Marijuana use and the risk of new onset seizures.
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Biomedical subjects
Publications and source records attributed to M Susser.
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In this paper, criteria used by many epidemiologists as aids in causal inference are reviewed and revised. The revised scheme emphasizes the distinction between essential properties of a cause and criteria useful for deciding on the presence of these properties in a given case. A systematic procedure for causal inference tests each essential causal property in turn against appropriate criteria. For a pragmatic epidemiology in which all determinants serve as causes, their essential properties are held to be association, time order, and direction, in an ascending hierarchy. Criteria for association are probabilistic and can be enhanced by strength and consistency. Given association, criteria for time order of the relevant variables follow from access to observation, which is dependent on design. Given association and time order, causal direction (or consequential change) calls on an array of criteria, namely, consistency and survivability, strength, specificity in cause and in effect, predictive performance, and coherence in all its forms (e.g., theoretical, factual, biologic, and statistical). The evolution of such criteria is traced through the epidemiologic literature in the light of historical context. Although Popper's philosophy cannot directly serve an inherently inductive judgmental process, his notion of survivability has here been added, alongside replicability, as a subclass of consistency. This criterion is proposed to bridge the gap between the particularity of designs and the generality required of causal relations. Designs are ordered and described in the framework of testing survivability. Finally, definitions are offered for the list of criteria deployed.
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The causal sequence maternal nutrition----maternal weight gain----infant birth weight is not sustained by available evidence except under extreme nutritional deprivation. For maternal weight change, diet effects of near starvation are unequivocal. With chronic undernutrition or social deprivation, diet effects are inapparent or modest (conditional on pregnancy stage, diet supplement, and prepregnancy weight). For birth-weight change, diet effects of near starvation are likewise unequivocal and modest with chronic undernutrition or social deprivation. The complete causal sequence has been demonstrated only below a famine threshold. Outside famine, effects are modest (conditional on baseline nutrition, timing, and content of diets, possibly also on infant sex and energy expenditure). High-protein concentrations have produced adverse effects. Micronutrients and consequent fluid retention could have favorable effects. Diet effects on birth weight apparently bypass maternal weight change. Hence, to enhance birth weight, maternal diet appears to deserve more attention than does weight gain.
We tested associations of caffeine from beverages with spontaneous abortions of known karyotype. Spontaneous abortions (cases) were classified as chromosomally normal (n = 510) or chromosomally aberrant (n = 389) and, within the latter category, by type of aberration (237 trisomies, 54 monosomies X, 49 triploidies, 49 others). Controls registered for prenatal care before 22 weeks gestation and delivered at 28 weeks or later (n = 1,423). Caffeine intake in the perifertilization period did not differ among case groups and controls. For the highest category, 225+ mg/day, odds ratios (OR), adjusted for payment group and maternal age, were 1.0 for chromosomally normal cases, 0.9 for trisomies, 1.6 for monosomies X, and 0.8 for triploidies. Caffeine intake during pregnancy was tested for associations with chromosomally normal loss using the chromosomally aberrant cases to provide a robust comparison group. Although the proportion of subjects with intake of 225+ mg/day of caffeine intake in the perifertilization period does not influence the risk of chromosomally normal loss or trisomy. For monosomy X and triploidy, no strong associations were observed, but numbers were insufficient to rule out moderate effects. For caffeine intake during pregnancy, we found little evidence to support an influence on chromosomally normal loss.
We tested whether marijuana use in the 2 months before the last menstrual period and during pregnancy affects the risk of spontaneous abortions of known karyotype. Spontaneous abortions (cases) were defined as chromosomally normal (n = 567) or chromosomally aberrant (n = 393) and, within the latter, by type of aberration (212 trisomies, 71 monosomies X, 49 triploidies, 61 others). Controls were women with prenatal care before 22 weeks gestation and delivering at 28 weeks or later (n = 2042). In comparison with controls, adjusted odds (OR) of reported marijuana use in chromosomally normal cases were 1.1 (95% confidence interval (CI) 0.7, 1.5) and in chromosomally aberrant cases combined 1.2 (95% CI 0.7, 1.9). With respect to specific aberrations, use in the perifertilisation period did not differ significantly from that in controls for trisomies (adjusted OR = 0.8, 95% CI 0.4, 1.8), monosomies X (adjusted OR = 1.8, 95% CI 0.7, 4.3), and triploidies (adjusted OR = 1.3, 95% CI 0.4, 4.5). Comparison of karyotype groups with each other yielded similar results. Our data do not support causal associations of marijuana use, at the levels represented in our sample, with either chromosomally normal or trisomic spontaneous abortion. With monosomy X and triploidy, no statistically significant associations were detected although numbers were insufficient to rule out moderate effects.
BACKGROUND: In the light of a possible link between stress and cancer promotion or progression, and of previously reported distress in residents near the Three Mile Island (TMI) nuclear power plant, we attempted to evaluate the impact of the March 1979 accident on community cancer rates. METHODS: Proximity of residence to the plant, which related to distress in previous studies, was taken as a possible indicator of accident stress; the postaccident pattern in cancer rates was examined in 69 "study tracts" within a 10-mile radius of TMI, in relation to residential proximity. RESULTS: A modest association was found between postaccident cancer rates and proximity (OR = 1.4; 95% CI = 1.3, 1.6). After adjusting for a gradient in cancer risk prior to the accident, the odds ratio contrasting those closest to the plant with those living farther out was 1.2 (95% CI = 1.0, 1.4). A postaccident increase in cancer rates near the Three Mile Island plant was notable in 1982, persisted for another year, and then declined. Radiation emissions, as modeled mathematically, did not account for the observed increase. CONCLUSION: Interpretation in terms of accident stress is limited by the lack of an individual measure of stress and by uncertainty about whether stress has a biological effect on cancer in humans. An alternative mechanism for the cancer increase near the plant is through changes in care-seeking and diagnostic practice arising from postaccident concern.
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In light of some recent reports concerning childhood leukaemia near nuclear installations, we examined rates of cancer in children in relation to background gamma ray exposure. Data from a national monitoring programme around nuclear facilities were used to map the distribution of background gamma radiation for 69 small geographical subunits (average population 2300) within ten miles of one US nuclear plant. An association was found for incidence of childhood cancers as a whole (odds ratio (OR) = 2.4; 95% confidence limits (CL) 1.2, 4.6). For leukaemias specifically, the odds ratio was also elevated but confidence limits were very wide (OR = 2.4; 95% CL 0.5, 12.9). Analyses adjusting for sociodemographic characteristics of study tracts (population density and income) gave similar results; data on other risk factors were unavailable. Conventional risk models would not predict a detectable increase in childhood cancer from background gamma radiation, particularly not an increase of this magnitude. The large effect for solid tumours as well as leukaemias is also somewhat counter to expectation. Since a priori the association we observed was unlikely, it is important to know if similar trends in childhood cancer with background radiation are seen in other areas before rejecting chance or bias as an explanation for the result.
The authors studied the use of heroin, marijuana, and cocaine before the onset of a first seizure in 308 patients with seizures and 294 controls at Harlem Hospital Center, New York City, between 1981 and 1984. Heroin use, both past and present, appeared to be a risk factor for all first seizures (adjusted odds ratio = 2.80, 95% confidence interval (CI) 1.53-5.74). For unprovoked seizures, the adjusted odds ratio was 2.58 (95% CI 1.36-4.90) for ever heroin use and 4.70 (95% CI 0.86-25.78) for heroin use within 24 hours of hospitalization. For provoked seizures, respective adjusted odds ratios were 3.65 (95% CI 1.54-8.65) and 27.74 (95% CI 3.57-215.52). Marijuana use appeared to be a protective factor against first seizures in men. For men with unprovoked seizures, the adjusted odds ratio was 0.42 (95% CI 0.22-0.82) for ever marijuana use and 0.36 (95% CI 0.18-0.74) for marijuana use within 90 days of hospitalization. For men with provoked seizures, respective adjusted odds ratios were 1.03 (95% CI 0.36-2.89) and 0.18 (95% CI 0.04-0.84). Cocaine use, while common among study subjects, was not shown to be a significant risk factor either for all first seizures or for subgroups of seizures, regardless of the time of last use. The authors conclude that heroin use is a risk factor and marijuana use a protective factor for new-onset seizures.
As a public charge, cancers among the 159,684 residents living within a 10-mile (16-km) radius of the Three Mile Island nuclear plant were studied relative to releases of radiation during the March 28, 1979, accident as well as to routine plant emissions. The principal cancers considered were leukemia and childhood malignancies. Estimates of the emissions delivered to small geographic study tracts were derived from mathematical dispersion models which accounted for modifying factors such as wind and terrain; the model of accident emissions was validated by readings from off-site dosimeters. Incident cancers among area residents for the period 1975-1985 (n = 5,493) were identified by a review of the records at all local and regional hospitals; preaccident and postaccident trends in cancer rates were examined. For accident emissions, the authors failed to find definite effects of exposure on the cancer types and population subgroups thought to be most susceptible to radiation. No associations were seen for leukemia in adults or for childhood cancers as a group. For leukemia in children, the odds ratio was raised, but cases were few (n = 4), and the estimate was highly variable. Moreover, rates of childhood leukemia in the Three Mile Island area are low compared with national and regional rates. For exposure to routine emissions, the odds ratios were raised for childhood cancers as a whole and for childhood leukemia, but confidence intervals were wide and included 1.0. For leukemia in adults, there was a negative trend. Trends for two types of cancer ran counter to expectation. Non-Hodgkin's lymphoma showed raised risks relative to both accident and routine emissions; lung cancer (adjusted only indirectly for smoking) showed raised risks relative to accident emissions, routine emissions, and background gamma radiation. Overall, the pattern of results does not provide convincing evidence that radiation releases from the Three Mile Island nuclear facility influenced cancer risk during the limited period of follow-up.
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We studied alcohol use before the onset of a first seizure in 308 patients with seizures and 294 controls. The risk of seizures increased with increasing current alcohol use. For unprovoked seizures (i.e., seizures occurring without an antecedent event, such as a recent stroke), the adjusted odds ratios rose from 3-fold at intakes of 51 to 100 g of ethanol per day (95 percent confidence limits, 1.3 and 6.3), to 8-fold at 101 to 200 g per day (95 percent confidence limits, 3.3 and 18.7), and to almost 20-fold at 201 to 300 g per day (95 percent confidence limits, 6.1 and 6.2). For provoked seizures, the odds ratios were lower and statistically significant only above 200 g per day (odds ratio, 10.1; 95 percent confidence limits, 2.3 and 43.8 at 201 to 300 g per day; odds ratio, 7.4; 95 percent confidence limits, 1.8 and 30.5 above 300 g per day). Among ex-drinkers (abstention greater than or equal to 1 year), no increased risk was detected. Alcohol withdrawal was not associated with the onset of seizures in this study; 16 percent of first seizures in drinkers fell outside the conventionally defined withdrawal period, and the remainder exhibited a seemingly random timing after the last drink. We conclude that the relation of seizures to alcohol use is dose dependent and appears to be causal, and that seizures can be interpreted as a disorder induced by the ingestion of alcohol, independently of alcohol withdrawal.