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Biomedical subjects

Miguel A Hernán

Publications and source records attributed to Miguel A Hernán.

At least 19 recordsLinked to original sources

Malnutrition among children younger than 5 years-old in conflict zones of Chiapas, Mexico.

We performed a cross-sectional, community-based survey, supplemented by interviews with community leaders in Chiapas, Mexico, to examine the prevalence and predictors of child malnutrition in regions affected by the Zapatista conflict. The prevalence rates of stunting, wasting, and underweight were 54.1%, 2.9%, and 20.3%, respectively, in 2666 children aged younger than 5 years. Stunting was associated with indigenous ethnicity, poverty, region of residence, and intracommunity division. The results indicate that malnutrition is a serious public health problem in the studied regions.

Child Nutrition Disorders↗

Smoking, snuff dipping and the risk of amyotrophic lateral sclerosis--a prospective cohort study.

BACKGROUND: Little is known about the etiology of amyotrophic lateral sclerosis (ALS). The association between cigarette smoking, but not other types of smoking and snuff dipping, and the risk of ALS has been evaluated in several epidemiologic studies. The findings were inconclusive. METHODS: We studied the association of smoking and snuff dipping with the risk of ALS in the Swedish Construction Workers Cohort, which includes 280,558 male construction workers enrolled between 1978 and 1993 with detailed information on tobacco use. Incident cases of ALS were identified through cross-linkage to the Swedish Inpatient Register. Relative risks and their corresponding 95% confidence intervals (CIs) were estimated using the Cox proportional hazards regression model. RESULTS: After a mean follow-up duration of 19.6 years, we identified 160 incident cases of ALS through 2004. Compared with non-tobacco use, the relative risk of ALS was 0.8 (95% CI 0.6-1.1) for tobacco smoking and 0.6 (95% CI 0.3-1.5) for snuff dipping, respectively. For tobacco smoking, further stratified analyses of smoking status or types of tobacco smoking did not reveal any excess risks in any strata. CONCLUSIONS: Our study provides no evidence that smoking or snuff dipping is associated with an increased ALS risk among men.

Adult↗

The birth weight "paradox" uncovered?

Low birth weight (LBW) infants have lower infant mortality in groups in which LBW is most frequent. For example, in 1991, US infants born to smokers had higher risks of both LBW and infant mortality than infants born to nonsmokers. However, among LBW infants, infant mortality was lower for infants born to smokers (relative rate = 0.79). There are competing theories regarding this so-called "paradox." One is that maternal smoking is beneficial for LBW infants. The authors use causal diagrams to show that, even in the absence of any beneficial effect of smoking, an inverse association due to stratification on birth weight can be found. This variable is affected by the exposure of interest and shares common causes with the outcome. That is, LBW infants born to smokers may have a lower risk of mortality than other LBW infants whose LBW is due to causes associated with high mortality (e.g., birth defects). Under realistic causal diagrams, adjustment for birth weight is unwarranted when the analytical goal is to estimate overall effects of prenatal variables on infant mortality. Even for estimating direct effects of prenatal variables, adjustment for birth weight may be invalid when there is an unmeasured common cause of LBW and mortality. An appropriate justification for conditioning on birth weight requires specifying 1) the causal question motivating this analytical approach and 2) the assumptions regarding the proposed underlying biologic mechanisms.

Causality↗

Tetanus vaccination and risk of multiple sclerosis: a systematic review.

OBJECTIVE: To conduct a systematic review on the association between tetanus vaccination and the risk of multiple sclerosis (MS). METHODS: The authors searched the databases Medline, LILACS, EMBASE, and Science Citation Index including the period 1966 to September 1, 2005. Eligible studies had to meet the following inclusion criteria: presentation of original data, case-control or cohort design, physician-confirmed diagnosis of MS as the outcome of interest, attempt to ascertain vaccinations in a period before the diagnosis, and report of an association measure between tetanus vaccination and incidence of MS, and its 95% CI or enough information to compute it. Study specific log ORs were weighted by the inverse of their variances to obtain a pooled estimate and its 95% CI. RESULTS: The OR of MS associated with history of tetanus vaccination was 0.67 (95% CI: 0.55 to 0.81). There was little indication of heterogeneity of results across studies. CONCLUSION: Tetanus vaccination is associated with a lower risk of multiple sclerosis.

Clinical Trials as Topic↗

Nonsteroidal anti-inflammatory drugs and the incidence of Parkinson disease.

Animal and epidemiologic studies suggest that nonsteroidal anti-inflammatory drugs (NSAIDs) decrease the incidence of Parkinson disease (PD). The authors studied 1,258 PD cases and 6,638 controls from the General Practice Research Database. The odds ratios (95% CI) for ever vs never use were 0.93 (0.80 to 1.08) for nonaspirin NSAIDs, 1.29 (1.05 to 1.58) for aspirin, and 1.16 (1.00 to 1.35) for acetaminophen. Nonaspirin NSAID use was associated with a higher risk in women and a lower risk in men.

Acetaminophen↗

Antibiotic use and risk of multiple sclerosis.

Some reports suggest that bacteria, including Chlamydophila pneumoniae, could be involved in the etiology of multiple sclerosis. If that is true, persons who used antibiotics active against these bacteria, compared with nonusers, might be at lower risk of multiple sclerosis. Using a 1993-2000 case-control study nested in the United Kingdom-based General Practice Research Database cohort, the authors identified 163 multiple sclerosis cases who were followed up for at least 3 years before their first symptoms (the index date). Up to 10 controls matched to the cases by age, sex, general practice, and time in the cohort were selected. Exposure to antibiotics was assessed through computerized medical records. Overall antibiotic use or use of antibiotics against C. pneumoniae was not associated with multiple sclerosis risk. However, use of penicillins in the 3 years before the index date decreased the risk of developing a first attack of multiple sclerosis (odds ratio=0.5, 95% confidence interval: 0.3, 0.9 for those who used penicillins for >or=15 days compared with no use). In conclusion, use of antibiotics active against C. pneumoniae was not associated with a decreased risk of short-term multiple sclerosis. The observed lower risk of multiple sclerosis for penicillin users needs to be confirmed in other populations.

Adult↗

Allergy, histamine 1 receptor blockers, and the risk of multiple sclerosis.

BACKGROUND: It is unclear whether allergic diseases are associated with multiple sclerosis (MS), but histamine 1 receptor blockers, used in the treatment of allergic conditions, decreased the severity of experimental autoimmune encephalomyelitis (an animal model of MS). OBJECTIVE: To assess the association of allergy history and use of histamine 1 receptor blockers with the risk of MS. METHODS: Using a case-control study nested in the United Kingdom-based General Practice Research Database cohort, the authors identified 163 incident cases of MS with at least 3 years of follow-up before their first symptoms (index date). Up to 10 controls matched to the cases by age, sex, general practice, and time in the cohort were selected. Previous history of allergic disease and use of histamine 1 receptor blockers in the 3 years before the index date were assessed through computerized medical records. RESULTS: History of any allergic condition in the 3 years before the index date was not associated with MS risk (adjusted odds ratio [OR] 1.2, 95% CI 0.8 to 1.8). However, use of sedating histamine 1 receptor blockers was associated with decreased MS risk (adjusted OR 0.2, 95% CI 0.1 to 0.8). CONCLUSION: These results do not support a strong link between allergic conditions and multiple sclerosis (MS) risk but suggest a possible beneficial effect of antihistamines on the onset of MS.

Case-Control Studies↗

Survival of Parkinson's disease patients in a large prospective cohort of male health professionals.

Parkinson's disease (PD) patients have higher mortality than individuals without PD. However, most of the previous studies were based on prevalent cases and few examined the potential effects of duration and smoking on the survival of PD patients. We compared the survival experience of 288 men with incident PD diagnosed between 1986 and 2000 with that of 51,012 men free of PD in the Health Professionals Follow-up Study. As of January 2002, 92 deaths occurred among PD cases and 8,485 among men without PD. After controlling for age, men with PD had 60% higher mortality than those without PD (95% CI: 1.3-2.0). PD mortality was strongly related to disease duration: compared with men without PD, the age-adjusted relative risk for PD patients was 1.1 during the first 5 years from diagnosis, 2.3 from 5 to 10 years, and 3.5 after 10 years (P < 0.0001 for trend). As expected, cigarette smoking was strongly and positively associated with total mortality among men free of PD (comparing >30 pack-years vs. never smokers, relative risk, 2.0; P < 0.0001 for trend), but this association was not observed among PD patients (RR: 1.0; P = 0.95 for trend). This study confirms that PD patients have a higher mortality than individuals without PD and that the excess mortality increases with disease duration. However, smoking seems to impose little additional risk among PD patients in this large cohort of health professionals.

Age Factors↗

Instruments for causal inference: an epidemiologist's dream?

The use of instrumental variable (IV) methods is attractive because, even in the presence of unmeasured confounding, such methods may consistently estimate the average causal effect of an exposure on an outcome. However, for this consistent estimation to be achieved, several strong conditions must hold. We review the definition of an instrumental variable, describe the conditions required to obtain consistent estimates of causal effects, and explore their implications in the context of a recent application of the instrumental variables approach. We also present (1) a description of the connection between 4 causal models-counterfactuals, causal directed acyclic graphs, nonparametric structural equation models, and linear structural equation models-that have been used to describe instrumental variables methods; (2) a unified presentation of IV methods for the average causal effect in the study population through structural mean models; and (3) a discussion and new extensions of instrumental variables methods based on assumptions of monotonicity.

Bias↗

Comparison of dynamic treatment regimes via inverse probability weighting.

Appropriate analysis of observational data is our best chance to obtain answers to many questions that involve dynamic treatment regimes. This paper describes a simple method to compare dynamic treatment regimes by artificially censoring subjects and then using inverse probability weighting (IPW) to adjust for any selection bias introduced by the artificial censoring. The basic strategy can be summarized in four steps: 1) define two regimes of interest, 2) artificially censor individuals when they stop following one of the regimes of interest, 3) estimate inverse probability weights to adjust for the potential selection bias introduced by censoring in the previous step, 4) compare the survival of the uncensored individuals under each regime of interest by fitting an inverse probability weighted Cox proportional hazards model with the dichotomous regime indicator and the baseline confounders as covariates. In the absence of model misspecification, the method is valid provided data are available on all time-varying and baseline joint predictors of survival and regime discontinuation. We present an application of the method to compare the AIDS-free survival under two dynamic treatment regimes in a large prospective study of HIV-infected patients. The paper concludes by discussing the relative advantages and disadvantages of censoring/IPW versus g-estimation of nested structural models to compare dynamic regimes.

Acquired Immunodeficiency Syndrome↗

Estimating causal effects from epidemiological data.

In ideal randomised experiments, association is causation: association measures can be interpreted as effect measures because randomisation ensures that the exposed and the unexposed are exchangeable. On the other hand, in observational studies, association is not generally causation: association measures cannot be interpreted as effect measures because the exposed and the unexposed are not generally exchangeable. However, observational research is often the only alternative for causal inference. This article reviews a condition that permits the estimation of causal effects from observational data, and two methods -- standardisation and inverse probability weighting -- to estimate population causal effects under that condition. 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 generalisation of inverse probability weighting.

Causality↗

Marginal structural models for estimating the effect of highly active antiretroviral therapy initiation on CD4 cell count.

The effect of highly active antiretroviral therapy (HAART) on the evolution of CD4-positive T-lymphocyte (CD4 cell) count among human immunodeficiency virus (HIV)-positive participants was estimated using inverse probability-of-treatment-and-censoring (IPTC)-weighted estimation of a marginal structural model. Of 1,763 eligible participants from two US cohort studies followed between 1996 and 2002, 60 percent initiated HAART. The IPTC-weighted estimate of the difference in mean CD4 cell count at 1 year among participants continuously treated versus those never treated was 71 cells/mm3 (95% confidence interval: 47.5, 94.6), which agrees with the reported results of randomized experiments. The corresponding estimate from a standard generalized estimating equations regression model that included baseline and most recent CD4 cell count and HIV type 1 RNA viral load as regressors was 26 cells/mm3 (95% confidence interval: 17.7, 34.3). These results indicate that nonrandomized studies of HIV treatment need to be analyzed with methods (e.g., IPTC-weighted estimation) that, in contrast to standard methods, appropriately adjust for time-varying covariates that are simultaneously confounders and intermediate variables. The 1-year estimate of 71 cells/mm3 was followed by an estimated continued increase of 29 cells/mm3 per year (estimated effect at 6 years: 216 cells/mm3), providing evidence that the large short-term effect found in randomized experiments persists and continues to improve over 6 years.

Acquired Immunodeficiency Syndrome↗

Cigarette smoking and the progression of multiple sclerosis.

An increased risk of multiple sclerosis among smokers has been found in several prospective epidemiological studies. The association between smoking and progression of multiple sclerosis has not been examined. We identified patients who had a first multiple sclerosis diagnosis recorded in the General Practice Research Database (GPRD) between January 1993 and December 2000. Their diagnosis and date of first symptoms were confirmed through examination of medical records. Smoking status was obtained from the computer records. To assess the association between smoking and risk of multiple sclerosis, we conducted a case-control study nested in the GPRD. Up to 10 controls per case were randomly selected, matched on age, sex, practice, date of joining the practice and availability of smoking data. To assess the association between smoking and progression of multiple sclerosis, we conducted a cohort study of multiple sclerosis cases with a relapsing-remitting onset. Our nested case-control study included 201 cases of multiple sclerosis and 1913 controls. The odds ratio [95% confidence interval (CI)] of multiple sclerosis was 1.3 (1.0-1.7) for ever smokers compared with never smokers. Our cohort study included 179 cases with a mean (median) length of follow-up of 5.3 (5.3) years. The hazard ratio of secondary progression was 3.6 (95% CI 1.3-9.9) for ever smokers compared with never smokers. These results support the hypothesis that cigarette smoking is associated with an increased risk of multiple sclerosis, and suggest that smoking may be a risk factor for transforming a relapsing-remitting clinical course into a secondary progressive course.

Adult↗

Pregnancy outcomes, site of delivery, and community schisms in regions affected by the armed conflict in Chiapas, Mexico.

The Zapatista armed conflict began in the state of Chiapas, Mexico, in 1994, and overlaps pre-existing local disputes about land, religion, and other issues. Related disruptions in access to and utilization of health services have been alleged to have compromised local health status, particularly in vulnerable subgroups such as indigenous women and infants. The study objective was to measure maternal and perinatal mortality ratios and utilization of pregnancy-related health services in the region affected by the Zapatista conflict, and to describe associations between these primary outcome measures, socioeconomic and demographic factors, and factors associated with inter-party and intra-community conflict. A cross-sectional, population-based survey was conducted in 46 communities in three regions. The study subjects were 1227 women, 13-49 years old, who had been pregnant during the preceding 2 years (1999-2001). Principal outcome measures were maternal and perinatal mortality, and site of delivery. Secondary analyses explored associations between primary outcomes and socioeconomic, demographic, and conflict-related factors. Most births (87.1%) occurred at home. The crude observed maternal and perinatal mortality ratios were 607/100,000 and 23.5/1000 live births, respectively. Those who died had difficulty accessing emergency obstetrical care. Both home birth and mortality were associated with descriptors of intra-community conflict. Observed maternal and perinatal mortality ratios were substantially higher than those officially reported for Mexico or Chiapas. Reduction of high reproductive mortality ratios will require attention to socioeconomic and conflict-related problems, in addition to improved access to emergency obstetrical services.

Adolescent↗

Activated injectable vitamin D and hemodialysis survival: a historical cohort study.

Patients with ESRD commonly experience secondary hyperparathyroidism, a condition primarily managed with activated injectable vitamin D. The biologic effects of vitamin D, however, are widespread, and it is possible that activated injectable vitamin D alters survival in ESRD. This hypothesis was tested in a historical cohort study of incident hemodialysis patients who lived throughout the United States between January 1996 and December 1999. The primary outcome was 2-yr survival among those who survived for at least 90 d after initiation of chronic hemodialysis. During this period, 51,037 chronic hemodialysis patients survived for at least 90 d from the initiation of hemodialysis, and in the ensuing 2 yr, 37,173 received activated injectable vitamin D and 13,864 did not. At 2 yr, mortality rates were 13.8/100 person-years in the group that received injectable vitamin D compared with 28.6/100 person-years in the group that did not (P < 0.001). Cox proportional hazards analyses adjusting for several potential confounders and examining injectable vitamin D therapy as a time-dependent exposure suggested that compared with patients who did not receive injectable vitamin D, the 2-yr survival advantage associated with the group that did receive injectable vitamin D was 20% (hazard ratio, 0.80; 95% confidence interval, 0.76 to 0.83). The incidence of cardiovascular-related mortality was 7.6/100 person-years in the injectable vitamin D group, compared with 14.6/100 person-years in the non-vitamin D group (P < 0.001). The benefit of injectable vitamin D was evident in 48 of 49 strata examined, including those with low serum levels of intact parathyroid hormone and elevated levels of serum calcium and phosphorus, situations in which injectable vitamin D is often withheld. Repeating the entire analysis using marginal structural models to adjust for time-dependent confounding by indication yielded a survival advantage of 26% (hazard ratio, 0.74; 95% confidence interval, 0.71 to 0.79) associated with the injectable vitamin D group. In this historical cohort study, chronic hemodialysis patients in the group that received injectable vitamin D had a significant survival advantage over patients who did not. Randomized clinical trials would permit definitive conclusions.

Calcitriol↗