CONTEXT: Secondary analyses of 2 randomized controlled trials and supportive epidemiologic and preclinical data indicated the potential of selenium and vitamin E for preventing prostate cancer. OBJECTIVE: To determine whether selenium, vitamin E, or both could prevent prostate cancer and other diseases with little or no toxicity in relatively healthy men. DESIGN, SETTING, AND PARTICIPANTS: A randomized, placebo-controlled trial (Selenium and Vitamin E Cancer Prevention Trial [SELECT]) of 35 533 men from 427 participating sites in the United States, Canada, and Puerto Rico randomly assigned to 4 groups (selenium, vitamin E, selenium + vitamin E, and placebo) in a double-blind fashion between August 22, 2001, and June 24, 2004. Baseline eligibility included age 50 years or older (African American men) or 55 years or older (all other men), a serum prostate-specific antigen level of 4 ng/mL or less, and a digital rectal examination not suspicious for prostate cancer. INTERVENTIONS: Oral selenium (200 mug/d from L-selenomethionine) and matched vitamin E placebo, vitamin E (400 IU/d of all rac-alpha-tocopheryl acetate) and matched selenium placebo, selenium + vitamin E, or placebo + placebo for a planned follow-up of minimum of 7 years and a maximum of 12 years. MAIN OUTCOME MEASURES: Prostate cancer and prespecified secondary outcomes, including lung, colorectal, and overall primary cancer. RESULTS: As of October 23, 2008, median overall follow-up was 5.46 years (range, 4.17-7.33 years). Hazard ratios (99% confidence intervals [CIs]) for prostate cancer were 1.13 (99% CI, 0.95-1.35; n = 473) for vitamin E, 1.04 (99% CI, 0.87-1.24; n = 432) for selenium, and 1.05 (99% CI, 0.88-1.25; n = 437) for selenium + vitamin E vs 1.00 (n = 416) for placebo. There were no significant differences (all P>.15) in any other prespecified cancer end points. There were statistically nonsignificant increased risks of prostate cancer in the vitamin E group (P = .06) and type 2 diabetes mellitus in the selenium group (relative risk, 1.07; 99% CI, 0.94-1.22; P = .16) but not in the selenium + vitamin E group. CONCLUSION: Selenium or vitamin E, alone or in combination at the doses and formulations used, did not prevent prostate cancer in this population of relatively healthy men.Trial Registration clinicaltrials.gov identifier: NCT00006392Published online December 9, 2008 (doi:10.1001/jama.2008.864).
 
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A number of previous studies have reported an inverse association between maternal smoking and preeclampsia. Additionally, some have suggested that smokers who develop preeclampsia have worse maternal and fetal outcomes than nonsmokers who develop preeclampsia. The authors examined the relation of smoking to preeclampsia among 674,250 singleton pregnancies in New York City between 1995 and 2003. Although smoking was associated with a reduced risk of preeclampsia overall (adjusted odds ratio = 0.88, 95% confidence interval: 0.82, 0.94), no association was found for preeclampsia superimposed on chronic hypertension (adjusted odds ratio = 1.04, 95% confidence interval: 0.90, 1.21). Furthermore, the apparent protection conferred by maternal smoking was restricted to women aged < or =30 years. Contrary to previous reports, the authors found evidence of a negative interaction between smoking and preeclampsia with respect to preterm delivery and birth weight; smokers who developed preeclampsia had a lower risk of preterm delivery, and a lower adjusted mean difference in birth weight, than would have been expected based on the independent effects of smoking and preeclampsia. These data suggest that smoking is only protective against preeclampsia without pregestational hypertension, and even then principally among younger women. Additionally, smokers who develop these disorders have no increased risk of adverse birth outcomes relative to nonsmokers who develop the same conditions.
 
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BACKGROUND: Smoking is a risk factor for many diseases and has been increasingly prevalent in economically developing regions of the world. We aimed to estimate the number of deaths attributable to smoking in China. METHODS: We conducted a large, prospective cohort study in a nationally representative sample of 169,871 Chinese adults who were 40 years of age or older. Investigators for the China National Hypertension Survey collected data on smoking and other risk factors at a baseline examination in 1991 using a standard protocol. Follow-up evaluation was conducted in 1999 and 2000, with a response rate of 93.4%. We used multivariable-adjusted relative risk, prevalence of smoking, mortality, and population size in each age group, stratified according to sex, to calculate the number of deaths attributable to smoking in 2005. RESULTS: There was a significant, dose-response association between pack-years smoked and death from any cause in both men and women after adjustment for multiple risk factors (P<0.001 for trend). We estimated that in 2005, a total of 673,000 deaths (95% confidence interval [CI], 564,700 to 781,400) were attributable to smoking in China: 538,200 (95% CI, 455,800 to 620,600) among men and 134,800 (95% CI, 108,900 to 160,800) among women. The leading causes of smoking-related deaths were as follows: cancer, 268,200 (95% CI, 214,500 to 321,900); cardiovascular disease, 146,200 (95% CI, 79,200 to 213,100); and respiratory disease, 66,800 (95% CI, 20,300 to 113,300). CONCLUSIONS: Our study documents that smoking is a major risk factor for mortality in China. Continued strengthening of national programs and initiatives for smoking prevention and cessation is needed to reduce smoking-related deaths in China. Copyright 2009 Massachusetts Medical Society.
 
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OBJECTIVE: To examine the association between physical activity in early pregnancy and risk of pre-eclampsia. DESIGN: Prospective cohort. SETTING: Denmark. POPULATION: A total of 85,139 pregnant Danish women, recruited between 1996 and 2002. METHODS: The authors assessed leisure time physical activity in first trimester by a telephone interview and categorised women a priori into seven groups: 0 (reference), 1-44, 45-74, 75-149, 150-269, 270-419 and 420+ minutes/week. Pre-eclampsia diagnoses were extracted from the Danish National Patient Registry. A number of potential confounders were adjusted for by logistic regression. MAIN OUTCOME MEASURES: Pre-eclampsia and severe pre-eclampsia. RESULTS: The two highest physical activity levels were associated with increased risk of severe pre-eclampsia compared with the nonexercising group, with adjusted odds ratios of 1.65 (95% CI: 1.11-2.43) and 1.78 (95% CI: 1.07-2.95), whereas more moderate levels of physical activity (1-270 minutes/week) had no statistically significant association with risk of pre-eclampsia (total n = 85,139). CONCLUSIONS: We were unable to document a protective effect of leisure time physical activity against pre-eclampsia. Our data even suggest that leisure time physical activity exceeding 270 minutes/week in first trimester may increase risk of severe pre-eclampsia.
 
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BACKGROUND: the mortality and morbidity of falls in older people is significant, with recurrent fallers being at an increased risk. The most effective way to reduce falls in this group is not clear. OBJECTIVE: to determine the effectiveness of two interventions, one based in primary care and the other in secondary care, at preventing further falls in recurrent fallers. DESIGN: cluster randomised controlled trial. PARTICIPANTS: sixty-five years or over, living in the community, two or more falls in the previous year and not presenting to an emergency department with index fall. SETTING: Mid Hampshire, UK. INTERVENTION: eighteen general practices were randomly allocated to one of three groups. The primary care group was assessed by nurses in the community, using a risk factor review and subsequent targeted referral to other professionals. The secondary care group received a multi-disciplinary assessment in a day hospital followed by identified appropriate interventions. The control group received usual care. Follow-up was for 1 year. RESULTS: five hundred and five participants were recruited. Follow-up was completed in 83% (421/505). The proportion of participants who fell again was significantly lower in the secondary care group (75%, 158/210) compared to the control group [84%, 133/159, adjusted odds ratio (OR) 0.52 (95% CI 0.35-0.79) P = 0.002]. The primary care group showed similar results to the control group [87%, 118/136, adjusted OR 1.17 (95% CI 0.57-2.37) P = 0.673]. CONCLUSION: a structured multi-disciplinary assessment of recurrent fallers significantly reduced the number experiencing further falls, but a community-based nurse-led assessment with targeted referral to other professionals did not.
 
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CONTEXT: Many individuals take vitamins in the hopes of preventing chronic diseases such as cancer, and vitamins E and C are among the most common individual supplements. A large-scale randomized trial suggested that vitamin E may reduce risk of prostate cancer; however, few trials have been powered to address this relationship. No previous trial in men at usual risk has examined vitamin C alone in the prevention of cancer. OBJECTIVE: To evaluate whether long-term vitamin E or C supplementation decreases risk of prostate and total cancer events among men. DESIGN, SETTING, AND PARTICIPANTS: The Physicians` Health Study II is a randomized, double-blind, placebo-controlled factorial trial of vitamins E and C that began in 1997 and continued until its scheduled completion on August 31, 2007. A total of 14,641 male physicians in the United States initially aged 50 years or older, including 1307 men with a history of prior cancer at randomization, were enrolled. INTERVENTION: Individual supplements of 400 IU of vitamin E every other day and 500 mg of vitamin C daily. MAIN OUTCOME MEASURES: Prostate and total cancer. RESULTS: During a mean follow-up of 8.0 years, there were 1008 confirmed incident cases of prostate cancer and 1943 total cancers. Compared with placebo, vitamin E had no effect on the incidence of prostate cancer (active and placebo vitamin E groups, 9.1 and 9.5 events per 1000 person-years; hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.85-1.09; P = .58) or total cancer (active and placebo vitamin E groups, 17.8 and 17.3 cases per 1000 person-years; HR, 1.04; 95% CI, 0.95-1.13; P = .41). There was also no significant effect of vitamin C on total cancer (active and placebo vitamin C groups, 17.6 and 17.5 events per 1000 person-years; HR, 1.01; 95% CI, 0.92-1.10; P = .86) or prostate cancer (active and placebo vitamin C groups, 9.4 and 9.2 cases per 1000 person-years; HR, 1.02; 95% CI, 0.90-1.15; P = .80). Neither vitamin E nor vitamin C had a significant effect on colorectal, lung, or other site-specific cancers. Adjustment for adherence and exclusion of the first 4 or 6 years of follow-up did not alter the results. Stratification by various cancer risk factors demonstrated no significant modification of the effect of vitamin E on prostate cancer risk or either agent on total cancer risk. CONCLUSIONS: In this large, long-term trial of male physicians, neither vitamin E nor C supplementation reduced the risk of prostate or total cancer. These data provide no support for the use of these supplements for the prevention of cancer in middle-aged and older men. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00270647.
 
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OBJECTIVES: This study sought to estimate the extent to which behavioral and pathophysiological risk factors account for the association between psychological distress and incident cardiovascular events. BACKGROUND: The intermediate processes through which psychological distress increases the risk of cardiovascular disease (CVD) are incompletely understood. An understanding of these processes is important for treating psychological distress in an attempt to reduce CVD risk. METHODS: In a prospective study of 6,576 healthy men and women (ages 50.9 +/- 13.1 years), we measured psychological distress (using the 12-item version of the General Health Questionnaire >/=4) and behavioral (smoking, alcohol, physical activity) and pathophysiological (C-reactive protein, fibrinogen, total and high-density lipoprotein cholesterol, obesity, hypertension) risk factors at baseline. The main outcome was CVD events (hospitalization for nonfatal myocardial infarction, coronary artery bypass, angioplasty, stroke, heart failure, and CVD-related mortality). RESULTS: Cigarette smoking, physical activity, alcohol intake, C-reactive protein, and hypertension were independently associated with psychological distress. There were 223 incident CVD events (63 fatal) over an average follow-up of 7.2 years. The risk of CVD increased in relation to presence of psychological distress in age- and sex-adjusted models (hazard ratio: 1.54, 95% confidence interval: 1.09 to 2.18, p = 0.013). In models that were adjusted for potential mediators, behavioral factors explained the largest proportion of variance ( approximately 65%), whereas pathophysiological factors accounted for a modest amount (C-reactive protein approximately 5.5%, hypertension, approximately 13%). CONCLUSIONS: The association between psychological distress and CVD risk is largely explained by behavioral processes. Therefore, treatment of psychological distress that aims to reduce CVD risk should primarily focus on health behavior change.
 
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OBJECTIVE: Our goal was to compare the safety and immunogenicity of a combination vaccine (DTaP(5)-IPV-Hib; Pentacel) with that of its separately administered, US-licensed equivalent vaccines (diphtheria, tetanus, 5-component acellular pertussis vaccine [DTaP(5); Daptacel], inactivated poliovirus vaccine [IPV; IPOL], and Haemophilus influenzae type b [Hib] vaccine [ActHIB]), when administered to infants and toddlers concomitantly with other routinely recommended vaccines and to assess antibody persistence from the fourth dose in toddlers to the fifth (preschool) DTaP(5) dose. SUBJECTS AND METHODS: In this randomized, multicenter study, 1939 healthy infants were immunized at 2, 4, and 6 months of age with 1 of 3 lots of DTaP(5) coadministered with IPV and Hib vaccines or 1 lot of DTaP(5)-IPV-Hib combination vaccine. Subsequently, 849 of these study participants were given a fourth dose of DTaP(5) and Hib vaccines or a fourth dose of DTaP(5)-IPV-Hib at 1 to 16 months of age. Safety was monitored throughout the study, and blood specimens were obtained to assess antibody responses. RESULTS: DTaP(5)-IPV-Hib elicited similar or fewer solicited injection-site and systemic reactions as compared with the separate administration of US-licensed DTaP(5), IPV, and Hib vaccines. Seroresponse and seroprotection rates elicited by DTaP(5)-IPV-Hib were noninferior to US-licensed equivalent vaccines after the infant series and after the fourth dose. Children immunized with DTaP(5)-IPV-Hib had higher antibody geometric mean concentrations to pertussis toxoid and filamentous hemagglutinin; children immunized with the separate vaccines had higher responses to pertactin. Hib antibody responses to Hib polysaccharide were nearly identical in the DTaP(5)-IPV-Hib and separate-vaccine groups. Persistence of antibodies to the fifth (preschool) dose was also similar between groups. CONCLUSIONS: DTaP(5)-IPV-Hib combination vaccine was shown to be immunogenic and well tolerated. No clinically important differences in the safety or immunologic profiles were noted for DTaP(5)-IPV-Hib versus the separately administered, US-licensed equivalent vaccines. DTaP(5)-IPV-Hib is a suitable replacement for separately administered DTaP, IPV, and Hib vaccines.
 
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A 40-year follow-up study was conducted to examine mortality among 1,664 patients in Japan suffering from ``Yusho,`` a disease caused by ingestion of rice oil contaminated with polychlorinated biphenyls and polychlorinated dibenzofurans. To evaluate the effects of exposure on mortality, the authors calculated standardized mortality ratios. National mortality rates for major causes of death were used as reference points. A total of 1,596 Yusho patients (95.9%) were followed until death or the end of the study (December 31, 2007). The standardized mortality ratios for most major causes of death were not significantly elevated, with the exceptions of all types of cancer (standardized mortality ratio (SMR) = 1.37, 95% confidence interval (CI): 1.11, 1.66), liver cancer (SMR = 1.82, 95% CI: 1.06, 2.91), and lung cancer (SMR = 1.75, 95% CI: 1.14, 2.57) in males. In addition, the standardized mortality ratios for all cancers, liver cancer, and lung cancer among males tended to decrease over time. Results from this study suggest that the carcinogenicity of polychlorinated biphenyls and polychlorinated dibenzofurans must be taken into account when evaluating mortality risk.
 
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BACKGROUND: The time-dependent association between metabolic syndrome and risk of chronic kidney disease (CKD) is not clear. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: The study cohort was composed of 10,685 healthy men without CKD, hypertension, or diabetes who participated in a health-checkup program at a large work site. PREDICTOR: Metabolic syndrome. OUTCOMES & MEASUREMENTS: CKD was defined as an estimated glomerular filtration rate (GFR) less than 60 mL/min/1.73 m(2). A standard Cox proportional hazards model and a time-dependent Cox model were used to calculate adjusted hazard ratios (HRs) in the CKD model. RESULTS: During 40,616.8 person-years of follow-up, 291 incident cases of CKD developed; 787 patients (7.4%) had metabolic syndrome at baseline and 1,444 (14.4%) developed incident metabolic syndrome during follow-up. After adjustment for age, baseline GFR, gamma-glutamyltransferase level, and uric acid level, metabolic syndrome at baseline was associated with a significantly increased risk of CKD (HR, 1.99; 95% confidence interval, 1.46 to 2.73). Metabolic syndrome over time as a time-dependent variable also predicted the development of CKD (HR, 1.75; 95% confidence interval, 1.28 to 2.39). The relationship between metabolic syndrome and incident CKD remained significant, even after further adjustment for the homeostasis model assessment of insulin resistance, high-sensitivity C-reactive protein level, current smoking, alcohol consumption, or regular exercise. In addition, there were graded relationships between number of metabolic syndrome traits or quintile of homeostasis model assessment of insulin resistance over time as a time-dependent variable and risk of CKD. Both increased triglyceride and low high-density lipoprotein cholesterol levels among metabolic syndrome traits were associated with significantly increased risk of CKD. These results were effectively unchanged, even after additional adjustment for incident hypertension and incident diabetes. LIMITATIONS: Estimated GFR was used instead of a directly measured GFR to define CKD. CONCLUSION: Metabolic syndrome is an independent risk factor for the development of CKD in Korean men without hypertension or diabetes, even with changes in status of metabolic syndrome over time.
 
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