Higher mortality of adults with asthma: A 15-year follow-up of a population-based cohort.

BACKGROUND: Higher all-cause mortality in asthmatics has been shown previously. Polysensitization is associated with higher morbidity among asthmatic children, and allergic rhinitis and/or allergic conjunctivitis (AR/AC) are associated with higher morbidity in adult asthmatics. Little is known about the effect of AR/AC and other factors on mortality among adult asthmatics. The aim was to study mortality and its risk factors in adults with and without asthma. METHODS: We randomly selected 1648 asthmatics with age over 30 years from national registers and matched the asthma sample with one or two controls. Baseline information was obtained by a questionnaire in 1997, and the study population was linked with the death certificate information of Statistics Finland from 1997 to 2013. Overall and cause-specific survival between the groups was compared in several adjusted models. RESULTS: During a mean follow-up period of 15.6 years, 221 deaths among 1052 asthma patients and 335 deaths among 1889 nonasthmatics were observed. Cardiovascular diseases were the main cause of death in both groups. Asthma was associated with increased all-cause mortality (adjusted HR 1.25; 95% CI 1.05-1.49, P = .011) as well as mortality from chronic obstructive pulmonary disease (HR 12.0, 4.18-34.2, P < .001) and malignant neoplasms of respiratory organs (HR 2.33, 1.25-4.42, P = .008). Among asthmatics, smoking was associated with increased all-cause mortality, and self-reported AR/AC was associated with decreased mortality. Among nonasthmatics, smoking, and obesity were associated with increased all-cause mortality, whereas female gender showed an association with a decreased risk. CONCLUSIONS: Increased mortality among adult asthmatics was largely explained by the development of COPD, malignant respiratory tract neoplasms, and cardiovascular diseases. Smoking cessation is important for reduction in total mortality in both asthmatic and nonasthmatic adults. AR/AC was associated with decreased mortality only in asthmatics. Thus, studies in other populations of larger size are needed to explore further the nature of this association.

Decline in the incidence of schizophrenia in Finnish cohorts born from 1954 to 1965.

BACKGROUND: The declining incidence of schizophrenia observed in several countries is believed by many to merely reflect methodological problems in the studies performed. We report the first nationwide historical cohort study of changes in the incidence of schizophrenia, in which many of the previous methodological problems were overcome. METHODS: We used the Finnish Population Register to identify everyone born in Finland from 1954 to 1965. These persons were followed up from their 16th to their 26th birthdays, and all cases of schizophrenia (International Classification of Diseases, Eighth Revision and International Classification of Diseases, Ninth Revision code 295) that emerged were identified from the National Hospital Discharge Register, the Pension Register, and the Free Medicine Register. Persons for whom an age of onset could be defined were included in the analyses (n = 5645). We used the Poisson regression model to estimate the effects of age, sex, birth cohort, period of diagnosis, and season of birth on the incidence of schizophrenia. The relative importance of cohort and period were assessed using an age-period-cohort model. RESULTS: The incidence declined significantly in each successive cohort, from 0.79 to 0.53 per 1000 among males and from 0.58 to 0.41 per 1000 among females. The effects of cohort and period on the change were both significant. CONCLUSIONS: The incidence of schizophrenia has declined in Finland. This was partly caused by confounding factors, as reflected in the significant period effect. The significant birth cohort effect suggests that the intensity or frequency of one or more risk factors for schizophrenia has decreased.

Season of birth among patients with schizophrenia and their siblings: evidence for the procreational habits hypothesis.

OBJECTIVE: The birth rate of patients with schizophrenia during the winter and spring months is 5%-8% higher worldwide than the birth rate of the general population in the winter and spring months. Seasonal variation of births among the unaffected siblings of patients with schizophrenia has not been studied with adequate sample sizes. The authors investigated the seasonal variation of births among siblings of patients with schizophrenia in a large, nationwide, representative patient and sibling population. METHOD: Finnish patients with schizophrenia born from 1950 to 1969 (N=15,389) were identified from three nationwide health care registers. Unaffected siblings of these patients born in the same time period (N=37,819) were identified from the Finnish National Population REGISTER: The seasonal variation of births among patients and siblings were examined by using a log-linear model. Explanatory variables were sex, year of birth categorized into four 5-year groups, and seasonal variation, which was analyzed by fitting a short Fourier series to the monthly birth data. RESULTS: The odds for having been born during the winter-spring months were slightly higher among both siblings and patients in all birth-year groups. However, patients born from 1955 to 1959 showed prominent seasonal variation of births, but the magnitude of this variation remained unchanged among siblings. CONCLUSIONS: Seasonal variation of births among patients with schizophrenia may consist of two factors: 1) parental procreational habits causing a slight excess of births of both patients and unaffected siblings during the winter-spring months and 2) irregular environmental factors that considerably increase the magnitude of the seasonal variation of births among patients but not their siblings.

The effect of alpha-tocopherol and beta-carotene supplementation on symptoms and progression of intermittent claudication in a controlled trial.

We evaluated the effect of long-term supplementation with vitamin E (alpha-tocopherol) and beta-carotene on occurrence of claudication symptoms and risk for peripheral vascular surgery among men with intermittent claudication. Subjects, 50-69-year old male smokers, were participants in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, who reported intermittent claudication through a structured questionnaire (Rose) at study entry (n=1484). They were randomly assigned to receive either 50 mg/day of alpha-tocopherol, or 20 mg/day of beta-carotene, or both, or placebo, in a 2 x 2 design. During follow-up, claudication was evaluated by repeating use of the questionnaire once a year. Information on peripheral vascular surgery came from the National Hospital Discharge Register. We observed no effect of alpha-tocopherol and beta-carotene supplementation on claudication during a mean follow-up of 3.7 years. A slightly increased risk (odds ratio (OR) 1.60, 95% confidence interval (CI) 1.05-2.44) for vascular surgery was observed among beta-carotene supplemented men compared to those who did not receive beta-carotene. Alpha-tocopherol supplementation had no effect. In conclusion, long-term supplementation with alpha-tocopherol and beta-carotene showed no beneficial effect on symptoms and progression of intermittent claudication.

Alpha-tocopherol (vitamin E) and beta-carotene supplementation does not affect the risk for large abdominal aortic aneurysm in a controlled trial.

Antioxidants may retard atherogenesis and limit inflammatory processes involved in aneurysm formation. We evaluated effects of alpha-tocopherol and beta-carotene supplementation on incidence of large abdominal aortic aneurysm (AAA) in a randomised, double-blind, placebo-controlled trial. Subjects (n=29133) were 50-69-years-old male smokers, participants in the Finnish alpha-Tocopherol, beta-Carotene Cancer Prevention (ATBC) Study. They were randomised to receive either 50 mg/day of alpha-tocopherol, or 20 mg/day of beta-carotene, or both, or placebo in a 2x2 design. Incidence of AAA was evaluated from mortality and hospital registers. During 5.8 years of follow-up, 181 men were diagnosed with either ruptured AAA (n=77) or nonruptured large AAA treated with aneurysmectomy (n=104). Relative risk (RR) for AAA was 0.83 (95% confidence interval [CI] 0.62-1.11) among men receiving alpha-tocopherol compared with those who did not, and 0.93 (95% CI 0.69-1.24) among men receiving beta-carotene compared with those who did not. A modest though nonsignificant decrease in risk for nonruptured AAA was observed among alpha-tocopherol supplemented men (RR 0.71, 95% CI 0.48-1.04) compared with men not receiving alpha-tocopherol. For beta-carotene, RR for nonruptured AAA was 0.86 (95% CI 0.59-1.27) compared with men not receiving beta-carotene. Neither antioxidant affected risk for ruptured AAA. In conclusion, long-term supplementation with alpha-tocopherol or beta-carotene had no preventive effect on large AAA among male smokers.

Effects of alpha tocopherol and beta carotene supplements on symptoms, progression, and prognosis of angina pectoris.

OBJECTIVE: To evaluate the effects of alpha tocopherol and beta carotene supplements on recurrence and progression of angina symptoms, and incidence of major coronary events in men with angina pectoris. DESIGN: Placebo controlled clinical trial. SETTING: The Finnish alpha tocopherol beta carotene cancer prevention study primarily undertaken to examine the effects of alpha tocopherol and beta carotene on cancer. SUBJECTS: Male smokers aged 50-69 years who had angina pectoris in the Rose chest pain questionnaire at baseline (n = 1795). INTERVENTIONS: alpha tocopherol (vitamin E) 50 mg/day, beta carotene 20 mg/day or both, or placebo in 2 x 2 factorial design. MAIN OUTCOME MEASURES: Recurrence of angina pectoris at annual follow up visits when the questionnaire was readministered; progression from mild to severe angina; incidence of major coronary events (non-fatal myocardial infarction and fatal coronary heart disease). RESULTS: There were 2513 recurrences of angina pectoris during follow up (median 4 years). Compared to placebo, the odds ratios for recurrence in the active treatment groups were: alpha tocopherol only 1.06 (95% confidence interval (CI) 0.85 to 1.33), alpha tocopherol and beta carotene 1.02 (0.82 to 1.27), beta carotene only 1.06 (0.84 to 1.33). There were no significant differences in progression to severe angina among the groups given supplements or placebo. Altogether 314 major coronary events were observed during follow up (median 5.5 years) and the risk for them did not differ significantly among the groups given supplements or placebo. CONCLUSIONS: There was no evidence of beneficial effects for alpha tocopherol or beta carotene supplements in male smokers with angina pectoris, indicating no basis for therapeutic or preventive use of these agents in such patients.

Beta-carotene concentration in buccal mucosal cells with and without dysplastic oral leukoplakia after long-term beta-carotene supplementation in male smokers.

OBJECTIVE: To measure the beta-carotene concentration in buccal mucosal cells in smoking men who had received long-term beta-carotene (BC) supplementation in a controlled trial. To assess the association of cellular BC on the prevalence of dysplasia in oral leukoplakia. DESIGN: An end-of-trial examination of a part of subjects in the Alpha-Tocopherol, Beta Carotene Cancer Prevention Study. SUBJECTS AND METHODS: 343 men who for 5-7 years had received BC (20 mg/d) or alpha-tocopherol (AT) (50 mg/d), or both of these or placebo. BC concentration of buccal mucosal cells was compared in the subjects with BC supplementation (n = 173) to that of those without it (n = 170). Oral mucosae were examined clinically and lesions showing leukoplakia histopathologically. RESULTS: Mean (s.d.) BC concentration in buccal mucosal cells was 7.7 (10.3)mg/kg protein in the subjects who received BC compared to 1.1 (1.7) mg/kg protein in those who did not. The BC concentration in the cells of supplemented subjects correlated with their serum BC levels (P < 0.001). AT supplementation had no effect on BC concentration nor was daily amount of smoking statistically significantly associated with the BC concentration in buccal cells. Altogether 17 subjects showed oral leukoplakia, 7 had dysplasia. In these 7 subjects, the BC concentration in buccal mucosal cells did not differ statistically significantly compared to subjects with only hyperkeratosis (n = 10) (F-test, P = 0.74). CONCLUSIONS: After long-term BC supplementation, BC concentration in oral mucosal cells was 7-fold greater than without supplementation. There was no evidence to support an association between cellular BC concentration and precancerous lesions among the few subjects having them in their oral mucosae.

The association between smoking cessation and periodontal status and salivary proteinase levels.

BACKGROUND: Little information is available about the effects of the cessation of cigarette smoking on oral health, although cigarette smoking has been shown to be associated with a variety of oral diseases. The aim of this study was to compare periodontal status, salivary proteolytic activity, especially collagenase-2 (MMP-8) levels, and oral mucosal status in individuals who had quit smoking for at least 6 months (mean 3.5, SD 1.3 years) and in regular smokers. METHODS: The subjects were 409 white male smokers aged 55 to 74 years with 15 or more remaining teeth. They had participated in a major cancer prevention study (ATBC Study). Eighty-two of the men had given up smoking and 327 were smokers. The subjects were examined clinically to determine the prevalence of periodontal pockets, gingival bleeding (BOP) and suppuration, and prevalence of keratotic oral mucosal lesions. The loss of alveolar bone was determined radiographically. Candida albicans was cultivated, and lesions showing leukoplakia were examined histopathologically. General proteolytic activity and collagenase-2 or matrix metalloproteinase-8 (MMP-8) levels in saliva, salivary pH, and buffering capacity were measured. Linear regression, logistic regression, or Fisher's exact test were used in statistical analysis. RESULTS: Salivary general proteolytic activity and MMP-8 levels were lower in current smokers than in ex-smokers (P <0.05 and P <0.05, respectively). The prevalence of > or = 4 mm deep pockets, gingival suppuration, and loss of crestal bone were statistically significantly lower (P = 0.003, P<0.001, and P<0.05, respectively) and salivary buffering capacity higher (P <0.05) in those who had quit smoking compared to current smokers; there was no difference in BOP. The prevalence of oral leukoplakia did not differ significantly between smokers and quitters, but was higher in those who smoked >15 cigarettes per day compared to quitters (odds ratio 3.5, 95% CI, 0.8 to 15.3). CONCLUSIONS: These data suggest that periodontal status and oral mucosal health are better in those who have quit cigarette smoking compared to current smokers. However, the data further suggest that smoking may significantly lower both general proteolytic enzyme activity and MMP-8 levels in saliva. Thus, care should be taken in interpreting results revealing salivary/mouthrinse proteinases as diagnostic markers for oral/periodontal disease activity.

Correction for covariate measurement error in generalized linear models--a bootstrap approach.

A two-phase bootstrap method is proposed for correcting covariate measurement error. Two data sets are needed: validation data for approximating the measurement model and data with a response variable. Bootstrap samples from both the data sets validation data are taken. Parameter estimates of the generalized linear model are calculated using expectations of the measurement model from the validation data as explanatory variables. The method is compared through simulation in logistic regression with the correction method proposed by Rosner, Willet, and Spiegelman (1991, Statistics in Medicine 8, 1051-1069). A real data example is also presented.

Decreasing seasonal variation of births in schizophrenia.

BACKGROUND: Patients with schizophrenia have a winter-spring excess of births compared with the general population, the cause of which is unresolved. Fluctuations in the magnitude of the seasonal variation may provide clues to its aetiology. METHODS: All Finnish patients with schizophrenia born between 1950 and 1969 (N = 15892) were identified from two nationwide health-care registers. Their background demographic information was obtained from the Population Register Centre, which also provided monthly numbers of births in each municipality of Finland as multidimensional tables, with sex and year, month and place of birth as marginals. The incidence of schizophrenia was modelled using Poisson regression analysis, with sex, onset age, birth cohort, place of birth (urban/rural), trend and seasonal variation as explanatory variables. We also constructed a monthly time series and decomposed it into three components--seasonal, trend and remainder. RESULTS: Seasonal variation of births among patients born in the 1950s, especially between 1955 and 1959, was marked, but decreased among patients born in the 1960s. No interaction between place of birth or sex and seasonal variation was observed. The incidence was higher among the rural-born than the urban-born, but declined more slowly among the urban-born than the rural-born. CONCLUSIONS: The intensity of the factor causing the seasonal variation of births in schizophrenia may be decreasing. Urban birth may be emerging as a risk factor for schizophrenia in Finland, as elsewhere.

Increased tendency towards gingival bleeding caused by joint effect of alpha-tocopherol supplementation and acetylsalicylic acid.

Alpha-tocopherol (vitamin E) may play a role in the treatment of arterial thromboembolic disease, possibly by inhibiting platelet aggregation. Thus far, no clinical evidence exists for this effect. The objective of this study was to assess the effect of alpha-tocopherol supplementation on gingival bleeding either in combination with acetylsalicylic acid (ASA) or without it. This study was an end-point examination of a random sample of male smokers who had participated in a controlled clinical trial, the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC Study) for 5-7 years. The study included 409 men aged 55-74 years of whom 191 received alpha-tocopherol supplementation (50 mg/day); 56 used ASA, 30 received both and 132 received neither. Gingival bleeding was examined by probing with a WHO probe and reported as a percentage of bleeding sites adjusted by the logistic regression model. Gingival bleeding was more common in those who received alpha-tocopherol compared with nonreceivers among subjects with a high prevalence of dental plaque (P < 0.05). ASA alone increased bleeding only slightly. The highest risk of gingival bleeding was among those who took both alpha-tocopherol and ASA (33.4% of probed sites bleeding vs 25.8% among subjects taking neither alpha-tocopherol nor ASA, P < 0.001). In the ATBC Study, more deaths from haemorrhagic stroke and fewer from ischaemic heart disease were observed among those participants who received alpha-tocopherol compared with those who did not. Based on the results of the present study and the ATBC Study, we conclude that alpha-tocopherol supplementation may increase the risk of clinically important bleedings, particularly when combined with ASA.

Life-style factors and risk for abdominal aortic aneurysm in a cohort of Finnish male smokers.

Prospective studies evaluating risk factors for abdominal aortic aneurysm are few. We studied the association of life-style factors with risk for abdominal aortic aneurysm among 29,133 male smokers 50-69 years of age, participants in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. During a mean follow-up of 5.8 years, 181 were diagnosed with ruptured abdominal aortic aneurysm or nonruptured abdominal aortic aneurysm plus aneurysmectomy. Risk for abdominal aortic aneurysm was positively associated with age [relative risk (RR) = 4.56, 95% confidence interval (CI) = 2.42-8.61 for > 65 vs < or = 55 years], smoking years (RR = 2.25, 95% CI = 1.33-3.81 for > 40 vs < or = 32 years), systolic blood pressure (RR = 1.92, 95% CI = 1.13-3.25 for > 160 vs < or = 130 mmHg), diastolic blood pressure (RR = 1.80, 95% CI = 1.05-3.08 for > 100 vs < or = 85 mmHg), and serum total cholesterol (RR = 1.85, 95% CI = 1.09-3.12 for > 6.5 vs < or = 5.0 mmol/liter). High-density lipoprotein cholesterol showed a strong inverse association with risk for aortic aneurysm (RR = 0.16, 95% CI = 0.08-0.32 for > 1.5 vs < or = 0.9 mmol/liter). High energy intake was associated with lower risk for aortic aneurysm (RR = 0.59, 95% CI = 0.38-0.94 for the highest quartile vs the lowest), whereas no associations with nutrients were evident. We conclude that classical risk factors for atherosclerotic diseases seem to be important in pathogenesis of large abdominal aortic aneurysms.

Prospective study of diet, lifestyle, and intermittent claudication in male smokers.

The association between dietary and lifestyle factors and intermittent claudication was investigated in the Finnish Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. The cohort comprised 26,872 male smokers aged 50-69 years who were free of claudication at study entry. At baseline (1985-1988), subjects completed a diet history questionnaire. During a median follow-up period of 4 years (ending in spring 1993), 2,578 men reported symptoms of claudication on the Rose questionnaire, which was administered annually. Smoking status was assessed every 4 months. Smoking, systolic blood pressure, serum total cholesterol, and diabetes mellitus were positively associated with risk for claudication, whereas serum high density lipoprotein cholesterol, education, and leisure time exercise were inversely associated with risk. Dietary carbohydrates, fiber, and n-6 polyunsaturated fatty acids were inversely associated with risk for claudication, as were some dietary and serum antioxidants: dietary vitamin C (highest quartile vs. lowest: relative risk (RR) = 0.86; 95% confidence interval (CI): 0.77, 0.97), dietary gamma-tocopherol (RR = 0.89; 95% CI: 0.79, 1.00), dietary carotenoids (RR = 0.82; 95% CI: 0.73, 0.92), serum alpha-tocopherol (RR = 0.88; 95% CI: 0.77, 1.00), and serum beta-carotene (RR = 0.77; 95% CI: 0.68, 0.86). Smoking cessation reduced subsequent risk for claudication (RR = 0.86; 95% CI: 0.75, 0.99). The authors conclude that classical risk factors for atherosclerosis are associated with claudication. High intakes of antioxidant vitamins may be protective. Further research is needed before antioxidants can be recommended for the prevention of intermittent claudication.

Effect of alpha-tocopherol (vitamin E) and beta-carotene supplementation on the incidence of intermittent claudication in male smokers.

We examined the primary preventive effect of vitamin E (alpha-tocopherol) and beta-carotene supplementation on intermittent claudication. The subjects--participants in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study--were male smokers aged 50 to 69 years who were randomly assigned to receive 50 mg of alpha-tocopherol daily, 20 mg of beta-carotene daily, both, or placebo. At baseline, there were 26 289 men with no history or symptoms of intermittent claudication. The Rose questionnaire on intermittent claudication was administered annually to discover incident cases. We observed 2704 cases of first occurrence of typical intermittent claudication during a median follow-up time of 4.0 years. Compared with placebo, the adjusted relative risk for typical intermittent claudication among those who received alpha-tocopherol only was 1.11 (95% confidence interval, 1.00-1.24); among those who received alpha-tocopherol and beta-carotene, 1.02 (0.91-1.13); and among those who received beta-carotene only, 1.02 (0.92-1.14). When we compared the alpha-tocopherol-supplemented subjects with those who received no alpha-tocopherol, the adjusted relative risk for typical intermittent claudication was 1.05 (0.98-1.14), and for beta-carotene-supplemented subjects compared with those who did not receive beta-carotene, the relative risk was 0.96 (0.89-1.04). In conclusion, no primary preventive effect on intermittent claudication was observed among middle-aged male smokers who were supplemented with alpha-tocopherol, beta-carotene, or both.

Effect of vitamin E and beta carotene on the incidence of angina pectoris. A randomized, double-blind, controlled trial.

OBJECTIVE: To examine the effect of supplementation with vitamin E (alpha tocopherol), beta carotene, or both on the incidence of angina pectoris in men without known previous coronary heart disease. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING AND PARTICIPANTS: Participants in the Alpha Tocopherol, Beta Carotene Cancer Prevention Study (N=29133) were male smokers aged 50 through 69 years who were living in southern and western Finland. Of these men, 22269 were considered free of coronary heart disease at baseline and were followed up for the incidence of angina pectoris. INTERVENTION: Participants were randomized to receive 50 mg/d of alpha tocopherol, 20 mg/d of beta carotene, both, or placebo in a 2x2 design. OUTCOME MEASURES: An incident case was defined as the first occurrence of typical angina pectoris identified in administering the annually repeated World Health Organization (Rose) Chest Pain Questionnaire. RESULTS: During a median follow-up time of 4.7 years (96427 person-years), 1983 new cases of angina pectoris were detected. Comparing alpha tocopherol-supplemented subjects with non-alpha tocopherol-supplemented subjects showed a relative risk (RR) of angina pectoris incidence of 0.91 (95% confidence interval[CI], 0.83 to 0.99; P=.04). The RR for incidence of angina pectoris for the beta carotene- supplemented subjects compared with those not receiving beta carotene was 1.06 (95% CI, 0.97 to 1.16; P=.19). Compared with those receiving placebo, the RRs for incidence of angina pectoris were 0.97 (95% CI, 0.85 to 1.10) and 0.96 (95% CI, 0.85 to 1.09) in the alpha tocopherol and alpha tocopherol plus beta carotene groups, respectively, and 1.13 (95% CI, 1.00 to 1.27) in the beta carotene group (P=.06). Baseline dietary intakes and serum levels of alpha tocopherol and beta carotene did not predict incidence of angina pectoris. CONCLUSIONS: Supplementation with alpha tocopherol was associated with only a minor decrease in the incidence of angina pectoris. Beta carotene had no preventive effect and was associated with a slight increase of angina.

The effects of supplementation with alpha-tocopherol and beta-carotene on the incidence and mortality of carcinoma of the pancreas in a randomized, controlled trial.

BACKGROUND: Dietary components may be both causal and protective in cases of pancreatic carcinoma, but the preventive potential of single constituents has not been evaluated. The authors report the effects of alpha-tocopherol and beta-carotene supplementations on the rates of incidence of and mortality from pancreatic carcinoma in a randomized, controlled trial. METHODS: The 29,133 participants in the Alpha-Tocopherol Beta-Carotene Cancer Prevention (ATBC) Study were male smokers who were ages 50-69 years at the time they were randomized into 1 of the following 4 intervention groups: dl-alpha-tocopherol (AT; 50 mg/day), beta-carotene (BC; 20 mg/day), both AT and BC, and placebo. The daily supplementation lasted for 5-8 years. Incident cancers were identified through the national Finnish Cancer Registry and death certificates of the Statistics Finland. Results were analyzed by supplementation with Cox regression models. RESULTS: Effects of both supplementations were statistically nonsignificant. The rate of incidence of pancreatic carcinoma was 25% lower for the men who received beta-carotene supplements (n = 38) compared with the rate for those who did not receive beta-carotene (n = 51) (95% CI, -51% to 14%). Supplementation with alpha-tocopherol (n = 51) increased the rate of incidence by 34% (95% CI, -12% to 105%) compared with the rate for those who did not receive alpha-tocopherol. Mortality from pancreatic carcinoma during the follow-up, adjusted for stage and anatomic location of the tumor, was 19% (95% CI, -47% to 26%) lower among those who received beta-carotene and 11% (95% CI, -28% to 72%) higher among those who received alpha-tocopherol as compared with those who did not receive supplementation. CONCLUSIONS: Supplementation with beta-carotene or alpha-tocopherol does not have a statistically significant effect on the rate of incidence of pancreatic carcinoma or the rate of mortality caused by this disease.