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Biomedical subjects

Kenneth J Rothman

Publications and source records attributed to Kenneth J Rothman.

At least 19 recordsLinked to original sources
PubMed2007

Incidence of IBS in a cohort of people with asthma.

We conducted a study to examine the relation of asthma and its treatment to irritable bowel syndrome (IBS). We identified cohorts of members with and without asthma from January 1996 though June 2002 and calculated rates of IBS in both cohorts. In a nested case-control study, we calculated odds ratios for oral steroid dispensing before IBS onset. To address differential IBS detection, we conducted a quantitative sensitivity analysis. We identified 91,237 people with asthma and sample of 24,518 people without asthma. There was a 20% increase in the incidence of IBS among people with asthma (standardized morbidity ratio = 1.2; 95% CI, 1.0-1.5), and no association between oral steroids and IBS among people with asthma (OR = 1.0; 95% CI, 0.9-1.1.) Misclassification of IBS would have biased the rate ratio toward the null. We observed a small increase in IBS among people with asthma, and no association between oral steroids and IBS onset among asthma patients.

Administration, Oral↗
PubMed2006

Migraine, fibromyalgia, and depression among people with IBS: a prevalence study.

BACKGROUND: Case descriptions suggest IBS patients are more likely to have other disorders, including migraine, fibromyalgia, and depression. We sought to examine the prevalence of these conditions in cohorts of people with and without IBS. METHODS: The source of data was a large U.S. health plan from January 1, 1996 though June 30, 2002. We identified all people with a medical claim associated with an ICD-9 code for IBS. A non-IBS cohort was a random sample of people with an ICD-9 code for routine medical care. In the cohorts, we identified all claims for migraine, depression, and fibromyalgia. We estimated the prevalence odds ratios (PORs) of each of the three conditions using the Mantel-Haenszel method. We conducted quantitative sensitivity analyses to quantify the impact of residual confounding and in differential outcome identification. RESULTS: We identified 97,593 people in the IBS cohort, and a random sample of 27,402 people to compose the non-IBS comparison cohort. With adjustment, there was a 60% higher odds in the IBS cohort of having any one of the three disorders relative to the comparison cohort (POR 1.6, 95% CI 1.5 - 1.7). There was a 40% higher odds of depression in the IBS cohort (POR 1.4, 95% CI 1.3 - 1.4). The PORs for fibromyalgia and migraine were similar (POR for fibromyalgia 1.8, 95% CI 1.7 - 1.9; POR for migraine 1.6, 95% CI 1.4 - 1.7). Differential prevalence of an unmeasured confounder, or imperfect sensitivity or specificity of outcome detection would have impacted the observed results. CONCLUSION: People in the IBS cohort had a 40% to 80% higher prevalence odds of migraine, fibromyalgia, and depression.

Adult↗
PubMed2006

Variable selection for propensity score models.

Despite the growing popularity of propensity score (PS) methods in epidemiology, relatively little has been written in the epidemiologic literature about the problem of variable selection for PS models. The authors present the results of two simulation studies designed to help epidemiologists gain insight into the variable selection problem in a PS analysis. The simulation studies illustrate how the choice of variables that are included in a PS model can affect the bias, variance, and mean squared error of an estimated exposure effect. The results suggest that variables that are unrelated to the exposure but related to the outcome should always be included in a PS model. The inclusion of these variables will decrease the variance of an estimated exposure effect without increasing bias. In contrast, including variables that are related to the exposure but not to the outcome will increase the variance of the estimated exposure effect without decreasing bias. In very small studies, the inclusion of variables that are strongly related to the exposure but only weakly related to the outcome can be detrimental to an estimate in a mean squared error sense. The addition of these variables removes only a small amount of bias but can increase the variance of the estimated exposure effect. These simulation studies and other analytical results suggest that standard model-building tools designed to create good predictive models of the exposure will not always lead to optimal PS models, particularly in small studies.

Confounding Factors, Epidemiologic↗
PubMed2006

Apgar score and hospitalization for epilepsy in childhood: a registry-based cohort study.

BACKGROUND: A depressed Apgar score at 5 minutes is a marker for perinatal insults, including neurologic damage. We examined the association between 5-minute Apgar score and the risk of epilepsy hospitalization in childhood. METHODS: Using records linked from population registries, we conducted a cohort study among singleton children born alive in the period 1978-2001 in North Jutland County, Denmark. The first hospital discharge diagnosis of epilepsy during the follow-up time was the main outcome. We followed each child for up to 12 years, calculated absolute risks and risk differences, and used a Poisson regression model to estimate risk ratios for epilepsy hospitalization. We adjusted risk ratio estimates for birth weight, gestational age, mode of delivery, birth presentation, mother's age at delivery, and birth defects. RESULTS: One percent of the 131,853 eligible newborns had a 5-minute Apgar score <7. These children were more likely to be hospitalized with epilepsy during the follow-up than were children with an Apgar score of 7 or greater. The crude risk difference for epilepsy hospitalization was 2.5 cases per 100 (95% confidence interval [CI] 1.3 to 3.8). The risk difference estimates were greater in the presence of other perinatal risk factors. The adjusted risk ratio was 2.4 (95% CI 1.5 to 3.8). Half of the 12-year risk for epilepsy hospitalization in those with a depressed Apgar score occurred during the first year of life. The risk ratio during the first year of life was 4.9 (95% CI 2.0 to 12.3). CONCLUSION: An Apgar score <7 at five minutes predicts an increase in the subsequent risk of epilepsy hospitalization. This association is amplified by other perinatal risk factors.

Apgar Score↗
PubMed2006

Beyond randomized controlled trials: a critical comparison of trials with nonrandomized studies.

Observational analogs of randomized clinical trials (RCTs) are well accepted in the study of disease risk factors, diagnosis, and prognosis. There is controversy about observational studies when the focus is on the intended benefit due to lack of blinding and poor control for unmeasured confounding. Well-designed randomized clinical trials are costly both in time and money. Therefore, existing databases are used increasingly and are often the only feasible source with which to examine delayed health effects. We reviewed the reasons for possible discrepancies between RCTs and observational studies. There can be different patient populations, differences in therapeutic regimen, control of confounding, follow-up, measuring outcome, and differences arising from the intention-to-treat analysis. Observational studies cannot replace trials, nor do trials make observational studies unnecessary. Both designs are susceptible to particular bias, so neither provides perfect information.

Observation↗
PubMed2006

Insights into different results from different causal contrasts in the presence of effect-measure modification.

PURPOSE: Both propensity score (PS) matching and inverse probability of treatment weighting (IPTW) allow causal contrasts, albeit different ones. In the presence of effect-measure modification, different analytic approaches produce different summary estimates. METHODS: We present a spreadsheet example that assumes a dichotomous exposure, covariate, and outcome. The covariate can be a confounder or not and a modifier of the relative risk (RR) or not. Based on expected cell counts, we calculate RR estimates using five summary estimators: Mantel-Haenszel (MH), maximum likelihood (ML), the standardized mortality ratio (SMR), PS matching, and a common implementation of IPTW. RESULTS: Without effect-measure modification, all approaches produce identical results. In the presence of effect-measure modification and regardless of the presence of confounding, results from the SMR and PS are identical, but IPTW can produce strikingly different results (e.g., RR = 0.83 vs. RR = 1.50). In such settings, MH and ML do not estimate a population parameter and results for those measures fall between PS and IPTW. CONCLUSIONS: Discrepancies between PS and IPTW reflect different weighting of stratum-specific effect estimates. SMR and PS matching assign weights according to the distribution of the effect-measure modifier in the exposed subpopulation, whereas IPTW assigns weights according to the distribution of the entire study population. In pharmacoepidemiology, contraindications to treatment that also modify the effect might be prevalent in the population, but would be rare among the exposed. In such settings, estimating the effect of exposure in the exposed rather than the whole population is preferable.

Bias↗
PubMed2006

Use of cyclo-oxygenase 2 inhibitors (COX-2) and prescription non-steroidal anti-inflammatory drugs (NSAIDS) in UK and USA populations. Implications for COX-2 cardiovascular profile.

BACKGROUND: COX-2 and NSAIDS differ in their gastrointestinal (GI) and cardiovascular (CV) toxicity from pharmacological, clinical and epidemiologic point of views. OBJECTIVE: Describe the patterns of use of NSAIDS and COX-2 in The Health Improvement Network (THIN) database in UK and the PharMetrics database in USA. METHODS: We examined the experience of 10 distinct cohorts of new users of diclofenac, naproxen, ibuprofen, piroxicam, other NSAIDS, meloxicam, celecoxib, etoricoxib, rofecoxib and valdecoxib. The study period was 1 January 1995 through 2004 (31 March in UK and 28 February in USA). We collected information on covariates including history of upper GI disease, CV disease, hepatic disease, dosage, concomitant medication, and visits to a rheumatologist. RESULTS: We identified 486 076 unique patient-drug pairs in UK and 1 533 239 in USA. In UK population 78 201 (16%) were COX-2 users and in PharMetrics 324 206 (21%) were COX-2 users. Diclofenac and ibuprofen (NSAIDS), and celecoxib and rofecoxib (COX-2) were the agents prescribed most frequently. The duration of therapy was longer among celecoxib and rofecoxib users than among other users. More COX-2 users than NSAIDS users received concomitant gastroprotective agents (GPA), corticosteroids and anti-platelet therapy, and had a history of thromboembolic events and hypertension. PharMetrics patients were prescribed higher doses of NSAIDS and COX-2. The use of any single agent for more than 90 days was uncommon, but more frequent in PharMetrics. Switching was uncommon and was generally to a NSAID. DISCUSSION: Our results confirm some previous findings from other authors such as the presence of both GI and CV channelling to COX-2 agents but refute others, such as the frequency of drug switching between these agents. The typical use of COX-2 agents in practice is for shorter duration, and at lower doses, than was employed in randomized clinical trials. This difference may help clarify the apparent discrepancy with respect to CV toxicity between the results from clinical trials, which showed a higher CV risk with these drugs, and non-experimental epidemiologic studies, which showed lower or no increase in risk.

Adolescent↗
PubMed2006

Short-term mortality of bacteraemia in elderly patients with haematological malignancies.

Bacterial infections are important complications in patients with haematological malignancies. We compared the outcome of bacteraemia among elderly and younger patients with haematological malignancies, and evaluated the impact of comorbidity on this association using population-based registries from 1992 to 2002. Among 358 patients with an incident haematological malignancy and an episode of bacteraemia, 207 (58%) were older than 60 years and 37 (10%) older than 80 years. The 7-d mortality was 10% among patients younger than 60 years, 21% among patients aged 60-79 years, and 27% for patients older than 80 years. When compared with patients younger than 60 years, the adjusted mortality rate ratios (MRRs) were 1.9 [95% confidence interval (CI): 0.9-3.8] for patients aged 60-79 years and 1.6 (95% CI: 0.6-4.2) for patients older than 80 years. The 30-d mortality was 23% among patients younger than 60 years of age, 35% among patients aged 60-79 years, and 54% among patients 80 years or older. Adjusted MRRs were 1.7 (95% CI: 1.1-2.7) and 2.3 (95% CI: 1.2-4.3), respectively. We found that increasing age was associated with increased mortality from bacteraemia in patients with haematological malignancies. An increased burden of comorbidity among the elderly did not explain this association.

Adolescent↗
PubMed2006

Exposure to fumonisins and the occurrence of neural tube defects along the Texas-Mexico border.

Along the Texas-Mexico border, the prevalence of neural tube defects (NTDs) among Mexican-American women doubled during 1990-1991. The human outbreak began during the same crop year as epizootics attributed to exposure to fumonisin, a mycotoxin that often contaminates corn. Because Mexican Americans in Texas consume large quantities of corn, primarily in the form of tortillas, they may be exposed to high levels of fumonisins. We examined whether or not maternal exposure to fumonisins increases the risk of NTDs in offspring using a population-based case-control study. We estimated fumonisin exposure from a postpartum sphinganine:sphingosine (sa:so) ratio, a biomarker for fumonisin exposure measured in maternal serum, and from maternal recall of periconceptional corn tortilla intake. After adjusting for confounders, moderate (301-400) compared with low (< or = 100) consumption of tortillas during the first trimester was associated with increased odds ratios (ORs) of having an NTD-affected pregnancy (OR = 2.4; 95% confidence interval, 1.1-5.3). No increased risks were observed at intakes higher than 400 tortillas (OR = 0.8 for 401-800, OR = 1.0 for > 800). Based on the postpartum sa:so ratio, increasing levels of fumonisin exposure were associated with increasing ORs for NTD occurrences, except for the highest exposure category (sa:so > 0.35). Our findings suggest that fumonisin exposure increases the risk of NTD, proportionate to dose, up to a threshold level, at which point fetal death may be more likely to occur. These results also call for population studies that can more directly measure individual fumonisin intakes and assess effects on the developing embryo.

Adolescent↗
PubMed2005

A review of the application of propensity score methods yielded increasing use, advantages in specific settings, but not substantially different estimates compared with conventional multivariable methods.

OBJECTIVE: Propensity score (PS) analyses attempt to control for confounding in nonexperimental studies by adjusting for the likelihood that a given patient is exposed. Such analyses have been proposed to address confounding by indication, but there is little empirical evidence that they achieve better control than conventional multivariate outcome modeling. STUDY DESIGN AND METHODS: Using PubMed and Science Citation Index, we assessed the use of propensity scores over time and critically evaluated studies published through 2003. RESULTS: Use of propensity scores increased from a total of 8 reports before 1998 to 71 in 2003. Most of the 177 published studies abstracted assessed medications (N=60) or surgical interventions (N=51), mainly in cardiology and cardiac surgery (N=90). Whether PS methods or conventional outcome models were used to control for confounding had little effect on results in those studies in which such comparison was possible. Only 9 of 69 studies (13%) had an effect estimate that differed by more than 20% from that obtained with a conventional outcome model in all PS analyses presented. CONCLUSIONS: Publication of results based on propensity score methods has increased dramatically, but there is little evidence that these methods yield substantially different estimates compared with conventional multivariable methods.

Bias↗
PubMed2005

Analytic strategies to adjust confounding using exposure propensity scores and disease risk scores: nonsteroidal antiinflammatory drugs and short-term mortality in the elderly.

Little is known about optimal application and behavior of exposure propensity scores (EPS) in small studies. In a cohort of 103,133 elderly Medicaid beneficiaries in New Jersey, the effect of nonsteroidal antiinflammatory drug use on 1-year all-cause mortality was assessed (1995-1997) based on the assumption that there is no protective effect and that the preponderance of any observed effect would be confounded. To study the comparative behavior of EPS, disease risk scores, and "conventional" disease models, the authors randomly resampled 1,000 subcohorts of 10,000, 1,000, and 500 persons. The number of variables was limited in disease models, but not EPS and disease risk scores. Estimated EPS were used to adjust for confounding by matching, inverse probability of treatment weighting, stratification, and modeling. The crude rate ratio of death was 0.68 for users of nonsteroidal antiinflammatory drugs. "Conventional" adjustment resulted in a rate ratio of 0.80 (95% confidence interval: 0.77, 0.84). The rate ratio closest to 1 (0.85) was achieved by inverse probability of treatment weighting (95% confidence interval: 0.82, 0.88). With decreasing study size, estimates remained further from the null value, which was most pronounced for inverse probability of treatment weighting (n = 500: rate ratio = 0.72, 95% confidence interval: 0.26, 1.68). In this setting, analytic strategies using EPS or disease risk scores were not generally superior to "conventional" models. Various ways to use EPS and disease risk scores behaved differently with smaller study size.

Aged↗