0.01) g/dl. The population was 52% women and 10% black. During a median follow-up period of 4.8 years (IQR: 3.3 to 6.2 years), there were 723 deaths. The unadjusted 5-year cumulative incidences across quartiles of the gamma gap (1.7–2.7, 2.8–3.0, 3.1–3.2, and 3.3–7.9 g/dl) were 5.7%, 4.2%, 5.5%, and 7.8%. After adjustment for risk factors, participants with a gamma gap of ≥3.1 g/dl had a 30% higher risk of death compared to participants with a gamma gap <3.1 g/dl (HR: 1.30; 95%CI: 1.08, 1.55; P = 0.006). Gamma gap (per 1.0 g/dl) was most strongly associated with death from pulmonary causes (HR 2.22; 95%CI: 1.19, 4.17; P = 0.01). Conclusions The gamma gap is an independent risk factor for all-cause mortality at values as low as 3.1 g/dl (in contrast to the traditional definition of 4.0 g/dl), and is strongly associated with death from pulmonary causes. Future studies should examine the biologic pathways underlying these associations. PMID:26629820

  5. Body Mass Index (BMI) and All-Cause Mortality Pooling Project

    Cancer.gov

    The BMI and All-Cause Mortality Pooling Project quantified the risk associated with being overweight and the extent to which the relationship between BMI and all-cause mortality varies by certain factors.

  6. Dairy Food Intake and All-Cause, Cardiovascular Disease, and Cancer Mortality: The Golestan Cohort Study.

    PubMed

    Farvid, Maryam S; Malekshah, Akbar F; Pourshams, Akram; Poustchi, Hossein; Sepanlou, Sadaf G; Sharafkhah, Maryam; Khoshnia, Masoud; Farvid, Mojtaba; Abnet, Christian C; Kamangar, Farin; Dawsey, Sanford M; Brennan, Paul; Pharoah, Paul D; Boffetta, Paolo; Willett, Walter C; Malekzadeh, Reza

    2017-03-29

    We investigated the association between dairy product consumption and all-cause, cardiovascular disease (CVD), and cancer mortality in the Golestan Cohort Study, a prospective cohort study launched in January 2004 in Golestan Province, northeastern Iran. A total of 42,403 men and women participated in the study and completed a diet questionnaire at enrollment. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals. We documented 3,291 deaths (1,467 from CVD and 859 from cancer) during 11 years of follow-up (2004-2015). The highest quintile of total dairy product consumption (versus the lowest) was associated with 19% lower all-cause mortality risk (hazard ratio (HR) = 0.81, 95% confidence interval (CI): 0.72, 0.91; Ptrend = 0.006) and 28% lower CVD mortality risk (HR = 0.72, 95% CI: 0.60, 0.86; Ptrend = 0.005). High consumption of low-fat dairy food was associated with lower risk of all-cause (HR = 0.83, 95% CI: 0.73, 0.94; Ptrend = 0.002) and CVD (HR = 0.74, 95% CI: 0.61, 0.89; Ptrend = 0.001) mortality. We noted 11% lower all-cause mortality and 16% lower CVD mortality risk with high yogurt intake. Cheese intake was associated with 16% lower all-cause mortality and 26% lower CVD mortality risk. Higher intake of high-fat dairy food and milk was not associated with all-cause or CVD mortality. Neither intake of individual dairy products nor intake of total dairy products was significantly associated with overall cancer mortality. High consumption of dairy products, especially yogurt and cheese, may reduce the risk of overall and CVD mortality.

  7. High-Efficiency Postdilution Online Hemodiafiltration Reduces All-Cause Mortality in Hemodialysis Patients

    PubMed Central

    Moreso, Francesc; Pons, Mercedes; Ramos, Rosa; Mora-Macià, Josep; Carreras, Jordi; Soler, Jordi; Torres, Ferran; Campistol, Josep M.; Martinez-Castelao, Alberto

    2013-01-01

    Retrospective studies suggest that online hemodiafiltration (OL-HDF) may reduce the risk of mortality compared with standard hemodialysis in patients with ESRD. We conducted a multicenter, open-label, randomized controlled trial in which we assigned 906 chronic hemodialysis patients either to continue hemodialysis (n=450) or to switch to high-efficiency postdilution OL-HDF (n=456). The primary outcome was all-cause mortality, and secondary outcomes included cardiovascular mortality, all-cause hospitalization, treatment tolerability, and laboratory data. Compared with patients who continued on hemodialysis, those assigned to OL-HDF had a 30% lower risk of all-cause mortality (hazard ratio [HR], 0.70; 95% confidence interval [95% CI], 0.53–0.92; P=0.01), a 33% lower risk of cardiovascular mortality (HR, 0.67; 95% CI, 0.44–1.02; P=0.06), and a 55% lower risk of infection-related mortality (HR, 0.45; 95% CI, 0.21–0.96; P=0.03). The estimated number needed to treat suggested that switching eight patients from hemodialysis to OL-HDF may prevent one annual death. The incidence rates of dialysis sessions complicated by hypotension and of all-cause hospitalization were lower in patients assigned to OL-HDF. In conclusion, high-efficiency postdilution OL-HDF reduces all-cause mortality compared with conventional hemodialysis. PMID:23411788

  8. Prospective study of coffee consumption and all-cause, cancer, and cardiovascular mortality in Swedish women.

    PubMed

    Löf, Marie; Sandin, Sven; Yin, Li; Adami, Hans-Olov; Weiderpass, Elisabete

    2015-09-01

    We investigated whether coffee consumption was associated with all-cause, cancer, or cardiovascular mortality in a prospective cohort of 49,259 Swedish women. Of the 1576 deaths that occurred in the cohort, 956 were due to cancer and 158 were due to cardiovascular disease. We used Cox proportional hazard models with adjustment for potential confounders to estimate multivariable relative risks (RR) and 95 % confidence intervals (CI). Compared to a coffee consumption of 0-1 cups/day, the RR for all cause-mortality was 0.81 (95 % CI 0.69-0.94) for 2-5 cups/day and 0.88 (95 % CI 0.74-1.05) for >5 cups/day. Coffee consumption was not associated with cancer mortality or cardiovascular mortality when analyzed in the entire cohort. However, in supplementary analyses of women over 50 years of age, the RR for all cause-mortality was 0.74 (95 % CI 0.62-0.89) for 2-5 cups/day and 0.86 (95 % CI 0.70-1.06) for >5 cups/day when compared to 0-1 cups/day. In this same subgroup, the RRs for cancer mortality were 1.06 (95 % CI 0.81-1.38) for 2-5 cups/day and 1.40 (95 % CI 1.05-1.89) for >5 cups/day when compared to 0-1 cups/day. No associations between coffee consumption and all-cause mortality, cancer mortality, or cardiovascular mortality were observed among women below 50 years of age. In conclusion, higher coffee consumption was associated with lower all-cause mortality when compared to a consumption of 0-1 cups/day. Furthermore, coffee may have differential effects on mortality before and after 50 years of age.

  9. Raw Water Consumption Does Not Affect All-Cause or Cardiovascular Mortality: A Secondary Analysis.

    PubMed

    Loomba, Rohit S; Aggarwal, Saurabh; Arora, Rohit R

    Previous studies have examined water quality and its association with all-cause and cardiovascular mortality. However, there is a lack of data regarding association between the amount of water consumption and risk of mortality. We used the third National Health and Nutrition Examination Survey (NHANES III) database and its subsequent follow-up data. Only patients older than 45 years who reported amount of average water consumption and for whom follow-up mortality data were available were included in the study. Patients were stratified into following groups of average daily raw water consumption: (1) no water consumption, (2) ≤2 cups, (3) >2 to ≤ 4 cups, (4) >4 to ≤6 cups, (5) >6 to ≤8 cups, and (6) ≥8 cups. End points studied were all-cause mortality, ischemia-related mortality, congestive heart failure-related mortality, and stroke-related mortality. Baseline characteristics were compared using t tests and Mann-Whitney U tests. Odds ratios, 95% confidence intervals, and P values were calculated for univariate analysis using >6 cups to ≤8 cups of water a day group as reference. Multivariate analysis was then performed adjusting for various factors. P values of less than 0.05 were considered statistically significant. A total of 7666 patients were ultimately included in the study. Multivariate analysis demonstrated no significant differences in all-cause, ischemia-related, heart failure-related, or stroke-related mortality among various raw water intake groups when compared with the reference group. The significance noted for all-cause mortality in >2 glasses to ≤4 glasses a day group in the univariate analysis was not seen with multivariate analysis (odds ratio: 0.747; 95% confidence interval: 0.437-1.276; P = 0.285). Daily raw water consumption does not seem to impact all-cause mortality or cause-specific cardiovascular mortality.

  10. Red meat and processed meat consumption and all-cause mortality: a meta-analysis.

    PubMed

    Larsson, Susanna C; Orsini, Nicola

    2014-02-01

    High consumption of red meat and processed meat has been associated with increased risk of several chronic diseases. We conducted a meta-analysis to summarize the evidence from prospective studies on red meat and processed meat consumption in relationship to all-cause mortality. Pertinent studies were identified by searching PubMed through May 2013 and by reviewing the reference lists of retrieved articles. Prospective studies that reported relative risks with 95% confidence intervals for the association of red meat or processed meat consumption with all-cause mortality were eligible. Study-specific results were combined by using a random-effects model. Nine prospective studies were included in the meta-analysis. The summary relative risks of all-cause mortality for the highest versus the lowest category of consumption were 1.10 (95% confidence interval (CI): 0.98, 1.22; n = 6 studies) for unprocessed red meat, 1.23 (95% CI: 1.17, 1.28; n = 6 studies) for processed meat, and 1.29 (95% CI: 1.24, 1.35; n = 5 studies) for total red meat. In a dose-response meta-analysis, consumption of processed meat and total red meat, but not unprocessed red meat, was statistically significantly positively associated with all-cause mortality in a nonlinear fashion. These results indicate that high consumption of red meat, especially processed meat, may increase all-cause mortality.

  11. Associations between antioxidants and all-cause mortality among US adults with obstructive lung function

    PubMed Central

    Ford, Earl S.; Li, Chaoyang; Cunningham, Timothy J.; Croft, Janet B.

    2015-01-01

    Chronic obstructive pulmonary disease is characterised by oxidative stress, but little is known about the associations between antioxidant status and all-cause mortality in adults with this disease. The objective of the present study was to examine the prospective associations between concentrations of α- and β-carotene, β-cryptoxanthin, lutein/zeaxanthin, lycopene, Se, vitamin C and α-tocopherol and all-cause mortality among US adults with obstructive lung function. Data collected from 1492 adults aged 20–79 years with obstructive lung function in the National Health and Nutrition Examination Survey III (1988–94) were used. Through 2006, 629 deaths were identified during a median follow-up period of 14 years. After adjustment for demographic variables, the concentrations of the following antioxidants modelled as continuous variables were found to be inversely associated with all-cause mortality among adults with obstructive lung function: α-carotene (P=0.037); β-carotene (P=0.022); cryptoxanthin (P=0.022); lutein/zeaxanthin (P=0.004); total carotenoids (P=0.001); vitamin C (P<0.001). In maximally adjusted models, only the concentrations of lycopene (P=0.013) and vitamin C (P=0.046) were found to be significantly and inversely associated with all-cause mortality. No effect modification by sex was detected, but the association between lutein/zeaxanthin concentrations and all-cause mortality varied by smoking status (Pinteraction = 0.048). The concentrations of lycopene and vitamin C were inversely associated with all-cause mortality in this cohort of adults with obstructive lung function. PMID:25315508

  12. Cheese Consumption and Risk of All-Cause Mortality: A Meta-Analysis of Prospective Studies

    PubMed Central

    Tong, Xing; Chen, Guo-Chong; Zhang, Zheng; Wei, Yu-Lu; Xu, Jia-Ying; Qin, Li-Qiang

    2017-01-01

    The association between cheese consumption and risk for major health endpoints has been investigated in many epidemiologic studies, but findings are inconsistent. As all-cause mortality can be viewed as the final net health effect of dietary intakes, we conducted a meta-analysis to examine the long-term association of cheese consumption with all-cause mortality. Relevant studies were identified by a search of the PubMed database through May 2016. Reference lists from retrieved articles were also reviewed. Summary relative risks (RR) and 95% confidence intervals (CI) were calculated using a random-effects model. Pre-specified stratified and dose-response analyses were also performed. The final analysis included nine prospective cohort studies involving 21,365 deaths. The summary RR of all-cause mortality for the highest compared with the lowest cheese consumption was 1.02 (95% CI: 0.97, 1.06), and little evidence of heterogeneity was observed. The association between cheese consumption and risk of all-cause mortality did not significantly differ by study location, sex, age, number of events, study quality score or baseline diseases excluded. There was no dose-response relationship between cheese consumption and risk of all-cause mortality (RR per 43 g/day = 1.03, 95% CI: 0.99–1.07). No significant publication bias was observed. Our findings suggest that long-term cheese consumption was not associated with an increased risk of all-cause mortality. PMID:28098767

  13. Asymmetric dimethylarginine and all-cause mortality: a systematic review and meta-analysis

    PubMed Central

    Zhou, Shaoli; Zhu, Qianqian; Li, Xiang; Chen, Chaojin; Liu, Jiping; Ye, Yuping; Ruan, Ying; Hei, Ziqing

    2017-01-01

    Asymmetrical dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase (NOS), impairs the beneficial effect of NO. The predictive value of ADMA for all-cause mortality remains controversial, though it is important in the development of cardiovascular disease (CVD) and progression to dialysis in renal disease. This systematic review and meta-analysis was conducted to investigate the association between circulating ADMA and all-cause mortality. Studies with data pertinent to the association between circulating ADMA and all-cause mortality were reviewed and OR, HR or RR with 95% CI derived from multivariate Cox’s proportional-hazards analysis were extracted. A total of 34 studies reporting 39137 participants were included in final analysis. The results demonstrated that circulating ADMA was independently associated with all-cause mortality (RR = 1.27, 95% CI: 1.20–1.34). The association was still statistically significant in patients with pre-existing renal disease (RR = 1.30, 95% CI: 1.19–1.43) and pre-existing CVD (RR = 1.26, 95% CI: 1.16–1.37). In those without pre-existing renal or CVD, ADMA also predicted all-cause mortality (RR = 1.31, 95% CI: 1.13–1.53). The present study suggests a positive association of circulating ADMA with all-cause mortality. Further studies are needed to investigate the effects of interventions on ADMA, and the value of ADMA as a biomarker. PMID:28294182

  14. Risks of all-cause and suicide mortality in mental disorders: a meta-review

    PubMed Central

    Chesney, Edward; Goodwin, Guy M; Fazel, Seena

    2014-01-01

    A meta-review, or review of systematic reviews, was conducted to explore the risks of all-cause and suicide mortality in major mental disorders. A systematic search generated 407 relevant reviews, of which 20 reported mortality risks in 20 different mental disorders and included over 1.7 million patients and over a quarter of a million deaths. All disorders had an increased risk of all-cause mortality compared with the general population, and many had mortality risks larger than or comparable to heavy smoking. Those with the highest all-cause mortality ratios were substance use disorders and anorexia nervosa. These higher mortality risks translate into substantial (10-20 years) reductions in life expectancy. Borderline personality disorder, anorexia nervosa, depression and bipolar disorder had the highest suicide risks. Notable gaps were identified in the review literature, and the quality of the included reviews was typically low. The excess risks of mortality and suicide in all mental disorders justify a higher priority for the research, prevention, and treatment of the determinants of premature death in psychiatric patients. PMID:24890068

  15. The Effect of Neurobehavioral Test Performance on the All-Cause Mortality among US Population.

    PubMed

    Peng, Tao-Chun; Chen, Wei-Liang; Wu, Li-Wei; Chen, Ying-Jen; Liaw, Fang-Yih; Wang, Gia-Chi; Wang, Chung-Ching; Yang, Ya-Hui

    2016-01-01

    Evidence of the association between global cognitive function and mortality is much, but whether specific cognitive function is related to mortality is unclear. To address the paucity of knowledge on younger populations in the US, we analyzed the association between specific cognitive function and mortality in young and middle-aged adults. We analyzed data from 5,144 men and women between 20 and 59 years of age in the Third National Health and Nutrition Examination Survey (1988-94) with mortality follow-up evaluation through 2006. Cognitive function tests, including assessments of executive function/processing speed (symbol digit substitution) and learning recall/short-term memory (serial digit learning), were performed. All-cause mortality was the outcome of interest. After adjusting for multiple variables, total mortality was significantly higher in males with poorer executive function/processing speed (hazard ratio (HR) 2.02; 95% confidence interval 1.36 to 2.99) and poorer recall/short-term memory (HR 1.47; 95% confidence interval 1.02 to 2.12). After adjusting for multiple variables, the mortality risk did not significantly increase among the females in these two cognitive tests groups. In this sample of the US population, poorer executive function/processing speed and poorer learning recall/short-term memory were significantly associated with increased mortality rates, especially in males. This study highlights the notion that poorer specific cognitive function predicts all-cause mortality in young and middle-aged males.

  16. Weight change and all-cause mortality in older adults: A meta-analysis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This meta-analysis of observational cohort studies examined the association between weight change (weight loss, weight gain, and weight fluctuation) and all-cause mortality among older adults. We used PubMed (MEDLINE), Web of Science, and Cochrane Library to identify prospective studies published in...

  17. Consumption of whole grains in relation to mortality from all causes, cardiovascular disease, and diabetes

    PubMed Central

    Li, Bailing; Zhang, Guanxin; Tan, Mengwei; Zhao, Libo; Jin, Lei; Tang, Xiaojun; Jiang, Gengxi; Zhong, Keng

    2016-01-01

    Abstract Background: To investigate the correlation between consumption of whole grains and the risk of all-cause, cardiovascular disease (CVD), and diabetes-specific mortality according to a dose–response meta-analysis of prospective cohort studies. Methods: Observational cohort studies, which reported associations between whole grains and the risk of death outcomes, were identified by searching articles in the MEDLINE, EMBASE, and the reference lists of relevant articles. The search was up to November 30, 2015. Data extraction was performed by 2 independent investigators, and a consensus was reached with involvement of a third. Results: Ten prospective cohort studies (9 publications) were eligible in this meta-analysis. During follow-up periods ranging from 5.5 to 26 years, there were 92,647 deaths among 782,751 participants. Overall, a diet containing greater amounts of whole grains may be associated with a lower risk of all-cause, CVD-, and coronary heart disease (CHD)-specific mortality. The summary relative risks (RRs) were 0.93 (95% confidence intervals [CIs]: 0.91–0.95; Pheterogeneity < 0.001) for all-cause mortality, 0.95 (95% CIs: 0.92–0.98; Pheterogeneity < 0.001) for CVD-specific mortality, and 0.92 (95% CIs: 0.88–0.97; Pheterogeneity < 0.001) for CHD-specific mortality for an increment of 1 serving (30 g) a day of whole grain intake. The combined estimates were robust across subgroup and sensitivity analyses. Higher consumption of whole grains was not appreciably associated with risk of mortality from stroke and diabetes. Conclusion: Evidence from observational cohort studies indicates inverse associations of intake of whole grains with risk of mortality from all-cause, CVD, and CHD. However, no associations with risk of deaths from stroke and diabetes were observed. PMID:27537552

  18. Predictive Value of Cumulative Blood Pressure for All-Cause Mortality and Cardiovascular Events.

    PubMed

    Wang, Yan Xiu; Song, Lu; Xing, Ai Jun; Gao, Ming; Zhao, Hai Yan; Li, Chun Hui; Zhao, Hua Ling; Chen, Shuo Hua; Lu, Cheng Zhi; Wu, Shou Ling

    2017-02-07

    The predictive value of cumulative blood pressure (BP) on all-cause mortality and cardiovascular and cerebrovascular events (CCE) has hardly been studied. In this prospective cohort study including 52,385 participants from the Kailuan Group who attended three medical examinations and without CCE, the impact of cumulative systolic BP (cumSBP) and cumulative diastolic BP (cumDBP) on all-cause mortality and CCEs was investigated. For the study population, the mean (standard deviation) age was 48.82 (11.77) years of which 40,141 (76.6%) were male. The follow-up for all-cause mortality and CCEs was 3.96 (0.48) and 2.98 (0.41) years, respectively. Multivariate Cox proportional hazards regression analysis showed that for every 10 mm Hg·year increase in cumSBP and 5 mm Hg·year increase in cumDBP, the hazard ratio for all-cause mortality were 1.013 (1.006, 1.021) and 1.012 (1.006, 1.018); for CCEs, 1.018 (1.010, 1.027) and 1.017 (1.010, 1.024); for stroke, 1.021 (1.011, 1.031) and 1.018 (1.010, 1.026); and for MI, 1.013 (0.996, 1.030) and 1.015 (1.000, 1.029). Using natural spline function analysis, cumSBP and cumDBP showed a J-curve relationship with CCEs; and a U-curve relationship with stroke (ischemic stroke and hemorrhagic stroke). Therefore, increases in cumSBP and cumDBP were predictive for all-cause mortality, CCEs, and stroke.

  19. Effect of Online Hemodiafiltration on All-Cause Mortality and Cardiovascular Outcomes

    PubMed Central

    Grooteman, Muriel P.C.; van den Dorpel, Marinus A.; Bots, Michiel L.; Penne, E. Lars; van der Weerd, Neelke C.; Mazairac, Albert H.A.; den Hoedt, Claire H.; van der Tweel, Ingeborg; Lévesque, Renée; Nubé, Menso J.; ter Wee, Piet M.

    2012-01-01

    In patients with ESRD, the effects of online hemodiafiltration on all-cause mortality and cardiovascular events are unclear. In this prospective study, we randomly assigned 714 chronic hemodialysis patients to online postdilution hemodiafiltration (n=358) or to continue low-flux hemodialysis (n=356). The primary outcome measure was all-cause mortality. The main secondary endpoint was a composite of major cardiovascular events, including death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, therapeutic coronary intervention, therapeutic carotid intervention, vascular intervention, or amputation. After a mean 3.0 years of follow-up (range, 0.4–6.6 years), we did not detect a significant difference between treatment groups with regard to all-cause mortality (121 versus 127 deaths per 1000 person-years in the online hemodiafiltration and low-flux hemodialysis groups, respectively; hazard ratio, 0.95; 95% confidence interval, 0.75–1.20). The incidences of cardiovascular events were 127 and 116 per 1000 person-years, respectively (hazard ratio, 1.07; 95% confidence interval, 0.83–1.39). Receiving high-volume hemodiafiltration during the trial associated with lower all-cause mortality, a finding that persisted after adjusting for potential confounders and dialysis facility. In conclusion, this trial did not detect a beneficial effect of hemodiafiltration on all-cause mortality and cardiovascular events compared with low-flux hemodialysis. On-treatment analysis suggests the possibility of a survival benefit among patients who receive high-volume hemodiafiltration, although this subgroup finding requires confirmation. PMID:22539829

  20. Symmetric Dimethylarginine as Predictor of Graft loss and All-Cause Mortality in Renal Transplant Recipients

    PubMed Central

    Pihlstrøm, Hege; Mjøen, Geir; Dahle, Dag Olav; Pilz, Stefan; Midtvedt, Karsten; März, Winfried; Abedini, Sadollah; Holme, Ingar; Fellström, Bengt; Jardine, Alan; Holdaas, Hallvard

    2014-01-01

    Background Elevated symmetric dimethylarginine (SDMA) has been shown to predict cardiovascular events and all cause mortality in diverse populations. The potential role of SDMA as a risk marker in renal transplant recipients (RTR) has not been investigated. Methods We analyzed SDMA in the placebo arm of the Assessment of Lescol in Renal Transplantation study, a randomized controlled trial of fluvastatin in RTR. Mean follow-up was 5.1 years. Patients were grouped into quartiles based on SDMA levels at study inclusion. Relationships between SDMA and traditional risk factors for graft function and all-cause mortality were analyzed in 925 RTR using univariate and multivariate survival analyses. Results In univariate analysis, SDMA was significantly associated with renal graft loss, all-cause death, and major cardiovascular events. After adjustment for established risk factors including estimated glomerular filtration rate, an elevated SDMA-level (4th quartile, >1.38 μmol/L) was associated with renal graft loss; hazard ratio (HR), 5.51; 95% confidence interval (CI), 1.95–15.57; P=0.001, compared to the 1st quartile. Similarly, SDMA in the 4th quartile was independently associated with all-cause mortality (HR, 4.56; 95% CI, 2.15–9.71; P<0.001), and there was a strong borderline significant trend for an association with cardiovascular mortality (HR, 2.86; 95% CI, 0.99–8.21; P=0.051). Conclusion In stable RTR, an elevated SDMA level is independently associated with increased risk of all-cause mortality and renal graft loss. PMID:24999963

  1. Predictive Value of Cumulative Blood Pressure for All-Cause Mortality and Cardiovascular Events

    NASA Astrophysics Data System (ADS)

    Wang, Yan Xiu; Song, Lu; Xing, Ai Jun; Gao, Ming; Zhao, Hai Yan; Li, Chun Hui; Zhao, Hua Ling; Chen, Shuo Hua; Lu, Cheng Zhi; Wu, Shou Ling

    2017-02-01

    The predictive value of cumulative blood pressure (BP) on all-cause mortality and cardiovascular and cerebrovascular events (CCE) has hardly been studied. In this prospective cohort study including 52,385 participants from the Kailuan Group who attended three medical examinations and without CCE, the impact of cumulative systolic BP (cumSBP) and cumulative diastolic BP (cumDBP) on all-cause mortality and CCEs was investigated. For the study population, the mean (standard deviation) age was 48.82 (11.77) years of which 40,141 (76.6%) were male. The follow-up for all-cause mortality and CCEs was 3.96 (0.48) and 2.98 (0.41) years, respectively. Multivariate Cox proportional hazards regression analysis showed that for every 10 mm Hg·year increase in cumSBP and 5 mm Hg·year increase in cumDBP, the hazard ratio for all-cause mortality were 1.013 (1.006, 1.021) and 1.012 (1.006, 1.018); for CCEs, 1.018 (1.010, 1.027) and 1.017 (1.010, 1.024); for stroke, 1.021 (1.011, 1.031) and 1.018 (1.010, 1.026); and for MI, 1.013 (0.996, 1.030) and 1.015 (1.000, 1.029). Using natural spline function analysis, cumSBP and cumDBP showed a J-curve relationship with CCEs; and a U-curve relationship with stroke (ischemic stroke and hemorrhagic stroke). Therefore, increases in cumSBP and cumDBP were predictive for all-cause mortality, CCEs, and stroke.

  2. Effect of online hemodiafiltration on all-cause mortality and cardiovascular outcomes.

    PubMed

    Grooteman, Muriel P C; van den Dorpel, Marinus A; Bots, Michiel L; Penne, E Lars; van der Weerd, Neelke C; Mazairac, Albert H A; den Hoedt, Claire H; van der Tweel, Ingeborg; Lévesque, Renée; Nubé, Menso J; ter Wee, Piet M; Blankestijn, Peter J

    2012-06-01

    In patients with ESRD, the effects of online hemodiafiltration on all-cause mortality and cardiovascular events are unclear. In this prospective study, we randomly assigned 714 chronic hemodialysis patients to online postdilution hemodiafiltration (n=358) or to continue low-flux hemodialysis (n=356). The primary outcome measure was all-cause mortality. The main secondary endpoint was a composite of major cardiovascular events, including death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, therapeutic coronary intervention, therapeutic carotid intervention, vascular intervention, or amputation. After a mean 3.0 years of follow-up (range, 0.4-6.6 years), we did not detect a significant difference between treatment groups with regard to all-cause mortality (121 versus 127 deaths per 1000 person-years in the online hemodiafiltration and low-flux hemodialysis groups, respectively; hazard ratio, 0.95; 95% confidence interval, 0.75-1.20). The incidences of cardiovascular events were 127 and 116 per 1000 person-years, respectively (hazard ratio, 1.07; 95% confidence interval, 0.83-1.39). Receiving high-volume hemodiafiltration during the trial associated with lower all-cause mortality, a finding that persisted after adjusting for potential confounders and dialysis facility. In conclusion, this trial did not detect a beneficial effect of hemodiafiltration on all-cause mortality and cardiovascular events compared with low-flux hemodialysis. On-treatment analysis suggests the possibility of a survival benefit among patients who receive high-volume hemodiafiltration, although this subgroup finding requires confirmation.

  3. Predictive Value of Cumulative Blood Pressure for All-Cause Mortality and Cardiovascular Events

    PubMed Central

    Wang, Yan Xiu; Song, Lu; Xing, Ai Jun; Gao, Ming; Zhao, Hai Yan; Li, Chun Hui; Zhao, Hua Ling; Chen, Shuo Hua; Lu, Cheng Zhi; Wu, Shou Ling

    2017-01-01

    The predictive value of cumulative blood pressure (BP) on all-cause mortality and cardiovascular and cerebrovascular events (CCE) has hardly been studied. In this prospective cohort study including 52,385 participants from the Kailuan Group who attended three medical examinations and without CCE, the impact of cumulative systolic BP (cumSBP) and cumulative diastolic BP (cumDBP) on all-cause mortality and CCEs was investigated. For the study population, the mean (standard deviation) age was 48.82 (11.77) years of which 40,141 (76.6%) were male. The follow-up for all-cause mortality and CCEs was 3.96 (0.48) and 2.98 (0.41) years, respectively. Multivariate Cox proportional hazards regression analysis showed that for every 10 mm Hg·year increase in cumSBP and 5 mm Hg·year increase in cumDBP, the hazard ratio for all-cause mortality were 1.013 (1.006, 1.021) and 1.012 (1.006, 1.018); for CCEs, 1.018 (1.010, 1.027) and 1.017 (1.010, 1.024); for stroke, 1.021 (1.011, 1.031) and 1.018 (1.010, 1.026); and for MI, 1.013 (0.996, 1.030) and 1.015 (1.000, 1.029). Using natural spline function analysis, cumSBP and cumDBP showed a J-curve relationship with CCEs; and a U-curve relationship with stroke (ischemic stroke and hemorrhagic stroke). Therefore, increases in cumSBP and cumDBP were predictive for all-cause mortality, CCEs, and stroke. PMID:28167816

  4. Statin Use Reduces Prostate Cancer All-Cause Mortality: A Nationwide Population-Based Cohort Study.

    PubMed

    Sun, Li-Min; Lin, Ming-Chia; Lin, Cheng-Li; Chang, Shih-Ni; Liang, Ji-An; Lin, I-Ching; Kao, Chia-Hung

    2015-09-01

    Studies have suggested that statin use is related to cancer risk and prostate cancer mortality. We conducted a population-based cohort study to determine whether using statins in prostate cancer patients is associated with reduced all-cause mortality rates. Data were obtained from the Taiwan National Health Insurance Research Database. The study cohort comprised 5179 patients diagnosed with prostate cancer who used statins for at least 6 months between January 1, 1998 and December 31, 2010. To form a comparison group, each patient was randomly frequency-matched (according to age and index date) with a prostate cancer patient who did not use any type of statin-based drugs during the study period. The study endpoint was mortality. The hazard ratio (HR) and 95% confidence interval (CI) were estimated using Cox regression models. Among prostate cancer patients, statin use was associated with significantly decreased all-cause mortality (adjusted HR = 0.65; 95% CI = 0.60-0.71). This phenomenon was observed among various types of statin, age groups, and treatment methods. Analyzing the defined daily dose of statins indicated that both low- and high-dose groups exhibited significantly decreased death rates compared with nonusers, suggesting a dose-response relationship. The results of this population-based cohort study suggest that using statins reduces all-cause mortality among prostate cancer patients, and a dose-response relationship may exist.

  5. Are psychosocial stressors associated with the relationship of alcohol consumption and all-cause mortality?

    PubMed Central

    2014-01-01

    Background Several studies have shown a protective association of moderate alcohol intake with mortality. However, it remains unclear whether this relationship could be due to misclassification confounding. As psychosocial stressors are among those factors that have not been sufficiently controlled for, we assessed whether they may confound the relationship between alcohol consumption and all-cause mortality. Methods Three cross-sectional MONICA surveys (conducted 1984–1995) including 11,282 subjects aged 25–74 years were followed up within the framework of KORA (Cooperative Health Research in the Region of Augsburg), a population-based cohort, until 2002. The prevalences of diseases as well as of lifestyle, clinical and psychosocial variables were compared in different alcohol consumption categories. To assess all-cause mortality risks, hazard ratios (HRs) were estimated by Cox proportional hazards models which included lifestyle, clinical and psychosocial variables. Results Diseases were more prevalent among non-drinkers than among drinkers: Moreover, non-drinkers showed a higher percentage of an unfavourable lifestyle and were more affected with psychosocial stressors at baseline. Multivariable-adjusted HRs for moderate alcohol consumption versus no consumption were 0.74 (95% confidence interval (CI): 0.58-0.94) in men and 0.87 (95% CI: 0.66-1.16) in women. In men, moderate drinkers had a significantly lower all-cause mortality risk than non-drinkers or heavy drinkers (p = 0.002) even after multivariable adjustment. In women, moderate alcohol consumption was not associated with lowered risk of death from all causes. Conclusions The present study confirmed the impact of sick quitters on mortality risk, but failed to show that the association between alcohol consumption and mortality is confounded by psychosocial stressors. PMID:24708657

  6. Renal Function and All-Cause Mortality Risk Among Cancer Patients.

    PubMed

    Yang, Yan; Li, Hui-Yan; Zhou, Qian; Peng, Zhen-Wei; An, Xin; Li, Wei; Xiong, Li-Ping; Yu, Xue-Qing; Jiang, Wen-Qi; Mao, Hai-Ping

    2016-05-01

    Renal dysfunction predicts all-cause mortality in general population. However, the prevalence of renal insufficiency and its relationship with mortality in cancer patients are unclear.We retrospectively studied 9465 patients with newly diagnosed cancer from January 2010 to December 2010. Renal insufficiency was defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m using the Chronic Kidney Disease Epidemiology Collaboration equation. The hazard ratio (HR) of all-cause mortality associated with baseline eGFR was assessed by Cox regression.Three thousand sixty-nine patients (32.4%) exhibited eGFR <90 mL/min/1.73 m and 3% had abnormal serum creatinine levels at the time of diagnosis. Over a median follow-up of 40.5 months, 2705 patients (28.6%) died. Compared with the reference group (eGFR ≥ 60 mL/min/1.73 m), an elevated all-cause mortality was observed among patients with eGFR < 60 mL/min/1.73 m stratified by cancer stage in the entire cohort, the corresponding hazard ratios were 1.87 (95% CI, 1.41-2.47) and 1.28 (95% CI, 1.01-1.62) for stage I to III and stage IV, respectively. However, this relationship was not observed after multivariate adjustment. Subgroup analysis found that eGFR < 60 mL/min/1.73 m independently predicted death among patients with hematologic (adjusted HR 2.93, 95% CI [1.36-6.31]) and gynecological cancer (adjusted HR 2.82, 95% CI [1.19-6.70]), but not in those with other cancer. Five hundred fifty-seven patients (6%) had proteinuria. When controlled for potential confounding factors, proteinuria was a risk factor for all-cause mortality among patients in the entire cohort, regardless of cancer stage and eGFR values. When patients were categorized by specific cancer type, the risk of all-cause death was only significant in patients with digestive system cancer (adjusted HR, 1.85 [1.48-2.32]).The prevalence of renal dysfunction was common in patients with newly diagnosed cancer. Patients with eGFR < 60 m

  7. Prediction of risk of diabetic retinopathy for all-cause mortality, stroke and heart failure

    PubMed Central

    Zhu, Xiao-Rong; Zhang, Yong-Peng; Bai, Lu; Zhang, Xue-Lian; Zhou, Jian-Bo; Yang, Jin-Kui

    2017-01-01

    Abstract To examine and quantify the potential relation between diabetic retinopathy (DR) and risk of all-cause mortality, stroke and heart failure (HF). The resources of meta-analysis of epidemiological observational studies were from Pub-med, EMBASE, CINAHL, Cochrane Library, conference, and proceedings. Random/fixed effects models were used to calculate pooled subgroup analysis stratified by different grades of DR was performed to explore the potential source of heterogeneity. Statistical manipulations were undertaken using program STATA. Of the included 25 studies, comprising 142,625 participants, 19 studies were concluded to find the relation of DR to all-cause mortality, 5 for stroke, and 3 for HF. Risk ratio (RR) for all-cause mortality with the presence of DR was 2.33 (95% CI 1.92–2.81) compared with diabetic individuals without DR. Evidences showed a higher risk of all-cause mortality associated with DR in patients with T2D or T1D (RR 2.25, 95% CI 1.91–2.65. RR 2.68, 95% CI 1.34–5.36). According to different grades of DR in patients with T2D, RR for all-cause mortality varied, the risk of nonproliferative diabetic retinopathy (NPDR) was 1.38 (1.11–1.70), while the risk of proliferative diabetic retinopathy (PDR) was 2.32 (1.75–3.06). There was no evidence of significant heterogeneity (Cochran Q test P = 0.29 vs 0.26, I2 = 19.6% vs 22.6%, respectively). Data from 5 studies in relation to DR and the risk of stroke showed that DR was significantly associated with increased risk of stroke (RR = 1.74, 95%CI: 1.35–2.24), compared with patients without DR. Furthermore, DR (as compared with individuals without DR) was associated with a marginal increased risk of HF in patients with diabetes mellitus (DM) (n = 3 studies; RR 2.24, 95% CI 0.98–5.14, P = 0.056). Our results showed that DR increased the risk of all-cause mortality, regardless of the different stages, compared with the diabetic individuals without DR. DR predicted

  8. Severe Hypoglycemia and Cardiovascular or All-Cause Mortality in Patients with Type 2 Diabetes

    PubMed Central

    Cha, Seon-Ah; Yun, Jae-Seung; Lim, Tae-Seok; Hwang, Seawon; Yim, Eun-Jung; Song, Ki-Ho; Yoo, Ki-Dong; Park, Yong-Moon; Ahn, Yu-Bae

    2016-01-01

    Background We investigated the association between severe hypoglycemia (SH) and the risk of cardiovascular (CV) or all-cause mortality in patients with type 2 diabetes. Methods The study included 1,260 patients aged 25 to 75 years with type 2 diabetes from the Vincent Type 2 Diabetes Resgistry (VDR), who consecutively enrolled (n=1,260) from January 2000 to December 2010 and were followed up until May 2015 with a median follow-up time of 10.4 years. Primary outcomes were death from any cause or CV death. We investigated the association between the CV or all-cause mortality and various covariates using Cox proportional hazards regression analysis. Results Among the 906 participants (71.9%) who completed follow-up, 85 patients (9.4%) had at least one episode of SH, and 86 patients (9.5%) died (9.1 per 1,000 patient-years). Patients who had died were older, had a longer duration of diabetes and hypertension, received more insulin, and had more diabetic microvascular complications at baseline, as compared with surviving patients. The experience of SH was significantly associated with an increased risk of all-cause mortality (hazard ratio [HR], 2.64; 95% confidence interval [CI], 1.39 to 5.02; P=0.003) and CV mortality (HR, 6.34; 95% CI, 2.02 to 19.87; P=0.002) after adjusting for sex, age, diabetic duration, hypertension, mean glycosylated hemoglobin levels, diabetic nephropathy, lipid profiles, and insulin use. Conclusion We found a strong association between SH and increased risk of all-cause and CV mortality in patients with type 2 diabetes. PMID:27098504

  9. Traffic air pollution and mortality from cardiovascular disease and all causes: a Danish cohort study

    PubMed Central

    2012-01-01

    Background Traffic air pollution has been linked to cardiovascular mortality, which might be due to co-exposure to road traffic noise. Further, personal and lifestyle characteristics might modify any association. Methods We followed up 52 061 participants in a Danish cohort for mortality in the nationwide Register of Causes of Death, from enrollment in 1993–1997 through 2009, and traced their residential addresses from 1971 onwards in the Central Population Registry. We used dispersion-modelled concentration of nitrogen dioxide (NO2) since 1971 as indicator of traffic air pollution and used Cox regression models to estimate mortality rate ratios (MRRs) with adjustment for potential confounders. Results Mean levels of NO2 at the residence since 1971 were significantly associated with mortality from cardiovascular disease (MRR, 1.26; 95% confidence interval [CI], 1.06–1.51, per doubling of NO2 concentration) and all causes (MRR, 1.13; 95% CI, 1.04–1.23, per doubling of NO2 concentration) after adjustment for potential confounders. For participants who ate < 200 g of fruit and vegetables per day, the MRR was 1.45 (95% CI, 1.13–1.87) for mortality from cardiovascular disease and 1.25 (95% CI, 1.11–1.42) for mortality from all causes. Conclusions Traffic air pollution is associated with mortality from cardiovascular diseases and all causes, after adjustment for traffic noise. The association was strongest for people with a low fruit and vegetable intake. PMID:22950554

  10. Oral health in relation to all-cause mortality: the IPC cohort study.

    PubMed

    Adolph, Margaux; Darnaud, Christelle; Thomas, Frédérique; Pannier, Bruno; Danchin, Nicolas; Batty, G David; Bouchard, Philippe

    2017-03-15

    We evaluated the association between oral health and mortality. The study population comprised 76,188 subjects aged 16-89 years at recruitment. The mean follow-up time was 3.4 ± 2.4 years. Subjects with a personal medical history of cancer or cardiovascular disease and death by casualty were excluded from the analysis. A full-mouth clinical examination was performed in order to assess dental plaque, dental calculus and gingival inflammation. The number of teeth and functional masticatory units <5 were recorded. Causes of death were ascertained from death certificates. Mortality risk was evaluated using Cox regression model with propensity score calibrated for each oral exposure. All-cause mortality risk were raised with dental plaque, gingival inflammation, >10 missing teeth and functional masticatory units <5. All-cancer mortality was positively associated with dental plaque and gingival inflammation. Non-cardiovascular and non-cancer mortality were also positively associated with high dental plaque (HR = 3.30, [95% CI: 1.76-6.17]), high gingival inflammation (HR = 2.86, [95% CI: 1.71-4.79]), >10 missing teeth (HR = 2.31, [95% CI: 1.40-3.82]) and functional masticatory units <5 (HR = 2.40 [95% CI 1.55-3.73]). Moreover, when ≥3 oral diseases were cumulated in the model, the risk increased for all-cause mortality (HR = 3.39, [95% CI: 2.51-5.42]), all-cancer mortality (HR = 3.59, [95% CI: 1.23-10.05]) and non-cardiovascular and non-cancer mortality (HR = 4.71, [95% CI: 1.74-12.7]). The present study indicates a postive linear association between oral health and mortality.

  11. Oral health in relation to all-cause mortality: the IPC cohort study

    PubMed Central

    Adolph, Margaux; Darnaud, Christelle; Thomas, Frédérique; Pannier, Bruno; Danchin, Nicolas; Batty, G. David; Bouchard, Philippe

    2017-01-01

    We evaluated the association between oral health and mortality. The study population comprised 76,188 subjects aged 16–89 years at recruitment. The mean follow-up time was 3.4 ± 2.4 years. Subjects with a personal medical history of cancer or cardiovascular disease and death by casualty were excluded from the analysis. A full-mouth clinical examination was performed in order to assess dental plaque, dental calculus and gingival inflammation. The number of teeth and functional masticatory units <5 were recorded. Causes of death were ascertained from death certificates. Mortality risk was evaluated using Cox regression model with propensity score calibrated for each oral exposure. All-cause mortality risk were raised with dental plaque, gingival inflammation, >10 missing teeth and functional masticatory units <5. All-cancer mortality was positively associated with dental plaque and gingival inflammation. Non-cardiovascular and non-cancer mortality were also positively associated with high dental plaque (HR = 3.30, [95% CI: 1.76–6.17]), high gingival inflammation (HR = 2.86, [95% CI: 1.71–4.79]), >10 missing teeth (HR = 2.31, [95% CI: 1.40–3.82]) and functional masticatory units <5 (HR = 2.40 [95% CI 1.55–3.73]). Moreover, when ≥3 oral diseases were cumulated in the model, the risk increased for all-cause mortality (HR = 3.39, [95% CI: 2.51–5.42]), all-cancer mortality (HR = 3.59, [95% CI: 1.23–10.05]) and non-cardiovascular and non-cancer mortality (HR = 4.71, [95% CI: 1.74–12.7]). The present study indicates a postive linear association between oral health and mortality. PMID:28294149

  12. Association between inflammatory biomarkers and all-cause, cardiovascular and cancer-related mortality

    PubMed Central

    Singh-Manoux, Archana; Shipley, Martin J.; Bell, Joshua A.; Canonico, Marianne; Elbaz, Alexis; Kivimäki, Mika

    2017-01-01

    BACKGROUND: The inflammatory biomarker α1-acid glycoprotein (AGP) was found to have the strongest association with 5-year mortality in a recent study of 106 biomarkers. We examined whether AGP is a better biomarker of mortality risk than the more widely used inflammatory biomarkers interleukin-6 (IL-6) and C-reactive protein (CRP). METHODS: We analyzed data for 6545 men and women aged 45–69 (mean 55.7) years from the Whitehall II cohort study. We assayed AGP, IL-6 and CRP levels from fasting serum samples collected in 1997–1999. Mortality followup was until June 2015. Cox regression analysis was used to model associations of inflammatory biomarkers with all-cause, cardiovascular and cancer-related mortality. RESULTS: Over the mean follow-up of 16.7 years, 736 deaths occurred, of which 181 were from cardiovascular disease and 347 from cancer. In the model adjusted for all covariates (age, sex, socioeconomic status, body mass index, health behaviours and chronic disease), AGP did not predict mortality beyond the first 5 years of follow-up; over this period, IL-6 and CRP had stronger associations with mortality. When we considered all covariates and biomarkers simultaneously, AGP no longer predicted all-cause mortality over the entire follow-up period (adjusted hazard ratio [HR] 0.99, 95% confidence interval [CI] 0.90–1.08). Only IL-6 predicted all-cause mortality (adjusted HR 1.22, 95% CI 1.12–1.33) and cancer-related mortality (adjusted HR 1.13, 95% CI 1.00–1.29) over the entire follow-up period, whereas CRP predicted only cardiovascular mortality (adjusted HR 1.30, 95% CI 1.06–1.61). INTERPRETATION: Our findings suggest that AGP is not a better marker of short-or long-term mortality risk than the more commonly used biomarkers IL-6 and CRP. PMID:27895145

  13. All-cause mortality risk in elderly individuals with disabilities: a retrospective observational study

    PubMed Central

    Wu, Li-Wei; Chen, Wei-Liang; Peng, Tao-Chun; Chiang, Sheng-Ta; Yang, Hui-Fang; Sun, Yu-Shan; Chan, James Yi-Hsin; Kao, Tung-Wei

    2016-01-01

    Objectives Disability is considered an important issue that affects the elderly population. This study aimed to explore the relationship between disability and all-cause mortality in US elderly individuals. Design Retrospective and longitudinal designs. Setting Data from the National Health and Nutrition Examination Survey (NHANES 1999–2002) conducted by the National Center for Health Statistics of the Centers for Disease Control and Prevention. Participants A total of 1834 participants in the age range 60–84 years from NHANES 1999–2002. Main outcome measures We acquired five major domains of disability (activities of daily living (ADL), general physical activities (GPA), instrumental ADL (IADL), lower extremity mobility (LEM) and leisure and social activities (LSA)) through self-reporting. We applied an extended-model approach with Cox (proportional hazards) regression analysis to investigate the relationship between different features of disability and all-cause mortality risk in the study population. Results During a mean follow-up of 5.7 years, 77 deaths occurred. An increased risk of all-cause mortality was identified in elderly individuals with disability after adjustment for potential confounders (HR 2.23; 95% CI 1.29 to 3.85; p=0.004). Participants with more than one domain of disability were associated with a higher risk of mortality (ptrend=0.047). Adjusted HRs and 95% CIs for each domain of disability were 2.53 (1.49 to 4.31), 1.99 (0.93 to 4.29), 1.74 (0.72 to 4.16), 1.57 (0.76 to 3.27) and 1.52 (0.93 to 2.48) for LEM, LSA, ADL, IADL and GPA, respectively. Conclusions The results of this study support an increased association between disability and all-cause mortality in the elderly in the USA. Disability in LEM may be a good predictor of high risk of all-cause mortality in elderly subjects. PMID:27625055

  14. Daily Sitting Time and All-Cause Mortality: A Meta-Analysis

    PubMed Central

    Chau, Josephine Y.; Grunseit, Anne C.; Chey, Tien; Stamatakis, Emmanuel; Brown, Wendy J.; Matthews, Charles E.; Bauman, Adrian E.; van der Ploeg, Hidde P.

    2013-01-01

    Objective To quantify the association between daily total sitting and all-cause mortality risk and to examine dose-response relationships with and without adjustment for moderate-to-vigorous physical activity. Methods Studies published from 1989 to January 2013 were identified via searches of multiple databases, reference lists of systematic reviews on sitting and health, and from authors’ personal literature databases. We included prospective cohort studies that had total daily sitting time as a quantitative exposure variable, all-cause mortality as the outcome and reported estimates of relative risk, or odds ratios or hazard ratios with 95% confidence intervals. Two authors independently extracted the data and summary estimates of associations were computed using random effects models. Results Six studies were included, involving data from 595,086 adults and 29,162 deaths over 3,565,569 person-years of follow-up. Study participants were mainly female, middle-aged or older adults from high-income countries; mean study quality score was 12/15 points. Associations between daily total sitting time and all-cause mortality were not linear. With physical activity adjustment, the spline model of best fit had dose-response HRs of 1.00 (95% CI: 0.98-1.03), 1.02 (95% CI: 0.99-1.05) and 1.05 (95% CI: 1.02-1.08) for every 1-hour increase in sitting time in intervals between 0-3, >3-7 and >7 h/day total sitting, respectively. This model estimated a 34% higher mortality risk for adults sitting 10 h/day, after taking physical activity into account. The overall weighted population attributable fraction for all-cause mortality for total daily sitting time was 5.9%, after adjusting for physical activity. Conclusions Higher amounts of daily total sitting time are associated with greater risk of all-cause mortality and moderate-to-vigorous physical activity appears to attenuate the hazardous association. These findings provide a starting point for identifying a threshold on which

  15. Fitness vs. fatness on all-cause mortality: a meta-analysis.

    PubMed

    Barry, Vaughn W; Baruth, Meghan; Beets, Michael W; Durstine, J Larry; Liu, Jihong; Blair, Steven N

    2014-01-01

    The purpose of this study was to quantify the joint association of cardiorespiratory fitness (CRF) and weight status on mortality from all causes using meta-analytical methodology. Studies were included if they were (1) prospective, (2) objectively measured CRF and body mass index (BMI), and (3) jointly assessed CRF and BMI with all-cause mortality. Ten articles were included in the final analysis. Pooled hazard ratios were assessed for each comparison group (i.e. normal weight-unfit, overweight-unfit and -fit, and obese-unfit and -fit) using a random-effects model. Compared to normal weight-fit individuals, unfit individuals had twice the risk of mortality regardless of BMI. Overweight and obese-fit individuals had similar mortality risks as normal weight-fit individuals. Furthermore, the obesity paradox may not influence fit individuals. Researchers, clinicians, and public health officials should focus on physical activity and fitness-based interventions rather than weight-loss driven approaches to reduce mortality risk.

  16. Heat-Related Mortality in India: Excess All-Cause Mortality Associated with the 2010 Ahmedabad Heat Wave

    PubMed Central

    Azhar, Gulrez Shah; Mavalankar, Dileep; Nori-Sarma, Amruta; Rajiva, Ajit; Dutta, Priya; Jaiswal, Anjali; Sheffield, Perry; Knowlton, Kim; Hess, Jeremy J.; Azhar, Gulrez Shah; Deol, Bhaskar; Bhaskar, Priya Shekhar; Hess, Jeremy; Jaiswal, Anjali; Khosla, Radhika; Knowlton, Kim; Mavalankar, Mavalankar; Rajiva, Ajit; Sarma, Amruta; Sheffield, Perry

    2014-01-01

    Introduction In the recent past, spells of extreme heat associated with appreciable mortality have been documented in developed countries, including North America and Europe. However, far fewer research reports are available from developing countries or specific cities in South Asia. In May 2010, Ahmedabad, India, faced a heat wave where the temperatures reached a high of 46.8°C with an apparent increase in mortality. The purpose of this study is to characterize the heat wave impact and assess the associated excess mortality. Methods We conducted an analysis of all-cause mortality associated with a May 2010 heat wave in Ahmedabad, Gujarat, India, to determine whether extreme heat leads to excess mortality. Counts of all-cause deaths from May 1–31, 2010 were compared with the mean of counts from temporally matched periods in May 2009 and 2011 to calculate excess mortality. Other analyses included a 7-day moving average, mortality rate ratio analysis, and relationship between daily maximum temperature and daily all-cause death counts over the entire year of 2010, using month-wise correlations. Results The May 2010 heat wave was associated with significant excess all-cause mortality. 4,462 all-cause deaths occurred, comprising an excess of 1,344 all-cause deaths, an estimated 43.1% increase when compared to the reference period (3,118 deaths). In monthly pair-wise comparisons for 2010, we found high correlations between mortality and daily maximum temperature during the locally hottest “summer” months of April (r = 0.69, p<0.001), May (r = 0.77, p<0.001), and June (r = 0.39, p<0.05). During a period of more intense heat (May 19–25, 2010), mortality rate ratios were 1.76 [95% CI 1.67–1.83, p<0.001] and 2.12 [95% CI 2.03–2.21] applying reference periods (May 12–18, 2010) from various years. Conclusion The May 2010 heat wave in Ahmedabad, Gujarat, India had a substantial effect on all-cause excess mortality, even in this city where hot

  17. Alcohol, drinking pattern and all-cause, cardiovascular and alcohol-related mortality in Eastern Europe.

    PubMed

    Bobak, Martin; Malyutina, Sofia; Horvat, Pia; Pajak, Andrzej; Tamosiunas, Abdonas; Kubinova, Ruzena; Simonova, Galina; Topor-Madry, Roman; Peasey, Anne; Pikhart, Hynek; Marmot, Michael G

    2016-01-01

    Alcohol has been implicated in the high mortality in Central and Eastern Europe but the magnitude of its effect, and whether it is due to regular high intake or episodic binge drinking remain unclear. The aim of this paper was to estimate the contribution of alcohol to mortality in four Central and Eastern European countries. We used data from the Health, Alcohol and Psychosocial factors in Eastern Europe is a prospective multi-centre cohort study in Novosibirsk (Russia), Krakow (Poland), Kaunas (Lithuania) and six Czech towns. Random population samples of 34,304 men and women aged 45-69 years in 2002-2005 were followed up for a median 7 years. Drinking volume, frequency and pattern were estimated from the graduated frequency questionnaire. Deaths were ascertained using mortality registers. In 230,246 person-years of follow-up, 2895 participants died from all causes, 1222 from cardiovascular diseases (CVD), 672 from coronary heart disease (CHD) and 489 from pre-defined alcohol-related causes (ARD). In fully-adjusted models, abstainers had 30-50% increased mortality risk compared to light-to-moderate drinkers. Adjusted hazard ratios (HR) in men drinking on average ≥60 g of ethanol/day (3% of men) were 1.23 (95% CI 0.95-1.59) for all-cause, 1.38 (0.95-2.02) for CVD, 1.64 (1.02-2.64) for CHD and 2.03 (1.28-3.23) for ARD mortality. Corresponding HRs in women drinking on average ≥20 g/day (2% of women) were 1.92 (1.25-2.93), 1.74 (0.76-3.99), 1.39 (0.34-5.76) and 3.00 (1.26-7.10). Binge drinking increased ARD mortality in men only. Mortality was associated with high average alcohol intake but not binge drinking, except for ARD in men.

  18. All-Cause and Cause-Specific Mortality Associated with Bariatric Surgery: A Review

    PubMed Central

    Mehta, Tapan S.; Davidson, Lance E.; Hunt, Steven C.

    2016-01-01

    The question of whether or not nonsurgical intentional or voluntary weight loss results in reduced mortality has been equivocal, with long-term mortality following weight loss being reported as increased, decreased, and not changed. In part, inconsistent results have been attributed to the uncertainty of whether the intentionality of weight loss is accurately reported in large population studies and also that achieving significant and sustained voluntary weight loss in large intervention trials is extremely difficult. Bariatric surgery has generally been free of these conflicts. Patients voluntarily undergo surgery and the resulting weight is typically significant and sustained. These elements, combined with possible non-weight loss-related mechanisms, have resulted in improved comorbidities, which likely contribute to a reduction in longterm mortality. This paper reviews the association between bariatric surgery and long-term mortality. From these studies, the general consensus is that bariatric surgical patients have: 1) significantly reduced long-term all-cause mortality when compared to severely obese non-bariatric surgical control groups; 2) greater mortality when compared to the general population, with the exception of one study; 3) reduced cardiovascular-, stroke-, and cancer-caused mortality when compared to severely obese non-operated controls; and 4) increased risk for externally caused death such as suicide. PMID:26496931

  19. Vitamin D status and incident cardiovascular disease and all-cause mortality: a general population study.

    PubMed

    Skaaby, Tea; Husemoen, Lise Lotte Nystrup; Pisinger, Charlotta; Jørgensen, Torben; Thuesen, Betina Heinsbæk; Fenger, Mogens; Linneberg, Allan

    2013-06-01

    Low vitamin D status has been associated with cardiovascular disease (CVD) and mortality primarily in selected groups, smaller studies, or with self-reported vitamin D intake. We investigated the association of serum vitamin D status with the incidence of a registry-based diagnosis of ischemic heart disease (IHD), stroke, and all-cause mortality in a large sample of the general population. A total of 9,146 individuals from the two population-based studies, Monica10 and Inter99, were included. Measurements of serum 25-hydroxyvitamin D at baseline were carried out using the IDS ISYS immunoassay system in Monica10 and High-performance liquid chromatography in Inter99. Information on CVDs and causes of death was obtained from Danish registries until 31 December 2008. There were 478 cases of IHD, 316 cases of stroke, and 633 deaths during follow-up (mean follow-up 10 years). Cox regression analyses with age as underlying time axis showed a significant association between vitamin D status and all-cause mortality with a HR = 0.95 (P = 0.005) per 10 nmol/l higher vitamin D level. We found no association between vitamin D status and incidence of IHD or stroke (HR = 1.01, P = 0.442 and HR = 1.00, P = 0.920, respectively). In this large general population study, the observed inverse association between serum vitamin D status and all-cause mortality was not explained by a similar inverse association with IHD or stroke.

  20. Joint associations of alcohol consumption and physical activity with all-cause and cardiovascular mortality.

    PubMed

    Soedamah-Muthu, Sabita S; De Neve, Melissa; Shelton, Nicola J; Tielemans, Susanne M A J; Stamatakis, Emmanuel

    2013-08-01

    Individual associations of alcohol consumption and physical activity with cardiovascular disease are relatively established, but the joint associations are not clear. Therefore, the aim of this study was to examine prospectively the joint associations between alcohol consumption and physical activity with cardiovascular mortality (CVM) and all-cause mortality. Four population-based studies in the United Kingdom were included, the 1997 and 1998 Health Surveys for England and the 1998 and 2003 Scottish Health Surveys. In men and women, respectively, low physical activity was defined as 0.1 to 5 and 0.1 to 4 MET-hours/week and high physical activity as ≥5 and ≥4 MET-hours/week. Moderate or moderately high alcohol intake was defined as >0 to 35 and >0 to 21 units/week and high levels of alcohol intake as >35 and >21 units/week. In total, there were 17,410 adults without prevalent cardiovascular diseases and complete data on alcohol and physical activity (43% men, median age 55 years). During a median follow-up period of 9.7 years, 2,204 adults (12.7%) died, 638 (3.7%) with CVM. Cox proportional-hazards models were adjusted for potential confounders such as marital status, social class, education, ethnicity, and longstanding illness. In the joint associations analysis, low activity combined with high levels of alcohol (CVM: hazard ratio [HR] 1.95, 95% confidence interval [CI] 1.28 to 2.96, p = 0.002; all-cause mortality: HR 1.64, 95% CI 1.32 to 2.03, p <0.001) and low activity combined with no alcohol (CVM: HR 1.93, 95% CI 1.35 to 2.76, p <0.001; all-cause mortality: HR 1.50, 95% CI 1.24 to 1.81, p <0.001) were linked to the highest risk, compared with moderate drinking and higher levels of physical activity. Within each given alcohol group, low activity was linked to increased CVM risk (e.g., HR 1.48, 95% CI 1.08 to 2.03, p = 0.014, for the moderate drinking group), but in the presence of high physical activity, high alcohol intake was not linked to increased CVM

  1. Association between domains of physical activity and all-cause, cardiovascular and cancer mortality.

    PubMed

    Autenrieth, Christine S; Baumert, Jens; Baumeister, Sebastian E; Fischer, Beate; Peters, Annette; Döring, Angela; Thorand, Barbara

    2011-02-01

    Few studies have investigated the independent effects of domain-specific physical activity on mortality. We sought to investigate the association of physical activity performed in different domains of daily living on all-cause, cardiovascular (CVD) and cancer mortality. Using a prospective cohort design, 4,672 men and women, aged 25-74 years, who participated in the baseline examination of the MONICA/KORA Augsburg Survey 1989/1990 were classified according to their activity level (no, light, moderate, vigorous). Domains of self-reported physical activity (work, transportation, household, leisure time) and total activity were assessed by the validated MOSPA (MONICA Optional Study on Physical Activity) questionnaire. After a median follow-up of 17.8 years, a total of 995 deaths occurred, with 452 from CVD and 326 from cancer. For all-cause mortality, hazard ratios and 95% confidence interval (HR, 95% CI) of the highly active versus the inactive reference group were 0.69 (0.48-1.00) for work, 0.48 (0.36-0.65) for leisure time, and 0.73 (0.59-0.90) for total activity after multivariable adjustments. Reduced risks of CVD mortality were observed for high levels of work (0.54, 0.31-0.93), household (0.80, 0.54-1.19), leisure time (0.50, 0.31-0.79) and total activity (0.75, 0.55-1.03). Leisure time (0.36, 0.23-0.59) and total activity (0.62, 0.43-0.88) were associated with reduced risks of cancer mortality. Light household activity was related to lower all-cause (0.82, 0.71-0.95) and CVD (0.72, 0.58-0.89) mortality. No clear effects were found for transportation activities. Our findings suggest that work, household, leisure time and total physical activity, but not transportation activity, may protect from premature mortality.

  2. Predicting all-cause mortality from basic physiology in the Framingham Heart Study.

    PubMed

    Zhang, William B; Pincus, Zachary

    2016-02-01

    Using longitudinal data from a cohort of 1349 participants in the Framingham Heart Study, we show that as early as 28-38 years of age, almost 10% of variation in future lifespan can be predicted from simple clinical parameters. Specifically, we found diastolic and systolic blood pressure, blood glucose, weight, and body mass index (BMI) to be relevant to lifespan. These and similar parameters have been well-characterized as risk factors in the relatively narrow context of cardiovascular disease and mortality in middle to old age. In contrast, we demonstrate here that such measures can be used to predict all-cause mortality from mid-adulthood onward. Further, we find that different clinical measurements are predictive of lifespan in different age regimes. Specifically, blood pressure and BMI are predictive of all-cause mortality from ages 35 to 60, while blood glucose is predictive from ages 57 to 73. Moreover, we find that several of these parameters are best considered as measures of a rate of 'damage accrual', such that total historical exposure, rather than current measurement values, is the most relevant risk factor (as with pack-years of cigarette smoking). In short, we show that simple physiological measurements have broader lifespan-predictive value than indicated by previous work and that incorporating information from multiple time points can significantly increase that predictive capacity. In general, our results apply equally to both men and women, although some differences exist.

  3. Gender differences and disparities in all-cause and coronary heart disease mortality: epidemiological aspects

    PubMed Central

    Barrett-Connor, Elizabeth

    2013-01-01

    This overview is primarily concerned with large recent prospective cohort studies of adult populations, not patients, because the latter studies are confounded by differences in medical and surgical management for men vs. women. When early papers are uniquely informative they are also included. Because the focus is on epidemiology, details of age, sex, sample size, and source as well as study methods are provided. Usually the primary outcomes were all-cause or coronary heart disease (CHD) mortality using baseline data from midlife or older adults. Fifty years ago few prospective cohort studies of all-cause or CHD mortality included women. Most epidemiologic studies that included community-dwelling adults did not include both sexes and still do not report men and women separately. Few studies consider both sex (biology) and gender (behavior and environment) differences. Lifespan studies describing survival after live birth are not considered here. The important effects of prenatal and early childhood biologic and behavioral factors on adult mortality are beyond the scope of this review. Clinical trials are not discussed. Overall, presumptive evidence for causality was equivalent for psychosocial and biological exposures, and these attributes were often associated with each other. Inconsistencies or gaps were particularly obvious for studies of sex or gender differences in age and optimal measures of body size for CHD outcomes, and in the striking interface of diabetes and people with the metabolic syndrome, most of whom have unrecognized diabetes. PMID:24054926

  4. Relation of aortic valve calcium detected by cardiac computed tomography to all-cause mortality.

    PubMed

    Blaha, Michael J; Budoff, Matthew J; Rivera, Juan J; Khan, Atif N; Santos, Raul D; Shaw, Leslee J; Raggi, Paolo; Berman, Daniel; Rumberger, John A; Blumenthal, Roger S; Nasir, Khurram

    2010-12-15

    Aortic valve calcium (AVC) can be quantified on the same computed tomographic scan as coronary artery calcium (CAC). Although CAC is an established predictor of cardiovascular events, limited evidence is available for an independent predictive value for AVC. We studied a cohort of 8,401 asymptomatic subjects (mean age 53 ± 10 years, 69% men), who were free of known coronary heart disease and were undergoing electron beam computed tomography for assessment of subclinical atherosclerosis. The patients were followed for a median of 5 years (range 1 to 7) for the occurrence of mortality from any cause. Multivariate Cox regression models were developed to predict all-cause mortality according to the presence of AVC. A total of 517 patients (6%) had AVC on electron beam computed tomography. During follow-up, 124 patients died (1.5%), for an overall survival rate of 96.1% and 98.7% for those with and without AVC, respectively (hazard ratio 3.39, 95% confidence interval 2.09 to 5.49). After adjustment for age, gender, hypertension, dyslipidemia, diabetes mellitus, smoking, and a family history of premature coronary heart disease, AVC remained a significant predictor of mortality (hazard ratio 1.82, 95% confidence interval 1.11 to 2.98). Likelihood ratio chi-square statistics demonstrated that the addition of AVC contributed significantly to the prediction of mortality in a model adjusted for traditional risk factors (chi-square = 5.03, p = 0.03) as well as traditional risk factors plus the presence of CAC (chi-square = 3.58, p = 0.05). In conclusion, AVC was associated with increased all-cause mortality, independent of the traditional risk factors and the presence of CAC.

  5. Racial-ethnic differences in all-cause and HIV mortality, Florida, 2000–2011

    PubMed Central

    Trepka, Mary Jo; Fennie, Kristopher P.; Sheehan, Diana M.; Niyonsenga, Theophile; Lieb, Spencer; Maddox, Lorene M.

    2016-01-01

    Purpose We compared all-cause and human immunodeficiency virus (HIV) mortality in a population-based, HIV-infected cohort. Methods Using records of people diagnosed with HIV during 2000–2009 from the Florida Enhanced HIV/Acquired Immunodeficiency Syndrome (AIDS) Reporting System, we conducted a proportional hazards analysis for all-cause mortality and a competing risk analysis for HIV mortality through 2011 controlling for individual level factors, neighborhood poverty, and rural/urban status and stratifying by concurrent AIDS status (AIDS within 3 months of HIV diagnosis). Results Of 59,880 HIV-infected people, 32.2% had concurrent AIDS, and 19.3% died. Adjusting for period of diagnosis, age group, sex, country of birth, HIV transmission mode, area level poverty and rural/urban status, non-Hispanic Black (NHB) and Hispanic people had an elevated adjusted hazards ratio (aHR) for HIV mortality relative to non-Hispanic whites (NHB concurrent AIDS: aHR 1.34, 95% CI 1.23–1.47; NHB without concurrent AIDS: aHR 1.41, 95% CI 1.26–1.57; Hispanic concurrent AIDS: aHR 1.18, 95% CI 1.05–1.32; Hispanic without concurrent AIDS: aHR 1.18, 95% CI 1.03–1.36). Conclusions Considering competing causes of death, NHB and Hispanic people had a higher risk of HIV mortality even among those without concurrent AIDS, indicating a need to identify and address barriers to HIV care in these populations. PMID:26948103

  6. Social isolation, loneliness, and all-cause mortality in older men and women.

    PubMed

    Steptoe, Andrew; Shankar, Aparna; Demakakos, Panayotes; Wardle, Jane

    2013-04-09

    Both social isolation and loneliness are associated with increased mortality, but it is uncertain whether their effects are independent or whether loneliness represents the emotional pathway through which social isolation impairs health. We therefore assessed the extent to which the association between social isolation and mortality is mediated by loneliness. We assessed social isolation in terms of contact with family and friends and participation in civic organizations in 6,500 men and women aged 52 and older who took part in the English Longitudinal Study of Ageing in 2004-2005. A standard questionnaire measure of loneliness was administered also. We monitored all-cause mortality up to March 2012 (mean follow-up 7.25 y) and analyzed results using Cox proportional hazards regression. We found that mortality was higher among more socially isolated and more lonely participants. However, after adjusting statistically for demographic factors and baseline health, social isolation remained significantly associated with mortality (hazard ratio 1.26, 95% confidence interval, 1.08-1.48 for the top quintile of isolation), but loneliness did not (hazard ratio 0.92, 95% confidence interval, 0.78-1.09). The association of social isolation with mortality was unchanged when loneliness was included in the model. Both social isolation and loneliness were associated with increased mortality. However, the effect of loneliness was not independent of demographic characteristics or health problems and did not contribute to the risk associated with social isolation. Although both isolation and loneliness impair quality of life and well-being, efforts to reduce isolation are likely to be more relevant to mortality.

  7. Association of All-Cause Mortality With Overweight and Obesity Using Standard Body Mass Index Categories

    PubMed Central

    Flegal, Katherine M.; Kit, Brian K.; Orpana, Heather; Graubard, Barry I.

    2016-01-01

    Importance Estimates of the relative mortality risks associated with normal weight, overweight, and obesity may help to inform decision making in the clinical setting. Objective To perform a systematic review of reported hazard ratios (HRs) of all-cause mortality for overweight and obesity relative to normal weight in the general population. Data Sources PubMed and EMBASE electronic databases were searched through September 30, 2012, without language restrictions. Study Selection Articles that reported HRs for all-cause mortality using standard body mass index (BMI) categories from prospective studies of general populations of adults were selected by consensus among multiple reviewers. Studies were excluded that used nonstandard categories or that were limited to adolescents or to those with specific medical conditions or to those undergoing specific procedures. PubMed searches yielded 7034 articles, of which 141 (2.0%) were eligible. An EMBASE search yielded 2 additional articles. After eliminating overlap, 97 studies were retained for analysis, providing a combined sample size of more than 2.88 million individuals and more than 270 000 deaths. Data Extraction Data were extracted by 1 reviewer and then reviewed by 3 independent reviewers. We selected the most complex model available for the full sample and used a variety of sensitivity analyses to address issues of possible overadjustment (adjusted for factors in causal pathway) or underadjustment (not adjusted for at least age, sex, and smoking). Results Random-effects summary all-cause mortality HRs for overweight (BMI of 25–<30), obesity (BMI of ≥30), grade 1 obesity (BMI of 30–<35), and grades 2 and 3 obesity (BMI of ≥35) were calculated relative to normal weight (BMI of 18.5–<25). The summary HRs were 0.94 (95% CI, 0.91–0.96) for overweight, 1.18 (95% CI, 1.12–1.25) for obesity (all grades combined), 0.95 (95% CI, 0.88–1.01) for grade 1 obesity, and 1.29 (95% CI, 1.18–1.41) for grades 2 and

  8. Association of TSH Elevation with All-Cause Mortality in Elderly Patients with Chronic Kidney Disease

    PubMed Central

    Chuang, Mei-hsing; Liao, Kuo-Meng; Hung, Yao-Min; Chou, Yi-Chang; Chou, Pesus

    2017-01-01

    Chronic kidney disease (CKD) is a widespread condition in the global population and is more common in the elderly. Thyroid-stimulating hormone (TSH) level increases with aging, and hypothyroidism is highly prevalent in CKD patients. However, the relationship between low thyroid function and mortality in CKD patients is unclear. Therefore, we conducted a retrospective cohort study to examine the relationship between TSH elevation and all-cause mortality in elderly patients with CKD. This retrospective cohort study included individuals ≥65 years old with CKD (n = 23,786) in Taipei City. Health examination data from 2005 to 2010 were provided by the Taipei Databank for Public Health Analysis. Subjects were categorized according to thyroid-stimulating hormone (TSH) level as follows: low normal (0.34mortality was evaluated using a Cox proportional hazard regression model adjusted for sex, age, hypertension, diabetes mellitus, CKD stage, serum albumin, high-density lipoprotein cholesterol, uric acid, hemoglobin, body mass index, glutamic-pyruvic transaminase, smoking, alcohol consumption, and history of cardiovascular disease (coronary artery disease, congestive heart failure, cerebral vascular disease), history of cancer, and history of chronic obstructive pulmonary disease. Our results showed that compared to the reference group (middle normal TSH), the risk of all-cause mortality was increased in the elevated I group (hazard ratio [HR], 1.21; 95% confidence interval [CI], 1.02–1.45) and elevated II group (HR, 1.30; 95% CI, 1.00–1.69). We found a significant association between TSH elevation and all-cause mortality in this cohort of elderly persons with CKD. However, determining the benefit of treatment for moderately elevated TSH level (5.2–10 mIU/L) in elderly patients with CKD will require a

  9. Association of TSH Elevation with All-Cause Mortality in Elderly Patients with Chronic Kidney Disease.

    PubMed

    Chuang, Mei-Hsing; Liao, Kuo-Meng; Hung, Yao-Min; Chou, Yi-Chang; Chou, Pesus

    2017-01-01

    Chronic kidney disease (CKD) is a widespread condition in the global population and is more common in the elderly. Thyroid-stimulating hormone (TSH) level increases with aging, and hypothyroidism is highly prevalent in CKD patients. However, the relationship between low thyroid function and mortality in CKD patients is unclear. Therefore, we conducted a retrospective cohort study to examine the relationship between TSH elevation and all-cause mortality in elderly patients with CKD. This retrospective cohort study included individuals ≥65 years old with CKD (n = 23,786) in Taipei City. Health examination data from 2005 to 2010 were provided by the Taipei Databank for Public Health Analysis. Subjects were categorized according to thyroid-stimulating hormone (TSH) level as follows: low normal (0.34mortality was evaluated using a Cox proportional hazard regression model adjusted for sex, age, hypertension, diabetes mellitus, CKD stage, serum albumin, high-density lipoprotein cholesterol, uric acid, hemoglobin, body mass index, glutamic-pyruvic transaminase, smoking, alcohol consumption, and history of cardiovascular disease (coronary artery disease, congestive heart failure, cerebral vascular disease), history of cancer, and history of chronic obstructive pulmonary disease. Our results showed that compared to the reference group (middle normal TSH), the risk of all-cause mortality was increased in the elevated I group (hazard ratio [HR], 1.21; 95% confidence interval [CI], 1.02-1.45) and elevated II group (HR, 1.30; 95% CI, 1.00-1.69). We found a significant association between TSH elevation and all-cause mortality in this cohort of elderly persons with CKD. However, determining the benefit of treatment for moderately elevated TSH level (5.2-10 mIU/L) in elderly patients with CKD will require a well

  10. Effect of Ezetimibe on Major Atherosclerotic Disease Events and All-Cause Mortality

    PubMed Central

    Hayek, Sami; Escaro, Fabrizio Canepa; Sattar, Assad; Gamalski, Steven; Wells, Karen E.; Divine, George; Ahmedani, Brian K.; Lanfear, David E.; Pladevall, Manel; Williams, L. Keoki

    2012-01-01

    Despite ezetimibe’s ability to reduce serum cholesterol levels, there are concerns over its vascular effects and whether it prevents or ameliorates atherosclerotic disease (AD). Our objective was to estimate the effect of ezetimibe use on major AD events and all-cause mortality and to compare these associations to those observed for hydroxy-methylglutaryl-CoA reductase inhibitor (i.e., statin) use. We identified 367 new ezetimibe users between November 1, 2002 and December 31, 2009. These individuals were ≥18 years of age and had no prior statin use. One to four statin user matches were identified for each ezetimibe user resulting in a total of 1,238 closely matched statin users. Pharmacy data and drug dosage information were used to estimate a moving window of ezetimibe and statin exposure for each day of study follow-up. The primary outcome was a composite of major AD events (coronary heart disease, cerebrovascular disease, and peripheral vascular disease events) and all-cause death. Both ezetimibe use (odds ratio [OR] 0.33, 95% CI 0.13–0.86) and statin use (OR 0.61, 95% CI 0.36–1.04) were associated with reductions in the likelihood of the composite outcome. These protective associations were most significant for cerebrovascular disease events and all-cause death. Subgroup analyses by sex, race-ethnicity, prior history of AD, diabetes status, and estimated renal function showed consistent estimates across strata with no significant differences between ezetimibe and statin use. In conclusion, ezetimibe appeared to have a protective effect on major AD events and all-cause death which was not significantly different from that observed for statin use. PMID:23219178

  11. Effect of ezetimibe on major atherosclerotic disease events and all-cause mortality.

    PubMed

    Hayek, Sami; Canepa Escaro, Fabrizio; Sattar, Assad; Gamalski, Steven; Wells, Karen E; Divine, George; Ahmedani, Brian K; Lanfear, David E; Pladevall, Manel; Williams, L Keoki

    2013-02-15

    Despite ezetimibe's ability to reduce serum cholesterol levels, there are concerns over its vascular effects and whether it prevents or ameliorates atherosclerotic disease (AD). The aims of this study were to estimate the effect of ezetimibe use on major AD events and all-cause mortality and to compare these associations to those observed for hydroxymethylglutaryl coenzyme A reductase inhibitor (statin) use. A total of 367 new ezetimibe users were identified from November 1, 2002, to December 31, 2009. These subjects were aged ≥18 years and had no previous statin use. One to 4 statin user matches were identified for each ezetimibe user, resulting in a total of 1,238 closely matched statin users. Pharmacy data and drug dosage information were used to estimate a moving window of ezetimibe and statin exposure for each day of study follow-up. The primary outcome was a composite of major AD events (coronary heart disease, cerebrovascular disease, and peripheral vascular disease events) and all-cause death. Ezetimibe use (odds ratio 0.33, 95% confidence interval 0.13 to 0.86) and statin use (odds ratio 0.61, 95% confidence interval 0.36 to 1.04) were associated with reductions in the likelihood of the composite outcome. These protective associations were most significant for cerebrovascular disease events and all-cause death. Subgroup analyses by gender, race or ethnicity, history of AD, diabetes status, and estimated renal function showed consistent estimates across strata, with no significant differences between ezetimibe and statin use. In conclusion, ezetimibe appeared to have a protective effect on major AD events and all-cause death that was not significantly different from that observed for statin use.

  12. DNA methylation signatures in peripheral blood strongly predict all-cause mortality

    PubMed Central

    Zhang, Yan; Wilson, Rory; Heiss, Jonathan; Breitling, Lutz P.; Saum, Kai-Uwe; Schöttker, Ben; Holleczek, Bernd; Waldenberger, Melanie; Peters, Annette; Brenner, Hermann

    2017-01-01

    DNA methylation (DNAm) has been revealed to play a role in various diseases. Here we performed epigenome-wide screening and validation to identify mortality-related DNAm signatures in a general population-based cohort with up to 14 years follow-up. In the discovery panel in a case-cohort approach, 11,063 CpGs reach genome-wide significance (FDR<0.05). 58 CpGs, mapping to 38 well-known disease-related genes and 14 intergenic regions, are confirmed in a validation panel. A mortality risk score based on ten selected CpGs exhibits strong association with all-cause mortality, showing hazard ratios (95% CI) of 2.16 (1.10–4.24), 3.42 (1.81–6.46) and 7.36 (3.69–14.68), respectively, for participants with scores of 1, 2–5 and 5+ compared with a score of 0. These associations are confirmed in an independent cohort and are independent from the ‘epigenetic clock'. In conclusion, DNAm of multiple disease-related genes are strongly linked to mortality outcomes. The DNAm-based risk score might be informative for risk assessment and stratification. PMID:28303888

  13. Differential white blood cell count and all-cause mortality in the Korean elderly.

    PubMed

    Kim, Kwang-Il; Lee, Jaebong; Heo, Nam Ju; Kim, Sejoong; Chin, Ho Jun; Na, Ki Young; Chae, Dong-Wan; Kim, Cheol-Ho; Kim, Suhnggwon

    2013-02-01

    The circulating white blood cell (WBC) count has been considered a good biomarker of systemic inflammation, but the predictive value of this inexpensive and universally obtained test result has not been fully explored in the elderly. The objective of this study was to assess the independent association of WBC count and its individual components with mortality in an elderly population. We studied a total of 9996 participants (age ≥65 years) who underwent routine health examinations at the 2 healthcare centers affiliated with Seoul National University. Mortality data were obtained from the National Statistics Office of Korea. The mean age of the study population was 69.7 (SD 4.3) years, and 5491 of the subjects (54.9%) were male. The median length of follow-up was 44.9 months (range, 1.2-78.7 months). There were 118 deaths (1.2%) during the follow-up period. The leading cause of death was cancer. Compared with the survivors, the deceased subjects were older, predominantly male, had increased levels of inflammatory markers, and had poor nutritional status. A significant difference in mortality was identified among patients in different WBC and WBC subtype quartile groups. Cox proportional hazards analysis indicated that monocyte count (HR: 5.18, 95% CI: 2.44-11.02) was a strongest predictor of all-cause mortality than total WBC count (HR: 1.57, 95% CI: 0.88-2.80), granulocyte count (HR: 2.11, 95% CI: 1.15-3.88), and lymphocyte count (HR: 1.11, 95% CI: 0.66-1.86), even after adjusting for possible confounding variables. Monocyte counts were associated with an increased risk of cardiovascular and cancer-related mortality in the elderly population. In conclusion, the total WBC count is an independent predictor of mortality in older adults, but the monocyte subtype provides greater predictive ability.

  14. Cohort study of all-cause mortality among tobacco users in Mumbai, India.

    PubMed Central

    Gupta, P. C.; Mehta, H. C.

    2000-01-01

    INTRODUCTION: Overall mortality rates are higher among cigarette smokers than non-smokers. However, very little is known about the health effects of other forms of tobacco use widely prevalent in India, such as bidi smoking and various forms of smokeless tobacco (e.g. chewing betel-quid). We therefore carried out a cohort study in the city of Mumbai, India, to estimate the relative risks for all-cause mortality among various kinds of tobacco users. METHODS: A baseline survey of all individuals aged > or = 35 years using voters' lists as a selection frame was conducted using a house-to-house approach and face-to-face interviews. RESULTS: Active follow-up of 52,568 individuals in the cohort was undertaken 5-6 years after the baseline study, and 97.6% were traced. A total of 4358 deaths were recorded among these individuals. The annual age-adjusted mortality rates were 18.4 per 1000 for men and 12.4 per 1000 for women. For men the mortality rates for smokers were higher than those of non-users of tobacco across all age groups, with the difference being greater for lower age groups (35-54 years). The relative risk was 1.39 for cigarette smokers and 1.78 for bidi smokers, with an apparent dose-response relationship for frequency of smoking. Women were basically smokeless tobacco users, with the relative risk among such users being 1.35 and a suggestion of a dose-response relationship. DISCUSSION: These findings establish bidi smoking as no less hazardous than cigarette smoking and indicate that smokeless tobacco use may also cause higher mortality. Further studies should be carried out to obtain cause-specific mortality rates and relative risks. PMID:10994260

  15. Diagnosis-specific sickness absence and all-cause mortality in the GAZEL study

    PubMed Central

    Ferrie, Jane E.; Vahtera, Jussi; Kivimäki, Mika; Westerlund, Hugo; Melchior, Maria; Alexanderson, Kristina; Head, Jenny; Chevalier, Anne; Leclerc, Annette; Zins, Marie; Goldberg, Marcel; Singh-Manoux, Archana

    2009-01-01

    Objective To examine diagnosis-specific sickness absence as a risk marker for all-cause mortality. Design Prospective occupational cohort (the GAZEL study). Medically-certified sickness absence spells greater than 7 days for 15 diagnostic categories, 1990–1992, were examined in relation to all-cause mortality, January 1993-February 2007. The reference group for each diagnostic category was participants with no spell >7 days for that diagnosis. Participants French public utility workers (5,271 women and 13,964 men) aged 37–51 in 1990, the GAZEL study. Over the follow-up period there were 144 deaths in women and 758 in men. Main results 7,875 employees (41.0%) had at least one spell of sickness absence >7 days over the three-year period. The commonest diagnoses were mental disorders, musculoskeletal diseases, respiratory diseases and external causes in both sexes; genitourinary diseases in women, and digestive and circulatory diseases in men. Of these common diagnoses mental disorders in women, hazard ratio (95% confidence intervals) 1.24 (1.1–1.4); and mental disorders 1.35 (1.3–1.5), digestive diseases 1.29 (1.1–1.6) and circulatory diseases 1.35 (1.2–1.6) in men were associated with mortality after adjustment for age, employment grade and sickness absence in all other diagnostic categories. Conclusions Employees with medically-certified absence spells of one week or more over a three-year period had a 60% excess risk of early death. In women and men, this excess risk was associated with some of the commonest diagnoses of sickness absence, in particular mental disorders. Sickness absence for mental disorders may be a useful early indicator of groups at increased risk of fatal disease. PMID:19039005

  16. Blood pressure and all-cause mortality among patients with type 2 diabetes

    PubMed Central

    Li, Weiqin; Katzmarzyk, Peter T.; Horswell, Ronald; Wang, Yujie; Johnson, Jolene; Hu, Gang

    2016-01-01

    Background The recommended goal for blood pressure (BP) control has recently been adjusted for people with diabetes, but the optimal BP control range for the diabetic population is still uncertain. Methods We performed a prospective cohort study of 35,261 patients with type 2 diabetes. Cox proportional hazards regression models were used to estimate the association of BP with all-cause mortality. Results During a mean follow-up period of 8.7 years, 4,199 deaths were identified. The multivariable-adjusted hazard ratios of all-cause mortality associated with different levels of systolic/diastolic BP (<110/65, 110–119/65–69, 120–129/70–80, 130–139/80–90 [reference group], 140–159/90–100, and ≥160/100 mmHg) were 1.70 (95% confidence interval [CI] 1.42–2.04), 1.26 (95% CI 1.07–1.50), 0.99 (95% CI 0.86–1.12), 1.00, 0.92 (95% CI 0.82–1.03), and 1.10 (95% CI 0.98–1.23) using baseline BP measurements, and 2.62 (95% CI 2.00–3.44), 1.77 (95% CI 1.51–2.09), 1.22 (95% CI 1.09–1.36), 1.00, 0.90 (95% CI 0.82–1.00), and 0.98 (95% CI 0.86–1.12) using an updated mean value of BP during follow-up, respectively. The U-shaped associations were confirmed in both African American and white patients, in both men and women, in those who were or were not taking antihypertensive drugs; and in patients aged 30–49 years and 50–59 years. Conclusions The current study found a U-shaped association between BP at baseline and during follow-up and the risk of all-cause mortality among patients with type 2 diabetes. PMID:26788685

  17. Parity and All-cause Mortality in Women and Men: A Dose-Response Meta-Analysis of Cohort Studies.

    PubMed

    Zeng, Yun; Ni, Ze-min; Liu, Shu-yun; Gu, Xue; Huang, Qin; Liu, Jun-an; Wang, Qi

    2016-01-13

    To quantitatively assess the association between parity and all-cause mortality, we conducted a meta-analysis of cohort studies. Relevant reports were identified from PubMed and Embase databases. Cohort studies with relative risks (RRs) and 95% confidence intervals (CIs) of all-cause mortality in three or more categories of parity were eligible. Eighteen articles with 2,813,418 participants were included. Results showed that participants with no live birth had higher risk of all-cause mortality (RR= 1.19, 95% CI = 1.03-1.38; I(2) = 96.7%, P < 0.001) compared with participants with one or more live births. Nonlinear dose-response association was found between parity and all-cause mortality (P for non-linearity < 0.0001). Our findings suggest that moderate-level parity is inversely associated with all-cause mortality.

  18. All cause mortality and incidence of cancer in workers in bauxite mines and alumina refineries.

    PubMed

    Fritschi, Lin; Hoving, Jan Lucas; Sim, Malcolm R; Del Monaco, Anthony; MacFarlane, Ewan; McKenzie, Dean; Benke, Geza; de Klerk, Nicholas

    2008-08-15

    Bauxite is a reddish clay that is refined to produce alumina, which is then reduced to aluminium. There have been studies examining the health of workers in aluminium smelters, but not workers in bauxite mining and alumina refining. A cohort of employees of 1 large aluminium company since 1983 was assembled (n = 6,485, 5,828 men). Deaths and incident cancers to 2002 were ascertained by linkage to national and state cancer and death registries. SIRs and SMRs were calculated compared to national rates standardizing for calendar year, sex and 5-year age group. The mortality from all causes (SMR 0.68, 95% CI: 0.60-0.77), and from circulatory and respiratory diseases, all cancers combined and injury in the male cohort were lower than in the Australian male population and were similar across work groups and with duration of employment. The only significant increased mortality risk was from pleural mesothelioma. The incidence of all cancers combined was similar to the Australian rate. The cohort had a lower risk of incident lymphohaematopoietic cancer (SIR 0.50, 95% CI: 0.31-0.88) and a higher risk of melanoma (SIR 1.30, 95% CI: 1.00-1.69) although no dose-responses were seen. There was also an increased risk of mesothelioma (SIR 3.49, 95% CI: 1.82-6.71), which was associated with exposures outside the aluminium industry. This study is the first to examine cancer and mortality amongst workers in bauxite mines and alumina refineries and found little evidence for increased cancer incidence or mortality in these workers.

  19. Wound healing and all-cause mortality in 958 wound patients treated in home care.

    PubMed

    Zarchi, Kian; Martinussen, Torben; Jemec, Gregor B E

    2015-09-01

    Skin wounds are associated with significant morbidity and mortality. Data are, however, not readily available for benchmarking, to allow prognostic evaluation, and to suggest when involvement of wound-healing experts is indicated. We, therefore, conducted an observational cohort study to investigate wound healing and all-cause mortality associated with different types of skin wounds. Consecutive skin wound patients who received wound care by home-care nurses from January 2010 to December 2011 in a district in Eastern Denmark were included in this study. Patients were followed until wound healing, death, or the end of follow-up on December 2012. In total, 958 consecutive patients received wound care by home-care nurses, corresponding to a 1-year prevalence of 1.2% of the total population in the district. During the study, wound healing was achieved in 511 (53.3%), whereas 90 (9.4%) died. During the first 3 weeks of therapy, healing was most likely to occur in surgical wounds (surgical vs. other wounds: adjusted hazard ratio [AHR] 2.21, 95% confidence interval 1.50-3.23), while from 3 weeks to 3 months of therapy, cancer wounds, and pressure ulcers were least likely to heal (cancer vs. other wounds: AHR 0.12, 0.03-0.50; pressure vs. other wounds: AHR 0.44, 0.27-0.74). Cancer wounds and pressure ulcers were further associated with a three times increased probability of mortality compared with other wounds (cancer vs. other wounds: AHR 3.19, 1.35-7.50; pressure vs. other wounds: AHR 2.91, 1.56-5.42). In summary, the wound type was found to be a significant predictor of healing and mortality with cancer wounds and pressure ulcers being associated with poor prognosis.

  20. Structural stigma and all-cause mortality in sexual minority populations.

    PubMed

    Hatzenbuehler, Mark L; Bellatorre, Anna; Lee, Yeonjin; Finch, Brian K; Muennig, Peter; Fiscella, Kevin

    2014-02-01

    Stigma operates at multiple levels, including intrapersonal appraisals (e.g., self-stigma), interpersonal events (e.g., hate crimes), and structural conditions (e.g., community norms, institutional policies). Although prior research has indicated that intrapersonal and interpersonal forms of stigma negatively affect the health of the stigmatized, few studies have addressed the health consequences of exposure to structural forms of stigma. To address this gap, we investigated whether structural stigma-operationalized as living in communities with high levels of anti-gay prejudice-increases risk of premature mortality for sexual minorities. We constructed a measure capturing the average level of anti-gay prejudice at the community level, using data from the General Social Survey, which was then prospectively linked to all-cause mortality data via the National Death Index. Sexual minorities living in communities with high levels of anti-gay prejudice experienced a higher hazard of mortality than those living in low-prejudice communities (Hazard Ratio [HR] = 3.03, 95% Confidence Interval [CI] = 1.50, 6.13), controlling for individual and community-level covariates. This result translates into a shorter life expectancy of approximately 12 years (95% C.I.: 4-20 years) for sexual minorities living in high-prejudice communities. Analysis of specific causes of death revealed that suicide, homicide/violence, and cardiovascular diseases were substantially elevated among sexual minorities in high-prejudice communities. Strikingly, there was an 18-year difference in average age of completed suicide between sexual minorities in the high-prejudice (age 37.5) and low-prejudice (age 55.7) communities. These results highlight the importance of examining structural forms of stigma and prejudice as social determinants of health and longevity among minority populations.

  1. Structural Stigma and All-Cause Mortality in Sexual Minority Populations

    PubMed Central

    Hatzenbuehler, Mark L.; Bellatorre, Anna; Lee, Yeonjin; Finch, Brian; Muennig, Peter; Fiscella, Kevin

    2013-01-01

    Stigma operates at multiple levels, including intrapersonal appraisals (e.g., self-stigma), interpersonal events (e.g., hate crimes), and structural conditions (e.g., community norms, institutional policies). Although prior research has indicated that intrapersonal and interpersonal forms of stigma negatively affect the health of the stigmatized, few studies have addressed the health consequences of exposure to structural forms of stigma. To address this gap, we investigated whether structural stigma—operationalized as living in communities with high levels of anti-gay prejudice—increases risk of premature mortality for sexual minorities. We constructed a measure capturing the average level of anti-gay prejudice at the community level, using data from the General Social Survey, which was then prospectively linked to all-cause mortality data via the National Death Index. Sexual minorities living in communities with high levels of anti-gay prejudice experienced a higher hazard of mortality than those living in low-prejudice communities (Hazard Ratio [HR] =3.03, 95% Confidence Interval [CI]=1.50, 6.13), controlling for individual and community-level covariates. This result translates into a shorter life expectancy of approximately 12 years (95% C.I.: 4-20 years) for sexual minorities living in high-prejudice communities. Analysis of specific causes of death revealed that suicide, homicide/violence, and cardiovascular diseases were substantially elevated among sexual minorities in high-prejudice communities. Strikingly, there was an 18-year difference in average age of completed suicide between sexual minorities in the high-prejudice (age 37.5) and low-prejudice (age 55.7) communities. These results highlight the importance of examining structural forms of stigma and prejudice as social determinants of health and longevity among minority populations. PMID:23830012

  2. Oxidative Stress Predicts All-Cause Mortality in HIV-Infected Patients

    PubMed Central

    Masiá, Mar; Padilla, Sergio; Fernández, Marta; Rodríguez, Carmen; Moreno, Ana; Oteo, Jose A.; Antela, Antonio; Moreno, Santiago; del Amo, Julia; Gutiérrez, Félix

    2016-01-01

    Objective We aimed to assess whether oxidative stress is a predictor of mortality in HIV-infected patients. Methods We conducted a nested case-control study in CoRIS, a contemporary, multicentre cohort of HIV-infected patients, antiretroviral-naïve at entry, launched in 2004. Cases were patients who died with available stored plasma samples collected. Two age and sex-matched controls for each case were selected. We measured F2-isoprostanes (F2-IsoPs) and malondialdehyde (MDA) plasma levels in the first blood sample obtained after cohort engagement. Results 54 cases and 93 controls were included. Median F2-IsoPs and MDA levels were significantly higher in cases than in controls. When adjustment was performed for age, HIV-transmission category, CD4 cell count and HIV viral load at cohort entry, and subclinical inflammation measured with highly-sensitive C-reactive protein (hsCRP), the association of F2-IsoPs with mortality remained significant (adjusted OR per 1 log10 increase, 2.34 [1.23–4.47], P = 0.009). The association of MDA with mortality was attenuated after adjustment: adjusted OR (95% CI) per 1 log10 increase, 2.05 [0.91–4.59], P = 0.080. Median hsCRP was also higher in cases, and it also proved to be an independent predictor of mortality in the adjusted analysis: OR (95% CI) per 1 log10 increase, 1.39 (1.01–1.91), P = 0.043; and OR (95% CI) per 1 log10 increase, 1.46 (1.07–1.99), P = 0.014, respectively, when adjustment included F2-IsoPs and MDA. Conclusion Oxidative stress is a predictor of all-cause mortality in HIV-infected patients. For plasma F2-IsoPs, this association is independent of HIV-related factors and subclinical inflammation. PMID:27111769

  3. Modeling the sssociation between 25[OH]D and all-cause mortality in a representative US population sample

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Vitamin D has been identified as a potential key risk factor for several chronic diseases and mortality. The association between all-cause mortality and circulating levels of 25-ydroxyvitamin D (25[OH]D) has been described as non-monotonic with excess mortality at both low and high levels (1). Howev...

  4. Coffee consumption and mortality from all causes, cardiovascular disease, and cancer: a dose-response meta-analysis.

    PubMed

    Crippa, Alessio; Discacciati, Andrea; Larsson, Susanna C; Wolk, Alicja; Orsini, Nicola

    2014-10-15

    Several studies have analyzed the relationship between coffee consumption and mortality, but the shape of the association remains unclear. We conducted a dose-response meta-analysis of prospective studies to examine the dose-response associations between coffee consumption and mortality from all causes, cardiovascular disease (CVD), and all cancers. Pertinent studies, published between 1966 and 2013, were identified by searching PubMed and by reviewing the reference lists of the selected articles. Prospective studies in which investigators reported relative risks of mortality from all causes, CVD, and all cancers for 3 or more categories of coffee consumption were eligible. Results from individual studies were pooled using a random-effects model. Twenty-one prospective studies, with 121,915 deaths and 997,464 participants, met the inclusion criteria. There was strong evidence of nonlinear associations between coffee consumption and mortality for all causes and CVD (P for nonlinearity < 0.001). The largest risk reductions were observed for 4 cups/day for all-cause mortality (16%, 95% confidence interval: 13, 18) and 3 cups/day for CVD mortality (21%, 95% confidence interval: 16, 26). Coffee consumption was not associated with cancer mortality. Findings from this meta-analysis indicate that coffee consumption is inversely associated with all-cause and CVD mortality.

  5. Effects of habitual coffee consumption on cardiometabolic disease, cardiovascular health, and all-cause mortality.

    PubMed

    O'Keefe, James H; Bhatti, Salman K; Patil, Harshal R; DiNicolantonio, James J; Lucan, Sean C; Lavie, Carl J

    2013-09-17

    Coffee, after water, is the most widely consumed beverage in the United States, and is the principal source of caffeine intake among adults. The biological effects of coffee may be substantial and are not limited to the actions of caffeine. Coffee is a complex beverage containing hundreds of biologically active compounds, and the health effects of chronic coffee intake are wide ranging. From a cardiovascular (CV) standpoint, coffee consumption may reduce the risk of type 2 diabetes mellitus and hypertension, as well as other conditions associated with CV risk such as obesity and depression; but it may adversely affect lipid profiles depending on how the beverage is prepared. Regardless, a growing body of data suggests that habitual coffee consumption is neutral to beneficial regarding the risks of a variety of adverse CV outcomes including coronary heart disease, congestive heart failure, arrhythmias, and stroke. Moreover, large epidemiological studies suggest that regular coffee drinkers have reduced risks of mortality, both CV and all-cause. The potential benefits also include protection against neurodegenerative diseases, improved asthma control, and lower risk of select gastrointestinal diseases. A daily intake of ∼2 to 3 cups of coffee appears to be safe and is associated with neutral to beneficial effects for most of the studied health outcomes. However, most of the data on coffee's health effects are based on observational data, with very few randomized, controlled studies, and association does not prove causation. Additionally, the possible advantages of regular coffee consumption have to be weighed against potential risks (which are mostly related to its high caffeine content) including anxiety, insomnia, tremulousness, and palpitations, as well as bone loss and possibly increased risk of fractures.

  6. All-cause and cause-specific mortality among US youth: socioeconomic and rural-urban disparities and international patterns.

    PubMed

    Singh, Gopal K; Azuine, Romuladus E; Siahpush, Mohammad; Kogan, Michael D

    2013-06-01

    We analyzed international patterns and socioeconomic and rural-urban disparities in all-cause mortality and mortality from homicide, suicide, unintentional injuries, and HIV/AIDS among US youth aged 15-24 years. A county-level socioeconomic deprivation index and rural-urban continuum measure were linked to the 1999-2007 US mortality data. Mortality rates were calculated for each socioeconomic and rural-urban group. Poisson regression was used to derive adjusted relative risks of youth mortality by deprivation level and rural-urban residence. The USA has the highest youth homicide rate and 6th highest overall youth mortality rate in the industrialized world. Substantial socioeconomic and rural-urban gradients in youth mortality were observed within the USA. Compared to their most affluent counterparts, youth in the most deprived group had 1.9 times higher all-cause mortality, 8.0 times higher homicide mortality, 1.5 times higher unintentional-injury mortality, and 8.8 times higher HIV/AIDS mortality. Youth in rural areas had significantly higher mortality rates than their urban counterparts regardless of deprivation levels, with suicide and unintentional-injury mortality risks being 1.8 and 2.3 times larger in rural than in urban areas. However, youth in the most urbanized areas had at least 5.6 times higher risks of homicide and HIV/AIDS mortality than their rural counterparts. Disparities in mortality differed by race and sex. Socioeconomic deprivation and rural-urban continuum were independently related to disparities in youth mortality among all sex and racial/ethnic groups, although the impact of deprivation was considerably greater. The USA ranks poorly in all-cause mortality, youth homicide, and unintentional-injury mortality rates when compared with other industrialized countries.

  7. Malaria’s Indirect Contribution to All-Cause Mortality in the Andaman Islands during the Colonial Era

    PubMed Central

    Shanks, G. Dennis; Hay, Simon I.; Bradley, David J.

    2009-01-01

    Malaria appears to have a substantial secondary effect on other causes of mortality. From the 19th century, malaria epidemics in the Andaman Islands Penal Colony were initiated by the brackish swamp breeding malaria vector Anopheles sundaicus and fueled by the importation of new prisoners. Malaria was a major determinant of the highly variable all-cause mortality rate (correlation coefficient r2=0.60, n=68, p< 0.0001) from 1872 to 1939. Directly attributed malaria mortality based on postmortem examinations rarely exceeded one fifth of total mortality. Infectious diseases such as pneumonia, tuberculosis, dysentery and diarrhea, which combined with malaria made up a majority of all-cause mortality, were positively correlated to malaria incidence over several decades. Deaths secondary to malaria (indirect malaria mortality) were at least as great as mortality directly attributed to malaria infections. PMID:18599354

  8. Plasma Biomarkers of Inflammation, the Kynurenine Pathway, and Risks of All-Cause, Cancer, and Cardiovascular Disease Mortality

    PubMed Central

    Zuo, Hui; Ueland, Per M.; Ulvik, Arve; Eussen, Simone J. P. M.; Vollset, Stein E.; Nygård, Ottar; Midttun, Øivind; Theofylaktopoulou, Despoina; Meyer, Klaus; Tell, Grethe S.

    2016-01-01

    We aimed to evaluate 10 biomarkers related to inflammation and the kynurenine pathway, including neopterin, kynurenine:tryptophan ratio, C-reactive protein, tryptophan, and 6 kynurenines, as potential predictors of all-cause and cause-specific mortality in a general population sample. The study cohort was participants involved in a community-based Norwegian study, the Hordaland Health Study (HUSK). We used Cox proportional hazards models to assess associations of the biomarkers with all-cause mortality and competing-risk models for cause-specific mortality. Of the 7,015 participants, 1,496 deaths were recorded after a median follow-up time of 14 years (1998–2012). Plasma levels of inflammatory markers (neopterin, kynurenine:tryptophan ratio, and C-reactive protein), anthranilic acid, and 3-hydroxykynurenine were positively associated with all-cause mortality, and tryptophan and xanthurenic acid were inversely associated. Multivariate-adjusted hazard ratios for the highest (versus lowest) quartiles of the biomarkers were 1.19–1.60 for positive associations and 0.73–0.87 for negative associations. All of the inflammatory markers and most kynurenines, except kynurenic acid and 3-hydroxyanthranilic acid, were associated with cardiovascular disease (CVD) mortality. In this general population, plasma biomarkers of inflammation and kynurenines were associated with risk of all-cause, cancer, and CVD mortality. Associations were stronger for CVD mortality than for mortality due to cancer or other causes. PMID:26823439

  9. Investigation of Gender Heterogeneity in the Associations of Serum Phosphorus with Incident Coronary Artery Disease and All-Cause Mortality

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Serum phosphorus levels are associated with increased morbidity and mortality in patients with chronic kidney disease. We examined whether serum phosphorus is associated with all-cause mortality and incident myocardial infarction in the general population using 13,998 middle age subjects from the At...

  10. Increased All-Cause Mortality Associated With Digoxin Therapy in Patients With Atrial Fibrillation: An Updated Meta-Analysis.

    PubMed

    Chen, Ying; Cai, Xiaoyan; Huang, Weijun; Wu, Yanxian; Huang, Yuli; Hu, Yunzhao

    2015-12-01

    Digoxin is still commonly used in atrial fibrillation (AF) patients with and without heart failure (HF) for heart rate control. Studies concerning the detrimental effects of digoxin therapy in AF patients are inconsistent. This updated meta-analysis examined the association of digoxin therapy with all-cause mortality in AF patients, stratified by heart function status. We included observational studies with multivariate-adjusted data on digoxin and all-cause mortality in the analysis. The relative risks (RRs) of all-cause mortality were calculated and reported with 95% confidence intervals (95% CIs). Seventeen studies comprising 408,660 patients were included. Overall, in AF patients, digoxin treatment was associated with a significant increase in all-cause mortality after multivariate-adjustment (RR = 1.22; 95% CI 1.15-1.30). When stratified by heart function status, digoxin treatment was associated with a 14% increase in all-cause mortality in AF patients with HF (RR = 1.14, 95% CI 1.04-1.24), and a 36% increase in those without HF (RR = 1.36, 95% CI 1.18-1.56). The increased risk of all-cause mortality was significantly higher in AF patients without HF compared with those with HF (P for interaction = 0.04). This meta-analysis demonstrates that digoxin therapy was associated with a significant increase in all-cause mortality in AF patients, especially in those without HF. Given other available options, digoxin should be avoided as a first-line agent for heart rate control in AF patients.

  11. Tea consumption and mortality of all cancers, CVD and all causes: a meta-analysis of eighteen prospective cohort studies.

    PubMed

    Tang, Jun; Zheng, Ju-Sheng; Fang, Ling; Jin, Yongxin; Cai, Wenwen; Li, Duo

    2015-09-14

    Epidemiological studies have demonstrated inconsistent associations between tea consumption and mortality of all cancers, CVD and all causes. To obtain quantitative overall estimates, we conducted a dose-response meta-analysis of prospective cohort studies. A literature search in PubMed and Embase up to April 2015 was conducted for all relevant papers published. Random-effects models were used to calculate pooled relative risks (RR) with 95 % CI. In eighteen prospective studies, there were 12 221, 11 306 and 55 528 deaths from all cancers, CVD and all causes, respectively. For all cancer mortality, the summary RR for the highest v. lowest category of green tea and black tea consumption were 1·06 (95 % CI 0·98, 1·15) and 0·79 (95 % CI 0·65, 0·97), respectively. For CVD mortality, the summary RR for the highest v. lowest category of green tea and black tea consumption were 0·67 (95 % CI 0·46, 0·96) and 0·88 (95 % CI 0·77, 1·01), respectively. For all-cause mortality, the summary RR for the highest v. lowest category of green tea and black tea consumption were 0·80 (95 % CI 0·68, 0·93) and 0·90 (95 % CI 0·83, 0·98), respectively. The dose-response analysis indicated that one cup per d increment of green tea consumption was associated with 5 % lower risk of CVD mortality and with 4 % lower risk of all-cause mortality. Green tea consumption was significantly inversely associated with CVD and all-cause mortality, whereas black tea consumption was significantly inversely associated with all cancer and all-cause mortality.

  12. Age- and gender-specific population attributable risks of metabolic disorders on all-cause and cardiovascular mortality in Taiwan

    PubMed Central

    2012-01-01

    Background The extent of attributable risks of metabolic syndrome (MetS) and its components on mortality remains unclear, especially with respect to age and gender. We aimed to assess the age- and gender-specific population attributable risks (PARs) for cardiovascular disease (CVD)-related mortality and all-cause mortality for public health planning. Methods A total of 2,092 men and 2,197 women 30 years of age and older, who were included in the 2002 Taiwan Survey of Hypertension, Hyperglycemia, and Hyperlipidemia (TwSHHH), were linked to national death certificates acquired through December 31, 2009. Cox proportional hazard models were used to calculate adjusted hazard ratios and PARs for mortality, with a median follow-up of 7.7 years. Results The respective PAR percentages of MetS for all-cause and CVD-related mortality were 11.6 and 39.2 in men, respectively, and 18.6 and 44.4 in women, respectively. Central obesity had the highest PAR for CVD mortality in women (57.5%), whereas arterial hypertension had the highest PAR in men (57.5%). For all-cause mortality, younger men and post-menopausal women had higher PARs related to Mets and its components; for CVD mortality, post-menopausal women had higher overall PARs than their pre-menopausal counterparts. Conclusions MetS has a limited application to the PAR for all-cause mortality, especially in men; its PAR for CVD mortality is more evident. For CVD mortality, MetS components have higher PARs than MetS itself, especially hypertension in men and waist circumference in post-menopausal women. In addition, PARs for diabetes mellitus and low HDL-cholesterol may exceed 20%. We suggest differential control of risk factors in different subpopulation as a strategy to prevent CVD-related mortality. PMID:22321049

  13. Usual walking speed and all-cause mortality risk in older people: A systematic review and meta-analysis.

    PubMed

    Liu, Bing; Hu, Xinhua; Zhang, Qiang; Fan, Yichuan; Li, Jun; Zou, Rui; Zhang, Ming; Wang, Xiuqi; Wang, Junpeng

    2016-02-01

    The purpose of this study was to investigate the relationship between slow usual walking speed and all-cause mortality risk in older people by conducting a meta-analysis. We searched through the Pubmed, Embase and Cochrane Library database up to March 2015. Only prospective observational studies that investigating the usual walking speed and all-cause mortality risk in older adulthood approaching age 65 years or more were included. Walking speed should be specifically assessed as a single-item tool over a short distance. Pooled adjusted risk ratio (RR) and 95% confidence interval (CI) were computed for the lowest versus the highest usual walking speed category. A total of 9 studies involving 12,901 participants were included. Meta-analysis with random effect model showed that the pooled adjusted RR of all-cause mortality was 1.89 (95% CI 1.46-2.46) comparing the lowest to the highest usual walk speed. Subgroup analyses indicated that risk of all-cause mortality for slow usual walking speed appeared to be not significant among women (RR 1.45; 95% CI 0.95-2.20). Slow usual walking speed is an independent predictor of all-cause mortality in men but not in women among older adulthood approaching age 65 years or more.

  14. Skipping Breakfast and Risk of Mortality from Cancer, Circulatory Diseases and All Causes: Findings from the Japan Collaborative Cohort Study

    PubMed Central

    Yokoyama, Yae; Onishi, Kazunari; Hosoda, Takenobu; Amano, Hiroki; Otani, Shinji; Kurozawa, Youichi; Tamakoshi, Akiko

    2016-01-01

    Background Breakfast eating habits are a dietary pattern marker and appear to be a useful predictor of a healthy lifestyle. Many studies have reported the unhealthy effects of skipping breakfast. However, there are few studies on the association between skipping breakfast and mortality. In the present study, we examined the association between skipping breakfast and mortality from cancer, circulatory diseases and all causes using data from a large-scale cohort study, the Japan Collaborative Cohort Study (JACC) Study. Methods A cohort study of 34,128 men and 49,282 women aged 40–79 years was conducted, to explore the association between lifestyle and cancer in Japan. Participants completed a baseline survey during 1988 to 1990 and were followed until the end of 2009. We classified participants into two groups according to dietary habits with respect to eating or skipping breakfast and carried out intergroup comparisons of lifestyle. Multivariate analysis was performed using the Cox proportional hazard regression model. Results There were 5,768 deaths from cancer and 5,133 cases of death owing to circulatory diseases and 17,112 cases for all causes of mortality during the median 19.4 years follow-up. Skipping breakfast was related to unhealthy lifestyle habits. After adjusting for confounding factors, skipping breakfast significantly increased the risk of mortality from circulatory diseases [hazard ratio (HR) = 1.42] and all causes (HR = 1.43) in men and all causes mortality (HR = 1.34) in women. Conclusion Our findings showed that skipping breakfast is associated with increasing risk of mortality from circulatory diseases and all causes among men and all causes mortality among women in Japan. PMID:27046951

  15. Milk Consumption and Mortality from All Causes, Cardiovascular Disease, and Cancer: A Systematic Review and Meta-Analysis

    PubMed Central

    Larsson, Susanna C.; Crippa, Alessio; Orsini, Nicola; Wolk, Alicja; Michaëlsson, Karl

    2015-01-01

    Results from epidemiological studies of milk consumption and mortality are inconsistent. We conducted a systematic review and meta-analysis of prospective studies assessing the association of non-fermented and fermented milk consumption with mortality from all causes, cardiovascular disease, and cancer. PubMed was searched until August 2015. A two-stage, random-effects, dose-response meta-analysis was used to combine study-specific results. Heterogeneity among studies was assessed with the I2 statistic. During follow-up periods ranging from 4.1 to 25 years, 70,743 deaths occurred among 367,505 participants. The range of non-fermented and fermented milk consumption and the shape of the associations between milk consumption and mortality differed considerably between studies. There was substantial heterogeneity among studies of non-fermented milk consumption in relation to mortality from all causes (12 studies; I2 = 94%), cardiovascular disease (five studies; I2 = 93%), and cancer (four studies; I2 = 75%) as well as among studies of fermented milk consumption and all-cause mortality (seven studies; I2 = 88%). Thus, estimating pooled hazard ratios was not appropriate. Heterogeneity among studies was observed in most subgroups defined by sex, country, and study quality. In conclusion, we observed no consistent association between milk consumption and all-cause or cause-specific mortality. PMID:26378576

  16. Population-level associations between antiretroviral therapy scale-up and all-cause mortality in South Africa.

    PubMed

    Larson, Elysia; Bendavid, Eran; Tuoane-Nkhasi, Maletela; Mbengashe, Thobile; Goldman, Thurma; Wilson, Melinda; Klausner, Jeffrey D

    2014-08-01

    Our aim was to describe the association between increasing access to antiretroviral therapy and all-cause mortality in South Africa from 2005 to 2009. We undertook a longitudinal, population-level study, using antiretroviral monitoring data reported by PEPFAR implementing partners and province-level and national all-cause mortality records from Statistics South Africa (provider of official South African government statistics) to analyse the association between antiretroviral therapy and mortality. Using mixed effects models with a random intercept for province, we estimated the contemporaneous and lagging association between antiretroviral therapy and all-cause mortality in South Africa. We also conducted subgroup analyses and estimated the number of deaths averted. For each 100 HIV-infected individuals on antiretroviral therapy reported by PEPFAR implementing partners in South African treatment programmes, there was an associated 2.9 fewer deaths that year (95% CI: 1.5, 4.2) and 6.3 fewer deaths the following year (95% CI: 4.6, 8.0). The associated decrease in mortality the year after treatment reporting was seen in both adults and children, and men and women. Treatment provided from 2005 to 2008 was associated with 28,305 deaths averted from 2006 to 2009. The scale-up of antiretroviral therapy in South Africa was associated with a significant reduction in national all-cause mortality.

  17. Relationships between cold-temperature indices and all causes and cardiopulmonary morbidity and mortality in a subtropical island.

    PubMed

    Lin, Yu-Kai; Wang, Yu-Chun; Lin, Pay-Liam; Li, Ming-Hsu; Ho, Tsung-Jung

    2013-09-01

    This study aimed to identify optimal cold-temperature indices that are associated with the elevated risks of mortality from, and outpatient visits for all causes and cardiopulmonary diseases during the cold seasons (November to April) from 2000 to 2008 in Northern, Central and Southern Taiwan. Eight cold-temperature indices, average, maximum, and minimum temperatures, and the temperature humidity index, wind chill index, apparent temperature, effective temperature (ET), and net effective temperature and their standardized Z scores were applied to distributed lag non-linear models. Index-specific cumulative 26-day (lag 0-25) mortality risk, cumulative 8-day (lag 0-7) outpatient visit risk, and their 95% confidence intervals were estimated at 1 and 2 standardized deviations below the median temperature, comparing with the Z score of the lowest risks for mortality and outpatient visits. The average temperature was adequate to evaluate the mortality risk from all causes and circulatory diseases. Excess all-cause mortality increased for 17-24% when average temperature was at Z=-1, and for 27-41% at Z=-2 among study areas. The cold-temperature indices were inconsistent in estimating risk of outpatient visits. Average temperature and THI were appropriate indices for measuring risk for all-cause outpatient visits. Relative risk of all-cause outpatient visits increased slightly by 2-7% when average temperature was at Z=-1, but no significant risk at Z=-2. Minimum temperature estimated the strongest risk associated with outpatient visits of respiratory diseases. In conclusion, the relationships between cold temperatures and health varied among study areas, types of health event, and the cold-temperature indices applied. Mortality from all causes and circulatory diseases and outpatient visits of respiratory diseases has a strong association with cold temperatures in the subtropical island, Taiwan.

  18. [The relevance of a decline in renal function for risk of renal failure, cardiovascular events and all-cause mortality].

    PubMed

    Bots, Michiel L; Blankestijn, Peter J

    2015-01-01

    It is well established that the presence of impaired renal function is associated with an increased risk of end-stage renal disease, cardiovascular events and all-cause mortality. Irrespective of the starting level of renal function, a decline in renal function over two years is a relevant and strong risk factor for end-stage renal disease, cardiovascular death and all-cause mortality. Even a decline of 20 to 30 per cent is associated with to a considerable increased risk and requires further attention.

  19. Delayed Effects of Obese and Overweight Population Conditions on All-Cause Adult Mortality Rate in the USA

    PubMed Central

    Okunade, Albert A.; Rubin, Rose M.; Okunade, Adeyinka K.

    2016-01-01

    Currently, there are few studies separating the linkage of pathological obese and overweight body mass indices (BMIs) to the all-cause mortality rate in adults. Consequently, this paper, using annual Behavioral Risk Factor Surveillance System data of the 50 US states and the District of Columbia, estimates empirical regression models linking the US adult overweight (25 ≤ BMI < 30) and obesity (BMI ≥ 30) rates to the all-cause deaths rate. The biochemistry of multi-period cumulative adiposity (saturated fatty acid) from unexpended caloric intakes (net energy storage) provides the natural theoretical foundation for tracing unhealthy BMI to all-cause mortality. Cross-sectional and panel data regression models are separately estimated for the delayed effects of obese and overweight BMIs on the all-cause mortality rate. Controlling for the independent effects of economic, socio-demographic, and other factors on the all-cause mortality rate, our findings confirm that the estimated panel data models are more appropriate. The panel data regression results reveal that the obesity-mortality link strengthens significantly after multiple years in the condition. The faster mortality response to obesity detected here is conjectured to arise from the significantly more obese. Compared with past studies postulating a static (rather than delayed) effects, the statistically significant lagged effects of adult population BMI pathology in this study are novel and insightful. And, as expected, these lagged effects are more severe in the obese than overweight population segment. Public health policy implications of this social science study findings agree with those of the clinical sciences literature advocating timely lifestyle modification interventions (e.g., smoking cessation) to slow premature mortality linked with unhealthy BMIs. PMID:27734013

  20. Effect of coffee consumption on all-cause and total cancer mortality: findings from the JACC study.

    PubMed

    Tamakoshi, Akiko; Lin, Yingsong; Kawado, Miyuki; Yagyu, Kiyoko; Kikuchi, Shogo; Iso, Hiroyasu

    2011-04-01

    Coffee consumption is known to be related to various health conditions. Recently, its antioxidant effects have been suggested to be associated with all-cause or cancer mortality by various cohort studies. However, there has been only one small Asian cohort study that has assessed this association. Thus, we tried to assess the association of coffee with all-cause and total cancer mortality by conducting a large-scale cohort study in Japan. A total of 97,753 Japanese men and women aged 40-79 years were followed for 16 years. Hazard ratios and 95% confidence intervals of all-cause and total cancer mortality in relation to coffee consumption were calculated from proportional-hazards regression models. A total of 19,532 deaths occurred during the follow-up period; 34.8% of these deaths were caused by cancer. The all-cause mortality risk decreased with increasing coffee consumption in both men and women, with a risk elevation at the highest coffee consumption level (≥4 cups/day) compared with the 2nd highest consumption level in women, although the number of subjects evaluated at this level was small. No association was found between coffee consumption and total cancer mortality among men, whereas a weak inverse association was found among women. The present cohort study among the Japanese population suggested that there are beneficial effects of coffee on all-cause mortality among both men and women. Furthermore, the results showed that coffee consumption might not be associated with an increased risk of total cancer mortality.

  1. The Role of Life Satisfaction and Depressive Symptoms in All-cause Mortality

    PubMed Central

    Collins, Amy Love; Glei, Dana A.; Goldman, Noreen

    2009-01-01

    The objective of our study was to investigate whether life satisfaction and depressive symptoms are independent predictors of mortality in a non-Western sample of adults. The sample included 5,131 adults (aged 50 – 95 at baseline) in Taiwan who participated in the Survey of Health and Living Status of the Near Elderly and Elderly. There were 1,815 deaths recorded over a 10-year period. Higher life satisfaction significantly predicted lower risk of mortality after controlling for age, sex, education, marital status and health status. Depressive symptoms significantly predicted higher risk of mortality. A significant interaction with age revealed that the protective effect of life satisfaction weakened with age. The results suggest that life satisfaction and depressive symptoms independently predict mortality risk in adults. PMID:19739925

  2. All-Cause Mortality for Diabetics or Individuals with Hyperglycemia Applying for Life Insurance.

    PubMed

    Freitas, Stephen A; MacKenzie, Ross; Wylde, David N; Roudebush, Bradley T; Bergstrom, Richard L; Holowaty, J Carl; Hart, Anna; Rigatti, Steven J; Gill, Stacy J

    2016-01-01

    Diabetics and individuals with lab results consistent with a diagnosis of diabetes or hyperglycemia were extracted from data covering US residents who applied for life insurance between January 2007 and January 2014. Information about these applicants was matched to the Social Security Death Master File (SSDMF) and another commercially available death source file to determine vital status. Due to the inconsistencies of reporting within the death files, there were two cohorts of death cases, one including the imputed year of birth (full cohort of deaths), and the second where the date of birth was known (reduced cohort of deaths). The study had approximately 8.5 million person-years of exposure. Actual to expected (A/E) mortality ratios were calculated using the Society of Actuaries 2008 Valuation Basic Table (2008VBT) select table, age last birthday and the 2010 US population as expected mortality rates. With the 2008VBT as an expected basis, the overall A/E mortality ratio was 3.15 for the full cohort of deaths and 2.56 for the reduced cohort of deaths. Using the US population as the expected basis, the overall A/E mortality ratio was 0.98 for the full cohort of deaths and 0.79 for the reduced cohort. Since there was no smoking status information in this study, all expected bases were not smoker distinct. A/E mortality ratios varied by disease treatment category and were considerably higher in individuals using insulin. A/E mortality ratios decreased with increasing age and took on a J-shaped distribution with increasing BMI (Body Mass Index). The lowest mortality ratios were observed for overweight and obese individuals. The A/E mortality ratio based on the 2008VBT decreased with the increase in applicant duration, which was defined as the time since initial life insurance application.

  3. Diabetes treatments and risk of heart failure, cardiovascular disease, and all cause mortality: cohort study in primary care

    PubMed Central

    Coupland, Carol

    2016-01-01

    Objective To assess associations between risks of cardiovascular disease, heart failure, and all cause mortality and different diabetes drugs in people with type 2 diabetes, particularly newer agents, including gliptins and thiazolidinediones (glitazones). Design Open cohort study. Setting 1243 general practices contributing data to the QResearch database in England. Participants 469 688 people with type 2 diabetes aged 25-84 years between 1 April 2007 and 31 January 2015. Exposures Diabetes drugs (glitazones, gliptins, metformin, sulphonylureas, insulin, other) alone and in combination. Main outcome measure First recorded diagnoses of cardiovascular disease, heart failure, and all cause mortality recorded on the patients’ primary care, mortality, or hospital record. Cox proportional hazards models were used to estimate hazard ratios for diabetes treatments, adjusting for potential confounders. Results During follow-up, 21 308 patients (4.5%) received prescriptions for glitazones and 32 533 (6.9%) received prescriptions for gliptins. Compared with non-use, gliptins were significantly associated with an 18% decreased risk of all cause mortality, a 14% decreased risk of heart failure, and no significant change in risk of cardiovascular disease; corresponding values for glitazones were significantly decreased risks of 23% for all cause mortality, 26% for heart failure, and 25% for cardiovascular disease. Compared with no current treatment, there were no significant associations between monotherapy with gliptins and risk of any complications. Dual treatment with gliptins and metformin was associated with a decreased risk of all three outcomes (reductions of 38% for heart failure, 33% for cardiovascular disease, and 48% for all cause mortality). Triple treatment with metformin, sulphonylureas, and gliptins was associated with a decreased risk of all three outcomes (reductions of 40% for heart failure, 30% for cardiovascular disease, and 51% for all cause

  4. Predictors, Including Blood, Urine, Anthropometry, and Nutritional Indices, of All-Cause Mortality among Institutionalized Individuals with Intellectual Disability

    ERIC Educational Resources Information Center

    Ohwada, Hiroko; Nakayama, Takeo; Tomono, Yuji; Yamanaka, Keiko

    2013-01-01

    As the life expectancy of people with intellectual disability (ID) increases, it is becoming necessary to understand factors affecting survival. However, predictors that are typically assessed among healthy people have not been examined. Predictors of all-cause mortality, including blood, urine, anthropometry, and nutritional indices, were…

  5. Association between whole grain intake and all-cause mortality: a meta-analysis of cohort studies

    PubMed Central

    Yang, Yang; Zhang, Qing-Li; Zheng, Jia-Li; Xiang, Yong-Bing

    2016-01-01

    Some observational studies have examined the association between dietary whole grain intake and all-cause mortality, but the results were inconclusive. We therefore conducted a meta-analysis to summarize the evidence from cohort studies regarding the association between whole grain intake and all-cause mortality. Pertinent studies were identified by searching PubMed, Embase and Web of Knowledge, up to February 28, 2016. Study-specific estimates were combined using random-effects models. Eleven prospective cohort studies involving 101,282 deaths and 843,749 participants were included in this meta-analysis. The pooled relative risk of all-cause mortality for the highest category of whole grain intake versus lowest category was 0.82 (95% confidence interval: 0.78, 0.87). There was a 7% reduction in risk associated with each 1 serving/day increase in whole grain intake (relative risk = 0.93; 95% confidence interval: 0.89, 0.97). No publication bias was found. This analysis indicates that higher intake of whole grain is associated with a reduced risk of all-cause mortality. The findings support current recommendations for increasing whole grain consumption to promote health and overall longevity. PMID:27566558

  6. Changes in physical activity and all-cause mortality in COPD.

    PubMed

    Vaes, Anouk W; Garcia-Aymerich, Judith; Marott, Jacob L; Benet, Marta; Groenen, Miriam T J; Schnohr, Peter; Franssen, Frits M E; Vestbo, Jørgen; Wouters, Emiel F M; Lange, Peter; Spruit, Martijn A

    2014-11-01

    Little is known about changes in physical activity in subjects with chronic obstructive pulmonary disease (COPD) and its impact on mortality. Therefore, we aimed to study changes in physical activity in subjects with and without COPD and the impact of physical activity on mortality risk. Subjects from the Copenhagen City Heart Study with at least two consecutive examinations were selected. Each examination included a self-administered questionnaire and clinical examination. 1270 COPD subjects and 8734 subjects without COPD (forced expiratory volume in 1 s 67±18 and 91±15% predicted, respectively) were included. COPD subjects with moderate or high baseline physical activity who reported low physical activity level at follow-up had the highest hazard ratios of mortality (1.73 and 2.35, respectively; both p<0.001). In COPD subjects with low baseline physical activity, no differences were found in survival between unchanged or increased physical activity at follow-up. In addition, subjects without COPD with low physical activity at follow-up had the highest hazard ratio of mortality, irrespective of baseline physical activity level (p≤0.05). A decline to low physical activity at follow-up was associated with an increased mortality risk in subjects with and without COPD. These observational data suggest that it is important to assess and encourage physical activity in the earliest stages of COPD in order to maintain a physical activity level that is as high as possible, as this is associated with better prognosis.

  7. Symptoms of depression and all-cause mortality in farmers, a cohort study: the HUNT study, Norway

    PubMed Central

    Letnes, Jon Magne; Hilt, Bjørn; Bjørngaard, Johan Håkon; Krokstad, Steinar

    2016-01-01

    Objectives To explore all-cause mortality and the association between symptoms of depression and all-cause mortality in farmers compared with other occupational groups, using a prospective cohort design. Methods We included adult participants with a known occupation from the second wave of the Nord-Trøndelag Health Study (Helseundersøkelsen i Nord-Trøndelag 2 (HUNT2) 1995–1997), Norway. Complete information on emigration and death from all causes was obtained from the National Registries. We used the depression subscale of the Hospital Anxiety and Depression Scale (HADS) to measure symptoms of depression. We compared farmers to 4 other occupational groups. Our baseline study population comprised 32 618 participants. Statistical analyses were performed using the Cox proportional hazards models. Results The estimated mortality risk in farmers was lower than in all other occupations combined, with a sex and age-adjusted HR (0.91, 95% CI 0.82 to 1.00). However, farmers had an 11% increased age-adjusted and sex-adjusted mortality risk compared with the highest ranked socioeconomic group (HR 1.11, 95% CI 0.98 to 1.25). In farmers, symptoms of depression were associated with a 13% increase in sex-adjusted and age-adjusted mortality risk (HR 1.13, 95% CI 0.88 to 1.45). Compared with other occupations this was the lowest HR, also after adjusting for education, marital status, long-lasting limiting somatic illness and lifestyle factors (HR 1.08, 95% CI 0.84 to 1.39). Conclusions Farmers had lower all-cause mortality compared with the other occupational groups combined. Symptoms of depression were associated with an increased mortality risk in farmers, but the risk increase was smaller compared with the other occupational groups. PMID:27188811

  8. Five-year all-cause mortality rates across five categories of substantiated elder abuse occurring in the community.

    PubMed

    Burnett, Jason; Jackson, Shelly L; Sinha, Arup K; Aschenbrenner, Andrew R; Murphy, Kathleen Pace; Xia, Rui; Diamond, Pamela M

    2016-01-01

    Elder abuse increases the likelihood of early mortality, but little is known regarding which types of abuse may be resulting in the greatest mortality risk. This study included N = 1,670 cases of substantiated elder abuse and estimated the 5-year all-cause mortality for five types of elder abuse (caregiver neglect, physical abuse, emotional abuse, financial exploitation, and polyvictimization). Statistically significant differences in 5-year mortality risks were found between abuse types and across gender. Caregiver neglect and financial exploitation had the lowest survival rates, underscoring the value of considering the long-term consequences associated with different forms of abuse. Likewise, mortality differences between genders and abuse types indicate the need to consider this interaction in elder abuse case investigations and responses. Further mortality studies are needed in this population to better understand these patterns and implications for public health and clinical management of community-dwelling elder abuse victims.

  9. Syndecan-4 Is an Independent Predictor of All-Cause as Well as Cardiovascular Mortality in Hemodialysis Patients

    PubMed Central

    Jaroszyński, Andrzej J.; Jaroszyńska, Anna; Przywara, Stanisław; Zaborowski, Tomasz; Książek, Andrzej; Dąbrowski, Wojciech

    2016-01-01

    Background Left ventricular hypertrophy is associated withincreased mortality in hemodialysis (HD) patients.Syndecan-4 plays a role in many processes that are involved in the heart fibrosis and hypertrophy.We designed this study to prospectively determine whether syndecan-4 was predictive of mortality in a group of HD patients. Methods In total, 191 HD patients were included. Clinical, biochemical and echocardiographic parameters were recorded. HD patients were followed-up for 23.18 ± 4.02 months. Results Syndecan-4 levels correlated strongly with geometrical echocardiographic parameters and ejection fraction. Relations with pressure-related parameters were weak and only marginally significant. Using the receiver operating characteristics the optimal cut-off points in predicting all-cause as well as cardiovascular (CV) mortality were evaluated and patients were divided into low and high syndecan-4 groups. A Kaplan–Meier analysis showed that the cumulative incidences of all-cause as well as CV mortality were higher in high serum syndecan-4 group compared with those with low serum syndecan-4 (p<0.001 in both cases).A multivariate Cox proportional hazards regression analysis revealed syndecan-4 concentration to be an independent and significant predictor of all-cause (hazard ratio, 2.99; confidence interval, 2.34 to 3.113; p<0.001)as well as CV mortality (hazard ratio, 2.81;confidence interval, 2.28to3.02; p<0.001). Conclusions Serum syndecan-4 concentration reflects predominantly geometrical echocardiographic parameters. In HD patients serum syndecan-4 concentration is independently associated with all-cause as well as CV mortality. PMID:27685148

  10. Dipstick Proteinuria as a Predictor of All-Cause and Cardiovascular Disease Mortality in Bangladesh: a Prospective Cohort Study

    PubMed Central

    Pesola, Gene R.; Argos, Maria; Chen, Yu; Parvez, Faruque; Ahmed, Alauddin; Hasan, Rabiul; Rakibuz-Zaman, Muhammad; Islam, Tariqul; Eunus, Mahbubul; Sarwar, Golam; Chinchilli, Vernon M.; Neugut, Alfred I.; Ahsan, Habibul

    2016-01-01

    Objective Baseline, persistent, incident, and remittent dipstick proteinuria have never been tested as predictors of mortality in an undeveloped country. The goal of this study was to determine which of these four types of proteinuria (if any) predict mortality. Methods Baseline data was collected from 2000–2002 in Bangladesh from 11,121 adults. Vital status was ascertained over 11–12 years. Cox models were used to evaluate proteinuria in relation to all-cause and cardiovascular disease (CVD) mortality. CVD mortality was evaluated only in those with baseline proteinuria. Persistent, remittent, and incident proteinuria were determined at the 2-year exam. Results Baseline proteinuria of 1+ or greater was significantly associated with all-cause (hazard ratio (HR) 2.87; 95% C.I., 1.71 – 4.80) and CVD mortality (HR: 3.55; 95% C.I., 1.81–6.95) compared to no proteinuria, adjusted for age, gender, arsenic well water concentration, education, hypertension, BMI, smoking, and diabetes mellitus. Persistent 1+ proteinuria had a stronger risk of death, 3.49 (1.64 – 7.41)-fold greater, than no proteinuria. Incident 1+ proteinuria had a 1.87 (0.92 – 3.78)-fold greater mortality over 9–10 years. Remittent proteinuria revealed no increased mortality. Conclusions Baseline, persistent, and incident dipstick proteinuria were predictors of all-cause mortality with persistent proteinuria having the greatest risk. In developing countries, those with 1+ dipstick proteinuria, particularly if persistent, should be targeted for definitive diagnosis and treatment. The two most common causes of proteinuria to search for are diabetes mellitus and hypertension. PMID:26190365

  11. All-cause and cause-specific mortality of immigrants and native born in the United States.

    PubMed Central

    Singh, G K; Siahpush, M

    2001-01-01

    OBJECTIVES: This study examined whether US-born people and immigrants 25 years or older differ in their risks of all-cause and cause-specific mortality and whether these differentials, if they exist, vary according to age, sex, and race/ethnicity. METHODS: Using data from the National Longitudinal Mortality Study (1979-1989), we derived mortality risks of immigrants relative to those of US-born people by using a Cox regression model after adjusting for age, race/ethnicity, marital status, urban/rural residence, education, occupation, and family income. RESULTS: Immigrant men and women had, respectively, an 18% and 13% lower risk of overall mortality than their US-born counterparts. Reduced mortality risks were especially pronounced for younger and for Black and Hispanic immigrants. Immigrants showed significantly lower risks of mortality from cardiovascular diseases, lung and prostate cancer, chronic obstructive pulmonary diseases, cirrhosis, pneumonia and influenza, unintentional injuries, and suicide but higher risks of mortality from stomach and brain cancer and infectious diseases. CONCLUSIONS: Mortality patterns for immigrants and for US-born people vary considerably, with immigrants experiencing lower mortality from several major causes of death. Future research needs to examine the role of sociocultural and behavioral factors in explaining the mortality advantage of immigrants. PMID:11236403

  12. All-Cause Mortality in Women With Severe Postpartum Psychiatric Disorders

    PubMed Central

    Johannsen, Benedicte Marie Winther; Larsen, Janne Tidselbak; Laursen, Thomas Munk; Bergink, Veerle; Meltzer-Brody, Samantha; Munk-Olsen, Trine

    2017-01-01

    Objective The postpartum period is associated with a high risk of psychiatric episodes. The authors studied mortality in women with first-onset severe psychiatric disorders following childbirth and compared their mortality rates with those in women from the background population including other female psychiatric patients (mothers and childless women). Method In a register-based cohort study with linked information from Danish population registers, the authors identified women with first psychiatric inpatient or outpatient contacts 0–3 months postpartum. The main outcome measure was mortality rate ratios (MRRs): deaths from natural causes (diseases and medical conditions) or unnatural causes (suicides, accidents, and homicides). The cohort included 1,545,857 women representing 68,473,423 person-years at risk. Results In total, 2,699 women had first-onset psychiatric disorders 0–3 months postpartum, and 96 of these died during follow-up. Women with postpartum psychiatric disorders had a higher MRR (3.74; 95% CI=3.06–4.57) than non-postpartum-onset mothers (MRR=2.73; 95% CI=2.67–2.79) when compared with mothers with no psychiatric history. However, childless women with psychiatric diagnoses had the highest MRR (6.15; 95% CI=5.94–6.38). Unnatural cause of death represented 40.6% of fatalities among women with postpartum psychiatric disorders, and within the first year after diagnosis, suicide risk was drastically increased (MRR=289.42; 95% CI=144.02–581.62) when compared with mothers with no psychiatric history. Conclusions Women with severe postpartum psychiatric disorders had increased MRRs compared with mothers without psychiatric diagnoses, and the first year after diagnosis represents a time of particularly high relative risk for suicide in this vulnerable group. PMID:26940804

  13. Apparent treatment-resistant hypertension and risk for stroke, coronary heart disease, and all-cause mortality.

    PubMed

    Irvin, Marguerite R; Booth, John N; Shimbo, Daichi; Lackland, Daniel T; Oparil, Suzanne; Howard, George; Safford, Monika M; Muntner, Paul; Calhoun, David A

    2014-06-01

    Apparent treatment-resistant hypertension (aTRH) is defined as uncontrolled hypertension despite the use of three or more antihypertensive medication classes or controlled hypertension while treated with four or more antihypertensive medication classes. We evaluated the association of aTRH with incident stroke, coronary heart disease (CHD), and all-cause mortality. Participants from the population-based REasons for Geographic And Racial Differences in Stroke (REGARDS) Study treated for hypertension with aTRH (n = 2043) and without aTRH (n = 12,479) were included. aTRH was further categorized as controlled aTRH (≥4 medication classes and controlled hypertension) and uncontrolled aTRH (≥3 medication classes and uncontrolled hypertension). Over a median of 5.9, 4.4, and 6.0 years of follow-up, the multivariable adjusted hazard ratio for stroke, CHD, and all-cause mortality associated with aTRH versus no aTRH was 1.25 (0.94-1.65), 1.69 (1.27-2.24), and 1.29 (1.14-1.46), respectively. Compared with controlled aTRH, uncontrolled aTRH was associated with CHD (hazard ratio, 2.33; 95% confidence interval, 1.21-4.48), but not stroke or mortality. Comparing controlled aTRH with no aTRH, risk of stroke, CHD, and all-cause mortality was not elevated. aTRH was associated with an increased risk for coronary heart disease and all-cause mortality.

  14. Association of CKD-MBD Markers with All-Cause Mortality in Prevalent Hemodialysis Patients: A Cohort Study in Beijing

    PubMed Central

    Li, Duo; Zhang, Ling; Zuo, Li; Jin, Cheng Gang; Li, Wen Ge; Chen, Jin-Bor

    2017-01-01

    The relationships between all-cause mortality and serum intact parathyroid hormone (iPTH), calcium, and phosphate are fairly diverse in patients on maintenance hemodialysis according to prior studies. This study evaluated the association of chronic kidney disease-mineral and bone disorder (CKD-MBD) markers with all-cause mortality in prevalent hemodialysis patients from 2007 to 2012 in Beijing, China. A cohort, involving 8530 prevalent hemodialysis patients who had undergone a 6–70 months follow-up program (with median as 40 months) was formed. Related data was recorded from the database in 120 hemodialysis centers of Beijing Health Bureau (2007 to 2012). Information regarding baseline demographics, blood CKD-MBD markers and all-cause mortality was retrospectively reviewed. By using multivariate Cox regression model analysis, patients with a low iPTH level at baseline were found to have greater risk of mortality (<75pg/ml, HR = 1.36, 95% confidence interval (CI) 1.16–1.60) than those with a baseline iPTH level within 150–300 pg/ml. Similarly, death risk showed an increase when the baseline serum calcium presented a low level (<2.1mmol/L, HR = 1.54; 95% CI 1.37–1.74). Levels of baseline serum phosphorus were not associated with the risk of death. Similar results appeared through the baseline competing risks regression analysis. Patients with a lower level of serum iPTH or calcium are at a higher risk of all-cause mortality compared with those within the range recommended by Kidney Disease Outcome Quality Initiative (KDOQI) guidelines. PMID:28045985

  15. Pre-dialysis systolic blood pressure-variability is independently associated with all-cause mortality in incident haemodialysis patients.

    PubMed

    Selvarajah, Viknesh; Pasea, Laura; Ojha, Sanjay; Wilkinson, Ian B; Tomlinson, Laurie A

    2014-01-01

    Systolic blood pressure variability is an independent risk factor for mortality and cardiovascular events. Standard measures of blood pressure predict outcome poorly in haemodialysis patients. We investigated whether systolic blood pressure variability was associated with mortality in incident haemodialysis patients. We performed a longitudinal observational study of patients commencing haemodialysis between 2005 and 2011 in East Anglia, UK, excluding patients with cardiovascular events within 6 months of starting haemodialysis. The main exposure was variability independent of the mean (VIM) of systolic blood pressure from short-gap, pre-dialysis blood pressure readings between 3 and 6 months after commencing haemodialysis, and the outcome was all-cause mortality. Of 203 patients, 37 (18.2%) patients died during a mean follow-up of 2.0 (SD 1.3) years. The age and sex-adjusted hazard ratio (HR) for mortality was 1.09 (95% confidence interval (CI) 1.02-1.17) for a one-unit increase of VIM. This was not altered by adjustment for diabetes, prior cardiovascular disease and mean systolic blood pressure (HR 1.09, 95% CI 1.02-1.16). Patients with VIM of systolic blood pressure above the median were 2.4 (95% CI 1.17-4.74) times more likely to die during follow-up than those below the median. Results were similar for all measures of blood pressure variability and further adjustment for type of dialysis access, use of antihypertensives and absolute or variability of fluid intake did not alter these findings. Diastolic blood pressure variability showed no association with all cause mortality. Our study shows that variability of systolic blood pressure is a strong and independent predictor of all-cause mortality in incident haemodialysis patients. Further research is needed to understand the mechanism as this may form a therapeutic target or focus for management.

  16. Perceived Social Support Trajectories and the All-Cause Mortality Risk of Older Mexican American Women and Men

    PubMed Central

    Hill, Terrence D.; Uchino, Bert N.; Eckhardt, Jessica L.; Angel, Jacqueline L.

    2016-01-01

    Although numerous studies of non-Hispanic whites and blacks show that social integration and social support tend to favor longevity, it is unclear whether this general pattern extends to the Mexican American population. Building on previous research, we employed seven waves of data from the Hispanic Established Populations for the Epidemiologic Study of the Elderly to examine the association between perceived social support trajectories and the all-cause mortality risk of older Mexican Americans. Growth mixture estimates revealed three latent classes of support trajectories: high, moderate, and low. Cox regression estimates indicated that older Mexican American men in the low support trajectory tend to exhibit a higher mortality risk than their counterparts in the high support trajectory. Social support trajectories were unrelated to the mortality risk of older Mexican American women. A statistically significant interaction term confirmed that social support was more strongly associated with the mortality risk of men. PMID:26966256

  17. Perceived Social Support Trajectories and the All-Cause Mortality Risk of Older Mexican American Women and Men.

    PubMed

    Hill, Terrence D; Uchino, Bert N; Eckhardt, Jessica L; Angel, Jacqueline L

    2016-04-01

    Although numerous studies of non-Hispanic Whites and Blacks show that social integration and social support tend to favor longevity, it is unclear whether this general pattern extends to the Mexican American population. Building on previous research, we employed seven waves of data from the Hispanic Established Populations for the Epidemiologic Study of the Elderly to examine the association between perceived social support trajectories and the all-cause mortality risk of older Mexican Americans. Growth mixture estimates revealed three latent classes of support trajectories: high, moderate, and low. Cox regression estimates indicated that older Mexican American men in the low support trajectory tend to exhibit a higher mortality risk than their counterparts in the high support trajectory. Social support trajectories were unrelated to the mortality risk of older Mexican American women. A statistically significant interaction term confirmed that social support was more strongly associated with the mortality risk of men.

  18. Relation of platelet C4d with all-cause mortality and ischemic stroke in patients with systemic lupus erythematosus.

    PubMed

    Kao, Amy H; McBurney, Christine A; Sattar, Abdus; Lertratanakul, Apinya; Wilson, Nicole L; Rutman, Sarah; Paul, Barbara; Navratil, Jeannine S; Scioscia, Andrea; Ahearn, Joseph M; Manzi, Susan

    2014-08-01

    Systemic lupus erythematosus (SLE) is an autoimmune disease associated with significant morbidity, including premature cardiovascular disease, and mortality. Platelets bearing complement protein C4d (P-C4d) were initially determined to be specific for diagnosis of SLE and were later found to be associated with acute ischemic stroke in non-SLE patients. P-C4d may identify a subset of SLE patients with a worse clinical prognosis. This study investigated the associations of P-C4d with all-cause mortality and vascular events in a lupus cohort. A cohort of 356 consecutive patients with SLE was followed from 2001 to 2009. Primary outcome was all-cause mortality. Secondary outcomes were vascular events (myocardial infarction, coronary artery bypass graft, percutaneous coronary transluminal angioplasty, ischemic stroke, venous thromboembolism, pulmonary embolism, or other thrombosis). P-C4d was measured at study baseline. Seventy SLE patients (19.7%) had P-C4d. Mean follow-up was 4.7 years. All-cause mortality was 4%. P-C4d was associated with all-cause mortality (hazard ratio 7.52, 95% confidence interval (CI) 2.14-26.45, p = 0.002) after adjusting for age, ethnicity, sex, cancer, and anticoagulant use. Vascular event rate was 21.6%. Patients with positive P-C4d were more likely to have had vascular events compared to those with negative P-C4d (35.7 vs. 18.2%, p = 0.001). Specifically, P-C4d was associated with ischemic stroke (odds ratio 4.54, 95% CI 1.63-12.69, p = 0.004) after adjusting for age, ethnicity, and antiphospholipid antibodies. Platelet-C4d is associated with all-cause mortality and stroke in SLE patients. P-C4d may be a prognostic biomarker as well as a pathogenic clue that links platelets, complement activation, and thrombosis.

  19. Mid-arm muscle circumference as a significant predictor of all-cause mortality in male individuals

    PubMed Central

    Wu, Li-Wei; Lin, Yuan-Yung; Kao, Tung-Wei; Lin, Chien-Ming; Liaw, Fang-Yih; Wang, Chung-Ching; Peng, Tao-Chun; Chen, Wei-Liang

    2017-01-01

    Background Emerging evidences indicate that mid-arm muscle circumference (MAMC) is one of the anthropometric indicators that reflect health and nutritional status, but its correlative effectiveness in all-cause mortality prediction of United States individuals remains uncertain. Methods and findings design We investigated the joint association between MAMC and all-cause mortality in the US general population. A population-based longitudinal study of 6,769 participants aged 40 to 90 years in the third National Health and Nutrition Examination Survey (NHANES III) conducted by the National Center for Health Statistics of the Centers for Disease Control and Prevention. All participants were divided into two groups based on the gender: male and female group; each group was then divided into three subgroups depending on their MAMC level. The tertiles were as follows: T1 (18<27.3), T2 (27.3<29.6), T3 (29.6≤40.0) cm in the male group and T1 (15<22.3), T2 (22.3<24.6), T3 (24.6≤44.0) cm in the female group. Multivariable Cox regression analyses and Kaplan–Meier survival probabilities were utilized to jointly relate all-cause mortality risk to different MAMC level. For all-cause mortality in male participants, multivariable adjusted hazard ratios (HRs) were 0.83 (95% confidence interval (CI): 0.69–0.98; p = 0.033) for MAMC of 27.3–29.6 cm compared with 18–27.3 cm, and 0.76 (95% CI: 0.61–0.95; p = 0.018) for MAMC of 29.6–40 cm compared with 18–27.3 cm. For all-cause mortality in female participants, multivariable adjusted hazard ratios (HRs) were 0.84 (95% confidence interval (CI): 0.69–1.02; p = 0.075) for MAMC of 22.3–24.6 cm compared with 15–22.3 cm, and 0.94 (95% CI: 0.75–1.17; p = 0.583) for MAMC of 24.6–44 cm compared with 15–22.3 cm. Conclusion Results support a lower MAMC is associated with a higher mortality risk in male individuals. PMID:28196081

  20. Association Between Tooth Loss, Body Mass Index, and All-Cause Mortality Among Elderly Patients in Taiwan

    PubMed Central

    Hu, Hsiao-Yun; Lee, Ya-Ling; Lin, Shu-Yi; Chou, Yi-Chang; Chung, Debbie; Huang, Nicole; Chou, Yiing-Jenq; Wu, Chen-Yi

    2015-01-01

    Abstract To date, the effect of tooth loss on all-cause mortality among elderly patients with a different weight group has not been assessed. This retrospective cohort study evaluated the data obtained from a government-sponsored, annual physical examination program for elderly citizens residing in Taipei City during 2005 to 2007, and follow-up to December 31, 2010. We recruited 55,651 eligible citizens of Taipei City aged ≥65 years, including 29,572 men and 26,079 women, in our study. Their mortality data were ascertained based on the national death files. The number of missing teeth was used as a representative of oral health status. We used multivariate Cox proportional hazards regression analysis to determine the association between tooth loss and all-cause mortality. After adjustment for all confounders, the hazard ratios (HRs) of all-cause mortality in participants with no teeth, 1 to 9 teeth, and 10 to 19 teeth were 1.36 [95% confidence interval (CI): 1.15–1.61], 1.24 (95% CI: 1.08–1.42), and 1.19 (95% CI: 1.09–1.31), respectively, compared with participants with 20 or more teeth. A significant positive correlation of body mass index (BMI) with all-cause mortality was found in underweight and overweight elderly patients and was represented as a U-shaped curve. Subgroup analysis revealed a significant positive correlation in underweight (no teeth: HR = 1.49, 95% CI: 1.21–1.83; 1–9 teeth: HR = 1.23, 95% CI: 1.03–1.47; 10–19 teeth: HR = 1.20, 95% CI: 1.06–1.36) and overweight participants (no teeth: HR = 1.37, 95% CI: 1.05–1.79; 1–9 teeth: HR = 1.27, 95% CI: 1.07–1.52). The number of teeth lost is associated with an increased risk of all-cause mortality, particularly for participants with underweight and overweight. PMID:26426618

  1. Relation of Periodontitis to Risk of Cardiovascular and All-Cause Mortality (from a Danish Nationwide Cohort Study).

    PubMed

    Hansen, Gorm Mørk; Egeberg, Alexander; Holmstrup, Palle; Hansen, Peter Riis

    2016-08-15

    Periodontitis and atherosclerosis are highly prevalent chronic inflammatory diseases, and it has been suggested that periodontitis is an independent risk factor of cardiovascular disease (CVD) and that a causal link may exist between the 2 diseases. Using Danish national registers, we identified a nationwide cohort of 17,691 patients who received a hospital diagnosis of periodontitis within a 15-year period and matched them with 83,003 controls from the general population. We performed Poisson regression analysis to determine crude and adjusted incidence rate ratios of myocardial infarction, ischemic stroke, cardiovascular death, major adverse cardiovascular events, and all-cause mortality. The results showed that patients with periodontitis were at higher risk of all examined end points. The findings remained significant after adjustment for increased baseline co-morbidity in periodontitis patients compared with controls, for example, with adjusted incidence rate ratio 2.02 (95% CI 1.87 to 2.18) for cardiovascular death and 2.70 (95% CI 2.60 to 2.81) for all-cause mortality. Patients with a hospital diagnosis of periodontitis have a high burden of co-morbidity and an increased risk of CVD and all-cause mortality. In conclusion, our results support that periodontitis may be an independent risk factor for CVD.

  2. Association between dietary fiber and lower risk of all-cause mortality: a meta-analysis of cohort studies.

    PubMed

    Yang, Yang; Zhao, Long-Gang; Wu, Qi-Jun; Ma, Xiao; Xiang, Yong-Bing

    2015-01-15

    Although in vitro and in vivo experiments have suggested that dietary fiber might have beneficial effects on health, results on the association between fiber intake and all-cause mortality in epidemiologic studies have been inconsistent. Therefore, we conducted a meta-analysis of prospective cohort studies to quantitatively assess this association. Pertinent studies were identified by searching articles in PubMed and Web of Knowledge through May 2014 and reviewing the reference lists of the retrieved articles. Study-specific risk estimates were combined using random-effects models. Seventeen prospective studies (1997-2014) that had a total of 67,260 deaths and 982,411 cohort members were included. When comparing persons with dietary fiber intakes in the top tertile with persons whose intakes were in the bottom tertile, we found a statistically significant inverse association between fiber intake and all-cause mortality, with an overall relative risk of 0.84 (95% confidence interval: 0.80, 0.87; I(2) = 41.2%). There was a 10% reduction in risk for per each 10-g/day increase in fiber intake (relative risk = 0.90; 95% confidence interval: 0.86, 0.94; I(2) = 77.2%). The combined estimate was robust across subgroup and sensitivity analyses. No publication bias was detected. A higher dietary fiber intake was associated with a reduced risk of death. These findings suggest that fiber intake may offer a potential public health benefit in reducing all-cause mortality.

  3. Waist circumference and waist/hip ratio in relation to all-cause mortality, cancer and sleep apnea.

    PubMed

    Seidell, J C

    2010-01-01

    Abdominal obesity assessed by waist or waist/hip ratio are both related to increased risk of all-cause mortality throughout the range of body mass index (BMI). The relative risks (RRs) seem to be relatively stronger in younger than in older adults and in those with relatively low BMI compared with those with high BMI. Absolute risks and risk differences are preferable measures of risk in a public health context but these are rarely presented. There is a great lack of studies in ethnic groups (groups of African and Asian descent particularly). Current cut-points as recommended by the World Health Organization seem appropriate, although it may be that BMI-specific and ethnic-specific waist cut-points may be warranted. Waist alone could replace both waist-hip ratio and BMI as a single risk factor for all-cause mortality. There is much less evidence for waist to replace BMI for cancer risk mainly because of the relative lack of prospective cohort studies on waist and cancer risk. Obesity is also a risk factor for sleep apnoea where neck circumference seems to give the strongest association, and waist-hip ratio is a risk factor especially in severe obstructive sleep apnoea syndrome. The waist circumference and waist-hip ratio seem to be better indicators of all-cause mortality than BMI.

  4. A systematic review and meta-analysis of nut consumption and incident risk of CVD and all-cause mortality.

    PubMed

    Mayhew, Alexandra J; de Souza, Russell J; Meyre, David; Anand, Sonia S; Mente, Andrew

    2016-01-28

    Dietary patterns containing nuts are associated with a lower risk of CVD mortality, and increased nut consumption has been shown to have beneficial effects on CVD risk factors including serum lipid levels. Recent studies have reported on the relationship between nut intake and CVD outcomes and mortality. Our objective was to systematically review the literature and quantify associations between nut consumption and CVD outcomes and all-cause mortality. Five electronic databases (through July 2015), previous reviews and bibliographies of qualifying articles were searched. In the twenty included prospective cohort studies (n 467 389), nut consumption was significantly associated with a lower risk of all-cause mortality (ten studies; risk ratio (RR) 0·81; 95 % CI 0·77, 0·85 for highest v. lowest quantile of intake, P het=0·04, I 2=43 %), CVD mortality (five studies; RR 0·73; 95 % CI 0·68, 0·78; P het=0·31, I 2=16 %), all CHD (three studies; RR 0·66; 95 % CI 0·48, 0·91; P het=0·0002, I 2=88 %) and CHD mortality (seven studies; RR 0·70; 95 % CI 0·64, 0·76; P het=0·65, I 2=0 %), as well as a statistically non-significant reduction in the risk of non-fatal CHD (three studies; RR 0·71; 95 % CI 0·49, 1·03; P het=0·03, I 2=72 %) and stroke mortality (three studies; RR 0·83; 95 % CI 0·69, 1·00; P het=0·54, I 2=0 %). No evidence of association was found for total stroke (two studies; RR 1·05; 95 % CI 0·69, 1·61; P het=0·04, I 2=77 %). Data on total CVD and sudden cardiac death were available from one cohort study, and they were significantly inversely associated with nut consumption. In conclusion, we found that higher nut consumption is associated with a lower risk of all-cause mortality, total CVD, CVD mortality, total CHD, CHD mortality and sudden cardiac death.

  5. The association between ischemic and jeopardized myocardia and all-cause mortality in patients with peripheral artery disease.

    PubMed

    Hammad, Tarek A; Yousefzai, Rayan; Venkatachalam, Sridhar; Lowry, Ashley; Gornik, Heather L; Jaber, Wael; Bartholomew, John R; Kim, Soo Hyun; Cerqueira, Manuel; Gray, Bruce H; Blackstone, Eugene H; Shishehbor, Mehdi H

    2016-04-01

    Peripheral artery disease (PAD) is associated with increased mortality and concomitant coronary artery disease (CAD). However, it is unclear whether uncovering the presence of functional coronary ischemia by single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) would further help stratifying that excess risk. From January 2000 to 2009, 4294 individuals underwent cardiac stress testing within 180 days of ankle-brachial index (ABI) measurements. Of these, 645 had PAD and SPECT MPI stress testing. Abnormal ABI was defined as ⩽ 0.9 or prior lower extremity arterial revascularization. Myocardial ischemic burden and total jeopardized myocardium were represented by the summed difference score (SDS) and summed stress score (SSS), respectively. Univariate and multivariable Cox proportional hazard analyses were used to study the impact of SDS and SSS on all-cause mortality. Additionally, using a hierarchical approach, we examined the step-wise addition of post-stress test coronary and lower extremity arterial revascularizations as time-varying covariates on outcomes. We found no significant difference in all-cause mortality between patients with ischemic myocardium (SDS > 0) and those without (SDS = 0) (adjusted HR: 0.94, 95% CI: 0.53-1.69; p = 0.84). Similarly, the presence of jeopardized myocardium (SSS > 0) did not have a significant impact on mortality (adjusted HR: 1.16, 95% CI: 0.67-2.00; p = 0.59). Moreover, adjustment for post-testing coronary and lower extremity arterial revascularizations did not affect our results. In conclusion, ischemic and jeopardized myocardia are not predictors of all-cause mortality in PAD; thus, SPECT MPI does not appear to be a useful risk stratification tool in these patients.

  6. Smoking increases the risk of all-cause and cardiovascular mortality in patients with chronic kidney disease.

    PubMed

    Nakamura, Koshi; Nakagawa, Hideaki; Murakami, Yoshitaka; Kitamura, Akihiko; Kiyama, Masahiko; Sakata, Kiyomi; Tsuji, Ichiro; Miura, Katsuyuki; Ueshima, Hirotsugu; Okamura, Tomonori

    2015-11-01

    Little is known about the magnitude and nature of the combined effect of chronic kidney disease (CKD) and smoking on cardiovascular diseases. We studied this in a Japanese population using a pooled analysis of 15,468 men and 19,154 women aged 40-89 years enrolled in 8 cohort studies. The risk of mortality from all-causes and cardiovascular disease was compared in 6 gender-specific categories of baseline CKD status (non-CKD or CKD) and smoking habits (lifelong never smoked, former smokers, or currently smoking). CKD was defined as a decreased level of estimated glomerular filtration rate (under 60 ml/min per 1.73 m(2)) and/or dipstick proteinuria. Hazard ratios were estimated for each category, relative to never smokers without CKD. During the follow-up period (mean 14.8 years), there were 6771 deaths, 1975 of which were due to cardiovascular diseases. In both men and women, current or former smokers with CKD had the first or second highest crude mortality rates from all-cause and cardiovascular diseases among the 6 categories. After adjustment for age and other major cardiovascular risk factors, the hazard ratios in male and female current smokers with CKD were 2.26 (95% confidence interval, 1.95-2.63) and 1.78 (1.36-2.32) for all-causes, and 2.66 (2.04-3.47) and 1.71 (1.10-2.67) for cardiovascular diseases, respectively. Thus, coexistence of CKD and smoking may markedly increase the risk of all-cause and cardiovascular mortality.

  7. Abdominal obesity modifies the risk of hypertriglyceridemia for all-cause and cardiovascular mortality in hemodialysis patients.

    PubMed

    Postorino, Maurizio; Marino, Carmen; Tripepi, Giovanni; Zoccali, Carmine

    2011-04-01

    Hypertriglyceridemia is the most prevalent lipid alteration in end-stage renal disease, and we studied the relationship between serum triglycerides and all-cause and cardiovascular death in these patients. Since abdominal fat modifies the effect of lipids on atherosclerosis, we analyzed the interaction between serum lipids and waist circumference (WC) as a metric of abdominal obesity. In a cohort of 537 hemodialysis patients, 182 died, 113 from cardiovascular causes, over an average follow-up of 29 months. In Cox models that included traditional and nontraditional risk factors, there were significant strong interactions between triglycerides and WC to both all-cause and cardiovascular death. A fixed (50 mg/dl) excess in triglycerides was associated with a progressive lower risk of all-cause and cardiovascular mortality in patients with threshold WC <95 cm but with a progressive increased risk in those above this threshold. A significant interaction between cholesterol and WC with all-cause and cardiovascular death emerged only in models excluding the triglycerides-WC interaction. Neither high-density lipoprotein (HDL) nor non-HDL cholesterol or their interaction terms with WC were associated with study outcomes. Thus, the predictive value of triglycerides and cholesterol for survival and atherosclerotic complications in hemodialysis patients is critically dependent on WC. Hence, intervention studies in end-stage renal disease should specifically target patients with abdominal obesity and hyperlipidemia.

  8. Diet Quality Scores and Prediction of All-Cause, Cardiovascular and Cancer Mortality in a Pan-European Cohort Study.

    PubMed

    Lassale, Camille; Gunter, Marc J; Romaguera, Dora; Peelen, Linda M; Van der Schouw, Yvonne T; Beulens, Joline W J; Freisling, Heinz; Muller, David C; Ferrari, Pietro; Huybrechts, Inge; Fagherazzi, Guy; Boutron-Ruault, Marie-Christine; Affret, Aurélie; Overvad, Kim; Dahm, Christina C; Olsen, Anja; Roswall, Nina; Tsilidis, Konstantinos K; Katzke, Verena A; Kühn, Tilman; Buijsse, Brian; Quirós, José-Ramón; Sánchez-Cantalejo, Emilio; Etxezarreta, Nerea; Huerta, José María; Barricarte, Aurelio; Bonet, Catalina; Khaw, Kay-Tee; Key, Timothy J; Trichopoulou, Antonia; Bamia, Christina; Lagiou, Pagona; Palli, Domenico; Agnoli, Claudia; Tumino, Rosario; Fasanelli, Francesca; Panico, Salvatore; Bueno-de-Mesquita, H Bas; Boer, Jolanda M A; Sonestedt, Emily; Nilsson, Lena Maria; Renström, Frida; Weiderpass, Elisabete; Skeie, Guri; Lund, Eiliv; Moons, Karel G M; Riboli, Elio; Tzoulaki, Ioanna

    2016-01-01

    Scores of overall diet quality have received increasing attention in relation to disease aetiology; however, their value in risk prediction has been little examined. The objective was to assess and compare the association and predictive performance of 10 diet quality scores on 10-year risk of all-cause, CVD and cancer mortality in 451,256 healthy participants to the European Prospective Investigation into Cancer and Nutrition, followed-up for a median of 12.8y. All dietary scores studied showed significant inverse associations with all outcomes. The range of HRs (95% CI) in the top vs. lowest quartile of dietary scores in a composite model including non-invasive factors (age, sex, smoking, body mass index, education, physical activity and study centre) was 0.75 (0.72-0.79) to 0.88 (0.84-0.92) for all-cause, 0.76 (0.69-0.83) to 0.84 (0.76-0.92) for CVD and 0.78 (0.73-0.83) to 0.91 (0.85-0.97) for cancer mortality. Models with dietary scores alone showed low discrimination, but composite models also including age, sex and other non-invasive factors showed good discrimination and calibration, which varied little between different diet scores examined. Mean C-statistic of full models was 0.73, 0.80 and 0.71 for all-cause, CVD and cancer mortality. Dietary scores have poor predictive performance for 10-year mortality risk when used in isolation but display good predictive ability in combination with other non-invasive common risk factors.

  9. Coffee consumption and risk of cardiovascular events and all-cause mortality among women with type 2 diabetes

    PubMed Central

    Zhang, W.L.; Lopez-Garcia, E.; Li, T. Y.; Hu, F. B.; van Dam, R. M.

    2009-01-01

    Aims/hypothesis Coffee has been linked to both beneficial and harmful health effects, but data on its relation with cardiovascular disease and mortality in patients with type 2 diabetes are sparse. Methods This is a prospective cohort study including 7,170 women with diagnosed type 2 diabetes but free of cardiovascular disease or cancer at baseline. Coffee consumption was assessed in 1980 and then every 2 to 4 years through validated questionnaires. A total of 658 incident cardiovascular events (434 coronary heart disease and 224 stroke) and 734 deaths from all causes were documented between 1980 and 2004. Results After adjustment for age, smoking, and other cardiovascular risk factors, the relative risks (RRs) were 0.76 (95% CI, 0.50 to 1.14) for cardiovascular diseases (p trend = 0.09) and 0.80 (95% CI, 0.55 to 1.14) for all-cause mortality (p trend = 0.05) for the consumption of ≥ 4 cups/day caffeinated coffee as compared with nondrinkers. Similarly, multivariable RRs were 0.96 (95% CI, 0.66 to 1.38) for cardiovascular diseases (p trend = 0.84) and 0.76 (95% CI, 0.54 to 1.07) for all-cause mortality (p trend = 0.08) for the consumption of ≥ 2 cups/day decaffeinated coffee as compared with nondrinkers. Higher decaffeinated coffee consumption was associated with lower concentrations of glycosylated hemoglobin (6.2% for ≥ 2 cups/d versus 6.7% for < 1 cup/mo; p trend = 0.02). Conclusions These data provides evidence that habitual coffee consumption is not associated with increased risk for cardiovascular diseases or premature mortality among diabetic women. PMID:19266179

  10. Tuberculin status, socioeconomic differences and differences in all-cause mortality: experience from Norwegian cohorts born 1910–49

    PubMed Central

    Liestøl, Knut; Tretli, Steinar; Tverdal, Aage; Mæhlen, Jan

    2009-01-01

    Background From 1948 to 1975, Norway had a mandatory tuberculosis (TB) screening programme with Pirquet testing, X-ray examinations and BCG vaccination. Electronic data registration in 1963–75 enabled the current study aimed at revealing (i) the relations between socioeconomic factors and tuberculosis infection and (ii) differences in later all-cause mortality according to TB infection status. Methods TB screening data were linked to information from the Norwegian Cause of Death Registry (1975–98) and the National Population and Housing Censuses (1960, 1970 and 1980). Analyses were done for 10 years cohorts born 1910–49, separately for men (∼534 000 individuals) and women (608 000), using logistic and Cox regressions. Results TB infection and X-ray data confirmed the strong regional pattern seen for TB mortality, with the highest rates in the three northernmost counties and higher rates in urban than rural areas. High socioeconomic status relates to lower odds both for TB infection and TB-related chest X-ray findings (odds ratios 0.6–0.7 for highest vs lowest educational groups). Those infected by TB, and especially those with chest X-ray findings, have increased all-cause mortality in at least a 20 years period following determination of tuberculin status (hazard ratios ∼1.15 and 1.30, respectively, higher for late than early cohorts). Conclusions TB particularly affected lower socioeconomic strata, but even those in higher strata were at high risk. The differences in all-cause mortality could partly be attributed to socioeconomic factors, but we hypothesize that developing TB infection may also indicate biological frailness. PMID:19339259

  11. Effect of Dipeptidyl Peptidase-4 Inhibitor on All-Cause Mortality and Coronary Revascularization in Diabetic Patients

    PubMed Central

    Park, Hyo Eun; Jeon, Jooyeong; Hwang, In-Chang; Sung, Jidong; Lee, Seung-Pyo; Kim, Hyung-Kwan; Cho, Goo-Yeong; Sohn, Dae-Won

    2015-01-01

    Background Anti-atherosclerotic effect of dipeptidyl peptidase-4 (DPP-4) inhibitors has been suggested from previous studies, and yet, its association with cardiovascular outcome has not been demonstrated. We aimed to evaluate the effect of DPP-4 inhibitors in reducing mortality and coronary revascularization, in association with baseline coronary computed tomography (CT). Methods The current study was performed as a multi-center, retrospective observational cohort study. All subjects with diabetes mellitus who had diagnostic CT during 2007-2011 were included, and 1866 DPP-4 inhibitor users and 5179 non-users were compared for outcome. The primary outcome was all-cause mortality and secondary outcome included any coronary revascularization therapy after 90 days of CT in addition to all-cause mortality. Results DPP-4 inhibitors users had significantly less adverse events [0.8% vs. 4.4% in users vs. non-users, adjusted hazard ratios (HR) 0.220, 95% confidence interval (CI) 0.102-0.474, p = 0.0001 for primary outcome, 4.1% vs. 7.6% in users vs. non-users, HR 0.517, 95% CI 0.363-0.735, p = 0.0002 for secondary outcome, adjusted variables were age, sex, presence of hypertension, high sensitivity C-reactive protein, glycated hemoglobin, statin use, coronary artery calcium score and degree of stenosis]. Interestingly, DPP-4 inhibitor seemed to be beneficial only in subjects without significant stenosis (adjusted HR 0.148, p = 0.0013 and adjusted HR 0.525, p = 0.0081 for primary and secondary outcome). Conclusion DPP-4 inhibitor is associated with reduced all-cause mortality and coronary revascularization in diabetic patients. Such beneficial effect was significant only in those without significant coronary stenosis, which implies that DPP-4 inhibitor may have beneficial effect in earlier stage of atherosclerosis. PMID:26755932

  12. Diet Quality Scores and Prediction of All-Cause, Cardiovascular and Cancer Mortality in a Pan-European Cohort Study

    PubMed Central

    Lassale, Camille; Gunter, Marc J.; Romaguera, Dora; Peelen, Linda M.; Van der Schouw, Yvonne T.; Beulens, Joline W. J.; Freisling, Heinz; Muller, David C.; Ferrari, Pietro; Huybrechts, Inge; Fagherazzi, Guy; Boutron-Ruault, Marie-Christine; Affret, Aurélie; Overvad, Kim; Dahm, Christina C.; Olsen, Anja; Roswall, Nina; Tsilidis, Konstantinos K.; Katzke, Verena A.; Kühn, Tilman; Buijsse, Brian; Quirós, José-Ramón; Sánchez-Cantalejo, Emilio; Etxezarreta, Nerea; Huerta, José María; Barricarte, Aurelio; Bonet, Catalina; Khaw, Kay-Tee; Key, Timothy J.; Trichopoulou, Antonia; Bamia, Christina; Lagiou, Pagona; Palli, Domenico; Agnoli, Claudia; Tumino, Rosario; Fasanelli, Francesca; Panico, Salvatore; Bueno-de-Mesquita, H. Bas; Boer, Jolanda M. A.; Sonestedt, Emily; Nilsson, Lena Maria; Renström, Frida; Weiderpass, Elisabete; Skeie, Guri; Lund, Eiliv; Moons, Karel G. M.; Riboli, Elio; Tzoulaki, Ioanna

    2016-01-01

    Scores of overall diet quality have received increasing attention in relation to disease aetiology; however, their value in risk prediction has been little examined. The objective was to assess and compare the association and predictive performance of 10 diet quality scores on 10-year risk of all-cause, CVD and cancer mortality in 451,256 healthy participants to the European Prospective Investigation into Cancer and Nutrition, followed-up for a median of 12.8y. All dietary scores studied showed significant inverse associations with all outcomes. The range of HRs (95% CI) in the top vs. lowest quartile of dietary scores in a composite model including non-invasive factors (age, sex, smoking, body mass index, education, physical activity and study centre) was 0.75 (0.72–0.79) to 0.88 (0.84–0.92) for all-cause, 0.76 (0.69–0.83) to 0.84 (0.76–0.92) for CVD and 0.78 (0.73–0.83) to 0.91 (0.85–0.97) for cancer mortality. Models with dietary scores alone showed low discrimination, but composite models also including age, sex and other non-invasive factors showed good discrimination and calibration, which varied little between different diet scores examined. Mean C-statistic of full models was 0.73, 0.80 and 0.71 for all-cause, CVD and cancer mortality. Dietary scores have poor predictive performance for 10-year mortality risk when used in isolation but display good predictive ability in combination with other non-invasive common risk factors. PMID:27409582

  13. TV viewing time is associated with increased all-cause mortality in Brazilian adults independent of physical activity.

    PubMed

    Turi, Bruna Camilo; Monteiro, Henrique Luiz; Ribeiro Lemes, Ítalo; Codogno, Jamile Sanches; Lynch, Kyle Robinson; Asahi Mesquita, Camila Angélica; Fernandes, Rômulo Araújo

    2017-03-22

    The purpose of this study was to investigate the association between television (TV) viewing and all-cause mortality among Brazilian adults after six years of follow-up. This longitudinal study started in 2010 in the city of Bauru, SP, Brazil, and involved 970 adults aged ≥ 50 years. Mortality was reported by relatives and confirmed in medical records of the Brazilian National Health System. Physical activity (PA) and TV viewing were assessed by the Baecke questionnaire. Health status, sociodemographic and behavioural covariates were considered as potential confounders. After six years of follow-up, 89 deaths were registered (9.2% [95%CI= 7.4% to 11%]). Type 2 diabetes mellitus was associated with higher risk of mortality (p-value= 0.012). Deaths correlated significantly with age (rho= 0.188; p-value= 0.001), overall PA score (rho= -0.128; p-value= 0.001) and TV viewing (rho= 0.086; p-value= 0.007). Lower percentage of participants reported TV viewing time as often (16%) and very often (5.7%), but there was an association between higher TV viewing time ("often" and "very often" grouped together) and increased mortality after six years of follow-up (p-value= 0.006). The higher TV viewing time was associated with a 44.7% increase in all-cause mortality (HR= 1.447 [1.019 to 2.055]), independently of other potential confounders. In conclusion, the findings from this cohort study identified increased risk of mortality among adults with higher TV viewing time, independently of physical activity and other variables. This article is protected by copyright. All rights reserved.

  14. Gender differences in education effects on all-cause mortality for white and black adults in the United States.

    PubMed

    Zajacova, Anna; Hummer, Robert A

    2009-08-01

    The existence of education differentials in adult mortality has been well established. The issue of gender differences in the education-mortality association, however, remains an open question, despite its importance for understanding of causal pathways through which education affects health outcomes. The goal of this paper is to analyze gender differences in education gradients in mortality among non-Hispanic white and black U.S. adults born between 1906 and 1965. The analysis is based on data from the 1986-2000 National Health Interview Surveys linked to the National Death Index through 2002 (NHIS-LMF) with over 700,000 respondents. Full-sample and cohort-stratified Cox proportional hazard models of all-cause mortality were estimated. Results indicate a great deal of similarity between men and women in the education-mortality association, with some exceptions. The most notable difference is the steeper educational gradient at high schooling levels for white men compared to white women. This difference was fully explained by marital status. No systematic gender differences in the relationship between education and adult mortality were observed among black adults in any birth cohorts. The findings suggest that men do not benefit from educational attainment uniformly more than women.

  15. Paleolithic and Mediterranean Diet Pattern Scores Are Inversely Associated with All-Cause and Cause-Specific Mortality in Adults.

    PubMed

    Whalen, Kristine A; Judd, Suzanne; McCullough, Marjorie L; Flanders, W Dana; Hartman, Terryl J; Bostick, Roberd M

    2017-04-01

    Background: Poor diet quality is associated with a higher risk of many chronic diseases that are among the leading causes of death in the United States. It has been hypothesized that evolutionary discordance may account for some of the higher incidence and mortality from these diseases.Objective: We investigated associations of 2 diet pattern scores, the Paleolithic and the Mediterranean, with all-cause and cause-specific mortality in the REGARDS (REasons for Geographic and Racial Differences in Stroke) study, a longitudinal cohort of black and white men and women ≥45 y of age.Methods: Participants completed questionnaires, including a Block food-frequency questionnaire (FFQ), at baseline and were contacted every 6 mo to determine their health status. Of the analytic cohort (n = 21,423), a total of 2513 participants died during a median follow-up of 6.25 y. We created diet scores from FFQ responses and assessed their associations with mortality using multivariable Cox proportional hazards regression models adjusting for major risk factors.Results: For those in the highest relative to the lowest quintiles of the Paleolithic and Mediterranean diet scores, the multivariable adjusted HRs for all-cause mortality were, respectively, 0.77 (95% CI: 0.67, 0.89; P-trend < 0.01) and 0.63 (95% CI: 0.54, 0.73; P-trend < 0.01). The corresponding HRs for all-cancer mortality were 0.72 (95% CI: 0.55, 0.95; P-trend = 0.03) and 0.64 (95% CI: 0.48, 0.84; P-trend = 0.01), and for all-cardiovascular disease mortality they were 0.78 (95% CI: 0.61, 1.00; P-trend = 0.06) and HR: 0.68 (95% CI: 0.53, 0.88; P-trend = 0.01).Conclusions: Findings from this biracial prospective study suggest that diets closer to Paleolithic or Mediterranean diet patterns may be inversely associated with all-cause and cause-specific mortality.

  16. Oxidative Balance Score as Predictor of All-Cause, Cancer, and Non-cancer Mortality in a Biracial US Cohort

    PubMed Central

    Kong, So Yeon; Goodman, Michael; Judd, Suzanne; Bostick, Roberd M.; Flanders, W. Dana; McClellan, William

    2015-01-01

    Purpose We previously proposed an oxidative balance score (OBS) that combines pro- and anti-oxidant exposures to represent the overall oxidative balance status of an individual. In this study, we investigated associations of the OBS with all-cause and cause-specific mortality, and explored alternative OBS weighting methods in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study cohort. Methods The OBS was calculated by combining information from 14 a priori selected pro- and anti-oxidant factors, and then divided into quartiles with the lowest quartile (predominance of pro-oxidants) as reference. Cox proportional hazard models were used to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CI) for each OBS category compared to the reference. Results Over a median 5.8 years of follow-up, 2,079 of the 21,031 participants died. The multivariable adjusted HRs (95% CI) for all-cause, cancer, and non-cancer mortality for those in the highest vs. the lowest equal-weighting OBS quartile were: 0.70 (0.61, 0.81), 0.50 (0.37, 0.67), and 0.77 (0.66, 0.89), respectively (P-trend < 0.01 for all). Similar results were observed with all weighting methods. Conclusion These results suggest that individuals with a greater balance of anti-oxidant to pro-oxidant lifestyle exposures may have lower mortality. PMID:25682727

  17. Predictors, including blood, urine, anthropometry, and nutritional indices, of all-cause mortality among institutionalized individuals with intellectual disability.

    PubMed

    Ohwada, Hiroko; Nakayama, Takeo; Tomono, Yuji; Yamanaka, Keiko

    2013-01-01

    As the life expectancy of people with intellectual disability (ID) increases, it is becoming necessary to understand factors affecting survival. However, predictors that are typically assessed among healthy people have not been examined. Predictors of all-cause mortality, including blood, urine, anthropometry, and nutritional indices, were examined among institutionalized people with ID. This retrospective cohort study involved 316 participants (191 males, 125 females; mean age, 36.5 ± 10.5 years) at a public facility for people with ID in Ibaraki Prefecture, Japan. During the follow-up from the examination day in 1984-1992 through December 31, 2007 (mean follow-up, 18.6 years), 44 deaths occurred. Mean age at death was 47.1 ± 10.0 years (range, 22.3-65.3 years). Early deaths within three years (n = 4) were treated as censored cases. Cox proportional hazard regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of all-cause mortality. Sex- and age-adjusted analysis (p<0.15) revealed positive associations with mortality for high serum cholesterol, high thymol turbidity test (TTT), and glucosuria and negative associations with mortality for high serum albumin, high uric acid, high potassium, high calcium, and high systolic blood pressure. Multivariate analysis revealed that male sex (HR, 4.11; 95% CI, 1.59-10.59), high serum cholesterol (1.01; 1.00-1.02), high serum TTT (1.21; 1.03-1.41), and epilepsy significantly increased the mortality risk. The results indicate that the predictors of life expectancy for people with ID included both factors that are shared with healthy people (male sex, high serum cholesterol) and factors specific to people with disabilities (high serum TTT and epilepsy).

  18. Prognostic role of copeptin with all-cause mortality after heart failure: a systematic review and meta-analysis

    PubMed Central

    Zhang, Peng; Wu, Xiaomei; Li, Guangxiao; Sun, Hao; Shi, Jingpu

    2017-01-01

    Background As the C-terminal section of vasopressin precursor, copeptin has been recently suggested as a new prognostic biomarker after heart failure (HF). Thus, the aim of this study was to evaluate the prognostic value of plasma copeptin level with all-cause mortality in patients with HF. Methods Comprehensive strategies were used to search relevant studies from electronic databases. Pooled hazard ratios (HRs) and standardized mean differences (SMDs) together with their 95% confidence intervals (CIs) were calculated. Subgroup analysis and sensitivity analysis were performed to find the potential sources of heterogeneity. Results A total of 5,989 participants from 17 prospective studies were included in this meta-analysis. A significant association was observed between circulating copeptin levels and risk of all-cause mortality in patients with HF (categorical copeptin: HR =1.69, 95% CI =1.42–2.01; per unit copeptin: HR =1.03, 95% CI =1.00–1.07; log unit copeptin: HR =3.26, 95% CI =0.95–11.25). Pooled SMD showed that copeptin levels were significantly higher in patients with HF who died during the follow-up period than in survivors (SMD =1.19, 95% CI =0.81–1.57). Subgroup analyses also confirmed this significant association, while sensitivity analyses indicated that the overall results were stable. Conclusion This study demonstrated that circulating copeptin seemed to be a novel biomarker to provide better prediction of all-cause mortality in patients with HF. PMID:28115852

  19. Risk factors of all-cause in-hospital mortality among Korean elderly bacteremic urinary tract infection (UTI) patients.

    PubMed

    Chin, Bum Sik; Kim, Myung Soo; Han, Sang Hoon; Shin, So Youn; Choi, Hee Kyung; Chae, Yun Tae; Jin, Sung Joon; Baek, Ji-Hyeon; Choi, Jun Yong; Song, Young Goo; Kim, Chang Oh; Kim, June Myung

    2011-01-01

    Urinary tract infection (UTI) is the most frequent cause of bacteremia/sepsis in elderly people and increasing antimicrobial resistance in uropathogens has been observed. To describe the characteristics of bacteremic UTI in elderly patients and to identify the independent risk factors of all-cause in-hospital mortality, a retrospective cohort study of bacteremic UTI patients of age over 65 was performed at a single 2000-bed tertiary hospital. Bacteremic UTI was defined as the isolation of the same organism from both urine and blood within 48 h. Eighty-six elderly bacteremic UTI patients were enrolled. Community-acquired infection was the case for most patients (79.1%), and Escherichia coli accounted for 88.6% (70/79) among Gram-negative organisms. Non-E. coli Gram-negative organisms were more frequent in hospital-acquired cases and male patients while chronic urinary catheter insertion was related with Gram-positive urosepsis. The antibiotic susceptibility among Gram-negative organisms was not different depending on the source of bacteremic UTI, while non-E. coli Gram-negative organisms were less frequently susceptible for cefotaxime, cefoperazone/sulbactam, and aztreonam. All-cause in-hospital mortality was 11.6%, and functional dependency (adjusted hazard ratio=HR=10.9, 95% confidence interval=95%CI=2.2-54.6) and low serum albumin (adjusted HR=27.0, 95%CI=2.0-361.2) were independently related with increased all-cause in-hospital mortality.

  20. Change of Nutritional Status Assessed Using Subjective Global Assessment Is Associated With All-Cause Mortality in Incident Dialysis Patients.

    PubMed

    Kwon, Young Eun; Kee, Youn Kyung; Yoon, Chang-Yun; Han, In Mee; Han, Seung Gyu; Park, Kyoung Sook; Lee, Mi Jung; Park, Jung Tak; Han, Seung H; Yoo, Tae-Hyun; Kim, Yong-Lim; Kim, Yon Su; Yang, Chul Woo; Kim, Nam-Ho; Kang, Shin-Wook

    2016-02-01

    Subjective global assessment (SGA) is associated with mortality in end-stage renal disease (ESRD) patients. However, little is known whether improvement or deterioration of nutritional status after dialysis initiation influences the clinical outcome. We aimed to elucidate the association between changes in nutritional status determined by SGA during the first year of dialysis and all-cause mortality in incident ESRD patients. This was a multicenter, prospective cohort study. Incident dialysis patients with available SGA data at both baseline and 12 months after dialysis commencement (n = 914) were analyzed. Nutritional status was defined as well nourished (WN, SGA A) or malnourished (MN, SGA B or C). The patients were divided into 4 groups according to the change in nutritional status between baseline and 12 months after dialysis commencement: group 1, WN to WN; group 2, MN to WN; group 3, WN to MN; and group 4, MN to MN. Cox proportional hazard analysis was performed to clarify the association between changes in nutritional status and mortality. Being in the MN group at 12 months after dialysis initiation, but not at baseline, was a significant risk factor for mortality. There was a significant difference in the 3-year survival rates among the groups (group 1, 92.2%; group 2, 86.0%; group 3, 78.2%; and group 4, 63.5%; log-rank test, P < 0.001). Multivariate Cox regression analysis revealed that the mortality risk was significantly higher in group 3 than in group 1 (hazard ratio [HR] 2.77, 95% confidence interval [CI] 1.27-6.03, P = 0.01) whereas the mortality risk was significantly lower in group 2 compared with group 4 (HR 0.35, 95% CI 0.17-0.71, P < 0.01) even after adjustment for confounding factors. Moreover, mortality risk of group 3 was significantly higher than in group 2 (HR 2.89, 95% CI 1.22-6.81, P = 0.02); there was no significant difference between groups 1 and 2. The changes in nutritional status assessed by SGA during the first

  1. Disability and all-cause mortality in the older population: evidence from the English Longitudinal Study of Ageing.

    PubMed

    Pongiglione, Benedetta; De Stavola, Bianca L; Kuper, Hannah; Ploubidis, George B

    2016-08-01

    Despite the vast body of literature studying disability and mortality, evidence to support their association is scarce. This work investigates the role of disability in explaining all-cause mortality among individuals aged 50+ who participated in the English Longitudinal Study of Aging. The aim is to explain the gender paradox in health and mortality by analysing whether the association of disability with mortality differs between women and men. Disability was conceived following the International Classification of Functioning, Disability and Health (ICF), proposed by the WHO, that conceptualizes disability as a combination of three components: impairment, activity limitation and participation restriction. Latent variable models were used to identify domain-specific factors and general disability. The association of the latter with mortality up to 10 years after enrolment was estimated using discrete-time survival analysis. Our work confirms the validity of the ICF framework and finds that disability is strongly associated with mortality, with a time-varying effect among men, and a smaller constant effect for women. Adjusting for demographic, socioeconomic and behavioural factors attenuated the association for both sexes, but overall the effects remained high and significant. These findings confirm the existence of gender paradox by showing that, when affected by disability, women survive longer than men, although if men survive the first years they appear to become more resilient to disability. Sensitivity analyses suggested that the gender paradox cannot be solely explained by gender-specific health conditions: there must be other mechanisms acting within the pathway between disability and mortality that need to be explored.

  2. Widening rural-urban disparities in all-cause mortality and mortality from major causes of death in the USA, 1969-2009.

    PubMed

    Singh, Gopal K; Siahpush, Mohammad

    2014-04-01

    This study examined trends in rural-urban disparities in all-cause and cause-specific mortality in the USA between 1969 and 2009. A rural-urban continuum measure was linked to county-level mortality data. Age-adjusted death rates were calculated by sex, race, cause-of-death, area-poverty, and urbanization level for 13 time periods between 1969 and 2009. Cause-of-death decomposition and log-linear and Poisson regression were used to analyze rural-urban differentials. Mortality rates increased with increasing levels of rurality overall and for non-Hispanic whites, blacks, and American Indians/Alaska Natives. Despite the declining mortality trends, mortality risks for both males and females and for blacks and whites have been increasingly higher in non-metropolitan than metropolitan areas, particularly since 1990. In 2005-2009, mortality rates varied from 391.9 per 100,000 population for Asians/Pacific Islanders in rural areas to 1,063.2 for blacks in small-urban towns. Poverty gradients were steeper in rural areas, which maintained higher mortality than urban areas after adjustment for poverty level. Poor blacks in non-metropolitan areas experienced two to three times higher all-cause and premature mortality risks than affluent blacks and whites in metropolitan areas. Disparities widened over time; excess mortality from all causes combined and from several major causes of death in non-metropolitan areas was greater in 2005-2009 than in 1990-1992. Causes of death contributing most to the increasing rural-urban disparity and higher rural mortality include heart disease, unintentional injuries, COPD, lung cancer, stroke, suicide, diabetes, nephritis, pneumonia/influenza, cirrhosis, and Alzheimer's disease. Residents in metropolitan areas experienced larger mortality reductions during the past four decades than non-metropolitan residents, contributing to the widening gap.

  3. Phosphodiesterase type-5 inhibitor use in type 2 diabetes is associated with a reduction in all-cause mortality

    PubMed Central

    Anderson, Simon G; Hutchings, David C; Woodward, Mark; Rahimi, Kazem; Rutter, Martin K; Kirby, Mike; Hackett, Geoff; Trafford, Andrew W; Heald, Adrian H

    2016-01-01

    Objective Experimental evidence has shown potential cardioprotective actions of phosphodiesterase type-5 inhibitors (PDE5is). We investigated whether PDE5i use in patients with type 2 diabetes, with high-attendant cardiovascular risk, was associated with altered mortality in a retrospective cohort study. Research design and methods Between January 2007 and May 2015, 5956 men aged 40–89 years diagnosed with type 2 diabetes before 2007 were identified from anonymised electronic health records of 42 general practices in Cheshire, UK, and were followed for 7.5 years. HRs from multivariable survival (accelerated failure time, Weibull) models were used to describe the association between on-demand PDE5i use and all-cause mortality. 10.1136/heartjnl-2015-309223.supp1 Supplementary appendix Results Compared with non-users, men who are prescribed PDE5is (n=1359) experienced lower percentage of deaths during follow-up (19.1% vs 23.8%) and lower risk of all-cause mortality (unadjusted HR=0.69 (95% CI: 0.64 to 0.79); p<0.001)). The reduction in risk of mortality (HR=0.54 (0.36 to 0.80); p=0.002) remained after adjusting for age, estimated glomerular filtration rate, smoking status, prior cerebrovascular accident (CVA) hypertension, prior myocardial infarction (MI), systolic blood pressure, use of statin, metformin, aspirin and β-blocker medication. PDE5i users had lower rates of incident MI (incidence rate ratio (0.62 (0.49 to 0.80), p<0.0001) with lower mortality (25.7% vs 40.1% deaths; age-adjusted HR=0.60 (0.54 to 0.69); p=0.001) compared with non-users within this subgroup. Conclusion In a population of men with type 2 diabetes, use of PDE5is was associated with lower risk of overall mortality and mortality in those with a history of acute MI. PMID:27465053

  4. Losing Life and Livelihood: A Systematic Review and Meta-Analysis of Unemployment and All-Cause Mortality

    PubMed Central

    Roelfs, David J.; Shor, Eran; Davidson, Karina W.; Schwartz, Joseph E.

    2011-01-01

    Unemployment rates in the United States remain near a 25-year high and global unemployment is rising. Previous studies have shown that unemployed persons have an increased risk of death, but the magnitude of the risk and moderating factors have not been explored. The study is a random-effects meta-analysis and meta-regression designed to assess the association between unemployment and all-cause mortality among working-age persons. We extracted 235 mortality risk estimates from 42 studies, providing data on more than 20 million persons. The mean hazard ratio (HR) for mortality was 1.63 among HRs adjusted for age and additional covariates. The mean effect was higher for men than for women. Unemployment was associated with an increased mortality risk for those in their early and middle careers, but less for those in their late-career. The risk of death was highest during the first 10 years of follow up, but decreased subsequently. The mean HR was 24% lower among the subset of studies controlling for health-related behaviors. Public health initiatives could target unemployed persons for more aggressive cardiovascular screening and interventions aimed at reducing risk-taking behaviors. PMID:21330027

  5. The Effect of Coffee and Quantity of Consumption on Specific Cardiovascular and All-Cause Mortality: Coffee Consumption Does Not Affect Mortality.

    PubMed

    Loomba, Rohit S; Aggarwal, Saurabh; Arora, Rohit R

    2016-01-01

    Previous studies have examined whether or not an association exists between the consumption of caffeinated coffee to all-cause and cardiovascular mortality. This study aimed to delineate this association using population representative data from the National Health and Nutrition Examination Survey III. Patients were included in the study if all the following criteria were met: (1) follow-up mortality data were available, (2) age of at least 45 years, and (3) reported amount of average coffee consumption. A total of 8608 patients were included, with patients stratified into the following groups of average daily coffee consumption: (1) no coffee consumption, (2) less than 1 cup, (3) 1 cup a day, (4) 2-3 cups, (5) 4-5 cups, (6) more than 6 cups a day. Odds ratios, 95% confidence intervals, and P values were calculated for univariate analysis to compare the prevalence of all-cause mortality, ischemia-related mortality, congestive heart failure-related mortality, and stroke-related mortality, using the no coffee consumption group as reference. These were then adjusted for confounding factors for a multivariate analysis. P < 0.05 were considered statistically significant. Univariate analysis demonstrated an association between coffee consumption and mortality, although this became insignificant on multivariate analysis. Coffee consumption, thus, does not seem to impact all-cause mortality or specific cardiovascular mortality. These findings do differ from those of recently published studies. Coffee consumption of any quantity seems to be safe without any increased mortality risk. There may be some protective effects but additional data are needed to further delineate this.

  6. Relation of ventilatory impairment and of chronic mucus hypersecretion to mortality from obstructive lung disease and from all causes.

    PubMed Central

    Lange, P; Nyboe, J; Appleyard, M; Jensen, G; Schnohr, P

    1990-01-01

    The relation of ventilatory impairment and chronic mucus hypersecretion to death from all causes and death from obstructive lung disease (chronic bronchitis, emphysema and asthma) was studied in 13,756 men and women randomly selected from the general population of the City of Copenhagen. During the 10 year follow up 2288 subjects died. In 164 subjects obstructive lung disease was considered to be an underlying or a contributory cause of death (obstructive lung disease related death); in 73 subjects it was considered to be the underlying cause of death (obstructive lung disease death). Forced expiratory volume in one second, expressed as a percentage of the predicted value (FEV1% pred), and the presence of chronic phlegm were used to characterise ventilatory function and chronic mucus hypersecretion respectively. For mortality analysis the proportional hazards regression model of Cox was used; it included age, sex, pack years, inhalation habit, body mass index, alcohol consumption, and the presence or absence of asthma, heart disease, and diabetes mellitus as confounding factors. By comparison with subjects with an FEV1 of 80% pred or more, subjects with an FEV1 below 40% pred had increased risk of dying from all causes (relative risk (RR) = 5.0 for women, 2.7 for men), a higher risk of obstructive lung disease related death (RR = 57 for women, 34 for men), and a higher risk of obstructive lung disease death (RR = 101 for women, 77 for men). Chronic mucus hypersecretion was associated with only a slightly higher risk of death from all causes (RR = 1.1 for women, 1.3 for men). The association between chronic mucus hypersecretion and obstructive lung disease death varied with the level of ventilatory function, being weak in subjects with normal ventilatory function (for an FEV1 of 80% pred the RR was 1.2), but more pronounced in subjects with reduced ventilatory function (for an FEV1 of 40% pred the RR was 4.2). A similar though statistically non-significant trend was

  7. Relation between all cause standardised mortality ratios and two indices of deprivation at regional and district level in England.

    PubMed Central

    Mays, N; Chinn, S

    1989-01-01

    The use of mortality data in the form of standardised mortality ratios (SMRs) to measure the need for health care resources in the Resource Allocation Working Party (RAWP) formula in England has been criticised for underestimating the wider effects of adverse socioeconomic conditions on need, particularly in inner city areas. To assess this criticism, we explored the relationships at NHS Regional and District levels in England between two indicators of illness from the 1981 Census, two contrasting indices of deprivation based on the 1981 Census (the Jarman 8 Underprivileged Area (UPA) score and Townsend's Index of Material Deprivation) and their constituent variables, and all cause SMRs for 1982-3. All cause SMRs were highly correlated at Regional and District level with permanent and temporary sickness rates. At Regional level, three of the Thames Regions showed relatively high deprivation scores in relation to their SMRs, in comparison to the remaining Regions where the relative level of deprivation closely matched the Region's mortality ranking. District level analyses of the relations between SMRs and the deprivation indices and their constituent variables showed that the Thames/non-Thames dichotomy was accounted for by the 14 Districts in inner London. These findings suggest that although there may be a prima facie case for including an allowance for deprivation in RAWP, it is still not clear how the deprivation variables available in the Census relate empirically to the need for additional health service resources. The analysis raises questions about the appropriate definition of need in this context and whether the Census is a suitable source for the construction of a deprivation weighting for use in national RAWP. PMID:2592910

  8. Isolated systolic hypertension in Dutch middle aged and all-cause mortality: a 25-year prospective study.

    PubMed

    van den Ban, G C; Kampman, E; Schouten, E G; Kok, F J; van der Heide, R M; van der Heide-Wessel, C

    1989-03-01

    In the early 1950s, the blood pressure of 3901 Dutch civil servants and their spouses aged 40-65 years was measured in a general health survey. Isolated systolic hypertension (systolic pressure greater than 160 mmHg, diastolic pressure less than 90 mmHg) was observed in 6.3% of the women and 3.0% of the men. The prevalence increased with age and it was more common in women in all age groups. Using logistic regression, with adjustment for potential confounders (age, smoking, serum cholesterol, Quetelet index, alcohol consumption, haemoglobin level, pulse rate and diastolic blood pressure) the association of 15- and 25-year total mortality with isolated systolic hypertension was determined. Compared to normotensive people (systolic pressure less than or equal to 135 mmHg, diastolic pressure less than 90 mmHg), the risk of death from all causes was significantly higher for men with isolated systolic hypertension after 15 and 25 years of follow-up (odds ratio OR = 2.4, 95% confidence interval (CI) 1.2-4.8 and OR = 3.2, 95% CI 1.3-8.0). For women 15-years mortality risk was strongly associated with isolated systolic hypertension (OR = 3.7, 95% CI 1.4-9.7). The increased risk was less pronounced after 25 years of follow-up (OR = 1.7, 95% CI 0.96-3.0). Our results support those of other studies and indicate that isolated systolic hypertension is an important independent risk factor for all-cause mortality. Since isolated systolic hypertension may be an indicator for the early onset of ageing, it is important to study its determinants and to pay more attention to its diagnosis and treatment in middle-aged populations.

  9. Association between Six Minute Walk Test and All-Cause Mortality, Coronary Heart Disease-Specific Mortality, and Incident Coronary Heart Disease

    PubMed Central

    Yazdanyar, Ali; Aziz, Michael M; Enright, Paul L; Edmundowicz, Daniel; Boudreau, Robert; Sutton-Tyrell, Kim; Kuller, Lewis; Newman, Anne B

    2015-01-01

    Objectives To examine the association between six-minute walk test (6 MWT) performance and all-cause mortality, coronary heart disease mortality, and incident coronary heart disease in older adults. Methods We conducted a time-to-event analysis of 1,665 Cardiovascular Health Study participants with a 6 MWT and without prevalent cardiovascular disease. Results During a mean follow-up of 8 years, there were 305 incident coronary heart disease events, 504 deaths of which 100 were coronary heart disease-related deaths. The 6 MWT performance in the shortest two distance quintiles was associated with increased risk of all-cause mortality (290-338 meters: HR 1.7; 95% CI, 1.2-2.5; <290 meters: HR 2.1; 95% CI, 1.4-3.0). The adjusted risk of coronary heart disease mortality incident events among those with a 6 MWT <290 meters was not significant. Discussion Performance on the 6 MWT is independently associated with all-cause mortality and is of prognostic utility in community-dwelling older adults. PMID:24695552

  10. The association of clinical indication for exercise stress testing with all-cause mortality: the FIT Project

    PubMed Central

    Kim, Joonseok; Al-Mallah, Mouaz; Juraschek, Stephen P.; Brawner, Clinton; Keteyian, Steve J.; Nasir, Khurram; Dardari, Zeina A.; Blumenthal, Roger S.

    2016-01-01

    Introduction We hypothesized that the indication for stress testing provided by the referring physician would be an independent predictor of all-cause mortality. Material and methods We studied 48,914 patients from The Henry Ford Exercise Testing Project (The FIT Project) without known congestive heart failure who were referred for a clinical treadmill stress test and followed for 11 ±4.7 years. The reason for stress test referral was abstracted from the clinical test order, and should be considered the primary concerning symptom or indication as stated by the ordering clinician. Hierarchical multivariable Cox proportional hazards regression was performed, after controlling for potential confounders including demographics, risk factors, and medication use as well as additional adjustment for exercise capacity in the final model. Results A total of 67% of the patients were referred for chest pain, 12% for shortness of breath (SOB), 4% for palpitations, 3% for pre-operative evaluation, 6% for abnormal prior testing, and 7% for risk factors only. There were 6,211 total deaths during follow-up. Compared to chest pain, those referred for palpitations (HR = 0.72, 95% CI: 0.60–0.86) and risk factors only (HR = 0.72, 95% CI: 0.63–0.82) had a lower risk of all-cause mortality, whereas those referred for SOB (HR = 1.15, 95% CI: 1.07–1.23) and pre-operative evaluation (HR = 2.11, 95% CI: 1.94–2.30) had an increased risk. In subgroup analysis, referral for palpitations was protective only in those without coronary artery disease (CAD) (HR = 0.75, 95% CI: 0.62–0.90), while SOB increased mortality risk only in those with established CAD (HR = 1.25, 95% CI: 1.10–1.44). Conclusions The indication for stress testing is an independent predictor of mortality, showing an interaction with CAD status. Importantly, SOB may be associated with higher mortality risk than chest pain, particularly in patients with CAD. PMID:27186173

  11. Decreased limb muscle and increased central adiposity are associated with 5-year all-cause mortality in HIV infection

    PubMed Central

    Scherzer, Rebecca; Heymsfield, Steven B.; Lee, Daniel; Powderly, William G.; Tien, Phyllis C.; Bacchetti, Peter; Shlipak, Michael G.; Grunfeld, Carl

    2014-01-01

    Background Unintentional loss of weight and muscle due to aging and disease has been associated with increased mortality. Wasting and weight loss occur in HIV infection even in the modern era of effective antiretroviral therapy. Methods We determined the association of MRI-measured regional and total skeletal muscle and adipose tissue with 5-year, all-cause mortality in 922 HIV-infected persons in the study of Fat Redistribution and Metabolic Change in HIV Infection (FRAM). Results After 5 years of follow-up, HIV-infected participants with arm skeletal muscle in the lowest tertile had a mortality rate of 23%, compared with 11 and 8% for those in the middle and highest tertiles. After multivariable adjustment for demographics, cardiovascular risk factors, HIV-related factors, inflammatory markers, and renal disease, we found that lower arm skeletal muscle, lower leg skeletal muscle and higher visceral adipose tissue (VAT) were each independently associated with increased mortality. Those in the lowest tertile of arm or leg skeletal muscle had higher odds of death [arm: odds ratio (OR)=2.0, 95% confidence interval (CI) 0.96–4.0; leg: OR=2.4, 95% CI 1.2–4.8] compared with the highest respective tertiles. Those in the highest tertile of VAT had 2.1-fold higher odds of death (95% CI 1.1–4.0) compared with the lowest VAT tertile. Conclusion Lower muscle mass and central adiposity appear to be important risk factors for mortality in HIV-infected individuals. A substantial proportion of this risk may be unrecognized because of the current reliance on body mass index in clinical practice. PMID:21572308

  12. All-Cause and Cause-Specific Mortality Among Men Released From State Prison, 1980–2005

    PubMed Central

    Rosen, David L.; Wohl, David A.

    2008-01-01

    Objectives. We compared mortality of ex-prisoners and other state residents to identify unmet health care needs among former prisoners. Methods. We linked North Carolina prison records with state death records for 1980 to 2005 to estimate the number of overall and cause-specific deaths among male ex-prisoners aged 20 to 69 years and used standardized mortality ratios (SMRs) to compare these observed deaths with the number of expected deaths had they experienced the same age-, race-, and cause-specific death rates as other state residents. Results. All-cause mortality among White (SMR = 2.08; 95% confidence interval [CI] = 2.04, 2.13) and Black (SMR = 1.03; 95% CI = 1.01, 1.05) ex-prisoners was greater than for other male NC residents. Ex-prisoners' deaths from homicide, accidents, substance use, HIV, liver disease, and liver cancer were greater than the expected number of deaths estimated using death rates among other NC residents. Deaths from cardiovascular disease, lung cancer, respiratory diseases, and diabetes were at least 30% greater than expected for White ex-prisoners, but less than expected for Black ex-prisoners. Conclusions. Ex-prisoners experienced more deaths than would have been expected among other NC residents. Excess deaths from injuries and medical conditions common to prison populations highlight ex-prisoners' medical vulnerability and the need to improve correctional and community preventive health services. PMID:18923131

  13. Cumulative Resting Heart Rate Exposure and Risk of All-Cause Mortality: Results from the Kailuan Cohort Study

    PubMed Central

    Zhao, Quanhui; Li, Haibin; Wang, Anxin; Guo, Jin; Yu, Junxing; Luo, Yanxia; Chen, Shuohua; Tao, Lixin; Li, Yuqing; Li, Aiping; Guo, Xiuhua; Wu, Shouling

    2017-01-01

    The relationship between cumulative exposure to resting heart rate (cumRHR) and mortality remain unclear in the general population. In the Kailuan cohort study, resting heart rate (RHR) was repeatedly measured at baseline and at years 2 and 4 by electrocardiogram among 47,311 adults aged 48.70 ± 11.68. The cumRHR was defined as the summed average RHR between two consecutive examinations multiplied by the time interval between with two examinations [(beats/min) * year]. A higher RHR was defined as ≥80 beats/min, and the number of visits with a higher RHR was counted. During a median of 4.06 years of follow-up, a total of 1,025 participants died. After adjusting for major traditional cardiovascular risk factors and baseline RHR, the hazard ratio for the highest versus lowest quartile of cumRHR was 1.39 (95% CI: 1.07–1.81) for all-cause mortality. Each 1-SD increment in cumRHR was associated with a 37% (HR: 1.37, 95% CI: 1.23–1.52) increased risk of death and displayed a J-shaped relationship. Compared with no exposure, adults who had a higher RHR at all 3 study visits were associated with a 1.86-fold higher risk (95% CI: 1.33–2.61) of mortality. In summary, cumulative exposure to higher RHR is independently associated with an increased risk of mortality. PMID:28067310

  14. External validation and comparison of two variants of the Elixhauser comorbidity measures for all-cause mortality

    PubMed Central

    Crispo, James A. G.; Cohen, Deborah; McNair, Douglas S.; Mattison, Donald R.; Krewski, Daniel

    2017-01-01

    Assessing prevalent comorbidities is a common approach in health research for identifying clinical differences between individuals. The objective of this study was to validate and compare the predictive performance of two variants of the Elixhauser comorbidity measures (ECM) for inhospital mortality at index and at 1-year in the Cerner Health Facts® (HF) U.S. database. We estimated the prevalence of select comorbidities for individuals 18 to 89 years of age who received care at Cerner contributing health facilities between 2002 and 2011 using the AHRQ (version 3.7) and the Quan Enhanced ICD-9-CM ECMs. External validation of the ECMs was assessed with measures of discrimination [c-statistics], calibration [Hosmer–Lemeshow goodness-of-fit test, Brier Score, calibration curves], added predictive ability [Net Reclassification Improvement], and overall model performance [R2]. Of 3,273,298 patients with a mean age of 43.9 years and a female composition of 53.8%, 1.0% died during their index encounter and 1.5% were deceased at 1-year. Calibration measures were equivalent between the two ECMs. Calibration performance was acceptable when predicting inhospital mortality at index, although recalibration is recommended for predicting inhospital mortality at 1 year. Discrimination was marginally better with the Quan ECM compared the AHRQ ECM when predicting inhospital mortality at index (cQuan = 0.887, 95% CI: 0.885–0.889 vs. cAHRQ = 0.880, 95% CI: 0.878–0.882; p < .0001) and at 1-year (cQuan = 0.884, 95% CI: 0.883–0.886 vs. cAHRQ = 0.880, 95% CI: 0.878–0.881, p < .0001). Both the Quan and the AHRQ ECMs demonstrated excellent discrimination for inhospital mortality of all-causes in Cerner Health Facts®, a HIPAA compliant observational research and privacy-protected data warehouse. While differences in discrimination performance between the ECMs were statistically significant, they are not likely clinically meaningful. PMID:28350807

  15. A population-based prospective study of energy-providing nutrients in relation to all-cause cancer mortality and cancers of digestive organs mortality.

    PubMed

    Argos, Maria; Melkonian, Stephanie; Parvez, Faruque; Rakibuz-Zaman, Muhammad; Ahmed, Alauddin; Chen, Yu; Ahsan, Habibul

    2013-11-15

    The effect of dietary composition on mortality in low-income countries is largely unknown. We evaluated whether percentages of dietary energy derived from protein, fat and carbohydrates were associated with all-cause and cancer mortalities in a Bangladeshi population. Data from a prospective population-based cohort study of 17,244 men and women were used. Percentages of dietary energy derived from protein, fat and carbohydrates, assessed using a validated food-frequency questionnaire at baseline, were analyzed in relation to mortality over an average of 9 years (155,126 person-years) of follow-up. Cox proportional hazards regression models were used to estimate hazard ratios for all cause, all cancer and cancers of the digestive organs mortalities. Percentage of dietary energy from protein appeared to be significantly associated with cancer mortality. Fully adjusted hazard ratios for cancer mortality in increasing tertiles of percentage of dietary energy from protein were 1.0 (reference), 1.21 (0.73, 2.00) and 1.84 (1.08, 3.15) (p for trend = 0.023). These associations were much stronger for deaths from cancers of the digestive organs with fully adjusted hazard ratios in increasing tertiles of percentage of dietary energy from protein being 1.0 (reference), 2.25 (0.91, 5.59) and 4.85 (1.88, 12.51) (p for trend = 0.001). No significant associations in relation to cancer-related mortality were observed for percentage of dietary energy from fat. Novel findings from this prospective study show protein is an important risk factor or proxy to an important risk factor for cancer mortality especially from digestive organ cancers in Bangladesh.

  16. A review and meta-analysis of the effect of weight loss on all-cause mortality risk.

    PubMed

    Harrington, Mary; Gibson, Sigrid; Cottrell, Richard C

    2009-06-01

    Overweight and obesity are associated with increased morbidity and mortality, although the range of body weights that is optimal for health is controversial. It is less clear whether weight loss benefits longevity and hence whether weight reduction is justified as a prime goal for all individuals who are overweight (normally defined as BMI>25 kg/m2). The purpose of the present review was to examine the evidence base for recommending weight loss by diet and lifestyle change as a means of prolonging life. An electronic search identified twenty-six eligible prospective studies that monitored subsequent mortality risk following weight loss by lifestyle change, published up to 2008. Data were extracted and further analysed by meta-analysis, giving particular attention to the influence of confounders. Moderator variables such as reason for weight loss (intentional, unintentional), baseline health status (healthy, unhealthy), baseline BMI (normal, overweight, obese), method used to estimate weight loss (measured weight loss, reported weight loss) and whether models adjusted for physical activity (adjusted data, unadjusted data) were used to classify subgroups for separate analysis. Intentional weight loss per se had a neutral effect on all-cause mortality (relative risk (RR) 1.01; P = 0.89), while weight loss which was unintentional or ill-defined was associated with excess risk of 22 to 39 %. Intentional weight loss had a small benefit for individuals classified as unhealthy (with obesity-related risk factors) (RR 0.87 (95 % CI 0.77, 0.99); P = 0.028), especially unhealthy obese (RR 0.84 (95 % CI 0.73, 0.97); P = 0.018), but appeared to be associated with slightly increased mortality for healthy individuals (RR 1.11 (95 % CI 1.00, 1.22); P = 0.05), and for those who were overweight but not obese (RR 1.09 (95 % CI 1.02, 1.17); P = 0.008). There was no evidence for weight loss conferring either benefit or risk among healthy obese. In conclusion, the available evidence does

  17. Risk of All-Cause and Prostate Cancer-Specific Mortality After Brachytherapy in Men With Small Prostate Size

    SciTech Connect

    Nguyen, Paul L.; Chen, Ming H.; Choueiri, Toni K.; Hoffman, Karen E.; Hu, Jim C.; Martin, Neil E.; Beard, Clair J.; Dosoretz, Daniel E.; Moran, Brian J.; Katin, Michael J.; Braccioforte, Michelle H.; Ross, Rudi; Salenius, Sharon A.; Kantoff, Philip W.; D'Amico, Anthony V.

    2011-04-01

    Background: Brachytherapy for prostate cancer can be technically challenging in men with small prostates ({<=}20 cc), but it is unknown whether their outcomes are different than those of men with larger prostates. Methods and Materials: We studied 6,416 men treated with brachytherapy in one of 21 community-based practices. Cox regression and Fine and Gray's regression were used to determine whether volume {<=}20 cc was associated with a higher risk of all-cause mortality (ACM) or prostate cancer-specific mortality (PCSM), respectively, after adjustment for other known prognostic factors. Results: 443 patients (6.9%) had a prostate volume {<=}20 cc. After a median follow-up of 2.91 years (interquartile range, 1.06-4.79), volume {<=}20 cc was associated with a significantly higher risk of ACM (adjusted hazard ratio = 1.33 [95% CI 1.08-1.65], p = 0.0085) with 3-year estimates of ACM for {<=}20 cc vs. >20 cc of 13.0% vs. 6.9% (p = 0.028). Only 23 men (0.36%) have died of prostate cancer, and no difference was seen in PCSM by volume (p = 0.4). Conclusion: Men with small prostates at the time of implant had a 33% higher risk of ACM, and the underlying cause of this remains uncertain. No increase in PCSM was observed in men with volume {<=}20cc, suggesting that a small prostate should not in itself be a contraindication for brachytherapy, but inasmuch as absolute rates of PCSM were small, further follow-up will be needed to confirm this finding.

  18. The Value of Geriatric Assessments in Predicting Treatment Tolerance and All-Cause Mortality in Older Patients With Cancer

    PubMed Central

    Vos, Alinda G.; Smorenburg, Carolien H.; de Rooij, Sophia E.; van Munster, Barbara C.

    2012-01-01

    Background. Awareness of the use of geriatric assessments for older patients with cancer is increasing. The aim of this review is to summarize all available evidence on the association between geriatric assessments and relevant oncologic outcomes. Method. A systematic search was conducted in Medline and Embase of studies on geriatric assessment in oncology, focusing on the association between baseline assessment and outcome. Results. The literature search identified 2008 reports; 51 publications from 37 studies were selected for inclusion in the review. The quality of studies was heterogeneous and generally poor. A median of five geriatric conditions were assessed per study (interquartile range: 4–8). Little consistency was found in the results of the studies. Furthermore, different tools appear to be predictive depending on the outcome measure: frailty, nutritional status, and comorbidity assessed by the Cumulative Illness Rating Scale for Geriatrics were predictive for all-cause mortality; frailty was predictive for toxicity of chemotherapy; cognitive impairment and activities of daily living impairment were predictive for chemotherapy completion; and instrumental activities of daily living impairment was predictive for perioperative complications. Conclusion. Although various geriatric conditions appear to be of some value in predicting outcome in elderly patients with cancer, the results are too inconsistent to guide treatment decisions. Further research is needed to elucidate the role of geriatric assessments in the oncologic decision-making process for these patients. PMID:22941970

  19. Urinary Sodium Concentration Is an Independent Predictor of All-Cause and Cardiovascular Mortality in a Type 2 Diabetes Cohort Population

    PubMed Central

    Gand, Elise; Ragot, Stéphanie; Bankir, Lise; Piguel, Xavier; Fumeron, Frédéric; Halimi, Jean-Michel; Marechaud, Richard; Roussel, Ronan; Hadjadj, Samy; Study group, SURDIAGENE

    2017-01-01

    Objective. Sodium intake is associated with cardiovascular outcomes. However, no study has specifically reported an association between cardiovascular mortality and urinary sodium concentration (UNa). We examined the association of UNa with mortality in a cohort of type 2 diabetes (T2D) patients. Methods. Patients were followed for all-cause death and cardiovascular death. Baseline UNa was measured from second morning spot urinary sample. We used Cox proportional hazard models to identify independent predictors of mortality. Improvement in prediction of mortality by the addition of UNa to a model including known risk factors was assessed by the relative integrated discrimination improvement (rIDI) index. Results. Participants (n = 1,439) were followed for a median of 5.7 years, during which 254 cardiovascular deaths and 429 all-cause deaths were recorded. UNa independently predicted all-cause and cardiovascular mortality. An increase of one standard deviation of UNa was associated with a decrease of 21% of all-cause mortality and 22% of cardiovascular mortality. UNa improved all-cause and cardiovascular mortality prediction beyond identified risk factors (rIDI = 2.8%, P = 0.04 and rIDI = 4.6%, P = 0.02, resp.). Conclusions. In T2D, UNa was an independent predictor of mortality (low concentration is associated with increased risk) and improved modestly its prediction in addition to traditional risk factors. PMID:28255559

  20. Statin use and its effect on all-cause mortality of melanoma patients: a population-based Dutch cohort study

    PubMed Central

    Livingstone, Elisabeth; Hollestein, Loes M; van Herk-Sukel, Myrthe P P; van de Poll-Franse, Lonneke; Joosse, Arjen; Schilling, Bastian; Nijsten, Tamar; Schadendorf, Dirk; de Vries, Esther

    2014-01-01

    Preclinical data showed anticancer effects of statins in melanoma, but meta-analyses could not demonstrate a reduced melanoma incidence in statin users. Rather than preventing occurrence, statins might reduce growth and metastatic spread of melanomas and ultimately improve survival. In this population-based study, we investigated the relationship between statin use and survival of melanoma patients. Patients ≥18 years who were diagnosed with cutaneous melanoma (Breslow thickness >1 mm) and registered in the Eindhoven Cancer Registry and in PHARMO Database Network between 1 January 1998 and 31 December 2010 were eligible. The hazard ratio (HR) of all-cause mortality was calculated by employing adjusted time-dependent and time-fixed Cox proportional hazard models. Disease-specific survival was estimated by means of 3-year relative survival rates (RSR). A control cohort of randomly selected patients using statins from PHARMO Database Network matched on age and gender was used to compare RSR of statin users to the general population. After melanoma diagnosis, 171 of 709 patients used statins. Use of statins showed a nonsignificantly decreased hazard of death (adjusted HR 0.76, 95% confidence interval [CI] 0.50–1.61). After stratification for gender, male but not female statin users showed a favorable outcome compared to nonusers (HR 0.57, 95% CI 0.32–0.99; HR 1.22, 95% CI 0.62–2.38, respectively). Three-year RSR for male statin users tended to be higher than for nonusers (91% vs. 80.5%, P = 0.06), no differences were observed in women (87.1% vs. 92.5%, P = 0.76). Statin use was not associated with an improved survival of melanoma patients. The trend for better survival of male in contrast to female statin users warrants further research. PMID:24935402

  1. Occupational Class Inequalities in All-Cause and Cause-Specific Mortality among Middle-Aged Men in 14 European Populations during the Early 2000s

    PubMed Central

    Toch-Marquardt, Marlen; Menvielle, Gwenn; Eikemo, Terje A.; Kulhánová, Ivana; Kulik, Margarete C.; Bopp, Matthias; Esnaola, Santiago; Jasilionis, Domantas; Mäki, Netta; Martikainen, Pekka; Regidor, Enrique; Lundberg, Olle; Mackenbach, Johan P.

    2014-01-01

    This study analyses occupational class inequalities in all-cause mortality and four specific causes of death among men, in Europe in the early 2000s, and is the most extensive comparative analysis of occupational class inequalities in mortality in Europe so far. Longitudinal data, obtained from population censuses and mortality registries in 14 European populations, from around the period 2000–2005, were used. Analyses concerned men aged 30–59 years and included all-cause mortality and mortality from all cancers, all cardiovascular diseases (CVD), all external, and all other causes. Occupational class was analysed according to five categories: upper and lower non-manual workers, skilled and unskilled manual workers, and farmers and self-employed combined. Inequalities were quantified with mortality rate ratios, rate differences, and population attributable fractions (PAF). Relative and absolute inequalities in all-cause mortality were more pronounced in Finland, Denmark, France, and Lithuania than in other populations, and the same countries (except France) also had the highest PAF values for all-cause mortality. The main contributing causes to these larger inequalities differed strongly between countries (e.g., cancer in France, all other causes in Denmark). Relative and absolute inequalities in CVD mortality were markedly lower in Southern European populations. We conclude that relative and absolute occupational class differences in all-cause and cause specific mortality have persisted into the early 2000's, although the magnitude differs strongly between populations. Comparisons with previous studies suggest that the relative gap in mortality between occupational classes has further widened in some Northern and Western European populations. PMID:25268702

  2. N-terminal pro-brain natriuretic peptide and cardiovascular or all-cause mortality in the general population: A meta-analysis

    PubMed Central

    Geng, Zhaohua; Huang, Lan; Song, Mingbao; Song, Yaoming

    2017-01-01

    The prognostic role of N-terminal pro-brain natriuretic peptide (NT-proBNP) in the general population remains controversial. We conducted this meta-analysis to investigate the association between baseline NT-proBNP concentrations and cardiovascular or all-cause mortality in the general population. PubMed and Embase databases were systematically searched from their inception to August 2016. Prospective observational studies that investigated the association between baseline NT-proBNP concentrations and cardiovascular or all-cause mortality in the general population were eligible. A summary of the hazard ratio (HR) and 95% confidence interval (CI) of mortality were calculated by the highest versus the lowest category of NT-proBNP concentrations. Eleven studies with a total of 25,715 individuals were included. Compared individuals in the highest with those in the lowest category of NT-proBNP, the pooled HR was 2.44 (95% CI 2.11–2.83) for all-cause mortality, 3.77 (95% CI 2.85–5.00) for cardiovascular mortality, and 2.35 (95% CI 1.45–3.82) for coronary heart disease mortality, respectively. Subgroup analyses indicated that the effects of NT-proBNP on the risk of cardiovascular mortality (RR 2.27) and all-cause mortality (RR 3.00) appeared to be slightly lower among men. Elevated NT-proBNP concentrations appeared to be independently associated with increased risk of cardiovascular and all-cause mortality in the general population. PMID:28134294

  3. Physical activity and risk of all-cause and cardiovascular disease mortality in diabetic adults from Great Britain: pooled analysis of 10 population-based cohorts.

    PubMed

    Sadarangani, Kabir P; Hamer, Mark; Mindell, Jenny S; Coombs, Ngaire A; Stamatakis, Emmanuel

    2014-04-01

    OBJECTIVE To examine associations between specific types of physical activity and all-cause and cardiovascular disease (CVD) mortality in a large nationally representative sample of adults with diabetes from Great Britain. RESEARCH DESIGN AND METHODS There were a total of 3,038 participants (675 deaths) with diabetes in the Health Survey for England and the Scottish Health Surveys conducted between 1997 and 2008. Participants aged ≥50 years at baseline were followed up for an average of 75.2 months for all-cause and CVD mortality. Data were collected on self-reported frequency, duration, and intensity of participation in sports and exercise, walking, and domestic physical activity, from which the number of MET-hours/week were derived. Sex-specific medians of time spent in each type of physical activity (for those physically active) were calculated, and Cox proportional hazards regression conducted to examine type-specific associations between the level of physical activity and all-cause and CVD mortality risk. RESULTS Inverse associations with all-cause and CVD mortality were observed for overall physical activity in a dose-response manner after adjusting for covariates. Compared with those who individuals were inactive, participants who reported some activity, but below the recommended amount, or who met the physical activity recommendations had a 26% (95% CI 39-11) and 35% (95% CI 47-21) lower all-cause mortality, respectively. Similar results were found for below/above median physical activity levels. Sports and exercise participation was inversely associated with all-cause (but not CVD) mortality, as were above average levels of walking. Domestic physical activity was not associated with mortality. CONCLUSIONS Moderate physical activity levels were associated with better prognosis in diabetic adults.

  4. The Pretreatment Neutrophil/Lymphocyte Ratio Is Associated with All-Cause Mortality in Black and White Patients with Non-metastatic Breast Cancer

    PubMed Central

    Rimando, Joseph; Campbell, Jeff; Kim, Jae Hee; Tang, Shou-Ching; Kim, Sangmi

    2016-01-01

    The pretreatment neutrophil/lymphocyte ratio (NLR), derived from differential white blood cell counts, has been previously associated with poor prognosis in breast cancer. Little data exist, however, concerning this association in Black patients, who are known to have lower neutrophil counts than other racial groups. We conducted a retrospective cohort study of 236 Black and 225 non-Hispanic White breast cancer patients treated at a single institution. Neutrophil and lymphocyte counts were obtained from electronic medical records. Univariate and multivariate Cox regression models were used to determine hazard ratios (HRs) and 95% confidence intervals (95% CIs) of all-cause mortality and breast cancer-specific mortality in relation to pretreatment NLR. Overall, there were no associations between an elevated pretreatment NLR (NLR ≥3.7) and all-cause or breast cancer-specific mortality. Among patients without metastasis at the time of diagnosis, an elevated pretreatment NLR was independently associated with all-cause mortality, with a multivariable HR of 2.31 (95% CI: 1.10–4.86). Black patients had significantly lower NLR values than White patients, but there was no evidence suggesting racial heterogeneity of the prognostic utility of NLR. Pretreatment NLR was an independent predictor of all-cause mortality but not breast cancer-specific mortality in non-metastatic breast cancer patients. PMID:27064712

  5. The effects of control of systolic and diastolic hypertension on cardiovascular and all-cause mortality in a community-based population cohort.

    PubMed

    Barengo, N C; Antikainen, R; Kastarinen, M; Laatikainen, T; Tuomilehto, J

    2013-11-01

    The objective of this study (follow-up of 26,113 people) was to investigate differences in the risk of cardiovascular disease (CVD) and all-cause mortality among hypertensive people according to the control of systolic blood pressure (SBP) and diastolic blood pressure (DBP). People with a history of coronary heart disease, heart failure, cancer or incomplete data at baseline (n=1113) were excluded from the study. The participants were classified into six groups according to their blood pressure status. Treated hypertensive individuals with controlled SBP and DBP did not experience an increase in all-cause mortality compared with normotensive people. The increase in all-cause mortality was 1.48-fold (95% confidence interval (CI) 1.09-2.01) among those who were treated with antihypertensive drugs and had only their DBP controlled and 1.45-fold (95% CI 1.04-2.02) among those who were treated and had only their SBP controlled. Treated patients with both SBP and DBP controlled did not have an increased risk of CVD mortality when compared with normotensive people. The risk of CVD mortality was statistically significantly higher in treated hypertensive people with SBP alone, DBP alone or both SBP and DBP uncontrolled. Our study indicates that uncontrolled SBP alone and DBP alone are risk factors of all-cause and CVD mortality.

  6. Population density, socioeconomic environment and all-cause mortality: a multilevel survival analysis of 2.7 million individuals in Denmark.

    PubMed

    Meijer, Mathias; Kejs, Anne Mette; Stock, Christiane; Bloomfield, Kim; Ejstrud, Bo; Schlattmann, Peter

    2012-03-01

    This study examines the relative effects of population density and area-level SES on all-cause mortality in Denmark. A shared frailty model was fitted with 2.7 million persons aged 30-81 years in 2,121 parishes. Residence in areas with high population density increased all-cause mortality for all age groups. For older age groups, residence in areas with higher proportions of unemployed persons had an additional effect. Area-level factors explained considerably more variation in mortality among the elderly than among younger generations. Overall this study suggests that structural prevention efforts in neighborhoods could help reduce mortality when mediating processes between area-level socioeconomic status, population density and mortality are found.

  7. Short-term effect of dust storms on the risk of mortality due to respiratory, cardiovascular and all-causes in Kuwait

    NASA Astrophysics Data System (ADS)

    Al-Taiar, Abdullah; Thalib, Lukman

    2014-01-01

    This study aimed to investigate the impact of dust storms on short-term mortality in Kuwait. We analyzed respiratory and cardiovascular mortality as well as all-cause mortality in relation to dust storm events over a 5-year study period, using data obtained through a population-based retrospective ecological time series study. Dust storm days were identified when the national daily average of PM10 exceeded 200 μg/m3. Generalized additive models with Poisson link were used to estimate the relative risk (RR) of age-stratified daily mortality associated with dust events, after adjusting for potential confounders including weather variables and long-term trends. There was no significant association between dust storm events and same-day respiratory mortality (RR = 0.96; 95 %CI 0.88-1.04), cardiovascular mortality (RR = 0.98; 95 %CI 0.96-1.012) or all-cause mortality (RR = 0.99; 95 %CI 0.97-1.00). Overall our findings suggest that local dust, that most likely originates from crustal materials, has little impact on short-term respiratory, cardiovascular or all-cause mortality.

  8. Systemic inflammation (Interleukin 6) predicts all-cause mortality in men: results from a 9-year follow-up of the MEMO Study.

    PubMed

    Baune, Bernhard T; Rothermundt, Matthias; Ladwig, Karl H; Meisinger, Christine; Berger, Klaus

    2011-06-01

    This study aimed to investigate the association of biomarkers among circulating pro-inflammatory cytokines with all-cause mortality in elderly community dwellings of the MEMO study, Germany. All-cause mortality (cancer, cardiovascular diseases (CVD), and other causes of death) was assessed in a general population sample (N = 385) of the elderly (age 65-83 years) 9 years after baseline assessment in 1998. As markers of inflammation, a variety of cytokines (IL-1beta, IL-4sR, IL-6, IL-8, IL-10, IL-12, TNF-alpha) were assessed in serum. Cox proportional Hazard model was used to estimate the association of cytokines with all-cause mortality over 9 years. In total, 110 deaths had occurred during follow-up (cancer N = 36; CVD N = 56; other = 18). Deaths were more frequent in male (N  = 76, 37.4%) as compared to females (N = 40, 21.9%; p  = 0.001). Among individual cytokines, IL-1 beta, IL-6, IL-8, IL-10, and TNF-alpha were associated with all-cause mortality, of which IL-6, IL-8, and IL-10 remained significant after adjusting for confounders. When the upper tertiles of these cytokines were compared to the lower tertiles, only IL-6 was consistently related to all-cause mortality independently of the level of adjustment and showing a dose-response relationship between IL-6 tertiles and risk of death. This effect originated in the male population. The study shows that IL-6 is a powerful predictor of all-cause mortality in male elderly community dwellings. Higher levels of IL-6 may reflect a chronic low-level systemic inflammation prospectively increasing the risk of death in the elderly.

  9. Is type D personality an independent risk factor for recurrent myocardial infarction or all-cause mortality in post-acute myocardial infarction patients?

    PubMed

    Condén, Emelie; Rosenblad, Andreas; Wagner, Philippe; Leppert, Jerzy; Ekselius, Lisa; Åslund, Cecilia

    2017-03-01

    Background Type D personality refers to a combination of simultaneously high levels of negative affectivity and social inhibition. The present study aimed to examine whether type D personality was independently associated with recurrent myocardial infarction or all-cause mortality in post-acute myocardial infarction patients, using any of the previously proposed methods for measuring type D personality. Design This was a prospective cohort study. Methods Utilising data from the Västmanland Myocardial Infarction Study, 946 post-acute myocardial infarction patients having data on the DS14 instrument used to measure type D personality were followed-up for recurrent myocardial infarction and all-cause mortality until 9 December 2015. Data were analysed using Cox regression, adjusted for established risk factors. Results In total, 133 (14.1%) patients suffered from type D personality. During a mean follow-up time for recurrent myocardial infarction of 5.7 (3.2) years, 166 (17.5%) patients were affected by recurrent myocardial infarction, of which 26 (15.7%) had type D personality, while during a mean follow-up time for all-cause mortality of 6.3 (2.9) years, 321 (33.9%) patients died, of which 42 (13.1%) had type D personality. After adjusting for established risk factors, type D personality was not significantly associated with recurrent myocardial infarction or all-cause mortality using any of the previously proposed methods for measuring type D personality. A weak association was found between the social inhibition part of type D personality and a decreased risk of all-cause mortality, but this association was not significant after taking missing data into account in a multiple imputation analysis. Conclusions No support was found for type D personality being independently associated with recurrent myocardial infarction or all-cause mortality in post-acute myocardial infarction patients, using any of the previously proposed methods for measuring type D personality.

  10. All-cause mortality in the cohorts of the Spanish AIDS Research Network (RIS) compared with the general population: 1997–2010

    PubMed Central

    2013-01-01

    Background Combination antiretroviral therapy (cART) has produced significant changes in mortality of HIV-infected persons. Our objective was to estimate mortality rates, standardized mortality ratios and excess mortality rates of cohorts of the AIDS Research Network (RIS) (CoRIS-MD and CoRIS) compared to the general population. Methods We analysed data of CoRIS-MD and CoRIS cohorts from 1997 to 2010. We calculated: (i) all-cause mortality rates, (ii) standardized mortality ratio (SMR) and (iii) excess mortality rates for both cohort for 100 person-years (py) of follow-up, comparing all-cause mortality with that of the general population of similar age and gender. Results Between 1997 and 2010, 8,214 HIV positive subjects were included, 2,453 (29.9%) in CoRIS-MD and 5,761 (70.1%) in CoRIS and 294 deaths were registered. All-cause mortality rate was 1.02 (95% CI 0.91-1.15) per 100 py, SMR was 6.8 (95% CI 5.9-7.9) and excess mortality rate was 0.8 (95% CI 0.7-0.9) per 100 py. Mortality was higher in patients with AIDS, hepatitis C virus (HCV) co-infection, and those from CoRIS-MD cohort (1997–2003). Conclusion Mortality among HIV-positive persons remains higher than that of the general population of similar age and sex, with significant differences depending on the history of AIDS or HCV coinfection. PMID:23961924

  11. Evidence for a black-white crossover in all-cause and coronary heart disease mortality in an older population: the North Carolina EPESE.

    PubMed Central

    Corti, M C; Guralnik, J M; Ferrucci, L; Izmirlian, G; Leveille, S G; Pahor, M; Cohen, H J; Pieper, C; Havlik, R J

    1999-01-01

    OBJECTIVES: This cohort study evaluated racial differences in mortality among Blacks and Whites 65 years and older. METHODS: A total of 4136 men and women (1875 Whites and 2261 Blacks) living in North Carolina were interviewed in 1986 and followed up for mortality until 1994. Hazard ratios (HRs) for all-cause and cause-specific mortality were calculated, with adjustment for sociodemographic and coronary heart disease (CHD) risk factors. RESULTS: Black persons had higher mortality rates than Whites at young-old age (65-80 years) but had significantly lower mortality rates after age 80. Black persons age 80 or older had a significantly lower risk of all-cause mortality (HR of Blacks vs Whites, 0.75; 95% confidence interval [CI] = 0.62, 0.90) and of CHD mortality (HR 0.44: 95% CI = 0.30, 0.66). These differences were not observed for other causes of death. CONCLUSIONS: Racial differences in mortality are modified by age. This mortality crossover could be attributed to selective survival of the healthiest oldest Blacks or to other biomedical factors affecting longevity after age 80. Because the crossover was observed for CHD deaths only, age overreporting by Black older persons seems an unlikely explanation of the mortality differences. PMID:10076478

  12. Vegetarian diet and all-cause mortality: Evidence from a large population-based Australian cohort - the 45 and Up Study.

    PubMed

    Mihrshahi, Seema; Ding, Ding; Gale, Joanne; Allman-Farinelli, Margaret; Banks, Emily; Bauman, Adrian E

    2017-04-01

    The vegetarian diet is thought to have health benefits including reductions in type 2 diabetes, hypertension, and obesity. Evidence to date suggests that vegetarians tend to have lower mortality rates when compared with non-vegetarians, but most studies are not population-based and other healthy lifestyle factors may have confounded apparent protective effects. The aim of this study was to evaluate the association between categories of vegetarian diet (including complete, semi and pesco-vegetarian) and all-cause mortality in a large population-based Australian cohort. The 45 and Up Study is a cohort study of 267,180 men and women aged ≥45years in New South Wales (NSW), Australia. Vegetarian diet status was assessed by baseline questionnaire and participants were categorized into complete vegetarians, semi-vegetarians (eat meat≤once/week), pesco-vegetarians and regular meat eaters. All-cause mortality was determined by linked registry data to mid-2014. Cox proportional hazards models quantified the association between vegetarian diet and all-cause mortality adjusting for a range of potential confounding factors. Among 243,096 participants (mean age: 62.3years, 46.7% men) there were 16,836 deaths over a mean 6.1years of follow-up. Following extensive adjustment for potential confounding factors there was no significant difference in all-cause mortality for vegetarians versus non-vegetarians [HR=1.16 (95% CI 0.93-1.45)]. There was also no significant difference in mortality risk between pesco-vegetarians [HR=0.79 (95% CI 0.59-1.06)] or semi-vegetarians [HR=1.12 (95% CI 0.96-1.31)] versus regular meat eaters. We found no evidence that following a vegetarian diet, semi-vegetarian diet or a pesco-vegetarian diet has an independent protective effect on all-cause mortality.

  13. Cardiac troponin and C-reactive protein for predicting all-cause and cardiovascular mortality in patients with chronic kidney disease: A meta-analysis

    PubMed Central

    Li, Wei-Jie; Chen, Xu-Miao; Nie, Xiao-Ying; Zhang, Jing; Cheng, Yun-Jiu; Lin, Xiao-Xiong; Wu, Su-Hua

    2015-01-01

    Elevated serum levels of cardiac troponin and C-reactive protein are associated with all-cause and cardiovascular mortality in patients with end-stage renal disease. However, the relationship between these two biomarker levels and mortality in patients with chronic kidney disease remains unclear. We conducted a meta-analysis to quantify the association of cardiac troponin and C-reactive protein levels with all-cause and cardiovascular mortality in patients with chronic kidney disease. Relevant studies were identified by searching the MEDLINE database through November 2013. Studies were included in the meta-analysis if they reported the long-term all-cause or cardiovascular mortality of chronic kidney disease patients with abnormally elevated serum levels of cardiac troponin or C-reactive protein. Summary estimates of association were obtained using a random-effects model. Thirty-two studies met our inclusion criteria. From the pooled analysis, cardiac troponin and C-reactive protein were significantly associated with all-cause (HR 2.93, 95% CI 1.97-4.33 and HR 1.21, 95% CI 1.14-1.29, respectively) and cardiovascular (HR 3.27, 95% CI 1.67-6.41 and HR 1.19, 95% CI 1.10-1.28, respectively) mortality. In the subgroup analysis of cardiac troponin and C-reactive protein, significant heterogeneities were found among the subgroups of population for renal replacement therapy and for the proportion of smokers and the C-reactive protein analysis method. Elevated serum levels of cardiac troponin and C-reactive protein are significant associated with higher risks of all-cause and cardiovascular mortality in patients with chronic kidney disease. Further studies are warranted to explore the risk stratification in chronic kidney disease patients. PMID:26017799

  14. Lower estimated glomerular filtration rate and higher albuminuria are associated with all-cause and cardiovascular mortality. A collaborative meta-analysis of high-risk population cohorts.

    PubMed

    van der Velde, Marije; Matsushita, Kunihiro; Coresh, Josef; Astor, Brad C; Woodward, Mark; Levey, Andrew; de Jong, Paul; Gansevoort, Ron T; van der Velde, Marije; Matsushita, Kunihiro; Coresh, Josef; Astor, Brad C; Woodward, Mark; Levey, Andrew S; de Jong, Paul E; Gansevoort, Ron T; Levey, Andrew; El-Nahas, Meguid; Eckardt, Kai-Uwe; Kasiske, Bertram L; Ninomiya, Toshiharu; Chalmers, John; Macmahon, Stephen; Tonelli, Marcello; Hemmelgarn, Brenda; Sacks, Frank; Curhan, Gary; Collins, Allan J; Li, Suying; Chen, Shu-Cheng; Hawaii Cohort, K P; Lee, Brian J; Ishani, Areef; Neaton, James; Svendsen, Ken; Mann, Johannes F E; Yusuf, Salim; Teo, Koon K; Gao, Peggy; Nelson, Robert G; Knowler, William C; Bilo, Henk J; Joosten, Hanneke; Kleefstra, Nanno; Groenier, K H; Auguste, Priscilla; Veldhuis, Kasper; Wang, Yaping; Camarata, Laura; Thomas, Beverly; Manley, Tom

    2011-06-01

    Screening for chronic kidney disease is recommended in people at high risk, but data on the independent and combined associations of estimated glomerular filtration rate (eGFR) and albuminuria with all-cause and cardiovascular mortality are limited. To clarify this, we performed a collaborative meta-analysis of 10 cohorts with 266,975 patients selected because of increased risk for chronic kidney disease, defined as a history of hypertension, diabetes, or cardiovascular disease. Risk for all-cause mortality was not associated with eGFR between 60-105 ml/min per 1.73 m², but increased at lower levels. Hazard ratios at eGFRs of 60, 45, and 15 ml/min per 1.73 m² were 1.03, 1.38 and 3.11, respectively, compared to an eGFR of 95, after adjustment for albuminuria and cardiovascular risk factors. Log albuminuria was linearly associated with log risk for all-cause mortality without thresholds. Adjusted hazard ratios at albumin-to-creatinine ratios of 10, 30 and 300 mg/g were 1.08, 1.38, and 2.16, respectively compared to a ratio of five. Albuminuria and eGFR were multiplicatively associated with all-cause mortality, without evidence for interaction. Similar associations were observed for cardiovascular mortality. Findings in cohorts with dipstick data were generally comparable to those in cohorts measuring albumin-to-creatinine ratios. Thus, lower eGFR and higher albuminuria are risk factors for all-cause and cardiovascular mortality in high-risk populations, independent of each other and of cardiovascular risk factors.

  15. Associations of All-Cause Mortality with Census-Based Neighbourhood Deprivation and Population Density in Japan: A Multilevel Survival Analysis

    PubMed Central

    Nakaya, Tomoki; Honjo, Kaori; Hanibuchi, Tomoya; Ikeda, Ai; Iso, Hiroyasu; Inoue, Manami; Sawada, Norie; Tsugane, Shoichiro

    2014-01-01

    Background Despite evidence that neighbourhood conditions affect residents' health, no prospective studies of the association between neighbourhood socio-demographic factors and all-cause mortality have been conducted in non-Western societies. Thus, we examined the effects of areal deprivation and population density on all-cause mortality in Japan. Methods We employed census and survival data from the Japan Public Health Center-based Prospective Study, Cohort I (n = 37,455), consisting of middle-aged residents (40 to 59 years at the baseline in 1990) living in four public health centre districts. Data spanned between 1990 and 2010. A multilevel parametric proportional-hazard regression model was applied to estimate the hazard ratios (HRs) of all-cause mortality by two census-based areal variables —areal deprivation index and population density—as well as individualistic variables such as socioeconomic status and various risk factors. Results We found that areal deprivation and population density had moderate associations with all-cause mortality at the neighbourhood level based on the survival data with 21 years of follow-ups. Even when controlling for individualistic socio-economic status and behavioural factors, the HRs of the two areal factors (using quartile categorical variables) significantly predicted mortality. Further, this analysis indicated an interaction effect of the two factors: areal deprivation prominently affects the health of residents in neighbourhoods with high population density. Conclusions We confirmed that neighbourhood socio-demographic factors are significant predictors of all-cause death in Japanese non-metropolitan settings. Although further study is needed to clarify the cause-effect relationship of this association, the present findings suggest that health promotion policies should consider health disparities between neighbourhoods and possibly direct interventions towards reducing mortality in densely populated and highly

  16. Cardiac troponin and C-reactive protein for predicting all-cause and cardiovascular mortality in patients with chronic kidney disease: a meta-analysis.

    PubMed

    Li, Wei-Jie; Chen, Xu-Miao; Nie, Xiao-Ying; Zhang, Jing; Cheng, Yun-Jiu; Lin, Xiao-Xiong; Wu, Su-Hua

    2015-04-01

    Elevated serum levels of cardiac troponin and C-reactive protein are associated with all-cause and cardiovascular mortality in patients with end-stage renal disease. However, the relationship between these two biomarker levels and mortality in patients with chronic kidney disease remains unclear. We conducted a meta-analysis to quantify the association of cardiac troponin and C-reactive protein levels with all-cause and cardiovascular mortality in patients with chronic kidney disease. Relevant studies were identified by searching the MEDLINE database through November 2013. Studies were included in the meta-analysis if they reported the long-term all-cause or cardiovascular mortality of chronic kidney disease patients with abnormally elevated serum levels of cardiac troponin or C-reactive protein. Summary estimates of association were obtained using a random-effects model. Thirty-two studies met our inclusion criteria. From the pooled analysis, cardiac troponin and C-reactive protein were significantly associated with all-cause (HR 2.93, 95% CI 1.97-4.33 and HR 1.21, 95% CI 1.14-1.29, respectively) and cardiovascular (HR 3.27, 95% CI 1.67-6.41 and HR 1.19, 95% CI 1.10-1.28, respectively) mortality. In the subgroup analysis of cardiac troponin and C-reactive protein, significant heterogeneities were found among the subgroups of population for renal replacement therapy and for the proportion of smokers and the C-reactive protein analysis method. Elevated serum levels of cardiac troponin and C-reactive protein are significant associated with higher risks of all-cause and cardiovascular mortality in patients with chronic kidney disease. Further studies are warranted to explore the risk stratification in chronic kidney disease patients.

  17. Meta-analysis of the effects of carvedilol versus metoprolol on all-cause mortality and hospitalizations in patients with heart failure.

    PubMed

    Briasoulis, Alexandros; Palla, Mohan; Afonso, Luis

    2015-04-15

    Long-term treatment with appropriate doses of carvedilol or metoprolol is currently recommended for patients with heart failure with reduced ejection fraction (HFrEF) to decrease the risk of death, hospitalizations, and patients' symptoms. It remains unclear if the β blockers used in patients with HFrEF are equal or carvedilol is superior to metoprolol types. We performed a meta-analysis of the comparative effects of carvedilol versus metoprolol tartrate and succinate on all-cause mortality and/or hospitalization. We conducted an Embase and MEDLINE search for prospective controlled trials and cohort studies of patients with HFrEF who were received to treatment with carvedilol versus metoprolol. We identified 4 prospective controlled and 6 cohort studies with 30,943 patients who received carvedilol and 69,925 patients on metoprolol types (tartrate and succinate) with an average follow-up duration of 36.4 months. All-cause mortality was reduced in prospective studies with carvedilol versus metoprolol tartrate. Neither all-cause mortality nor hospitalizations were significantly different between carvedilol and metoprolol succinate in the cohort studies. In conclusion, in patients with HFrEF, carvedilol and metoprolol succinate have similar effects in reducing all-cause mortality.

  18. The reverse J shaped association between serum total 25- hydroxyvitamin D and all-cause mortality: The impact of assay standardization

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The impact of standardizing the originally measured serum total 25-hydroxyvitamin D [25(OH)D] values from Third National Health and Nutrition Examination Survey (NHANES III, 1988-1994) on the association between 25(OH)D and rate of all-cause mortality was evaluated. Values were standardized to gold ...

  19. The Influence of Source of Social Support and Size of Social Network on All-Cause Mortality

    PubMed Central

    Becofsky, Katie M.; Shook, Robin P.; Sui, Xuemei; Wilcox, Sara; Lavie, Carl J.; Blair, Steven N.

    2015-01-01

    Objective To examine associations between relative, friend, and partner support, as well as size and source of weekly social network, on mortality risk in the Aerobics Center Longitudinal Study (ACLS). Patients and Methods In a mail-back survey completed between January 1, 1990 and December 31, 1990, adult ACLS participants (n=12,709) answered questions regarding whether they received social support from relatives, friends, and spouse/partner (yes or no for each), and the number of friends and relatives they had contact with at least once per week. Participants were followed until December 31, 2003 or death. Cox proportional hazard regression evaluated the strength of the associations, controlling for covariates. Results Participants (25% women) averaged 53.0 years at baseline. During a median 13.5 years of follow-up, 1,139 deaths occurred. Receiving social support from relatives reduced mortality risk 19% (HR 0.81, 95% CI 0.68–0.95). Receiving spousal/partner support also reduced mortality risk 19% (HR 0.81, 95% CI 0.66-.99). Receiving social support from friends was not associated with mortality risk (HR 0.90, 95% CI 0.75–1.09), however, participants reporting social contact with 6 or 7 friends on a weekly basis had a 24% lower mortality risk than those in contact with ≤ 1 friend (HR 0.76, 95% CI 0.58–0.98). Contact with 2–5 or ≥8 friends was not associated with mortality risk, nor was number of weekly relative contacts. Conclusions Receiving social support from one’s spouse/partner and relatives and maintaining weekly social interaction with 6–7 friends reduced mortality risk. Such data may inform interventions to improve long-term survival. PMID:26055526

  20. Vaccination and All-Cause Child Mortality From 1985 to 2011: Global Evidence From the Demographic and Health Surveys

    PubMed Central

    McGovern, Mark E.; Canning, David

    2015-01-01

    Based on models with calibrated parameters for infection, case fatality rates, and vaccine efficacy, basic childhood vaccinations have been estimated to be highly cost effective. We estimated the association of vaccination with mortality directly from survey data. Using 149 cross-sectional Demographic and Health Surveys, we determined the relationship between vaccination coverage and the probability of dying between birth and 5 years of age at the survey cluster level. Our data included approximately 1 million children in 68,490 clusters from 62 countries. We considered the childhood measles, bacillus Calmette-Guérin, diphtheria-pertussis-tetanus, polio, and maternal tetanus vaccinations. Using modified Poisson regression to estimate the relative risk of child mortality in each cluster, we also adjusted for selection bias that resulted from the vaccination status of dead children not being reported. Childhood vaccination, and in particular measles and tetanus vaccination, is associated with substantial reductions in childhood mortality. We estimated that children in clusters with complete vaccination coverage have a relative risk of mortality that is 0.73 (95% confidence interval: 0.68, 0.77) times that of children in a cluster with no vaccinations. Although widely used, basic vaccines still have coverage rates well below 100% in many countries, and our results emphasize the effectiveness of increasing coverage rates in order to reduce child mortality. PMID:26453618

  1. Vaccination and all-cause child mortality from 1985 to 2011: global evidence from the Demographic and Health Surveys.

    PubMed

    McGovern, Mark E; Canning, David

    2015-11-01

    Based on models with calibrated parameters for infection, case fatality rates, and vaccine efficacy, basic childhood vaccinations have been estimated to be highly cost effective. We estimated the association of vaccination with mortality directly from survey data. Using 149 cross-sectional Demographic and Health Surveys, we determined the relationship between vaccination coverage and the probability of dying between birth and 5 years of age at the survey cluster level. Our data included approximately 1 million children in 68,490 clusters from 62 countries. We considered the childhood measles, bacillus Calmette-Guérin, diphtheria-pertussis-tetanus, polio, and maternal tetanus vaccinations. Using modified Poisson regression to estimate the relative risk of child mortality in each cluster, we also adjusted for selection bias that resulted from the vaccination status of dead children not being reported. Childhood vaccination, and in particular measles and tetanus vaccination, is associated with substantial reductions in childhood mortality. We estimated that children in clusters with complete vaccination coverage have a relative risk of mortality that is 0.73 (95% confidence interval: 0.68, 0.77) times that of children in a cluster with no vaccinations. Although widely used, basic vaccines still have coverage rates well below 100% in many countries, and our results emphasize the effectiveness of increasing coverage rates in order to reduce child mortality.

  2. A meta-analysis of the effects of statin treatment on cardiovascular events and all-cause mortality in diabetic dialysis patients

    PubMed Central

    Yang, Man; Xie, Xi-Sheng; Yuan, Wei-Jie

    2015-01-01

    Objectives: Diabetic dialysis patients have higher risk of cardiovascular disease (CVD) than general population. While statin treatment is effective in prevention of CVD and all-cause mortality in general population, the use of statin in diabetic dialysis patients remains controversial. Thus, we aimed to assess the effects of statin treatment on prevention of CVD and all-cause mortality in diabetic dialysis patients by meta-analysis. Materials and methods: Pubmed, Embase and Cochrane Library were searched between each database’s inception and July, 2014. Hazard ratio (HR) with 95% confidence interval (CI) for CVD and all-cause mortality was extracted from each study. The pooled analysis was performed using random-effects models by Stata 12.0. Results: Our search yielded five eligible articles including two RCTs and three observational studies. By pooled estimate, statin treatment was associated with a decreased risk of the cardiac endpoint which included cardiac death and nonfatal MI (HR=0.84, 95% CI: 0.78-0.90) and all cardiac events combined (HR=0.89, 95% CI: 0.82-0.96). There was no difference in the overall incidence of fatal or nonfatal stroke (HR=1.24, 95% CI: 0.99-1.53) and all cerebrovascular events combined (HR=1.14, 95% CI: 0.98-1.33) between statin treatment and control group. Finally, statin treatment was associated with a decreased risk of all-cause mortality (HR=0.81, 95% CI: 0.71-0.92). Conclusions: Statin treatment may be beneficial for reducing the risk of cardiac events and all-cause mortality while have no effect on overall cerebrovascular events in diabetic dialysis patients. More RCTs were needed to validate the results. PMID:26309494

  3. Effect of Urate-Lowering Therapy on All-Cause and Cardiovascular Mortality in Hyperuricemic Patients without Gout: A Case-Matched Cohort Study

    PubMed Central

    Chen, Jiunn-Horng; Lan, Joung-Liang; Cheng, Chi-Fung; Liang, Wen-Miin; Lin, Hsiao-Yi; Tsay, Gregory J; Yeh, Wen-Ting; Pan, Wen-Harn

    2015-01-01

    Objectives An increased risk of mortality in patients with hyperuricemia has been reported. We examined (1) the risk of all-cause and cardiovascular disease (CVD) mortality in untreated hyperuricemic patients who did not receive urate-lowering therapy (ULT), and (2) the impact of ULT on mortality risk in patients with hyperuricemia. Methods In this retrospective case-matched cohort study during a mean follow-up of 6.4 years, 40,118 Taiwanese individuals aged ≥17 years who had never used ULT and who had never had gout were examined. The mortality rate was compared between 3,088 hyperuricemic patients who did not receive ULT and reference subjects (no hyperuricemia, no gout, no ULT) matched for age and sex (1:3 hyperuricemic patients/reference subjects), and between 1,024 hyperuricemic patients who received ULT and 1,024 hyperuricemic patients who did not receive ULT (matched 1:1 based on their propensity score and the index date of ULT prescription). Cox proportional hazard modeling was used to estimate the respective risk of all-cause and CVD (ICD-9 code 390–459) mortality. Results After adjustment, hyperuricemic patients who did not receive ULT had increased risks of all-cause (hazard ratio, 1.24; 95% confidence interval, 0.97–1.59) and CVD (2.13; 1.34–3.39) mortality relative to the matched reference subjects. Hyperuricemic patients treated with ULT had a lower risk of all-cause death (0.60; 0.41–0.88) relative to hyperuricemic patients who did not receive ULT. Conclusion Under-treatment of hyperuricemia has serious negative consequences. Hyperuricemic patients who received ULT had potentially better survival than patients who did not. PMID:26683302

  4. Meta-analysis: low-dose intake of vitamin E combined with other vitamins or minerals may decrease all-cause mortality.

    PubMed

    Jiang, Shan; Pan, Zhenyu; Li, Hui; Li, Fenglan; Song, Yanyan; Qiu, Yu

    2014-01-01

    It has been suggested that vitamin E alone or combined with other vitamins or minerals can prevent oxidative stress and slow oxidative injury-related diseases, such as cardiovascular disease and cancer. A comprehensive search of PubMed/MEDLINE, EMBASE and the Cochrane Library was performed. Relative risk was used as an effect measure to compare the intervention and control groups. A total of 33 trials were included in the meta-analysis. Neither vitamin E intake alone (RR=1.01; 95% CI, 0.97 to 1.04; p=0.77) nor vitamin E intake combined with other agents (RR=0.97; 95% CI, 0.89 to 1.06; p=0.55) was correlated with all-cause mortality. Subgroup analyses revealed that low-dose vitamin E supplementation combined with other agents is associated with a statistically significant reduction in all-cause mortality (RR=0.92; 95% CI, 0.86 to 0.98; p=0.01), and vitamin E intake combined with other agents is associated with a statistically significant reduction in mortality rates among individuals without probable or confirmed diseases (RR=0.92; 95% CI, 0.86 to 0.99; p=0.02). Neither vitamin E intake alone nor combined with other agents is associated with a reduction in all-cause mortality. But a low dose (<400 IU/d) of vitamin E combined with other agents is correlated with a reduction in all-cause mortality, and vitamin E intake combined with other agents is correlated with a reduction in the mortality rate among individuals without probable or confirmed diseases.

  5. Whole-Grain Intake and Mortality from All Causes, Cardiovascular Disease, and Cancer: A Systematic Review and Dose-Response Meta-Analysis of Prospective Cohort Studies.

    PubMed

    Benisi-Kohansal, Sanaz; Saneei, Parvane; Salehi-Marzijarani, Mohammad; Larijani, Bagher; Esmaillzadeh, Ahmad

    2016-11-01

    No conclusive information is available about the relation between the consumption of whole grains and the risk of mortality. We aimed to conduct a meta-analysis of prospective cohort studies to summarize the relation between whole-grain intake and risk of mortality from all causes, cardiovascular disease, and total and specific cancers. A systematic search of the literature published earlier than March 2015 was conducted in Medline and PubMed, SCOPUS, EMBASE, and Cochrane Library to identify relevant articles. Prospective cohort studies that examined the association of total whole-grain intake or specific whole-grain foods with risk of mortality from all causes, cardiovascular disease, and total and specific cancers were considered. Twenty prospective cohort studies were included in the systematic review: 9 studies reported total whole-grain intake and 11 others reported specific whole-grain food intake. In a follow-up period of 5.5 to 26 y, there were 191,979 deaths (25,595 from cardiovascular disease, 32,746 from total cancers, and 2671 from specific cancers) in 2,282,603 participants. A greater intake of both total whole grains and specific whole-grain foods was significantly associated with a lower risk of all-cause mortality in the meta-analysis. The pooled RR for all-cause mortality for an increase of 3 servings total whole grains/d (90 g/d) was 0.83 (95% CI: 0.79, 0.88). Total whole-grain intake (0.84; 95% CI: 0.76, 0.93) and specific whole-grain foods (0.82; 95% CI: 0.75, 0.90) were also associated with a reduced risk of mortality from cardiovascular disease. Each additional 3 servings total whole grains/d was associated with a 25% lower risk of mortality from cardiovascular disease. An inverse association was observed between whole-grain intake and risk of mortality from total cancers (0.94; 95% CI: 0.91, 0.98). We found an inverse association between whole-grain intake and mortality from all causes, cardiovascular disease, and total cancers.

  6. Frailty Index Predicts All-Cause Mortality for Middle-Aged and Older Taiwanese: Implications for Active-Aging Programs

    PubMed Central

    Lin, Shu-Yu; Lee, Wei-Ju; Chou, Ming-Yueh; Peng, Li-Ning; Chiou, Shu-Ti; Chen, Liang-Kung

    2016-01-01

    Background Frailty Index, defined as an individual’s accumulated proportion of listed health-related deficits, is a well-established metric used to assess the health status of old adults; however, it has not yet been developed in Taiwan, and its local related structure factors remain unclear. The objectives were to construct a Taiwan Frailty Index to predict mortality risk, and to explore the structure of its factors. Methods Analytic data on 1,284 participants aged 53 and older were excerpted from the Social Environment and Biomarkers of Aging Study (2006), in Taiwan. A consensus workgroup of geriatricians selected 159 items according to the standard procedure for creating a Frailty Index. Cox proportional hazard modeling was used to explore the association between the Taiwan Frailty Index and mortality. Exploratory factor analysis was used to identify structure factors and produce a shorter version–the Taiwan Frailty Index Short-Form. Results During an average follow-up of 4.3 ± 0.8 years, 140 (11%) subjects died. Compared to those in the lowest Taiwan Frailty Index tertile (< 0.18), those in the uppermost tertile (> 0.23) had significantly higher risk of death (Hazard ratio: 3.2; 95% CI 1.9–5.4). Thirty-five items of five structure factors identified by exploratory factor analysis, included: physical activities, life satisfaction and financial status, health status, cognitive function, and stresses. Area under the receiver operating characteristic curves (C-statistics) of the Taiwan Frailty Index and its Short-Form were 0.80 and 0.78, respectively, with no statistically significant difference between them. Conclusion Although both the Taiwan Frailty Index and Short-Form were associated with mortality, the Short-Form, which had similar accuracy in predicting mortality as the full Taiwan Frailty Index, would be more expedient in clinical practice and community settings to target frailty screening and intervention. PMID:27537684

  7. The interactive effects of type 2 diabetes mellitus and schizophrenia on all-cause mortality: The Fremantle Diabetes Study.

    PubMed

    Davis, Wendy Angela; Starkstein, Sergio E; Bruce, David G; Davis, Timothy M E

    2015-01-01

    In a study of the effects of type 2 diabetes and schizophrenia on mortality in 1296 community-based diabetic patients followed for a mean±SD 12.9±6.1years and in 5159 matched non-diabetic residents, 0.4% of each group had schizophrenia. Patients with both conditions had a six-fold adjusted increased risk of death.

  8. Digoxin Is Associated With Increased All-cause Mortality in Patients With Atrial Fibrillation Regardless of Concomitant Heart Failure: A Meta-analysis.

    PubMed

    Wang, Zhi-Quan; Zhang, Rui; Chen, Man-Tian; Wang, Qun-Shan; Zhang, Yi; Huang, Xiao-Hong; Wang, Jun; Yan, Jian-Hua; Li, Yi-Gang

    2015-09-01

    For decades, digoxin has been widely used to control ventricular rate in atrial fibrillation (AF). However, it remains controversial as to whether digoxin is associated with increased mortality in AF. In this study, we searched relevant studies that were published before December 1, 2014, in PubMed, EMBASE, and the Cochrane central databases. We systematically reviewed the references and performed a meta-analysis of 8 carefully selected studies with 302,738 patients who were included for the final analysis. It was shown that digoxin use was associated with increased risk of all-cause mortality in AF overall [hazard ratio (HR) = 1.375, 95% confidence intervals (CI), 1.201-1.574, P = 0.0001]. Subgroup analysis further revealed that digoxin was associated with increased all-cause mortality in patients with AF, which was complicated by heart failure (HF) (HR = 1.201, CI, 1.074- 1.344, P = 0.001), and in those subjects without HF (HR = 1.172, CI, 1.148-1.198, P = 0.0001). Sensitivity analyses found results to be robust. Our findings indicated that digoxin use was associated with significantly increased all-cause mortality in patients with AF regardless of concomitant HF. We suggest that digoxin should not be preferentially used over other rate control medications in AF.

  9. Examining the association between serum lactic dehydrogenase and all-cause mortality in patients with metabolic syndrome: a retrospective observational study

    PubMed Central

    Wu, Li-Wei; Kao, Tung-Wei; Lin, Chien-Ming; Yang, Hui-Fang; Sun, Yu-Shan; Liaw, Fang-Yih; Wang, Chung-Ching; Peng, Tao-Chun; Chen, Wei-Liang

    2016-01-01

    Objectives Emerging evidence indicates that elevated serum lactic dehydrogenase (LDH) levels are associated with increased cardiovascular mortality, but the mechanisms for this relationship remain uncertain. Since metabolic syndrome (MetS) is correlated with a higher risk of cardiovascular complications, we investigated the joint association between serum LDH levels and all-cause mortality in the US general population with MetS. Design Retrospective study. Setting The USA. Participants A retrospective observational study of 3872 adults with MetS and 7516 adults without MetS in the National Health and Nutrition Examination Survey III was performed. Main outcome measures Participants with and without MetS were both divided into 3 groups according to their serum LDH level. Multivariable Cox regression analyses and Kaplan-Meier survival probabilities were used to jointly relate all-cause, cardiovascular and cancer mortality risk to different serum LDH levels. Results For all-cause mortality in participants with MetS, multivariable adjusted HRs were 1.006 (95% CI 0.837 to 1.210; p=0.947) for serum LDH of 149–176 U/L compared with 65–149 U/L, and 1.273 (95% CI 1.049 to 1.547; p=0.015) for serum LDH of 176–668 U/L compared with 65–149 U/L. Conclusions Results support a positive association between higher level of serum LDH and mortality from all causes in individuals with MetS. PMID:27217285

  10. Association between the markers of metabolic acid load and higher all-cause and cardiovascular mortality in a general population with preserved renal function.

    PubMed

    Park, Minseon; Jung, Sung Jae; Yoon, Seoyoung; Yun, Jae Moon; Yoon, Hyung-Jin

    2015-06-01

    Although metabolic acid load has been associated with many well-known risk factors for mortality, its clinical implications are not yet clear. To evaluate the association between biomarkers of metabolic acid load, such as serum bicarbonate, serum anion gap and urine pH and mortality, we analyzed the health records of 31,590 adults who underwent a health screening between January 2001 and December 2010 and had an estimated glomerular filtration rate ⩾60 ml min(-1) per 1.73 m2. Urine pH was measured by a dipstick test performed on fast morning urine sample and categorized as acidic (urine pH ⩽5.5), neutral and alkaline (urine pH ⩾8.0). Using the Cox proportional hazard model, the adjusted hazard ratio (aHR) of all-cause mortality of the lowest quartile of serum bicarbonate was 1.460 (95% confidence interval (CI) 1.068-1.995) compared with the highest quartile, after a median follow-up of 93 months. The aHRs of cardiovascular and cancer mortality of the lowest quartile of serum bicarbonate were 2.647 (95% CI 1.148-6.103) and 1.604 (95% CI 1.024-2.513), respectively, compared with the highest quartile. Acidic and neutral urine pH were significantly associated with a higher all-cause mortality (aHR 2.550, 95% CI 1.316-4.935; aHR 2.376 95% CI 1.254-4.501, respectively), compared with an alkaline urine pH. In conclusion, higher metabolic acid load was associated with an increased all-cause and cardiovascular mortality in a healthy population. The association between metabolic acid load and mortality and the causality of the relationship need to be confirmed.

  11. Impact of microalbuminuria on incident coronary heart disease, cardiovascular and all-cause mortality: a meta-analysis of prospective studies.

    PubMed

    Xia, Fang; Liu, Guanghua; Shi, Yifu; Zhang, Yan

    2015-01-01

    This study is to investigate the magnitude of relationship between microalbuminuria and incident coronary heart disease (CHD) and mortality in the general population by conducting a meta-analysis. A comprehensive literature search in Pubmed and Embase database was performed prior to March 2014. Only prospective studies investigating the presence of microalbuminuria and incident CHD, cardiovascular disease (CVD), and mortality and were selected. Pooled risk ratio (RR) and 95% confidence interval (CI) were calculated by the presence of microalbuminuria versus without microalbuminuria. Finally, we identified 8 prospective studies involving 114,105 individuals. Participants with microalbuminuria were associated with 69% greater risk of CVD (RR=1.69; 95% CI 1.41-2.02) and 41% greater risk of CHD (RR=1.41; 95% CI 1.17-1.69). Participants with microalbuminuria were also associated with 57% greater risk of cardiovascular mortality (RR=1.57; 95% CI 1.20-2.06) and 65% greater risk of all-cause mortality (RR=1.65; 95% CI 1.45-1.88). Microalbuminuria is an independent predictor for CHD, CVD, and all-cause mortality in the general population. Early detection of microalbuminuria in the general population is likely to identify patients at increased risk of CVD and mortality.

  12. 15-Year Prognostic Utility of Coronary Artery Calcium Scoring for All-Cause Mortality in the Elderly

    PubMed Central

    Hartaigh, Bríain ó; Valenti, Valentina; Cho, Iksung; Schulman-Marcus, Joshua; Gransar, Heidi; Knapper, Joseph; Kelkar, Anita A.; Xie, Joseph X.; Chang, Hyuk-Jae; Shaw, Leslee J.; Callister, Tracy Q.; Min, James K.

    2016-01-01

    Introduction Prior studies have demonstrated a decline in the predictive ability of conventional risk factors (RF) with advancing age, emphasizing the need for novel tools to improve risk stratification in the elderly. Coronary artery calcification (CAC) is a robust predictor of adverse cardiovascular events, but its long-term prognostic utility beyond RFs in elderly persons is unknown. Methods A consecutive series of 9,715 individuals underwent CAC scoring and were followed for a mean of 14.6±1.1 years. Multivariable Cox proportional hazards regression (HR) with 95% confidence intervals (95% CI) was employed to assess the independent relationship of CAC and RFs with all-cause death. The incremental value of CAC, stratified by age, was examined by using an area under the receiver operator characteristic curve (AUC) and category-free net reclassification improvement (NRI). Results Of the overall study sample, 728 (7.5%) adults (mean age 74.2±4.2 years; 55.6% female) were 70 years or older, of which 157 (21.6%) died. The presence of any CAC was associated with a >4-fold (95% CI = 2.84–6.59) adjusted risk of death for those over the age of 70, which was higher compared with younger study counterparts, or other measured RFs. For individuals 70 years or older, the discriminatory ability of CAC improved upon that of RFs alone (C statistics 0.764 vs. 0.675, P <0.001). CAC also enabled improved reclassification (category-free NRI = 84%, P <0.001) when added to RFs. Conclusion In a large-scale observational cohort registry, CAC improves prediction, discrimination, and reclassification of elderly individuals at risk for future death. PMID:26841073

  13. Dietary sodium-to-potassium ratio as a risk factor for stroke, cardiovascular disease and all-cause mortality in Japan: the NIPPON DATA80 cohort study

    PubMed Central

    Okayama, Akira; Okuda, Nagako; Miura, Katsuyuki; Okamura, Tomonori; Hayakawa, Takehito; Akasaka, Hiroshi; Ohnishi, Hirofumi; Saitoh, Shigeyuki; Arai, Yusuke; Kiyohara, Yutaka; Takashima, Naoyuki; Yoshita, Katsushi; Fujiyoshi, Akira; Zaid, Maryam; Ohkubo, Takayoshi; Ueshima, Hirotsugu

    2016-01-01

    Objectives To evaluate the impact of dietary sodium and potassium (Na–K) ratio on mortality from total and subtypes of stroke, cardiovascular disease (CVD) and all causes, using 24-year follow-up data of a representative sample of the Japanese population. Setting Prospective cohort study. Participants In the 1980 National Cardiovascular Survey, participants were followed for 24 years (NIPPON DATA80, National Integrated Project for Prospective Observation of Non-communicable Disease And its Trends in the Aged). Men and women aged 30–79 years without hypertensive treatment, history of stroke or acute myocardial infarction (n=8283) were divided into quintiles according to dietary Na–K ratio assessed by a 3-day weighing dietary record at baseline. Age-adjusted and multivariable-adjusted HRs were calculated using the Mantel-Haenszel method and Cox proportional hazards model. Primary outcome measures Mortality from total and subtypes of stroke, CVD and all causes. Results A total of 1938 deaths from all causes were observed over 176 926 person-years. Na–K ratio was significantly and non-linearly related to mortality from all stroke (p=0.002), CVD (p=0.005) and total mortality (p=0.001). For stroke subtypes, mortality from haemorrhagic stroke was positively related to Na–K ratio (p=0.024). Similar relationships were observed for men and women. The observed relationships remained significant after adjustment for other risk factors. Quadratic non-linear multivariable-adjusted HRs (95% CI) in the highest quintile versus the lowest quintile of Na–K ratio were 1.42 (1.07 to 1.90) for ischaemic stroke, 1.57 (1.05 to 2.34) for haemorrhagic stroke, 1.43 (1.17 to 1.76) for all stroke, 1.39 (1.20 to 1.61) for CVD and 1.16 (1.06 to 1.27) for all-cause mortality. Conclusions Dietary Na–K ratio assessed by a 3-day weighing dietary record was a significant risk factor for mortality from haemorrhagic stroke, all stroke, CVD and all causes among a Japanese population

  14. Coffee consumption and risk of all-cause, cardiovascular, and cancer mortality in smokers and non-smokers: a dose-response meta-analysis.

    PubMed

    Grosso, Giuseppe; Micek, Agnieszka; Godos, Justyna; Sciacca, Salvatore; Pajak, Andrzej; Martínez-González, Miguel A; Giovannucci, Edward L; Galvano, Fabio

    2016-12-01

    Coffee consumption has been associated with several benefits toward human health. However, its association with mortality risk has yielded contrasting results, including a non-linear relation to all-cause and cardiovascular disease (CVD) mortality and no association with cancer mortality. As smoking habits may affect the association between coffee and health outcomes, the aim of the present study was to update the latest dose-response meta-analysis of prospective cohort studies on the association between coffee consumption and mortality risk and conduct stratified analyses by smoking status and other potential confounders. A systematic search was conducted in electronic databases to identify relevant studies, risk estimates were retrieved from the studies, and dose-response analysis was modeled by using restricted cubic splines. A total of 31 studies comprising 1610,543 individuals and 183,991 cases of all-cause, 34,574 of CVD, and 40,991 of cancer deaths were selected. Analysis showed decreased all-cause [relative risk (RR) = 0.86, 95 % confidence interval (CI) = 0.82, 0.89)] and CVD mortality risk (RR = 0.85, 95 % CI = 0.77, 0.93) for consumption of up to 4 cups/day of coffee, while higher intakes were associated with no further lower risk. When analyses were restricted only to non-smokers, a linear decreased risk of all-cause (RR = 0.94, 95 % CI = 0.93, 0.96), CVD (RR = 0.94, 95 % CI = 0.91, 0.97), and cancer mortality (RR = 0.98, 95 % CI = 0.96, 1.00) for 1 cup/day increase was found. The search for other potential confounders, including dose-response analyses in subgroups by gender, geographical area, year of publication, and type of coffee, showed no relevant differences between strata. In conclusion, coffee consumption is associated with decreased risk of mortality from all-cause, CVD, and cancer; however, smoking modifies the observed risk when studying the role of coffee on human health.

  15. Cooking Coal Use and All-Cause and Cause-Specific Mortality in a Prospective Cohort Study of Women in Shanghai, China

    PubMed Central

    Kim, Christopher; Seow, Wei Jie; Shu, Xiao-Ou; Bassig, Bryan A.; Rothman, Nathaniel; Chen, Bingshu E.; Xiang, Yong-Bing; Hosgood, H. Dean; Ji, Bu-Tian; Hu, Wei; Wen, Cuiju; Chow, Wong-Ho; Cai, Qiuyin; Yang, Gong; Gao, Yu-Tang; Zheng, Wei; Lan, Qing

    2016-01-01

    Background: Nearly 4.3 million deaths worldwide were attributable to exposure to household air pollution in 2012. However, household coal use remains widespread. Objectives: We investigated the association of cooking coal and all-cause and cause-specific mortality in a prospective cohort of primarily never-smoking women in Shanghai, China. Methods: A cohort of 74,941 women were followed from 1996 through 2009 with annual linkage to the Shanghai vital statistics database. Cause-specific mortality was identified through 2009. Use of household coal for cooking was assessed through a residential history questionnaire. Cox proportional hazards models estimated the risk of mortality associated with household coal use. Results: In this cohort, 63% of the women ever used coal (n = 46,287). Compared with never coal use, ever use of coal was associated with mortality from all causes [hazard ratio (HR) = 1.12; 95% confidence interval (CI): 1.05, 1.21], cancer (HR = 1.14; 95% CI: 1.03, 1.27), and ischemic heart disease (overall HR = 1.61; 95% CI: 1.14, 2.27; HR for myocardial infarction specifically = 1.80; 95% CI: 1.16, 2.79). The risk of cardiovascular mortality increased with increasing duration of coal use, compared with the risk in never users. The association between coal use and ischemic heart disease mortality diminished with increasing years since cessation of coal use. Conclusions: Evidence from this study suggests that past use of coal among women in Shanghai is associated with excess all-cause mortality, and from cardiovascular diseases in particular. The decreasing association with cardiovascular mortality as the time since last use of coal increased emphasizes the importance of reducing use of household coal where use is still widespread. Citation: Kim C, Seow WJ, Shu XO, Bassig BA, Rothman N, Chen BE, Xiang YB, Hosgood HD III, Ji BT, Hu W, Wen C, Chow WH, Cai Q, Yang G, Gao YT, Zheng W, Lan Q. 2016. Cooking coal use and all-cause and cause-specific mortality in

  16. Historical Trends and Regional Differences in All-Cause and Amenable Mortality Among American Indians and Alaska Natives Since 1950

    PubMed Central

    Kunitz, Stephen J.; Veazie, Mark; Henderson, Jeffrey A.

    2014-01-01

    American Indian and Alaska Native (AI/AN) death rates declined over most of the 20th century, even before the Public Health Service became responsible for health care in 1956. Since then, rates have declined further, although they have stagnated since the 1980s. These overall patterns obscure substantial regional differences. Most significant, rates in the Northern and Southern Plains have declined far less since 1949 to 1953 than those in the East, Southwest, or Pacific Coast. Data for Alaska are not available for the earlier period, so its trajectory of mortality cannot be ascertained. Socioeconomic measures do not adequately explain the differences and rates of change, but migration, changes in self-identification as an AI/AN person, interracial marriage, and variations in health care effectiveness all appear to be implicated. PMID:24754651

  17. Sleep duration and risk of all-cause mortality: A flexible, non-linear, meta-regression of 40 prospective cohort studies.

    PubMed

    Liu, Tong-Zu; Xu, Chang; Rota, Matteo; Cai, Hui; Zhang, Chao; Shi, Ming-Jun; Yuan, Rui-Xia; Weng, Hong; Meng, Xiang-Yu; Kwong, Joey S W; Sun, Xin

    2017-04-01

    Approximately 27-37% of the general population experience prolonged sleep duration and 12-16% report shortened sleep duration. However, prolonged or shortened sleep duration may be associated with serious health problems. A comprehensive, flexible, non-linear meta-regression with restricted cubic spline (RCS) was used to investigate the dose-response relationship between sleep duration and all-cause mortality in adults. Medline (Ovid), Embase, EBSCOhost-PsycINFO, and EBSCOhost-CINAHL Plus databases, reference lists of relevant review articles, and included studies were searched up to Nov. 29, 2015. Prospective cohort studies investigating the association between sleep duration and all-cause mortality in adults with at least three categories of sleep duration were eligible for inclusion. We eventually included in our study 40 cohort studies enrolling 2,200,425 participants with 271,507 deaths. A J-shaped association between sleep duration and all-cause mortality was present: compared with 7 h of sleep (reference for 24-h sleep duration), both shortened and prolonged sleep durations were associated with increased risk of all-cause mortality (4 h: relative risk [RR] = 1.05; 95% confidence interval [CI] = 1.02-1.07; 5 h: RR = 1.06; 95% CI = 1.03-1.09; 6 h: RR = 1.04; 95% CI = 1.03-1.06; 8 h: RR = 1.03; 95% CI = 1.02-1.05; 9 h: RR = 1.13; 95% CI = 1.10-1.16; 10 h: RR = 1.25; 95% CI = 1.22-1.28; 11 h: RR = 1.38; 95% CI = 1.33-1.44; n = 29; P < 0.01 for non-linear test). With regard to the night-sleep duration, prolonged night-sleep duration was associated with increased all-cause mortality (8 h: RR = 1.01; 95% CI = 0.99-1.02; 9 h: RR = 1.08; 95% CI = 1.05-1.11; 10 h: RR = 1.24; 95% CI = 1.21-1.28; n = 13; P < 0.01 for non-linear test). Subgroup analysis showed females with short sleep duration a day (<7 h) were at high risk of all-cause mortality (4 h: RR = 1.07; 95% CI = 1.02-1.13; 5 h: RR = 1.08; 95

  18. All-cause, drug-related, and HIV-related mortality risk by trajectories of jail incarceration and homelessness among adults in New York City.

    PubMed

    Lim, Sungwoo; Harris, Tiffany G; Nash, Denis; Lennon, Mary Clare; Thorpe, Lorna E

    2015-02-15

    We studied a cohort of 15,620 adults who had experienced at least 1 jail incarceration and 1 homeless shelter stay in 2001-2003 in New York City to identify trajectories of these events and tested whether a particular trajectory was associated with all-cause, drug-related, or human immunodeficiency virus (HIV)-related mortality risk in 2004-2005. Using matched data on jail time, homeless shelter stays, and vital statistics, we performed sequence analysis and assessed mortality risk using standardized mortality ratios (SMRs) and marginal structural modeling. We identified 6 trajectories. Sixty percent of the cohort members had a temporary pattern, which was characterized by sporadic experiences of brief incarceration and homelessness, whereas the rest had the other 5 patterns, which reflected experiences of increasing, decreasing, or persistent jail or shelter stays. Mortality risk among individuals with a temporary pattern was significantly higher than those of adults who had not been incarcerated or stayed in a homeless shelter during the study period (all-cause SMR: 1.35, 95% confidence interval (CI): 1.14, 1.59; drug-related SMR: 4.60, 95% CI: 3.17, 6.46; HIV-related SMR: 1.54, 95% CI: 1.03, 2.21); all-cause and HIV-related SMRs in other patterns were not statistically significantly different. When we compared all 6 trajectories, the temporary pattern was more strongly associated with higher mortality risk than was the continuously homelessness pattern. Institutional interventions to reduce recurrent cycles of incarceration and homelessness are needed to augment behavioral interventions to reduce mortality risk.

  19. Upper gastrointestinal bleeding as a risk factor for dialysis and all-cause mortality: a cohort study of chronic kidney disease patients in Taiwan

    PubMed Central

    Liang, Chih-Chia; Chang, Chiz-Tzung; Wang, I-Kuan; Huang, Chiu-Ching

    2016-01-01

    Objective Impaired renal function is associated with higher risk of upper gastrointestinal bleeding (UGIB) in patients with chronic kidney disease and not on dialysis (CKD-ND). It is unclear if UGIB increases risk of chronic dialysis. The aim of the study was to investigate risk of chronic dialysis in CKD-ND patients with UGIB. Setting All CKD-ND stage 3–5 patients of a CKD programme in one hospital between 2003 and 2009 were enrolled and prospectively followed until September 2012. Primary and secondary outcome measures Chronic dialysis (dialysis for more than 3 months) started and all-cause mortality. The risk of chronic dialysis was analysed using Cox proportional hazard regression with adjustments for age, gender and renal function, followed by competing-risks analysis. Results We analysed 3126 CKD-ND patients with a mean age of 65±14 years for 2.8 years. Of 3126 patients, 387 (12.4%) patients developed UGIB, 989 (31.6%) patients started chronic dialysis and 197 (6.3%) patients died. UGIB increased all-cause mortality (adjusted HR (aHR): 1.51, 95% CI 1.07 to 2.13) and the risk of chronic dialysis (aHR; 1.29, 95% CI 1.11 to 1.50). The subdistribution HR (SHR) of UGIB for chronic dialysis (competing event: all-cause mortality) was 1.37 (95% CI 1.15 to 1.64) in competing-risks analysis with adjustments for age, renal function, gender, diabetes, haemoglobin, albumin and urine protein/creatinine ratio. Conclusions UGIB is associated with increased risk of chronic dialysis and all-cause mortality in patients with CKD-ND stages 3–5. This association is independent of age, gender, basal renal function, haemoglobin, albumin and urine protein levels. PMID:27150184

  20. Combined associations of body weight and lifestyle factors with all cause and cause specific mortality in men and women: prospective cohort study

    PubMed Central

    Veronese, Nicola; Li, Yanping; Manson, JoAnn E; Willett, Walter C; Fontana, Luigi

    2016-01-01

    Objective To evaluate the combined associations of diet, physical activity, moderate alcohol consumption, and smoking with body weight on risk of all cause and cause specific mortality. Design Longitudinal study with up to 32 years of follow-up. Setting Nurses’ Health Study (1980-2012) and Health Professionals Follow-up Study (1986-2012). Participants 74 582 women from the Nurses’ Health Study and 39 284 men from the Health Professionals Follow-up Study who were free from cardiovascular disease and cancer at baseline. Main outcome measures Exposures included body mass index (BMI), score on the alternate healthy eating index, level of physical activity, smoking habits, and alcohol drinking while outcome was mortality (all cause, cardiovascular, cancer). Cox proportional hazard models were used to calculate the adjusted hazard ratios of all cause, cancer, and cardiovascular mortality with their 95% confidence intervals across categories of BMI, with 22.5-24.9 as the reference. Results During up to 32 years of follow-up, there were 30 013 deaths (including 10 808 from cancer and 7189 from cardiovascular disease). In each of the four categories of BMI studied (18.5-22.4, 22.5-24.9, 25-29.9, ≥30), people with one or more healthy lifestyle factors had a significantly lower risk of total, cardiovascular, and cancer mortality than individuals with no low risk lifestyle factors. A combination of at least three low risk lifestyle factors and BMI between 18.5-22.4 was associated with the lowest risk of all cause (hazard ratio 0.39, 95% confidence interval 0.35 to 0.43), cancer (0.40, 0.34 to 0.47), and cardiovascular (0.37, 0.29 to 0.46) mortality, compared with those with BMI between 22.5-24.9 and none of the four low risk lifestyle factors. Conclusion Although people with a higher BMI can have lower risk of premature mortality if they also have at least one low risk lifestyle factor, the lowest risk of premature mortality is in people in the 18

  1. Impact of diabetes mellitus on risk of cardiovascular disease and all-cause mortality: Evidence on health outcomes and antidiabetic treatment in United States adults

    PubMed Central

    Liu, Longjian; Simon, Barbara; Shi, Jinggaofu; Mallhi, Arshpreet Kaur; Eisen, Howard J

    2016-01-01

    AIM To examine the epidemic of diabetes mellitus (DM) and its impact on mortality from all-cause and cardiovascular disease (CVD), and to test the effect of antidiabetic therapy on the mortality in United States adults. METHODS The analysis included a randomized population sample of 272149 subjects ages ≥ 18 years who participated in the National Health Interview Surveys (NHIS) in 2000-2009. Chronic conditions (hypertension, DM and CVD) were classified by participants’ self-reports of physician diagnosis. NHIS-Mortality Linked Files, and NHIS-Medical Expenditure Panel Survey Linkage Files on prescribed medicines for patients with DM were used to test the research questions. χ2, Poisson and Cox’s regression models were applied in data analysis. RESULTS Of all participants, 22305 (8.2%) had DM. The prevalence of DM significantly increased from 2000 to 2009 in all age groups (P < 0.001). Within an average 7.39 (SD = 3) years of follow-up, male DM patients had 1.56 times higher risk of death from all-cause (HR = 1.56, 95%CI: 1.49-1.64), 1.72 times higher from heart disease [1.72 (1.53-1.93)], 1.48 times higher from cerebrovascular disease [1.48 (1.18-1.85)], and 1.67 times higher from CVD [1.67 (1.51-1.86)] than subjects without DM, respectively. Similar results were observed in females. In males, 10% of DM patients did not use any antidiabetic medications, 38.1% used antidiabetic monotherapy, and 51.9% used ≥ 2 antidiabetic medications. These corresponding values were 10.3%, 40.4% and 49.4% in females. A significant protective effect of metformin monotherapy or combination therapy (except for insulin) on all-cause mortality and a protective but non-significant effect on CVD mortality were observed. CONCLUSION This is the first study using data from multiple linkage files to confirm a significant increased prevalence of DM in the last decade in the United States. Patients with DM have significantly higher risk of death from all-cause and CVD than those without

  2. Low systolic blood pressure and mortality from all-cause and vascular diseases among the rural elderly in Korea; Kangwha cohort study.

    PubMed

    Yi, Sang-Wook; Hong, Seri; Ohrr, Heechoul

    2015-01-01

    The association between low systolic blood pressure (SBP) and vascular diseases is unclear. The aim of this study was to prospectively examine the association between SBP, especially low SBP, and mortality from all causes and vascular diseases among the elderly in Korea. Six thousand two hundred ninety four residents in a rural community were followed-up for deaths from 1985 to 2008. The adjusted hazard ratios (aHR) and 95% confidence intervals were calculated by Cox proportional hazard model. A stratified analysis was conducted by age at enrollment. Among the elderly aged 65 and above, the lowest SBP (<100 mm Hg) group had an elevated aHR for mortality from vascular diseases (aHR = 2.1, 95% CI = 1.2-3.9) including stroke (aHR = 2.4, 95% CI = 0.9-6.3) and ischemic heart diseases (aHR = 5.1, 95% CI = 1.0-26.0) compared to those with SBP of 100-119 mm Hg, while higher SBP was associated with higher mortality. This J-curve association was generally maintained when analysis was restricted to those with fair or good self-rated health, or those with no known vascular diseases. In people below 65, increasing SBP nearly monotonically increased the mortality from all-cause and vascular diseases. Our results suggest that elderly persons with low SBP should be treated with caution, since low SBP may increase vascular mortality.

  3. Physical Health Indicators Improve Prediction of Cardiovascular and All-cause Mortality among Middle-Aged and Older People: a National Population-based Study

    PubMed Central

    Lee, Wei-Ju; Peng, Li-Ning; Chiou, Shu-Ti; Chen, Liang-Kung

    2017-01-01

    The effectiveness of established methods for stratifying cardiovascular risk, for example, the Framingham risk score (FRS), may be improved by adding extra variables. This study evaluated the potential benefits of adding physical health indicators (handgrip strength, walking speed, and peak expiratory flow) to the FRS in predicting cardiovascular and all-cause mortality by using a nationwide population-based cohort study data. During median follow-up of 4.1 years, 67 of 911 study subjects had died. In Cox regression analysis, all additional physical health indicators, except walking speed, significantly predicted cardiovascular and all-cause mortality (P < 0.05). Compared with the conventional FRS, c statistics were significantly increased when dominant handgrip strength or relative handgrip strength (handgrip strength adjusted for body mass index), or combination with walking speed or peak expiratory flow were incorporated into the FRS prediction model, both in the whole cohort and also in participants who did not have prevalent cardiovascular diseases at baseline. In conclusion, dominant or relative handgrip strength are simple and inexpensive physical health indicators that substantially improve the accuracy of the FRS in predicting cardiovascular and all-cause mortality among middle-aged and older people. PMID:28079182

  4. The Association between Sulfonylurea Use and All-Cause and Cardiovascular Mortality: A Meta-Analysis with Trial Sequential Analysis of Randomized Clinical Trials

    PubMed Central

    Varvaki Rados, Dimitris; Catani Pinto, Lana; Reck Remonti, Luciana; Bauermann Leitão, Cristiane; Gross, Jorge Luiz

    2016-01-01

    Background Sulfonylureas are an effective and inexpensive treatment for type 2 diabetes. There is conflicting data about the safety of these drugs regarding mortality and cardiovascular outcomes. The objective of the present study was to evaluate the safety of the sulfonylureas most frequently used and to use trial sequential analysis (TSA) to analyze whether the available sample was powered enough to support the results. Methods and Findings Electronic databases were reviewed from 1946 (Embase) or 1966 (MEDLINE) up to 31 December 2014. Randomized clinical trials (RCTs) of at least 52 wk in duration evaluating second- or third-generation sulfonylureas in the treatment of adults with type 2 diabetes and reporting outcomes of interest were included. Primary outcomes were all-cause and cardiovascular mortality. Additionally, myocardial infarction and stroke events were evaluated. Data were summarized with Peto odds ratios (ORs), and the reliability of the results was evaluated with TSA. Forty-seven RCTs with 37,650 patients and 890 deaths in total were included. Sulfonylureas were not associated with all-cause (OR 1.12 [95% CI 0.96 to 1.30]) or cardiovascular mortality (OR 1.12 [95% CI 0.87 to 1.42]). Sulfonylureas were also not associated with increased risk of myocardial infarction (OR 0.92 [95% CI 0.76 to 1.12]) or stroke (OR 1.16 [95% CI 0.81 to 1.66]). TSA could discard an absolute difference of 0.5% between the treatments, which was considered the minimal clinically significant difference. The major limitation of this review was the inclusion of studies not designed to evaluate safety outcomes. Conclusions Sulfonylureas are not associated with increased risk for all-cause mortality, cardiovascular mortality, myocardial infarction, or stroke. Current evidence supports the safety of sulfonylureas; an absolute risk of 0.5% could be firmly discarded. Review registration PROSPERO CRD42014004330 PMID:27071029

  5. The aspartate aminotransferase-to-alanine aminotransferase ratio predicts all-cause and cardiovascular mortality in patients with type 2 diabetes

    PubMed Central

    Zoppini, Giacomo; Cacciatori, Vittorio; Negri, Carlo; Stoico, Vincenzo; Lippi, Giuseppe; Targher, Giovanni; Bonora, Enzo

    2016-01-01

    Abstract An increased aspartate aminotransferase-to-alanine aminotransferase ratio (AAR) has been widely used as a marker of advanced hepatic fibrosis. Increased AAR was also shown to be significantly associated with the risk of developing cardiovascular (CV) disease. The aim of this study was to assess the relationship between the AAR and mortality risk in a well-characterized cohort of patients with type 2 diabetes. A cohort of 2529 type 2 diabetic outpatients was followed-up for 6 years to collect cause-specific mortality. Cox regression analyses were modeled to estimate the independent association between AAR and the risk of all-cause and CV mortality. Over the 6-year follow-up period, 12.1% of patients died, 47.5% of whom from CV causes. An increased AAR, but not its individual components, was significantly associated with an increased risk of all-cause (adjusted-hazard risk 1.83, confidence interval [CI] 95% 1.14–2.93, P = 0.012) and CV (adjusted-hazard risk 2.60, CI 95% 1.38–4.90, P < 0.003) mortality after adjustment for multiple clinical risk factors and potential confounding variables. The AAR was independently associated with an increased risk of both all-cause and CV mortality in patients with type 2 diabetes. These findings suggest that an increased AAR may reflect more systemic derangements that are not simply limited to liver damage. Further studies are needed to elucidate the pathophysiological implications of an increased AAR. PMID:27787357

  6. Association of green tea consumption with mortality from all-cause, cardiovascular disease and cancer in a Chinese cohort of 165,000 adult men.

    PubMed

    Liu, Junxiu; Liu, Shiwei; Zhou, Haiming; Hanson, Timothy; Yang, Ling; Chen, Zhengming; Zhou, Maigeng

    2016-09-01

    Tea is the most ancient and popular beverage in the world, and its beneficial health effects has attracted tremendous attention worldwide. However, the prospective evidence relating green tea consumption to total and cause-specific mortality is still limited and inconclusive. We recruited 164,681 male participants free of pre-existing disease during 1990-1991, with green tea consumption and other covariates assessed by the standardized questionnaire and mortality follow up continued until 2006 (mean 11 years; total person-years: 1,961,791). Cox regression analyses were used to quantify the associations of green tea consumption with all-cause (n = 32,700), CVD (n = 11,839) and cancer (n = 7002) mortality, adjusting simultaneously for potential confounders. At baseline, 18 % reported regular consumption of green tea. Compared with non-green tea drinkers, regular drinkers had significantly lower all-cause mortality, with adjusted hazard ratios (HRs) being 0.94 (95 % CI 0.89, 0.99) for ≤5 g/day, 0.95 (0.91, 0.99) for 5-10 g/day and 0.89 (0.85, 0.93) for >10 g/day. For CVD mortality, the corresponding HRs were 0.93 (0.85, 1.01) 0.91 (0.85, 0.98) and 0.86 (0.79, 0.93), respectively, while for cancer they were 0.86 (0.78, 0.98), 0.92 (0.83, 1.00) and 0.79 (0.71, 0.88), respectively. The patterns of these associations varied by smoking, alcohol drinking and locality. This large prospective study shows that regular green tea consumption is associated with significantly reduced risk of death from all-cause, CVD and cancer among Chinese adults.

  7. Incidence and influence of hospitalization for recurrent syncope and its effect on short- and long-term all-cause and cardiovascular mortality.

    PubMed

    Ruwald, Martin H; Numé, Anna-Karin; Lamberts, Morten; Hansen, Carolina M; Hansen, Morten L; Vinther, Michael; Kober, Lars; Torp-Pedersen, Christian; Hansen, Jim; Gislason, Gunnar H

    2014-05-15

    Recurrence of syncope is a common event, but the influence of recurrent syncope on the risk of death has not previously been investigated on a large scale. We examined the prognostic impact of recurrent syncope in a nationwide cohort of patients with syncope. All patients (n = 70,819) hospitalized from 2001 to 2009 in Denmark with a first-time diagnosis of syncope aged from 15 to 90 years were identified from national registries. Recurrence of syncope was incorporated as a time-dependent variable in multivariable-adjusted Cox models on the outcomes of 30-day, 1-year, and long-term all-cause mortality and cardiovascular death. During a mean follow-up of 3.9 ± 2.6 years, a total of 11,621 patients (16.4%) had at least 1 hospitalization for recurrent syncope, with a median time to recurrence of 251 days (33 to 364). A total of 14,270 patients died, and 3,204 deaths were preceded by a hospitalization for recurrent syncope. The long-term risk of all-cause death was significantly associated with recurrent syncope (hazard ratio 2.64, 95% confidence interval 2.54 to 2.75) compared with those with no recurrence. On 1-year mortality, recurrent syncope was associated with a 3.2-fold increase in risk and on 30-day mortality associated with a threefold increase. The increased mortality risk was consistent over age groups 15 to 39, 40 to 59, and 60 to 89 years, and a similar pattern of increase in both long-term and short-term risk of cardiovascular death was evident. In conclusion, recurrent syncope is independently associated with all-cause and cardiovascular mortality across all age groups exhibiting a high prognostic influence. Increased awareness on high short- and long-term risk of adverse events in subjects with recurrent syncope is warranted for future risk stratification.

  8. No Obesity Paradox-BMI Incapable of Adequately Capturing the Relation of Obesity with All-Cause Mortality: An Inception Diabetes Cohort Study.

    PubMed

    Bozorgmanesh, Mohammadreza; Arshi, Banafsheh; Sheikholeslami, Farhad; Azizi, Fereidoun; Hadaegh, Farzad

    2014-01-01

    Background. To reconcile "the obesity paradox," we tested if (1) the contribution of anthropometric measures to mortality was nonlinear and (2) the confounding of hip circumference contributed to the obesity paradox recently observed among diabetic patients. Methods. We analyzed data of diabetic patients attending a community-based prospective, "Tehran lipid and glucose study." In the mortality analysis, anthropometric measures-body mass index (BMI), waist, and hip circumference-were assessed using Cox models incorporating cubic spline functions. Results. During 12 990 person-years follow-up, BMI levels below 27 and those above 40 kg·m(-2) were associated with increased mortality. When we added waist circumference to the BMI in the multivariate-adjusted model, the steepness of BMI-mortality association curve slope for values below 27 kg·m(-2) increased, whereas the steepness of BMI-mortality association curve slope for values above this threshold decreased. Further adjusting the model for hip circumference, the steepness of the slopes of the association curve moved towards null on both extremes and no associations between BMI and all-cause mortality remained. Conclusion. BMI harbors intermixed positive and negative confounding effects on mortality of waist and hip circumference. Failing to control for the confounding effect of hip circumference may stymie unbiased hazard estimation and render conclusions paradoxical.

  9. Meta-Analysis of the Relation of Ventricular Arrhythmias to All-Cause Mortality After Implantation of a Left Ventricular Assist Device.

    PubMed

    Makki, Nader; Mesubi, Olurotimi; Steyers, Curtis; Olshansky, Brian; Abraham, William T

    2015-11-01

    Ventricular arrhythmias (VAs) are commonly reported after implantation of left ventricular assist devices (LVADs). Their relation to all-cause mortality and potential risk factors remains unclear. We conducted a meta-analysis of observational studies with the primary objective of evaluating the association of post-LVAD VAs with all-cause mortality at 60, 120, and 180 days. The secondary end point was the association of potential risk factors (cause of cardiomyopathy, indication for LVAD, and history of VA) with mortality in patients with post-LVAD VAs. We searched MEDLINE, Embase, and Cochrane Central from 2001 to 2015. Two reviewers independently searched, selected, and assessed quality of included studies with differences resolved by consensus. Data were collected and analyzed using random- and fixed-effect model, as appropriate, with inverse-variance weighting. Of 2,393 studies identified, 9 observational studies were eligible including 1,179 patients with a mean follow-up of 220 days. Post-LVAD VAs were associated with increased risk of all-cause mortality after adjusting for competing risk factors at 60 days (adjusted odds ratio [OR] 1.91, 95% confidence interval [CI] 1.18 to 3.11, p = 0.001), 120 days (adjusted OR 1.97, 95% CI 1.01 to 3.85, p = 0.05), and 180 days (adjusted OR 2.04, 95% CI 1.01 to 4.15, p = 0.05). Using meta-regression analysis, it was found that only history of VA was a risk factor for mortality after LVAD implantation. In conclusion, post-LVAD VA is associated with an increased risk of all-cause mortality with pre-LVAD VAs acting as a risk factor. This meta-analysis, despite being only hypothesis generating, sets the stage for prospective collection of VA information in a prospective device trial or in the Interagency Registry for Mechanically Assisted Circulatory Support.

  10. Nucleated Red Blood Cells as Predictors of All-Cause Mortality in Cardiac Intensive Care Unit Patients: A Prospective Cohort Study

    PubMed Central

    Monteiro Júnior, José Gildo de Moura; Torres, Dilênia de Oliveira Cipriano; da Silva, Maria Cleide Freire Clementino; Ramos, Tadzia Maria de Brito; Alves, Marilene Leite; Filho, Wellington Jorge Nunes; Damasceno, Edgar Paulo; Brunet, Antônio Fernandes; Bittencourt, Márcio Sommer; Pedrosa, Rodrigo Pinto; Filho, Dário Celestino Sobral

    2015-01-01

    Background The presence of nucleated red blood cells (NRBCs) in the peripheral blood of critically ill patients is associated with a poorer prognosis, though data on cardiovascular critical care patients is lacking. The aim of the present study was to assess the role of NRBCs as a predictor of intensive care unit (ICU) and in hospital all-cause mortality among cardiologic patients. Methods NRBCs were measured daily in consecutive cardiac ICU patients, including individuals with both coronary and non-coronary acute cardiac care. We excluded patients younger than 18 years, with cancer or hematological disease, on glucocorticoid therapy, those that were readmitted after hospital discharge and patients who died in the first 24 hours after admission. We performed a multiple logistic analysis to identify independent predictors of mortality. Results We included 152 patients (60.6 ± 16.8 years, 51.8% female, median ICU stay of 7 [4–11] days). The prevalence of NRBCs was 54.6% (83/152). The presence of NRBC was associated with a higher ICU mortality (49.4% vs 21.7%, P<0.001) as well as in-hospital mortality (61.4% vs 33.3%, p = 0.001). NRBC were equally associated with mortality among coronary disease (64.71% vs 32.5% [OR 3.80; 95%CI: 1.45–10.0; p = 0.007]) and non-coronary disease patients (61.45% vs 33.3% [OR 3.19; 95%CI: 1.63–6.21; p<0.001]). In a multivariable model, the inclusion of NRBC to the APACHE II score resulted in a significant improvement in the discrimination (p = 0.01). Conclusions NRBC are predictors of all-cause in-hospital mortality in patients admitted to a cardiac ICU. This predictive value is independent and complementary to the well validated APACHE II score. PMID:26713613

  11. A non-exercise testing method for estimating cardiorespiratory fitness: associations with all-cause and cardiovascular mortality in a pooled analysis of eight population-based cohorts

    PubMed Central

    Stamatakis, Emmanuel; Hamer, Mark; O'Donovan, Gary; Batty, George David; Kivimaki, Mika

    2013-01-01

    Aims Cardiorespiratory fitness (CRF) is a key predictor of chronic disease, particularly cardiovascular disease (CVD), but its assessment usually requires exercise testing which is impractical and costly in most health-care settings. Non-exercise testing cardiorespiratory fitness (NET-F)-estimating methods are a less resource-demanding alternative, but their predictive capacity for CVD and total mortality has yet to be tested. The objective of this study is to examine the association of a validated NET-F algorithm with all-cause and CVD mortality. Methods and results The participants were 32 319 adults (14 650 men) aged 35–70 years who took part in eight Health Survey for England and Scottish Health Survey studies between 1994 and 2003. Non-exercise testing cardiorespiratory fitness (a metabolic equivalent of VO2max) was calculated using age, sex, body mass index (BMI), resting heart rate, and self-reported physical activity. We followed participants for mortality until 2008. Two thousand one hundred and sixty-five participants died (460 cardiovascular deaths) during a mean 9.0 [standard deviation (SD) = 3.6] year follow-up. After adjusting for potential confounders including diabetes, hypertension, smoking, social class, alcohol, and depression, a higher fitness score according to the NET-F was associated with a lower risk of mortality from all-causes (hazard ratio per SD increase in NET-F 0.85, 95% confidence interval: 0.78–0.93 in men; 0.88, 0.80–0.98 in women) and CVD (men: 0.75, 0.63–0.90; women: 0.73, 0.60–0.92). Non-exercise testing cardiorespiratory fitness had a better discriminative ability than any of its components (CVD mortality c-statistic: NET-F = 0.70–0.74; BMI = 0.45–0.59; physical activity = 0.60–0.64; resting heart rate = 0.57–0.61). The sensitivity of the NET-F algorithm to predict events occurring in the highest risk quintile was better for CVD (0.49 in both sexes) than all-cause mortality (0.44 and 0.40 for men and women

  12. Traditional and Emerging Lifestyle Risk Behaviors and All-Cause Mortality in Middle-Aged and Older Adults: Evidence from a Large Population-Based Australian Cohort

    PubMed Central

    Ding, Ding; Rogers, Kris; van der Ploeg, Hidde; Stamatakis, Emmanuel; Bauman, Adrian E.

    2015-01-01

    Background Lifestyle risk behaviors are responsible for a large proportion of disease burden worldwide. Behavioral risk factors, such as smoking, poor diet, and physical inactivity, tend to cluster within populations and may have synergistic effects on health. As evidence continues to accumulate on emerging lifestyle risk factors, such as prolonged sitting and unhealthy sleep patterns, incorporating these new risk factors will provide clinically relevant information on combinations of lifestyle risk factors. Methods and Findings Using data from a large Australian cohort of middle-aged and older adults, this is the first study to our knowledge to examine a lifestyle risk index incorporating sedentary behavior and sleep in relation to all-cause mortality. Baseline data (February 2006– April 2009) were linked to mortality registration data until June 15, 2014. Smoking, high alcohol intake, poor diet, physical inactivity, prolonged sitting, and unhealthy (short/long) sleep duration were measured by questionnaires and summed into an index score. Cox proportional hazards analysis was used with the index score and each unique risk combination as exposure variables, adjusted for socio-demographic characteristics. During 6 y of follow-up of 231,048 participants for 1,409,591 person-years, 15,635 deaths were registered. Of all participants, 31.2%, 36.9%, 21.4%, and 10.6% reported 0, 1, 2, and 3+ risk factors, respectively. There was a strong relationship between the lifestyle risk index score and all-cause mortality. The index score had good predictive validity (c index = 0.763), and the partial population attributable risk was 31.3%. Out of all 96 possible risk combinations, the 30 most commonly occurring combinations accounted for more than 90% of the participants. Among those, combinations involving physical inactivity, prolonged sitting, and/or long sleep duration and combinations involving smoking and high alcohol intake had the strongest associations with all-cause

  13. Retinal Vessel Diameters and Their Relationship with Cardiovascular Risk and All-Cause Mortality in the Inter99 Eye Study: A 15-Year Follow-Up

    PubMed Central

    Munch, Inger Christine; Glümer, Charlotte; Faerch, Kristine; Kessel, Line; Larsen, Michael

    2016-01-01

    Purpose. To describe associations between retinal vessel diameters and cardiovascular risk markers and mortality. Methods. The present study included 908 persons aged 30 to 60 years. Vessel diameters were expressed as central retinal venular equivalent (CRVE) and central retinal arteriolar equivalent (CRAE). Multiple linear regression analyses and Cox regression models were used. Results. Multiple linear regression analyses showed that narrower CRAE was associated with higher systolic blood pressure, age, and higher HDL cholesterol, whereas wider CRAE and CRVE were associated with smoking. Narrower CRVE was associated with higher HDL cholesterol. In an age-adjusted model, associations between wider CRVE and risk of ischemic heart disease were found (P < 0.001). Wider CRVE was associated with all-cause mortality (HR = 2.02, P = 0.033) in a model adjusted for age, gender, and blood pressure. However, the association was not statistically significant after additional adjustment for smoking. Conclusions. The associations between retinal vessel diameters and known cardiovascular risk factors were confirmed. All-cause mortality was not associated with retinal vessel diameters when adjusting for relevant confounders. PMID:28053777

  14. Milk and dairy consumption and risk of cardiovascular diseases and all-cause mortality: dose-response meta-analysis of prospective cohort studies.

    PubMed

    Guo, Jing; Astrup, Arne; Lovegrove, Julie A; Gijsbers, Lieke; Givens, David I; Soedamah-Muthu, Sabita S

    2017-04-03

    With a growing number of prospective cohort studies, an updated dose-response meta-analysis of milk and dairy products with all-cause mortality, coronary heart disease (CHD) or cardiovascular disease (CVD) have been conducted. PubMed, Embase and Scopus were searched for articles published up to September 2016. Random-effect meta-analyses with summarised dose-response data were performed for total (high-fat/low-fat) dairy, milk, fermented dairy, cheese and yogurt. Non-linear associations were investigated using the spine models and heterogeneity by subgroup analyses. A total of 29 cohort studies were available for meta-analysis, with 938,465 participants and 93,158 mortality, 28,419 CHD and 25,416 CVD cases. No associations were found for total (high-fat/low-fat) dairy, and milk with the health outcomes of mortality, CHD or CVD. Inverse associations were found between total fermented dairy (included sour milk products, cheese or yogurt; per 20 g/day) with mortality (RR 0.98, 95% CI 0.97-0.99; I(2) = 94.4%) and CVD risk (RR 0.98, 95% CI 0.97-0.99; I(2) = 87.5%). Further analyses of individual fermented dairy of cheese and yogurt showed cheese to have a 2% lower risk of CVD (RR 0.98, 95% CI 0.95-1.00; I(2) = 82.6%) per 10 g/day, but not yogurt. All of these marginally inverse associations of totally fermented dairy and cheese were attenuated in sensitivity analyses by removing one large Swedish study. This meta-analysis combining data from 29 prospective cohort studies demonstrated neutral associations between dairy products and cardiovascular and all-cause mortality. For future studies it is important to investigate in more detail how dairy products can be replaced by other foods.

  15. Increased all-cause mortality with use of psychotropic medication in dementia patients and controls: A population-based register study.

    PubMed

    Jennum, Poul; Baandrup, Lone; Ibsen, Rikke; Kjellberg, Jakob

    2015-11-01

    We aimed to evaluate all-cause mortality of middle-aged and elderly subjects diagnosed with dementia and treated with psychotropic drugs as compared with controls subjects. Using data from the Danish National Patient Registry, n=26,821 adults with a diagnosis of dementia were included. They were compared with 44,286 control subjects with a minimum follow-up of four years and matched on age, gender, marital status, and community location. Information about psychotropic medication use (benzodiazepines, antidepressants, antipsychotics) was obtained from the Danish Medicinal Product Statistics. All-cause mortality was higher in patients with dementia as compared to control subjects. Mortality hazard ratios were increased for subjects prescribed serotonergic antidepressant drugs (respectively, HR=1.355 (SD=0.023), P=0.001 in patients; HR=1.808 (0.033), P<0.001 in controls), tricyclic antidepressants (HR=1.004 (0.046), P=0.925; HR=1.406 (0.061), P<0.001), benzodiazepines (HR=1.131 (0.039), P=0.060); HR=1.362 (0.028), P<0.001), benzodiazepine-like drugs (HR=1.108 (0.031), P=0.078; HR=1.564 (0.037, P<0.001), first-generation antipsychotics (HR=1.183 (0.074), P=0.022; HR=2.026 (0.114), P<0.001), and second-generation antipsychotics (HR=1.380 (0.042), P<0.001; HR=1.785 (0.088), P<0.001), as compared with no drug use. Interaction analysis suggested statistically significantly higher mortality hazard ratios for most classes of psychotropic drugs in controls than in dementia patients. We found that use of psychotropic drugs is associated with increased all-cause mortality in both patients with dementia and control subjects. Thus, the frequently reported increased mortality with antipsychotic drugs in dementia is not restricted to subjects with impaired cognition and is not restricted to only one class of psychotropic drugs.

  16. Glycated Hemoglobin and All-Cause and Cause-Specific Mortality in Singaporean Chinese Without Diagnosed Diabetes: The Singapore Chinese Health Study

    PubMed Central

    Bancks, Michael P.; Odegaard, Andrew O.; Pankow, James S.; Koh, Woon-Puay; Yuan, Jian-Min; Gross, Myron D.

    2014-01-01

    OBJECTIVE Glycated hemoglobin (HbA1c) is a robust biomarker of the preceding 2 to 3 months average blood glucose level. The aim of this study was to examine the association between HbA1c and mortality in a cohort of Southeast Asians. RESEARCH DESIGN AND METHODS Analysis of 7,388 men and women, mean age 62 years, from the Singapore Chinese Health Study who provided a blood sample at the follow-up I visit (1999–2004) and reported no history of diabetes, previous adverse cardiovascular events, or cancer. A total of 888 deaths were identified through 31 December 2011 via registry linkage. Participants represented a random study sample of potential control subjects for a nested case-control genome-wide association study of type 2 diabetes in the population. Hazard ratios (HRs) for all-cause and cause-specific mortality by six categories of HbA1c were estimated with Cox regression models. RESULTS Relative to participants with an HbA1c of 5.4–5.6% (36–38 mmol/mol), participants with HbA1c ≥6.5% (≥48 mmol/mol) had an increased risk of all-cause, cardiovascular, and cancer mortality during an average of 10.1 years of follow-up; HRs (95% CIs) were 1.96 (1.56–2.46), 2.63 (1.77–3.90), and 1.51 (1.04–2.18), respectively. No level of HbA1c was associated with increased risk of respiratory mortality. Levels <6.5% HbA1c were not associated with mortality during follow-up. The results did not materially change after excluding observation of first 3 years post–blood draw. CONCLUSIONS HbA1c levels consistent with undiagnosed type 2 diabetes (≥6.5%) are associated with an increased risk of all-cause and cause-specific mortality in Chinese men and women. PMID:25216509

  17. Examining Non-Linear Associations between Accelerometer-Measured Physical Activity, Sedentary Behavior, and All-Cause Mortality Using Segmented Cox Regression

    PubMed Central

    Lee, Paul H.

    2016-01-01

    Healthy adults are advised to perform at least 150 min of moderate-intensity physical activity weekly, but this advice is based on studies using self-reports of questionable validity. This study examined the dose-response relationship of accelerometer-measured physical activity and sedentary behaviors on all-cause mortality using segmented Cox regression to empirically determine the break-points of the dose-response relationship. Data from 7006 adult participants aged 18 or above in the National Health and Nutrition Examination Survey waves 2003–2004 and 2005–2006 were included in the analysis and linked with death certificate data using a probabilistic matching approach in the National Death Index through December 31, 2011. Physical activity and sedentary behavior were measured using ActiGraph model 7164 accelerometer over the right hip for 7 consecutive days. Each minute with accelerometer count <100; 1952–5724; and ≥5725 were classified as sedentary, moderate-intensity physical activity, and vigorous-intensity physical activity, respectively. Segmented Cox regression was used to estimate the hazard ratio (HR) of time spent in sedentary behaviors, moderate-intensity physical activity, and vigorous-intensity physical activity and all-cause mortality, adjusted for demographic characteristics, health behaviors, and health conditions. Data were analyzed in 2016. During 47,119 person-year of follow-up, 608 deaths occurred. Each additional hour per day of sedentary behaviors was associated with a HR of 1.15 (95% CI 1.01, 1.31) among participants who spend at least 10.9 h per day on sedentary behaviors, and each additional minute per day spent on moderate-intensity physical activity was associated with a HR of 0.94 (95% CI 0.91, 0.96) among participants with daily moderate-intensity physical activity ≤14.1 min. Associations of moderate physical activity and sedentary behaviors on all-cause mortality were independent of each other. To conclude, evidence from

  18. Drugs with anticholinergic effects and cognitive impairment, falls and all-cause mortality in older adults: A systematic review and meta-analysis

    PubMed Central

    Ruxton, Kimberley; Woodman, Richard J; Mangoni, Arduino A

    2015-01-01

    Aim The aim was to investigate associations between drugs with anticholinergic effects (DACEs) and cognitive impairment, falls and all-cause mortality in older adults. Methods A literature search using CINAHL, Cochrane Library, Embase and PubMed databases was conducted for randomized controlled trials, prospective and retrospective cohort and case-control studies examining the use of DACEs in subjects ≥65 years with outcomes on falls, cognitive impairment and all-cause mortality. Retrieved articles were published on or before June 2013. Anticholinergic exposure was investigated using drug class, DACE scoring systems (anticholinergic cognitive burden scale, ACB; anticholinergic drug scale, ADS; anticholinergic risk scale, ARS; anticholinergic component of the drug burden index, DBIAC) or assessment of individual DACEs. Meta-analyses were performed to pool the results from individual studies. Results Eighteen studies fulfilled the inclusion criteria (total 124 286 participants). Exposure to DACEs as a class was associated with increased odds of cognitive impairment (OR 1.45, 95% CI 1.16, 1.73). Olanzapine and trazodone were associated with increased odds and risk of falls (OR 2.16, 95% CI 1.05, 4.44; RR 1.79, 95% CI 1.60, 1.97, respectively), but amitriptyline, paroxetine and risperidone were not (RR 1.73, 95% CI 0.81, 2.65; RR 1.80, 95% CI 0.81, 2.79; RR 1.39, 95% CI 0.59, 3.26, respectively). A unit increase in the ACB scale was associated with a doubling in odds of all-cause mortality (OR 2.06, 95% CI 1.82, 2.33) but there were no associations with the DBIAC (OR 0.88, 95% CI 0.55, 1.42) or the ARS (OR 3.56, 95% CI 0.29, 43.27). Conclusions Certain individual DACEs or increased overall DACE exposure may increase the risks of cognitive impairment, falls and all-cause mortality in older adults. PMID:25735839

  19. Extracellular Fluid/Intracellular Fluid Volume Ratio as a Novel Risk Indicator for All-Cause Mortality and Cardiovascular Disease in Hemodialysis Patients

    PubMed Central

    Kim, Eun-Jung; Choi, Myung-Jin; Lee, Jeoung-Hwan; Oh, Ji-Eun; Seo, Jang-Won; Lee, Young-Ki; Yoon, Jong-Woo; Kim, Hyung-Jik; Noh, Jung-Woo

    2017-01-01

    Background In hemodialysis patients, fluid overload and malnutrition are accompanied by extracellular fluid (ECF) expansion and intracellular fluid (ICF) depletion, respectively. We investigated the relationship between ECF/ICF ratio (as an integrated marker reflecting both fluid overload and malnutrition) and survival and cardiovascular disease (CVD) in the context of malnutrition-inflammation-arteriosclerosis (MIA) complex. Methods Seventy-seven patients from a single hemodialysis unit were prospectively enrolled. The ECF/ICF volume was measured by segmental multi-frequency bioimpedance analysis. MIA and volume status were measured by serum albumin, C-reactive protein (CRP), pulse wave velocity (PWV) and plasma B-type natriuretic peptide (BNP), respectively. Results The mean ECF/ICF ratio was 0.56±0.06 and the cut-off value for maximum discrimination of survival was 0.57. Compared with the low ECF/ICF group, the high ECF/ICF group (ratio≥0.57, 42%) had higher all-cause mortality, CVD, CRP, PWV, and BNP, but lower serum albumin. During the 5-year follow-up, 24 all-cause mortality and 38 CVD occurred (18 and 24, respectively, in the high ECF/ICF group versus 6 and 14 respectively in the low ECF/ICF group, P<0.001). In the adjusted Cox analysis, the ECF/ICF ratio nullifies the effects of the MIA and volume status on survival and CVD and was an independent predictor of all-cause mortality and CVD: hazard ratio (95% confidence interval); 1.12 (1.01–1.25) and 1.09 (1.01–1.18) for a 0.01 increase in the ECF/ICF ratio. The degree of malnutrition (albumin), inflammation (CRP), arteriosclerosis (PWV), and fluid overload (BNP) were correlated well with the ECF/ICF ratio. Conclusions Hemodialysis patients with high ECF/ICF ratio are not only fluid overloaded, but malnourished and have stiff artery with more inflammation. The ECF/ICF ratio is highly related to the MIA complex, and is a major risk indicator for all-cause mortality and CVD. PMID:28099511

  20. Association of body mass index with all-cause mortality in patients with diabetes: a systemic review and meta-analysis

    PubMed Central

    Chang, Hsiao-Wen; Li, Yi-Hwei; Hsieh, Chang-Hsun; Liu, Pang-Yen

    2016-01-01

    Background The obesity paradox phenomenon has been found in different populations, such as heart failure and coronary heart disease, which suggest that patients with established cardiovascular disease (CVD) and with normal weight had higher risk of mortality than those with overweight or obesity. However, the obesity paradox is controversial among patients with diabetes which has been considered as the coronary heart disease equivalent. The aim of our study was to summarize current findings on the relationship between body mass index (BMI) and all-cause mortality in patients with diabetes and make a meta-analysis. Methods We searched previous studies from MEDLINE, EMBASE, and the Cochrane databases using the keywords: BMI, mortality, diabetes, and obesity paradox or reverse epidemiology. Finally, sixteen studies were identified and 385,925 patients were included. Patients were divided into five groups based on BMI (kg/m2) levels: underweight (<18.5), normal weight (18.5–24.9), overweight (25–29.9), mild obesity (30–34.9), and morbid obesity (>35). A random effect meta-analysis was performed by the inverse variance method. Results As compared with the normal weight, the underweight had higher risk of mortality [hazard ratio (HR): 1.59, 95% confidence interval (CI): 1.32–1.91]. In contrast, the overweight and the mild obesity had lower risk of mortality than the normal weight (HR: 0.86, 95% CI: 0.78–0.96, and 0.88, 95% CI: 0.78–1.00, respectively), but the morbid obesity did not (HR: 0.99, 95% CI: 0.84–1.16). In addition, the subgroup analysis by sex showed that the overweight had the lowest mortality as compared with the normal weight (HR: 0.82, 95% CI: 0.74–0.90) and the obesity in males, but the risk of mortality did not differ among groups in females. Notably, the heterogeneity was significant in most of group comparisons. Conclusions Our meta-analysis showed a U-shaped relationship between BMI and all-cause mortality in patients with diabetes

  1. Higher Diet Quality Is Associated with Decreased Risk of All-Cause, Cardiovascular Disease, and Cancer Mortality among Older Adults12

    PubMed Central

    Reedy, Jill; Krebs-Smith, Susan M.; Miller, Paige E.; Liese, Angela D.; Kahle, Lisa L.; Park, Yikyung; Subar, Amy F.

    2014-01-01

    Increased attention in dietary research and guidance has been focused on dietary patterns, rather than on single nutrients or food groups, because dietary components are consumed in combination and correlated with one another. However, the collective body of research on the topic has been hampered by the lack of consistency in methods used. We examined the relationships between 4 indices—the Healthy Eating Index–2010 (HEI-2010), the Alternative Healthy Eating Index–2010 (AHEI-2010), the alternate Mediterranean Diet (aMED), and Dietary Approaches to Stop Hypertension (DASH)—and all-cause, cardiovascular disease (CVD), and cancer mortality in the NIH-AARP Diet and Health Study (n = 492,823). Data from a 124-item food-frequency questionnaire were used to calculate scores; adjusted HRs and 95% CIs were estimated. We documented 86,419 deaths, including 23,502 CVD- and 29,415 cancer-specific deaths, during 15 y of follow-up. Higher index scores were associated with a 12–28% decreased risk of all-cause, CVD, and cancer mortality. Specifically, comparing the highest with the lowest quintile scores, adjusted HRs for all-cause mortality for men were as follows: HEI-2010 HR: 0.78 (95% CI: 0.76, 0.80), AHEI-2010 HR: 0.76 (95% CI: 0.74, 0.78), aMED HR: 0.77 (95% CI: 0.75, 0.79), and DASH HR: 0.83 (95% CI: 0.80, 0.85); for women, these were HEI-2010 HR: 0.77 (95% CI: 0.74, 0.80), AHEI-2010 HR: 0.76 (95% CI: 0.74, 0.79), aMED HR: 0.76 (95% CI: 0.73, 0.79), and DASH HR: 0.78 (95% CI: 0.75, 0.81). Similarly, high adherence on each index was protective for CVD and cancer mortality examined separately. These findings indicate that multiple scores reflect core tenets of a healthy diet that may lower the risk of mortality outcomes, including federal guidance as operationalized in the HEI-2010, Harvard’s Healthy Eating Plate as captured in the AHEI-2010, a Mediterranean diet as adapted in an Americanized aMED, and the DASH Eating Plan as included in the DASH score. PMID

  2. Socioeconomic inequalities in all-cause mortality in the Czech Republic, Russia, Poland and Lithuania in the 2000s: findings from the HAPIEE Study

    PubMed Central

    Vandenheede, Hadewijch; Vikhireva, Olga; Pikhart, Hynek; Kubinova, Ruzena; Malyutina, Sofia; Pajak, Andrzej; Tamosiunas, Abdonas; Peasey, Anne; Simonova, Galina; Topor-Madry, Roman; Marmot, Michael; Bobak, Martin

    2014-01-01

    Background Relatively large socioeconomic inequalities in health and mortality have been observed in Central and Eastern Europe (CEE) and the former Soviet Union (FSU). Yet comparative data are sparse and virtually all studies include only education. The aim of this study is to quantify and compare socioeconomic inequalities in all-cause mortality during the 2000s in urban population samples from four CEE/FSU countries, by three different measures of socioeconomic position (SEP) (education, difficulty buying food and household amenities), reflecting different aspects of SEP. Methods Data from the prospective population-based HAPIEE (Health, Alcohol, and Psychosocial factors in Eastern Europe) study were used. The baseline survey (2002–2005) included 16 812 men and 19 180 women aged 45–69 years in Novosibirsk (Russia), Krakow (Poland), Kaunas (Lithuania) and seven Czech towns. Deaths in the cohorts were identified through mortality registers. Data were analysed by direct standardisation and Cox regression, quantifying absolute and relative SEP differences. Results Mortality inequalities by the three SEP indicators were observed in all samples. The magnitude of inequalities varied according to gender, country and SEP measure. As expected, given the high mortality rates in Russian men, largest absolute inequalities were found among Russian men (educational slope index of inequality was 19.4 per 1000 person-years). Largest relative inequalities were observed in Czech men and Lithuanian subjects. Disadvantage by all three SEP measures remained strongly associated with increased mortality after adjusting for the other SEP indicators. Conclusions The results emphasise the importance of all SEP measures for understanding mortality inequalities in CEE/FSU. PMID:24227051

  3. Is the adiposity-associated FTO gene variant related to all-cause mortality independent of adiposity? Meta-analysis of data from 169,551 Caucasian adults

    PubMed Central

    Mirza, S. S.; Zhao, J. H.; Chasman, D. I.; Fischer, K.; Qi, Q.; Smith, A. V.; Thinggaard, M.; Jarczok, M. N.; Nalls, M. A.; Trompet, S.; Timpson, N. J.; Schmidt, B.; Jackson, A. U.; Lyytikäinen, L. P.; Verweij, N.; Mueller-Nurasyid, M.; Vikström, M.; Marques-Vidal, P.; Wong, A.; Meidtner, K.; Middelberg, R. P.; Strawbridge, R. J.; Christiansen, L.; Kyvik, K. O.; Hamsten, A.; Jääskeläinen, T.; Tjønneland, A.; Eriksson, J. G.; Whitfield, J. B.; Boeing, H.; Hardy, R.; Vollenweider, P.; Leander, K.; Peters, A.; van der Harst, P.; Kumari, M.; Lehtimäki, T.; Meirhaeghe, A.; Tuomilehto, J.; Jöckel, K.-H.; Ben-Shlomo, Y.; Sattar, N.; Baumeister, S. E.; Smith, G. Davey; Casas, J. P.; Houston, D. K.; März, W.; Christensen, K.; Gudnason, V.; Hu, F. B.; Metspalu, A.; Ridker, P. M.; Wareham, N. J.; Loos, R. J. F.; Tiemeier, H.; Sonestedt, E.; Sørensen, T. I. A.

    2015-01-01

    Summary Previously, a single nucleotide polymorphism (SNP), rs9939609, in the FTO gene showed a much stronger association with all-cause mortality than expected from its association with body mass index (BMI), body fat mass index (FMI) and waist circumference (WC). This finding implies that the SNP has strong pleiotropic effects on adiposity and adiposity-independent pathological pathways that leads to increased mortality. To investigate this further, we conducted a meta-analysis of similar data from 34 longitudinal studies including 169,551 adult Caucasians among whom 27,100 died during follow-up. Linear regression showed that the minor allele of the FTO SNP was associated with greater BMI (n = 169,551; 0.32 kg m−2; 95% CI 0.28–0.32, P < 1 × 10−32), WC (n = 152,631; 0.76 cm; 0.68–0.84, P < 1 × 10−32) and FMI (n = 48,192; 0.17 kg m−2; 0.13–0.22, P = 1.0 × 10−13). Cox proportional hazard regression analyses for mortality showed that the hazards ratio (HR) for the minor allele of the FTO SNPs was 1.02 (1.00–1.04, P = 0.097), but the apparent excess risk was eliminated after adjustment for BMI and WC (HR: 1.00; 0.98–1.03, P = 0.662) and for FMI (HR: 1.00; 0.96–1.04, P = 0.932). In conclusion, this study does not support that the FTO SNP is associated with all-cause mortality independently of the adiposity phenotypes. PMID:25752329

  4. Is the adiposity-associated FTO gene variant related to all-cause mortality independent of adiposity? Meta-analysis of data from 169,551 Caucasian adults.

    PubMed

    Zimmermann, E; Ängquist, L H; Mirza, S S; Zhao, J H; Chasman, D I; Fischer, K; Qi, Q; Smith, A V; Thinggaard, M; Jarczok, M N; Nalls, M A; Trompet, S; Timpson, N J; Schmidt, B; Jackson, A U; Lyytikäinen, L P; Verweij, N; Mueller-Nurasyid, M; Vikström, M; Marques-Vidal, P; Wong, A; Meidtner, K; Middelberg, R P; Strawbridge, R J; Christiansen, L; Kyvik, K O; Hamsten, A; Jääskeläinen, T; Tjønneland, A; Eriksson, J G; Whitfield, J B; Boeing, H; Hardy, R; Vollenweider, P; Leander, K; Peters, A; van der Harst, P; Kumari, M; Lehtimäki, T; Meirhaeghe, A; Tuomilehto, J; Jöckel, K-H; Ben-Shlomo, Y; Sattar, N; Baumeister, S E; Davey Smith, G; Casas, J P; Houston, D K; März, W; Christensen, K; Gudnason, V; Hu, F B; Metspalu, A; Ridker, P M; Wareham, N J; Loos, R J F; Tiemeier, H; Sonestedt, E; Sørensen, T I A

    2015-04-01

    Previously, a single nucleotide polymorphism (SNP), rs9939609, in the FTO gene showed a much stronger association with all-cause mortality than expected from its association with body mass index (BMI), body fat mass index (FMI) and waist circumference (WC). This finding implies that the SNP has strong pleiotropic effects on adiposity and adiposity-independent pathological pathways that leads to increased mortality. To investigate this further, we conducted a meta-analysis of similar data from 34 longitudinal studies including 169,551 adult Caucasians among whom 27,100 died during follow-up. Linear regression showed that the minor allele of the FTO SNP was associated with greater BMI (n = 169,551; 0.32 kg m(-2) ; 95% CI 0.28-0.32, P < 1 × 10(-32) ), WC (n = 152,631; 0.76 cm; 0.68-0.84, P < 1 × 10(-32) ) and FMI (n = 48,192; 0.17 kg m(-2) ; 0.13-0.22, P = 1.0 × 10(-13) ). Cox proportional hazard regression analyses for mortality showed that the hazards ratio (HR) for the minor allele of the FTO SNPs was 1.02 (1.00-1.04, P = 0.097), but the apparent excess risk was eliminated after adjustment for BMI and WC (HR: 1.00; 0.98-1.03, P = 0.662) and for FMI (HR: 1.00; 0.96-1.04, P = 0.932). In conclusion, this study does not support that the FTO SNP is associated with all-cause mortality independently of the adiposity phenotypes.

  5. Seasonal variations of all-cause and cause-specific mortality by age, gender, and socioeconomic condition in urban and rural areas of Bangladesh

    PubMed Central

    2011-01-01

    Background Mortality exhibits seasonal variations, which to a certain extent can be considered as mid-to long-term influences of meteorological conditions. In addition to atmospheric effects, the seasonal pattern of mortality is shaped by non-atmospheric determinants such as environmental conditions or socioeconomic status. Understanding the influence of season and other factors is essential when seeking to implement effective public health measures. The pressures of climate change make an understanding of the interdependencies between season, climate and health especially important. Methods This study investigated daily death counts collected within the Sample Vital Registration System (VSRS) established by the Bangladesh Bureau of Statistics (BBS). The sample was stratified by location (urban vs. rural), gender and socioeconomic status. Furthermore, seasonality was analyzed for all-cause mortality, and several cause-specific mortalities. Daily deviation from average mortality was calculated and seasonal fluctuations were elaborated using non parametric spline smoothing. A seasonality index for each year of life was calculated in order to assess the age-dependency of seasonal effects. Results We found distinctive seasonal variations of mortality with generally higher levels during the cold season. To some extent, a rudimentary secondary summer maximum could be observed. The degree and shape of seasonality changed with the cause of death as well as with location, gender, and SES and was strongly age-dependent. Urban areas were seen to be facing an increased summer mortality peak, particularly in terms of cardiovascular mortality. Generally, children and the elderly faced stronger seasonal effects than youths and young adults. Conclusion This study clearly demonstrated the complex and dynamic nature of seasonal impacts on mortality. The modifying effect of spatial and population characteristics were highlighted. While tropical regions have been, and still are

  6. Association of self-reported recurrent mild hypoglycemia with incident cardiovascular disease and all-cause mortality in patients with type 2 diabetes

    PubMed Central

    Luk, Andrea On Yan; Ho, Tony S.T.; Lau, Eric S.H.; Ko, Gary T.C.; Ozaki, Risa; Tsang, Chiu-Chi; Kong, Alice P.S.; Ma, Ronald C.W.; So, Wing-Yee; Chow, Francis C.C.; Chan, Juliana C.N.

    2016-01-01

    Abstract Severe hypoglycemia is an established risk marker for cardiovascular complications of diabetes, but whether mild hypoglycemia confers similar risks is unclear. We examined the association of self-reported recurrent mild hypoglycemic events with cardiovascular disease (CVD) and all-cause mortality in a prospective cohort of Chinese adults with type 2 diabetes. From June 2007 to May 2015, 19,019 patients in Hong Kong underwent comprehensive assessment of metabolic and complication status using the Joint Asia Diabetes Evaluation program. Recurrent mild hypoglycemic event was determined by self-report of mild-to-moderate hypoglycemic symptoms at least once monthly in previous 3 months. Incident cardiovascular events were identified using hospital discharge diagnosis codes and death using Hong Kong Death Registry. Patients reporting recurrent mild hypoglycemia (n = 1501, 8.1%) were younger, had longer disease duration, worse glycemic control, and higher frequencies of vascular complications at baseline. Over 3.9 years of follow-up, respective incidences of CVD and all-cause death were 18.1 and 10.3 per 1000 person-years and 15.4 and 9.9 per 1000 person-years in patients with and without recurrent mild hypoglycemia. Using multivariate Cox regression analysis, recurrent mild hypoglycemia was not associated with CVD or all-cause mortality. In subgroup analysis, mild hypoglycemia was related to CVD in patients with chronic kidney disease (hazard ratio 1.36, 95% confidence interval 1.01–1.84, P = 0.0435) and those on insulin (hazard ratio 1.37, 95% confidence interval 1.01–1.86, P = 0.0402) adjusted for confounders. Mild hypoglycemia by self-report was frequent in patients with type 2 diabetes and was associated with increased risk of CVD in susceptible groups. PMID:27828844

  7. The combined relationship of occupational and leisure-time physical activity with all-cause mortality among men, accounting for physical fitness.

    PubMed

    Clays, Els; Lidegaard, Mark; De Bacquer, Dirk; Van Herck, Koen; De Backer, Guy; Kittel, France; de Smet, Patrick; Holtermann, Andreas

    2014-03-01

    The aim of this study was to assess the combined relationship of occupational physical activity and leisure-time physical activity with all-cause mortality among men, while accounting for physical fitness. The prospective Belgian Physical Fitness Study included 1,456 male workers aged 40-55 years who were free of coronary heart disease at baseline. Baseline data were collected through questionnaires and clinical examinations from 1976 to 1978. To estimate physical fitness, a submaximal graded exercise test was performed on a bicycle ergometer. Total mortality was registered during a mean follow-up period of 16.9 years. Main results were obtained through Cox proportional hazards regression analysis. A total of 145 deaths were registered during follow-up. After adjustment for confounders, a significantly increased mortality rate was observed in workers who had low levels of both physical activity types (hazard ratio = 2.07, 95% confidence interval: 1.03, 4.19) but also in workers combining high occupational physical activity and low leisure-time physical activity (hazard ratio = 2.04, 95% confidence interval: 1.07, 3.91); the latter finding was particularly pronounced among workers with a low physical fitness level. The present results confirm the existence of a complex interplay among different physical activity settings and fitness levels in predicting mortality.

  8. Daytime napping and the risk of all-cause and cause-specific mortality: a 13-year follow-up of a British population.

    PubMed

    Leng, Yue; Wainwright, Nick W J; Cappuccio, Francesco P; Surtees, Paul G; Hayat, Shabina; Luben, Robert; Brayne, Carol; Khaw, Kay-Tee

    2014-05-01

    Epidemiologic studies have reported conflicting results on the relationship between daytime napping and mortality risk, and there are few data on the potential association in the British population. We investigated the associations between daytime napping and all-cause or cause-specific mortality in the European Prospective Investigation Into Cancer-Norfolk study, a British population-based cohort study. Among the 16,374 men and women who answered questions on napping habits between 1998 and 2000, a total of 3,251 died during the 13-year follow-up. Daytime napping was associated with an increased risk of all-cause mortality (for napping less than 1 hour per day on average, hazard ratio = 1.14, 95% confidence interval: 1.02, 1.27; for napping 1 hour or longer per day on average, hazard ratio = 1.32, 95% confidence interval: 1.04, 1.68), independent of age, sex, social class, educational level, marital status, employment status, body mass index, physical activity level, smoking status, alcohol intake, depression, self-reported general health, use of hypnotic drugs or other medications, time spent in bed at night, and presence of preexisting health conditions. This association was more pronounced for death from respiratory diseases (for napping less than 1 hour, hazard ratio = 1.40, 95% confidence interval: 0.95, 2.05; for napping 1 hour or more, hazard ratio = 2.56, 95% confidence interval: 1.34, 4.86) and in individuals 65 years of age or younger. Excessive daytime napping might be a useful marker of underlying health risk, particularly of respiratory problems, especially among those 65 years of age or younger. Further research is required to clarify the nature of the observed association.

  9. Relation of blood pressure and all-cause mortality in 180,000 Japanese participants: pooled analysis of 13 cohort studies.

    PubMed

    Murakami, Yoshitaka; Hozawa, Atsushi; Okamura, Tomonori; Ueshima, Hirotsugu

    2008-06-01

    Hypertension is a leading cause of death because of cardiovascular disease and predominantly affects total mortality. To reduce avoidable deaths from hypertension, we need to collect blood pressure data and assess their impact on total mortality. To examine this issue, a meta-analysis of 13 cohort studies was conducted in Japan. Poisson regression was used for estimating all-cause mortality rates and ratios. In the model, blood pressure data were treated as continuous (10-mm Hg increase) and categorical (every 10 mm Hg) according to recommendations of the Seventh Joint National Committee on Prevention, Detection, Evaluation, and Treatment of Hypertension. Potential confounders included body mass index, smoking, drinking, and cohort. The impact of hypertension was measured by the population-attributable fraction. After excluding participants with cardiovascular disease history, 176 389 participants were examined in the analysis. Adjusted mortality rates became larger as the blood pressure increased, and these were more distinct in younger men and women. Hazard ratios also showed the same trends, and these trends were more apparent in younger men (hazard ratio [unit: 10-mm Hg increase] aged 40 to 49 years: systolic blood pressure 1.37 (range: 1.15 to 1.62); diastolic blood pressure 1.46 [range: 1.05 to 2.03]) than older ones (hazard ratio: aged 80 to 89 years: systolic blood pressure 1.09 [range: 1.05 to 1.13]and diastolic blood pressure 1.12 [range: 1.03 to 1.22]). Population-attributable fraction of hypertension was approximately 20% when the normal category was used as a reference level and was 10% when we included the prehypertension group in the reference level. In conclusion, high blood pressure raised the risk of total mortality, and this trend was higher in the younger Japanese population.

  10. Association between Insulin Monotherapy versus Insulin plus Metformin and the Risk of All-Cause Mortality and Other Serious Outcomes: A Retrospective Cohort Study

    PubMed Central

    Holden, Sarah E.; Jenkins-Jones, Sara; Currie, Craig J.

    2016-01-01

    Aims To determine if concomitant metformin reduced the risk of death, major adverse cardiac events (MACE), and cancer in people with type 2 diabetes treated with insulin. Methods For this retrospective cohort study, people with type 2 diabetes who progressed to insulin with or without metformin from 2000 onwards were identified from the UK Clinical Practice Research Datalink (≈7% sample of the UK population). The risks of all-cause mortality, MACE and incident cancer were evaluated using multivariable Cox models comparing insulin monotherapy with insulin plus metformin. We accounted for insulin dose. Results 12,020 subjects treated with insulin were identified, including 6,484 treated with monotherapy. There were 1,486 deaths, 579 MACE (excluding those with a history of large vessel disease), and 680 cancer events (excluding those in patients with a history of cancer). Corresponding event rates were 41.5 (95% CI 39.4–43.6) deaths, 20.8 (19.2–22.5) MACE, and 21.6 (20.0–23.3) cancer events per 1,000 person-years. The adjusted hazard ratios (aHRs) for people prescribed insulin plus metformin versus insulin monotherapy were 0.60 (95% CI 0.52–0.68) for all-cause mortality, 0.75 (0.62–0.91) for MACE, and 0.96 (0.80–1.15) for cancer. For patients who were propensity-score matched, the corresponding aHRs for all-cause mortality and cancer were 0.62 (0.52–0.75) and 0.99 (0.78–1.26), respectively. For MACE, the aHR was 1.06 (0.75–1.49) prior to 1,275 days and 1.87 (1.22–2.86) after 1,275 days post-index. Conclusions People with type 2 diabetes treated with insulin plus concomitant metformin had a reduced risk of death and MACE compared with people treated with insulin monotherapy. There was no statistically significant difference in the risk of cancer between people treated with insulin as monotherapy or in combination with metformin. PMID:27152598

  11. All cause mortality and the case for age specific alcohol consumption guidelines: pooled analyses of up to 10 population based cohorts

    PubMed Central

    Coombs, Ngaire; Stamatakis, Emmanuel; Biddulph, Jane P

    2015-01-01

    Objectives To examine the suitability of age specific limits for alcohol consumption and to explore the association between alcohol consumption and mortality in different age groups. Design Population based data from Health Survey for England 1998-2008, linked to national mortality registration data and pooled for analysis using proportional hazards regression. Analyses were stratified by sex and age group (50-64 and ≥65 years). Setting Up to 10 waves of the Health Survey for England, which samples the non-institutionalised general population resident in England. Participants The derivation of two analytical samples was based on the availability of comparable alcohol consumption data, covariate data, and linked mortality data among adults aged 50 years or more. Two samples were used, each utilising a different variable for alcohol usage: self reported average weekly consumption over the past year and self reported consumption on the heaviest day in the past week. In fully adjusted analyses, the former sample comprised Health Survey for England years 1998-2002, 18 368 participants, and 4102 deaths over a median follow-up of 9.7 years, whereas the latter comprised Health Survey for England years 1999-2008, 34 523 participants, and 4220 deaths over a median follow-up of 6.5 years. Main outcome measure All cause mortality, defined as any death recorded between the date of interview and the end of data linkage on 31 March 2011. Results In unadjusted models, protective effects were identified across a broad range of alcohol usage in all age-sex groups. These effects were attenuated across most use categories on adjustment for a range of personal, socioeconomic, and lifestyle factors. After the exclusion of former drinkers, these effects were further attenuated. Compared with self reported never drinkers, significant protective associations were limited to younger men (50-64 years) and older women (≥65 years). Among younger men, the range of protective effects was

  12. Community coverage with insecticide-treated mosquito nets and observed associations with all-cause child mortality and malaria parasite infections.

    PubMed

    Larsen, David A; Hutchinson, Paul; Bennett, Adam; Yukich, Joshua; Anglewicz, Philip; Keating, Joseph; Eisele, Thomas P

    2014-11-01

    Randomized trials and mathematical modeling suggest that insecticide-treated mosquito nets (ITNs) provide community-level protection to both those using ITNs and those without individual access. Using nationally representative household survey datasets from 17 African countries, we examined whether community ITN coverage is associated with malaria infections in children < 5 years old and all-cause child mortality (ACCM) among children < 5 years old in households with one or more ITNs versus without any type of mosquito net (treated or untreated). Increasing ITN coverage (> 50%) was protective against malaria infections and ACCM for children in households with an ITN, although this protection was not conferred to children in households without ITNs in these data. Children in households with ITNs were protected against malaria infections and ACCM with ITN coverage > 30%, but this protection was not significant with ITN coverage < 30%. Results suggest that ITNs are more effective with higher ITN coverage.

  13. Marked sex differences in all-cause mortality on antiretroviral therapy in low- and middle-income countries: a systematic review and meta-analysis

    PubMed Central

    Beckham, Sarah W; Beyrer, Chris; Luckow, Peter; Doherty, Meg; Negussie, Eyerusalem K; Baral, Stefan D

    2016-01-01

    Introduction While women and girls are disproportionately at risk of HIV acquisition, particularly in low- and middle-income countries (LMIC), globally men and women comprise similar proportions of people living with HIV who are eligible for antiretroviral therapy. However, men represent only approximately 41% of those receiving antiretroviral therapy globally. There has been limited study of men’s outcomes in treatment programmes, despite data suggesting that men living with HIV and engaged in treatment programmes have higher mortality rates. This systematic review (SR) and meta-analysis (MA) aims to assess differential all-cause mortality between men and women living with HIV and on antiretroviral therapy in LMIC. Methods A SR was conducted through searching PubMed, Ovid Global Health and EMBASE for peer-reviewed, published observational studies reporting differential outcomes by sex of adults (≥15 years) living with HIV, in treatment programmes and on antiretroviral medications in LMIC. For studies reporting hazard ratios (HRs) of mortality by sex, quality assessment using Newcastle–Ottawa Scale (cohort studies) and an MA using a random-effects model (Stata 14.0) were conducted. Results A total of 11,889 records were screened, and 6726 full-text articles were assessed for eligibility. There were 31 included studies in the final MA reporting 42 HRs, with a total sample size of 86,233 men and 117,719 women, and total time on antiretroviral therapy of 1555 months. The pooled hazard ratio (pHR) showed a 46% increased hazard of death for men while on antiretroviral treatment (1.35–1.59). Increased hazard was significant across geographic regions (sub-Saharan Africa: pHR 1.41 (1.28–1.56); Asia: 1.77 (1.42–2.21)) and persisted over time on treatment (≤12 months: 1.42 (1.21–1.67); 13–35 months: 1.48 (1.23–1.78); 36–59 months: 1.50 (1.18–1.91); 61 to 108 months: 1.49 (1.29–1.71)). Conclusions Men living with HIV have consistently and

  14. Trajectory of body shape in early and middle life and all cause and cause specific mortality: results from two prospective US cohort studies

    PubMed Central

    Hu, Frank B; Wu, Kana; Must, Aviva; Chan, Andrew T; Willett, Walter C; Giovannucci, Edward L

    2016-01-01

    Objective To assess body shape trajectories in early and middle life in relation to risk of mortality. Design Prospective cohort study. Setting Nurses’ Health Study and Health Professionals Follow-up Study. Population 80 266 women and 36 622 men who recalled their body shape at ages 5, 10, 20, 30, and 40 years and provided body mass index at age 50, followed from age 60 over a median of 15-16 years for death. Main outcome measures All cause and cause specific mortality. Results Using a group based modeling approach, five distinct trajectories of body shape from age 5 to 50 were identified: lean-stable, lean-moderate increase, lean-marked increase, medium-stable/increase, and heavy-stable/increase. The lean-stable group was used as the reference. Among never smokers, the multivariable adjusted hazard ratio for death from any cause was 1.08 (95% confidence interval 1.02 to 1.14) for women and 0.95 (0.88 to 1.03) for men in the lean-moderate increase group, 1.43 (1.33 to 1.54) for women and 1.11 (1.02 to 1.20) for men in the lean-marked increase group, 1.04 (0.97 to 1.12) for women and 1.01 (0.94 to 1.09) for men in the medium-stable/increase group, and 1.64 (1.49 to 1.81) for women and 1.19 (1.08 to 1.32) for men in the heavy-stable/increase group. For cause specific mortality, participants in the heavy-stable/increase group had the highest risk, with a hazard ratio among never smokers of 2.30 (1.88 to 2.81) in women and 1.45 (1.23 to 1.72) in men for cardiovascular disease, 1.37 (1.14 to 1.65) in women and 1.07 (0.89 to 1.30) in men for cancer, and 1.59 (1.38 to 1.82) in women and 1.10 (0.95 to 1.29) in men for other causes. The trajectory-mortality association was generally weaker among ever smokers than among never smokers (for all cause mortality: P for interaction <0.001 in women and 0.06 in men). When participants were classified jointly according to trajectories and history of type 2 diabetes, the increased risk of death associated with heavier

  15. Heat effects of ambient apparent temperature on all-cause mortality in Cape Town, Durban and Johannesburg, South Africa: 2006-2010.

    PubMed

    Wichmann, Janine

    2017-06-01

    Due to climate change, an increase of 3-4°C in ambient temperature is projected along the South African coast and 6-7°C inland during the next 80years. The objective of this study was to investigate the association between daily ambient apparent temperature (Tapp) and daily all-cause non-accidental mortality (hereafter mortality) in Cape Town, Durban and Johannesburg during a 5-year study period (2006-2010). Susceptibility by sex and age groups (<15years, 15-64years and ≥65years) was also investigated. The associations were investigated with the time-stratified case-crossover epidemiological design. Models were controlled for PM10, public holidays and influenza epidemics. City-specific Tapp thresholds were determined using quasi-Poisson generalised additive models. The pooled estimates by sex and age groups were determined in meta-analyses. The city-specific Tapp thresholds were 18.6°C, 24.8°C and 18.7°C, respectively for Cape Town, Durban and Johannesburg. A 3.3%, 2.6% and 2.8% increase in mortality per IQR increase in Tapp (lag0-1) was observed in Cape Town, Durban and Johannesburg, respectively above the city-specific thresholds. The elderly were more at risk in Cape Town and Johannesburg. No difference in risk was observed for males and females in the three cities. In the meta-analysis an overall significant increase of 0.9% in mortality per 1°C increase in Tapp (lag0-1) was observed for all age groups combined in the three cities. For the ≥65year group a significant increase of 2.1% in mortality was observed. In conclusion, the risks for all age groups combined and the elderly are similar to those reported in studies from developed and developing countries. The results can be used in present-day early warning systems and in risk assessments to estimate the impact of increased Tapp in the country due to climate change. Future research should investigate the association between Tapp and cause-specific mortality and also morbidity.

  16. Serum 25(OH)D Is a 2-Year Predictor of All-Cause Mortality, Cardiac Death and Sudden Cardiac Death in Chest Pain Patients from Northern Argentina

    PubMed Central

    Naesgaard, Patrycja A.; León De La Fuente, Ricardo A.; Nilsen, Stein Tore; Woie, Leik; Aarsland, Torbjoern; Brede, Cato; Staines, Harry; Nilsen, Dennis W. T.

    2012-01-01

    Background Several studies have shown an association between vitamin D deficiency and cardiovascular risk. Vitamin D status is assessed by determination of 25-hydroxyvitamin D [25(OH)D] in serum. Methods We assessed the prognostic utility of 25(OH)D in 982 chest-pain patients with suspected acute coronary syndrome (ACS) from Salta, Northern Argentina. 2-year follow-up data including all-cause mortality, cardiac death and sudden cardiac death were analyzed in quartiles of 25(OH)D, applying univariate and multivariate analysis. Results There were statistically significant changes in seasonal 25(OH)D levels. At follow-up, 119 patients had died. The mean 25(OH)D levels were significantly lower among patients dying than in long-term survivors, both in the total population and in patients with a troponin T (TnT) release (n = 388). When comparing 25(OH)D in the highest quartile to the lowest quartile in a multivariable Cox regression model for all-cause mortality, the hazard ratio (HR) for cardiac death and sudden cardiac death in the total population was 0.37 (95% CI, 0.19–0.73), p = 0.004, 0.23 (95% CI, 0.08–0.67), p = 0.007, and 0.32 (95% CI, 0.11–0.94), p = 0.038, respectively. In patients with TnT release, the respective HR was 0.24 (95% CI, 0.10–0.54), p = 0.001, 0.18 (95% CI, 0.05–0.60), p = 0.006 and 0.25 (95% CI, 0.07–0.89), p = 0.033. 25(OH)D had no prognostic value in patients with no TnT release. Conclusion Vitamin D was shown to be a useful biomarker for prediction of mortality when obtained at admission in chest pain patients with suspected ACS. Trial registration ClinicalTrials.gov NCT01377402 PMID:22970121

  17. Risk of cardiovascular events, arrhythmia and all-cause mortality associated with clarithromycin versus alternative antibiotics prescribed for respiratory tract infections: a retrospective cohort study

    PubMed Central

    Berni, Ellen; de Voogd, Hanka; Butler, Christopher C; Bannister, Christian A; Jenkins-Jones, Sara; Jones, Bethan; Ouwens, Mario; Currie, Craig J

    2017-01-01

    Objective To determine whether treatment with clarithromycin for respiratory tract infections was associated with an increased risk of cardiovascular (CV) events, arrhythmias or all-cause mortality compared with other antibiotics. Design Retrospective cohort design comparing clarithromycin monotherapy for lower (LRTI) or upper respiratory tract infection (URTI) with other antibiotic monotherapies for the same indication. Setting Routine primary care data from the UK Clinical Practice Research Datalink and inpatient data from the Hospital Episode Statistics (HES). Participants Patients aged ≥35 years prescribed antibiotic monotherapy for LRTI or URTI 1998–2012 and eligible for data linkage to HES. Main outcome measures The main outcome measures were: adjusted risk of first-ever CV event, within 37 days of initiation, in commonly prescribed antibiotics compared with clarithromycin. Secondarily, adjusted 37-day risks of first-ever arrhythmia and all-cause mortality. Results Of 700 689 treatments for LRTI and eligible for the CV analysis, there were 2071 CV events (unadjusted event rate: 29.6 per 10 000 treatments). Of 691 998 eligible treatments for URTI, there were 688 CV events (9.9 per 10 000 treatments). In LRTI and URTI, there were no significant differences in CV risk between clarithromycin and all other antibiotics combined: OR=1.00 (95% CI 0.82 to 1.22) and 0.82 (0.54 to 1.25), respectively. Adjusted CV risk in LRTI versus clarithromycin ranged from OR=1.42 (cefalexin; 95% CI 1.08 to 1.86) to 0.92 (doxycycline; 0.64 to 1.32); in URTI, from 1.17 (co-amoxiclav; 0.68 to 2.01) to 0.67 (erythromycin; 0.40 to 1.11). Adjusted mortality risk versus clarithromycin in LRTI ranged from 0.42 to 1.32; in URTI, from 0.75 to 1.43. For arrhythmia, adjusted risks in LRTI ranged from 0.68 to 1.05; in URTI, from 0.70 to 1.22. Conclusions CV events were more likely after LRTI than after URTI. When analysed by specific indication, CV risk associated with

  18. Risk Factors for Incidence of Cardiovascular Diseases and All-Cause Mortality in a Middle Eastern Population over a Decade Follow-up: Tehran Lipid and Glucose Study

    PubMed Central

    Sardarinia, Mahsa; Akbarpour, Samaneh; Lotfaliany, Mojtaba; Bagherzadeh-Khiabani, Farideh; Bozorgmanesh, Mohammadreza; Sheikholeslami, Farhad; Azizi, Fereidoun; Hadaegh, Farzad

    2016-01-01

    Background To examine the association between potentially modifiable risk factors with cardiovascular disease (CVD) and all-cause mortality and to quantify their population attributable fractions (PAFs) among a sample of Tehran residents. Methods Overall, 8108 participants (3686 men) aged≥30 years, were investigated. To examine the association between risk factors and outcomes, multivariate sex-adjusted Cox proportional hazard regression analysis were conducted, using age as time-scale in two models including general/central adiposity: 1)adjusted for different independent variables including smoking, education, family history of CVD and sex for both outcomes and additionally adjusted for prevalent CVD for all-cause mortality 2)further adjusted for obesity mediators (hypertension, diabetes, lipid profile and chronic kidney disease). Separate models were used including either general or central adiposity. Results During median follow-up of >10 years, 827 first CVD events and 551 deaths occurred. Both being overweight (hazard ratio (HR), 95%CI: 1.41, 1.18–1.66, PAF 13.66) and obese (1.51, 1.24–1.84, PAF 9.79) played significant roles for incident CVD in the absence of obesity mediators. Predicting CVD, in the presence of general adiposity and its mediators, significant positive associations were found for hypercholesterolemia (1.59, 1.36–1.85, PAF 16.69), low HDL-C (1.21, 1.03–1.41, PAF 12.32), diabetes (1.86, 1.57–2.27, PAF 13.87), hypertension (1.79, 1.46–2.19, PAF 21.62) and current smoking (1.61, 1.34–1.94, PAF 7.57). Central adiposity remained a significant positive predictor, even after controlling for mediators (1.17, 1.01–1.35, PAF 7.55). For all-cause mortality, general/central obesity did not have any risk even in the absence of obesity mediators. Predictors including diabetes (2.56, 2.08–3.16, PAF 24.37), hypertension (1.43, 1.11–1.84, PAF 17.13), current smoking (1.75, 1.38–2.22, PAF 7.71), and low education level (1.59, 1.01–2

  19. Early Fungicidal Activity as a Candidate Surrogate Endpoint for All-Cause Mortality in Cryptococcal Meningitis: A Systematic Review of the Evidence

    PubMed Central

    Montezuma-Rusca, Jairo M.; Powers, John H.; Follmann, Dean; Wang, Jing; Sullivan, Brigit; Williamson, Peter R.

    2016-01-01

    Background Cryptococcal meningitis (CM) is a leading cause of HIV-associated mortality. In clinical trials evaluating treatments for CM, biomarkers of early fungicidal activity (EFA) in cerebrospinal fluid (CSF) have been proposed as candidate surrogate endpoints for all- cause mortality (ACM). However, there has been no systematic evaluation of the group-level or trial-level evidence for EFA as a candidate surrogate endpoint for ACM. Methods We conducted a systematic review of randomized trials in treatment of CM to evaluate available evidence for EFA measured as culture negativity at 2 weeks/10 weeks and slope of EFA as candidate surrogate endpoints for ACM. We performed sensitivity analysis on superiority trials and high quality trials as determined by Cochrane measures of trial bias. Results Twenty-seven trials including 2854 patients met inclusion criteria. Mean ACM was 15.8% at 2 weeks and 27.0% at 10 weeks with no overall significant difference between test and control groups. There was a statistically significant group-level correlation between average EFA and ACM at 10 weeks but not at 2 weeks. There was also no statistically significant group-level correlation between CFU culture negativity at 2weeks/10weeks or average EFA slope at 10 weeks. A statistically significant trial-level correlation was identified between EFA slope and ACM at 2 weeks, but is likely misleading, as there was no treatment effect on ACM. Conclusions Mortality remains high in short time periods in CM clinical trials. Using published data and Institute of Medicine criteria, evidence for use of EFA as a surrogate endpoint for ACM is insufficient and could provide misleading results from clinical trials. ACM should be used as a primary endpoint evaluating treatments for cryptococcal meningitis. PMID:27490100

  20. Influence of Androgen Deprivation Therapy on All-Cause Mortality in Men With High-Risk Prostate Cancer and a History of Congestive Heart Failure or Myocardial Infarction

    SciTech Connect

    Nguyen, Paul L.; Chen, Ming-Hui; Beckman, Joshua A.; Beard, Clair J.; Martin, Neil E.; Choueiri, Toni K.; Hu, Jim C.; Dosoretz, Daniel E.; Moran, Brian J.; Salenius, Sharon A.; Braccioforte, Michelle H.; Kantoff, Philip W.; D'Amico, Anthony V.; Ennis, Ronald D.

    2012-03-15

    Purpose: It is unknown whether the excess risk of all-cause mortality (ACM) observed when androgen deprivation therapy (ADT) is added to radiation for men with prostate cancer and a history of congestive heart failure (CHF) or myocardial infarction (MI) also applies to those with high-risk disease. Methods and Materials: Of 14,594 men with cT1c-T3aN0M0 prostate cancer treated with brachytherapy-based radiation from 1991 through 2006, 1,378 (9.4%) with a history of CHF or MI comprised the study cohort. Of these, 22.6% received supplemental external beam radiation, and 42.9% received a median of 4 months of neoadjuvant ADT. Median age was 71.8 years. Median follow-up was 4.3 years. Cox multivariable analysis tested for an association between ADT use and ACM within risk groups, after adjusting for treatment factors, prognostic factors, and propensity score for ADT. Results: ADT was associated with significantly increased ACM (adjusted hazard ratio [AHR] = 1.76; 95% confidence interval [CI], 1.32-2.34; p = 0.0001), with 5-year estimates of 22.71% with ADT and 11.62% without ADT. The impact of ADT on ACM by risk group was as follows: high-risk AHR = 2.57; 95% CI, 1.17-5.67; p = 0.019; intermediate-risk AHR = 1.75; 95% CI, 1.13-2.73; p = 0.012; low-risk AHR = 1.52; 95% CI, 0.96-2.43; p = 0.075). Conclusions: Among patients with a history of CHF or MI treated with brachytherapy-based radiation, ADT was associated with increased all-cause mortality, even for patients with high-risk disease. Although ADT has been shown in Phase III studies to improve overall survival in high-risk disease, the small subgroup of high-risk patients with a history of CHF or MI, who represented about 9% of the patients, may be harmed by ADT.

  1. Personality and all-cause mortality: individual-participant meta-analysis of 3,947 deaths in 76,150 adults.

    PubMed

    Jokela, Markus; Batty, G David; Nyberg, Solja T; Virtanen, Marianna; Nabi, Hermann; Singh-Manoux, Archana; Kivimäki, Mika

    2013-09-01

    Personality may influence the risk of death, but the evidence remains inconsistent. We examined associations between personality traits of the five-factor model (extraversion, neuroticism, agreeableness, conscientiousness, and openness to experience) and the risk of death from all causes through individual-participant meta-analysis of 76,150 participants from 7 cohorts (the British Household Panel Survey, 2006-2009; the German Socio-Economic Panel Study, 2005-2010; the Household, Income and Labour Dynamics in Australia Survey, 2006-2010; the US Health and Retirement Study, 2006-2010; the Midlife in the United States Study, 1995-2004; and the Wisconsin Longitudinal Study's graduate and sibling samples, 1993-2009). During 444,770 person-years at risk, 3,947 participants (54.4% women) died (mean age at baseline = 50.9 years; mean follow-up = 5.9 years). Only low conscientiousness-reflecting low persistence, poor self-control, and lack of long-term planning-was associated with elevated mortality risk when taking into account age, sex, ethnicity/nationality, and all 5 personality traits. Individuals in the lowest tertile of conscientiousness had a 1.4 times higher risk of death (hazard ratio = 1.37, 95% confidence interval: 1.18, 1.58) compared with individuals in the top 2 tertiles. This association remained after further adjustment for health behaviors, marital status, and education. In conclusion, of the higher-order personality traits measured by the five-factor model, only conscientiousness appears to be related to mortality risk across populations.

  2. Elevated levels of plasma osteoprotegerin are associated with all-cause mortality risk and atherosclerosis in patients with stages 3 to 5 chronic kidney disease

    PubMed Central

    Nascimento, M.M.; Hayashi, S.Y.; Riella, M.C.; Lindholm, B.

    2014-01-01

    Osteoprotegerin (OPG) regulates bone mass by inhibiting osteoclast differentiation and activation, and plays a role in vascular calcification. We evaluated the relationship between osteoprotegerin levels and inflammatory markers, atherosclerosis, and mortality in patients with stages 3-5 chronic kidney disease. A total of 145 subjects (median age 61 years, 61% men; 36 patients on hemodialysis, 55 patients on peritoneal dialysis, and 54 patients with stages 3-5 chronic kidney disease) were studied. Clinical characteristics, markers of mineral metabolism (including fibroblast growth factor-23 [FGF-23]) and inflammation (high-sensitivity C-reactive protein [hsCRP] and interleukin-6 [IL-6]), and the intima-media thickness (IMT) in the common carotid arteries were measured at baseline. Cardiac function was assessed by color tissue Doppler echocardiography. After 36 months follow-up, the survival rate by Kaplan-Meier analysis was significantly different according to OPG levels (χ 2=14.33; P=0.002). Increased OPG levels were positively associated with IL-6 (r=0.38, P<0.001), FGF-23 (r=0.26, P<0.001) and hsCRP (r=0.0.24, P=0.003). In addition, OPG was positively associated with troponin I (r=0.54, P<0.001) and IMT (r=0.39, P<0.0001). Finally, in Cox analysis, only OPG (HR=1.07, 95%CI=1.02-1.13) and hsCRP (HR=1.02, 95%CI=1.01-1.04) were independently associated with increased risk of death. These results suggested that elevated levels of serum OPG might be associated with atherosclerosis and all-cause mortality in patients with chronic kidney disease. PMID:25296363

  3. Prior-Cancer Diagnosis in Men with Nonmetastatic Prostate Cancer and the Risk of Prostate-Cancer-Specific and All-Cause Mortality

    PubMed Central

    Chen, Ming-Hui; D'Amico, Anthony V.

    2014-01-01

    Purpose. We evaluated the impact a prior cancer diagnosis had on the risk of prostate-cancer-specific mortality (PCSM) and all-cause mortality (ACM) in men with PC. Methods. Using the SEER data registry, 166,104 men (median age: 66) diagnosed with PC between 2004 and 2007 comprised the study cohort. Competing risks and Cox regression were used to evaluate whether a prior cancer diagnosis impacted the risk of PCSM and ACM adjusting for known prognostic factors PSA level, age at and year of diagnosis, race, and whether PC treatment was curative, noncurative, or active surveillance (AS)/watchful waiting (WW). Results. At a median followup of 2.75 years, 12,453 men died: 3,809 (30.6%) from PC. Men with a prior cancer were followed longer, had GS 8 to 10 PC more often, and underwent WW/AS more frequently (P < 0.001). Despite these differences that should increase the risk of PCSM, the adjusted risk of PCSM was significantly decreased (AHR: 0.66 (95% CI: (0.45, 0.97); P = 0.033), while the risk of ACM was increased (AHR: 2.92 (95% CI: 2.64, 3.23); P < 0.001) in men with a prior cancer suggesting that competing risks accounted for the reduction in the risk of PCSM. Conclusion. An assessment of the impact that a prior cancer has on life expectancy is needed at the time of PC diagnosis to determine whether curative treatment for unfavorable-risk PC versus AS is appropriate. PMID:24634786

  4. Adherence to a healthy diet according to the World Health Organization guidelines and all-cause mortality in elderly adults from Europe and the United States.

    PubMed

    Jankovic, Nicole; Geelen, Anouk; Streppel, Martinette T; de Groot, Lisette C P G M; Orfanos, Philippos; van den Hooven, Edith H; Pikhart, Hynek; Boffetta, Paolo; Trichopoulou, Antonia; Bobak, Martin; Bueno-de-Mesquita, H B; Kee, Frank; Franco, Oscar H; Park, Yikyung; Hallmans, Göran; Tjønneland, Anne; May, Anne M; Pajak, Andrzej; Malyutina, Sofia; Kubinova, Růžena; Amiano, Pilar; Kampman, Ellen; Feskens, Edith J

    2014-11-15

    The World Health Organization (WHO) has formulated guidelines for a healthy diet to prevent chronic diseases and postpone death worldwide. Our objective was to investigate the association between the WHO guidelines, measured using the Healthy Diet Indicator (HDI), and all-cause mortality in elderly men and women from Europe and the United States. We analyzed data from 396,391 participants (42% women) in 11 prospective cohort studies who were 60 years of age or older at enrollment (in 1988-2005). HDI scores were based on 6 nutrients and 1 food group and ranged from 0 (least healthy diet) to 70 (healthiest diet). Adjusted cohort-specific hazard ratios were derived by using Cox proportional hazards regression and subsequently pooled using random-effects meta-analysis. During 4,497,957 person-years of follow-up, 84,978 deaths occurred. Median HDI scores ranged from 40 to 54 points across cohorts. For a 10-point increase in HDI score (representing adherence to an additional WHO guideline), the pooled adjusted hazard ratios were 0.90 (95% confidence interval (CI): 0.87, 0.93) for men and women combined, 0.89 (95% CI: 0.85, 0.92) for men, and 0.90 (95% CI: 0.85, 0.95) for women. These estimates translate to an increased life expectancy of 2 years at the age of 60 years. Greater adherence to the WHO guidelines is associated with greater longevity in elderly men and women in Europe and the United States.

  5. Anemia as a risk factor for cardiovascular disease and all-cause mortality in diabetes: the impact of chronic kidney disease.

    PubMed

    Vlagopoulos, Panagiotis T; Tighiouart, Hocine; Weiner, Daniel E; Griffith, John; Pettitt, Dan; Salem, Deeb N; Levey, Andrew S; Sarnak, Mark J

    2005-11-01

    Anemia is a potential nontraditional risk factor for cardiovascular disease (CVD). This study evaluated whether anemia is a risk factor for adverse outcomes in people with diabetes and whether the risk is modified by the presence of chronic kidney disease (CKD). Persons with diabetes from four community-based studies were pooled: Atherosclerosis Risk in Communities, Cardiovascular Health Study, Framingham Heart Study, and Framingham Offspring Study. Anemia was defined as a hematocrit <36% in women and <39% in men. CKD was defined as an estimated GFR of 15 to 60 ml/min per 1.73 m(2). Study outcomes included a composite of myocardial infarction (MI)/fatal coronary heart disease (CHD)/stroke/death and each outcome separately. Cox regression analysis was used to study the effect of anemia on the risk for outcomes after adjustment for potential confounders. The study population included 3015 individuals: 30.4% were black, 51.6% were women, 8.1% had anemia, and 13.8% had CKD. Median follow-up was 8.6 yr. There were 1215 composite events, 600 MI/fatal CHD outcomes, 300 strokes, and 857 deaths. In a model with a CKD-anemia interaction term, anemia was associated with the following hazard ratios (95% confidence intervals) in patients with CKD: 1.70 (1.24 to 2.34) for the composite outcome, 1.64 (1.03 to 2.61) for MI/fatal CHD, 1.81 (0.99 to 3.29) for stroke, and 1.88 (1.33 to 2.66) for all-cause mortality. Anemia was not a risk factor for any outcome in those without CKD (P > 0.2 for all outcomes). In persons with diabetes, anemia is primarily a risk factor for adverse outcomes in those who also have CKD.

  6. Smoking increases risks of all-cause and breast cancer specific mortality in breast cancer individuals: a dose-response meta-analysis of prospective cohort studies involving 39725 breast cancer cases.

    PubMed

    Wang, Kang; Li, Feng; Zhang, Xiang; Li, Zhuyue; Li, Hongyuan

    2016-12-13

    Smoking is associated with the risks of mortality from breast cancer (BC) or all causes in BC survivors. Two-stage dose-response meta-analysis was conducted. A search of PubMed and Embase was performed, and a random-effect model was used to yield summary hazard ratios (HRs). Eleven prospective cohort studies were included. The summary HR per 10 cigarettes/day, 10 pack-years, 10 years increase were 1.10 (95% confidence interval (CI) = 1.04-1.16), 1.09 (95% CI = 1.06-1.12), 1.10 (95% CI = 1.06-1.14) for BC specific mortality, and 1.15 (95% CI = 1.10-1.19), 1.15 (95% CI = 1.10-1.20), 1.17 (95% CI = 1.11-1.23) for all-cause mortality, respectively. The linear or non-linear associations between smoking and risks of mortality from BC or all causes were revealed. Subgroup analyses suggested a positive association between ever or former smoking and the risk of all-cause mortality in BC patients, especially in high doses consumption. In conclusion, higher smoking intensity, more cumulative amount of cigarettes consumption and longer time for smoking is associated with elevated risk of mortality from BC and all causes in BC individuals. The results regarding smoking cessation and "ever or former" smokers should be treated with caution due to limited studies.

  7. Is poor oral health a risk marker for incident cardiovascular disease hospitalisation and all-cause mortality? Findings from 172 630 participants from the prospective 45 and Up Study

    PubMed Central

    Joshy, Grace; Arora, Manish; Korda, Rosemary J; Chalmers, John; Banks, Emily

    2016-01-01

    Objective To investigate the relationship between oral health and incident hospitalisation for ischaemic heart disease (IHD), heart failure (HF), ischaemic stroke and peripheral vascular disease (PVD) and all-cause mortality. Design Prospective population-based study of Australian men and women aged 45 years or older, who were recruited to the 45 and Up Study between January 2006 and April 2009; baseline questionnaire data were linked to hospitalisations and deaths up to December 2011. Study exposures include tooth loss and self-rated health of teeth and gums at baseline. Setting New South Wales, Australia. Participants Individuals aged 45–75 years, excluding those with a history of cancer/cardiovascular disease (CVD) at baseline; n=172 630. Primary outcomes Incident hospitalisation for IHD, HF, ischaemic stroke and PVD and all-cause mortality. Results During a median follow-up of 3.9 years, 3239 incident hospitalisations for IHD, 212 for HF, 283 for ischaemic stroke and 359 for PVD, and 1908 deaths, were observed. Cox proportional hazards models examined the relationship between oral health indicators and incident hospitalisation for CVD and all-cause mortality, adjusting for potential confounding factors. All-cause mortality and incident CVD hospitalisation risk increased significantly with increasing tooth loss for all outcomes except ischaemic stroke (ptrend<0.05). In those reporting no teeth versus ≥20 teeth left, risks were increased for HF (HR, 95% CI 1.97, 1.27 to 3.07), PVD (2.53, 1.81 to 3.52) and all-cause mortality (1.60, 1.37 to 1.87). The risk of IHD, PVD and all-cause mortality (but not HF or ischaemic stroke) increased significantly with worsening self-rated health of teeth and gums (ptrend<0.05). In those reporting poor versus very good health of teeth and gums, risks were increased for IHD (1.19, 1.03 to 1.38), PVD (1.66, 1.13 to 2.43) and all-cause mortality (1.76, 1.50 to 2.08). Conclusions Tooth loss and, to a lesser extent, self

  8. Associations of objectively measured moderate-to-vigorous-intensity physical activity and sedentary time with all-cause mortality in a population of adults at high risk of type 2 diabetes mellitus.

    PubMed

    Bakrania, Kishan; Edwardson, Charlotte L; Khunti, Kamlesh; Henson, Joseph; Stamatakis, Emmanuel; Hamer, Mark; Davies, Melanie J; Yates, Thomas

    2017-03-01

    The relationships of physical activity and sedentary time with all-cause mortality in those at high risk of type 2 diabetes mellitus (T2DM) are unexplored. To address this gap in knowledge, we examined the associations of objectively measured moderate-to-vigorous-intensity physical activity (MVPA) and sedentary time with all-cause mortality in a population of adults at high risk of T2DM. In 2010-2011, 712 adults (Leicestershire, U.K.), identified as being at high risk of T2DM, consented to be followed up for mortality. MVPA and sedentary time were assessed by accelerometer; those with valid data (≥ 10 hours of wear-time/day with ≥ 4 days of data) were included. Cox proportional hazards regression models, adjusted for potential confounders, were used to investigate the independent associations of MVPA and sedentary time with all-cause mortality. 683 participants (250 females (36.6%)) were included and during a mean follow-up period of 5.7 years, 26 deaths were registered. Every 10% increase in MVPA time/day was associated with a 5% lower risk of all-cause mortality [Hazard Ratio (HR): 0.95 (95% Confidence Interval (95% CI): 0.91, 0.98); p = 0.004]; indicating that for the average adult in this cohort undertaking approximately 27.5 minutes of MVPA/day, this benefit would be associated with only 2.75 additional minutes of MVPA/day. Conversely, sedentary time showed no association with all-cause mortality [HR (every 10-minute increase in sedentary time/day): 0.99 (95% CI: 0.95, 1.03); p = 0.589]. These data support the importance of MVPA in adults at high risk of T2DM. The association between sedentary time and mortality in this population needs further investigation.

  9. Socioeconomic Factors and All Cause and Cause-Specific Mortality among Older People in Latin America, India, and China: A Population-Based Cohort Study

    PubMed Central

    Ferri, Cleusa P.; Acosta, Daisy; Guerra, Mariella; Huang, Yueqin; Llibre-Rodriguez, Juan J.; Salas, Aquiles; Sosa, Ana Luisa; Williams, Joseph D.; Gaona, Ciro; Liu, Zhaorui; Noriega-Fernandez, Lisseth; Jotheeswaran, A. T.; Prince, Martin J.

    2012-01-01

    Background Even in low and middle income countries most deaths occur in older adults. In Europe, the effects of better education and home ownership upon mortality seem to persist into old age, but these effects may not generalise to LMICs. Reliable data on causes and determinants of mortality are lacking. Methods and Findings The vital status of 12,373 people aged 65 y and over was determined 3–5 y after baseline survey in sites in Latin America, India, and China. We report crude and standardised mortality rates, standardized mortality ratios comparing mortality experience with that in the United States, and estimated associations with socioeconomic factors using Cox's proportional hazards regression. Cause-specific mortality fractions were estimated using the InterVA algorithm. Crude mortality rates varied from 27.3 to 70.0 per 1,000 person-years, a 3-fold variation persisting after standardisation for demographic and economic factors. Compared with the US, mortality was much higher in urban India and rural China, much lower in Peru, Venezuela, and urban Mexico, and similar in other sites. Mortality rates were higher among men, and increased with age. Adjusting for these effects, it was found that education, occupational attainment, assets, and pension receipt were all inversely associated with mortality, and food insecurity positively associated. Mutually adjusted, only education remained protective (pooled hazard ratio 0.93, 95% CI 0.89–0.98). Most deaths occurred at home, but, except in India, most individuals received medical attention during their final illness. Chronic diseases were the main causes of death, together with tuberculosis and liver disease, with stroke the leading cause in nearly all sites. Conclusions Education seems to have an important latent effect on mortality into late life. However, compositional differences in socioeconomic position do not explain differences in mortality between sites. Social protection for older people, and the

  10. Predictive Validity of the American College of Cardiology/American Heart Association Pooled Cohort Equations in Predicting All-Cause and Cardiovascular Disease-Specific Mortality in a National Prospective Cohort Study of Adults in the United States.

    PubMed

    Loprinzi, Paul D; Addoh, Ovuokerie

    2016-06-01

    The predictive validity of the Pooled Cohort risk (PCR) equations for cardiovascular disease (CVD)-specific and all-cause mortality among a national sample of US adults has yet to be evaluated, which was this study's purpose. Data from the 1999-2010 National Health and Nutrition Examination Survey were used, with participants followed up through December 31, 2011, to ascertain mortality status via the National Death Index probabilistic algorithm. The analyzed sample included 11,171 CVD-free adults (40-79 years of age). The 10-year risk of a first atherosclerotic cardiovascular disease (ASCVD) event was determined from the PCR equations. For the entire sample encompassing 849,202 person-months, we found an incidence rate of 1.00 (95% CI, 0.93-1.07) all-cause deaths per 1000 person-months and an incidence rate of 0.15 (95% CI, 0.12-0.17) CVD-specific deaths per 1000 person-months. The unweighted median follow-up duration was 72 months. For nearly all analyses (unadjusted and adjusted models with ASCVD expressed as a continuous variable as well as dichotomized at 7.5% and 20%), the ASCVD risk score was significantly associated with all-cause and CVD-specific mortality (P<.05). In the adjusted model, the increased all-cause mortality risk ranged from 47% to 77% based on an ASCVD risk of 20% or higher and 7.5% or higher, respectively. Those with an ASCVD score of 7.5% or higher had a 3-fold increased risk of CVD-specific mortality. The 10-year predicted risk of a first ASCVD event via the PCR equations was associated with all-cause and CVD-specific mortality among those free of CVD at baseline. In this American adult sample, the PCR equations provide evidence of predictive validity.

  11. Smoking increases risks of all-cause and breast cancer specific mortality in breast cancer individuals: a dose-response meta-analysis of prospective cohort studies involving 39725 breast cancer cases

    PubMed Central

    Wang, Kang; Li, Feng; Zhang, Xiang; Li, Zhuyue; Li, Hongyuan

    2016-01-01

    Smoking is associated with the risks of mortality from breast cancer (BC) or all causes in BC survivors. Two-stage dose-response meta-analysis was conducted. A search of PubMed and Embase was performed, and a random-effect model was used to yield summary hazard ratios (HRs). Eleven prospective cohort studies were included. The summary HR per 10 cigarettes/day, 10 pack-years, 10 years increase were 1.10 (95% confidence interval (CI) = 1.04–1.16), 1.09 (95% CI = 1.06–1.12), 1.10 (95% CI = 1.06–1.14) for BC specific mortality, and 1.15 (95% CI = 1.10–1.19), 1.15 (95% CI = 1.10–1.20), 1.17 (95% CI = 1.11–1.23) for all-cause mortality, respectively. The linear or non-linear associations between smoking and risks of mortality from BC or all causes were revealed. Subgroup analyses suggested a positive association between ever or former smoking and the risk of all-cause mortality in BC patients, especially in high doses consumption. In conclusion, higher smoking intensity, more cumulative amount of cigarettes consumption and longer time for smoking is associated with elevated risk of mortality from BC and all causes in BC individuals. The results regarding smoking cessation and “ever or former” smokers should be treated with caution due to limited studies. PMID:27863414

  12. All-cause cancer mortality over 15 years in multi-ethnic Mauritius: the impact of diabetes and intermediate forms of glucose tolerance.

    PubMed

    Harding, Jessica L; Soderberg, Stefan; Shaw, Jonathan E; Zimmet, Paul Z; Pauvaday, Vassen; Kowlessur, Sudhir; Tuomilehto, Jaakko; Alberti, K George M M; J Magliano, Dianna

    2012-11-15

    There are accumulating data describing the association between diabetes and cancer mortality from Westernised populations. There are no data describing the relationship between diabetes and cancer mortality in African or South Asian populations from developing countries. We explored the relationship of abnormal glucose tolerance and diabetes on cancer mortality risk in a large, multi-ethnic cohort from the developing nation of Mauritius. Population-based surveys were undertaken in 1987, 1992 and 1998. The 9559 participants comprised 66% of South Asian (Indian), 27% of African (Creole), and 7% of Chinese descent. Cox's proportional hazards model with time varying covariates was used to obtain hazard ratios (HRs) and 95% confidence intervals (95% CI) for risk of cancer mortality, after adjustment for confounding factors. In men, but not women, cancer mortality risk increased with rising 2h-PG levels with HR for the top versus bottom quintile of 2.77 (95%CI: 1.28 to 5.98). South Asian men with known diabetes had a significantly greater risk of cancer mortality than those with normal glucose tolerance (NGT) HR: 2.74 (95%CI: 1.00-7.56). Overall, impaired glucose tolerance was associated with an elevated risk of cancer mortality compared to NGT (HR: 1.47, 95% CI: 0.98-2.19), though this was not significant. We have shown that the association between abnormal glucose tolerance and cancer extends to those of African and South Asian descent. These results highlight the importance of understanding this relationship in a global context to direct future health policy given the rapid increase in type 2 diabetes, especially in developing nations.

  13. Blood pressure and risk of all-cause mortality in advanced chronic kidney disease and hemodialysis: the chronic renal insufficiency cohort study.

    PubMed

    Bansal, Nisha; McCulloch, Charles E; Rahman, Mahboob; Kusek, John W; Anderson, Amanda H; Xie, Dawei; Townsend, Raymond R; Lora, Claudia M; Wright, Jackson; Go, Alan S; Ojo, Akinlolu; Alper, Arnold; Lustigova, Eva; Cuevas, Magda; Kallem, Radhakrishna; Hsu, Chi-Yuan

    2015-01-01

    Studies of hemodialysis patients have shown a U-shaped association between systolic blood pressure (SBP) and mortality. These studies have largely relied on dialysis-unit SBP measures and have not evaluated whether this U-shape also exists in advanced chronic kidney disease, before starting hemodialysis. We determined the association between SBP and mortality at advanced chronic kidney disease and again after initiation of hemodialysis. This was a prospective study of Chronic Renal Insufficiency Cohort participants with advanced chronic kidney disease followed through initiation of hemodialysis. We studied the association between SBP and mortality when participants (1) had an estimated glomerular filtration rate <30 mL/min/1.73 m2 (n=1705), (2) initiated hemodialysis and had dialysis-unit SBP measures (n=403), and (3) initiated hemodialysis and had out-of-dialysis-unit SBP measured at a Chronic Renal Insufficiency Cohort study visit (n=326). Cox models were adjusted for demographics, cardiovascular risk factors, and dialysis parameters. A quadratic term for SBP was included to test for a U-shaped association. At advanced chronic kidney disease, there was no association between SBP and mortality (hazard ratio, 1.02 [95% confidence interval, 0.98-1.07] per every 10 mm Hg increase). Among participants who started hemodialysis, a U-shaped association between dialysis-unit SBP and mortality was observed. In contrast, there was a linear association between out-of-dialysis-unit SBP and mortality (hazard ratio, 1.26 [95% confidence interval, 1.14-1.40] per every 10 mm Hg increase). In conclusion, more efforts should be made to obtain out-of-dialysis-unit SBP, which may merit more consideration as a target for clinical management and in interventional trials.

  14. Relation of digoxin use in atrial fibrillation and the risk of all-cause mortality in patients ≥65 years of age with versus without heart failure.

    PubMed

    Shah, Mitesh; Avgil Tsadok, Meytal; Jackevicius, Cynthia A; Essebag, Vidal; Behlouli, Hassan; Pilote, Louise

    2014-08-01

    Previous studies on digoxin use in patients with atrial fibrillation (AF) and the risk of all-cause mortality found conflicting results. We conducted a population-based, retrospective, cohort study of patients aged ≥65 years admitted to a hospital with a primary or secondary diagnosis of AF, in Quebec province, Canada, from 1998 to 2012. The AF cohort was grouped into patients with and without heart failure (HF) and into digoxin and no-digoxin users according to the first prescription filled for digoxin within 30 days after AF hospital discharge. We derived propensity score-matched digoxin and no-digoxin treatment groups for the groups of patients with and without HF, respectively, and conducted multivariable Cox proportional hazards regression analyses to determine association between digoxin use and all-cause mortality. The AF propensity score-matched cohorts of patients with and without HF were well balanced on baseline characteristics. In the propensity score-matched HF group, digoxin use was associated with a 14% greater risk of all-cause mortality (adjusted hazard ratio 1.14, 95% confidence interval 1.10 to 1.17). In the propensity score-matched no-HF group, digoxin use was associated with a 17% greater risk of all-cause mortality (adjusted hazard ratio 1.17, 95% confidence interval 1.14 to 1.19). In conclusion, our retrospective analyses found that digoxin use was associated with a greater risk for all-cause mortality in patients aged ≥65 years with AF regardless of concomitant HF. Large, multicenter, randomized controlled trials or prospective cohort studies are required to clarify this issue.

  15. Fluid Intelligence Is Independently Associated with All-Cause Mortality over 17 Years in an Elderly Community Sample: An Investigation of Potential Mechanisms

    ERIC Educational Resources Information Center

    Batterham, Philip J.; Christensen, Helen; Mackinnon, Andrew J.

    2009-01-01

    The long-term relationship between lower intelligence and mortality risk in later life is well established, even when controlling for a range of health and sociodemographic measures. However, there is some evidence for differential effects in various domains of cognitive performance. Specifically, tests of fluid intelligence may have a stronger…

  16. Nonmedical Opioid Pain Relievers and All-Cause Mortality: A 27-Year Follow-Up From the Epidemiologic Catchment Area Study

    PubMed Central

    Hu, Hui; Smallwood, Bryan A.; Anthony, James C.; Wu, Li-Tzy; Eaton, William W.

    2016-01-01

    Objectives. We investigated whether nonmedical opioid pain reliever use is associated with higher mortality in the general US population. Methods. We assessed the history of nonmedical opioid pain reliever use among 9985 people interviewed at baseline of the Epidemiologic Catchment Area Program initiated in 1981 to 1983 in Baltimore, Maryland; St. Louis, Missouri; and Durham, North Carolina. We linked the data with the National Death Index through 2007. Results. Nonmedical opioid pain reliever use was 1.4%. Compared with no nonmedical drug use, mortality was increased for nonmedical opioid pain reliever use (hazard ratio [HR] = 1.60; 95% confidence interval [CI] = 1.01, 2.53) or nonmedical use of other drugs (HR = 1.31; 95% CI = 1.07, 1.62). Mortality was also higher for males and for those beginning nonmedical opioid pain reliever use before aged 15 years. Conclusions. A history of nonmedical opioid pain reliever use was associated with increased mortality, in particular for males and early onset users. PMID:26691106

  17. Bringing the individual back to small-area variation studies: a multilevel analysis of all-cause mortality in Andalusia, Spain.

    PubMed

    Merlo, Juan; Viciana-Fernández, Francisco J; Ramiro-Fariñas, Diego

    2012-10-01

    We performed a multilevel analysis (including individuals, households, census tracts, municipalities and provinces) on a 10% sample (N=230,978) from the Longitudinal Database of the Andalusian Population (LDAP). We aimed to investigate place effects on 8-year individual mortality risk. Moreover, besides calculating association (yielding odds ratios, ORs) between area socio-economic circumstances and individual risk, we wanted to estimate variance and clustering using the variance partition coefficient (VPC). We explicitly proclaim the relevance of considering general contextual effects (i.e. the degree to which the context, as a whole, affects individual variance in mortality risk) under at least two circumstances. The first of these concerns the interpretation of specific contextual effects (i.e. the association between a particular area characteristic and individual risk) obtained from multilevel regression analyses. The second involves the interpretation of geographical variance obtained from classic ecological spatial analyses. The so-called "ecological fallacy" apart, the lack of individual-level information renders geographical variance unrelated to the total individual variation and, therefore, difficult to interpret. Finally, we stress the importance of considering the familial household in multilevel analyses. We observed an association between percentage of people with a low educational level in the census tract and individual mortality risk (OR, highest v. lowest quintile=1.14; 95% confidence interval, CI 1.08-1.20). However, only a minor proportion of the total individual variance in the probability of dying was at the municipality (M) and census tract (CT) levels (VPC(M)=0.2% and VPC(CT)=0.3%). Conversely, the household (H) level appeared much more relevant (VPC(H)=18.6%) than the administrative geographical areas. Without considering general contextual effects, both multilevel analyses of specific contextual effects and ecological studies of small

  18. Joint effects of tobacco use and body mass on all-cause mortality in Mumbai, India: results from a population-based cohort study.

    PubMed

    Pednekar, Mangesh S; Gupta, Prakash C; Hebert, James R; Hakama, Matti

    2008-02-01

    The joint effects of tobacco use and body mass on mortality have not been well characterized, although evidence regarding the effect of smoking on the association between body mass and mortality is accumulating. To study the joint effects of these important risk factors, the authors conducted a prospective cohort study of 148,173 men and women aged > or =35 years in Mumbai, India. Subjects were recruited during 1991-1997 and then followed for approximately 5-6 years (1997-2003). During 774,129 person-years of follow-up, 13,261 deaths were observed. Tobacco use increased the risk of death across different categories of body mass, with particularly high risks being observed in extreme body mass categories. Among men, obese smokers and obese never users of tobacco were at 56% and 34% increased risks of death, respectively, compared with overweight never users of tobacco. Similarly, at highest risk were extremely thin males who smoked bidis (relative risk = 3.45) or cigarettes (relative risk = 3.32). Body mass and all forms of tobacco use had independent as well as multiplicative joint effects on mortality risk. Tobacco use and undernutrition are serious problems in India. The current study indicates that obesity may emerge as a serious public health problem with which tobacco use may interact.

  19. Intake of saturated and trans unsaturated fatty acids and risk of all cause mortality, cardiovascular disease, and type 2 diabetes: systematic review and meta-analysis of observational studies

    PubMed Central

    de Souza, Russell J; Mente, Andrew; Maroleanu, Adriana; Cozma, Adrian I; Kishibe, Teruko; Uleryk, Elizabeth; Budylowski, Patrick; Schünemann, Holger; Beyene, Joseph

    2015-01-01

    Objective To systematically review associations between intake of saturated fat and trans unsaturated fat and all cause mortality, cardiovascular disease (CVD) and associated mortality, coronary heart disease (CHD) and associated mortality, ischemic stroke, and type 2 diabetes. Design Systematic review and meta-analysis. Data sources Medline, Embase, Cochrane Central Registry of Controlled Trials, Evidence-Based Medicine Reviews, and CINAHL from inception to 1 May 2015, supplemented by bibliographies of retrieved articles and previous reviews. Eligibility criteria for selecting studies Observational studies reporting associations of saturated fat and/or trans unsaturated fat (total, industrially manufactured, or from ruminant animals) with all cause mortality, CHD/CVD mortality, total CHD, ischemic stroke, or type 2 diabetes. Data extraction and synthesis Two reviewers independently extracted data and assessed study risks of bias. Multivariable relative risks were pooled. Heterogeneity was assessed and quantified. Potential publication bias was assessed and subgroup analyses were undertaken. The GRADE approach was used to evaluate quality of evidence and certainty of conclusions. Results For saturated fat, three to 12 prospective cohort studies for each association were pooled (five to 17 comparisons with 90 501-339 090 participants). Saturated fat intake was not associated with all cause mortality (relative risk 0.99, 95% confidence interval 0.91 to 1.09), CVD mortality (0.97, 0.84 to 1.12), total CHD (1.06, 0.95 to 1.17), ischemic stroke (1.02, 0.90 to 1.15), or type 2 diabetes (0.95, 0.88 to 1.03). There was no convincing lack of association between saturated fat and CHD mortality (1.15, 0.97 to 1.36; P=0.10). For trans fats, one to six prospective cohort studies for each association were pooled (two to seven comparisons with 12 942-230 135 participants). Total trans fat intake was associated with all cause mortality (1.34, 1.16 to 1.56), CHD mortality

  20. The ability of three different models of frailty to predict all-cause mortality: results from the European Male Aging Study (EMAS).

    PubMed

    Ravindrarajah, Rathi; Lee, David M; Pye, Stephen R; Gielen, Evelien; Boonen, Steven; Vanderschueren, Dirk; Pendleton, Neil; Finn, Joseph D; Tajar, Abdelouahid; O'Connell, Matthew D L; Rockwood, Kenneth; Bartfai, György; Casanueva, Felipe F; Forti, Gianni; Giwercman, Aleksander; Han, Thang S; Huhtaniemi, Ilpo T; Kula, Krzysztof; Lean, Michael E J; Punab, Margus; Wu, Frederick C W; O'Neill, Terence W

    2013-01-01

    Few studies have directly compared the ability of the most commonly used models of frailty to predict mortality among community-dwelling individuals. Here, we used a frailty index (FI), frailty phenotype (FP), and FRAIL scale (FS) to predict mortality in the EMAS. Participants were aged 40-79 years (n=2929) at baseline and 6.6% (n=193) died over a median 4.3 years of follow-up. The FI was generated from 39 deficits, including self-reported health, morbidities, functional performance and psychological assessments. The FP and FS consisted of five phenotypic criteria and both categorized individuals as robust when they had 0 criteria, prefrail as 1-2 criteria and frail as 3+ criteria. The mean FI increased linearly with age (r(2)=0.21) and in Cox regression models adjusted for age, center, smoking and partner status the hazard ratio (HR) for death for each unit increase of the FI was 1.49. Men who were prefrail or frail by either the FP or FS definitions, had a significantly increased risk of death compared to their robust counterparts. Compared to robust men, those who were FP frail at baseline had a HR for death of 3.84, while those who were FS frail had a HR of 3.87. All three frailty models significantly predicted future mortality among community-dwelling, middle-aged and older European men after adjusting for potential confounders. Our data suggest that the choice of frailty model may not be of paramount importance when predicting future risk of death, enabling flexibility in the approach used.

  1. Association of D-dimer levels with all-cause mortality in a healthy adult population: findings from the MOLI-SANI study.

    PubMed

    Di Castelnuovo, Augusto; de Curtis, Amalia; Costanzo, Simona; Persichillo, Mariarosaria; Olivieri, Marco; Zito, Francesco; Donati, Maria Benedetta; de Gaetano, Giovanni; Iacoviello, Licia

    2013-09-01

    Elevated D-dimer levels are reportedly associated with higher risk of total mortality in patients with different diseases. We investigated whether a similar association could be found in a large, apparently healthy population. A large sample of individuals (N=17,359, 47% men, age ≥ 35 years) free of clinically recognized cardiovascular and cancer disease, for whom baseline D-dimer level was available, were studied within the MOLI-SANI cohort, randomly recruited from the general adult population of Southern Italy. The cohort was followed for a median of 4.2 years (73,807 person-years). D-dimer was measured in fresh citrated plasma by an automated latex-enhanced immunoassay. Hazard ratios were calculated using three Cox-proportional hazard models. Two hundred and eighty deaths were recorded. When modeled as a continuous variable, D-dimer level at baseline showed a non-linear association with mortality, whose incidence increased only in the upper quartile of the distribution (D-dimer ≥ 221 ng/mL). Thus, the group of individuals with D-dimer <221 ng/mL (75% of the population) acted as the reference group, while the remaining individuals were subdivided in tertiles and compared with the former group. Multivariable hazard ratios for mortality were 1.06, 1.45 and 1.97, respectively (P for trend <0.0001) across the three categories of increasing D-dimer concentration. The association was slightly attenuated, but still highly significant (P for trend 0.0002), after further adjustment for white blood cell count and C-reactive protein. In conclusion, Elevated D-dimer levels were independently associated with increased risk of death from any cause in an apparently healthy adult population.

  2. The effect of statins on microalbuminuria, proteinuria, progression of kidney function, and all-cause mortality in patients with non-end stage chronic kidney disease: A meta-analysis.

    PubMed

    Zhang, Zhenhong; Wu, Pingsheng; Zhang, Jiping; Wang, Shunyin; Zhang, Gengxin

    2016-03-01

    Conclusive evidence regarding the effect of statins on non-end stage chronic kidney disease (CKD) has not been reported previously. This meta-analysis evaluated the association between statins and microalbuminuria, proteinuria, progression, and all-cause mortality in patients with non-end stage CKD. Databases (e.g., PubMed, Embase and the Cochrane Library) were searched for randomized controlled trials (RCTs) with data on statins, microalbuminuria, proteinuria, renal health endpoints, and all-cause mortality patients with non-end stage CKD to perform this meta-analysis. The mean difference (MD) of the urine albumin excretion ratios (UAER), 24-h urine protein excretion, and risk ratios (RR) of all-cause mortality and renal health endpoints were calculated, and the results are presented with 95% confidence intervals (CI). A total of 23 RCTs with 39,419 participants were selected. The analysis demonstrated that statins statistically reduced UAER to 26.73 μg/min [95%CI (-51.04, -2.43), Z=2.16, P<0.05], 24-h urine protein excretion to 682.68 mg [95%CI (-886.72, -478.63), Z=6.56, P<0.01] and decreased all-cause mortality [RR=0.78, 95%CI (0.72, 0.84), Z=6.08, P<0.01]. However, the analysis results did not indicate that statins reduced the events of renal health endpoints [RR=0.96, 95%CI (0.91,1.01), Z=1.40, P>0.05]. In summary, our study indicates that statins statistically reduced microalbuminuria, proteinuria, and clinical deaths, but statins did not effectively slow the clinical progression of non-end stage CKD.

  3. Does oral polio vaccine have non-specific effects on all-cause mortality? Natural experiments within a randomised controlled trial of early measles vaccine

    PubMed Central

    Aaby, Peter; Andersen, Andreas; Martins, Cesário L; Fisker, Ane B; Rodrigues, Amabelia; Whittle, Hilton C; Benn, Christine S

    2016-01-01

    Background BCG and measles vaccine (MV) may have beneficial non-specific effects (NSEs). If an unplanned intervention with a vaccine (a natural experiment) modifies the estimated effect in a randomised controlled trial (RCT), this suggests NSEs. We used this approach to test NSEs of triple oral polio vaccine (OPV). Methods During an RCT of 2 doses of MV at 4.5 and 9 months versus 1 dose of MV at 9 months of age, we experienced 2 natural experiments with OPV. We assessed whether these OPV experiments modified the effect of 2-dose MV in the MV trial. Setting MV RCT conducted in urban Guinea-Bissau 2003–2009. Interventions Natural experiments with OPV due to missing vaccine and the implementation of OPV campaigns. Main outcome measure Changes in the mortality rate ratio (MRR) for 2-dose MV versus 1-dose MV. Results First, the MRR (2-dose/1-dose MV) overall was 0.70 (0.52 to 0.94), but the MRR was 1.04 (0.53 to 2.04) when OPV at birth (OPV0) was not given, suggesting that early priming with OPV was important for the effect of 2-dose MV. The effect of OPV0 depended on age of administration; the MRR (2-dose/1-dose MV) was 0.45 (0.29 to 0.71) for children receiving OPV0 in the first week of life, but 3.63 (0.87 to 15.2) for those receiving OPV0 after the first month of life (p=0.007, test of no interaction). Second, campaign-OPV may have reduced the difference between the randomisation groups since the MRR (2-dose/1-dose MV) was 0.60 (0.42 to 0.85) for children who had not received campaign-OPV before RCT-enrolment versus 0.72 (0.23 to 2.31) and 1.42 (0.70 to 2.90) for children who had received 1 or 2 doses of campaign-OPV-before-enrolment, respectively. Conclusions Bissau had no polio infection during this trial, so OPV0 and campaign-OPV may have NSEs since they modified the effect of 2-dose MV in an RCT. Different interventions may interact to a much larger effect than usually assumed. PMID:28011813

  4. The Impact of Educational Status on 10-Year (2004-2014) Cardiovascular Disease Prognosis and All-cause Mortality Among Acute Coronary Syndrome Patients in the Greek Acute Coronary Syndrome (GREECS) Longitudinal Study

    PubMed Central

    Notara, Venetia; Kogias, Yannis; Stravopodis, Petros; Antonoulas, Antonis; Zombolos, Spyros; Mantas, Yannis; Pitsavos, Christos

    2016-01-01

    Objectives: The association between educational status and 10-year risk for acute coronary syndrome (ACS) and all-cause mortality was evaluated. Methods: From October 2003 to September 2004, 2172 consecutive ACS patients from six Greek hospitals were enrolled. In 2013 to 2014, a 10-year follow-up (2004-2014) assessment was performed for 1918 participants (participation rate, 88%). Each patient’s educational status was classified as low (<9 years of school), intermediate (9 to 14 years), or high (>14 years). Results: Overall all-cause mortality was almost twofold higher in the low-education group than in the intermediate-education and high-education groups (40% vs. 22% and 19%, respectively, p<0.001). Additionally, 10-year recurrent ACS events (fatal and non-fatal) were more common in the low-education group than in the intermediate-education and high-education groups (42% vs. 30% and 35%, p<0.001), and no interactions between sex and education on the investigated outcomes were observed. Moreover, patients in the high-education group were more physically active, had a better financial status, and were less likely to have hypertension, diabetes, or ACS than the participants with the least education (p<0.001); however, when those characteristics and lifestyle habits were accounted for, no moderating effects regarding the relationship of educational status with all-cause mortality and ACS events were observed. Conclusions: A U-shaped association may be proposed for the relationship between ACS prognosis and educational status, with participants in the low-education and high-education groups being negatively affected by other factors (e.g., job stress, depression, or loneliness). Public health policies should be aimed at specific social groups to reduce the overall burden of cardiovascular disease morbidity. PMID:27499164

  5. Matrix-assisted laser desorption/ionisation (MALDI) TOF analysis identifies serum angiotensin II concentrations as a strong predictor of all-cause and breast cancer (BCa)-specific mortality following breast surgery.

    PubMed

    Boccardo, Francesco; Rubagotti, Alessandra; Nuzzo, Pier Vitale; Argellati, Francesca; Savarino, Grazia; Romano, Paolo; Damonte, Gianluca; Rocco, Mattia; Profumo, Aldo

    2015-11-15

    MALDI-TOF MS was used to recognise serum peptidome profiles predictive of mortality in women affected by early BCa. Mortality was analysed based on signal profiling, and appropriate statistics were used. The results indicate that four signals were increased in deceased patients compared with living patients. Three of the four signals were individually associated with all-cause mortality, but only one having mass/charge ratio (m/z) 1,046.49 was associated with BCa-specific mortality and was the only peak to maintain an independent prognostic role after multivariate analysis. Two groups exhibiting different mortality probabilities were identified after clustering patients based on the expression of the four peptides, but m/z 1,046.49 was exclusively expressed in the cluster exhibiting the worst mortality outcome, thus confirming the crucial value of this peptide. The specific role of this peak was confirmed by competing risk analysis. MS findings were validated by ELISA analysis after demonstrating that m/z 1,046.49 structurally corresponded to Angiotensin II (ATII). In fact, mortality results obtained after arbitrarily dividing patients according to an ATII serum value of 255 pg/ml (which corresponds to the 66(th) percentile value) were approximately comparable to those previously demonstrated when the same patients were analysed according to the expression of signal m/z 1,046.49. Similarly, ATII levels were specifically correlated with BCa-related deaths after competing risk analysis. In conclusion, ATII levels were increased in women who exhibited worse mortality outcomes, reinforcing the evidence that this peptide potentially significantly affects the natural history of early BCa. Our findings also confirm that MALDI-TOF MS is an efficient screening tool to identify novel tumour markers and that MS findings can be rapidly validated through less complex techniques, such as ELISA.

  6. Is Impact of Statin Therapy on All-Cause Mortality Different in HIV-Infected Individuals Compared to General Population? Results from the FHDH-ANRS CO4 Cohort

    PubMed Central

    Lang, Sylvie; Lacombe, Jean-Marc; Mary-Krause, Murielle; Partisani, Marialuisa; Bidegain, Frédéric; Cotte, Laurent; Aslangul, Elisabeth; Chéret, Antoine; Boccara, Franck; Meynard, Jean-Luc; Pradier, Christian; Roger, Pierre-Marie; Tattevin, Pierre; Costagliola, Dominique; Molina, Jean-Michel

    2015-01-01

    Background The effect of statins on all-cause mortality in the general population has been estimated as 0.86 (95%CI 0.79-0.94) for primary prevention. Reported values in HIV-infected individuals have been discordant. We assessed the impact of statin-based primary prevention on all-cause mortality among HIV-infected individuals. Methods Patients were selected among controls from a multicentre nested case-control study on the risk of myocardial infarction. Patients with prior cardiovascular or cerebrovascular disorders were not eligible. Potential confounders, including variables that were associated either with statin use and/or death occurrence and statin use were evaluated within the last 3 months prior to inclusion in the case-control study. Using an intention to continue approach, multiple imputation of missing data, Cox’s proportional hazard models or propensity based weighting, the impact of statins on the 7-year all-cause mortality was evaluated. Results Among 1,776 HIV-infected individuals, 138 (8%) were statins users. During a median follow-up of 53 months, 76 deaths occurred, including 6 in statin users. Statin users had more cardiovascular risk factors and a lower CD4 T cell nadir than statin non-users. In univariable analysis, the death rate was higher in statins users (11% vs 7%, HR 1.22, 95%CI 0.53-2.82). The confounders accounted for were age, HIV transmission group, current CD4 T cell count, haemoglobin level, body mass index, smoking status, anti-HCV antibodies positivity, HBs antigen positivity, diabetes and hypertension. In the Cox multivariable model the estimated hazard ratio of statin on all-cause mortality was estimated as 0.86 (95%CI 0.34-2.19) and it was 0.83 (95%CI 0.51-1.35) using inverse probability treatment weights. Conclusion The impact of statin for primary prevention appears similar in HIV-infected individuals and in the general population. PMID:26200661

  7. Association between Highly Active Antiretroviral Therapy and Type of Infectious Respiratory Disease and All-Cause In-Hospital Mortality in Patients with HIV/AIDS: A Case Series

    PubMed Central

    Báez-Saldaña, Renata; Villafuerte-García, Adriana; Cruz-Hervert, Pablo; Delgado-Sánchez, Guadalupe; Ferreyra-Reyes, Leticia; Ferreira-Guerrero, Elizabeth; Mongua-Rodríguez, Norma; Montero-Campos, Rogelio; Melchor-Romero, Ada; García-García, Lourdes

    2015-01-01

    Background Respiratory manifestations of HIV disease differ globally due to differences in current availability of effective highly active antiretroviral therapy (HAART) programs and epidemiology of infectious diseases. Objective To describe the association between HAART and discharge diagnosis and all-cause in-hospital mortality among hospitalized patients with infectious respiratory disease and HIV/AIDS. Material and Methods We retrospectively reviewed the records of patients hospitalized at a specialty hospital for respiratory diseases in Mexico City between January 1st, 2010 and December 31st, 2011. We included patients whose discharge diagnosis included HIV or AIDS and at least one infectious respiratory diagnosis. The information source was the clinical chart. We analyzed the association between HAART for 180 days or more and type of respiratory disease using polytomous logistic regression and all-cause hospital mortality by multiple logistic regressions. Results We studied 308 patients, of whom 206 (66.9%) had been diagnosed with HIV infection before admission to the hospital. The CD4+ lymphocyte median count was 68 cells/mm3 [interquartile range (IQR): 30–150]. Seventy-five (24.4%) cases had received HAART for more than 180 days. Pneumocystis jirovecii pneumonia (PJP) (n = 142), tuberculosis (n = 63), and bacterial community-acquired pneumonia (n = 60) were the most frequent discharge diagnoses. Receiving HAART for more than 180 days was associated with a lower probability of PJP [Adjusted odd ratio (aOR): 0.245, 95% Confidence Interval (CI): 0.08–0.8, p = 0.02], adjusted for sociodemographic and clinical covariates. HAART was independently associated with reduced odds (aOR 0.214, 95% CI 0.06–0.75) of all-cause in-hospital mortality, adjusting for HIV diagnosis previous to hospitalization, age, access to social security, low socioeconomic level, CD4 cell count, viral load, and discharge diagnoses. Conclusions HAART for 180 days or more was associated

  8. Physical activity and all-cause mortality across levels of overall and abdominal adiposity in European men and women: the European Prospective Investigation into Cancer and Nutrition Study (EPIC)123456

    PubMed Central

    Ward, Heather A; Norat, Teresa; Luan, Jian’an; May, Anne M; Weiderpass, Elisabete; Sharp, Stephen J; Overvad, Kim; Østergaard, Jane Nautrup; Tjønneland, Anne; Johnsen, Nina Føns; Mesrine, Sylvie; Fournier, Agnès; Fagherazzi, Guy; Trichopoulou, Antonia; Lagiou, Pagona; Trichopoulos, Dimitrios; Li, Kuanrong; Kaaks, Rudolf; Ferrari, Pietro; Licaj, Idlir; Jenab, Mazda; Bergmann, Manuela; Boeing, Heiner; Palli, Domenico; Sieri, Sabina; Panico, Salvatore; Tumino, Rosario; Vineis, Paolo; Peeters, Petra H; Monnikhof, Evelyn; Bueno-de-Mesquita, H Bas; Quirós, J Ramón; Agudo, Antonio; Sánchez, María-José; Huerta, José María; Ardanaz, Eva; Arriola, Larraitz; Hedblad, Bo; Wirfält, Elisabet; Sund, Malin; Johansson, Mattias; Key, Timothy J; Travis, Ruth C; Khaw, Kay-Tee; Brage, Søren; Wareham, Nicholas J; Riboli, Elio

    2015-01-01

    Background: The higher risk of death resulting from excess adiposity may be attenuated by physical activity (PA). However, the theoretical number of deaths reduced by eliminating physical inactivity compared with overall and abdominal obesity remains unclear. Objective: We examined whether overall and abdominal adiposity modified the association between PA and all-cause mortality and estimated the population attributable fraction (PAF) and the years of life gained for these exposures. Design: This was a cohort study in 334,161 European men and women. The mean follow-up time was 12.4 y, corresponding to 4,154,915 person-years. Height, weight, and waist circumference (WC) were measured in the clinic. PA was assessed with a validated self-report instrument. The combined associations between PA, BMI, and WC with mortality were examined with Cox proportional hazards models, stratified by center and age group, and adjusted for sex, education, smoking, and alcohol intake. Center-specific PAF associated with inactivity, body mass index (BMI; in kg/m2) (>30), and WC (≥102 cm for men, ≥88 cm for women) were calculated and combined in random-effects meta-analysis. Life-tables analyses were used to estimate gains in life expectancy for the exposures. Results: Significant interactions (PA × BMI and PA × WC) were observed, so HRs were estimated within BMI and WC strata. The hazards of all-cause mortality were reduced by 16–30% in moderately inactive individuals compared with those categorized as inactive in different strata of BMI and WC. Avoiding all inactivity would theoretically reduce all-cause mortality by 7.35% (95% CI: 5.88%, 8.83%). Corresponding estimates for avoiding obesity (BMI >30) were 3.66% (95% CI: 2.30%, 5.01%). The estimates for avoiding high WC were similar to those for physical inactivity. Conclusion: The greatest reductions in mortality risk were observed between the 2 lowest activity groups across levels of general and abdominal adiposity, which

  9. Repeated measures of body mass index and C-reactive protein in relation to all-cause mortality and cardiovascular disease: results from the consortium on health and ageing network of cohorts in Europe and the United States (CHANCES).

    PubMed

    O'Doherty, Mark G; Jørgensen, Torben; Borglykke, Anders; Brenner, Hermann; Schöttker, Ben; Wilsgaard, Tom; Siganos, Galatios; Kavousi, Maryam; Hughes, Maria; Müezzinler, Aysel; Holleczek, Bernd; Franco, Oscar H; Hofman, Albert; Boffetta, Paolo; Trichopoulou, Antonia; Kee, Frank

    2014-12-01

    Obesity has been linked with elevated levels of C-reactive protein (CRP), and both have been associated with increased risk of mortality and cardiovascular disease (CVD). Previous studies have used a single 'baseline' measurement and such analyses cannot account for possible changes in these which may lead to a biased estimation of risk. Using four cohorts from CHANCES which had repeated measures in participants 50 years and older, multivariate time-dependent Cox proportional hazards was used to estimate hazard ratios (HR) and 95 % confidence intervals (CI) to examine the relationship between body mass index (BMI) and CRP with all-cause mortality and CVD. Being overweight (≥25-<30 kg/m(2)) or moderately obese (≥30-<35) tended to be associated with a lower risk of mortality compared to normal (≥18.5-<25): ESTHER, HR (95 % CI) 0.69 (0.58-0.82) and 0.78 (0.63-0.97); Rotterdam, 0.86 (0.79-0.94) and 0.80 (0.72-0.89). A similar relationship was found, but only for overweight in Glostrup, HR (95 % CI) 0.88 (0.76-1.02); and moderately obese in Tromsø, HR (95 % CI) 0.79 (0.62-1.01). Associations were not evident between repeated measures of BMI and CVD. Conversely, increasing CRP concentrations, measured on more than one occasion, were associated with an increasing risk of mortality and CVD. Being overweight or moderately obese is associated with a lower risk of mortality, while CRP, independent of BMI, is positively associated with mortality and CVD risk. If inflammation links CRP and BMI, they may participate in distinct/independent pathways. Accounting for independent changes in risk factors over time may be crucial for unveiling their effects on mortality and disease morbidity.

  10. Determinants of all-cause mortality in different age groups in patients with severe systolic left ventricular dysfunction receiving an implantable cardioverter defibrillator (from the Italian ClinicalService Multicenter Observational Project).

    PubMed

    Fumagalli, Stefano; Gasparini, Maurizio; Landolina, Maurizio; Lunati, Maurizio; Boriani, Giuseppe; Proclemer, Alessandro; Santini, Massimo; Mangoni, Lorenza; Padeletti, Margherita; Marchionni, Niccolò; Padeletti, Luigi

    2014-05-15

    Heart failure (HF) is a common condition in elderly patients. Despite great improvements in medical therapy, HF mortality remains high. Implantable cardioverter defibrillator (ICD) significantly lengthens the survival rate of subjects with severe HF, but little evidence exists on its effect in elderly persons. Aim of this study was to compare the age-related determinants of prognosis in a large population of patients with ICD. We divided all patients who underwent an ICD implantation in 117 Italian centers of the "ClinicalService Project" into 3 age groups (<65, 65 to 74, ≥ 75 years), and collected clinical and instrumental variables at baseline and during follow-up (median length: 27 months). Between 2004 and 2011, 6,311 patients were enrolled (5,174 men; left ventricular ejection fraction 29% ± 9%); 1,510 subjects were ≥ 75 years (23.9%; mean age 78 ± 3 years). The prevalence of co-morbidities increased with age. HF was most frequently due to coronary artery disease in the elderly, who also showed the worst New York Heart Association class. At multivariate analysis, older age, coronary artery disease, chronic obstructive pulmonary disease, chronic renal failure, diabetes, complex ventricular arrhythmias, and left ventricular ejection fraction were significant predictors of all-cause mortality. After adjustment, the hazard ratio(age group) for mortality was 22.6% less than at univariate analysis. When groups were analyzed separately, age alone predicted mortality in the oldest. In conclusion, a large proportion of our population was aged ≥ 75 years. Mortality was related to age and several co-morbidities, except for the oldest patients in whom age alone resulted predictive.

  11. Effect of increased convective clearance by on-line hemodiafiltration on all cause and cardiovascular mortality in chronic hemodialysis patients – the Dutch CONvective TRAnsport STudy (CONTRAST): rationale and design of a randomised controlled trial [ISRCTN38365125

    PubMed Central

    Penne, E Lars; Blankestijn, Peter J; Bots, Michiel L; van den Dorpel, Marinus A; Grooteman, Muriel P; Nubé, Menso J; van der Tweel, Ingeborg; ter Wee, Piet M

    2005-01-01

    Background The high incidence of cardiovascular disease in patients with end stage renal disease (ESRD) is related to the accumulation of uremic toxins in the middle and large-middle molecular weight range. As online hemodiafiltration (HDF) removes these molecules more effectively than standard hemodialysis (HD), it has been suggested that online HDF improves survival and cardiovascular outcome. Thus far, no conclusive data of HDF on target organ damage and cardiovascular morbidity and mortality are available. Therefore, the CONvective TRAnsport STudy (CONTRAST) has been initiated. Methods CONTRAST is a Dutch multi-center randomised controlled trial. In this trial, approximately 800 chronic hemodialysis patients will be randomised between online HDF and low-flux HD, and followed for three years. The primary endpoint is all cause mortality. The main secondary outcome variables are fatal and non-fatal cardiovascular events. Conclusion The study is designed to provide conclusive evidence whether online HDF leads to a lower mortality and less cardiovascular events as compared to standard HD. PMID:15907201

  12. Statins decrease all-cause mortality only in CKD patients not requiring dialysis therapy--a meta-analysis of 11 randomized controlled trials involving 21,295 participants.

    PubMed

    Barylski, Marcin; Nikfar, Shekoufeh; Mikhailidis, Dimitri P; Toth, Peter P; Salari, Pooneh; Ray, Kausik K; Pencina, Michael J; Rizzo, Manfredi; Rysz, Jacek; Abdollahi, Mohammad; Nicholls, Stephen J; Banach, Maciej

    2013-06-01

    The available studies have reported the benefits of statins on all-cause and cardiovascular mortality in chronic kidney disease (CKD) patients. However studies in end-stage renal disease patients on dialysis yielded conflicting results. Therefore, we performed a meta-analysis and provide the most reliable trial data to date on the impact of statin therapy on cardiovascular events and death from all causes in CKD patients. Data from PubMed, Web of Science, Cochrane Library, and Scopus for the years 1966 to October 2012 were searched. The final meta-analysis included 11 randomized controlled trials involving 21,295 participants with CKD. Among them 6857 were on dialysis. The use of statins in subjects with non-dialysis-dependent CKD resulted in a marked reduction in death from all causes (relative risk [RR]: 0.66; 95% confidence interval [CI]: 0.55-0.79; p<0.0001), cardiac causes (RR: 0.69; 95%CI: 0.55-0.68; p=0.0012), cardiovascular events (RR: 0.55; 95%CI: 0.4-0.75; p=0.0001) and stroke (RR: 0.66; 95%CI: 0.5-0.88; p=0.0022). The use of statins in dialysis-dependent CKD patients resulted in a non-significant effect on death from all causes (RR: 0.99; 95%CI: 0.88-1.11; p=0.85) and stroke (RR: 1.31; 95%CI: 0.9-1.89; p>0.05), but had the effect of reducing death from cardiac causes (RR: 0.79; 95%CI: 0.64-0.98; p<0.05) and cardiovascular events (RR: 0.81; 95%CI: 0.7-0.94; p<0.05). In conclusion, the use of statins should be indicated in cardiovascular disease prevention especially in patients with non-dialysis-dependent CKD. According to the very limited data the obtained results suggest caution in expecting a reduction in cardiovascular events in patients on dialysis.

  13. Long-term blood pressure variability in patients with rheumatoid arthritis (RA) and its impact on cardiovascular events and all-cause mortality in RA: a population-based comparative cohort study

    PubMed Central

    Myasoedova, Elena; Crowson, Cynthia S.; Green, Abigail B.; Matteson, Eric L.; Gabriel, Sherine E.

    2014-01-01

    Objectives To examine long-term visit-to-visit blood pressure (BP) variability in rheumatoid arthritis (RA) vs non-RA subjects and to assess its impact on cardiovascular events and mortality in RA. Methods Clinic BP measures were collected in a population-based incident cohort of RA patients (1987 ACR criteria met between 1/1/1995 and 1/1/2008) and non-RA subjects. BP variability was defined as within-subject standard deviation (SD) in systolic and diastolic BP. Results Study included 442 RA patients (mean age 55.5 years, 70% females) and 424 non-RA subjects (mean age 55.7 years, 69% females). RA patients had higher visit-to-visit variability in systolic BP (13.8±4.7 mm Hg), than non-RA subjects (13.0±5.2 mm Hg, p=0.004). Systolic BP variability declined after the index date in RA (p<0.001), but not in the non-RA cohort (p=0.73), adjusting for age, sex and calendar year of RA. During the mean follow-up of 7.1 years, 33 cardiovascular events and 57 deaths occurred in RA cohort. Visit-to-visit systolic BP variability was associated with increased risk of cardiovascular events (hazard ratio [HR] per 1 mm Hg increase in BP variability 1.12, 95% confidence interval [CI] 1.01-1.25); diastolic BP variability was associated with all-cause mortality in RA (HR 1.14, 95%CI 1.03-1.27), adjusting for systolic and diastolic BP, body mass index, smoking, diabetes, dyslipidemia, use of antihypertensives. Conclusion Patients with RA had higher visit-to-visit systolic BP variability vs non-RA subjects. There was a significant decline in systolic BP variability after RA incidence. Higher visit-to-visit BP variability was associated with adverse cardiovascular outcomes and all-cause mortality in RA. PMID:24986852

  14. Role of body mass index in the prediction of all cause mortality in over 62,000 men and women. The Italian RIFLE Pooling Project. Risk Factor and Life Expectancy

    PubMed Central

    Seccareccia, F.; Lanti, M.; Menotti, A.; Scanga, M.

    1998-01-01

    STUDY OBJECTIVE: To evaluate the relation of body mass index (BMI) to short-term mortality in a large Italian population sample. DESIGN: Within the Italian RIFLE pooling project, BMI was measured in 47 population samples made of 32,741 men and 30,305 women ages 20-69 years (young 20-44, mature 45-69). Data on mortality were collected for the next six years. MAIN OUTCOME MEASURES: Age adjusted death rates in quintile classes of BMI and Cox proportional hazards models with six year all causes mortality as end point, BMI as covariate and age, smoking, systolic blood pressure as possible confounders were computed. Multivariate analysis was tested in all subjects and after the exclusion of smokers, early (first two years) deaths, and both categories. RESULTS: The univariate analysis failed to demonstrate in all cases a U or inverse J shaped relation. The Cox coefficients for the linear and quadratic terms of BMI proved significant for both young and mature women. The minimum of the curve was located at 27.0 (24.0, 30.0, 95% confidence limits, CL) and 31.8 (25.5, 38.2, 95% CL) units of BMI, for young and mature women respectively. Similar findings were obtained even when exclusion were performed. No relation was found for young men while for mature adult men only the model for all subjects retained significant curvilinear relation (minimum 29.3; 22.4, 36.2, 95% CL). CONCLUSION: These uncommon high values of BMI carrying the minimum risk of death seems to be in contrast with weight guidelines. A confirmation of these findings in other population groups might induce the consideration of changes in the suggested healthy values of BMI.   PMID:9604037

  15. Vitamin D Predicts All-Cause and Cardiac Mortality in Females with Suspected Acute Coronary Syndrome: A Comparison with Brain Natriuretic Peptide and High-Sensitivity C-Reactive Protein

    PubMed Central

    Naesgaard, Patrycja A.; León de la Fuente, Ricardo A.; Nilsen, Stein Tore; Woie, Leik; Aarsland, Torbjoern; Staines, Harry; Nilsen, Dennis W. T.

    2013-01-01

    Vitamin D may not only reflect disease but may also serve as a prognostic indicator. Our aim was to assess the gender-specific utility of vitamin D measured as 25-hydroxy-vitamin D [25(OH)D] to predict all-cause and cardiac death in patients with suspected acute coronary syndrome (ACS) and to compare its prognostic utility to brain natriuretic peptide (BNP) and high-sensitivity C-reactive protein (hsCRP). Blood samples were harvested on admission in 982 patients. Forty percent were women (65.9 ± 12.6 years). Mortality was evaluated in quartiles of 25(OH)D, BNP, and hsCRP, respectively, during a 5-year follow-up, applying univariate and multivariate analyses. One hundred and seventy-three patients died; 78 were women. In 92 patients (37 women), death was defined as cardiac. In women, the univariate hazard ratio (HR) for total death of 25(OH)D in Quartile (Q) 2 versus Q1, Q3 versus Q1, and Q4 versus Q1 was 0.55 (95% CI 0.33–0.93), 0.29 (95% CI 0.15–0.55), and 0.13 (95% CI 0.06–0.32), respectively. In females, it was an independent predictor of total and cardiac death, whereas BNP and hsCRP were less gender-specific. No gender differences in 25(OH)D were noted in a reference material. Accordingly, vitamin D independently predicts mortality in females with suspected ACS. PMID:24349821

  16. Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013

    PubMed Central

    2015-01-01

    Summary Background Up-to-date evidence on levels and trends for age-sex-specific all-cause and cause-specific mortality is essential for the formation of global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013) we estimated yearly deaths for 188 countries between 1990, and 2013. We used the results to assess whether there is epidemiological convergence across countries. Methods We estimated age-sex-specific all-cause mortality using the GBD 2010 methods with some refinements to improve accuracy applied to an updated database of vital registration, survey, and census data. We generally estimated cause of death as in the GBD 2010. Key improvements included the addition of more recent vital registration data for 72 countries, an updated verbal autopsy literature review, two new and detailed data systems for China, and more detail for Mexico, UK, Turkey, and Russia. We improved statistical models for garbage code redistribution. We used six different modelling strategies across the 240 causes; cause of death ensemble modelling (CODEm) was the dominant strategy for causes with sufficient information. Trends for Alzheimer’s disease and other dementias were informed by meta-regression of prevalence studies. For pathogen-specific causes of diarrhoea and lower respiratory infections we used a counterfactual approach. We computed two measures of convergence (inequality) across countries: the average relative difference across all pairs of countries (Gini coefficient) and the average absolute difference across countries. To summarise broad findings, we used multiple decrement life-tables to decompose probabilities of death from birth to exact age 15 years, from exact age 15 years to exact age 50 years, and from exact age 50 years to exact age 75 years, and life expectancy at birth into major causes. For all quantities reported, we computed 95% uncertainty intervals (UIs). We constrained cause-specific fractions within each age

  17. Risk assessment of mortality for all-cause, ischemic heart disease, cardiopulmonary disease, and lung cancer due to the operation of the world's largest coal-fired power plant

    NASA Astrophysics Data System (ADS)

    Kuo, Pei-Hsuan; Tsuang, Ben-Jei; Chen, Chien-Jen; Hu, Suh-Woan; Chiang, Chun-Ju; Tsai, Jeng-Lin; Tang, Mei-Ling; Chen, Guan-Jie; Ku, Kai-Chen

    2014-10-01

    Based on recent understanding of PM2.5 health-related problems from fossil-fueled power plants emission inventories collected in Taiwan, we have determined the loss of life expectancy (LLE) and the lifetime (75-year) risks for PM2.5 health-related mortalities as attributed to the operation of the world's largest coal-fired power plant; the Taichung Power Plant (TCP), with an installed nominal electrical capacity of 5780 MW in 2013. Five plausible scenarios (combinations of emission controls, fuel switch, and relocation) and two risk factors were considered. It is estimated that the lifetime (75-y) risk for all-cause mortality was 0.3%-0.6% for males and 0.2%-0.4% for females, and LLE at 84 days in 1997 for the 23 million residents of Taiwan. The risk has been reduced to one-fourth at 0.05%-0.10% for males and 0.03%-0.06% for females, and LLE at 15 days in 2007, which was mainly attributed to the installation of desulfurization and de-NOx equipment. Moreover, additional improvements can be expected if we can relocate the power plant to a downwind site on Taiwan, and convert the fuel source from coal to natural gas. The risk can be significantly reduced further to one-fiftieth at 0.001%-0.002% for males and 0.001% for females, and LLE at 0.3 days. Nonetheless, it is still an order higher than the commonly accepted elevated-cancer risk at 0.0001% (10-6), indicating that the PM2.5 health-related risk for operating such a world-class power plant is not negligible. In addition, this study finds that a better-chosen site (involving moving the plant to the leeward side of Taiwan) can reduce the risk significantly as opposed to solely transitioning the fuel source to natural gas. Note that the fuel cost of using natural gas (0.11 USD/kWh in 2013) in Taiwan is about twice the price of using coal fuel (0.05 USD/kWh in 2013).

  18. Prognostic Contribution of Exercise Capacity, Heart Rate Recovery, Chronotropic Incompetence, and Myocardial Perfusion Single-Photon Emission Computerized Tomography in the Prediction of Cardiac Death and All-Cause Mortality.

    PubMed

    Arbit, Boris; Azarbal, Babak; Hayes, Sean W; Gransar, Heidi; Germano, Guido; Friedman, John D; Thomson, Louise; Berman, Daniel S

    2015-12-01

    Chronotropic incompetence, measured by the percentage (%) of heart rate (HR) reserve achieved (%HR reserve), abnormal HR recovery, reduced exercise capacity (EC), and myocardial perfusion single-photon emission computerized tomography (SPECT MPS) abnormalities are known predictors of all-cause mortality (ACM) and cardiac death (CD). The aim of this study was to determine if EC, %HR reserve, and HR recovery add incremental value to MPS in the prediction of ACM and CD. A total of 11,218 patients without valvular disease and not on β blockers underwent symptom-limited exercise MPS. %HR reserve was (peak HR - rest HR)/(220 - age - rest HR) × 100, with %HR reserve <80 defined as low. HR recovery was peak HR - recovery HR. An HR recovery <22 beats/min at 2 minutes after peak exercise was considered abnormal. Poor EC was defined as exercise duration ≤6 minutes (7 metabolic equivalents). Summed stress scores (SSSs) were calculated using a 20-segment, 5-point MPS model. Statistical analysis was performed using Cox regression models. There were 445 deaths (148 CD) during a mean follow-up of 3.2 ± 2.5 years. In multivariate analysis, the independent predictors of ACM were age, χ(2) = 154.81; EC, χ(2) = 74.00; SSS, χ(2) = 32.99; %HR reserve, χ(2) = 24.74; abnormal electrocardiogram at rest, χ(2) = 23.13; HR recovery, χ(2) = 18.45; diabetes, χ(2) = 17.75; and previous coronary artery disease, χ(2) = 11.85 (p ≤0.0006). The independent predictors of CD were SSS, χ(2) = 54.25; EC, χ(2) = 49.34; age, χ(2) = 46.45; abnormal electrocardiogram at rest, χ(2) = 30.60; previous coronary artery disease, χ(2) = 20.69; Duke treadmill score, χ(2) = 19.50; %HR reserve, χ(2) = 11.43; diabetes, χ(2) = 10.23 (all p ≤0.0014); and HR recovery, χ(2) = 5.30 (p = 0.0214). The exercise variables showed increases in Harrell's C static and net improvement reclassification, with EC showing the strongest incremental improvement in predicting ACM and CD (respective C-index 76

  19. B-type natriuretic peptide and high sensitive C-reactive protein predict 2-year all cause mortality in chest pain patients: a prospective observational study from Salta, Argentina

    PubMed Central

    2011-01-01

    Background Several mechanisms are involved in the pathophysiology of the Acute Coronary Syndrome (ACS). We have addressed whether B-type natriuretic peptide (BNP) and high-sensitive C-reactive protein (hsCRP) in admission samples may improve risk stratification in chest pain patients with suspected ACS. Methods We included 982 patients consecutively admitted with chest pain and suspected ACS at nine hospitals in Salta, Northern Argentina. Total and cardiac mortality were recorded during a 2-year follow up period. Patients were divided into quartiles according to BNP and hsCRP levels, respectively, and inter quartile differences in mortality were statistically evaluated applying univariate and multivariate analyses. Results 119 patients died, and the BNP and hsCRP levels were significantly higher among these patients than in survivors. In a multivariable Cox regression model for total death and cardiac death in all patients, the hazard ratio (HR) in the highest quartile (Q4) as compared to the lowest quartile (Q1) of BNP was 2.32 (95% confidence interval (CI), 1.24-4.35), p = 0.009 and 3.34 (95% CI, 1.26-8.85), p = 0.015, respectively. In the TnT positive patients (TnT > 0.01 ng/mL), the HR for total death and cardiac death in Q4 as compared to Q1 was 2.12 (95% CI, 1.07-4.18), p = 0.031 and 3.42 (95% CI, 1.13-10.32), p = 0.029, respectively. The HR for total death for hsCRP in Q4 as compared to Q1 was 1.97 (95% CI, 1.17-3.32), p = 0.011, but this biomarker did not predict cardiac death (p = 0.21). No prognostic impact of these two biomarkers was found in the TnT negative patients. Conclusion BNP and hsCRP may act as clinically useful biomarkers when obtained at admission in a population with suspected ACS. Trial Registration ClinicalTrials.gov Identifier: NCT01377402. PMID:21958326

  20. Why do thin people have elevated all-cause mortality? Evidence on confounding and reverse causality in the association of adiposity and COPD from the British Women's Heart and Health Study.

    PubMed

    Dale, Caroline; Nüesch, Eveline; Prieto-Merino, David; Choi, Minkyoung; Amuzu, Antoinette; Ebrahim, Shah; Casas, Juan P; Davey-Smith, George

    2015-01-01

    Low adiposity has been linked to elevated mortality from several causes including respiratory disease. However, this could arise from confounding or reverse causality. We explore the association between two measures of adiposity (BMI and WHR) with COPD in the British Women's Heart and Health Study including a detailed assessment of the potential for confounding and reverse causality for each adiposity measure. Low BMI was found to be associated with increased COPD risk while low WHR was not (OR = 2.2; 95% CI 1.3-3.1 versus OR = 1.2; 95% CI 0.7-1.6). Potential confounding variables (e.g. smoking) and markers of ill-health (e.g. unintentional weight loss) were found to be higher in low BMI but not in low WHR. Women with low BMI have a detrimental profile across a broad range of health markers compared to women with low WHR, and women with low WHR do not appear to have an elevated COPD risk, lending support to the hypothesis that WHR is a less confounded measure of adiposity than BMI. Low adiposity does not in itself appear to increase the risk of respiratory disease, and the apparent adverse consequences of low BMI may be due to reverse causation and confounding.

  1. Impact of a combined community and primary care prevention strategy on all-cause and cardiovascular mortality: a cohort analysis based on 1 million person-years of follow-up in Västerbotten County, Sweden, during 1990–2006

    PubMed Central

    Blomstedt, Yulia; Norberg, Margareta; Stenlund, Hans; Nyström, Lennarth; Lönnberg, Göran; Boman, Kurt; Wall, Stig; Weinehall, Lars

    2015-01-01

    Objective To evaluate the impact of the Västerbotten Intervention Programme (VIP) by comparing all eligible individuals (target group impact) according to the intention-to-treat principle and VIP participants with the general Swedish population. Design Dynamic cohort study. Setting/participants All individuals aged 40, 50 or 60 years, residing in Västerbotten County, Sweden, between 1990 and 2006 (N=101 918) were followed from their first opportunity to participate in the VIP until age 75, study end point or prior death. Intervention The VIP is a systematic, long-term, county-wide cardiovascular disease (CVD) intervention that is performed within the primary healthcare setting and combines individual and population approaches. The core component is a health dialogue based on a physical examination and a comprehensive questionnaire at the ages of 40, 50 and 60 years. Primary outcomes All-cause and CVD mortality. Results For the target group, there were 5646 deaths observed over 1 054 607 person-years. Compared to Sweden at large, the standardised all-cause mortality ratio was 90.6% (95% CI 88.2% to 93.0%): for women 87.9% (95% CI 84.1% to 91.7%) and for men 92.2% (95% CI 89.2% to 95.3%). For CVD, the ratio was 95.0% (95% CI 90.7% to 99.4%): for women 90.4% (95% CI 82.6% to 98.7%) and for men 96.8% (95% CI 91.7 to 102.0). For participants, subject to further impact as well as selection, when compared to Sweden at large, the standardised all-cause mortality ratio was 66.3% (95% CI 63.7% to 69.0%), whereas the CVD ratio was 68.9% (95% CI 64.2% to 73.9%). For the target group as well as for the participants, standardised mortality ratios for all-cause mortality were reduced within all educational strata. Conclusions The study suggests that the VIP model of CVD prevention is able to impact on all-cause and cardiovascular mortality when evaluated according to the intention-to-treat principle. PMID:26685034

  2. Biochemical observation during 28 days of space flight

    NASA Technical Reports Server (NTRS)

    Leach, C. S.; Kambaut, P. C.

    1975-01-01

    With the completion of the 28-day flight of Skylab 2, the sum of biochemical data on human reaction to the weightless environment was significantly extended both quantitatively and qualitatively. The biochemical studies were divided into two broad categories. One group included the more routine blood studies similar to those used in everyday medical practice. The second category encompassed those analyses used to investigate more thoroughly the endocrinological and fluid changes first seen in the crewmembers following the Gemini, Apollo, and Soviet missions. Significant biochemical changes were observed that varied in magnitude and direction, but all disappeared shortly after return to earth. Most of changes indicate successful adaptation by the body to the combined stresses of weightlessness. Results of the biochemical observation are presented in the form of data tables and graphs.

  3. All-cause mortality benefit of coronary revascularization vs. medical therapy in patients without known coronary artery disease undergoing coronary computed tomographic angiography: results from CONFIRM (COronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter Registry)

    PubMed Central

    Min, James K.; Berman, Daniel S.; Dunning, Allison; Achenbach, Stephan; Al-Mallah, Mouaz; Budoff, Matthew J.; Cademartiri, Filippo; Callister, Tracy Q.; Chang, Hyuk-Jae; Cheng, Victor; Chinnaiyan, Kavitha; Chow, Benjamin J.W.; Cury, Ricardo; Delago, Augustin; Feuchtner, Gudrun; Hadamitzky, Martin; Hausleiter, Joerg; Kaufmann, Philipp; Karlsberg, Ronald P.; Kim, Yong-Jin; Leipsic, Jonathon; Lin, Fay Y.; Maffei, Erica; Plank, Fabian; Raff, Gilbert; Villines, Todd; Labounty, Troy M.; Shaw, Leslee J.

    2012-01-01

    Aims To date, the therapeutic benefit of revascularization vs. medical therapy for stable individuals undergoing invasive coronary angiography (ICA) based upon coronary computed tomographic angiography (CCTA) findings has not been examined. Methods and results We examined 15 223 patients without known coronary artery disease (CAD) undergoing CCTA from eight sites and six countries who were followed for median 2.1 years (interquartile range 1.4–3.3 years) for an endpoint of all-cause mortality. Obstructive CAD by CCTA was defined as a ≥50% luminal diameter stenosis in a major coronary artery. Patients were categorized as having high-risk CAD vs. non-high-risk CAD, with the former including patients with at least obstructive two-vessel CAD with proximal left anterior descending artery involvement, three-vessel CAD, and left main CAD. Death occurred in 185 (1.2%) patients. Patients were categorized into two treatment groups: revascularization (n = 1103; 2.2% mortality) and medical therapy (n = 14 120, 1.1% mortality). To account for non-randomized referral to revascularization, we created a propensity score developed by logistic regression to identify variables that influenced the decision to refer to revascularization. Within this model (C index 0.92, χ2 = 1248, P < 0.0001), obstructive CAD was the most influential factor for referral, followed by an interaction of obstructive CAD with pre-test likelihood of CAD (P = 0.0344). Within CCTA CAD groups, rates of revascularization increased from 3.8% for non-high-risk CAD to 51.2% high-risk CAD. In multivariable models, when compared with medical therapy, revascularization was associated with a survival advantage for patients with high-risk CAD [hazards ratio (HR) 0.38, 95% confidence interval 0.18–0.83], with no difference in survival for patients with non-high-risk CAD (HR 3.24, 95% CI 0.76–13.89) (P-value for interaction = 0.03). Conclusion In an intermediate-term follow-up, coronary revascularization is

  4. Utility of models to predict 28-day or 30-day unplanned hospital readmissions: an updated systematic review

    PubMed Central

    Zhou, Huaqiong; Della, Phillip R; Roberts, Pamela; Goh, Louise; Dhaliwal, Satvinder S

    2016-01-01

    Objective To update previous systematic review of predictive models for 28-day or 30-day unplanned hospital readmissions. Design Systematic review. Setting/data source CINAHL, Embase, MEDLINE from 2011 to 2015. Participants All studies of 28-day and 30-day readmission predictive model. Outcome measures Characteristics of the included studies, performance of the identified predictive models and key predictive variables included in the models. Results Of 7310 records, a total of 60 studies with 73 unique predictive models met the inclusion criteria. The utilisation outcome of the models included all-cause readmissions, cardiovascular disease including pneumonia, medical conditions, surgical conditions and mental health condition-related readmissions. Overall, a wide-range C-statistic was reported in 56/60 studies (0.21–0.88). 11 of 13 predictive models for medical condition-related readmissions were found to have consistent moderate discrimination ability (C-statistic ≥0.7). Only two models were designed for the potentially preventable/avoidable readmissions and had C-statistic >0.8. The variables ‘comorbidities’, ‘length of stay’ and ‘previous admissions’ were frequently cited across 73 models. The variables ‘laboratory tests’ and ‘medication’ had more weight in the models for cardiovascular disease and medical condition-related readmissions. Conclusions The predictive models which focused on general medical condition-related unplanned hospital readmissions reported moderate discriminative ability. Two models for potentially preventable/avoidable readmissions showed high discriminative ability. This updated systematic review, however, found inconsistent performance across the included unique 73 risk predictive models. It is critical to define clearly the utilisation outcomes and the type of accessible data source before the selection of the predictive model. Rigorous validation of the predictive models with moderate-to-high discriminative

  5. Evaluation of Genotoxicity and 28-day Oral Dose Toxicity on Freeze-dried Powder of Tenebrio molitor Larvae (Yellow Mealworm).

    PubMed

    Han, So-Ri; Yun, Eun-Young; Kim, Ji-Young; Hwang, Jae Sam; Jeong, Eun Ju; Moon, Kyoung-Sik

    2014-06-01

    The larval form of Tenebrio molitor (T. molitor) has been eaten in many countries and provides benefits as a new food source of protein for humans. However, no information exists regarding its safety for humans. The objective of the present study was to evaluate the genotoxicity and repeated dose oral toxicity of the freeze-dried powder of T. molitor larvae. The genotoxic potential was evaluated by a standard battery testing: bacterial reverse mutation test, in vitro chromosome aberration test, and in vivo micronucleus test. To assess the repeated dose toxicity, the powder was administered once daily by oral gavage to Sprague-Dawley (SD) rats at dose levels of 0, 300, 1000 and 3000 mg/kg/day for 28 days. The parameters which were applied to the study were mortality, clinical signs, body and organ weights, food consumption, ophthalmology, urinalysis, hematology, serum chemistry, gross findings and histopathologic examination. The freezedried powder of T. molitor larvae was not mutagenic or clastogenic based on results of in vitro and in vivo genotoxicity assays. Furthermore, no treatment-related changes or findings were observed in any parameters in rats after 28 days oral administration. In conclusion, the freeze-dried powder of T. molitor larvae was considered to be non-genotoxic and the NOAEL (No Observed Adverse Effect Level) was determined to be 3000 mg/kg/day in both sexes of SD rats under our experimental conditions.

  6. Evaluation of Genotoxicity and 28-day Oral Dose Toxicity on Freeze-dried Powder of Tenebrio molitor Larvae (Yellow Mealworm)

    PubMed Central

    Han, So-Ri; Yun, Eun-Young; Kim, Ji-Young; Hwang, Jae Sam; Jeong, Eun Ju

    2014-01-01

    The larval form of Tenebrio molitor (T. molitor) has been eaten in many countries and provides benefits as a new food source of protein for humans. However, no information exists regarding its safety for humans. The objective of the present study was to evaluate the genotoxicity and repeated dose oral toxicity of the freeze-dried powder of T. molitor larvae. The genotoxic potential was evaluated by a standard battery testing: bacterial reverse mutation test, in vitro chromosome aberration test, and in vivo micronucleus test. To assess the repeated dose toxicity, the powder was administered once daily by oral gavage to Sprague-Dawley (SD) rats at dose levels of 0, 300, 1000 and 3000 mg/kg/day for 28 days. The parameters which were applied to the study were mortality, clinical signs, body and organ weights, food consumption, ophthalmology, urinalysis, hematology, serum chemistry, gross findings and histopathologic examination. The freezedried powder of T. molitor larvae was not mutagenic or clastogenic based on results of in vitro and in vivo genotoxicity assays. Furthermore, no treatment-related changes or findings were observed in any parameters in rats after 28 days oral administration. In conclusion, the freeze-dried powder of T. molitor larvae was considered to be non-genotoxic and the NOAEL (No Observed Adverse Effect Level) was determined to be 3000 mg/kg/day in both sexes of SD rats under our experimental conditions. PMID:25071922

  7. Acute, 28days sub acute and genotoxic profiling of Quercetin-Magnesium complex in Swiss albino mice.

    PubMed

    Ghosh, Nilanjan; Sandur, Rajendra; Ghosh, Deepanwita; Roy, Souvik; Janadri, Suresh

    2017-02-01

    Quercetin-Magnesium complex is one of the youngest alkaline rare earth metal (Magnesium) complexes with flavonoids (Quercetin) in organo-metalic family. Earlier studies describe the details of the complex formation, characterization and antioxidant study of the complex but toxicity profile is still under darkness. The present study was taken up to investigate the oral acute toxicity, 28days repeated oral sub-acute toxicity study and genotoxicity study of Quercetin-Magnesium complex in Swiss albino mice. Quercetin-Magnesium complex showed mortality at a dose of 185mg/kg in the Swiss albino mice. In 28days repeated oral toxicity study, Quercetin-Magnesium complex was administered to both sex of Swiss albino mice at dose levels of 150, 130 and 100mg/kg body weight respectively. Where 150mg/kg dose shows increased levels of white blood cells and changes in total protein, serum creatinine and blood urea nitrogen. Histopathological study of Quercetin-Magnesium complex shows minor structural alteration in kidney at 150mg/kg dose. No observed toxic level found in 130mg/kg or below doses. No genotoxic effect found in any doses of the complex. Therefore 130mg/kg or below dose level could be better for further study.

  8. 28-Day emergency surgical re-admission rates as a clinical indicator of performance.

    PubMed Central

    Courtney, Edward D. J.; Ankrett, Sarah; McCollum, Peter T.

    2003-01-01

    With the introduction of clinical governance, the NHS Executive has identified 28-day emergency re-admission rates as a clinical indicator to be used to assess and compare performance between NHS trusts. We undertook a 3-month retrospective audit of patients identified from the trust computer as having been re-admitted as an emergency within 28 days of discharge from the general surgical division. We wanted to examine reasons for re-admission, possible errors in coding and any preventable factors in these patients subsequently re-admitted acutely. PMID:12648333

  9. The Return Home: Transitioning from a 28-Day Remote Outdoor Education Programme

    ERIC Educational Resources Information Center

    McNatty, Shannon

    2016-01-01

    This article addresses the challenges for students transitioning from the remote Te Kahu (pseudonym) outdoor education programme back into their home and school city environments. Students must develop methods of coping and readjust to society to continue the personal growth and process the learning affected through the 28-day programme. The…

  10. Red blood cell distribution width is an independent predictor of mortality in patients with gram-negative bacteremia.

    PubMed

    Ku, Nam Su; Kim, Hye-Won; Oh, Hyung Jung; Kim, Yong Chan; Kim, Min Hyung; Song, Je Eun; Oh, Dong Hyun; Ahn, Jin Young; Kim, Sun Bean; Jeong, Su Jin; Han, Sang Hoon; Kim, Chang Oh; Song, Young Goo; Kim, June Myung; Choi, Jun Yong

    2012-08-01

    Red blood cell distribution width (RDW) is known to be a predictor of severe morbidity and mortality in some chronic diseases such as congestive heart failure. However, to our knowledge, little is known about RDW as a predictor of mortality in patients with Gram-negative bacteremia, a major nosocomial cause of intra-abdominal infections, urinary tract infections, and primary bacteremia. Therefore, we investigated whether RDW is an independent predictor of mortality in patients with Gram-negative bacteremia. Clinical characteristics, laboratory parameters, and outcomes of 161 patients with Gram-negative bacteremia from November 2010 to March 2011 diagnosed at Severance Hospital, Yonsei University College of Medicine, Seoul, Korea, were retrospectively analyzed. The main outcome measure was 28-day all-cause mortality. The 28-day mortality rate was significantly higher in the increased RDW group compared with the normal RDW group (P < 0.001). According to multivariate Cox proportional hazard analysis, RDW levels at the onset of bacteremia (per 1% increase, P = 0.036), the Charlson index (per 1-point increase, P < 0.001), and the Sequential Organ Failure Assessment score (per 1-point increase, P = 0.001) were independent risk factors for 28-day mortality. Moreover, the nonsurvivor group had significantly higher RDW levels 72 h after the onset of bacteremia than did the survivor group (P = 0.001). In addition, the area under the curve of RDW at the onset of bacteremia, the 72-h RDW, and the Sequential Organ Failure Assessment score for 28-day mortality were 0.764 (P = 0.001), 0.802 (P < 0.001), and 0.703 (P = 0.008), respectively. Red blood cell distribution width at the onset of bacteremia was an independent predictor of mortality in patients with Gram-negative bacteremia. Also, 72-h RDW could be a predictor for all-cause mortality in patients with Gram-negative bacteremia.

  11. Acute toxicity and the 28-day repeated dose study of a Siddha medicine Nuna Kadugu in rats

    PubMed Central

    2012-01-01

    Background Nuna Kadugu (NK), a Siddha medicine prepared from leaves and fruits of Morinda Pubescens, used for the treatment of various skin diseases. Though NK has been widely used for several decades, no scientific report was available on its safety. Present study was undertaken to demonstrate the oral toxicity of NK in Sprague Dawley rats. Methods Acute and 28-day repeated oral toxicity studies were performed following OECD test guidelines 423 and 407, respectively, with minor modifications. In acute oral toxicity study, NK was administered at 2000mg/kg b.wt., p.o and animals were observed for toxic signs at 0, 0.5, 1, 4, 24 h and for next 14 days. Gross pathology was performed at the end of the study. In repeated dose, the 28- day oral toxicity study, NK was administered at 300, 600 and 900 mg/kg b.wt./p.o/day. Two satellite groups (control and high dose) were also maintained to determine the delayed onset toxicity of NK. Animals were observed for mortality, morbidity, body weight changes, feed and water intake. Haematology, clinical biochemistry, electrolytes, gross pathology, relative organ weight and histopathological examination were performed. Results In acute toxicity study, no treatment related death or toxic signs were observed with NK administration. In the repeated dose study, no significant differences in body weight changes, food / water intake, haematology, clinical biochemistry and electrolytes content were observed between control and NK groups. No gross pathological findings and difference in relative organ weights were observed between control and NK treated rats. Histopathological examination revealed no abnormalities with NK treatment. Conclusion Acute study reveals that the LD50 of NK is greater than 2000mg/kg, b.wt. in fasted female rats and can be classified as Category 5. 28-day repeated oral toxicity demonstrates that the No Observed Adverse Effect Level of NK is greater than 900 mg/kg b.wt./day, p.o in rats. There were no delayed effects

  12. Pulmonary function and pathology in cats exposed 28 days to diesel exhaust

    SciTech Connect

    Pepelko, W.E.; Mattox, J.K.; Yang, Y.Y.; Moore, W. Jr.

    1980-09-01

    Young adult male cats were exposed 28 days, 20 hrs per day, to a 1:14 dilution of diesel exhaust emissions. Following termination of exposure, the following pulmonary function measurements were carried out: lung volumes, maximum expiratory flow rates (MEF), MEF at 50%, 25% and 10% of vital capacity (VC): forced expiratory volume (FEV) after 0.2, 0.3 and 0.4 sec, dynamic compliance, resistance and helium washout at 25, 50, 75, and 100 breaths per min. The only significant functional change was a decrease in MEF at 10% of VC (P x .02). The lungs of the exposed cats appeared charcoal grey with frequent focal black spots visible on the pleural surface. Pathologic changes in the exposed cats included a predominantly peribronchiolar localization of black-pigmented macrophages within the alveoli producing a focal pneumonitis or alveolitis. In general, evidence of serious lung damage was not observed following the 28-day exposure period.

  13. Mortality Risk Factors for Patients with Septic Shock after Implementation of the Surviving Sepsis Campaign Bundles

    PubMed Central

    Kim, Moo Hyun; Jeong, Woo Yong; Jung, In Young; Oh, Dong Hyun; Kim, Yong Chan; Kim, Eun Jin; Jeong, Su Jin; Ku, Nam Su; Kim, June Myung

    2016-01-01

    Background Septic shock remains a leading cause of death, despite advances in critical care management. The Surviving Sepsis Campaign (SSC) has reduced morbidity and mortality. This study evaluated risk factors for mortality in patients with septic shock who received treatment following the SSC bundles. Materials and Methods This retrospective cohort study included patients with septic shock who received treatments following SSC bundles in an urban emergency department between November 2007 and November 2011. Primary and secondary endpoints were all-cause 7- and 28-day mortality. Results Among 436 patients, 7- and 28-day mortality rates were 7.11% (31/436) and 14% (61/436), respectively. In multivariate analysis, high lactate level (odds ratio [OR], 1.286; 95% confidence interval [CI], 1.016–1.627; P=0.036) and low estimated glomerular filtration rate (OR, 0.953; 95% CI, 0.913–0.996; P=0.032) were independent risk factors for 7-day mortality. Risk factors for 28-day mortality were high lactate level (OR, 1.346; 95% CI, 1.083–1.673; P=0.008) and high Acute Physiology and Chronic Health Evaluation II score (OR, 1.153; 95% CI, 1.029–1.293; P=0.014). Conclusion The risk of mortality of septic shock patients remains high in patients with high lactate levels and acute kidney injury. PMID:27659434

  14. Mineral and nitrogen balance study - Results of metabolic observations on Skylab II 28-day orbital mission

    NASA Technical Reports Server (NTRS)

    Whedon, G. D.; Lutwak, L.; Reid, J.; Rambaut, P.; Whittle, M.; Smith, M.; Leach, C.

    1975-01-01

    The prediction that various stresses of flight, particularly weightlessness, would bring about significant derangements in the metabolism of the musculoskeletal system has been based on various balance-study observations of long-term immobilized or inactive bed rest. The three astronauts of Skylab II consumed a planned dietary intake of major metabolic elements in mixed foods and beverages and provided virtually complete collections of excreta for 31 days preflight, 28 days inflight, and 17 days postflight. Analyses showed that, in varying degree among the crewmen, urinary calcium increased gradually during flight in a pattern similar to that observed in bed-rest studies. Fecal calcium excretion did not change significantly, but calcium balance, owing to the urinary calcium rise, became either negative or less positive than in preflight measurement. Increased excretion and negative nitrogen and phosphorus balances inflight indicated appreciable loss of muscle tissue in all three crewmen. Significant losses also occurred inflight in potassium, sodium, and magnesium. Based on the similarity in pattern and degree between these observations of calcium, phosphorus, and nitrogen loss, musculoskeletal integrity would not be threatened in space flights of up to at least 3 months. However, if similar changes occur in the planed Skylab flights for considerably more than 28 days, concern for capable musculoskeletal function should be serious for flights of very many months' duration.

  15. Coenzyme Q10 Abrogated the 28 Days Aluminium Chloride Induced Oxidative Changes in Rat Cerebral Cortex

    PubMed Central

    Majumdar, Anuradha S.; Nirwane, Abhijit; Kamble, Rahul

    2014-01-01

    Objective: The present study was designed to elucidate the impact of oral administration of aluminium chloride for 28 days with respect to oxidative stress in the cerebral cortex of female rats. Further, to investigate the potentials of Coenzyme (Co) Q10 (4, 8, and 12 mg/kg, i.p.) in mitigating the detrimental changes. Materials and Methods: Biochemical estimations of cerebral lipid peroxidation (LPO), reduced glutathione (GSH), vitamin E and activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were carried out after 28 days of aluminium chloride (AlCl3) and Co Q10 exposures along with histopathological examination of cerebral cortex of the rats. Results: Subacute exposure to AlCl3(5 mg/kg) led to significant decrease in levels of GSH, vitamin E and activities of SOD, CAT, GPx, and an increase in LPO of cerebral cortex. These aberrations were restored by Co Q10 (12 mg/kg, i.p.). This protection offered was comparable to that of L-deprenyl (1 mg/kg, i.p.) which served as a reference standard. Histopathological evaluations confirmed that the normal cerebral morphology was maintained by Co Q10. Conclusion: Thus, AlCl3 exposure hampers the activities of various antioxidant enzymes and induces oxidative stress in cerebral cortex of female Wistar rats. Supplementation with intraperitoneal Co Q10 abrogated these deleterious effects of AlCl3. PMID:25253934

  16. Consuming a multi-ingredient thermogenic supplement for 28 days is apparently safe in healthy adults

    PubMed Central

    Vogel, Roxanne M.; Joy, Jordan M.; Falcone, Paul H.; Mosman, Matt M.; Kim, Michael P.; Moon, Jordan R.

    2015-01-01

    Background Thermogenic (TRM) supplements are often used by people seeking to decrease body weight. Many TRM supplements are formulated with multiple ingredients purported to increase energy expenditure and maximize fat loss. However, in the past some TRM ingredients have been deemed unsafe and removed from the market. Therefore, it is important to verify the safety of multi-ingredient TRM supplements with chronic consumption. Objective To assess the safety of daily consumption of a multi-ingredient TRM supplement over a 28-day period in healthy adults. Design Twenty-three recreationally active adults (11M, 12F; 27.1±5.4 years, 171.6±9.6 cm, 76.8±16.1 kg, 26±5 BMI) were randomly assigned either to consume a multi-ingredient TRM supplement (SUP; n=9) or remain unsupplemented (CRL; n=14) for 28 days. Participants maintained their habitual dietary and exercise routines for the duration of the study. Fasting blood samples, resting blood pressure, and heart rate were taken before and after the supplementation period. Samples were analyzed for complete blood counts, comprehensive metabolic, and lipid panels. Results Significant (p<0.05) group by time interactions were present for diastolic BP, creatinine, estimated glomerular filtration rate (eGFR), chloride, CO2, globulin, albumin:globulin (A/G), and high-density lipoprotein (HDL). Dependent t-tests conducted on significant variables revealed significant (p<0.05) within-group differences in SUP for diastolic BP (+6.2±5.3 mmHG), creatinine (+0.09±0.05 mg/dL), eGFR (−11.2±5.8 mL/min/1.73), globulin (−0.29±0.24 g/dL), A/G (+0.27±0.23), and HDL (−5.0±5.5 mg/dL), and in CRL for CO2 (−1.9±1.5 mmol/L) between time points. Each variable remained within the accepted physiological range. Conclusion Results of the present study support the clinical safety of a multi-ingredient TRM containing caffeine, green tea extract, and cayenne powder. Although there were statistically significant (p<0.05) intragroup

  17. A microfluidic culture model of the human reproductive tract and 28-day menstrual cycle

    PubMed Central

    Xiao, Shuo; Coppeta, Jonathan R.; Rogers, Hunter B.; Isenberg, Brett C.; Zhu, Jie; Olalekan, Susan A.; McKinnon, Kelly E.; Dokic, Danijela; Rashedi, Alexandra S.; Haisenleder, Daniel J.; Malpani, Saurabh S.; Arnold-Murray, Chanel A.; Chen, Kuanwei; Jiang, Mingyang; Bai, Lu; Nguyen, Catherine T.; Zhang, Jiyang; Laronda, Monica M.; Hope, Thomas J.; Maniar, Kruti P.; Pavone, Mary Ellen; Avram, Michael J.; Sefton, Elizabeth C.; Getsios, Spiro; Burdette, Joanna E.; Kim, J. Julie; Borenstein, Jeffrey T.; Woodruff, Teresa K.

    2017-01-01

    The endocrine system dynamically controls tissue differentiation and homeostasis, but has not been studied using dynamic tissue culture paradigms. Here we show that a microfluidic system supports murine ovarian follicles to produce the human 28-day menstrual cycle hormone profile, which controls human female reproductive tract and peripheral tissue dynamics in single, dual and multiple unit microfluidic platforms (Solo-MFP, Duet-MFP and Quintet-MPF, respectively). These systems simulate the in vivo female reproductive tract and the endocrine loops between organ modules for the ovary, fallopian tube, uterus, cervix and liver, with a sustained circulating flow between all tissues. The reproductive tract tissues and peripheral organs integrated into a microfluidic platform, termed EVATAR, represents a powerful new in vitro tool that allows organ–organ integration of hormonal signalling as a phenocopy of menstrual cycle and pregnancy-like endocrine loops and has great potential to be used in drug discovery and toxicology studies. PMID:28350383

  18. Physiological effects following administration of Citrus aurantium for 28 days in rats

    SciTech Connect

    Hansen, Deborah K.; Pellicore, Linda S.

    2012-06-15

    Background: Since ephedra-containing dietary supplements were banned from the US market, manufacturers changed their formulations by eliminating ephedra and replacing with other botanicals, including Citrus aurantium, or bitter orange. Bitter orange contains, among other compounds, synephrine, a chemical that is chemically similar to ephedrine. Since ephedrine may have cardiovascular effects, the goal of this study was to investigate the cardiovascular effects of various doses of bitter orange extract and pure synephrine in rats. Method: Female Sprague–Dawley rats were dosed daily by gavage for 28 days with synephrine from two different extracts. One extract contained 6% synephrine, and the other extract contained 95% synephrine. Doses were 10 or 50 mg synephrine/kg body weight from each extract. Additionally, caffeine was added to these doses, since many dietary supplements also contain caffeine. Telemetry was utilized to monitor heart rate, blood pressure, body temperature and QT interval in all rats. Results and conclusion: Synephrine, either as the bitter orange extract or as pure synephrine, increased heart rate and blood pressure. Animals treated with 95% synephrine showed minimal effects on heart rate and blood pressure; more significant effects were observed with the bitter orange extract suggesting that other components in the botanical can alter these physiological parameters. The increases in heart rate and blood pressure were more pronounced when caffeine was added. None of the treatments affected uncorrected QT interval in the absence of caffeine.

  19. Identification of hydroxylated metabolites of hexabromocyclododecane in wildlife and 28-days exposed Wistar rats.

    PubMed

    Brandsma, Sicco H; Van der Ven, Leo T M; De Boer, Jacob; Leonards, Pim E G

    2009-08-01

    We studied the presence of hydroxylated metabolites of hexabromocyclododecane (HBCD) in three wildlife species (tern egg, seal, and flounder) and in Wistar rats exposed to 30 and 100 mg HBCD/kg bw/day for 28 days. A nondestructive extraction, fractionation, and cleanup method was developed to separate the hydroxylated HBCD metabolites from the biotic sample matrix. Four different groups of hydroxylated HBCD metabolites were identified in rat adipose, liver, lung, and muscle tissues by liquid and gas chromatography (LC and GC) combined with mass spectrometry (MS): monohydroxy metabolites of HBCD, pentabromocyclododecene (PBCDe), tetrabromocyclododecene (TBCDe), and dihydroxy-HBCD. Dihydroxy-PBCDe was identified by GC-MS but could not be confirmed by LCMS. Debromination of HBCD to PBCDe was another metabolic pathway observed. In tern eggs from the Western Scheldt the monohydroxy-HBCD was found and in the blubber of harbor seal (Wadden Sea) the monohydroxy metabolites of HBCD and PBCDe were found. No hydroxylated metabolites were detected in the tissue of flounder (Wadden Sea). To our knowledge, this is the first study to identify different hydroxylated metabolite groups of HBCD in rat and wildlife samples.

  20. Oral 28-day and developmental toxicity studies of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate

    PubMed Central

    Clarke, Kieran; Tchabanenko, Kirill; Pawlosky, Robert; Carter, Emma; Knight, Nicholas S.; Murray, Andrew J.; Cochlin, Lowri E.; King, M. Todd; Wong, Andrea W.; Roberts, Ashley; Robertson, Jeremy; Veech, Richard L.

    2013-01-01

    (R)-3-Hydroxybutyl (R)-3-hydroxybutyrate (ketone monoester) has been developed as an oral source of ketones, which may be utilized for energy. In a 28-day toxicity study, Crl:WI (Wistar) rats received diets containing, as 30% of the calories, ketone monoester (12 and 15 g/kg body weight/day for male and female rats, respectively). Control groups received either carbohydrate- or fat-based diets. Rats in the test group consumed less feed and gained less weight than control animals; similar findings have been documented in studies of ketogenic diets. Between-group differences were noted in selected hematology, coagulation, and serum chemistry parameters; however, values were within normal physiological ranges and/or were not accompanied by other changes indicative of toxicity. Upon gross and microscopic evaluation, there were no findings associated with the ketone monoester. In a developmental toxicity study, pregnant Crl:WI (Han) rats were administered 2 g/kg body weight/day ketone monoester or water (control) via gavage on days 6 through 20 of gestation. No Caesarean-sectioning or litter parameters were affected by the test article. The overall incidence of fetal alterations was higher in the test group; however, there were no specific alterations attributable to the test substance. The results of these studies support the safety of ketone monoester. PMID:22504461

  1. 28-day intraocular pressure reduction with a single dose of brimonidine tartrate-loaded microspheres.

    PubMed

    Fedorchak, Morgan V; Conner, Ian P; Medina, Carlos A; Wingard, Jeremy B; Schuman, Joel S; Little, Steven R

    2014-08-01

    Treatment of glaucoma by intraocular pressure (IOP) reduction is typically accomplished through the administration of eye drops, the difficult and frequent nature of which contributes to extremely low adherence rates. Poor adherence to topical treatment regimens in glaucoma patients can lead to irreversible vision loss and increased treatment costs. Currently there are no approved treatments for glaucoma that address the inherent inefficiencies in drug delivery and patient adherence. Brimonidine tartrate (BT), a common glaucoma medication, requires dosing every 8-12 h, with up to 97% of patients not taking it as prescribed. This study provides proof-of-principle testing of a controlled release BT formulation. BT was encapsulated in poly(lactic-co-glycolic) acid microspheres and drug release was quantified using UV-Vis spectroscopy. For in vivo studies, rabbits were randomized to receive a single subconjunctival injection of blank (no drug) or BT-loaded microspheres or twice daily topical 0.2% BT drops. The microspheres released an average of 2.1 ± 0.37 μg BT/mg microspheres/day in vitro. In vivo, the percent decrease in IOP from baseline was significantly greater in the treated eye for both topical drug and drug-loaded microspheres versus blank microspheres throughout the 4-week study, with no evidence of migration or foreign body response. IOP measurements in the contralateral, untreated eyes also suggested a highly localized effect from the experimental treatment. A treatment designed using the release systems described in this study would represent a vast improvement over the current clinical standard of 56-84 topical doses over 28 days.

  2. 28-Day repeated dose toxicity study of dried microorganism in rats.

    PubMed

    Kitano, M; Hosoe, K; Fukutomi, N; Hidaka, T; Imai, N; Kawabe, M

    2004-11-01

    Ubidecarenone, also known as CoQ(10), is currently sold as a dietary supplement in the United States, with a majority of these products derived from the fermentation of carbohydrates or tobacco leaf extracts. In addition to its availability in dietary supplements, CoQ(10) is now being considered for use in foods. Accordingly, as part of the process for attaining "Generally Recognized as Safe" status, and to supplement information already available regarding the safety of CoQ(10) per se, a 28-day oral toxicity study in rats was conducted to evaluate the subacute safety of a microorganism biomass used as a new source in CoQ(10) production. Groups of Crj:CD(SD) rats (SPF) (6 males or females per group, 4 groups per sex) received dried microorganism at doses of 0, 500, 1000 or 2000 mg/kg/day via intragastric intubation. Clinical observations were recorded, and body weight, and food and water consumptions measured throughout the study. At the end of the study, aortic blood samples were collected from all animals for analysis of hematological and clinical chemistry parameters, and gross pathologic examination was performed. Histopathologic examination was performed on select tissues from the control and high-dose groups. There were no treatment-related changes that were considered to be of toxicological significance. Since rats treated with 2000 mg/kg of dried microorganism did not demonstrate any treatment-related changes, the no-observable-adverse-effect level (NOAEL) for dried microorganism was estimated to be greater than 2000 mg/kg/day under the present study conditions.

  3. Short-term (28 days) prognosis between genders according to the type of coronary event (Q-wave versus non-Q-wave acute myocardial infarction versus unstable angina pectoris).

    PubMed

    Marrugat, Jaume; García, María; Elosua, Roberto; Aldasoro, Elena; Tormo, María José; Zurriaga, Oscar; Arós, Fernando; Masiá, Rafael; Sanz, Ginés; Valle, Vicente; López De Sá, Esteban; Sala, Joan; Segura, Antonio; Rubert, Catalina; Moreno, Concepción; Cabadés, Adolfo; Molina, Lluís; López-Sendón, José Luís; Gil, Miguel

    2004-11-01

    The type of acute coronary syndrome may account for different prognoses between men and women after myocardial infarction. This study assessed gender differences in 28-day mortality rates for first or recurrent Q-wave and non-Q-wave myocardial infarctions and unstable angina by using data from 5 registries that included 20,836 patients (24.8% women). Mortality rates were higher in women with first Q-wave myocardial infarction but not in the other patients after adjusting for confounding variables.

  4. Supra-nutritional vitamin E supplementation for 28 days before slaughter maximises muscle vitamin E concentration in finisher pigs.

    PubMed

    Kim, J C; Jose, C G; Trezona, M; Moore, K L; Pluske, J R; Mullan, B P

    2015-12-01

    A 4 × 3 factorial experiment (n=8 pigs per treatment combination) was conducted with 96 female Landrace × Large White pigs to examine the required level of dietary vitamin E and optimum feeding duration before slaughter to maximise muscle vitamin E content in the Longissimus thoracis et lumborum (LTL) muscle. The respective factors were four dietary levels of vitamin E (supplemented as dl-α-tocopheryl acetate; 35, 300, 500, and 700 IU/kg) and three feeding durations (14, 28 and 42 days before slaughter). Vitamin E concentration in the LTL was maximised at 6 mg/kg, which was achieved by feeding a 700 IU vitamin E diet for 28 days before slaughter (P<0.001). There was no further increase in the vitamin E content of the LTL by feeding the high vitamin E diet more than 28 days before slaughter.

  5. Acute and 28-Day Subacute Toxicity Studies of Hexane Extracts of the Roots of Lithospermum erythrorhizon in Sprague-Dawley Rats

    PubMed Central

    Han, Chung-Tack; Kim, Myoung-Jun; Moon, Seol-Hee; Jeon, Yu-Rim; Hwang, Jae-Sik; Nam, Chunja; Park, Chong-Woo; Lee, Sun-Ho; Na, Jae-Bum; Park, Chan-Sung; Park, Hee-Won; Lee, Jung-Min; Jang, Ho-Song; Park, Sun-Hee; Han, Kyoung-Goo; Choi, Young Whan

    2015-01-01

    Lithospermum erythrorhizon has long been used as a traditional oriental medicine. In this study, the acute and 28-day subacute oral dose toxicity studies of hexane extracts of the roots of L. erythrorhizon (LEH) were performed in Sprague-Dawley rats. In the acute toxicity study, LEH was administered once orally to 5 male and 5 female rats at dose levels of 500, 1,000, and 2,000 mg/kg. Mortality, clinical signs, and body weight changes were monitored for 14 days. Salivation, soft stool, soiled perineal region, compound-colored stool, chromaturia and a decrease in body weight were observed in the extract-treated groups, and no deaths occurred during the study. Therefore, the approximate lethal dose (ALD) of LEH in male and female rats was higher than 2,000 mg/kg. In the subacute toxicity study, LEH was administered orally to male and female rats for 28 days at dose levels of 25, 100, and 400 mg/kg/day. There was no LEH-related toxic effect in the body weight, food consumption, ophthalmology, hematology, clinical chemistry and organ weights. Compound-colored (black) stool, chromaturia and increased protein, ketone bodies, bilirubin and occult blood in urine were observed in the male and female rats treated with the test substance. In addition, the necropsy revealed dark red discoloration of the kidneys, and the histopathological examination showed presence of red brown pigment or increased hyaline droplets in the renal tubules of the renal cortex. However, there were no test substance-related toxic effects in the hematology and clinical chemistry, and no morphological changes were observed in the histopathological examination of the kidneys. Therefore, it was determined that there was no significant toxicity because the changes observed were caused by the intrinsic color of the test substance. These results suggest that the no-observed-adverse-effect Level (NOAEL) of LEH is greater than 400 mg/kg/day in both sexes. PMID:26877842

  6. Responses in the respiratory tract of rats following exposure to sulphuric acid aerosols for 5 or 28 days.

    PubMed

    Kilgour, Joanne D; Foster, John; Soames, Anthony; Farrar, David G; Hext, Paul M

    2002-01-01

    Sulphuric acid mists have been classified by the International Agency for Research on Cancer as being carcinogenic to humans based on epidemiological findings of respiratory tract tumours. To determine if early changes in the respiratory tract following exposure to sulphuric acid (H(2)SO(4)) aerosols are consistent with the possible development of tumours after extended periods of exposure, groups of female rats were exposed to respirable aerosols of H(2)SO(4) at target concentrations of 0, 0.2, 1.0 or 5.0 mg m(-3) for 6 h per day for either 5 days or for 5 days a week over a 28-day period. Additional groups exposed to 0 or 5.0 mg m(-3) over the 28-day period were retained after exposure for 4 or 8 weeks to assess recovery. Histopathological examinations and quantitative cell proliferation measurements were conducted on the nasal passages, larynx and lung. Achieved concentrations were 0.3, 1.38 and 5.52 mg m(-3) H(2)SO(4). Histological and cell proliferative changes were confined to the larynx and no effects were seen in the nasal passages or lungs. At the two highest concentrations, squamous metaplasia accompanied by significant cell proliferation was apparent after 5 and 28 days of exposure and there was a reduction in the severity of the pathological changes following the recovery periods. No effects were seen at 0.3 mg m(-3) after 5 days of exposure and only minimal metaplastic change was seen after 28 days in a few animals and was not accompanied by cell proliferation. The toxicological relevance of these findings is discussed.

  7. Downregulation of immediate-early genes linking to suppression of neuronal plasticity in rats after 28-day exposure to glycidol

    SciTech Connect

    Akane, Hirotoshi; Saito, Fumiyo; Shiraki, Ayako; Takeyoshi, Masahiro; Imatanaka, Nobuya; Itahashi, Megu; Murakami, Tomoaki; Shibutani, Makoto

    2014-09-01

    We previously found that the 28-day oral toxicity study of glycidol at 200 mg/kg/day in rats resulted in axonopathy in both the central and peripheral nervous systems and aberrations in the late-stage of hippocampal neurogenesis targeting the process of neurite extension. To capture the neuronal parameters in response to glycidol toxicity, these animals were subjected to region-specific global gene expression profiling in four regions of cerebral and cerebellar architectures, followed by immunohistochemical analysis of selected gene products. Expression changes of genes related to axonogenesis and synaptic transmission were observed in the hippocampal dentate gyrus, cingulate cortex and cerebellar vermis at 200 mg/kg showing downregulation in most genes. In the corpus callosum, genes related to growth, survival and functions of glial cells fluctuated their expression. Immunohistochemically, neurons expressing gene products of immediate-early genes, i.e., Arc, Fos and Jun, decreased in their number in the dentate granule cell layer, cingulate cortex and cerebellar vermis. We also applied immunohistochemical analysis in rat offspring after developmental exposure to glycidol through maternal drinking water. The results revealed increases of Arc{sup +} neurons at 1000 ppm and Fos{sup +} neurons at ≥ 300 ppm in the dentate granule cell layer of offspring only at the adult stage. These results suggest that glycidol suppressed neuronal plasticity in the brain after 28-day exposure to young adult animals, in contrast to the operation of restoration mechanism to increase neuronal plasticity at the adult stage in response to aberrations in neurogenesis after developmental exposure. - Highlights: • Neuronal toxicity parameters after 28-day glycidol treatment were examined in rats. • Region-specific global gene expression profiling was conducted in brain regions. • Cortical tissues downregulated genes on axonogenesis and synaptic transmission. • Cortical tissues

  8. 28-day repeated dose oral toxicity of human copper-zinc superoxide dismutase from recombinant Pichia pastori in rats.

    PubMed

    Zhu, Liang; Tian, Ying-Juan; Zhu, Si-Ming

    2012-04-01

    Human copper/zinc superoxide dismutase from recombinant Pichia pastori (RH-Cu/Zn-SOD) was orally administered, via gavage, to Sprague-Dawley rats at 500, 1,000, and 2,000 mg/kg body weight/day for 28 days. During the 28-day period, animals were examined for evidence of toxicity; there were no deaths, and in-life physical signs were normal. On day 29, the animals were exsanguinated, examined for gross pathology, and tissues were preserved for histopathology. Although statistical differences were noted in some hematology and clinical chemistry, they were of questionable biological significance. The results of the 28-day oral administration demonstrated a lack of toxicity of RH-Cu/Zn-SOD in rats. There were no treatment-related, toxicologically relevant changes in clinical signs, growth, food consumption, hematology, clinical chemistry, organ weights, or pathology. The no observed adverse effect level was greater than 2,000 mg/kg/day for RH-Cu/Zn-SOD in rats.

  9. Relative toxicity of bifenthrin to Hyalella azteca in 10 day versus 28 day exposures.

    PubMed

    Anderson, Brian S; Phillips, Bryn M; Voorhees, Jennifer P; Petersen, Megan A; Jennings, Lydia L; Fojut, Tessa L; Vasquez, Martice E; Siegler, Catherine; Tjeerdema, Ronald S

    2015-04-01

    Many watersheds in the Central Valley region of California are listed as impaired due to pyrethroid-associated sediment toxicity. The Central Valley Regional Water Quality Control Board is developing numeric sediment quality criteria for pyrethroids, beginning with bifenthrin. Criteria are being developed using existing data, along with data from 10 d and 28 d toxicity tests with Hyalella azteca conducted as part of the current study. A single range-finder and 2 definitive tests were conducted for each test duration. Median lethal concentrations (LC50s), as well as LC20s and inhibition concentrations (IC20s) were calculated based on measured whole sediment bifenthrin concentrations and interstitial water concentrations. Sediment LC50s were also corrected for organic C content. Average LC50s were not significantly different in 10 d versus 28 d tests with H. azteca: 9.1 and 9.6 ng/g bifenthrin for 10 d and 28 d tests, respectively. Average LC20 values were also similar with concentrations at 7.1 and 7.0 for 10 d and 28 d tests, respectively. Bifenthrin inhibition concentrations (IC20s) based on amphipod growth were variable, particularly in the 28 d tests, where a clear dose-response relationship was observed in only 1 of the definitive experiments. Average amphipod growth IC20s were 3.9 and 9.0 ng/g for 10 d and 28 d tests, respectively. Amphipod growth calculated as biomass resulted in IC20s of 4.1 and 6.3 ng/g for the 10 d and 28 d tests, respectively. Lack of a clear growth effect in the longer term test may be related to the lack of food adjustment to account for amphipod mortality in whole sediment exposures. The average C-corrected LC50s were 1.03 and 1.09 μg/g OC for the 10 d and 28 d tests, respectively. Interstitial water LC50s were determined as the measured dissolved concentration of bifenthrin relative to interstitial water dissolved organic carbon. The average LC50s for dissolved interstitial water bifenthrin were

  10. Effects of 28 days silicon dioxide aerosol exposure on respiratory parameters, blood biochemical variables and lung histopathology in rats.

    PubMed

    Deb, Utsab; Lomash, Vinay; Raghuvanshi, Suchita; Pant, S C; Vijayaraghavan, R

    2012-11-01

    Inhalation toxicity of silicon dioxide aerosol (150, 300 mg/m(3)) daily over a period of 28 days was carried out in rats. The changes in respiratory variables during the period of exposure were monitored using a computer programme that recognizes the modifications of the breathing pattern. Exposure to the aerosol caused a time dependent decrease in tidal volume, with an increase in respiratory frequency compared to the control. Biochemical variables and histopathological observation were noted at 28th day following the start of exposure. Biochemical markers of silica induced lung injury like plasma alkaline phosphatase, lactate dehydrogenase and angiotensine converting enzyme activities increased in a concentration dependent manner compared to control. Increase in the plasma enzymatic activities indicates endothelial lung damage, increased lung membrane permeability. Histopathological observation of the lungs confirmed concentration dependent granulomatous inflammation, fibrosis and proteinacious degeneration. Aggregates of mononuclear cells with entrapped silica particles circumscribed by fibroblast were observed in 300 mg/m(3) silica aerosol exposed group at higher magnification. Decrease in tidal volume and increase in respiratory frequency might be due to the thickening of the alveolar wall leading to a decreased alveolar volume and lowered elasticity of the lung tissue. The trends in histological and biochemical data are in conformity with the respiratory data in the present study. This study reports for the first time, the changes in respiratory variables during silica aerosol exposure over a period of 28 days.

  11. Optimization of Hyalella azteca IQ Toxicity Test{trademark} for prediction of 28-day sediment toxicity tests

    SciTech Connect

    Novotny, A.N.; Ezzard, C.L.; Douglas, W.S.; Home, M.T.

    1995-12-31

    The IQ Toxicity Test, which is a rapid screening toxicity test consisting of the observation of in-vivo inhibition of an enzymatic process using a fluorescent substrate, has proven successful for the determination of 24 and 48-hour EC50`s of D. magna, C. dubia, D. pulex and M. bahia. The application of this concept to utilize the freshwater amphipod Hyalella azteca may be an excellent way in which to reduce the standard 28-day chronic sediment toxicity test to possibly one hour`s time. This study incorporates an additive experimental design to explore the effects of and interactions between five specific variables: size of the amphipod, exposure time to the toxicant, concentration of substrate, exposure time to the substrate, and length of time starved prior to testing. The results of the IQ toxicity test were compared to those of a 28-day chronic sediment toxicity test. Preliminary data indicate that there is an optimal combination of these variables which results in a concise, reproducible toxicity test for use with Hyalella azteca, and would potentially be applicable to other freshwater amphipods in the future.

  12. Serum kinetics, distribution and excretion of silver in rabbits following 28 days after a single intravenous injection of silver nanoparticles.

    PubMed

    Lee, Yeonjin; Kim, Pilje; Yoon, Junheon; Lee, Byoungcheun; Choi, Kyunghee; Kil, Ki-Hyun; Park, Kwangsik

    2013-09-01

    Serum kinetics, tissue distribution, and excretion of citrate-coated silver nanoparticles (AgNPs) were investigated in rabbits (n = 4) up to 28 days after a single intravenous injection. Following a single injection of AgNPs, the AUC(last) was reported to be 3.65 ± 0.68 μg·day/ml in 5 mg/kg-treated group and 0.90 ± 0.16 μg·day/ml in 0.5 mg/kg-treated group, respectively. The accumulation of silver was observed in all the tested organs including liver, kidney, spleen, lung, brain, testis, and thymus at 1 day, 7 day, and 28 day of measurement. The liver and spleen seemed to be the major targets because of high accumulation of silver. Excretion via feces and urine was also monitored during the entire experimental period. Unexpectedly, much more excretion of silver occurred via feces than through urine after an intravenous injection, which suggests biliary excretion of AgNPs. General toxicity was analyzed and histopathological changes were also evaluated.

  13. Safety assessment of SDA soybean oil: results of a 28-day gavage study and a 90-day/one generation reproduction feeding study in rats.

    PubMed

    Hammond, Bruce G; Lemen, Joan K; Ahmed, Gulam; Miller, Kathleen D; Kirkpatrick, Jeannie; Fleeman, Tammye

    2008-12-01

    Long chain polyunsaturated fatty acids (LC-PUFAs) in the diet reduce risk of cardiac mortality. Fish oils are a dietary source of LC-PUFAs (EPA, DHA) but intake is low in Western diets. Adding beneficial amounts of LC-PUFAs to foods is limited by their instability and potential to impart off-flavors. Stearidonic acid (SDA), a precursor of EPA in man, is more stable than EPA/DHA in food matrices. SDA is present in fish oils (0.5-4%) and in nutraceuticals (echium, borage oil). Genes for Delta6, Delta15 desaturases were introduced into soybeans that convert linoleic and alpha-linolenic acid to SDA (15-30% fatty acids). Since addition of SDA soybean oil into human foods increases SDA intake, toxicology studies were undertaken to assess its safety. In a 28-day pilot study, rats were gavaged with SDA soybean oil at dosages up to 3g/kg body weight/day; no treatment-related adverse effects were observed. A 90-day/one generation rat reproduction study was subsequently conducted where SDA soybean oil was added to diets to provide daily doses of 1.5 and 4 g/kg body weight. There were no treatment-related adverse effects on parental animals or on reproductive performance and progeny development.

  14. Risks of all-cause and site-specific fractures among hospitalized patients with COPD

    PubMed Central

    Liao, Kuang-Ming; Liang, Fu-Wen; Li, Chung-Yi

    2016-01-01

    Abstract Patients with chronic obstructive pulmonary disease (COPD) have a high prevalence of osteoporosis. The clinical sequel of osteoporosis is fracture. Patients with COPD who experience a fracture also have increased morbidity and mortality. Currently, the types of all-cause and site-specific fracture among patients with COPD are unknown. Thus, we elucidated the all-cause and site-specific fractures among patients with COPD. A retrospective, population-based, cohort study was conducted utilizing the Taiwan Longitudinal Health Insurance Database. Patients with COPD were defined as those who were hospitalized with an International Classification of Diseases, Ninth Revision, Clinical Modification code of 490 to 492 or 496 between 2001 and 2011. The index date was set as the date of discharge. The study patients were followed from the index date to the date when they sought care for any type of fracture, date of death, date of health insurance policy termination, or the last day of 2013. The types of fracture analyzed in this study included vertebral, rib, humeral, radial and ulnar/wrist, pelvic, femoral, and tibial and fibular fractures. The cohort consisted of 11,312 patients with COPD. Among these patients, 1944 experienced fractures. The most common site-specific fractures were vertebral, femoral, rib, and forearm fractures (radius, ulna, and wrist) at 32.4%, 31%, 12%, and 11.8%, respectively. The adjusted hazard ratios of fracture were 1.71 [95% confidence interval (95% CI) = 1.56–1.87] for female patient with COPD and 1.50 (95% CI = 1.39–1.52) for patients with osteoporosis after covariate adjustment. Vertebral and hip fractures are common among patients with COPD, especially among males with COPD. Many comorbidities contribute to the high risk of fracture among patients with COPD. PMID:27749576

  15. VS411 Reduced Immune Activation and HIV-1 RNA Levels in 28 Days: Randomized Proof-of-Concept Study for AntiViral-HyperActivation Limiting Therapeutics

    PubMed Central

    Lori, Franco; De Forni, Davide; Katabira, Elly; Baev, Denis; Maserati, Renato; Calarota, Sandra A.; Cahn, Pedro; Testori, Marco; Rakhmanova, Aza; Stevens, Michael R.

    2012-01-01

    Background A new class of antiretrovirals, AntiViral-HyperActivation Limiting Therapeutics (AV-HALTs), has been proposed as a disease-modifying therapy to both reduce Human Immunodeficiency Virus Type 1 (HIV-1) RNA levels and the excessive immune activation now recognized as the major driver of not only the continual loss of CD4+ T cells and progression to Acquired Immunodeficiency Syndrome (AIDS), but also of the emergence of both AIDS-defining and non-AIDS events that negatively impact upon morbidity and mortality despite successful (ie, fully suppressive) therapy. VS411, the first-in-class AV-HALT, combined low-dose, slow-release didanosine with low-dose hydroxycarbamide to accomplish both objectives with a favorable toxicity profile during short-term administration. Five dose combinations were administered as VS411 to test the AV-HALT Proof-of-Concept in HIV-1-infected subjects. Methods Multinational, double-blind, 28-day Phase 2a dose-ranging Proof-of-Concept study of antiviral activity, immunological parameters, safety, and genotypic resistance in 58 evaluable antiretroviral-naïve HIV-1-infected adults. Randomization and allocation to study arms were carried out by a central computer system. Results were analyzed by ANOVA, Kruskal-Wallis, ANCOVA, and two-tailed paired t tests. Results VS411 was well-tolerated, produced significant reductions of HIV-1 RNA levels, increased CD4+ T cell counts, and led to significant, rapid, unprecedented reductions of immune activation markers after 28 days despite incomplete viral suppression and without inhibiting HIV-1-specific immune responses. The didanosine 200 mg/HC 900 mg once-daily formulation demonstrated the greatest antiviral efficacy (HIV-1 RNA: −1.47 log10 copies/mL; CD4+ T cell count: +135 cells/mm3) and fewest adverse events. Conclusions VS411 successfully established the Proof-of-Concept that AV-HALTs can combine antiviral efficacy with rapid, potentially beneficial reductions in the excessive immune system

  16. Downregulation of immediate-early genes linking to suppression of neuronal plasticity in rats after 28-day exposure to glycidol.

    PubMed

    Akane, Hirotoshi; Saito, Fumiyo; Shiraki, Ayako; Takeyoshi, Masahiro; Imatanaka, Nobuya; Itahashi, Megu; Murakami, Tomoaki; Shibutani, Makoto

    2014-09-01

    We previously found that the 28-day oral toxicity study of glycidol at 200mg/kg/day in rats resulted in axonopathy in both the central and peripheral nervous systems and aberrations in the late-stage of hippocampal neurogenesis targeting the process of neurite extension. To capture the neuronal parameters in response to glycidol toxicity, these animals were subjected to region-specific global gene expression profiling in four regions of cerebral and cerebellar architectures, followed by immunohistochemical analysis of selected gene products. Expression changes of genes related to axonogenesis and synaptic transmission were observed in the hippocampal dentate gyrus, cingulate cortex and cerebellar vermis at 200mg/kg showing downregulation in most genes. In the corpus callosum, genes related to growth, survival and functions of glial cells fluctuated their expression. Immunohistochemically, neurons expressing gene products of immediate-early genes, i.e., Arc, Fos and Jun, decreased in their number in the dentate granule cell layer, cingulate cortex and cerebellar vermis. We also applied immunohistochemical analysis in rat offspring after developmental exposure to glycidol through maternal drinking water. The results revealed increases of Arc(+) neurons at 1000ppm and Fos(+) neurons at ≥300ppm in the dentate granule cell layer of offspring only at the adult stage. These results suggest that glycidol suppressed neuronal plasticity in the brain after 28-day exposure to young adult animals, in contrast to the operation of restoration mechanism to increase neuronal plasticity at the adult stage in response to aberrations in neurogenesis after developmental exposure.

  17. VO2max and ventilatory threshold of trained cyclists are not affected by 28-day L-arginine supplementation.

    PubMed

    Sunderland, Kyle L; Greer, Felicia; Morales, Jacobo

    2011-03-01

    The ergogenic effect of L-arginine on an endurance-trained population is not well studied. The few studies that have investigated L-arginine on this population have not been conducted in a laboratory setting or measured aerobic variables. The purpose of the current study is to determine if 28 days of L-arginine supplementation in trained male cyclists affects VO2max and ventilatory threshold (VT). Eighteen (18) endurance-trained male cyclists (mean ± SD, age: 36.3 ± 7.9 years; height: 182.4 ± 4.6 cm; and body mass: 79.5 ± 4.7 kg) performed a graded exercise test (GXT; 50 W + 25 W·min) before and after 28 days of supplementation with L-arginine (ARG; 2 × 6 g·d) or placebo (PLA; cornstarch). The GXT was conducted on the subject's own bicycle using the RacerMate CompuTrainer (Seattle, WA, USA). VO2 was continuously recorded using the ParvoMedics TrueOne 2400 metabolic cart (Salt Lake City, UT, USA) and VT was established by plotting the ventilatory equivalent for O2 (VE/VO2) and the ventilatory equivalent for CO2 (VE/VCO2) and identifying the point at which VE/VO2 increases with no substantial changes in VE/VCO2. L-arginine supplementation had no effect from initial VO2max (PL, 58.7 ± 7.1 ml·kg·min; ARG, 63.5 ± 7.3 ml·kg·min) to postsupplement VO2max (PL, 58.9 ± 6.0 ml·kg·min; ARG, 63.2 ± 7.2 ml·kg·min). Also, no effect was seen from initial VT (PL, 75.7 ± 4.6% VO2max; ARG, 76.0 ± 5.3% VO2max) to postsupplement VT (PL, 74.3 ± 8.1% VO2max; ARG, 74.2 ± 6.4% VO2max). These results indicate that L-arginine does not impact VO2max or VT in trained male cyclists.

  18. Psychomotor performance during a 28 day head-down tilt with and without lower body negative pressure

    NASA Astrophysics Data System (ADS)

    Traon, A. Pavy-le; de Feneyrols, A. Rous; Cornac, A.; Abdeseelam, R.; N'uygen, D.; Lazerges, M.; Güell, A.; Bes, A.

    Several factors may affect psychomotor performance in space: sensory-motor changes, sleep disturbances, psychological modifications induced by the social isolation and confinement. However, psychomotor performance is difficult to assess. A battery of standardized and computerized tests, so-called "Automated Portable Test System" (APTS) was devised to ascertain the cognitive, perceptive and motor abilities and their possible fluctuations according to environmental effects. Antiorthostatic bedrest, often used to simulate weightlessness, (particularly cardiovascular modifications) also constitutes a situation of social confinement and isolation. During two bedrest experiments (with head-down tilt of -6°) of 28 days each, we intended to assess psychomotor performance of 6 males so as to determine whether: —on the one hand, it could be altered by remaining in decubitus; —on the other, the Lower Body Negative Pressure sessions, designed to prevent orthostatic intolerance back on Earth, could improve the performance. To accomplish this, part of the APTS tests as well as an automated perceptive attention test were performed. No downgrading of psychomotor performance was observed. On the contrary, the tasks were more accurately performed over time. In order to assess the experimental conditions on the acquisition phase, the learning curves were modelled. A beneficial effect of the LBNP sessions on simple tests involving the visual-motor coordination and attention faculties can only be regarded as a mere trend. Methods used in this experiment are also discussed.

  19. Phenolic acid protects of renal damage induced by ochratoxin A in a 28-days-oral treatment in rats.

    PubMed

    Cariddi, L N; Escobar, F M; Sabini, M C; Campra, N A; Bagnis, G; Decote-Ricardo, D; Freire-de-Lima, C G; Mañas, F; Sabini, L I; Dalcero, A M

    2016-04-01

    The present study aimed to characterize the chlorogenic acid (ChlA) capacity to reverse the toxic effects induced by ochratoxin A (OTA) in a subacute toxicity test in rats. Male Wistar rats were fed orally by gavage for 28 days with OTA (0.4mg/kg bw/day), ChlA (5mg/kg bw/day) or the combination OTA (0.4mg/kg bw/day)+ChlA (5mg/kg bw/day). No deaths, no decrease in feed intake or body weight in any experimental group were recorded. The negative control group and the animals treated with ChlA alone showed no changes in any parameters evaluated. In OTA-treated group significant changes such as decrease in urine volume, proteinuria, occult blood, increase in serum creatinine values; decrease in absolute and relative kidney weight and characteristics histopathological lesions that indicated kidney damage were observed. However, limited effect on oxidative stress parameters were detected in kidneys of OTA-treated group. Animals treated with the combination OTA+ChlA were showed as negative control group in the evaluation of several parameters of toxicity. In conclusion, ChlA, at given concentration, improved biochemical parameters altered in urine and serum and pathological damages in kidneys induced by OTA exposure, showing a good protective activity, but not by an apparent antioxidant mechanism.

  20. Comparative hazard identification of nano- and micro-sized cerium oxide particles based on 28-day inhalation studies in rats.

    PubMed

    Gosens, Ilse; Mathijssen, Liesbeth E A M; Bokkers, Bas G H; Muijser, Hans; Cassee, Flemming R

    2014-09-01

    There are many uncertainties regarding the hazard of nanosized particles compared to the bulk material of the parent chemical. Here, the authors assess the comparative hazard of two nanoscale (NM-211 and NM-212) and one microscale (NM-213) cerium oxide materials in 28-day inhalation toxicity studies in rats (according to Organisation for Economic Co-operation and Development technical guidelines). All three materials gave rise to a dose-dependent pulmonary inflammation and lung cell damage but without gross pathological changes immediately after exposure. Following NM-211 and NM-212 exposure, epithelial cell injury was observed in the recovery groups. There was no evidence of systemic inflammation or other haematological changes following exposure of any of the three particle types. The comparative hazard was quantified by application of the benchmark concentration approach. The relative toxicity was explored in terms of three exposure metrics. When exposure levels were expressed as mass concentration, nanosized NM-211 was the most potent material, whereas when expression levels were based on surface area concentration, micro-sized NM-213 material induced the greatest extent of pulmonary inflammation/damage. Particles were equipotent based on particle number concentrations. In conclusion, similar pulmonary toxicity profiles including inflammation are observed for all three materials with little quantitative differences. Systemic effects were virtually absent. There is little evidence for a dominant predicting exposure metric for the observed effects.

  1. Acute and 28-Day Subchronic Oral Toxicity of an Ethanol Extract of Zingiber zerumbet (L.) Smith in Rodents

    PubMed Central

    Chang, Chia Ju; Tzeng, Thing-Fong; Liou, Shorong-Shii; Chang, Yuan-Shiun; Liu, I-Min

    2012-01-01

    The objective of this study was to evaluate the acute and subacute toxicity (28 days) of the ethanol extract of Z. zerumbet rhizomes (EEZZ) via the oral route in Wistar rats of both sexes. In the acute toxicity study, Wistar rats were administered a single dose of 15 g kg−1 of body weight by gavage, and were monitored for 14 days. EEZZ did not produce any toxic signs or deaths; the 50% lethal dose must be higher than 15 g kg−1. In the subchronic toxicity study, EEZZ was administered by gavage at doses of 1000, 2000 and 3000 mg/kg daily for 4 weeks to Wistar rats. The subacute treatment with EEZZ did not alter either the body weight gain or the food and water consumption. The hematological and biochemical analysis did not show significant differences in any of the parameters examined in female or male groups. Necropsy and histopathological examination, did not reveal any remarkable and treatment related changes. A no-observed adverse-effect level for EEZZ is 3000 mg kg−1 for rats under the conditions of this study. Hence, consumption of EEZZ for various medicinal purposes is safe. PMID:22536288

  2. Assessing sediment toxicity from navigational pools of the Upper Mississippi River using a 28-day Hyalella azteca test

    USGS Publications Warehouse

    Kemble, N.E.; Brunson, E.L.; Canfield, T.J.; Dwyer, F.J.; Ingersoll, C.G.

    1998-01-01

    To assess the extent of sediment contamination in the Upper Mississippi River (UMR) system after the flood of 1993, sediment samples were collected from 24 of the 26 navigational pools in the river and from one site in the Saint Croix River in the summer of 1994. Whole-sediment tests were conducted with the amphipod Hyalella azteca for 28 days measuring the effects on survival, growth, and sexual maturation. Amphipod survival was significantly reduced in only one sediment (13B) relative to the control and reference sediments. Body length of amphipods was significantly reduced relative to the control and reference sediments in only one sample (26C). Sexual maturation was not significantly reduced in any treatment when compared to the control and reference sediments. No significant correlations were observed between survival, growth, and maturation to either the physical or chemical characteristics of the sediment samples from the river. When highly reliable effect range medians (ERMs) were used to evaluate sediment chemistry, 47 of 49 (96%) of the samples were correctly classified as nontoxic. These results indicate that sediment samples from the Upper Mississippi River are relatively uncontaminated compared to other areas of known contamination in the United States.

  3. Presenting symptoms, pre-hospital delay time and 28-day case fatality in patients with peripheral arterial disease and acute myocardial infarction from the MONICA/KORA Myocardial Infarction Registry.

    PubMed

    Kirchberger, Inge; Amann, Ute; Heier, Margit; Kuch, Bernhard; Thilo, Christian; Peters, Annette; Meisinger, Christa

    2017-02-01

    Background Previous studies have indicated that patients with acute myocardial infarction (AMI) who have a history of peripheral arterial disease (PAD) have different characteristics and poorer outcomes than patients without PAD. However, data on short-term mortality are conflicting and it is unclear whether patients with PAD have a different scope of AMI symptoms or differences in pre-hospital delay time (PHDT) compared with patients without PAD. The objective of this study was to determine the associations between a history of PAD and presenting AMI symptoms, PHDT and 28-day case fatality in a population-based sample of patients with AMI. Design This was an observational study. Methods Information on history of PAD was obtained from the patients' medical records and their AMI symptoms were assessed by interviews with patients. Multivariable logistic regression models were used to determine the association of PAD with AMI symptoms and 28-day case fatality. A multivariable linear regression model was developed to examine the relations between PAD and PHDT. Results From the 5848 patients with AMI included in this study, 9.8% had a history of PAD. Patients with PAD were significantly less likely to report chest symptoms (odds ratio (OR) 0.52, 95% confidence interval (CI) 0.41-0.66) or pain in the upper left extremity (OR 0.67, 95% CI 0.54-0.84) than patients without PAD. PAD was significantly related with longer PHDT in patients <69 years of age ( p = 0.0117) and men ( p = 0.0104). A significantly higher 28-day case fatality (OR 2.09, 95% CI 1.47-2.96) was found in patients with PAD compared with patients without PAD. Conclusions Patients with PAD should receive comprehensive education on the possibility of atypical AMI symptoms and the need to call emergency medical services immediately.

  4. Toxicological evaluation of isopropylparaben and isobutylparaben mixture in Sprague-Dawley rats following 28 days of dermal exposure.

    PubMed

    Kim, Min Ji; Kwack, Seung Jun; Lim, Seong Kwang; Kim, Yeon Joo; Roh, Tae Hyun; Choi, Seul Min; Kim, Hyung Sik; Lee, Byung Mu

    2015-11-01

    The alkyl esters of p-hydroxybenzoic acid (Parabens) have been of concern due to their probable endocrine disrupting property especially in baby consumer products. The safety of parabens for use as a preservative in cosmetics has come into controversy, and thus consumer demand for paraben-free products is ever increasing. Thus, more comprehensive studies are needed to conclusively determine the safety of the multiple prolonged exposure to parabens with cosmetic ingredients. This study was conducted to investigate the potential repeated 28 days dermal toxicity (50, 100, 300, or 600 mg/kg bw/day) of isopropylparaben (IPP), isobutylparaben (IBP), or the mixture of IPP and IBP in rats. There were no significant changes in body and organ weights in any group. However, histopathological examinations showed that weak or moderate skin damages were observed in female rats by macroscopic and microscopic evaluations. In female rats, no observed adverse effect levels (NOAELs) of IPP with no skin lesion and IBP for skin hyperkeratosis, were estimated to be 600 mg/kg bw/day, and 50 mg/kg bw/day, respectively. With regard skin hyperkeratosis, the lowest observed adverse effect level (LOAEL) of the mixture of IPP and IBP was estimated to be 50 mg/kg bw/day. Analysis of six serum hormones (estrogen, testosterone, insulin, T3, TSH, or FSH) in animals showed that only FSH was dose-dependently decreased in the mixture groups of 100 mg/kg bw/day or higher. These data suggest that the mixture of IPP and IBP showed a synergistic dermal toxicity in rats and should be considered for future use in consumer products.

  5. Effects of 28-day mechanical and chewing stress on content of bound and diffusible ions in muscles of mastication.

    PubMed

    Gedrange, T; Kuhn, U D; Walter, B; Harzer, W; Bauer, R

    2001-06-01

    Type I and type II muscle fibres have different ion concentrations. Muscles adapt to chronic stress by changing of fibre types and remodelling of the myosin heavy chains in the muscle fibres. The present investigation on ionic change during muscular contraction was carried out on 10-week-old pigs (6 treated animals, 6 controls) over a 28-day period. Six pigs received acrylic build-ups to induce mechanical advancement of the lower jaw and chronic chewing stress. Muscle tissue was taken from the masseter (M1, M2, M3), temporal (TP1, TP2), medial pterygoid (PM) and geniohyoid (GH) muscles by a standardized method. Eighty-four muscle samples were used for histological fibre differentiation with mATPase. Energy-dispersive X-ray microanalysis of muscles was carried out in an environmental scanning electron microscope. Endurance stress in the stressed muscles was seen as an increase of type I fibres (P < 0.001). This histological change and ionic alterations were measured in the anterior region of the masseter (M1 and M2) and in the posterior region of the temporal muscle (TP2). Smaller changes were found in the medial pterygoid muscle. We measured in this muscles increases in potassium, sulphur, chloride (P < 0.05) and even larger increases in phosphate (up to 1.5 mmol/g to 2.3 mmol/g, P < 0.001) and sodium (3-fold, P < 0.001). The results reveal the effects of chronic stress on muscle fibres and ion concentration in the muscle. Chronic stress resulted in an increase of type I fibres and increased ion concentration in the same muscle region. These are considered to be indicators of more efficient contraction. The changes in ion concentration are an important factor in muscle contraction.

  6. Toxicological evaluation of silver nanoparticles and silver nitrate in rats following 28 days of repeated oral exposure.

    PubMed

    Qin, Guangqiu; Tang, Song; Li, Shibin; Lu, Haoliang; Wang, Yanwu; Zhao, Peng; Li, Bin; Zhang, Jiehong; Peng, Liang

    2017-02-01

    The increasing application of silver nanoparticles (AgNPs) has been raising concerns about their potential adverse effects to human and the environment. However, the knowledge on the systemic toxicity of AgNPs in mammalian systems is still limited. The present study investigated the toxicity of PVP-coated AgNPs in rats treated with repeated oral administration, and compared that with equivalent dose of AgNO3 . Specifically, one hundred male and female rats were orally administrated with particulate or ionic forms of silver (Ag) separately at doses of 0.5 and 1 mg kg(-1) body weight daily for 28 days. The results reveal no significant toxic effects of AgNPs and AgNO3 up to 1 mg kg(-1) body weight, with respect to the body weight, organ weight, food intake, and histopathological examination. Ag distribution pattern in organs of rats treated with AgNPs was similar to that of AgNO3 treated rats, showing liver and kidneys are the main target organs followed by testis and spleen. The total Ag contents in organs were significantly lower in the AgNPs treated rats than those in the AgNO3 treated rats. However, the comparisons between AgNPs and AgNO3 treatments further indicated more potent of AgNPs in biochemical and hematological parameters in rats, including red blood cell count (RBC), platelet count (PLT), white blood cell count (WBC) and aspartate transaminase (AST). Results of this study suggested that particulate Ag at least partially contributed to the observed toxicity of AgNPs, and both ionic and particulate Ag should be taken into consideration in toxicological evaluation of AgNPs. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 609-618, 2017.

  7. Characterization of pulmonary protein profiles in response to zinc oxide nanoparticles in mice: a 24-hour and 28-day follow-up study

    PubMed Central

    Pan, Chih-Hong; Chuang, Kai-Jen; Chen, Jen-Kun; Hsiao, Ta-Chih; Lai, Ching-Huang; Jones, Tim P; BéruBé, Kelly A; Hong, Gui-Bing; Ho, Kin-Fai; Chuang, Hsiao-Chi

    2015-01-01

    Although zinc oxide nanoparticles (ZnONPs) are recognized to cause systemic disorders, little is known about the mechanisms that underlie the time-dependent differences that occur after exposure. The objective of this study was to investigate the mechanistic differences at 24 hours and 28 days after the exposure of BALB/c mice to ZnONPs via intratracheal instillation. An isobaric tag for the relative and absolute quantitation coupled with liquid chromatography/tandem mass spectrometry was used to identify the differential protein expression, biological processes, molecular functions, and pathways. A total of 18 and 14 proteins displayed significant changes in the lung tissues at 24 hours and 28 days after exposure, respectively, with the most striking changes being observed for S100-A9 protein. Metabolic processes and catalytic activity were the main biological processes and molecular functions, respectively, in the responses at the 24-hour and 28-day follow-up times. The glycolysis/gluconeogenesis pathway was continuously downregulated from 24 hours to 28 days, whereas detoxification pathways were activated at the 28-day time-point after exposure. A comprehensive understanding of the potential time-dependent effects of exposure to ZnONPs was provided, which highlights the metabolic mechanisms that may be important in the responses to ZnONP. PMID:26251593

  8. Characterization of pulmonary protein profiles in response to zinc oxide nanoparticles in mice: a 24-hour and 28-day follow-up study.

    PubMed

    Pan, Chih-Hong; Chuang, Kai-Jen; Chen, Jen-Kun; Hsiao, Ta-Chih; Lai, Ching-Huang; Jones, Tim P; BéruBé, Kelly A; Hong, Gui-Bing; Ho, Kin-Fai; Chuang, Hsiao-Chi

    2015-01-01

    Although zinc oxide nanoparticles (ZnONPs) are recognized to cause systemic disorders, little is known about the mechanisms that underlie the time-dependent differences that occur after exposure. The objective of this study was to investigate the mechanistic differences at 24 hours and 28 days after the exposure of BALB/c mice to ZnONPs via intratracheal instillation. An isobaric tag for the relative and absolute quantitation coupled with liquid chromatography/tandem mass spectrometry was used to identify the differential protein expression, biological processes, molecular functions, and pathways. A total of 18 and 14 proteins displayed significant changes in the lung tissues at 24 hours and 28 days after exposure, respectively, with the most striking changes being observed for S100-A9 protein. Metabolic processes and catalytic activity were the main biological processes and molecular functions, respectively, in the responses at the 24-hour and 28-day follow-up times. The glycolysis/gluconeogenesis pathway was continuously downregulated from 24 hours to 28 days, whereas detoxification pathways were activated at the 28-day time-point after exposure. A comprehensive understanding of the potential time-dependent effects of exposure to ZnONPs was provided, which highlights the metabolic mechanisms that may be important in the responses to ZnONP.

  9. Long Pentraxin 3 as a Predictive Marker of Mortality in Severe Septic Patients Who Received Successful Early Goal-Directed Therapy

    PubMed Central

    Kim, Sun Bean; Lee, Kyoung Hwa; Lee, Ji Un; Ann, Hea Won; Ahn, Jin Young; Jeon, Yong Duk; Kim, Jung Ho; Ku, Nam Su; Choi, Jun Yong; Song, Young Goo; Kim, June Myung

    2017-01-01

    Purpose Pentraxin 3 (PTX3) has been suggested to be a prognostic marker of mortality in severe sepsis. Currently, there are limited data on biomarkers including PTX3 that can be used to predict mortality in severe sepsis patients who have undergone successful initial resuscitation through early goal-directed therapy (EGDT). Materials and Methods A prospective cohort study was conducted among 83 severe sepsis patients with fulfillment of all EGDT components and the achievement of final goal. Plasma PTX3 levels were measured by sandwich ELISA on hospital day (HD) 0, 3, and 7. The data for procalcitonin, C-reactive protein and delta neutrophil index were collected by electric medical record. The primary outcome was 28-day all-cause mortality. Results 28-day all-cause mortality was 19.3% and the median (interquartile range) APHCH II score of total patients was 16 (13–19). The non-survivors (n=16) had significantly higher PTX3 level at HD 0 [201.4 (56.9–268.6) ng/mL vs. 36.5 (13.7–145.3) ng/mL, p=0.008]. PTX3 had largest AUCROC value for the prediction of mortality among PTX3, procalcitonin, delta neutrophil index, CRP and APACHE II/SOFA sore at HD 0 [0.819, 95% confidence interval (CI) 0.677–0.961, p=0.008]. The most valid cut-off level of PTX3 at HD 0 was 140.28 ng/mL (sensitivity 66.7%, specificity 73.8%). The PTX3 and procalcitonin at HD 0 showed strong correlation (r=0.675, p<0.001). However, PTX3 at HD 0 was the only independent predictive marker in Cox's proportional hazards model (≥140 ng/mL; hazard rate 7.16, 95% CI 2.46–15.85, p=0.001). Conclusion PTX3 at HD 0 could be a powerful predictive biomarker of 28-day all-cause mortality in severe septic patients who have undergone successful EGDT. PMID:28120568

  10. Smoking and Risk of All-cause Deaths in Younger and Older Adults: A Population-based Prospective Cohort Study Among Beijing Adults in China.

    PubMed

    Li, Kuibao; Yao, Chonghua; Di, Xuan; Yang, Xinchun; Dong, Lei; Xu, Li; Zheng, Meili

    2016-01-01

    Cigarette smoking is the leading preventable cause of death worldwide. Few studies, however, have examined the modified effects of age on the association between smoking and all-cause mortality.In the current study, the authors estimated the association between smoking and age-specific mortality in adults from Beijing, China. This is a large community-based prospective cohort study comprising of 6209 Beijing adults (aged ≥40 years) studied for approximately 8 years (1991-1999). Hazard ratios (HRs) and attributable fractions associated with smoking were estimated by Cox proportional hazard models, adjusting for age, sex, alcohol intake, body mass index, systolic blood pressure, hypertension, and heart rate.The results showed, compared with nonsmokers, the multivariable-adjusted HRs for all-cause mortality were 2.7(95% confidence interval (CI):1.56-4.69) in young adult smokers (40-50 years) and 1.31 (95% CI: 1.13-1.52) in old smokers (>50 years); and the interaction term between smoking and age was significant (P = 0.026). Attributable fractions for all-cause mortality in young and old adults were 63% (95% CI: 41%-85%) and 24% (95% CI: 12%-36%), respectively. The authors estimated multivariate adjusted absolute risk (mortality) by Poisson regression and calculated risk differences and 95% CI by bootstrap estimation. Mortality differences (/10,000 person-years) were 15.99 (95% CI: 15.34-16.64) in the young and 74.61(68.57-80.65) in the old. Compared with current smokers, the HRs of all-cause deaths for former smokers in younger and older adults were 0.57 (95% CI: 0.23-1.42) and 0.96 (95% CI: 0.73-1.26), respectively.The results indicate smoking significantly increases the risks of all-cause mortality in both young and old Beijing adults from the relative and absolute risk perspectives. Smoking cessation could also reduce the excess risk of mortality caused by continuing smoking in younger adults compared with older individuals.

  11. Correlation among the toxicity profiling (28-days repeated oral dose toxicity), toxicokinetics and tissue distribution data of ulifloxacin, the active metabolite of prulifloxacin in Wistar albino rats.

    PubMed

    Nandi, Utpal; Roy, Bikash; Das, Anjan Kumar; Pal, Tapan Kumar

    2012-09-01

    This experiment was designed to investigate correlation among 28-days repeated oral dose toxicity, toxicokinetics and tissue distribution data of ulifloxacin (active metabolite of prulifloxacin) in Wistar albino rats. Prulifloxacin was administered for 28-days in rats at 0, 100, 200, 400mg/kg/day followed by 14-days recovery period. Simultaneously different toxicokinetic parameters and tissue distributions of ulifloxacin was examined by LC-MS/MS method. Plasma levels and tissue concentrations of ulifloxacin were increased with dose-related manner. Ulifloxacin was also distributed to many tissues, and concentration in lungs nearly equivalent to the plasma concentration. Based on these results it was concluded that long-term repeated dose of prulifloxacin may produce different blood parameters abnormality, liver damage, stomach ulcer, joint damage and dysfunction of lungs in rats which relates to high tissue distribution and accumulation of ulifloxacin in these tissues. These findings help in management of prulifloxacin induced adverse effects by appropriate dose selection in clinical practice.

  12. Repeated dose 28-days oral toxicity study of Carica papaya L. leaf extract in Sprague Dawley rats.

    PubMed

    Afzan, Adlin; Abdullah, Noor Rain; Halim, Siti Zaleha; Rashid, Badrul Amini; Semail, Raja Hazlini Raja; Abdullah, Noordini; Jantan, Ibrahim; Muhammad, Hussin; Ismail, Zakiah

    2012-04-10

    Carica papaya L. leaves have been used in ethnomedicine for the treatment of fevers and cancers. Despite its benefits, very few studies on their potential toxicity have been described. The aim of the present study was to characterize the chemical composition of the leaf extract from 'Sekaki' C. papaya cultivar by UPLC-TripleTOF-ESI-MS and to investigate the sub-acute oral toxicity in Sprague Dawley rats at doses of 0.01, 0.14 and 2 g/kg by examining the general behavior, clinical signs, hematological parameters, serum biochemistry and histopathology changes. A total of twelve compounds consisting of one piperidine alkaloid, two organic acids, six malic acid derivatives, and four flavonol glycosides were characterized or tentatively identified in the C. papaya leaf extract. In the sub-acute study, the C. papaya extract did not cause mortality nor were treatment-related changes in body weight, food intake, water level, and hematological parameters observed between treatment and control groups. Some biochemical parameters such as the total protein, HDL-cholesterol, AST, ALT and ALP were elevated in a non-dose dependent manner. Histopathological examination of all organs including liver did not reveal morphological alteration. Other parameters showed non-significant differences between treatment and control groups. The present results suggest that C. papaya leaf extract at a dose up to fourteen times the levels employed in practical use in traditional medicine in Malaysia could be considered safe as a medicinal agent.

  13. Evaluation of in vivo genotoxicity by thioacetamide in a 28-day repeated-dose liver micronucleus assay using male young adult rats.

    PubMed

    Sui, Hajime; Matsumoto, Hirotaka; Wako, Yumi; Kawasako, Kazufumi

    2015-03-01

    The repeated-dose liver micronucleus (RDLMN) assay has the potential to detect liver carcinogens and can be integrated into general toxicological studies. In this study, thioacetamide (TAA) was tested in 14- and 28-day RDLMN assays to assess the performance of the assay. The test substance, TAA, was administered orally to 6-week-old male Crl:CD (SD) rats once daily for 14 or 28 days at a dosage of 5, 10 or 20mg/kg/day. Hepatocytes were collected approximately 24h after the last TAA administration, and the incidence of micronuclei was assessed. In this study, bone marrow micronucleus assays were also conducted in the same animals. The 14- and 28-day RDLMN assays indicated that none of the TAA dosages significantly increased the proportion of micronucleated hepatocytes. Bone marrow micronucleus assays with TAA also provided negative results. It is known that TAA is a liver carcinogen in mice and rats. In the previous genotoxic studies, the Ames test and the chromosomal aberration test using CHL/IU cells have yielded negative results [1-4]. The liver micronucleus assay using young adult rats singly dosed with TAA (75 and 150mg/kg) also produced negative results [5]. TAA gave positive results only in the mouse bone marrow micronucleus assays [6,7].

  14. Postmenopausal hormone therapy is not associated with risk of all-cause dementia and Alzheimer's disease.

    PubMed

    O'Brien, Jacqueline; Jackson, John W; Grodstein, Francine; Blacker, Deborah; Weuve, Jennifer

    2014-01-01

    The relationship of postmenopausal hormone therapy with all-cause dementia and Alzheimer's disease dementia has been controversial. Given continued interest in the role of hormone therapy in chronic disease prevention and the emergence of more prospective studies, we conducted a systematic review to identify all epidemiologic studies meeting prespecified criteria reporting on postmenopausal hormone therapy use and risk of Alzheimer's disease or dementia. A systematic search of Medline and Embase through December 31, 2012, returned 15 articles meeting our criteria. Our meta-analysis of any versus never use did not support the hypothesis that hormone therapy reduces risk of Alzheimer's disease (summary estimate = 0.88, 95% confidence interval: 0.66, 1.16). Exclusion of trial findings did not change this estimate. There were not enough all-cause dementia results for a separate meta-analysis, but when we combined all-cause dementia results (n = 3) with Alzheimer's disease results (n = 7), the summary estimate remained null (summary estimate = 0.94, 95% confidence interval: 0.71, 1.26). The limited explorations of timing of use-both duration and early initiation-did not yield consistent findings. Our findings support current recommendations that hormone therapy should not be used for dementia prevention. We discuss trends in hormone therapy research that could explain our novel findings and highlight areas where additional data are needed.

  15. All-Cause and Cause-Specific Risk of Emergency Transport Attributable to Temperature: A Nationwide Study.

    PubMed

    Onozuka, Daisuke; Hagihara, Akihito

    2015-12-01

    Although several studies have estimated the associations between mortality or morbidity and extreme temperatures in terms of relative risk, few studies have investigated the risk of emergency transport attributable to the whole temperature range nationwide.We acquired data on daily emergency ambulance dispatches in all 47 prefectures of Japan from 2007 to 2010. We examined the relationship between emergency transport and temperature for each prefecture using a Poisson regression model in a distributed lag nonlinear model with adjustment for time trends. A random-effect multivariate meta-analysis was then applied to pool the estimates at the national level. Attributable morbidity was calculated for high and low temperatures, which were defined as those above or below the optimum temperature (ie, the minimum morbidity temperature) and for moderate and also extreme temperatures, which were defined using cutoffs at the 2.5th and 97.5th temperature percentiles.A total of 15,868,086 cases of emergency transport met the inclusion criteria. The emergency transport was attributable to nonoptimal temperature. The median minimum morbidity percentile was in the 79th percentile for all causes, the 96th percentile for cardiovascular disease, and the 92th percentile for respiratory disease. The fraction attributable to low temperature was 6.94% (95% eCI: 5.93-7.70) for all causes, 17.93% (95% eCI: 16.10-19.25) for cardiovascular disease, and 12.19% (95% eCI: 9.90-13.66) for respiratory disease, whereas the fraction attributable to high temperature was small (all causes = 1.01%, 95% eCI: 0.90-1.11; cardiovascular disease = 0.10%, 95% eCI: 0.04-0.14; respiratory disease = 0.29%, 95% eCI: 0.07-0.50). The all-cause morbidity risk that was attributable to temperature was related to moderate cold, with an overall estimate of 6.41% (95% eCI: 5.47-7.20). Extreme temperatures were responsible for a small fraction, which corresponded to 0.57% (95% eCI: 0.50-0.62) for extreme

  16. Incremental effects of 28 days of beta-alanine supplementation on high-intensity cycling performance and blood lactate in masters female cyclists.

    PubMed

    Glenn, J M; Gray, M; Stewart, R; Moyen, N E; Kavouras, S A; DiBrezzo, R; Turner, R; Baum, J

    2015-12-01

    Within the aging population, there exists a subset of individuals termed masters athletes (MA). As masters-level competition increases in popularity, MA must find methods to enhance individual athletic performance. Longitudinal beta-alanine (BA) supplementation is suggested to enhance physical capability during exercise; however, these effects have not been evaluated in MA. To examine the longitudinal effects of BA on time to exhaustion (TTE), total work completed (TWC), and lactate clearance in female MA cyclists. Twenty-two female MA (age = 53.3 ± 1.0) participated in this double-blind design. Subjects were randomly assigned to BA (n = 11; 800 mg BA + 8 g dextrose) or placebo (PLA; n = 11; 8 g dextrose) groups and supplemented 4 doses/day over 28 days. Every 7 days, subjects completed a cycling TTE at 120% VO2max, and TWC was calculated. Blood lactate was measured at baseline, immediate post, and 20-min post each TTE. No significant differences existed between groups for any variable at baseline (p > 0.05). After 28 days supplementation, BA had greater TTE (23 vs 1% change) and TWC (21 vs 2% change) than PLA (p < 0.05). Following the 20-min TTE recovery, lactate was 24% lower in BA compared to PLA (4.35 vs. 5.76 mmol/L, respectively). No differences existed for variables during intermittent weeks. 28 days of BA supplementation increased cycling performance via an enhanced time to exhaustion and total work completed with associated lactate clearance during passive rest in female MA.

  17. Prognostic factors of 28 days survival rate in patients with a first acute myocardial infarction based on gender in Isfahan, Iran (2000-2009)

    PubMed Central

    Mohammadian, Mahdi; Hosseini, Shidokht; Salehiniya, Hamid; Sadeghi, Masoumeh; Sarrafzadegan, Nizal; Roohafza, Hamid Reza; Khazaei, Salman; Soltani, Shahin; Sarrafkia, Ali; Golshahi, Jafar; Mohammadian-Hafshejani, Abdollah

    2015-01-01

    BACKGROUND Determinant prognostic factors of 28 days survival rate in patients with a first acute myocardial infarction (AMI) based on gender in teen year’s period in Isfahan, Iran, was the aim of this study. METHODS This study is a prospective hospital-based study that consisted, all patients with AMI admitted to all hospitals (private and universal hospitals) in Isfahan and Najafabad (Iran) during 2000-2009. To determinant the prognostic factors of 28 days survival rate in patients based on gender, analysis conducted separately for male and female. In analysis, we use of t-test, log Rank tests, Kaplan-Meier method, and univariate and multivariate Cox regression model. RESULTS Short-term (28 days) survival rate was 92.5% in male and 86.7% in female (P < 0.001). The adjusted hazard ratio (HR) of death for age group 80 years and older was 12.7 [95% confidence interval (CI): 5.14-31.3] in male and 8.78 (95% CI: 1.2-63.1) in female. HR for acute transmural MI of the unspecified site in male was 8.9 (95% CI: 4.68-16.97) and in female 9.33 (95% CI: 4.42-19.7). HR for receive of streptokinase in male was 1.11 (95% CI: 0.94-1.31) and in female was 0.69 (95% CI: 0.56-0.84). CONCLUSION Short-term survival rate in male was a higher than female. In male age, anatomic location of MI and hospital status and in female streptokinase use and anatomic location of MI was the most important prognostic factors of survival in-patient with AMI in Isfahan. PMID:26862341

  18. Determination of enrofloxacin stability and in vitro efficacy against Staphylococcus pseudintermedius and Pseudomonas aeruginosa in four ear cleaner solutions over a 28 day period.

    PubMed

    Metry, Catherine A; Maddox, Carol W; Dirikolu, Levent; Johnson, Yvette J; Campbell, Karen L

    2012-02-01

    Chemical stability and in vitro bactericidal efficacy of 0.9% enrofloxacin-compounded solutions were evaluated following storage at room temperature for 28 days. Chemical stability of enrofloxacin was determined by high-performance liquid chromatography (HPLC) in five compounded solutions, including sterile water. Bactericidal efficacy was determined by spiral plating serial 10-fold dilutions of bacteria and solutions followed by colony counts. Tris-EDTA [TrizEDTA(®) (TE)], Tris-EDTA and 0.15% chlorhexidine [TrizChlor(®) (TC)], 2.5% lactic acid, 0.1% salicylic acid and 0.1% parachlorometaxylenol [Epi-Otic (EO)], and 0.1% free salicylic acid, 0.1% parachlorometaxylenol and 0.5% EDTA [Epi-Otic Advanced (EA)] were used. High-performance liquid chromatography was carried out with one-step liquid/liquid extraction to detect and quantify enrofloxacin stability. Mean recoveries for compounded samples run in triplicate at 28 days were 97.7% (TE), 99.9% (TC), 98.1% (EO) and 97.8% (EA). Kruskal-Wallis analysis showed no significant difference in the percentage recovery (H=0.0539, df=3, P=0.9967). American Type Culture Collection strains of Staphylococcus pseudintermedius and Pseudomonas aeruginosa were used to evaluate in vitro efficacy following 30 min incubation on days 0, 14 and 28. Consistent in vitro bactericidal efficacy of all compounded solutions, indicated by killing >2.3×10(7) colony-forming units/mL, was seen; however, bactericidal efficacy decreased for compounded TC on day 14. Pseudomonas aeruginosa was more sensitive to the ear cleaners and enrofloxacin than S. pseudintermedius. The HPLC and in vitro data suggest that 0.9% enrofloxacin compounded with sterile water, TE, EO and EA maintains chemical stability and bactericidal efficacy for 28 days.

  19. Immunotoxicological profile of chloramine in female B6C3F1 mice when administered in the drinking water for 28 days.

    PubMed

    Guo, Tai L; Germolec, Dori R; Collins, Bradley J; Luebke, Robert W; Auttachoat, Wimolnut; Smith, Matthew J; White, Kimber L

    2011-01-01

    Monochloramine has been used to provide a disinfecting residual in water distribution systems where it is difficult to maintain an adequate free-chlorine residual or where disinfection by-product formation is of concern. The goal of this study was to characterize the immunotoxic effects of chloramine in female B(6)C(3)F(1) mice when administered via the drinking water. Mice were exposed to chloramine-containing deionized tap water at 2, 10, 20, 100, or 200 ppm for 28 days. No statistically significant differences in drinking water consumption, body weight, body weight gain, organ weights, or hematological parameters between the exposed and control animals were noted during the experimental period. There were no changes in the percentages and numbers of total B-lymphocytes, T-lymphocytes, CD4(+) and CD8(+) T-lymphocytes, natural killer (NK) cells, and macrophages in the spleen. Exposure to chloramine did not affect the IgM antibody-forming cell response to sheep red blood cells (SRBC) or anti-SRBC IgM antibody production. Minimal effects, judged to be biologically insignificant, were observed in the mixed-leukocyte response and NK activity. In conclusion, chloramine produced no toxicological and immunotoxic effects in female B(6)C(3)F(1) mice when administered for 28 days in the drinking water at concentrations ranging from 2-200 ppm.

  20. Cuprizone decreases intermediate and late-stage progenitor cells in hippocampal neurogenesis of rats in a framework of 28-day oral dose toxicity study

    SciTech Connect

    Abe, Hajime; Tanaka, Takeshi; Kimura, Masayuki; Mizukami, Sayaka; Saito, Fumiyo; Imatanaka, Nobuya; Akahori, Yumi; Yoshida, Toshinori; Shibutani, Makoto

    2015-09-15

    Developmental exposure to cuprizone (CPZ), a demyelinating agent, impairs intermediate-stage neurogenesis in the hippocampal dentate gyrus of rat offspring. To investigate the possibility of alterations in adult neurogenesis following postpubertal exposure to CPZ in a framework of general toxicity studies, CPZ was orally administered to 5-week-old male rats at 0, 120, or 600 mg/kg body weight/day for 28 days. In the subgranular zone (SGZ), 600 mg/kg CPZ increased the number of cleaved caspase-3{sup +} apoptotic cells. At ≥ 120 mg/kg, the number of SGZ cells immunoreactive for TBR2, doublecortin, or PCNA was decreased, while that for SOX2 was increased. In the granule cell layer, CPZ at ≥ 120 mg/kg decreased the number of postmitotic granule cells immunoreactive for NEUN, CHRNA7, ARC or FOS. In the dentate hilus, CPZ at ≥ 120 mg/kg decreased phosphorylated TRKB{sup +} interneurons, although the number of reelin{sup +} interneurons was unchanged. At 600 mg/kg, mRNA levels of Bdnf and Chrna7 were decreased, while those of Casp4, Casp12 and Trib3 were increased in the dentate gyrus. These data suggest that CPZ in a scheme of 28-day toxicity study causes endoplasmic reticulum stress-mediated apoptosis of granule cell lineages, resulting in aberrations of intermediate neurogenesis and late-stage neurogenesis and following suppression of immediate early gene-mediated neuronal plasticity. Suppression of BDNF signals to interneurons caused by decreased cholinergic signaling may play a role in these effects of CPZ. The effects of postpubertal CPZ on neurogenesis were similar to those observed with developmental exposure, except for the lack of reelin response, which may contribute to a greater decrease in SGZ cells. - Highlights: • Effect of 28-day CPZ exposure on hippocampal neurogenesis was examined in rats. • CPZ suppressed intermediate neurogenesis and late-stage neurogenesis in the dentate gyrus. • CPZ suppressed BDNF signals to interneurons by decrease of

  1. A repeated 28-day oral dose toxicity study of nonylphenol in rats, based on the 'Enhanced OECD Test Guideline 407' for screening of endocrine-disrupting chemicals.

    PubMed

    Woo, Gye-Hyeong; Shibutani, Makoto; Ichiki, Tsutomu; Hamamura, Masao; Lee, Kyoung-Youl; Inoue, Kaoru; Hirose, Masao

    2007-02-01

    A 28-day repeated oral dose toxicity study of nonylphenol (NP) was performed for an international validation of the 'Enhanced OECD Test Guideline 407' paying particular attention to the sensitivity of individual endocrine-related parameters. Sprague-Dawley rats, each group consisting of ten males and ten females, were administered NP once daily by gavage at doses of 0 (control), 10, 50, or 250 mg/kg body weight. At 250 mg/kg, three females died or became moribund during the experiment. At this dose, hepatic and renal toxicity was evident in both sexes with increase of relative liver and kidney weights as well as histopathological changes, such as centrilobular liver cell hypertrophy and a variety of renal tubular lesions, and alteration of serum biochemical parameters, some of them being evident from 50 mg/kg in females (glucose and inorganic phosphates). Hematologically, development of anemia was evident at 250 mg/kg in both sexes. Regarding endocrine-related effects, increase of thyroid weight in males was detected from 50 mg/kg. At 250 mg/kg, males exhibited reduction of relative weights of the ventral prostate and seminal vesicles, and females developed irregular estrous cyclicity and vaginal mucosal hyperplasia. Although changes in serum hormone levels were detected in both sexes, magnitude of the changes was small to be regarded as a low toxicological significance. In summary, repeated oral doses of NP to rats for 28 days resulted in hepato-renal toxicity from 50 mg/kg and anemia at 250 mg/kg. Effects on the endocrine system were observed from 50 mg/kg, and assessment of weights and histopathology of endocrine-related organs and estrous cyclicity may be valid in a battery for detecting endocrine effects of NP. The no-observed-adverse-effect level of NP was estimated to be 10 mg/kg per day.

  2. Comparison of the toxicity of several fumonisin derivatives in a 28-day feeding study with female B6C3F(1) mice.

    PubMed

    Howard, Paul C; Couch, Letha H; Patton, Ralph E; Eppley, Robert M; Doerge, Daniel R; Churchwell, Mona I; Marques, M Matilde; Okerberg, Carlin V

    2002-12-15

    Fumonisinmycotoxins are produced by Fusaria fungi that grow worldwide primarily on corn. Fumonisin B(1), the most predominant form in corn samples, is a renal carcinogen in male F344/N rats and a hepatocarcinogen in female B6C3F(1) mice when fed at concentrations higher than 50 ppm (70 micromol/kg) in the diet for 2 years. We sought to determine the relative toxicities of several naturally occurring fumonisin derivatives when included in the diet of female B6C3F(1) mice. Mice were fed diets containing fumonisin B(1), fumonisin B(2), fumonisin B(3), fumonisin P1, hydrolyzed-fumonisin B(1), N-(acetyl)fumonisin B(1), or N-(carboxymethyl)fumonisin B(1) (approximately 0, 14, 70, and 140 micromol/kg diet) for 28 days. None of the doses used caused a decrease in body weight gain over the 28 days. Serum levels of total bile acids, cholesterol, and alkaline phosphatase were increased only in mice receiving 72 and 143 micromol/kg fumonisin B(1), suggesting that only fumonisin B(1) was hepatotoxic in the mice. Corroborating this observation, the liver weight, relative to body weight, was decreased only in the mice that consumed 143 micromol/kg fumonisin B(1). Consistent with fumonisin B(1) inhibition of ceramide synthase, the liver sphinganine-to-sphingosine ratio was increased and the liver ceramide levels were decreased only in the mice receiving 72 and 143 micromol/kg fumonisin B(1). Increased hepatocellular apoptosis, hepatocellular hypertrophy, Kupffer cell hyperplasia, and macrophage pigmentation were detected in the mice consuming 72 and 143 micromol/kg fumonisin B(1). The other fumonisin derivatives did not alter serum analytes, organ weights, or hepatic structure. These results suggest that, of the naturally occurring fumonisins, fumonisin B(1) is the principal hepatotoxic derivative in the B6C3F(1) mouse.

  3. Renal hemodynamic and morphological changes after 7 and 28 days of leptin treatment: the participation of angiotensin II via the AT1 receptor.

    PubMed

    Thieme, Karina; Oliveira-Souza, Maria

    2015-01-01

    The role of hyperleptinemia in cardiovascular diseases is well known; however, in the renal tissue, the exact site of leptin's action has not been established. This study was conducted to assess the effect of leptin treatment for 7 and 28 days on renal function and morphology and the participation of angiotensin II (Ang II), through its AT1 receptor. Rats were divided into four groups: sham, losartan (10 mg/kg/day, s.c.), leptin (0.5 mg/kg/day for the 7 days group and 0.25 mg/kg/day for the 28 days group) and leptin plus losartan. Plasma leptin, Ang II and endothelin 1 (ET-1) levels were measured using an enzymatic immuno assay. The systolic blood pressure (SBP) was evaluated using the tail-cuff method. The renal plasma flow (RPF) and the glomerular filtration rate (GFR) were determined by p-aminohippuric acid and inulin clearance, respectively. Urinary Na+ and K+ levels were also analyzed. Renal morphological analyses, desmin and ED-1 immunostaining were performed. Proteinuria was analyzed by silver staining. mRNA expression of renin-angiotensin system (RAS) components, TNF-α and collagen type III was analyzed by quantitative PCR. Our results showed that leptin treatment increased Ang II plasma levels and progressively increased the SBP, achieving a pre-hypertension state. Rats treated with leptin 7 days showed a normal RPF and GFR, but increased filtration fraction (FF) and natriuresis. However, rats treated with leptin for 28 showed a decrease in the RPF, an increase in the FF and no changes in the GFR or tubular function. Leptin treatment-induced renal injury was demonstrated by: glomerular hypertrophy, increased desmin staining, macrophage infiltration in the renal tissue, TNF-α and collagen type III mRNA expression and proteinuria. In conclusion, our study demonstrated the progressive renal morphological changes in experimental hyperleptinemia and the interaction between leptin and the RAS on these effects.

  4. 17alpha-methyltestosterone: 28-day oral toxicity study in the rat based on the "Enhanced OECD Test Guideline 407" to detect endocrine effects.

    PubMed

    Wason, Sheila; Pohlmeyer-Esch, Gabriele; Pallen, Catherine; Palazzi, Xavier; Espuña, Gemma; Bars, Remi

    2003-11-05

    A 28-day oral gavage toxicity study in the rat with 17alpha-methyltestosterone was conducted as part of the international validation exercise on the modified Enhanced OECD Test Guideline 407 (Organisation for Economic Co-operation and Development, Paris). Special emphasis was placed on the endocrine mediated effects exerted by 17alpha-methyltestosterone, a potent androgen agonist. The test compound was administered daily by oral gavage for at least 28 days to groups of 7-week-old-Wistar rats. Dose levels were 0, 10, 40 and 200 mg/kg body weight per day for males and 0, 10, 100 and 600 mg/kg body weight per day for females. In addition, and outside the remit of the enhanced protocol, testosterone levels in males, oestradiol levels in females and luteinizing hormone (LH) levels in both sexes were measured, to provide a broader profile on the hormonally mediated effects of 17alpha-methyltestosterone. Furthermore, stage-specific quantification of Terminal deoxynucleotidyl transferase-mediated dUTP Nick-End Labeling (TUNEL)-labeled germ cells (apoptotic germ cells) in the seminiferous tubules was also performed, in an effort to demonstrate the precise stages in the spermatogenic cycle 17alpha-methyltestosterone exerts its effect. In this study, the most critical additional parameters contained in the Enhanced OECD Test Guideline 407 for the detection of endocrine disruption were considered to be the histopathological assessment and organ weight data of endocrine-related tissues. Beyond the scope of this validation exercise, an increase in apoptosis in specific germ cell types was detected using the TUNEL assay in male rats treated at 200 and 40 mg/kg.

  5. Cuprizone decreases intermediate and late-stage progenitor cells in hippocampal neurogenesis of rats in a framework of 28-day oral dose toxicity study.

    PubMed

    Abe, Hajime; Tanaka, Takeshi; Kimura, Masayuki; Mizukami, Sayaka; Saito, Fumiyo; Imatanaka, Nobuya; Akahori, Yumi; Yoshida, Toshinori; Shibutani, Makoto

    2015-09-15

    Developmental exposure to cuprizone (CPZ), a demyelinating agent, impairs intermediate-stage neurogenesis in the hippocampal dentate gyrus of rat offspring. To investigate the possibility of alterations in adult neurogenesis following postpubertal exposure to CPZ in a framework of general toxicity studies, CPZ was orally administered to 5-week-old male rats at 0, 120, or 600mg/kg body weight/day for 28days. In the subgranular zone (SGZ), 600mg/kg CPZ increased the number of cleaved caspase-3(+) apoptotic cells. At ≥120mg/kg, the number of SGZ cells immunoreactive for TBR2, doublecortin, or PCNA was decreased, while that for SOX2 was increased. In the granule cell layer, CPZ at ≥120mg/kg decreased the number of postmitotic granule cells immunoreactive for NEUN, CHRNA7, ARC or FOS. In the dentate hilus, CPZ at ≥120mg/kg decreased phosphorylated TRKB(+) interneurons, although the number of reelin(+) interneurons was unchanged. At 600mg/kg, mRNA levels of Bdnf and Chrna7 were decreased, while those of Casp4, Casp12 and Trib3 were increased in the dentate gyrus. These data suggest that CPZ in a scheme of 28-day toxicity study causes endoplasmic reticulum stress-mediated apoptosis of granule cell lineages, resulting in aberrations of intermediate neurogenesis and late-stage neurogenesis and following suppression of immediate early gene-mediated neuronal plasticity. Suppression of BDNF signals to interneurons caused by decreased cholinergic signaling may play a role in these effects of CPZ. The effects of postpubertal CPZ on neurogenesis were similar to those observed with developmental exposure, except for the lack of reelin response, which may contribute to a greater decrease in SGZ cells.

  6. The novel marker LTBP2 predicts all-cause and pulmonary death in patients with acute dyspnoea.

    PubMed

    Breidthardt, Tobias; Vanpoucke, Griet; Potocki, Mihael; Mosimann, Tamina; Ziller, Ronny; Thomas, Gregoire; Laroy, Wouter; Moerman, Piet; Socrates, Thenral; Drexler, Beatrice; Mebazaa, Alexandre; Kas, Koen; Mueller, Christian

    2012-11-01

    The risk stratification in patients presenting with acute dyspnoea remains a challenge. We therefore conducted a prospective, observational cohort study enrolling 292 patients presenting to the emergency department with acute dyspnoea. A proteomic approach for antibody-free targeted protein quantification based on high-end MS was used to measure LTBP2 [latent TGF (transforming growth factor)-binding protein 2] levels. Final diagnosis and death during follow-up were adjudicated blinded to LTBP2 levels. AHF (acute heart failure) was the final diagnosis in 54% of patients. In both AHF (P<0.001) and non-AHF (P=0.015) patients, LTBP2 levels at presentation were significantly higher in non-survivors compared with survivors with differences on median levels being 2.2- and 1.5-fold respectively. When assessing the cause of death, LTBP2 levels were significantly higher in patients dying from pulmonary causes (P=0.0005). Overall, LTBP2 powerfully predicted early pulmonary death {AUC (area under the curve), 0.95 [95% CI (confidence interval), 0.91-0.98]}. In ROC (receiver operating characteristic) curve analyses for the prediction of 1-year mortality LTBP2 achieved an AUC of 0.77 (95% CI, 0.71-0.84); comparable with the predictive potential of NT-proBNP [N-terminal pro-B-type natriuruetic peptide; 0.77 (95% CI, 0.72-0.82)]. Importantly, the predictive potential of LTBP2 persisted in patients with AHF as the cause of dypnea (AUC 0.78) and was independent of renal dysfunction (AUC 0.77). In a multivariate Cox regression analysis, LTBP2 was the strongest independent predictor of death [HR (hazard ratio), 3.76 (95% CI, 2.13-6.64); P<0.0001]. In conclusion, plasma levels of LTBP2 present a novel and powerful predictor of all-cause mortality, and particularly pulmonary death. Cause-specific prediction of death would enable targeted prevention, e.g. with pre-emptive antibiotic therapy.

  7. Influence of Exercise on the Metabolic Profile Caused by 28 days of Bed Rest with Energy Deficit and Amino Acid Supplementation in Healthy Men

    PubMed Central

    Brooks, Naomi E.; Cadena, Samuel M.; Cloutier, Gregory; Vega-López, Sonia; Roubenoff, Ronenn; Castaneda-Sceppa, Carmen

    2014-01-01

    Objective Muscle loss and metabolic changes occur with disuse [i.e. bed rest (BR)]. We hypothesized that BR would lead to a metabolically unhealthy profile defined by: increased circulating tumor necrosis factor (TNF)-α, decreased circulating insulin-like-growth-factor (IGF)-1, decreased HDL-cholesterol, and decreased muscle density (MD; measured by mid-thigh computerized tomography). Methods We investigated the metabolic profile after 28 days of BR with 8±6% energy deficit in male individuals (30-55 years) randomized to resistance exercise with amino acid supplementation (RT, n=24) or amino acid supplementation alone (EAA, n=7). Upper and lower body exercises were performed in the horizontal position. Blood samples were taken at baseline, after 28 days of BR and 14 days of recovery. Results We found a shift toward a metabolically unfavourable profile after BR [compared to baseline (BLN)] in both groups as shown by decreased HDL-cholesterol levels (EAA: BLN: 39±4 vs. BR: 32±2 mg/dL, RT: BLN: 39±1 vs. BR: 32±1 mg/dL; p<0.001) and Low MD (EAA: BLN: 27±4 vs. BR: 22±3 cm2, RT: BLN: 28±2 vs. BR: 23±2 cm2; p<0.001). A healthier metabolic profile was maintained with exercise, including NormalMD (EAA: BLN: 124±6 vs. BR: 110±5 cm2, RT: BLN: 132±3 vs. BR: 131±4 cm2; p<0.001, time-by-group); although, exercise did not completely alleviate the unfavourable metabolic changes seen with BR. Interestingly, both groups had increased plasma IGF-1 levels (EAA: BLN:168±22 vs. BR 213±20 ng/mL, RT: BLN:180±10 vs. BR: 219±13 ng/mL; p<0.001) and neither group showed TNFα changes (p>0.05). Conclusions We conclude that RT can be incorporated to potentially offset the metabolic complications of BR. PMID:25317071

  8. Estimation of acute oral toxicity using the No Observed Adverse Effect Level (NOAEL) from the 28 day repeated dose toxicity studies in rats.

    PubMed

    Bulgheroni, Anna; Kinsner-Ovaskainen, Agnieszka; Hoffmann, Sebastian; Hartung, Thomas; Prieto, Pilar

    2009-02-01

    Acute systemic toxicity is one of the areas of particular concern due to the 2009 deadline set by the 7th Amendment of the Cosmetics Directive (76/768/EEC), which introduces a testing and marketing ban of cosmetic products with ingredients tested on animals. The scientific community is putting considerable effort into developing and validating non-animal alternatives in this area. However, it is unlikely that validated and regulatory accepted alternative methods and/or strategies will be available in March 2009. Following the initiatives undertaken in the pharmaceutical industry to waive the acute oral toxicity testing before going to clinical studies by using information from other in vivo studies, we proposed an approach to identify non-toxic compounds (LD50>2000mg/kg) using information from 28 days repeated dose toxicity studies. Taking into account the high prevalence of non-toxic substances (87%) in the New Chemicals Database, it was possible to set a NOAEL threshold of 200mg/kg that allowed the correct identification of 63% of non-toxic compounds, while <1% of harmful compounds were misclassified as non-toxic. Since repeated dose toxicity studies can be performed in vivo until 2013, the proposed approach could have an immediate impact for the testing of cosmetic ingredients.

  9. A 28-day rat inhalation study with an integrated molecular toxicology endpoint demonstrates reduced exposure effects for a prototypic modified risk tobacco product compared with conventional cigarettes.

    PubMed

    Kogel, Ulrike; Schlage, Walter K; Martin, Florian; Xiang, Yang; Ansari, Sam; Leroy, Patrice; Vanscheeuwijck, Patrick; Gebel, Stephan; Buettner, Ansgar; Wyss, Christoph; Esposito, Marco; Hoeng, Julia; Peitsch, Manuel C

    2014-06-01

    Towards a systems toxicology-based risk assessment, we investigated molecular perturbations accompanying histopathological changes in a 28-day rat inhalation study combining transcriptomics with classical histopathology. We demonstrated reduced biological activity of a prototypic modified risk tobacco product (pMRTP) compared with the reference research cigarette 3R4F. Rats were exposed to filtered air or to three concentrations of mainstream smoke (MS) from 3R4F, or to a high concentration of MS from a pMRTP. Histopathology revealed concentration-dependent changes in response to 3R4F that were irritative stress-related in nasal and bronchial epithelium, and inflammation-related in the lung parenchyma. For pMRTP, significant changes were seen in the nasal epithelium only. Transcriptomics data were obtained from nasal and bronchial epithelium and lung parenchyma. Concentration-dependent gene expression changes were observed following 3R4F exposure, with much smaller changes for pMRTP. A computational-modeling approach based on causal models of tissue-specific biological networks identified cell stress, inflammation, proliferation, and senescence as the most perturbed molecular mechanisms. These perturbations correlated with histopathological observations. Only weak perturbations were observed for pMRTP. In conclusion, a correlative evaluation of classical histopathology together with gene expression-based computational network models may facilitate a systems toxicology-based risk assessment, as shown for a pMRTP.

  10. A 28-day oral toxicity evaluation of small interfering RNAs and a long double-stranded RNA targeting vacuolar ATPase in mice.

    PubMed

    Petrick, Jay S; Moore, William M; Heydens, William F; Koch, Michael S; Sherman, James H; Lemke, Shawna L

    2015-02-01

    New biotechnology-derived crop traits have been developed utilizing the natural process of RNA interference (RNAi). However, plant-produced double stranded RNAs (dsRNAs) are not known to present a hazard to mammals because numerous biological barriers limit uptake and potential for activity. To evaluate this experimentally, dsRNA sequences matching the mouse vATPase gene (an established target for control of corn rootworms) were evaluated in a 28-day toxicity study with mice. Test groups were orally gavaged with escalating doses of either a pool of four 21-mer vATPase small interfering RNAs (siRNAs) or a 218-base pair vATPase dsRNA. There were no treatment-related effects on body weight, food consumption, clinical observations, clinical chemistry, hematology, gross pathology, or histopathology endpoints. The highest dose levels tested were considered to be the no observed adverse effect levels (NOAELs) for the 21-mer siRNAs (48 mg/kg/day) and the 218 bp dsRNA (64 mg/kg/day). As an additional exploratory endpoint, vATPase gene expression, was evaluated in selected gastrointestinal tract and systemic tissues. The results of this assay did not indicate treatment-related suppression of vATPase. The results of this study indicate that orally ingested dsRNAs, even those targeting a gene in the test species, do not produce adverse health effects in mammals.

  11. Repeated dose (28-day) administration of silver nanoparticles of varied size and coating does not significantly alter the indigenous murine gut microbiome.

    PubMed

    Wilding, Laura A; Bassis, Christine M; Walacavage, Kim; Hashway, Sara; Leroueil, Pascale R; Morishita, Masako; Maynard, Andrew D; Philbert, Martin A; Bergin, Ingrid L

    2016-01-01

    Silver nanoparticles (AgNPs) have been used as antimicrobials in a number of applications, including topical wound dressings and coatings for consumer products and biomedical devices. Ingestion is a relevant route of exposure for AgNPs, whether occurring unintentionally via Ag dissolution from consumer products, or intentionally from dietary supplements. AgNP have also been proposed as substitutes for antibiotics in animal feeds. While oral antibiotics are known to have significant effects on gut bacteria, the antimicrobial effects of ingested AgNPs on the indigenous microbiome or on gut pathogens are unknown. In addition, AgNP size and coating have been postulated as significantly influential towards their biochemical properties and the influence of these properties on antimicrobial efficacy is unknown. We evaluated murine gut microbial communities using culture-independent sequencing of 16S rRNA gene fragments following 28 days of repeated oral dosing of well-characterized AgNPs of two different sizes (20 and 110 nm) and coatings (PVP and Citrate). Irrespective of size or coating, oral administration of AgNPs at 10 mg/kg body weight/day did not alter the membership, structure or diversity of the murine gut microbiome. Thus, in contrast to effects of broad-spectrum antibiotics, repeat dosing of AgNP, at doses equivalent to 2000 times the oral reference dose and 100-400 times the effective in vitro anti-microbial concentration, does not affect the indigenous murine gut microbiome.

  12. Effects of SiO₂, ZrO₂, and BaSO₄ nanomaterials with or without surface functionalization upon 28-day oral exposure to rats.

    PubMed

    Buesen, Roland; Landsiedel, Robert; Sauer, Ursula G; Wohlleben, Wendel; Groeters, Sibylle; Strauss, Volker; Kamp, Hennicke; van Ravenzwaay, Bennard

    2014-10-01

    The effects of seven nanomaterials (four amorphous silicon dioxides with or without surface functionalization, two surface-functionalized zirconium dioxides, and barium sulfate) upon 28-day oral exposure to male or female rats were investigated. The studies were performed as limit tests in accordance with OECD Test Guideline 407 applying 1,000 mg test substance/kg body weight/day. Additionally, the acute phase proteins haptoglobin and α2-macroglobulin as well as cardiac troponin I were determined, and metabolome analysis was performed in plasma samples. There were no test substance-related adverse effects for any of the seven nanomaterials. Moreover, metabolomics changes were below the threshold of effects. Since test substance organ burden was not analyzed, it was not possible to establish whether the lack of findings related to the absence of systemic exposure of the tested nanomaterials or if the substances are devoid of any potential for toxicity. The few published subacute oral or short-term inhalation studies investigating comparable nanomaterials (SiO₂, ZrO₂, and BaSO₄) also do not report the occurrence of pronounced treatment-related findings. Overall, the results of the present survey provide a first indication that the tested nanomaterials neither cause local nor systemic effects upon subacute oral administration under the selected experimental conditions. Further investigations should aim at elucidating the extent of gastrointestinal absorption of surface-functionalized nanomaterials.

  13. A 28-day repeat dose toxicity study of steroidal glycoalkaloids, alpha-solanine and alpha-chaconine in the Syrian Golden hamster.

    PubMed

    Langkilde, Søren; Mandimika, Tafadzwa; Schrøder, Malene; Meyer, Otto; Slob, Wout; Peijnenburg, Ad; Poulsen, Morten

    2009-06-01

    Glycoalkaloids alpha-solanine and alpha-chaconine are naturally present toxicants in the potato plant (Solanumtuberosum). Human intake of high doses of glycoalkaloids has led to acute intoxication, in severe cases coma and death. Previous studies have indicated that the ratio of alpha-solanine to alpha-chaconine may determine the degree and nature of the glycoalkaloid toxicity in potatoes, as the toxicity of the two alkaloids act synergistically. The aim of the present study was to investigate whether an altered ratio of alpha-solanine and alpha-chaconine would reduce the toxicity of the glycoalkaloids. The Syrian Golden hamster was given daily doses of alpha-solanine and alpha-chaconine by gavage for 28 days. Doses of up to 33.3 mg total glycoalkaloids/kg body weight were applied in ratios of 1:3.7 and 1:70 (alpha-solanine:alpha-chaconine). Administration of the highest doses of both ratios resulted in distended and fluid filled small intestines and stomach. Animals receiving the ratio with the reduced content of alpha-solanine were less affected compared to those receiving the other ratio. Gene expression profiling experiments were conducted using RNA from epithelial scrapings from the small intestines of the hamsters administered the highest doses of the glycoalkaloid treatments. In general, more differential gene expression was observed in the epithelial scrapings of the hamsters fed the ratio of 1:3.7. Mostly, pathways involved in lipid and energy metabolism were affected by the ratio of 1:3.7.

  14. Liver and kidney damage induced by 4-aminopyridine in a repeated dose (28 days) oral toxicity study in rats: gene expression profile of hybrid cell death.

    PubMed

    Frejo, María Teresa; Del Pino, Javier; Lobo, Margarita; García, Jimena; Capo, Miguel Andrés; Díaz, María Jesús

    2014-03-03

    4-Aminopyridine (4-AP) is an orphan drug indicated for the treatment of neuromuscular disorders. There is a great controversy around the use of this drug because of its narrow safety index and because a large number of adverse effects have been reported. Moreover, it was shown to induce cell death in different cell lines, being reported mainly apoptosis and necrosis as the principal pathways of cell death mediated by blockage of K channels or the Na, K-ATPase, but until now it was not described in vivo cell death induced by 4-aminipyridine. To provide new subchronic toxicity data and specifically, evaluate if 4-AP is able to induce in vivo cell death process and the main pathways related to it, a repeated dose (28 days) oral toxicity study, at therapeutic range of doses, was conducted in rats. The anatomical pathology, the biochemical and hematological parameters were analyzed and a real-time PCR array analysis was developed with an Ingenuity Pathway Analysis (IPA). The leucocytes number, the lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) enzymatic activity were increased at all dose but the erythrocytes number, the hemoglobin concentration, the alkaline phosphatase (FAL) and alanine aminotransferase (ALT) enzymatic activity were increased only at highest dose studied. However, glucose levels decreased at all doses. The biochemical results are indicative of hepatic damage. The anatomy pathology studies showed cell death only on liver and kidney, and the real-time PCR array on liver tissue expressed a gene expression profile of necrotic and apoptotic induced cell death. The present work shows for the first time in vivo cell death on liver and kidney with features of apoptosis and necrosis induced by 4-AP and the gene expression profile shows that the cell death is mediated by necrotic and apoptotic pathways that support this finding.

  15. A 28-day repeated dose toxicity study of ultraviolet absorber 2-(2'-hydroxy-3',5'-di-tert-butylphenyl) benzotriazole in rats.

    PubMed

    Hirata-Koizumi, Mutsuko; Watari, Nobuaki; Mukai, Daisuke; Imai, Toshio; Hirose, Akihiko; Kamata, Eiichi; Ema, Makoto

    2007-01-01

    To examine the possible repeated-dose toxicity of an ultraviolet absorber, 2-(2'-hydroxy-3',5'-di-tert-butylphenyl)benzotriazole (HDBB), CD(SD)IGS rats were administered HDBB by gavage at a dose of 0 (vehicle: corn oil), 0.5, 2.5, 12.5, or 62.5 mg kg(-1) day(-1) for 28 days. At the completion of the administration period, a decrease in red blood cells, hemoglobin, and hematocrit was noted only in males at 2.5 mg/kg and more. Blood biochemical changes were noted at 0.5 mg/kg and more in males and at 62.5 mg/kg in females. Histopathologic changes were observed principally in the liver (vacuolar degeneration and hypertrophy of hepatocytes, bile duct proliferation, etc.) and in the heart (degeneration and hypertrophy of myocardium and cell infiltration). These changes were noted at 0.5 mg/kg and more in males and at 12.5 mg/kg and more in females. At higher doses, hypertrophy of tubular epithelium in the kidneys and diffuse follicular cell hyperplasia in the thyroids in both sexes and increased severity of basophilic tubules in the kidneys and extramedullary hematopoiesis in the spleen in males were also detected. After the 14-day recovery period, these changes mostly recovered in females but not in males. Based on these findings, no observed adverse effect level (NOAEL) was concluded to be less than 0.5 mg kg(-1) day(-1) in male rats and 2.5 mg kg(-1) day(-1) in female rats.

  16. Tissue distribution of inhaled micro- and nano-sized cerium oxide particles in rats: results from a 28-day exposure study.

    PubMed

    Geraets, Liesbeth; Oomen, Agnes G; Schroeter, Jeffry D; Coleman, Victoria A; Cassee, Flemming R

    2012-06-01

    In order to obtain more insight into the tissue distribution, accumulation, and elimination of cerium oxide nanoparticles after inhalation exposure, blood and tissue kinetics were investigated during and after a 28-day inhalation study in rats with micro- and nanocerium oxide particles (nominal primary particle size: < 5000, 40, and 5-10 nm). Powder aerosolization resulted in comparable mass median aerodynamic diameter (1.40, 1.17, and 1.02 μm). After single exposure, approximately 10% of the inhaled dose was measured in lung tissue, as was also estimated by a multiple path particle dosimetry model (MPPD). Though small differences in pulmonary deposition efficiencies of cerium oxide were observed, no consistent differences in pulmonary deposition between the micro- and nanoparticles were observed. Each cerium oxide sample was also distributed to tissues other than lung after a single 6-h exposure, such as liver, kidney, and spleen and also brain, testis, and epididymis. No clear particle size-dependent effect on extrapulmonary tissue distribution was observed. Repeated exposure to cerium oxide resulted in significant accumulation of the particles in the (extra)pulmonary tissues. In addition, tissue clearance was shown to be slow, and, overall, insignificant amounts of cerium oxide were eliminated from the body at 48- to 72-h post-exposure. In conclusion, no clear effect of the primary particle size or surface area on pulmonary deposition and extrapulmonary tissue distribution could be demonstrated. This is most likely explained by similar aerodynamic diameter of the cerium oxide particles in air because of the formation of aggregates and irrespective possible differences in surface characteristics. The implications of the accumulation of cerium oxide particles for systemic toxicological effects after repeated chronic exposure via ambient air are significant and require further exploration.

  17. No Increases in Biomarkers of Genetic Damage or Pathological Changes in Heart and Brain Tissues in Male Rats Administered Methylphenidate Hydrochloride (Ritalin) for 28 Days

    PubMed Central

    Witt, Kristine L.; Malarkey, David E.; Hobbs, Cheryl A.; Davis, Jeffrey P.; Kissling, Grace E.; Caspary, William; Travlos, Gregory; Recio, Leslie

    2009-01-01

    Following a 2005 report of chromosomal damage in children with attention deficit/hyperactivity disorder (ADHD) who were treated with the commonly prescribed medication methylphenidate (MPH), numerous studies have been conducted to clarify the risk for MPH-induced genetic damage. Although most of these studies reported no changes in genetic damage endpoints associated with exposure to MPH, one recent study (Andreazza et al. 2007) reported an increase in DNA damage detected by the Comet assay in blood and brain cells of Wistar rats treated by intraperitoneal injection with 1, 2, or 10 mg/kg MPH; no increases in micronucleated lymphocyte frequencies were observed in these rats. To clarify these findings, we treated adult male Wistar Han rats with 0, 2, 10, or 25 mg/kg MPH by gavage once daily for 28 consecutive days and measured micronucleated reticulocyte (MN-RET) frequencies in blood, and DNA damage in blood, brain, and liver cells 4 hr after final dosing. Flow cytometric evaluation of blood revealed no significant increases in MN-RET. Comet assay evaluations of blood leukocytes and cells of the liver, as well as of the striatum, hippocampus, and frontal cortex of the brain showed no increases in DNA damage in MPH-treated rats in any of the three treatment groups. Thus, the previously reported observations of DNA damage in blood and brain tissue of rats exposed to MPH for 28 days were not confirmed in this study. Additionally, no histopathological changes in brain or heart, or elevated serum biomarkers of cardiac injury were observed in these MPH-exposed rats. PMID:19634155

  18. No increases in biomarkers of genetic damage or pathological changes in heart and brain tissues in male rats administered methylphenidate hydrochloride (Ritalin) for 28 days.

    PubMed

    Witt, Kristine L; Malarkey, David E; Hobbs, Cheryl A; Davis, Jeffrey P; Kissling, Grace E; Caspary, William; Travlos, Gregory; Recio, Leslie

    2010-01-01

    Following a 2005 report of chromosomal damage in children with attention deficit/hyperactivity disorder (ADHD) who were treated with the commonly prescribed medication methylphenidate (MPH), numerous studies have been conducted to clarify the risk for MPH-induced genetic damage. Although most of these studies reported no changes in genetic damage endpoints associated with exposure to MPH, one recent study (Andreazza et al. [2007]: Prog Neuropsychopharmacol Biol Psychiatry 31:1282-1288) reported an increase in DNA damage detected by the Comet assay in blood and brain cells of Wistar rats treated by intraperitoneal injection with 1, 2, or 10 mg/kg MPH; no increases in micronucleated lymphocyte frequencies were observed in these rats. To clarify these findings, we treated adult male Wistar Han rats with 0, 2, 10, or 25 mg/kg MPH by gavage once daily for 28 consecutive days and measured micronucleated reticulocyte (MN-RET) frequencies in blood, and DNA damage in blood, brain, and liver cells 4 hr after final dosing. Flow cytometric evaluation of blood revealed no significant increases in MN-RET. Comet assay evaluations of blood leukocytes and cells of the liver, as well as of the striatum, hippocampus, and frontal cortex of the brain showed no increases in DNA damage in MPH-treated rats in any of the three treatment groups. Thus, the previously reported observations of DNA damage in blood and brain tissue of rats exposed to MPH for 28 days were not confirmed in this study. Additionally, no histopathological changes in brain or heart, or elevated serum biomarkers of cardiac injury were observed in these MPH-exposed rats.

  19. Cellular distribution of cell cycle-related molecules in the renal tubules of rats treated with renal carcinogens for 28 days: relationship between cell cycle aberration and carcinogenesis.

    PubMed

    Taniai, Eriko; Hayashi, Hitomi; Yafune, Atsunori; Watanabe, Maiko; Akane, Hirotoshi; Suzuki, Kazuhiko; Mitsumori, Kunitoshi; Shibutani, Makoto

    2012-09-01

    Some renal carcinogens can induce karyomegaly, which reflects aberrant cell division in the renal tubules, from the early stages of exposure. To clarify the cell cycle-related changes during the early stages of renal carcinogenesis, we performed immunohistochemical analysis of tubular cells in male F344 rats treated with carcinogenic doses of representative renal carcinogens for 28 days. For this purpose, the karyomegaly-inducing carcinogens ochratoxin A (OTA), ferric nitrilotriacetic acid, and monuron, and the non-karyomegaly-inducing carcinogens tris(2-chloroethyl) phosphate and potassium bromate were examined. For comparison, a karyomegaly-inducing non-carcinogen, p-nitrobenzoic acid, and a non-carcinogenic non-karyomegaly-inducing renal toxicant, acetaminophen, were also examined. The outer stripe of the outer medulla (OSOM) and the cortex + OSOM were subjected to morphometric analysis of immunoreactive proximal tubular cells. Renal carcinogens, irrespective of their karyomegaly-inducing potential, increased proximal tubular cell proliferation accompanied by an increase in topoisomerase IIα-immunoreactive cells, suggesting a reflection of cell proliferation. Karyomegaly-inducing carcinogens increased nuclear Cdc2-, γH2AX-, and phosphorylated Chk2-immunoreactive cells in both areas, the former two acting in response to DNA damage and the latter one suggestive of sustained G₂. OTA, an OSOM-targeting carcinogen, could easily be distinguished from untreated controls and non-carcinogens by evaluation of molecules responding to DNA damage and G₂/M transition in the OSOM. Thus, all renal carcinogens examined facilitated proximal tubular proliferation by repeated short-term treatment. Among these, karyomegaly-inducing carcinogens may cause DNA damage and G₂ arrest in the target tubular cells.

  20. Integration of Pig-a, micronucleus, chromosome aberration and comet assay endpoints in a 28-day rodent toxicity study with urethane

    PubMed Central

    Stankowski, Leon F.; Aardema, Marilyn J.; Lawlor, Timothy E.; Pant, Kamala; Roy, Shambhu; Xu, Yong; Elbekai, Reem

    2015-01-01

    As part of the international Pig-a validation trials, we examined the induction of Pig-a mutant reticulocytes and red blood cells (RETCD59− and RBCCD59−, respectively) in peripheral blood of male Sprague Dawley® rats treated with urethane (25, 100 and 250mg/kg/day) or saline by oral gavage for 29 days. Additional endpoints integrated into this study were: micronucleated reticulocytes (MN-RET) in peripheral blood; chromosome aberrations (CAb) and DNA damage (%tail intensity via the comet assay) in peripheral blood lymphocytes (PBL); micronucleated polychromatic erythrocytes (MN-PCE) in bone marrow; and DNA damage (comet) in various organs at termination (the 29th dose was added for the comet endpoint at sacrifice). Ethyl methanesulfonate (EMS; 200mg/kg/day on Days 3, 4, 13, 14, 15, 27, 28 and 29) was evaluated as the concurrent positive control (PC). All animals survived to termination and none exhibited overt toxicity, but there were significant differences in body weight and body weight gain in the 250-mg/kg/day urethane group, as compared with the saline control animals. Statistically significant, dose-dependent increases were observed for urethane for: RETCD59− and RBCCD59− (on Days 15 and 29); MN-RET (on Days 4, 15 and 29); and MN-PCE (on Day 29). The comet assay yielded positive results in PBL (Day 15) and liver (Day 29), but negative results for PBL (Days 4 and 29) and brain, kidney and lung (Day 29). No significant increases in PBL CAb were observed at any sample time. Except for PBL CAb (likely due to excessive cytotoxicity), EMS-induced significant increases in all endpoints/tissues. These results compare favorably with earlier in vivo observations and demonstrate the utility and sensitivity of the Pig-a in vivo gene mutation assay, and its ability to be easily integrated, along with other standard genotoxicity endpoints, into 28-day rodent toxicity studies. PMID:25934985

  1. A Retrospective Study of the Clinical Burden of Hospitalized All-Cause and Pneumococcal Pneumonia in Canada.

    PubMed

    McNeil, Shelly A; Qizilbash, Nawab; Ye, Jian; Gray, Sharon; Zanotti, Giovanni; Munson, Samantha; Dartois, Nathalie; Laferriere, Craig

    2016-01-01

    Background. Routine vaccination against Streptococcus pneumoniae is recommended in Canada for infants, the elderly, and individuals with chronic comorbidity. National incidence and burden of all-cause and pneumococcal pneumonia in Canada (excluding Quebec) were assessed. Methods. Incidence, length of stay, and case-fatality rates of hospitalized all-cause and pneumococcal pneumonia were determined for 2004-2010 using ICD-10 discharge data from the Canadian Institutes for Health Information Discharge Abstract Database. Population-at-risk data were obtained from the Statistics Canada census. Temporal changes in pneumococcal and all-cause pneumonia rates in adults ≥65 years were analyzed by logistic regression. Results. Hospitalization for all-cause pneumonia was highest in children <5 years and in adults >70 years and declined significantly from 1766/100,000 to 1537/100,000 per year in individuals aged ≥65 years (P < 0.001). Overall hospitalization for pneumococcal pneumonia also declined from 6.40/100,000 to 5.08/100,000 per year. Case-fatality rates were stable (11.6% to 12.3%). Elderly individuals had longer length of stay and higher case-fatality rates than younger groups. Conclusions. All-cause and pneumococcal pneumonia hospitalization rates declined between 2004 and 2010 in Canada (excluding Quebec). Direct and indirect effects from pediatric pneumococcal immunization may partly explain some of this decline. Nevertheless, the burden of disease from pneumonia remains high.

  2. A Retrospective Study of the Clinical Burden of Hospitalized All-Cause and Pneumococcal Pneumonia in Canada

    PubMed Central

    McNeil, Shelly A.; Qizilbash, Nawab; Ye, Jian; Gray, Sharon; Zanotti, Giovanni; Munson, Samantha; Dartois, Nathalie; Laferriere, Craig

    2016-01-01

    Background. Routine vaccination against Streptococcus pneumoniae is recommended in Canada for infants, the elderly, and individuals with chronic comorbidity. National incidence and burden of all-cause and pneumococcal pneumonia in Canada (excluding Quebec) were assessed. Methods. Incidence, length of stay, and case-fatality rates of hospitalized all-cause and pneumococcal pneumonia were determined for 2004–2010 using ICD-10 discharge data from the Canadian Institutes for Health Information Discharge Abstract Database. Population-at-risk data were obtained from the Statistics Canada census. Temporal changes in pneumococcal and all-cause pneumonia rates in adults ≥65 years were analyzed by logistic regression. Results. Hospitalization for all-cause pneumonia was highest in children <5 years and in adults >70 years and declined significantly from 1766/100,000 to 1537/100,000 per year in individuals aged ≥65 years (P < 0.001). Overall hospitalization for pneumococcal pneumonia also declined from 6.40/100,000 to 5.08/100,000 per year. Case-fatality rates were stable (11.6% to 12.3%). Elderly individuals had longer length of stay and higher case-fatality rates than younger groups. Conclusions. All-cause and pneumococcal pneumonia hospitalization rates declined between 2004 and 2010 in Canada (excluding Quebec). Direct and indirect effects from pediatric pneumococcal immunization may partly explain some of this decline. Nevertheless, the burden of disease from pneumonia remains high. PMID:27445530

  3. Toxicologic effects of 28-day dietary exposure to the flame retardant 1,2-dibromo-4-(1,2-dibromoethyl)-cyclohexane (TBECH) in F344 rats.

    PubMed

    Curran, Ivan H A; Liston, Virginia; Nunnikhoven, Andrée; Caldwell, Don; Scuby, Matthew J S; Pantazopoulos, Peter; Rawn, Dorothea F K; Coady, Laurie; Armstrong, Cheryl; Lefebvre, David E; Bondy, Genevieve S

    2017-02-15

    The brominated flame retardant TBECH is used as an additive to delay ignition and inhibit fires in construction materials and consumer goods. Trends in human exposure are not clear, although humans may be exposed to TBECH via indoor dust and air. In birds and fish there is some evidence of disruption in endocrine and reproductive parameters due to TBECH. In vitro studies indicate that TBECH is an androgen receptor agonist. In this study rats were exposed to 0, 10, 50, 250, 1250 or 5000mg/kg technical TBECH for 28days in diet, corresponding to 0, 0.9, 4.2, 21.3, 98.0 or 328.9mg TBECH/kg bw/d in males and 0, 0.8, 3.9, 19.4, 91.7 or 321.4mg TBECH/kg bw/d in females. Dose-dependent increases in α- and β- TBECH were detected in serum, liver and adipose. Rats in the 5000mg/kg group lost weight rapidly and were euthanized after 15-18days. At study termination rats displayed dose-dependent clinical and histopathological changes consistent with mild hepatic and renal inflammation. In male rats, evidence of gender-specific alpha2u-globulin nephropathy was not considered predictive of renal toxicity in humans. Frank immunosuppression or inappropriate immunostimulation were not apparent, nor was there a primary effect of TBECH on adaptive immunity. Some evidence of hormone disruption was observed, including changes in serum testosterone levels in males and changes in serum T3 and T4 levels in females. Apparent increases in thyroid follicular cell hypertrophy and hyperplasia in male and female rats were not statistically significant. Benchmark dose (BMD) modelling indicated that clinical changes indicative of mild nephrotoxicity and increased blood monocyte numbers indicative of inflammation and tissue damage were the most sensitive outcomes of TBECH exposure that could be modelled. Preliminary evidence of hormone disruption supports the need for rodent studies using more sensitive models of growth, development and reproduction.

  4. A Randomized, Double-Blind, Placebo-Controlled, Multicenter, 28-Day, Polysomnographic Study of Gabapentin in Transient Insomnia Induced by Sleep Phase Advance

    PubMed Central

    Furey, Sandy A.; Hull, Steven G.; Leibowitz, Mark T.; Jayawardena, Shyamalie; Roth, Thomas

    2014-01-01

    Study Objective: To evaluate multiple doses of gabapentin 250 mg on polysomnography (PSG) and participant-reported sleep assessments in a 5-h phase advance insomnia model. Methods: Adults reporting occasional disturbed sleep received gabapentin 250 mg (n = 128) or placebo (n = 128). On Days 1 and 28, participants received medication 30 min before bedtime and were in bed from 17:00 to 01:00, ∼5 h before their habitual bedtime. Sleep was assessed by PSG, a post sleep questionnaire, and the Karolinska Sleep Diary. Next-day residual effects and tolerability were evaluated. On Days 2-27, participants took medication at home 30 min before their habitual bedtime. Results: Treatment-group demographics were comparable. Gabapentin resulted in significantly less PSG wake after sleep onset (WASO) compared with placebo on Day 1 (primary endpoint, mean: 107.0 versus 149.1 min, p ≤ 0.001) and Day 28 (113.6 versus 152.3 min, p = 0.002), and significantly greater total sleep time (TST; Day 1: 347.6 versus 283.9 min; Day 28: 335.3 versus 289.1 min) (p ≤ 0.001). Participant-reported WASO and TST also showed significant treatment effects on both days. Gabapentin was associated with less %stage1 on Day 1, and greater %REM on Day 28, versus placebo. During home use, gabapentin resulted in significantly less participant-reported WASO and higher ratings of sleep quality. Gabapentin was well tolerated (most common adverse events: headache, somnolence) with no evidence of next-day impairment. Conclusion: Gabapentin 250 mg resulted in greater PSG and participant-reported sleep duration following a 5-h phase advance on Day 1 and Day 28 of use without evidence of next-day impairment, and greater sleep duration during at-home use. Citation: Furey SA, Hull SG, Leibowitz MT, Jayawardena S, Roth T. A randomized, double-blind, placebo-controlled, multicenter, 28-day, polysomnographic study of gabapentin in transient insomnia induced by sleep phase advance. J Clin Sleep Med 2014

  5. Nitrogen removal and mass balance in newly-formed Myriophyllum aquaticum mesocosm during a single 28-day incubation with swine wastewater treatment.

    PubMed

    Liu, Feng; Zhang, Shunan; Wang, Yi; Li, Yong; Xiao, Runlin; Li, Hongfang; He, Yang; Zhang, Miaomiao; Wang, Di; Li, Xi; Wu, Jinshui

    2016-01-15

    The aim of this research was to assess the applicability of Myriophyllum (M.) aquaticum for swine wastewater treatment. Nitrogen (N) removal processes were investigated in M. aquaticum mesocosms with swine wastewater (SW), 50% diluted swine wastewater (50% SW), and two strengths of synthetic wastewater, 200 mg [Formula: see text] L(-1) (200 [Formula: see text] ) and 400 mg [Formula: see text] L(-1) (400 [Formula: see text] ). During a 28-day incubation period, the average [Formula: see text] and TN removal rates were 99.8% and 94.2% for 50% SW and 99.8% and 93.8% for SW, which were greater than 86.5% and 83.7% for 200 [Formula: see text] , and 73.7% and 74.1% for 400 [Formula: see text] , respectively. A maximum areal total nitrogen (TN) removal rate of 157.8 mg N m(-2) d(-1) was found in M. aquaticum mesocosms with SW. During the incubation period, the observed dynamics of [Formula: see text] concentrations in water and gene copy numbers of ammonia-oxidizing archaea (AOA), ammonia-oxidizing bacteria (AOB), nirK and nirS in soil unraveled strong nitrification and denitrification processes occurring in M. aquaticum mesocosms with swine wastewater. The N mass balance analysis indicated that plant uptake and soil N accumulation accounted for 17.9-42.2% and 18.0-43.8% of the initial TN load, respectively. The coupled nitrification and denitrification process was calculated to account for, on average, 36.8% and 62.8% of TN removal for 50% SW and SW, respectively. These findings demonstrated that the N uptake by M. aquaticum contributed to a considerable proportion of N removal. In particular, the activities of ammonia-oxidizing and denitrification microbes responsible for nitrification and denitrification processes in M. aquaticum mesocosm accelerated [Formula: see text] and TN removal from swine wastewater.

  6. The Nottingham Prognostic Index: five- and ten-year data for all-cause Survival within a Screened Population

    PubMed Central

    Evans, J; Brook, D; Kenkre, J; Jarvis, P; Gower-Thomas, K

    2015-01-01

    Introduction The Nottingham Prognostic Index (NPI) is an established prognostication tool in the management of breast cancers (BCs). Latest ten-year survival data have demonstrated an improved outlook for each NPI category and the latest UK five- and ten-year survival from BC has been reported to be 85% and 77%, respectively. We compared survival of each NPI category for BCs diagnosed within the national breast screening service in Wales (Breast Test Wales (BTW)) to the latest data, and reviewed its validity in unselected cases within a screened population. Methods All women screened between 1998 and 2001 within BTW were included. The NPI score for each cancer was calculated using the size, nodal status, and grade of the primary tumour. Survival data (all-cause) were calculated after ten years of follow-up. Results In the three-year screening period, 199,082 women were screened. A total of 1,712 cancers were diagnosed, and 1,546 had data available for calculating the NPI. Overall five-year and ten-year survival was 94% and 82%, respectively. Conclusions Overall five-year and ten-year survival (all-cause) has improved even when compared with UK data for BC-specific survival. We found that the NPI remains valid for BC treatment, and that our data provide a reference for updating the all-cause survival of women diagnosed with BCs within a screened population. PMID:25723691

  7. Is there a reverse J-shaped association between 25-Hydroxyvitamin D and all-cause mortality? Results from the US Nationally Representative NHANES

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The concentration or threshold of 25-Hydroxyvitamin D [25(OH)D] needed to maximally suppress intact serum parathyroid hormone (iPTH) has been suggested as a measure of optimal vitamin D status. Depending upon the definition of maximal suppression of iPTH and the two-phase regression approach used, ...

  8. The relationship of mental and behavioral disorders to all-cause mortality in a 27-year follow-up of 4 epidemiologic catchment area samples.

    PubMed

    Eaton, William W; Roth, Kimberly B; Bruce, Martha; Cottler, Linda; Wu, Litzy; Nestadt, Gerald; Ford, Dan; Bienvenu, O Joseph; Crum, Rosa M; Rebok, George; Anthony, James C; Muñoz, Alvaro

    2013-11-01

    Subjects from the Epidemiologic Catchment Area Program, interviewed during 1979-1983, were linked to data in the National Death Index through 2007 to estimate the association of mental and behavioral disorders with death. There were more than 25 years of follow-up for 15,440 individuals, with 6,924 deaths amounting to 307,881 person-years of observation. Data were analyzed by using age as the time scale and parametric approaches to quantify the years of life lost due to disorders. Alcohol, drug use, and antisocial personality disorders were associated with increased risk of death, but there was no strong association with mood and anxiety disorders. Results of high- and low-quality matches with the National Death Index were similar. The 3 behavioral disorders were associated with 5-15 years of life lost, estimated along the life course via the generalized gamma model. Regression tree analyses showed that risk of death was associated with alcohol use disorders in nonblacks and with drug disorders in blacks. Phobia interacted with alcohol use disorders in nonblack women, and obsessive-compulsive disorder interacted with drug use disorders in black men. Both of these anxiety disorders were associated with lower risk of death early in life and higher risk of death later in life.

  9. Accident mortality among children

    PubMed Central

    Swaroop, S.; Albrecht, R. M.; Grab, B.

    1956-01-01

    The authors present statistics on mortality from accidents, with special reference to those relating to the age-group 1-19 years. For a number of countries figures are given for the proportional mortality from accidents (the number of accident deaths expressed as a percentage of the number of deaths from all causes) and for the specific death-rates, per 100 000 population, from all causes of death, from selected causes, from all causes of accidents, and from various types of accident. From these figures it appears that, in most countries, accidents are becoming relatively increasingly prominent as a cause of death in childhood, primarily because of the conquest of other causes of death—such as infectious and parasitic diseases, which formerly took a heavy toll of children and adolescents—but also to some extent because the death-rate from motor-vehicle accidents is rising and cancelling out the reduction in the rate for other causes of accidental death. In the authors' opinion, further epidemiological investigations into accident causation are required for the purpose of devising quicker and more effective methods of accident prevention. PMID:13383361

  10. Safety profile and gender specific differences of a methanol extract of Eriosema laurentii (Leguminosae) in acute and subchronic (28 days) oral toxicity studies in Wistar rats.

    PubMed

    Ateba, Sylvin Benjamin; Simo, Rudy Valdès; Mbanya, Jean Claude; Krenn, Liselotte; Njamen, Dieudonné

    2014-03-01

    Despite widespread use of Eriosema laurentii De Wild (Leguminosae) in West and Central Africa as herbal medicine and food additive the toxicity of this plant is unknown. Therefore, we performed the safety evaluation of a methanol extract (AEL). In acute toxicity, single oral administration of 2000mg/kg AEL caused neither toxicological symptoms nor mortality and the LD50 was estimated >5000mg/kg. In the subchronic oral toxicity, AEL induced no phenotypical signs of toxicity during and after treatment. Only a delayed decrease of relative spleen weight in males at the highest dose of 400mg/kg occurred. High density lipoprotein (HDL) increased significantly in females at 200 and 400mg/kg. Non-persistent increases in alanine aminotransferase activity within normal ranges were noted at 200mg/kg in males and at all doses in females. In males, AEL induced a decrease of white blood cell count at 400mg/kg, whereas lymphocytes increased at 200 and 400mg/kg and granulocytes at 400mg/kg. In females, no differences in haematological parameters occurred. Neither differences in bilirubin, creatinine and total protein levels were observed nor histological alterations in organs. The results indicate a broad safety margin for AEL.

  11. Risk factors for early mortality in haematological malignancy patients with pulmonary mucormycosis.

    PubMed

    Lewis, Russell E; Georgiadou, Sarah P; Sampsonas, Fotis; Chamilos, George; Kontoyiannis, Dimitrios P

    2014-01-01

    Pulmonary mucormycosis (PM) is a life-threatening opportunistic mycosis with a variable clinical evolution and few prognostic markers for outcome assessment. Several clinical risk factors for poor outcome present at the diagnosis of PM were analyzed in 75 consecutive hematology patients from 2000-2012. Significant variables (P < 0.1) were entered into a multivariate Cox-proportional hazard regression model adjusting for baseline APACHE II to identify independent risk factors for mortality within 28 days. Twenty-eight of 75 patients died within 4-week follow up. A lymphocyte count < 100/mm³ at the time of diagnosis (adjusted hazard ratio 4.0, 1.7-9.4, P = 0.01) and high level of lactate dehydrogenase (AHR 3.7, 1.3-10.2, P = 0.015) were independent predictors along with APACHE II score for 28-day mortality. A weighted risk score based on these 3 baseline variables accurately identified non-surviving patients at 28 days (area under the receiver-operator curve of 0.87, 0.77-0.93, P < 0.001). A risk score > 22 was associated with 8-fold high rates of mortality (P < 0.0001) within 28 days of diagnosis and median survival of 7 days versus ≥28 days in patients with risk scores ≤22. We found that APACHE II score, severe lymphocytopenia and high LDH levels at the time of PM diagnosis were independent markers for rapid disease progression and death.

  12. Carbapenemase-producing Klebsiella pneumoniae bloodstream infections: lowering mortality by antibiotic combination schemes and the role of carbapenems.

    PubMed

    Daikos, George L; Tsaousi, Sophia; Tzouvelekis, Leonidas S; Anyfantis, Ioannis; Psichogiou, Mina; Argyropoulou, Athina; Stefanou, Ioanna; Sypsa, Vana; Miriagou, Vivi; Nepka, Martha; Georgiadou, Sarah; Markogiannakis, Antonis; Goukos, Dimitris; Skoutelis, Athanasios

    2014-01-01

    Carbapenemase-producing Klebsiella pneumoniae strains (CP-Kps) are currently among the most important nosocomial pathogens. An observational study was conducted during 2009 to 2010 in two hospitals located in a high-prevalence area (Athens, Greece). The aims were (i) to evaluate the clinical outcome of patients with CP-Kp bloodstream infections (BSIs), (ii) to identify predictors of mortality, and (iii) to evaluate the various antibiotic schemes employed. A total of 205 patients with CP-Kp BSIs were identified: 163 (79.5%) were infected with KPC or KPC and VIM, and 42 were infected with VIM producers. For definitive treatment, 103 patients received combination therapy (two or more active drugs), 72 received monotherapy (one active drug), and 12 received therapy with no active drug. The remaining 18 patients died within 48 h after the onset of bacteremia. The all-cause 28-day mortality was 40%. A significantly higher mortality rate was observed in patients treated with monotherapy than in those treated with combination therapy (44.4% versus 27.2%; P=0.018). The lowest mortality rate (19.3%) was observed in patients treated with carbapenem-containing combinations. In the Cox proportion hazards model, ultimately fatal disease (hazards ratio [HR], 3.25; 95% confidence interval [CI], 1.51 to 7.03; P=0.003), the presence of rapidly fatal underlying diseases (HR, 4.20; 95% CI, 2.19 to 8.08; P<0.001), and septic shock (HR, 2.15; 95% CI, 1.16 to 3.96; P=0.015) were independent predictors of death. Combination therapy was strongly associated with survival (HR of death for monotherapy versus combination, 2.08; 95% CI, 1.23 to 3.51; P=0.006), mostly due to the effectiveness of the carbapenem-containing regimens.

  13. Non-melanoma skin cancer and risk of Alzheimer’s disease and all-cause dementia

    PubMed Central

    Schmidt, Sigrun A. J.; Ording, Anne G.; Horváth-Puhó, Erzsébet; Sørensen, Henrik T.; Henderson, Victor W.

    2017-01-01

    Cancer patients may be at decreased risk of Alzheimer’s disease. This hypothesis is best developed for non-melanoma skin cancer (NMSC), but supportive epidemiological data are sparse. We therefore conducted a nationwide cohort study of the association between NMSC and Alzheimer’s disease (main outcome) and all-cause dementia. Using Danish medical databases, we identified adults diagnosed with NMSC between 1 January 1980 and 30 November 2013 (n = 216,221) and a comparison cohort of five individuals matched to each NMSC patient by sex and birth year (n = 1,081,097). We followed individuals from the time of diagnosis, or corresponding date for matched comparators, until a dementia diagnosis, death, emigration, or 30 November 2013, whichever came first. We used stratified Cox regression adjusted for comorbidities to compute hazard ratios (HRs) associating NMSC with dementia. We computed cumulative risks of dementia, treating death as a competing risk. NMSC was associated with a HR of 0.95 (95% confidence interval [CI]: 0.92–0.98) for Alzheimer’s disease and 0.92 (95% CI: 0.90–0.94) for all-cause dementia. HRs were similar for basal cell and squamous cell carcinoma, the two most common forms of NMSC. Estimates of risk reduction were more pronounced in the beginning of follow-up, reaching null after 5–10 years. At the end of follow-up (34 years), cumulative risk of Alzheimer’s disease was 4.6% (95% CI: 4.4%–4.8%) among patients with NMSC vs. 4.7% (95% CI: 4.6%–4.9%) in the comparison cohort. In conclusion, NMSC was associated with 2%–10% reductions in relative risks of Alzheimer’s disease and all-cause dementia. However, these small inverse associations may have been caused by ascertainment bias due to decreased awareness of NMSC tumors in persons with undiagnosed early cognitive impairment or by confounding from a more neuroprotective lifestyle among persons with NMSC. PMID:28225789

  14. SOCIOECONOMIC DISPARITIES IN MORTALITY AMONG CHINESE ELDERLY*

    PubMed Central

    Luo, Weixiang; Xie, Yu

    2014-01-01

    This study examines the association of three different SES indicators (education, economic independence, and household per-capita income) with mortality, using a large, nationally representative longitudinal sample of 12,437 Chinese ages 65 and older. While the results vary by measures used, we find overall strong evidence for a negative association between SES and all-cause mortality. Exploring the association between SES and cause-specific mortality, we find that SES is more strongly related to a reduction of mortality from more preventable causes (i.e., circulatory disease and respiratory disease) than from less preventable causes (i.e., cancer). Moreover, we consider mediating causal factors such as support networks, health-related risk behaviors, and access to health care in contributing to the observed association between SES and mortality. Among these mediating factors, medical care is of greatest importance. This pattern holds true for both all-cause and cause-specific mortality. PMID:25098961

  15. The Effect of Predialysis Fistula Attempt on Risk of All-Cause and Access-Related Death.

    PubMed

    Quinn, Robert R; Oliver, Matthew J; Devoe, Daniel; Poinen, Krishnan; Kabani, Rameez; Kamar, Fareed; Mysore, Priyanka; Lewin, Adriane M; Hiremath, Swapnil; MacRae, Jennifer; James, Matthew T; Miller, Lisa; Hemmelgarn, Brenda R; Moist, Louise M; Garg, Amit X; Chowdhury, Tanvir T; Ravani, Pietro

    2017-02-01

    Whether the lower risk of mortality associated with arteriovenous fistula use in hemodialysis patients is due to the avoidance of catheters or if healthier patients are simply more likely to have fistulas placed is unknown. To provide clarification, we determined the proportion of access-related deaths in a retrospective cohort study of patients aged ≥18 years who initiated hemodialysis between 2004 and 2012 at five Canadian dialysis programs. A total of 3168 patients initiated dialysis at the participating centers; 2300 met our inclusion criteria. Two investigators independently adjudicated cause of death using explicit criteria and determined whether a death was access-related. We observed significantly lower mortality in individuals who underwent a predialysis fistula attempt than in those without a predialysis fistula attempt in patients aged <65 years (hazard ratio [HR], 0.49; 95% confidence interval [95% CI], 0.29 to 0.82) and in the first 2 years of follow-up in those aged ≥65 years (HR0-24 months, 0.60; 95% CI, 0.43 to 0.84; HR24+ months, 1.83; 95% CI, 1.25 to 2.67). Sudden deaths that occurred out of hospital accounted for most of the deaths, followed by deaths due to cardiovascular disease and infectious complications. We found only 2.3% of deaths to be access-related. In conclusion, predialysis fistula attempt may associate with a lower risk of mortality. However, the excess mortality observed in patients treated with catheters does not appear to be due to direct, access-related complications but is likely the result of residual confounding, unmeasured comorbidity, or treatment selection bias.

  16. Cholesterol trials and mortality.

    PubMed

    Warren, John B; Dimmitt, Simon B; Stampfer, Hans G

    2016-07-01

    An overview of clinical trials can reveal a class effect on mortality that is not apparent from individual trials. Most large trials of lipid pharmacotherapy are not powered to detect differences in mortality and instead assess efficacy with composite cardiovascular endpoints. We illustrate the importance of all-cause mortality data by comparing survival in three different sets of the larger controlled lipid trials that underpin meta-analyses. These trials are for fibrates and statins. Fibrate treatment in five of the six main trials was associated with a decrease in survival, one fibrate trial showed a non-significant reduction in mortality that can be explained by a different target population. In secondary prevention, statin treatment increased survival in all five of the main trials, absolute mean increase ranged from 0.43% to 3.33%, the median change was 1.75%, which occurred in the largest trial. In primary prevention, statin treatment increased survival in six of the seven main trials, absolute mean change in survival ranged from -0.09% to 0.89%, median 0.49%. Composite safety endpoints are rare in these trials. The failure to address composite safety endpoints in most lipid trials precludes a balanced summary of risk-benefit when a composite has been used for efficacy. Class effects on survival provide informative summaries of the risk-benefit of lipid pharmacotherapy. We consider that the presentation of key mortality/survival data adds to existing meta-analyses to aid personal treatment decisions.

  17. D-aspartic acid supplementation combined with 28 days of heavy resistance training has no effect on body composition, muscle strength, and serum hormones associated with the hypothalamo-pituitary-gonadal axis in resistance-trained men.

    PubMed

    Willoughby, Darryn S; Leutholtz, Brian

    2013-10-01

    It was hypothesized that D-aspartic acid (D-ASP) supplementation would not increase endogenous testosterone levels or improve muscular performance associated with resistance training. Therefore, body composition, muscle strength, and serum hormone levels associated with the hypothalamo-pituitary-gonadal axis were studied after 28 days of resistance training and D-ASP supplementation. Resistance-trained men resistance trained 4 times/wk for 28 days while orally ingesting either 3 g of placebo or 3 g of D-ASP. Data were analyzed with 2 × 2 analysis of variance (P < .05). Before and after resistance training and supplementation, body composition and muscle strength, serum gonadal hormones, and serum D-ASP and d-aspartate oxidase (DDO) were determined. Body composition and muscle strength were significantly increased in both groups in response to resistance training (P < .05) but not different from one another (P > .05). Total and free testosterone, luteinizing hormone, gonadotropin-releasing hormone, and estradiol were unchanged with resistance training and D-ASP supplementation (P > .05). For serum D-ASP and DDO, D-ASP resulted in a slight increase compared with baseline levels (P > .05). For the D-ASP group, the levels of serum DDO were significantly increased compared with placebo (P < .05). The gonadal hormones were unaffected by 28 days of D-ASP supplementation and not associated with the observed increases in muscle strength and mass. Therefore, at the dose provided, D-ASP supplementation is ineffective in up-regulating the activity of the hypothalamo-pituitary-gonadal axis and has no anabolic or ergogenic effects in skeletal muscle.

  18. Infant Mortality

    MedlinePlus

    ... Control and Prevention. (2013). CDC health disparities and inequalities report—United States, 2013. Morbidity and Mortality Weekly ... M. (2008). The fall and rise of U.S. inequalities in premature mortality: 1960–2002. PLOS Medicine, 5 ( ...

  19. A Prospective Longitudinal Cohort to Investigate the Effects of Early Life Giardiasis on Growth and All Cause Diarrhea

    PubMed Central

    Donowitz, Jeffrey R.; Alam, Masud; Kabir, Mamun; Ma, Jennie Z.; Nazib, Forida; Platts-Mills, James A.; Bartelt, Luther A.; Haque, Rashidul; Petri, William A.

    2016-01-01

    Background. Growth stunting in children under 2 years of age in low-income countries is common. Giardia is a ubiquitous pathogen in this age group but studies investigating Giardia's effect on both growth and diarrhea have produced conflicting results. Methods. We conducted a prospective longitudinal birth cohort study in Dhaka, Bangladesh, with monthly Giardia and continuous diarrheal surveillance. Results. 629 children were enrolled within the first 72 hours of life, and 445 completed 2 years of the study. 12% of children were stunted at birth with 57% stunted by 2 years. 7% of children had a Giardia positive surveillance stool in the first 6 months of life, whereas 74% had a positive stool by 2 years. The median time to first Giardia positive surveillance stool was 17 months. Presence of Giardia in a monthly surveillance stool within the first 6 months of life decreased length-for-age Z score at 2 years by 0.4 (95% confidence interval, −.80 to −.001; P value .05) whereas total number of Giardia positive months over the 2-year period of observation did not. Neither variable was associated with weight-for-age Z score at 2 years. In our model to examine predictors of diarrhea only exclusive breastfeeding was significantly associated with decreased diarrhea (P value <.001). Concomitant giardiasis was neither a risk factor nor protective. Conclusions. Early life Giardia was a risk factor for stunting at age 2 but not poor weight gain. Presence of Giardia neither increased nor decreased odds of acute all cause diarrhea. PMID:27313261

  20. 28-day oral safety evaluation of extracellular polysaccharopeptides produced in submerged culture from the turkey tail medicinal mushroom Trametes versicolor (L.:Fr.) Pilát LH-1 in mice.

    PubMed

    Lai, Chun-Hong; Teng, Ju-Fang; Hsu, Tai-Hao; Lin, Fang-Yi; Yang, Po-Wen; Lo, Hui-chen

    2011-01-01

    Turkey tail medicinal mushroom, Trametes versicolor (TV), is a species with a variety of pharmacological activities. Its intracellular polysaccharopeptides are widely commercialized. Recently, we found a novel TV strain LH-1 in Taiwan and demonstrated that the extracellular polysaccharopeptide (ePSP) of LH-1 obtained from submerged culture exhibits significant immunomodulatory activity. In this in vivo study, we further evaluated the safety of orally administered LH-1 ePSP using both male and female ICR mice. The LH-1 ePSP was orally administered to mice at levels of 0 (water), 100 (low dose), 500 (medium dose), or 1000 mg/kg/day (high dose) for 28 days. Clinical observations, growth, food consumption, histopathological examination, and clinical biochemical analyses revealed no adverse effects of LH-1 ePSP in mice. There were no significant differences in the results of target organ weights, hematological analyses, and urinalysis examination among groups. However, male mice that ingested high doses of LH-1 ePSP tended to have decreased lung weights and platelet numbers. In conclusion, the results of the present study suggested that oral administration of LH-1 ePSP for 28 days is accompanied by no obvious signs of toxicity. The lack of toxicity supports the potential use of LH-1 ePSP as a food or dietary supplement.

  1. Exposures and mortality among chrysotile asbestos workers. Part II: mortality

    SciTech Connect

    Dement, J.M.; Harris, R.L. Jr.; Symons, M.J.; Shy, C.M.

    1983-01-01

    A retrospective cohort mortality study was conducted among a cohort of 1,261 white males employed one or more months in chrysotile asbestos textile operations and followed between 1940 and 1975. Statistically significant excess mortality was observed for all causes combined (standardized mortality ratio (SMR) . 150), lung cancer (SMR . 135), diseases of the circulatory system (SMR . 125), nonmalignant respiratory diseases (SMR . 294), and accidents (SMR . 134). Using estimated fiber exposure levels in conjunction with detailed worker job histories, exposure-response relationships were investigated. Strong exposure-response relationships for lung cancer and asbestos related non-malignant respiratory diseases were observed. Compared with data for chrysotile miners and millers, chrysotile textile workers were found to experience significantly greater lung cancer mortality at lower lifetime cumulative exposure levels. Factors such as differences in airborne fiber characteristics may partially account for the large differences in exposure response between textile workers and miners and millers.

  2. Polymyxin B-immobilised haemoperfusion and mortality in critically ill patients with sepsis/septic shock: a protocol for a systematic review and meta-analysis

    PubMed Central

    Fujii, Tomoko; Ganeko, Riki; Kataoka, Yuki; Featherstone, Robin; Bagshaw, Sean M

    2016-01-01

    Introduction Polymyxin-B immobilised haemoperfusion (PMX-HP) is a promising adjuvant strategy for the treatment of sepsis and septic shock. PMX-HP therapy works by clearing circulating endotoxin through binding to polymyxin-immobilised fibres during haemoperfusion. Small clinical trials have shown that PMX-HP therapy is associated with improved haemodynamic profile, oxygenation and survival. However, clear inferences have been largely inconclusive due to limitations in study design (eg, small, unblinded) and generalisability. We therefore propose to perform an up-to-date systematic review and evidence synthesis to describe the efficacy, safety and effectiveness of PMX-HP for adult patients with sepsis or septic shock. Methods and analysis We will search the following databases from 1946 to 2016 MEDLINE (Ovid), EMBASE (Ovid), Cochrane Library, Health Technology Assessment Database (HTA), Cumulative Index to Nursing and Allied Health Literature (CINAHL), PubMed and ‘Igaku Chuo Zasshi’ (ICHUSHI) for randomised controlled trials of PMX-HP in critically ill patients with sepsis or septic shock. There will be no language restrictions in the electronic search for studies. Two reviewers will extract data and appraise the quality of each study independently. The primary outcome will be the pooled risk ratio of 28-day all-cause mortality. Serious adverse events and changes in organ dysfunction scores will also be evaluated. The secondary outcomes will be 90-day all-cause mortality, changes in haemodynamic profile and endotoxin levels, and health services use. Ethics and dissemination Our systematic review will synthesise the evidence on use of the PMX-HP as an adjuvant therapy in sepsis/septic shock to improve patient-centred, physiological and health services outcomes. Research ethics is not required for this review. The study will be disseminated by peer-reviewed publication and conference presentation. Trial registration number CRD42016038356. PMID:27872122

  3. Effects of 28 days of resistance exercise and consuming a commercially available pre-workout supplement, NO-Shotgun®, on body composition, muscle strength and mass, markers of satellite cell activation, and clinical safety markers in males

    PubMed Central

    Shelmadine, Brian; Cooke, Matt; Buford, Thomas; Hudson, Geoffrey; Redd, Liz; Leutholtz, Brian; Willoughby, Darryn S

    2009-01-01

    Purpose This study determined the effects of 28 days of heavy resistance exercise combined with the nutritional supplement, NO-Shotgun®, on body composition, muscle strength and mass, markers of satellite cell activation, and clinical safety markers. Methods Eighteen non-resistance-trained males participated in a resistance training program (3 × 10-RM) 4 times/wk for 28 days while also ingesting 27 g/day of placebo (PL) or NO-Shotgun® (NO) 30 min prior to exercise. Data were analyzed with separate 2 × 2 ANOVA and t-tests (p < 0.05). Results Total body mass was increased in both groups (p = 0.001), but without any significant increases in total body water (p = 0.77). No significant changes occurred with fat mass (p = 0.62); however fat-free mass did increase with training (p = 0.001), and NO was significantly greater than PL (p = 0.001). Bench press strength for NO was significantly greater than PL (p = 0.003). Myofibrillar protein increased with training (p = 0.001), with NO being significantly greater than PL (p = 0.019). Serum IGF-1 (p = 0.046) and HGF (p = 0.06) were significantly increased with training and for NO HGF was greater than PL (p = 0.002). Muscle phosphorylated c-met was increased with training for both groups (p = 0.019). Total DNA was increased in both groups (p = 0.006), while NO was significantly greater than PL (p = 0.038). For DNA/protein, PL was decreased and NO was not changed (p = 0.014). All of the myogenic regulatory factors were increased with training; however, NO was shown to be significantly greater than PL for Myo-D (p = 0.008) and MRF-4 (p = 0.022). No significant differences were located for any of the whole blood and serum clinical chemistry markers (p > 0.05). Conclusion When combined with heavy resistance training for 28 days, NO-Shotgun® is not associated with any negative side effects, nor does it abnormally impact any of the clinical chemistry markers. Rather, NO-Shotgun® effectively increases muscle strength and mass

  4. Lactate clearance is associated with mortality in septic patients with acute kidney injury requiring continuous renal replacement therapy

    PubMed Central

    Passos, Rogério da Hora; Ramos, Joao Gabriel Rosa; Gobatto, André; Mendonça, Evandro José Bulhões; Miranda, Eva Alves; Dutra, Fábio Ricardo Dantas; Coelho, Maria Fernanda R; Pedroza, Andrea C; Batista, Paulo Benigno Pena; Dutra, Margarida Maria Dantas

    2016-01-01

    Abstract The aim of the study was to assess the clinical utility of lactate measured at different time points to predict mortality at 48 hours and 28 days in septic patients with acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT). Consecutive critically ill patients with septic AKI requiring CRRT were prospectively studied. Variables were collected at initiation of CRRT and 24 hours later. In total, 186 patients were analyzed. Overall mortality at 48 hours was 28% and at 28 days was 69%. Initial lactate, lactate at 24 hours and the proportion of patients with a lactate clearance superior to 10% were different between survivors at 28 days [2.0 mmol/L, 1.95 mmol/L and 18/45 (40%)] and nonsurvivors [3.46 mmol, 4.66 mmol, and 18/94 (19%)]. Multivariate analysis demonstrated that lactate at 24 hours and lactate clearance, but not initial lactate, were independently associated to mortality. Area under the ROC curves for 28-day mortality was 0.635 for initial lactate; 0.828 for lactate at 24 hours and 0.701 for lactate clearance. Lactate clearance and lactate after 24 hours of CRRT, but not initial lactate, were independently associated with mortality in septic AKI patients undergoing CRRT. Serial lactate measurements may be useful prognostic markers than initial lactate in these patients. PMID:27749594

  5. Toxicity of aerosols of nicotine and pyruvic acid (separate and combined) in Sprague-Dawley rats in a 28-day OECD 412 inhalation study and assessment of systems toxicology.

    PubMed

    Phillips, Blaine; Esposito, Marco; Verbeeck, Jan; Boué, Stéphanie; Iskandar, Anita; Vuillaume, Gregory; Leroy, Patrice; Krishnan, Subash; Kogel, Ulrike; Utan, Aneli; Schlage, Walter K; Bera, Monali; Veljkovic, Emilija; Hoeng, Julia; Peitsch, Manuel C; Vanscheeuwijck, Patrick

    2015-01-01

    Toxicity of nebulized nicotine (Nic) and nicotine/pyruvic acid mixtures (Nic/Pyr) was characterized in a 28-day Organization for Economic Co-operation and Development 412 inhalation study with additional transcriptomic and lipidomic analyses. Sprague-Dawley rats were nose-only exposed, 6 h/day, 5 days/week to filtered air, saline, nicotine (50 µg/l), sodium pyruvate (NaPyr, 33.9 µg/l) or equimolar Nic/Pyr mixtures (18, 25 and 50 µg nicotine/l). Saline and NaPyr caused no health effects, but rats exposed to nicotine-containing aerosols had decreased body weight gains and concentration-dependent increases in liver weight. Blood neutrophil counts were increased and lymphocyte counts decreased in rats exposed to nicotine; activities of alkaline phosphatase and alanine aminotransferase were increased, and levels of cholesterol and glucose decreased. The only histopathologic finding in non-respiratory tract organs was increased liver vacuolation and glycogen content. Respiratory tract findings upon nicotine exposure (but also some phosphate-buffered saline aerosol effects) were observed only in the larynx and were limited to adaptive changes. Gene expression changes in the lung and liver were very weak. Nic and Nic/Pyr caused few significant changes (including Cyp1a1 gene upregulation). Changes were predominantly related to energy metabolism and fatty acid metabolism but did not indicate an obvious toxicity-related response. Nicotine exposure lowered plasma lipids, including cholesteryl ester (CE) and free cholesterol and, in the liver, phospholipids and sphingolipids. Nic, NaPyr and Nic/Pyr decreased hepatic triacylglycerol and CE. In the lung, Nic and Nic/Pyr increased CE levels. These data suggest that only minor biologic effects related to inhalation of Nic or Nic/Pyr aerosols were observed in this 28-day study.

  6. Identification of epigenetically downregulated Tmem70 and Ube2e2 in rat liver after 28-day treatment with hepatocarcinogenic thioacetamide showing gene product downregulation in hepatocellular preneoplastic and neoplastic lesions produced by tumor promotion.

    PubMed

    Mizukami, Sayaka; Yafune, Atsunori; Watanabe, Yousuke; Nakajima, Kota; Jin, Meilan; Yoshida, Toshinori; Shibutani, Makoto

    2017-01-15

    The present study identified genes showing promoter region hypermethylation by CpG island microarrays in the liver of rats treated with hepatocarcinogen thioacetamide (TAA) for 28days. Among 47 hypermethylated genes, Hist1h2aa, Tmem70, Ube2e2, and Slk were confirmed to show hypermethylation by methylation-specific quantitative polymerase chain reaction (PCR) and pyrosequencing analyses as well as downregulation of transcript levels by real-time reverse transcription-PCR analysis in the livers of rats treated with TAA. All gene products of the 4 selected genes showed decreased immunoreactivity forming negative liver cell foci in a subpopulation of glutathione S-transferase placental form (GST-P)(+) foci in TAA-promoted rat livers in a two-stage hepatocarcinogenesis model. Among them, TMEM70 and UBE2E2 showed increased incidences of negative foci in GST-P(+) foci by promotion of all examined TAA, β-naphthoflavone, piperonyl butoxide, fenbendazole and phenobarbital, while HIST1H2AA and SLK did not respond to all promotive treatments. In the late stage of tumor promotion by TAA, the incidence of GST-P(+) proliferative lesions with downregulation of TMEM70 or UBE2E2 was higher in adenomas and carcinomas than liver cell foci. TMEM70 plays a role in mitochondrial oxidative phosphorylation, and UBE2E2 participates in the stabilization of cell cycle regulatory proteins. Therefore, our results indicate that aberrant epigenetic gene downregulation suggestive of a metabolic shift of cellular respiration from oxidative phosphorylation to glycolysis and aberrant cell cycle regulation facilitating cell proliferation from as early as 28days after hepatocarcinogen treatment contribute to tumor development.

  7. Mortality prediction in patients with severe septic shock: a pilot study using a target metabolomics approach

    PubMed Central

    Ferrario, Manuela; Cambiaghi, Alice; Brunelli, Laura; Giordano, Silvia; Caironi, Pietro; Guatteri, Luca; Raimondi, Ferdinando; Gattinoni, Luciano; Latini, Roberto; Masson, Serge; Ristagno, Giuseppe; Pastorelli, Roberta

    2016-01-01

    Septic shock remains a major problem in Intensive Care Unit, with high lethality and high-risk second lines treatments. In this preliminary retrospective investigation we examined plasma metabolome and clinical features in a subset of 20 patients with severe septic shock (SOFA score >8), enrolled in the multicenter Albumin Italian Outcome Sepsis study (ALBIOS, NCT00707122). Our purpose was to evaluate the changes of circulating metabolites in relation to mortality as a pilot study to be extended in a larger cohort. Patients were analyzed according to their 28-days and 90-days mortality. Metabolites were measured using a targeted mass spectrometry-based quantitative metabolomic approach that included acylcarnitines, aminoacids, biogenic amines, glycerophospholipids, sphingolipids, and sugars. Data-mining techniques were applied to evaluate the association of metabolites with mortality. Low unsaturated long-chain phosphatidylcholines and lysophosphatidylcholines species were associated with long-term survival (90-days) together with circulating kynurenine. Moreover, a decrease of these glycerophospholipids was associated to the event at 28-days and 90-days in combination with clinical variables such as cardiovascular SOFA score (28-day mortality model) or renal replacement therapy (90-day mortality model). Early changes in the plasma levels of both lipid species and kynurenine associated with mortality have potential implications for early intervention and discovering new target therapy. PMID:26847922

  8. Risk factors for early infant mortality in Sarlahi district, Nepal.

    PubMed Central

    Katz, Joanne; West, Keith P.; Khatry, Subarna K.; Christian, Parul; LeClerq, Steven C.; Pradhan, Elizabeth Kimbrough; Shrestha, Sharada Ram

    2003-01-01

    OBJECTIVES: Early infant mortality has not declined as rapidly as child mortality in many countries. Identification of risk factors for early infant mortality may help inform the design of intervention strategies. METHODS: Over the period 1994-97, 15,469 live-born, singleton infants in rural Nepal were followed to 24 weeks of age to identify risk factors for mortality within 0-7 days, 8-28 days, and 4-24 weeks after the birth. FINDINGS: In multivariate models, maternal and paternal education reduced mortality between 4 and 24 weeks only: odds ratios (OR) 0.28 (95% confidence interval (CI) = 0.12-0.66) and 0.63 (95% CI = 0.44-0.88), respectively. Miscarriage in the previous pregnancy predicted mortality in the first week of life (OR = 1.98, 95% CI = 1.37-2.87), whereas prior child deaths increased the risk of post-neonatal death (OR = 1.85, 95% CI 1.24-2.75). A larger maternal mid-upper arm circumference reduced the risk of infant death during the first week of life (OR = 0.88, 95% CI = 0.81-0.95). Infants of women who did not receive any tetanus vaccinations during pregnancy or who had severe illness during the third trimester were more likely to die in the neonatal period. Maternal mortality was strongly associated with infant mortality (OR = 6.43, 95% CI = 2.35-17.56 at 0-7 days; OR = 11.73, 95% CI = 3.82-36.00 at 8-28 days; and OR = 51.68, 95% CI = 20.26-131.80 at 4-24 weeks). CONCLUSION: Risk factors for early infant mortality varied with the age of the infant. Factors amenable to intervention included efforts aimed at maternal morbidity and mortality and increased arm circumference during pregnancy. PMID:14758431

  9. Musculoskeletal Fitness and Risk of Mortality.

    ERIC Educational Resources Information Center

    Katzmarzyk, Peter T.; Craig, Cora L.

    2002-01-01

    Quantified the relationship between musculoskeletal fitness and all-cause mortality in Canada, using measures of musculoskeletal fitness (situps, pushups, grip strength, and sit- and-reach trunk flexibility) from adult male and female participants in the Canadian Fitness Survey. Results indicated that some components of musculoskeletal fitness,…

  10. Beverage Habits and Mortality in Chinese Adults12

    PubMed Central

    Odegaard, Andrew O; Koh, Woon-Puay; Yuan, Jian-Min; Pereira, Mark A

    2015-01-01

    Background: There is limited research examining beverage habits, one of the most habitual dietary behaviors, with mortality risk. Objective: This study examined the association between coffee, black and green tea, sugar-sweetened beverages (soft drinks and juice), and alcohol and all-cause and cause-specific mortality. Methods: A prospective data analysis was conducted with the use of the Singapore Chinese Health Study, including 52,584 Chinese men and women (aged 45–74 y) free of diabetes, cardiovascular disease (CVD), and cancer at baseline (1993–1998) and followed through 2011 with 10,029 deaths. Beverages were examined with all-cause and cause-specific (cancer, CVD, and respiratory disease) mortality risk with the use of Cox proportional hazards regression. Results: The associations between coffee, black tea, and alcohol intake and all-cause mortality were modified by smoking status. Among never-smokers there was an inverse dose-response association between higher amounts of coffee and black tea intake and all-cause, respiratory-related, and CVD mortality (black tea only). The fully adjusted HRs for all-cause mortality for coffee for <1/d, 1/d, and ≥2/d relative to no coffee intake were 0.89, 0.86, and 0.83, respectively (P-trend = 0.0003). For the same black tea categories the HRs were 0.95, 0.90, and 0.72, respectively (P-trend = 0.0005). Among ever-smokers there was no association between coffee or black tea and the outcomes. Relative to no alcohol, light to moderate intake was inversely associated with all-cause mortality (HR: 0.87; 95% CI: 0.79, 0.96) in never-smokers with a similar magnitude of association in ever-smokers. There was no association between heavy alcohol intake and all-cause mortality in never-smokers and a strong positive association in ever-smokers (HR: 1.56; 95% CI: 1.40, 1.74). Green tea and sugar-sweetened beverages were not associated with all-cause or cause-specific mortality. Conclusions: Higher coffee and black tea intake was

  11. Benzo[a]pyrene (BP) DNA adduct formation in DNA repair–deficient p53 haploinsufficient [Xpa(−/−)p53(+/−)] and wild-type mice fed BP and BP plus chlorophyllin for 28 days

    PubMed Central

    Poirier, Miriam C.

    2012-01-01

    We have evaluated DNA damage (DNA adduct formation) after feeding benzo[a]pyrene (BP) to wild-type (WT) and cancer-susceptible Xpa(−/−)p53(+/−) mice deficient in nucleotide excision repair and haploinsufficient for the tumor suppressor p53. DNA damage was evaluated by high-performance liquid chromatography/electrospray ionization tandem mass spectrometry (HPLC/ES-MS/MS), which measures r7,t8,t9-trihydroxy-c-10-(N 2-deoxyguanosyl)-7,8,9,10-tetrahydrobenzo[a]pyrene (BPdG), and a chemiluminescence immunoassay (CIA), using anti-r7,t8-dihydroxy-t-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE)–DNA antiserum, which measures both BPdG and the other stable BP-DNA adducts. When mice were fed 100 ppm BP for 28 days, BP-induced DNA damage measured in esophagus, liver and lung was typically higher in Xpa(−/−)p53(+/−) mice, compared with WT mice. This result is consistent with the previously observed tumor susceptibility of Xpa(−/−)p53(+/−) mice. BPdG, the major DNA adduct associated with tumorigenicity, was the primary DNA adduct formed in esophagus (a target tissue in the mouse), whereas total BP-DNA adducts predominated in higher levels in the liver (a non-target tissue in the mouse). In an attempt to lower BP-induced DNA damage, we fed the WT and Xpa(−/−)p53(+/−) mice 0.3% chlorophyllin (CHL) in the BP-containing diet for 28 days. The addition of CHL resulted in an increase of BP–DNA adducts in esophagus, liver and lung of WT mice, a lowering of BPdG in esophagi of WT mice and livers of Xpa(−/−)p53(+/−) mice and an increase of BPdG in livers of WT mice. Therefore, the addition of CHL to a BP-containing diet showed a lack of consistent chemoprotective effect, indicating that oral CHL administration may not reduce PAH–DNA adduct levels consistently in human organs. PMID:22828138

  12. Benzo[a]pyrene (BP) DNA adduct formation in DNA repair-deficient p53 haploinsufficient [Xpa(-/-)p53(+/-)] and wild-type mice fed BP and BP plus chlorophyllin for 28 days.

    PubMed

    John, Kaarthik; Pratt, M Margaret; Beland, Frederick A; Churchwell, Mona I; McMullen, Gail; Olivero, Ofelia A; Pogribny, Igor P; Poirier, Miriam C

    2012-11-01

    We have evaluated DNA damage (DNA adduct formation) after feeding benzo[a]pyrene (BP) to wild-type (WT) and cancer-susceptible Xpa(-/-)p53(+/-) mice deficient in nucleotide excision repair and haploinsufficient for the tumor suppressor p53. DNA damage was evaluated by high-performance liquid chromatography/electrospray ionization tandem mass spectrometry (HPLC/ES-MS/MS), which measures r7,t8,t9-trihydroxy-c-10-(N (2)-deoxyguanosyl)-7,8,9,10-tetrahydrobenzo[a]pyrene (BPdG), and a chemiluminescence immunoassay (CIA), using anti-r7,t8-dihydroxy-t-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE)-DNA antiserum, which measures both BPdG and the other stable BP-DNA adducts. When mice were fed 100 ppm BP for 28 days, BP-induced DNA damage measured in esophagus, liver and lung was typically higher in Xpa(-/-)p53(+/-) mice, compared with WT mice. This result is consistent with the previously observed tumor susceptibility of Xpa(-/-)p53(+/-) mice. BPdG, the major DNA adduct associated with tumorigenicity, was the primary DNA adduct formed in esophagus (a target tissue in the mouse), whereas total BP-DNA adducts predominated in higher levels in the liver (a non-target tissue in the mouse). In an attempt to lower BP-induced DNA damage, we fed the WT and Xpa(-/-)p53(+/-) mice 0.3% chlorophyllin (CHL) in the BP-containing diet for 28 days. The addition of CHL resulted in an increase of BP-DNA adducts in esophagus, liver and lung of WT mice, a lowering of BPdG in esophagi of WT mice and livers of Xpa(-/-)p53(+/-) mice and an increase of BPdG in livers of WT mice. Therefore, the addition of CHL to a BP-containing diet showed a lack of consistent chemoprotective effect, indicating that oral CHL administration may not reduce PAH-DNA adduct levels consistently in human organs.

  13. Suicide Compared to Other Causes of Mortality in Physicians

    ERIC Educational Resources Information Center

    Torre, Dario M.; Wang, Nae-Yuh; Meoni, Lucy A.; Young, J. Hunter; Klag, Michael J.; Ford, Daniel E.

    2005-01-01

    Physicians frequently are early adopters of healthy behaviors based on their knowledge and economic resources. The mortality patterns of physicians in the United States, particularly suicide, have not been rigorously described for over a decade. Previous studies have shown lower all-cause mortality among physicians yet reported conflicting results…

  14. Defining Sickle Cell Disease Mortality Using a Population-Based Surveillance System, 2004 through 2008

    PubMed Central

    Paulukonis, Susan T.; Eckman, James R.; Snyder, Angela B.; Hagar, Ward; Feuchtbaum, Lisa B.; Zhou, Mei; Grant, Althea M.

    2016-01-01

    Objective Population-based surveillance data from California and Georgia for years 2004 through 2008 were linked to state death record files to determine the all-cause death rate among 12,143 patients identified with sickle cell disease (SCD). Methods All-cause death rates, by age, among these SCD patients were compared with all-cause death rates among both African Americans and the total population in the two states. All-cause death rates were also compared with death rates for SCD derived from publicly available death records: the compressed mortality files and multiple cause of death files. Results Of 12,143 patients identified with SCD, 615 patients died. The all-cause mortality rate for the SCD population was lower than the all-cause mortality rate among African Americans and similar to the total population all-cause mortality rates from birth through age 4 years, but the rate was higher among those with SCD than both the African American and total population rates from ages 5 through 74 years. The count of deceased patients identified by using population-based surveillance data (n=615) was more than twice as high as the count identified in compressed mortality files using SCD as the underlying cause of death alone (n=297). Conclusion Accurate assessment of all-cause mortality and age at death requires long-term surveillance via population-based registries of patients with accurately diagnosed SCD. PMID:26957672

  15. Antioxidant Vitamin Intake and Mortality

    PubMed Central

    Paganini-Hill, Annlia; Kawas, Claudia H.; Corrada, María M.

    2015-01-01

    To assess the relationship between antioxidant vitamin intake and all-cause mortality in older adults, we examined these associations using data from the Leisure World Cohort Study, a prospective study of residents of the Leisure World retirement community in Laguna Hills, California. In the early 1980s, participants (who were aged 44–101 years) completed a postal survey, which included details on use of vitamin supplements and dietary intake of foods containing vitamins A and C. Age-adjusted and multivariate-adjusted (for factors related to mortality in this cohort—smoking, alcohol intake, caffeine consumption, exercise, body mass index, and histories of hypertension, angina, heart attack, stroke, diabetes, rheumatoid arthritis, and cancer) hazard ratios for death were calculated using Cox regression for 8,640 women and 4,983 men (median age at entry, 74 years). During follow-up (1981–2013), 13,104 participants died (median age at death, 88 years). Neither dietary nor supplemental intake of vitamin A or vitamin C nor supplemental intake of vitamin E was significantly associated with mortality after multivariate adjustment. A compendium that summarizes previous findings of cohort studies evaluating vitamin intake and mortality is provided. Attenuation in the observed associations between mortality and antioxidant vitamin use after adjustment for confounders in our study and in previous studies suggests that such consumption identifies persons with other mortality-associated lifestyle and health risk factors. PMID:25550360

  16. Mortality patterns among workers exposed to acrylamide

    SciTech Connect

    Collins, J.J.; Swaen, G.M.; Marsh, G.M.; Utidjian, H.M.; Caporossi, J.C.; Lucas, L.J. )

    1989-07-01

    A cohort of 8854 men, 2293 of whom were exposed to acrylamide, was examined from 1925 to 1983 for mortality. This cohort consisted of four plant populations in two countries: the United States and The Netherlands. No statistically significant excess of all-cause or cause-specific mortality was found among acrylamide workers. Analysis by acrylamide exposure levels showed no trend of increased risk of mortality from several cancer sites. These results do not support the hypothesis that acrylamide is a human carcinogen.

  17. The impact of anemia on child mortality: an updated review.

    PubMed

    Scott, Samuel P; Chen-Edinboro, Lenis P; Caulfield, Laura E; Murray-Kolb, Laura E

    2014-12-22

    Iron deficiency anemia and child mortality are public health problems requiring urgent attention. However, the degree to which iron deficiency anemia contributes to child mortality is unknown. Here, we utilized an exhaustive article search and screening process to identify articles containing both anemia and mortality data for children aged 28 days to 12 years. We then estimated the reduction in risk of mortality associated with a 1-g/dL increase in hemoglobin (Hb). Our meta-analysis of nearly 12,000 children from six African countries revealed a combined odds ratio of 0.76 (0.62-0.93), indicating that for each 1-g/dL increase in Hb, the risk of death falls by 24%. The feasibility of a 1-g/dL increase in Hb has been demonstrated via simple iron supplementation strategies. Our finding suggests that ~1.8 million deaths in children aged 28 days to five years could be avoided each year by increasing Hb in these children by 1 g/dL.

  18. Mortality among female manual workers.

    PubMed Central

    Gunnarsdóttir, H; Rafnsson, V

    1992-01-01

    STUDY OBJECTIVE--The aim was to determine whether female manual workers have higher mortality than other women. DESIGN--This was a retrospective cohort study in which mortality was compared with that of the general female population. Main outcome measures were standardised mortality ratio (SMR) and 95% confidence intervals (CI). SETTING--Reykjavík region. PARTICIPANTS--Participants were 18,878 women, the cumulated members of a pension fund for manual workers between 1970 and 1986. MAIN RESULTS--A healthy worker effect was observed in the total cohort. The study was then restricted to those who had contributed to the pension fund any time after reaching 20 years of age, and a 10 year latency period was instituted. When analysing subcohorts by duration of employment the standardised mortality ratios for all causes of death and all cancers increased with longer employment time up to 10 years. However, the ratios were low in the group with over 10 years of employment. Those who began contributing to the fund in 1977 or later had higher mortality than those who began earlier. There was an excess of lung and bladder cancer in the total cohort and in all the subcohorts except in the group with over 10 years' employment. Mortality from accidents and suicides was in excess in all the groups. CONCLUSIONS--Mortality is high among some groups of female manual workers. A deficit was found among those with the longest employment. Differences in mortality have widened in recent years. An excess of suicides shows that women in this group have, for some reason, less will to live than other women. PMID:1494075

  19. A 28-day oral gavage toxicity study of 3-monochloropropane-1,2-diol (3-MCPD) in CB6F1-non-Tg rasH2 mice.

    PubMed

    Lee, Byoung-Seok; Park, Sang-Jin; Kim, Yong-Bum; Han, Ji-Seok; Jeong, Eun-Ju; Moon, Kyoung-Sik; Son, Hwa-Young

    2015-12-01

    3-Monochloro-1,2-propanediol (3-MCPD) is a well-known contaminant of foods containing hydrolyzed vegetable protein. However, limited toxicity data are available for the risk assessment of 3-MCPD and its carcinogenic potential is controversial. To evaluate the potential toxicity and determine the dose levels for a 26-week carcinogenicity test using Tg rasH2 mice, 3-MCPD was administered once daily by oral gavage at doses of 0, 25, 50, and 100 mg/kg body weight (b.w.)/day for 28 days to male and female CB6F1-non-Tg rasH2 mice (N = 5 males and females per dose). The standard toxicological evaluations were conducted during the in-life and post-mortem phase. In the 100 mg/kg b.w./day group, 3 males and 1 female died during the study and showed clinical signs such as thin appearance and subdued behavior accompanied by significant decreases in mean b.w. Microscopy revealed tubular basophilia in the kidneys, exfoliated degenerative germ cells in the lumen of the seminiferous tubule of the testes, vacuolation in the brain, axonal degeneration of the sciatic nerve, and cardiomyopathy in the 100, ≥25, ≥50, 100, and 100 mg/kg b.w./day groups, respectively. In conclusion, 3-MCPD's target organs were the kidneys, testes, brain, sciatic nerve, and heart. The "no-observed-adverse-effect level" (NOAEL) of 3-MCPD was ≤25 and 25 mg/kg b.w./day in males and females, respectively.

  20. Dietary and lifestyle determinants of mortality among German vegetarians.

    PubMed

    Chang-Claude, J; Frentzel-Beyme, R

    1993-04-01

    Lifestyle characteristics of a cohort of 1904 Germans adhering mainly to a vegetarian diet were examined in relation to their mortality after 11 years of follow-up. Poisson regression modelling was performed to consider the simultaneous effects of different variables on mortality from all causes, cancer (ICD 140-208) and cardiovascular diseases (ICD 390-459). Compared to a low level of self-reported physical activity, those with a medium or high level of activity experienced only half the mortality from all causes and from cardiovascular diseases. Physical activity showed no beneficial effect for cancer mortality in this cohort. The body mass index (BMI) was an independent risk factor for mortality among men but essentially unrelated to mortality among women. Those in the middle third of the BMI distribution experienced the lowest mortality. A negative association between BMI and cancer mortality lost statistical significance when the first 5 years of follow-up were deleted, suggesting that a lower BMI was a consequence of prevalent disease. Both the duration of vegetarianism and the vegetarian status (strict versus moderate) showed a moderate effect on all cause and cancer mortality. A longer duration of vegetarianism (> or = 20 years) was associated with a lower risk, pointing to a real protective effect of this lifestyle. A lower risk of death among moderate vegetarians suggests that sound nutritional planning may be more important than absolute avoidance of meat.

  1. The healthy immigrant effect and mortality rates.

    PubMed

    Ng, Edward

    2011-12-01

    According to the 2006 Census, almost the Canadian population were foreign-born, a percentage that is projected to reach at least 25% by 2031. Studies based on age-standardized mortality rates (ASMR) have found a healthy immigrant effect, with lower overall rates among immigrants. A duration effect has also been observed-immigrants' mortality advantage lessened as their time in Canada increased. ASMRs based on the 1991 to 2001 census mortality follow-up study indicate a healthy immigrant effect and a duration effect at the national level for all-cause mortality for both sexes. However, at the national level, the mortality rate among women from the United States and from Sub-Saharan Africa was similar to that of Canadian-born women. For the three largest Census Metropolitan Areas (Toronto, Montreal and Vancouver), a healthy immigrant effect was not observed among women or among most men from the United States or Sub-Saharan Africa.

  2. Seasonal Influenza Infections and Cardiovascular Disease Mortality

    PubMed Central

    Nguyen, Jennifer L.; Yang, Wan; Ito, Kazuhiko; Matte, Thomas D.; Shaman, Jeffrey; Kinney, Patrick L.

    2016-01-01

    IMPORTANCE Cardiovascular deaths and influenza epidemics peak during winter in temperate regions. OBJECTIVES To quantify the temporal association between population increases in seasonal influenza infections and mortality due to cardiovascular causes and to test if influenza incidence indicators are predictive of cardiovascular mortality during the influenza season. DESIGN, SETTING, AND PARTICIPANTS Time-series analysis of vital statistics records and emergency department visits in New York City, among cardiovascular deaths that occurred during influenza seasons between January 1, 2006, and December 31, 2012. The 2009 novel influenza A(H1N1) pandemic period was excluded from temporal analyses. EXPOSURES Emergency department visits for influenza-like illness, grouped by age (≥0 years and ≥65 years) and scaled by laboratory surveillance data for viral types and subtypes, in the previous 28 days. MAIN OUTCOMES AND MEASURES Mortality due to cardiovascular disease, ischemic heart disease, and myocardial infarction. RESULTS Among adults 65 years and older, who accounted for 83.0% (73 363 deaths) of nonpandemic cardiovascular mortality during influenza seasons, seasonal average influenza incidence was correlated year to year with excess cardiovascular mortality (Pearson correlation coefficients ≥0.75, P≤.05 for 4 different influenza indicators). In daily time-series analyses using 4 different influenza metrics, interquartile range increases in influenza incidence during the previous 21 days were associated with an increase between 2.3% (95% CI, 0.7%–3.9%) and 6.3% (95% CI, 3.7%–8.9%) for cardiovascular disease mortality and between 2.4% (95% CI, 1.1%–3.6%) and 6.9% (95% CI, 4.0%–9.9%) for ischemic heart disease mortality among adults 65 years and older. The associations were most acute and strongest for myocardial infarction mortality, with each interquartile range increase in influenza incidence during the previous 14 days associated with mortality

  3. The influence of weather on human mortality in Hong Kong.

    PubMed

    Yan, Y Y

    2000-02-01

    This study is the first attempt to investigate mortality seasonality and weather-mortality relationships in Hong Kong from 1980 to 1994. Monthly mortality data from all causes of death, neoplasm, circulatory and respiratory diseases were obtained from the Census and Statistics Department and the weather data were obtained from the Hong Kong Observatory. Regression analyses and ANOVA were employed. Significant winter peaks in sex specific and total deaths from all causes, circulatory and respiratory diseases were ascertained. Cancer mortality, however, was not seasonal. Mortality seasonality only existed in age groups 45-64 and > or =65. For the impact of weather on mortality, no significant relationship between weather variables and cancer mortality was observed. A significant negative association between minimum temperature and a positive relationship between cloud and deaths were found. This suggests that colder and cloudy conditions may heighten mortality. Wind was discovered to have a negative association with mortality. This finding revealed that the stressful effect of wind on mortality was negligible. There was no apparent sex difference. Deaths from the younger age groups (0-24 yr old) were not weather related. Weak weather connection with mortality for age group 25-44 was discovered, with Adj r2 values ranging from 0.05 to 0.07. The elderly (age > or =65) were more vulnerable to weather stress and strong weather-mortality relationship was uncovered, with Adj r2 values from 0.36 to 0.66. These results are important information for formulating public health policies.

  4. Mortality rates among Arab Americans in Michigan.

    PubMed

    Dallo, Florence J; Schwartz, Kendra; Ruterbusch, Julie J; Booza, Jason; Williams, David R

    2012-04-01

    The objectives of this study were to: (1) calculate age-specific and age-adjusted cause-specific mortality rates for Arab Americans; and (2) compare these rates with those for blacks and whites. Mortality rates were estimated using Michigan death certificate data, an Arab surname and first name list, and 2000 U.S. Census data. Age-specific rates, age-adjusted all-cause and cause-specific rates were calculated. Arab Americans (75+) had higher mortality rates than whites and blacks. Among men, all-cause and cause-specific mortality rates for Arab Americans were in the range of whites and blacks. However, Arab American men had lower mortality rates from cancer and chronic lower respiratory disease compared to both whites and blacks. Among women, Arab Americans had lower mortality rates from heart disease, cancer, stroke, and diabetes than whites and blacks. Arab Americans are growing in number. Future study should focus on designing rigorous separate analyses for this population.

  5. Nonalcoholic fatty liver disease and increased risk of 1-year all-cause and cardiac hospital readmissions in elderly patients admitted for acute heart failure

    PubMed Central

    Valbusa, Filippo; Bonapace, Stefano; Agnoletti, Davide; Scala, Luca; Grillo, Cristina; Arduini, Pietro; Turcato, Emanuela; Mantovani, Alessandro; Zoppini, Giacomo; Arcaro, Guido; Byrne, Christopher; Targher, Giovanni

    2017-01-01

    Nonalcoholic fatty liver disease (NAFLD) is an emerging risk factor for heart failure (HF). Although some progress has been made in improving survival among patients admitted for HF, the rates of hospital readmissions and the related costs continue to rise dramatically. We sought to examine whether NAFLD and its severity (diagnosed at hospital admission) was independently associated with a higher risk of 1-year all-cause and cardiac re-hospitalization in patients admitted for acute HF. We studied 212 elderly patients who were consecutively admitted with acute HF to the Hospital of Negrar (Verona) over a 1-year period. Diagnosis of NAFLD was based on ultrasonography, whereas the severity of advanced NAFLD fibrosis was based on the fibrosis (FIB)-4 score and other non-invasive fibrosis scores. Patients with acute myocardial infarction, severe valvular heart diseases, end-stage renal disease, cancer, known liver diseases or decompensated cirrhosis were excluded. Cox regression was used to estimate hazard ratios (HR) for the associations between NAFLD and the outcome(s) of interest. The cumulative rate of 1-year all-cause re-hospitalizations was 46.7% (n = 99, mainly due to cardiac causes). Patients with NAFLD (n = 109; 51.4%) had remarkably higher 1-year all-cause and cardiac re-hospitalization rates compared with their counterparts without NAFLD. Both event rates were particularly increased in those with advanced NAFLD fibrosis. NAFLD was associated with a 5-fold increased risk of 1-year all-cause re-hospitalization (adjusted-hazard ratio 5.05, 95% confidence intervals 2.78–9.10, p<0.0001) after adjustment for established risk factors and potential confounders. Similar results were found for 1-year cardiac re-hospitalization (adjusted-hazard ratio 8.05, 95% confidence intervals 3.77–15.8, p<0.0001). In conclusion, NAFLD and its severity were strongly and independently associated with an increased risk of 1-year all-cause and cardiac re-hospitalization in elderly

  6. Dietary patterns and mortality in a Chinese population123

    PubMed Central

    Odegaard, Andrew O; Koh, Woon-Puay; Yuan, Jian-Min; Gross, Myron D; Pereira, Mark A

    2014-01-01

    Background: Limited research has examined the association between dietary patterns and mortality, especially in non-Western populations. Objective: We examined the association of dietary patterns with all-cause mortality and cause-specific mortality in the Singapore Chinese Health Study, which included a unique ethnic population with strong Western and South Asian cultural influences. Design: We conducted a prospective data analysis of the Singapore Chinese Health Study, which included 52,584 Chinese men and women (aged 45–74 y) who were free of diabetes, cardiovascular disease (CVD), and cancer at baseline (1993–1998) and followed through 2011 with 10,029 deaths. The following 2 major dietary patterns were identified by using a principal components analysis: a vegetable-, fruit-, and soy-rich (VFS) pattern and a dim sum– and meat-rich (DSM) dietary pattern. Pattern scores for each participant were calculated and examined with all-cause and cause-specific mortality risks by using a Cox proportional hazards regression. Results: The VFS pattern was inversely associated with all-cause mortality and each cause-specific category (CVD, cancer, and respiratory) of mortality during the follow-up period. Compared with the lowest quintile of the VFS pattern, HRs for quintiles 2–5 for all-cause mortality were 0.90, 0.79, 0.80, and 0.75, respectively (P-trend < 0.0001). The DSM pattern was positively associated with CVD mortality in the whole population (HR for fifth quintile compared with first quintile: 1.23; 95% CI: 1.07, 1.40; P-trend = 0.001). Positive associations between the DSM pattern and cancer and all-cause mortality were only present in ever-smokers. In ever-smokers, relative to the first quintile, HRs for quintiles 2–5 of the DSM pattern for all-cause mortality were 1.04, 1.04, 1.13, and 1.24, respectively (P-trend < 0.0001). Similarly, HRs for quintiles 2–5 for cancer mortality were 1.08, 1.03, 1.25, and 1.34, respectively (P-trend < 0.0001). The DSM

  7. Blood Lactate Levels Cutoff and Mortality Prediction in Sepsis—Time for a Reappraisal? a Retrospective Cohort Study

    PubMed Central

    Filho, Roberto Rabello; Rocha, Leonardo Lima; Corrêa, Thiago Domingos; Pessoa, Camila Menezes Souza; Colombo, Giancarlo; Assuncao, Murillo Santucci Cesar

    2016-01-01

    Abstract The objective of this study was to identify the initial value of blood lactate that best correlates with 28-day mortality in resuscitated septic shock patients. This was a retrospective cohort study including 443 patients admitted to an intensive care unit (ICU) with severe sepsis or septic shock from the emergency department. A receiver-operating characteristic (ROC) curve was drawn to obtain the best cutoff value for initial blood lactate associated with 28-day mortality. Patients were then dichotomized according to the chosen lactate cutoff, and sensitivity, specificity, and positive and negative predictive values were calculated. Baseline blood lactate level more than 2.5 mmol/L showed the largest area under the ROC curve to predict 28-day mortality (ROC area, 0.70; 95% confidence interval [CI], 0.62–0.79), with sensitivity, specificity, and negative predictive value of 67.4%, 61.7%, and 94.2%, respectively. Mortality at 28 days was 16.9% (31/183) in patients with initial lactate more than 2.5 mmol/L and 5.8% (15/260) in patients with initial lactate at most 2.5 mmol/L (relative risk, 2.93; 95% CI, 1.63–5.28; P < 0.001). Initial blood lactate levels more than 2.5 mmol/L (hazard ratio [HR], 2.86; 95% CI, 1.53–5.33; P = 0.001) and Sepsis-related Organ Failure Assessment score at ICU admission (HR, 1.18; 95% CI, 1.09–1.27; P < 0.001) were associated with increased 28-day mortality in the adjusted Cox regression. In this retrospective cohort study, a lactate level more than 2.5 mmol/L was the best threshold to predict 28-day mortality among severe sepsis and septic shock patients. Further prospective studies should address the impact on morbidity and mortality of this threshold as a trigger to resuscitation in this population of critically ill patients. PMID:27380535

  8. Continuing the search for a fundamental law of mortality

    SciTech Connect

    Carnes, B.A.; Grahn, D.; Olshansky, S.J.

    1997-08-01

    For 170 years, scientists have attempted to explain why consistent temporal patterns of death are observed among individuals within populations. Historical efforts to identify a {open_quotes}law of mortality{close_quotes} from these patterns ended in 1935 when it was declared that such a law did not exist. These empirical tests for a law of mortality were constructed using mortality curves based on all causes of death. We predicted that patterns of mortality consistent with the historical concept of a law would be revealed if mortality curves for species were constructed using only senescent causes of death. Using data on senescent mortality for laboratory animals and humans, we demonstrate that patterns of mortality overlap when compared on a biologically comparable time scale. These results are consistent with the existence of a law of mortality following sexual maturity as asserted by Benjamin Gompertz and Raymond Pearl. The societal, medical, and research implications of such a law are discussed.

  9. Continuing the search for a fundamental law of mortality

    SciTech Connect

    Carnes, B.A.; Grahn, D.; Olshansky, S.J.

    1996-03-01

    for 170 years, scientists have attempted to explain why consistent temporal patterns of death are observed among individuals within populations. Historical efforts to identify a `law of mortality` from these patterns ended in 1935 when it was declared that such a law did not exist. These empirical tests for a law of mortality were constructed using mortality curves based on all causes of death. We predicted patterns of mortality consistent with the historical concept of a law would be revealed if mortality curves for species were constructed using only senescent causes of death. Using data on senescent mortality for laboratory animals and humans, we demonstrate patterns of mortality overlap when compared on a biologically comparable time scale. The results are consistent with the existence of a law of mortality following sexual maturity. The societal, medical, and research implications of such a law are discussed.

  10. Higher all-cause hospitalization among patients with chronic hepatitis C: the Chronic Hepatitis Cohort Study (CHeCS), 2006-2013.

    PubMed

    Teshale, E H; Xing, J; Moorman, A; Holmberg, S D; Spradling, P R; Gordon, S C; Rupp, L B; Lu, M; Boscarino, J A; Trinacity, C M; Schmidt, M A; Xu, F

    2016-10-01

    In the United States, hospitalization among patients with chronic hepatitis C virus (HCV) infection is high. The healthcare burden associated with hospitalization is not clearly known. We analysed data from the Chronic Hepatitis Cohort Study, an observational cohort of patients receiving care at four integrated healthcare systems, collected from 2006 to 2013 to determine all-cause hospitalization rates of patients with chronic HCV infection and the other health system patients. To compare the hospitalization rates, we selected two health system patients for each chronic HCV patient using their propensity score (PS). Propensity score matching was conducted by site, gender, race, age and household income to minimize differences attributable to these characteristics. We also compared primary reason for hospitalization between chronic HCV patients and the other health system patients. Overall, 10 131 patients with chronic HCV infection and 20 262 health system patients were selected from the 1 867 802 health system patients and were matched by PS. All-cause hospitalization rates were 27.4 (27.0-27.8) and 7.4 (7.2-7.5) per 100 persons-year (PY) for chronic HCV patients and for the other health system patients, respectively. Compared to health system patients, hospitalization rates were significantly higher by site, gender, age group, race and household income among chronic HCV patients (P < 0.001). Compared to health system patients, chronic HCV patients were more likely to be hospitalized from liver-related conditions (RR = 24.8, P < 0.001). Hence, patients with chronic HCV infection had approximately 3.7-fold higher all-cause hospitalization rate than other health system patients. These findings highlight the incremental costs and healthcare burden of patients with chronic HCV infection associated with hospitalization.

  11. Socio-demographic Characteristics and Leading Causes of Death Among the Casualties of Meteorological Events Compared With All-cause Deaths in Korea, 2000-2011

    PubMed Central

    Lee, Kyung Eun; Myung, Hyung-Nam; Na, Wonwoong

    2013-01-01

    Objectives This study investigated the socio-demographic characteristics and medical causes of death among meteorological disaster casualties and compared them with deaths from all causes. Methods Based on the death data provided by the National Statistical Office from 2000 to 2011, the authors analyzed the gender, age, and region of 709 casualties whose external causes were recorded as natural events (X330-X389). Exact matching was applied to compare between deaths from meteorological disasters and all deaths. Results The total number of deaths for last 12 years was 2 728 505. After exact matching, 642 casualties of meteorological disasters were matched to 6815 all-cause deaths, which were defined as general deaths. The mean age of the meteorological disaster casualties was 51.56, which was lower than that of the general deaths by 17.02 (p<0.001). As for the gender ratio, 62.34% of the meteorological event casualties were male. While 54.09% of the matched all-cause deaths occurred at a medical institution, only 7.6% of casualties from meteorological events did. As for occupation, the rate of those working in agriculture, forestry, and fishery jobs was twice as high in the casualties from meteorological disasters as that in the general deaths (p<0.001). Meteorological disaster-related injuries like drowning were more prevalent in the casualties of meteorological events (57.48%). The rate of amputation and crushing injury in deaths from meteorological disasters was three times as high as in the general deaths. Conclusions The new information gained on the particular characteristics contributing to casualties from meteorological events will be useful for developing prevention policies. PMID:24137528

  12. Contribution of the long-term care insurance certificate for predicting 1-year all-cause readmission compared with validated risk scores in elderly patients with heart failure

    PubMed Central

    Takahashi, Kayo; Saito, Makoto; Inaba, Shinji; Morofuji, Toru; Aisu, Hiroe; Sumimoto, Takumi; Ogimoto, Akiyoshi; Ikeda, Shuntaro; Higaki, Jitsuo

    2016-01-01

    Objectives Readmission is a common and serious problem associated with heart failure (HF). Unfortunately, conventional risk models have limited predictive value for predicting readmission. The recipients of long-term care insurance (LTCI) are frail and have mental and physical impairments. We hypothesised that adjustment of the conventional risk score with an LTCI certificate enables a more accurate appreciation of readmission for HF. Methods We investigated 452 patients with HF who were followed up for 1 year to determine all-cause readmission. We obtained their clinical and socioeconomic data, including LTCI. The three clinical risk scores used in our evaluation were Keenan (2008), Krumholz (2000) and Charlson (1994). We used net reclassification improvement (NRI) to assess the incremental benefit. Results Patients with LTCI were significantly older, and had a higher prevalence of cerebrovascular disease and dementia than those without LTCI. One-year all-cause readmission (n=193, 43%) was significantly associated with all risk scores, receiving LTCI and the category of LTCI. Receiving LTCI was associated with readmission independent of all risk scores (HR, 1.59 to 1.63; all p<0.01). Adding LTCI to all risk scores led to a significantly improved reclassification, which was observed in the subgroup of patients with HF with preserved ejection fraction (≥50%) but not in the subgroup with reduced ejection fraction (<50%). Conclusions Possession of an LTCI certificate was independently associated with 1-year all-cause readmission after adjusting for validated clinical risk scores in patients with HF. Adding LTCI status significantly improved the model performance for readmission risk, particularly in patients with HF and preserved ejection fraction. PMID:27933194

  13. Body mass index versus waist circumference as predictors of mortality in Canadian adults

    PubMed Central

    Staiano, AE; Reeder, BA; Elliott, S; Joffres, MR; Pahwa, P; Kirkland, SA; Paradis, G; Katzmarzyk, PT

    2014-01-01

    BACKGROUND Elevated body mass index (BMI) and waist circumference (WC) are associated with increased mortality risk, but it is unclear which anthropometric measurement most highly relates to mortality. We examined single and combined associations between BMI, WC, waist–hip ratio (WHR) and all-cause, cardiovascular disease (CVD) and cancer mortality. METHODS We used Cox proportional hazard regression models to estimate relative risks of all-cause, CVD and cancer mortality in 8061 adults (aged 18–74 years) in the Canadian Heart Health Follow-Up Study (1986–2004). Models controlled for age, sex, exam year, smoking, alcohol use and education. RESULTS There were 887 deaths over a mean 13 (SD 3.1) years follow-up. Increased risk of death from all-causes, CVD and cancer were associated with elevated BMI, WC and WHR (P < 0.05). Risk of death was consistently higher from elevated WC versus BMI or WHR. Ascending tertiles of each anthropometric mea