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Results for “prior odds of causality”

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PubMed2024

BICEP: Bayesian inference for rare genomic variant causality evaluation in pedigrees.

Next-generation sequencing is widely applied to the investigation of pedigree data for gene discovery. However, identifying plausible disease-causing variants within a robust statistical framework is challenging. Here, we introduce BICEP: a Bayesian inference tool for rare variant causality evaluation in pedigree-based cohorts. BICEP calculates the posterior odds that a genomic variant is causal for a phenotype based on the variant cosegregation as well as a priori evidence such as deleteriousness and functional consequence. BICEP can correctly identify causal variants for phenotypes with both Mendelian and complex genetic architectures, outperforming existing methodologies. Additionally, BICEP can correctly down-weight common variants that are unlikely to be involved in phenotypic liability in the context of a pedigree, even if they have reasonable cosegregation patterns. The output metrics from BICEP allow for the quantitative comparison of variant causality within and across pedigrees, which is not possible with existing approaches.

Pedigree↗

PubMed2003

Risk factors for pediatric ventriculoperitoneal shunt infection and predictors of infectious pathogens.

Identification of risk factors for shunt infection and predictors of infectious pathogens may improve current methods to prevent and treat shunt infections. We reviewed data on 820 consecutive ventriculoperitoneal (VP) shunt placement procedures in 442 pediatric patients at our institution during 1992-1998. Ninety-two shunts (11%) developed infection a median of 19 days (interquartile range, 11-35 days) after insertion. Premature birth (relative risk [RR], 4.81; 95% confidence interval [CI], 2.19-10.87), previous shunt infection (RR, 3.83; 95% CI, 2.40-6.13), and intraoperative use of the neuroendoscope (RR, 1.58; 95% CI, 1.01-2.50) were independent risk factors for shunt infection. The bacterial organisms early after shunt surgery (<14 days) were the same as those late after shunt surgery (>14 days). As determined by an analysis of the 92 infected shunts, hospital stay of >3 days at the time of shunt insertion (odds ratio [OR], 5.27; 95% CI, 1.15-25.3) and prior Staphylococcus aureus shunt infection (OR, 5.91; 95% CI, 1.35-25.9) independently increased the odds that S. aureus was the causal pathogen.

Adolescent↗

PubMed1993

Diet and melanoma. An exploratory case-control study.

This population-based case-control study contrasted nutrient intakes of 41 women with cutaneous malignant melanoma to those of 297 women sampled from the same community (Brisbane, Australia). Diet was assessed by a comprehensive food frequency questionnaire. The strong inverse relation we observed between high intakes of polyunsaturated fatty acids and melanoma (P < 0.01) adds sufficient weight to prior findings for this persisting causal hypothesis to be abandoned. A relatively strong association with alcohol was observed: Women drinking 20 g or more (two or more drinks) daily had 2.5 (odds ratio) times the risk of melanoma as nondrinkers (95% confidence interval, 0.87 to 7.4). However, previous data are inconsistent. With regard to potential protective factors, our data fit with prior speculation that antioxidants (beta-carotene and vitamin E), zinc, and iron warrant further investigation. The nonsignificant (P = 0.18) 40% reduction in risk seen for those eating the most fish (> or = 15 g daily versus < 5 g) suggests the effects of marine oils and omega-3 fatty acids may deserve specific attention.

Adult↗

PubMedDate not supplied

Case-control studies and Bayesian inference.

We outline the methods of Bayesian inference for applications to case-control studies. These methods appear as the natural way of making inferences, since much of the controversy that surrounds a specific case-control study is subjective. We derive conjugate prior distributions of exposure, posterior distributions of the ratio of the odds of being incident with a disease both with and without exposure to a potential causal agent, and convenient approximations. In particular, we show how one may carry out 'case-control studies' without necessarily having a control group. We illustrate these ideas with the data that first showed the relationship between in utero exposure to diethylstilbestrol and cancer of the vagina in young girls.

Adenocarcinoma↗

PubMed2003

Is the risk of adult coeliac disease causally related to cigarette exposure?

OBJECTIVE: Previous studies have shown an association between cigarette smoking and coeliac disease, but it has yet to be established whether this relationship is causal. The aim of this study was to assess causality using the Bradford Hill criteria. METHODS: A matched case-control study using a questionnaire to establish a detailed smoking history for 138 incident cases of adult coeliac disease and 276 age-matched and sex-matched controls. Subjects were categorized according to their active cigarette exposure prior to diagnosis of the matched case, and odds ratios and tests for linear trends were calculated. RESULTS: At the time of diagnosis, 10% of cases and 30% of controls were current smokers (odds ratio, 0.21 and 95% confidence interval, 0.11-0.40 for coeliac disease in current smokers versus never smokers). A biological gradient was demonstrated for total, recent and current cigarette exposure. The greatest risk reduction related to current exposure (odds ratio, 0.15, and 95% confidence interval, 0.06-0.37 for coeliac disease in current heavy smokers versus never smokers). CONCLUSIONS: This study strengthens the case for a causal relationship between smoking and coeliac disease by demonstrating a strong, temporally appropriate and dose-dependent effect, thus meeting the Bradford Hill criteria. This suggests that cigarette smoking truly protects against the development of adult coeliac disease.

Adult↗

PubMed1993

Association of overweight, trauma and workload with coxarthrosis. A health survey of 7,217 persons.

In a population sample health survey, body mass, previous trauma and physical stress were studied for associations with coxarthrosis. A sample of 8,000 persons representative of the Finnish population aged 30 or over was invited for examination, and 90 percent participated. On the basis of a standardized clinical examination, a physician diagnosed coxarthrosis in 6 percent of the women and 4 percent of the men. The prevalence rose with age. In persons with a past traumatic lower-limb injury, the odds ratio of unilateral coxarthrosis was 2.1 and of bilateral coxarthrosis 1.5, as adjusted for sex, age and other determinants using logistic regression. The sum index reflecting self-reported features of physical stress in present or previous occupations was directly proportional to the prevalence of coxarthrosis. Body mass index (kg/m2) was closely associated with bilateral coxarthrosis; the adjusted odds ratio (95 percent confidence intervals) for indices > 35, compared to those < 25, was 2.8 (1.4-5.7). In terms of the population attributable fraction, prior trauma, physical stress and body mass were estimated to explain 59 percent of the prevalence of coxarthrosis. The potential for primary prevention may be great, but longitudinal population studies are necessary to elucidate causal significance of the risk factors.

Adult↗

PubMed1996

Investigation of a cluster of ten cases of Hodgkin's disease in an occupational setting.

The objective of this study was to identify occupational exposures that might be etiologically linked to an unusual cluster of ten cases of Hodgkin's disease. The cases were identified within the active workforce of a large chemical manufacturing firm over a 23-year period by the medical director of the facilities. Based on comparison with regional cancer incidence rates, the standardized incidence ratio for Hodgkin's disease was 497 (95% confidence interval: 238-915) for the period from the construction of the facilities in 1966 through early 1992. A nested case-control study was undertaken with 200 controls selected according to case-cohort sampling. Simultaneously, efforts were initiated to confirm and characterize each case more fully. Occupational exposures were identified and categorized using process, work history, medical record, and industrial hygiene data. Tissue slides were available for eight cases and a second review confirmed the diagnosis of Hodgkin's disease. For one case, a final diagnosis of large-cell anaplastic lymphoma was determined after histology review. Among 214 different chemical agents studied, eight were identified to which three or more of the cases had been exposed prior to the date of their initial diagnosis. Exposure odds ratios were statistically elevated for five of these agents; dose-response evaluations for two of the agents, ethylene oxide and benzene, failed to provide additional support for a causal relationship. In conclusion, although several statistical associations were identified, no substance emerged as a likely candidate for explaining the observed Hodgkin's disease cluster.

Benzene↗

PubMed2004

Antibiotic use and the development of Crohn's disease.

BACKGROUND: Few environmental determinants of Crohn's disease are well established. Some observational data exist to implicate antibiotic use as a risk factor but these are derived from studies using questionnaires to assess reported antibiotic use that were susceptible to recall bias. We have therefore explored this relationship in prospectively gathered data. METHODS: We selected incident cases of Crohn's disease from the General Practice Research Database with at least five years of data prior to diagnosis. Controls with five years of complete data were randomly selected. Data were extracted on smoking, drug prescriptions, age, sex, and a variety of symptoms and diagnoses that might be indicative of occult Crohn's disease. Logistic regression was used to investigate the relationship between antibiotic use and Crohn's disease. RESULTS: A total of 587 Crohn's disease cases and 1460 controls were available for analysis. We found that antibiotic use 2-5 years pre-diagnosis occurred in 71% of cases compared with 58% of controls (p<0.001), and the median number of courses was two in the cases and one in the controls (p<0.001). Adjusting for age, sex, smoking, and use of other drugs, antibiotic use had an odds ratio of 1.32 (1.05-1.65). We were unable to show specificity to any subgroup of antibacterials. Associations similar to that with antibiotics were also found with oral contraceptive, cardiovascular, and neurological drugs. CONCLUSIONS: We found a statistically significant association between Crohn's disease and prior antibiotic use. This cannot be explained by recall bias, but due to lack of specificity it is unclear whether it is causal.

Adolescent↗

PubMed2002

Thrombotic thrombocytopenic purpura associated with clopidogrel: further evaluation.

BACKGROUND: Eleven cases of thrombotic thrombocytopenic purpura (TTP) associated with clopidogrel therapy have been published. OBJECTIVES: To perform a comprehensive causality assessment of the 11 published cases of TTP to assess quantitatively the extent to which clopidogrel was the causative factor. METHODS: The 11 reports of TTP were analyzed using the Bayesian Adverse Reaction Diagnostic Instrument to calculate the posterior probability (PsP) that clopidogrel caused the TTP based on epidemiological and clinical trials data (expressed as prior odds) and the clinical characteristics of each case (expressed as likelihood ratios). RESULTS: Clopidogrel was implicated as the causative factor of the TTP (PsP>0.75) in only five of the 11 cases. The PsP for clopidogrel was lowered by concomitant use of a statin, a history of cancer and the occurrence of relapsing TTP (in the absence of clopidogrel) in the remaining six cases. CONCLUSIONS: This systematic analysis provides strong evidence, based on the case information reported, that clopidogrel was the causative factor in at least some cases of TTP.

Bayes Theorem↗

PubMed1998

A closer look at confounding.

BACKGROUND AND OBJECTIVES: Confounding is one of the most common and important biases in primary care research. This article explains the genesis and effects of two common misconceptions of confounding: 1) Confounding can be assessed with a statistical test. 2) All covariates should be included in a multivariate model to control confounding. Assessment of confounding by testing the statistical significance of baseline differences or the significance of a potential confounding factor in a multivariate model can produce underestimates or overestimates of the true association between an exposure and an outcome. Inclusion of all covariates in a multivariate model may lead to controlling for variables that are not, in fact, confounders. This may produce underestimates or overestimates of the effect in question, as well as artificially widened confidence intervals. Both of these misconceptions can lead to profound misinterpretation of research results. To prevent problems resulting from these misunderstandings, researchers should consider drawing causal models prior to conducting the research and use the change-in-estimate criterion, rather than a statistical test, to detect confounding.

Bias↗

PubMed1986

The place of child-spacing as a factor in infant mortality: a recursive model.

This study investigates the role of a preceding birth interval in infant mortality by considering a causal ordering of seven variables. Data are from the 1974 World Fertility Survey for Korea and cover the survival of 6,161 index children. A two-stage logit model was used. The analysis suggests that infant mortality is directly influenced by the preceding birth interval which, in turn, is influenced by five other explanatory variables: maternal age, birth order, immediately preceding infant's death, education of mother, and place of residence. Maternal age and prior infant death also exert direct effects on mortality. In terms of relative risk, prior infant death has the strongest effect of all the explanatory variables. A longer birth interval increases the odds of an infant's survival by 25 per cent, whereas the death of a preceding child decreases the odds by 45 per cent. However, infant deaths in Korea occur infrequently in comparison with short birth intervals. Thus, the two factors present comparable attributable risks in unadjusted measurements. The first-stage causal structure affecting a birth interval is more complicated than the second-stage structure affecting infant mortality.

Adult↗

PubMed1989

Reye's syndrome.

The most important recent development in our understanding of Reye's syndrome is the epidemiologic evidence linking this disease to aspirin in the United States. Assessment of epidemiologic issues of concern raised in prior studies did not explain the extremely high odds ratios observed in more recent studies. The observation of a dose-response relation between risk of Reye's syndrome and dose of aspirin ingested during the antecedent illness provides further supportive evidence for a causal link between Reye's syndrome and aspirin. Additional evidence for this association in the United States is provided by a marked decline in the use of aspirin among children in the United States, which has been accompanied by a dramatic decline in the incidence of Reye's syndrome. In contrast to experience in the United States, Reye's syndrome affecting primarily children aged 5-15 years has been relatively rare in Great Britain and Australia where acetaminophen rather than aspirin is the primary analgesic/antipyretic used. With the declining incidence of aspirin use in the United States, Reye's syndrome among children aged 5-15 years is becoming increasingly rare in the United States as well and, as in Great Britain and Australia, an increasing proportion of cases are being reported in children aged less than five years. Recent reports have suggested that many children younger than age five years who are thought to have the disease may be shown to have other metabolic disorders.(ABSTRACT TRUNCATED AT 250 WORDS)

Aspirin↗

PubMed2000

[Increase in musculo-skeletal symptoms of upper limbs among women after the introduction of the flow-line in the fish-fillet plants.].

OBJECTIVES: An earlier study of workers in fish-fillet plants in Iceland showed higher prevalence of musculoskeletal symptoms as compared to a random sample of the Icelandic population. Since that study a new manufacturing process, the flow-line, has been introduced. The aim of this study was to evaluate whether this new work situation changed the prevalence of musculoskeletal symptoms among the workers of the fish-fillet plants. MATERIAL AND METHODS: The same standardised Nordic Questionnaire was used in both surveys. RESULTS: The monotony and the repetitiveness of the work increased with the new technique. The results showed that women had higher prevalence of symptoms of the upper limbs when working at the flow-line than before. The Mantel-Haenszel odds ratio for symptoms of elbows, fingers and wrists during the last seven days prior to the study was 2.1 (95% confidence interval (CI) 1.0-4.4), 1.9 (95% CI 1.1-3.2) and 1.7 (95% CI 1.0-2.7). The odds ratio for knees and ankles was less than one. CONCLUSIONS: The higher prevalence of symptoms of the upper limbs seems to be causally related to the increase of monotonous and repetitive work in the fish industry.

English Abstract↗

PubMed2005

Smoking during pregnancy and bulimia nervosa in offspring.

Because smoking during pregnancy is implicated in influencing appetite and impulse control in offspring, the aim of this study was to establish if it is associated with bulimia nervosa in offspring. Bulimia was identified at age 30 years among 4046 females, born 5-11 April, 1970. After adjustment for potential confounding factors including body mass index (BMI) and maternal psychiatric morbidity, smoking during pregnancy was associated with bulimia in offspring by age 30 years. Compared with non-smoking mothers, the adjusted odds ratios (95% confidence intervals) for bulimia in offspring were 0.74 (0.25-2.21) for those who gave up before pregnancy, 3.04 (1.16-7.95) for giving up during pregnancy and 2.64 (1.47-4.74) for smoking throughout pregnancy. Smoking during pregnancy was not associated with anorexia nervosa in offspring. Neither BMI nor variation between childhood and adult BMI explain the association. If the association of smoking during pregnancy with bulimia in offspring is causal, then it may operate through compromised central nervous system development and its influence on impulse or appetite control. The increased risk associated with mothers who gave up smoking during pregnancy emphasizes the importance of smoking cessation prior to conception.

Adult↗

PubMed2001

Recreational physical activity and endometrial cancer risk.

To investigate the association between recreational physical activity and endometrial cancer risk, a population-based case-control study was conducted in Washington State. The study included 822 incident cases of endometrial cancer diagnosed between 1985 and 1991 and 1,111 randomly selected population-based controls. Detailed information on recreational physical activities as well as other endometrial cancer risk factors was obtained in structured, in-person interviews. Unconditional logistic regression, adjusted for age, county, energy intake, unopposed estrogen use, income, and, in separate models, body mass index (kg/m(2)), was used to estimate the odds ratios and their 95% confidence intervals, relating endometrial cancer to each level of physical activity. A greater proportion of controls (49.3%) than cases (40.5%) reported doing regular exercise (compared with no exercise: adjusted odds ratio = 0.62, 95% confidence interval: 0.51, 0.76) in the 2-year period prior to diagnosis date. There was little evidence of a trend of decreasing risk with increasing duration or intensity of recreational physical activities. These results provide support for an association between the lack of recent recreational physical activity and endometrial cancer risk. However, the absence of a difference by duration or intensity levels and the inconsistent results from other studies suggest caution before interpreting this association as causal.

Aged↗

PubMed1997

Cardiovascular disease risk from prior Chlamydia pneumoniae infection can be related to certain antigens recognized in the immunoblot profile.

Chlamydia pneumoniae infection has been described as a risk factor for atherosclerosis on the basis of raised seroreactivity against complete elementary bodies among cardiovascular disease (CVD) patients. In order to identify antigens of possible pathogenetic relevance, C. pneumoniae IgG and IgA immunoblot profiles were compared for CVD patients (IgG: n = 159; IgA: n = 72) and for controls (IgG: n = 158; IgA: n = 115), all with prior C. pneumoniae infection. IgG and IgA recognition patterns were very similar, and a broad range of antigens was commonly recognized. However, statistical analysis demonstrated IgG seroresponses to 40, 54, 60, 75, and 98 kDa antigens to be more frequent among patients and resulting in odds ratios between 2.3 (98 kDa) and 29.4 (40 kDa) for development of CVD. This relation remained evident after adjustment for age and sex. Cardiovascular risk from prior chlamydial infection can thus be linked to certain antigens. Thus, for the first time potential atherogenetic virulence factors of C. pneumoniae are described. Though causal relation of chlamydial and atherosclerotic disease cannot be proven yet, evidence is growing that chlamydial structures play a part in the multifactorial pathogenesis of one of the most prevalent health hazards world-wide.

Antigens, Bacterial↗

PubMed2002

A new Poisson and Bayesian-based method to assign risk and causality in patients with suspected hepatic adverse drug reactions: a report of two new cases of ticlopidine-induced hepatotoxicity.

OBJECTIVE: The diagnosis of drug-induced hepatotoxicity is based on circumstantial evidence and is often inaccurate. We have designed a method based on published data to assign causality to suspected cases of drug-induced hepatotoxicity. DESIGN: Forty-seven published cases of ticlopidine-induced hepatotoxicity were identified by a Medline-based literature search. Data regarding abnormal liver function in patients receiving ticlopidine were obtained from the only published placebo-ticlopidine clinical trial (the Canadian American Ticlopidine Study; CATS). Thus, we calculated the maximum number of expected hepatotoxicity cases in patients exposed to ticlopidine and those not exposed to the drug by means of the Poisson distribution. The calculated odds ratio was used as a prior odd for subsequent quantification, using a Bayesian-based approach, of individual ticlopidine-induced hepatotoxicity likelihood. Concretely, the prior odd is modified by several separate likelihood ratios: age; sex; AST level; ALT level; alkaline phosphatase level; total bilirubin level; latent period of adverse reaction appearance; and period of remission of adverse reaction. This methodology was applied to two new cases of suspected ticlopidine-induced hepatotoxicity. RESULTS: The prior probability of ticlopidine-induced hepatotoxicity derived from CATS data is 61.29%. This is in contrast with the 28.83% incidence rate of drug-induced liver alterations in the general population. Alkaline phosphatase levels and total bilirubin levels were six times the normal values among individuals with ticlopidine-induced hepatotoxicity than in the general population. They were the most relevant likelihood ratios of the Bayesian model to establish a high level of causality relationship between a hepatotoxicity event and ticlopidine use. CONCLUSIONS: The proposed method, which links information from clinical trials with the profile of clinical hepatotoxicity of a drug defined from published cases reported after a drug is marketed, can be a useful tool for drug postmarketing surveillance research.

Adult↗

PubMed1998

Body size in different periods of life and breast cancer risk in post-menopausal women.

Adult obesity has been associated with an increased risk of post-menopausal breast cancer, but it is unclear whether this relationship reflects a causal role of obesity during childhood and adolescence, of weight gain during adult life or of adult obesity per se. In a population-based case-control study in all of Sweden, we included 3,345 (84% of all eligible) women aged 50-74 years with invasive breast cancer, and 3,454 (82% of all selected) controls of similar age. Mailed questionnaires and telephone interviews were used to collect detailed information on anthropometric measures. Odds ratios were estimated through multiple logistic regression. Women with the leanest somatotype at age 7 had about a 3-fold higher risk of breast cancer than the most obese (P for trend 0.0009). A suggested protective effect of a high body mass at age 18 and a detrimental influence of body mass 1 year prior to data collection largely reflected the effect of weight gain after age 18, a strong predictor of breast cancer risk. Among women at least 20 years post menopause, those who had gained 30 kg or more since age 18 had an odds ratio of 2.04 (95% confidence interval 1.20-3.48) of breast cancer compared with those who had maintained their weight unchanged. The effect of weight gain was unequivocal among non-users but not among users of hormone replacement therapy. Our findings have important implications, suggesting weight preservation as a means for prevention of post-menopausal breast cancer as well as a causal role of childhood body build in breast cancer etiology.

Age Factors↗