Biomedical subjects

M A Hernán

Publications and source records attributed to M A Hernán.

At least 19 recordsLinked to original sources

PubMed2005

Physical activity and the risk of Parkinson disease.

OBJECTIVE: To investigate whether greater physical activity is associated with a lower risk of Parkinson disease (PD). METHODS: The authors prospectively followed 48,574 men and 77,254 women who provided information on physical activity in 1986 or in early adulthood. During the follow-up, a total of 252 (male) and 135 (female) incident PD cases were identified. RESULTS: In men, greater baseline physical activity was associated with a lower PD risk; compared with the lowest quintile, the multivariate relative risk (RR) of PD for the highest quintile was 0.7 (95% CI 0.5 to 1.1; p value, test for trend = 0.007), and the inverse association was still present after excluding the first 10 years of follow-up (RR = 0.5; p value, test for trend = 0.02). Further, strenuous exercise in early adult life was also inversely related to PD risk in men: compared with men who regularly exercised < or =2 months/year, those with > or =10 months of strenuous exercise had a 60% lower PD risk (RR = 0.4; p value, test for trend = 0.005). In women, physical activity assessed at baseline was not related to PD risk, whereas strenuous exercise in early adulthood tended to be inversely related to PD risk later in life (highest vs lowest categories, RR = 0.5, 95% CI 0.2 to 1.4; p value, test for trend = 0.06). CONCLUSION: This study suggests either that higher levels of physical activity may lower the risk of Parkinson disease (PD) in men or that men predisposed to PD tend to avoid strenuous physical activity in their early adult years.

Adult↗

PubMed2004

Vitamin D intake and incidence of multiple sclerosis.

BACKGROUND: A protective effect of vitamin D on risk of multiple sclerosis (MS) has been proposed, but no prospective studies have addressed this hypothesis. METHODS: Dietary vitamin D intake was examined directly in relation to risk of MS in two large cohorts of women: the Nurses' Health Study (NHS; 92,253 women followed from 1980 to 2000) and Nurses' Health Study II (NHS II; 95,310 women followed from 1991 to 2001). Diet was assessed at baseline and updated every 4 years thereafter. During the follow-up, 173 cases of MS with onset of symptoms after baseline were confirmed. RESULTS: The pooled age-adjusted relative risk (RR) comparing women in the highest quintile of total vitamin D intake at baseline with those in the lowest was 0.67 (95% CI = 0.40 to 1.12; p for trend = 0.03). Intake of vitamin D from supplements was also inversely associated with risk of MS; the RR comparing women with intake of >or=400 IU/day with women with no supplemental vitamin D intake was 0.59 (95% CI = 0.38 to 0.91; p for trend = 0.006). No association was found between vitamin D from food and MS incidence. CONCLUSION: These results support a protective effect of vitamin D intake on risk of developing MS.

Adolescent↗

PubMed2004

A definition of causal effect for epidemiological research.

Estimating the causal effect of some exposure on some outcome is the goal of many epidemiological studies. This article reviews a formal definition of causal effect for such studies. For simplicity, the main description is restricted to dichotomous variables and assumes that no random error attributable to sampling variability exists. The appendix provides a discussion of sampling variability and a generalisation of this causal theory. The difference between association and causation is described-the redundant expression "causal effect" is used throughout the article to avoid confusion with a common use of "effect" meaning simply statistical association-and shows why, in theory, randomisation allows the estimation of causal effects without further assumptions. The article concludes with a discussion on the limitations of randomised studies. These limitations are the reason why methods for causal inference from observational data are needed.

Causality↗

PubMed2002

Intakes of vitamins E and C, carotenoids, vitamin supplements, and PD risk.

BACKGROUND: Oxidative damage has been implicated in the pathogenesis of PD. Limited and mostly retrospective epidemiologic data suggest a reduction or no change in risk of PD associated with high vitamin E intake. OBJECTIVE: To examine prospectively the associations between intakes of vitamins E and C, carotenoids, vitamin supplements, and risk of PD. METHODS: The authors documented the occurrence of PD within two large cohorts of men and women who completed detailed and validated semiquantitative food frequency questionnaires. A total of 371 incident PD cases were ascertained in the Nurses' Health Study, which comprised 76,890 women who were followed for 14 years, and the Health Professionals Follow-Up Study, which comprised 47,331 men who were followed for 12 years. RESULTS: Neither intake of total vitamins E or C or use of vitamin E or vitamin C supplements or multivitamins was significantly associated with risk of PD. The risk of PD, however, was significantly reduced among men and women with high intake of dietary vitamin E (from foods only). The pooled multivariate relative risk (RR) comparing individuals in the highest quintile with those in the lowest quintile was 0.68 (95% CI, 0.49 to 0.93). Consumption of nuts was also significantly associated with a reduced risk of PD (for >or=5/week vs <1/month, pooled RR, 0.57; 95% CI, 0.34 to 0.95). Intakes of dietary vitamin C and carotenoids were not significantly associated with risk of PD. CONCLUSIONS: Use of vitamin supplements and high intake of carotenoids do not appear to reduce the risk of PD. The reduction in risk of PD associated with high dietary vitamin E intake suggests that other constituents of foods rich in vitamin E may be protective. Alternatively, moderate amounts of vitamin E may reduce risk of PD, but this benefit may be lost with higher intakes.

Adult↗

PubMed2002

MAOB intron 13 and COMT codon 158 polymorphisms, cigarette smoking, and the risk of PD.

BACKGROUND: A polymorphism (G to A transition) in intron 13 of the mitochondrial enzyme monoamine oxidase B (MAOB) gene may modify, alone or by interacting with the catechol-O-methyltransferase (COMT(LL)) genotype (low enzymatic activity), the risk of idiopathic PD. Also, the association between never smoking and PD risk may be present only in people with the MAOB G allele. METHODS: The authors studied two ongoing prospective cohorts-the Nurses' Health Study (121,700 women aged 30 to 55 in 1976) and the Health Professionals' Follow-up Study (51,529 men aged 40 to 75 in 1986). They identified new PD cases through 1996, selected random control subjects matched on age and study cohort, and obtained DNA samples from blood or buccal smears from 85% of the eligible cases and 84% of the control subjects. They included genotypes from 214 cases and 449 control subjects, all Caucasian. RESULTS: The odds ratio of PD was 1.2 (95% CI 0.9, 1.7) for MAOB genotypes G/GG/GA compared with genotypes A/AA, and 1.1 (0.7, 1.8) for COMT genotypes LL compared with HH. The odds ratio (95% CI) was 1.7 (0.7, 3.9) for those with MAOB G/GG and COMT(LL) genotypes compared with those with MAOB A/AA and COMT(HH). There was a strong association between never smoking and PD risk in all groups defined by MAOB and COMT genotypes. CONCLUSION: The findings do not support a major role of the MAOB intron 13 polymorphism in the development of PD, either by itself or by interacting with smoking.

Adult↗

PubMed2001

Epstein-Barr virus antibodies and risk of multiple sclerosis: a prospective study.

CONTEXT: Epidemiological studies suggest an association between infection with Epstein-Barr virus (EBV) and risk of multiple sclerosis (MS). OBJECTIVE: To determine whether elevation in serum antibody titers to EBV viral capsid antigen (VCA), nuclear antigens (EBNA, EBNA-1, and EBNA-2), and diffuse and restricted early antigen (EA-D and EA-R) as well as to cytomegalovirus (CMV) precede the occurrence of MS. DESIGN, SETTING, AND SUBJECTS: Prospective, nested case-control study. Of 62 439 women participating in the Nurses' Health Study (aged 30-55 years in 1976) and Nurses' Health Study II (aged 25-42 years in 1989) who gave blood samples in 1989-1990 and 1996-1999, respectively, and were followed up through 1999, 144 women with definite or probable MS and 288 healthy age-matched controls were included in the analysis. MAIN OUTCOME MEASURE: Serum antibody titers to the specific EBV and CMV antigens, compared between cases and controls. RESULTS: We documented 18 cases of MS with blood collected before disease onset. Compared with their matched controls, these women had higher serum geometric mean titers (GMTs) of antibodies to EBV but not CMV. Elevations were significant for antibodies to EBNA-1 (GMT, 515 vs 203; P =.03), EBNA-2 (GMT, 91 vs 40; P =.01), and EA-D (15.9 vs 5.9; P =.04). The strongest association was found for antibodies to EBNA-2; a 4-fold difference in titers was associated with a relative risk (RR) of MS of 3.9 (95% confidence interval [CI], 1.1-13.7). The corresponding RRs were 1.6 (95% CI, 0.7-3.7) for VCA, 2.5 (95% CI, 1.0-6.3) for EBNA, 1.8 (95% CI, 1.0-3.1) for EA-D, and 1.0 (95% CI, 0.6-1.7) for CMV. Significant but generally weaker elevations in anti-EBV antibodies were also found in analyses of 126 cases of MS with blood collected after disease onset and their matched controls. CONCLUSIONS: Our results support a role of EBV in the etiology of MS.

Adult↗

PubMed2001

Intakes of carotenoids, vitamin C, and vitamin E and MS risk among two large cohorts of women.

BACKGROUND: Antioxidant nutrients may reduce the risk of MS. In a recent case-control study, vitamin C intake was significantly inversely associated with MS risk among women. However, no prospective data are available. OBJECTIVE: To examine prospectively the associations of intakes of carotenoids, vitamin C, and vitamin E with the risk of MS among women. METHODS: The authors documented the occurrence of definite and probable MS within two large cohorts of women who completed detailed and validated semiquantitative food frequency questionnaires. One cohort (Nurses' Health Study) comprised 81,683 women aged 38 to 63 years in 1984, who were followed for 12 years; the other (Nurses' Health Study II) comprised 95,056 women aged 27 to 44 years in 1991, who were followed for 6 years. RESULTS: The authors documented a total of 214 cases of MS. After adjustments for age, latitude of birthplace, pack-years of smoking, and total energy intake, the pooled multivariate relative risks (95% CIs) comparing women in the highest quintile with those in the lowest quintile were 1.1 (0.7 to 1.7) for alpha-carotene, 1.1 (0.7 to 1.6) for beta-carotene, 1.4 (0.8 to 2.2) for beta-cryptoxanthin, 1.0 (0.6 to 1.5) for lycopene, 1.0 (0.7 to 1.6) for lutein/zeaxanthin, 1.4 (0.9 to 2.1) for total vitamin C, 1.3 (0.9 to 2.0) for dietary vitamin C, 0.8 (0.6 to 1.3) for total vitamin E, and 0.9 (0.6 to 1.4) for dietary vitamin E. The authors found no associations between intakes of fruits and vegetables and risk of MS. Use of vitamin C, vitamin E, and multivitamin supplements was also unrelated to risk of MS. CONCLUSIONS: These findings do not support hypotheses relating higher intakes of dietary carotenoids, vitamin C, and vitamin E to reduced risk of MS in women.

Adult↗

PubMed2001

Cigarette smoking and incidence of multiple sclerosis.

Experimental data suggest that cigarette smoking may play a role in the development of multiple sclerosis (MS), but epidemiologic studies have been small and inconclusive. The authors assessed the association between MS incidence and smoking in two cohort studies of US women, the Nurses' Health Study (121,700 women aged 30-55 years at baseline in 1976) and the Nurses' Health Study II (116,671 women aged 25-42 years at baseline in 1989). Smoking history was assessed at baseline and updated on biennial questionnaires. A total of 315 definite or probable cases of MS were documented. Compared with that for women who never smoked, the relative incidence rate was 1.6 (95% confidence interval: 1.2, 2.1) among current smokers and 1.2 (95% confidence interval: 0.9, 1.6) among past smokers after adjustment for age, latitude, and ancestry. The relative rate increased significantly with cumulative exposure to smoking (p for trend < 0.05), from 1.1 (95% confidence interval: 0.8, 1.6) for 1-9 pack-years to 1.5 (95% confidence interval: 1.2, 2.1) for 10-24 pack-years and 1.7 (95% confidence interval: 1.2, 2.4) for 25 or more pack-years. Similar results were obtained after adjustment for other potential confounding factors. Although these prospective results do not prove a cause-and-effect relation, they suggest that smoking is associated with an increased risk of MS.

Adult↗

PubMed2001

Hepatitis B vaccination and the risk of multiple sclerosis.

BACKGROUND: Reports of multiple sclerosis developing after hepatitis B vaccination have led to the concern that this vaccine might be a cause of multiple sclerosis in previously healthy subjects. METHODS: We conducted a nested case-control study in two large cohorts of nurses in the United States, those in the Nurses' Health Study (which has followed 121,700 women since 1976) and those in the Nurses' Health Study II (which has followed 116,671 women since 1989). For each woman with multiple sclerosis, we selected as controls five healthy women and one woman with breast cancer. Information about hepatitis B vaccination was obtained by means of a mailed questionnaire and was confirmed by means of vaccination certificates. The analyses included 192 women with multiple sclerosis and 645 matched controls and were conducted with the use of conditional logistic regression. RESULTS: The multivariate relative risk of multiple sclerosis associated with exposure to the hepatitis B vaccine at any time before the onset of the disease was 0.9 (95 percent confidence interval, 0.5 to 1.6). The relative risk associated with hepatitis B vaccination within two years before the onset of the disease was 0.7 (95 percent confidence interval, 0.3 to 1.8). The results were similar in analyses restricted to women with multiple sclerosis that began after the introduction of the recombinant hepatitis B vaccine. There was also no association between the number of doses of vaccine received and the risk of multiple sclerosis. CONCLUSIONS: These results indicate no association between hepatitis B vaccination and the development of multiple sclerosis.

Case-Control Studies↗

PubMed2001

Cigarette smoking and the incidence of Parkinson's disease in two prospective studies.

An inverse association between cigarette smoking and idiopathic Parkinson's disease has been reported in several retrospective studies, but prospective evidence is available only for men. We assessed the association between the incidence of Parkinson's disease and smoking in two large prospective cohort studies comprising men and women. New cases of Parkinson's disease were identified in the Nurses' Health Study for 1976-1996, and in the Health Professionals Follow-up Study for 1986-1996. Smoking history was assessed at baseline and updated on subsequent biennial questionnaires. In women, the age-adjusted rate ratios (95% confidence intervals) for Parkinson's disease relative to never-smokers were 0.7 (0.5, 1.0) for past smokers, and 0.4 (0.2, 0.7) for current smokers. In men, the age-adjusted rate ratios for Parkinson's disease relative to never-smokers were 0.5 (0.4, 0.7) for past smokers, and 0.3 (0.1, 0.8) for current smokers. In both cohorts, the strength of the association decreased with time since quitting (among past smokers), increased with number of cigarettes per day (among current smokers), and increased with pack-years of smoking. These prospective findings confirm that an inverse association between smoking and the incidence of Parkinson's disease exists in both men and women.

Adult↗

PubMed2001

Prospective study of caffeine consumption and risk of Parkinson's disease in men and women.

Results of case-control studies and of a prospective investigation in men suggest that consumption of coffee could protect against the risk of Parkinson's disease, but the active constituent is not clear. To address the hypothesis that caffeine is protective against Parkinson's disease, we examined the relationship of coffee and caffeine consumption to the risk of this disease among participants in two ongoing cohorts, the Health Professionals' Follow-Up Study (HPFS) and the Nurses' Health Study (NHS). The study population comprised 47,351 men and 88,565 women who were free of Parkinson's disease, stroke, or cancer at baseline. A comprehensive life style and dietary questionnaire was completed by the participants at baseline and updated every two to four years. During the follow-up (10 years in men, 16 years in women), we documented a total of 288 incident cases of Parkinson's disease. Among men, after adjustment for age and smoking, the relative risk of Parkinson's disease was 0.42 (95% CI: 0.23-0.78; p for trend < 0.001) for men in the top one-fifth of caffeine intake compared to those in the bottom one-fifth. An inverse association was also observed with consumption of coffee (p for trend = 0.004), caffeine from noncoffee sources (p for trend < 0.001), and tea (p for trend = 0.02) but not decaffeinated coffee. Among women, the relationship between caffeine or coffee intake and risk of Parkinson's disease was U-shaped, with the lowest risk observed at moderate intakes (1-3 cups of coffee/day, or the third quintile of caffeine consumption). These results support a possible protective effect of moderate doses of caffeine on risk of Parkinson's disease.

Adult↗

PubMed2001

Multiple sclerosis and age at infection with common viruses.

Increased risk of multiple sclerosis has been reported among individuals with a history of measles and other common childhood diseases during adolescence, infectious mononucleosis, or exposure to the canine distemper virus. We investigated these associations in a case-control study nested within the Nurses' Health Study (121,700 women traced since 1976) and the Nurses' Health Study II (116,671 women traced since 1989). Age at diagnosis of common viral diseases and birth order were obtained through a questionnaire. Our results include 301 cases with multiple sclerosis and their (up to six) matched controls. Except for infectious mononucleosis, which was a moderate risk factor (odds ratio = 2.1, 95% confidence interval = 1.5-2.9), we found little association between history of common viral diseases or exposure to canine distemper virus and risk of multiple sclerosis. We did find a relation between mumps after 15 years of age (odds ratio = 2.3, 95% confidence interval = 1.2-4.3) or measles after age 15 years of age (odds ratio = 2.8, 95% confidence interval = 0.8-9.1) and multiple sclerosis. Birth order was not materially related to multiple sclerosis. Our findings support the hypothesis that individuals who suffered from infectious mononucleosis, a marker of late infection with the Epstein-Barr virus, have an increased risk of multiple sclerosis. Late infection with other common viruses may also be associated with increased risk.

Adult↗

PubMed2001

Factors associated with noncompliance with psychiatric outpatient visits.

Adherence to recommended services is essential for long-term effectiveness of ambulatory treatment programs, but factors associated with such adherence are not securely established. We evaluated attendance at 896 scheduled psychiatric clinic visits for 62 patients at a major psychiatric teaching hospital. Visit adherence was found to be significantly higher among patients in an acute stage of illness, those with a personality disorder, those with a post-high-school education, and those living alone. Adherence was also higher when visits were routinely scheduled, when the intervisit interval was shorter, and when the visit entailed psychotherapy rather than pharmacotherapy.

Adult↗

PubMed2000

Dietary fat in relation to risk of multiple sclerosis among two large cohorts of women.

Ecologic correlations suggest that higher intake of saturated fat and lower intake of polyunsaturated fat might increase the risk of multiple sclerosis (MS), but the results of case-control studies have been inconsistent. Because no prospective data are available, the authors examined these associations in two large cohorts, the Nurses' Health Study, which consisted of 92,422 women with 14 years of follow-up (1980-1994) and the Nurses' Health Study II, which consisted of 95,389 women with 4 years of follow-up (1991-1995). They documented 195 new cases of MS. The pooled multivariate relative risks comparing women in the highest quintile with those in the lowest were 1.1 (95% confidence interval: 0.7, 1.7) for total fat, 0.7 (95% confidence interval: 0.5, 1.2) for animal fat, 1.2 (95% confidence interval: 0.7, 2.1) for vegetable fat, 0.8 (95% confidence interval: 0.5, 1.3) for saturated fat, 1.1 (95% confidence interval: 0.7, 1.7) for monounsaturated fat, 1.7 (95% confidence interval 1.0, 2.8) for n-6 polyunsaturated fat, 1.3 (95% confidence interval: 0.8, 2.0) for trans unsaturated fat, and 0.7 (95% confidence interval: 0.4, 1.1) for cholesterol. Omega-3 fatty acids from fish were also unrelated to risk. However, the authors observed a nonsignificantly lower risk of MS for a higher intake of linolenic acid. These findings do not support relations between intakes of total fat or major specific types of fat and the risk of MS.

Adult↗

PubMed2000

Oral contraceptives and the incidence of multiple sclerosis.

BACKGROUND: Experimental and clinical data suggest a protective effect of estrogens on the development and progression of MS. METHODS: We assessed whether MS incidence was associated with oral contraceptive use or parity in two cohort studies of U.S. women, the Nurses' Health Study (NHS; 121,700 women aged 30 to 55 years at baseline in 1976) and the Nurses' Health Study II (NHS II; 116,671 women aged 25 to 42 years at baseline in 1989). Participants with a diagnosis of MS before baseline were excluded. Oral contraceptive history and parity were assessed at baseline and updated biennially. During follow-ups of 18 years (NHS) and 8 years (NHS II) we documented a total of 315 definite or probable cases of MS. RESULTS: Neither use of oral contraceptives nor parity were significantly associated with the risk of MS. As compared with women who never used oral contraceptives, the age-adjusted relative risk (95% CI) was 1.2 (0.9, 1.5) for past users, and 1.0 (0.6, 1.7) for current users. Similar results were obtained after adjustment for latitude, ancestry, and other potential confounding factors. There was no clear trend of MS risk with either increasing duration of use or time elapsed since last use. Age at first birth was also not associated with the risk of MS. CONCLUSIONS: These prospective results do not support a lasting protective effect of oral contraceptive use or pregnancy on the risk of MS. The decision to use hormonal contraception should not be affected by its effects on the risk of MS.

Adult↗

PubMed2000

Marginal structural models and causal inference in epidemiology.

In observational studies with exposures or treatments that vary over time, standard approaches for adjustment of confounding are biased when there exist time-dependent confounders that are also affected by previous treatment. This paper introduces marginal structural models, a new class of causal models that allow for improved adjustment of confounding in those situations. The parameters of a marginal structural model can be consistently estimated using a new class of estimators, the inverse-probability-of-treatment weighted estimators.

Anti-HIV Agents↗

PubMed2000

Marginal structural models to estimate the causal effect of zidovudine on the survival of HIV-positive men.

Standard methods for survival analysis, such as the time-dependent Cox model, may produce biased effect estimates when there exist time-dependent confounders that are themselves affected by previous treatment or exposure. Marginal structural models are a new class of causal models the parameters of which are estimated through inverse-probability-of-treatment weighting; these models allow for appropriate adjustment for confounding. We describe the marginal structural Cox proportional hazards model and use it to estimate the causal effect of zidovudine on the survival of human immunodeficiency virus-positive men participating in the Multicenter AIDS Cohort Study. In this study, CD4 lymphocyte count is both a time-dependent confounder of the causal effect of zidovudine on survival and is affected by past zidovudine treatment. The crude mortality rate ratio (95% confidence interval) for zidovudine was 3.6 (3.0-4.3), which reflects the presence of confounding. After controlling for baseline CD4 count and other baseline covariates using standard methods, the mortality rate ratio decreased to 2.3 (1.9-2.8). Using a marginal structural Cox model to control further for time-dependent confounding due to CD4 count and other time-dependent covariates, the mortality rate ratio was 0.7 (95% conservative confidence interval = 0.6-1.0). We compare marginal structural models with previously proposed causal methods.

Anti-HIV Agents↗

PubMed1999

Geographic variation of MS incidence in two prospective studies of US women.

OBJECTIVE: To estimate the incidence of MS and its relation to latitude in two ongoing prospective studies of US women. BACKGROUND: A higher incidence of MS has been found in northern areas compared with southern areas of the United States and other countries, but the attenuation of this gradient in Europe in the last few decades and the consideration of ethnic factors have led some authors to question the existence of a strong association between MS and latitude. METHODS: The authors identified new cases of MS among participants in the Nurses' Health Study (NHS), which took place between 1976 and 1994, and in the Nurses' Health Study II (NHS II), which took place between 1989 and 1995. The NHS included women born between 1920 and 1946, and the NHS II included women born between 1947 and 1964. RESULTS: The incidence of MS among NHS participants (181 definite/probable patients) increased significantly with latitude (p = 0.03, trend). Adjusted rate ratios were 3.5 (95% CI, 1.1, 11.3) for the north and 2.7 (95% CI, 0.8, 8.9) for the middle tiers relative to the southern tier. Among NHS II women (131 definite/probable patients), no association between latitude and MS was found (p = 0.89, trend). Adjusted rate ratios were 0.8 (95% CI, 0.4, 1.6) for the northern areas and 0.9 (95%, 0.4, 1.8) for the middle areas, relative to the southern areas. CONCLUSION: The association between latitude and risk of MS in the United States was corroborated, but there was an attenuation of the north-south gradient over time. If confirmed, this finding could provide new clues to identifying environmental causes of the disease.

Adult↗