M A Hernán

..The intention-to-treat comparison is the primary, if not the only, analytic approach of many randomized clinical trials...

..The parameters of nested structural models are estimated by g-estimation and those of marginal structural models by inverse probability weighting...

..With more carefully framed questions, the results of epidemiologic studies can be of greater value to decision-makers...

..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...

..We conjecture that selection bias due to censoring by death may be the main explanation for the reversal of the relative rate with increasing age...

..7 (0.5-0.9) for one to three drinks of beer per month, and 0.7 (0.5, 0.9) for one or more drinks of beer per week. The risk of PD was similar in individuals who usually consume moderate amounts of alcohol and in abstainers...

..We conclude that consistency violations not only preclude the estimation of well-defined causal effects but also compromise our ability to estimate ill-defined causal effects...

..Observational studies had previously suggested reduced CHD risk in hormone users...

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..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...

..g., "adiposity"). The authors conclude that causal diagrams need to be used to represent biases arising not only from confounding and selection but also from measurement...

..This classification also leads to a unified approach to adjust for selection bias...

..Our case-control study included 1,019 cases and 10,123 matched controls. Overall, we did not find a lower incidence of PD among alcoholics compared with nonalcoholics (odds ratio: 1.09; 95 % CI: 0.67, 1.78)...

..Further research is required on the biological mechanisms underlying this potentially protective effect...

..8,12.7) CD4 lymphocytes/l per additional study visit while on zidovudine therapy. We also explain the theory and implementation of MSMs for repeated measures data and draw upon a simple example to illustrate the basic ideas...

..To conduct a systematic review on the association between tetanus vaccination and the risk of multiple sclerosis (MS)...

..Experimental and clinical data suggest a protective effect of estrogens on the development and progression of MS...

..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...

..A potential link between the recombinant hepatitis B vaccine and an increased risk of multiple sclerosis (MS) has been evaluated in several studies, but some of them have substantial methodologic limitations...

..These prospective findings confirm that an inverse association between smoking and the incidence of Parkinson's disease exists in both men and women...

..Also, the association between never smoking and PD risk may be present only in people with the MAOB G allele...

..65 (95% confidence interval: 0.46, 0.94) should be used because the adjusted odds ratio is invalid. Causal diagrams are used to encode qualitative a priori subject matter knowledge...

..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...

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..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...

..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...

..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...

..These results support a possible protective effect of moderate doses of caffeine on risk of Parkinson's disease...

..To investigate whether greater physical activity is associated with a lower risk of Parkinson disease (PD)...

..A protective effect of vitamin D on risk of multiple sclerosis (MS) has been proposed, but no prospective studies have addressed this hypothesis...

..Standard Cox analysis failed to detect a clear net benefit, because it does not appropriately adjust for time-dependent covariates, such as HIV RNA level and CD4 cell count, that are simultaneously confounders and intermediate variables...

..3 per 1,000 in women and 2.3 per 1,000 in men. These results confirm the relatively high incidence of MS in the UK and show marked differences in the sex-specific pattern of MS incidence by clinical course from onset...

..The present study assessed the association between history of allergy and autoimmune diseases, and the risk of MS...

..Epidemiological studies suggest an association between infection with Epstein-Barr virus (EBV) and risk of multiple sclerosis (MS)...

..Antioxidants increase the resistance of low-density lipoprotein to oxidation and may thereby reduce risk for atherosclerosis...

..Animal experiments and epidemiological studies have suggested that high potassium intake may reduce the risk of stroke, but the evidence is inconclusive, and the role of other nutrients in potassium-rich foods remains unknown...

..This work represents the first large-scale application of the parametric g-formula in an epidemiologic cohort study...

..350 × 10(9) cells/L initiate combined antiretroviral therapy (cART), but the optimal CD4 cell count at which cART should be initiated remains a matter of debate...

..and compare the advantages and disadvantages of using history-adjusted MSMs, as opposed to SNMs, to examine effect modification by time-dependent covariates...

..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...

..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...

..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...

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..To summarize current evidence on statin use and fracture risk and to explore potential sources of heterogeneity among study results...

..Taken together, these two approaches can facilitate discussion of underlying biological mechanisms...

..However, the sensitivity of this algorithm is lower for preterm deliveries, suggesting limited validity to assess drug safety for pregnancy outcomes associated with prematurity...

..To evaluate the effect of antidepressant use on lung cancer risk...

..There was a suggestion of a small increased risk with ibuprofen. Also, data suggest a small reduced risk for naproxen present only in non-users of aspirin, mainly people free of clinically apparent vascular disease...

..Because folate intake can reduce homocysteine levels, we investigated the association between dietary folate intake and nonfatal myocardial infarction...

..34) for aspirin. In conclusion, prescription of non-aspirin NSAIDs for at least 1 year might be associated with a slightly reduced risk of lung cancer. Aspirin was not associated with a risk reduction, perhaps due to residual confounding...

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..Current evidence is insufficient to support or refute a carcinogenic effect of antibiotics...

..We assessed the PPV of diagnosis codes in THIN, a primary-care medical-record database, to ascertain individuals with uncomplicated PU, and to identify UGIC and Helicobacter pylori infection status (HPIS) among these patients...

..Underappreciated sources of exposure include phthalates in the polymers coating some oral medications...

..The purpose of this study was to assess the effects of treatment with selective serotonin reuptake inhibitors (SSRIs) on the risks of gestational hypertension and preeclampsia...

..64; 95% CI = 1.24 to 2.18). The methods described here are also applicable to observational studies with time-varying treatments...

..The associations between prenatal exposure to antidepressants and preterm delivery and fetal growth restriction are controversial and poorly understood. We studied the relation between antidepressant use and these outcomes...

..We furthermore show these tests for mechanistic interaction can be extended to scenarios in which the genetic and environmental factors are negatively associated in the population rather than independent...

..Therefore, we evaluated the role of birth weight, being breastfed, and preterm birth on the incidence of SLE in participants in the Nurses' Health Study (NHS) and the Nurses' Health Study II (NHSII)...

..For illustration, we applied our method to a family study of binge eating disorder and bipolar disorder...

..Given that HIV infection is chronic and that exposure to HAART is likely to be life-long, there is a need to evaluate the long-term effect of HAART on survival in this population...

..We investigated the association of preterm birth and being breastfed with the incidence of rheumatoid arthritis (RA) in 2 large prospective cohorts...

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..Estrogen plus progestin therapy increases the risk for coronary heart disease (CHD) in postmenopausal women. However, this increased risk might be limited to the first years of use and to women who start therapy late in menopause...

..A simulation study is also presented to compare effect estimates across the three models...

..03) for waist-to-hip ratio. The results do not support a role of overall obesity in PD pathogenesis; however, central obesity may be associated with higher PD risk among never smokers, and this finding merits further investigation...

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..002). In conclusion, weight loss in PD patients appears to be a continuous process that starts several years before the diagnosis and is not caused by reduced energy intake...

..Nonsteroidal anti-inflammatory drugs (NSAIDs) reduce dopaminergic neuron degeneration in animal models of Parkinson disease (PD). However, no epidemiological data have been available on NSAID use and the risk of PD...

..65, 95% CI: 0.46, 0.91; p for trend = 0.05). Results do not support an important role of overall fat intake in the pathogenesis of Parkinson's disease, but a possible adverse effect of saturated fat for men could not be excluded...

..Intake of vitamin B(6) or vitamin B(12) also was not related to the risk of Parkinson's disease. The current study does not support the hypothesis that higher intake of folate or related B vitamins lowers the risk of Parkinson's disease...

..Our results suggest that higher intake of dairy products may increase the risk of PD in men; however, this finding needs further evaluation, and the underlying active components need to be identified...

..The purpose of this study was to describe recent trends in folic acid awareness and use in the periconceptional period among pregnant women in relation to maternal sociodemographic and other relevant factors...

..CONCLUSIONS: These results support a positive association between Cpn infection and progressive MS...

..However, as with all methods, diagnostics and sensitivity analyses are essential for proper use...

..In conclusion, the clinically important protective effect of HAART on dampening viral load appears to be rapid, present at CD4 cell counts greater than 350 cells/mm(3), and sustained beyond 6 years...

..Exogenous estrogens affect the onset and clinical course of experimental allergic encephalomyelitis. Oral contraceptives, a frequent source of exogenous estrogens in humans, could have a role in the development of multiple sclerosis (MS)...

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..The risk of birth defects after antenatal exposure to selective serotonin-reuptake inhibitors (SSRIs) remains controversial...

..It is also unknown whether the fetal genotype is relevant, or whether folic acid supplementation modifies this association...

..We used case-crossover, case-time-control, and bidirectional case-crossover designs to supplement findings from a case-control study of maternal smoking and oral clefts among offspring in a large birth registry...

..Together with selected demographic characteristics that differentiate early- vs. late-onset NVP, these findings warrant further investigation...

..To investigate whether pre-eclampsia is more common in first pregnancies solely because fewer affected women, who presumably have a higher risk of recurrence, go on to have subsequent pregnancies...

..This survival benefit of methotrexate would set a standard against which new disease-modifying antirheumatic drugs could be compared...

..When the weights are non-parametrically estimated, this method is equivalent to direct standardization of the survival curves to the combined study population...

..Randomized clinical trials would permit definitive conclusions...

..None of these studies, however, evaluated the potential association between gout, a condition characterized by hyperuricemia, and the risk of PD...

..9 (95% CI: 1.2, 7.2), but it requires controls. In the presence of gestational time trends of exposure, the new designs do not offer clear advantages over the case-control design...

..To investigate the association between infertility treatments and gestational hypertension and preeclampsia...

..We describe the patterns of over-the-counter medication use among pregnant women...

..We performed a case-control study to determine possible antenatal and perinatal predictors of persistent pulmonary hypertension of the newborn...

..TA extracellular BPI, LBP, and sCD14 were positively correlated. TAs from intubated neonates demonstrate endotoxin accumulation and mobilization of endotoxin-directed innate immunity, potentially contributing to pulmonary inflammation...

..Reduction of high reproductive mortality ratios will require attention to socioeconomic and conflict-related problems, in addition to improved access to emergency obstetrical services...