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Kenneth J Rothman

Publications and source records attributed to Kenneth J Rothman.

At least 37 records · Page 2Linked to original sources
PubMed2005

Causation and causal inference in epidemiology.

Concepts of cause and causal inference are largely self-taught from early learning experiences. A model of causation that describes causes in terms of sufficient causes and their component causes illuminates important principles such as multi-causality, the dependence of the strength of component causes on the prevalence of complementary component causes, and interaction between component causes. Philosophers agree that causal propositions cannot be proved, and find flaws or practical limitations in all philosophies of causal inference. Hence, the role of logic, belief, and observation in evaluating causal propositions is not settled. Causal inference in epidemiology is better viewed as an exercise in measurement of an effect rather than as a criterion-guided process for deciding whether an effect is present or not.

Causality↗
PubMed2004

Seasonal variation in hospitalization and case fatality of subarachnoid hemorrhage - a nationwide danish study on 9,367 patients.

Seasonal variation in the occurrence of cerebrovascular disease has been reported, but data about subarachnoid hemorrhage (SAH) are few and inconclusive. We conducted a nationwide population-based study in Denmark to examine any seasonal pattern of hospitalization and case fatality of SAH. We identified 9,367 patients with SAH and found a modest indication of overall seasonal variation for the risk of hospitalization with this diagnosis. The seasonal pattern, with the highest incidence in January and the nadir in July, was mostly apparent for subjects aged >65 years (peak-to-trough ratio = 1.18; 95% CI 1.04-1.32). There was little difference by sex. The overall 30-day case fatality rate was 38% and showed less seasonal variation. We found evidence of weak seasonal variation in hospitalization for SAH and almost no seasonal variation in a 30-day case fatality rate after SAH.

Age Factors↗
PubMed2004

The reporting odds ratio and its advantages over the proportional reporting ratio.

PURPOSE: The proportional reporting ratio (PRR) is the proportion of spontaneous reports for a given drug that are linked to a specific adverse outcome, divided by the corresponding proportion for all or several other drugs. The PRR is similar to the proportional mortality ratio (PMR), an old epidemiologic measure calculated from death registries and constructed in similar fashion to the PRR. The PMR has important deficiencies, however, which the PRR shares. Miettinen and Wang demonstrated that the PMR could be improved by reformulating it as an odds ratio and applying the principles of a case-control study to the measure. In this paper, we review the problem with the PRR and show how the corresponding odds ratio represents an improvement over the PRR. METHODS: The method used is discussion and illustration by way of a hypothetical example. RESULTS: The PRR does not estimate relative risk. If, however, a spontaneous report database is viewed as source data for a case-control study, the reporting odds ratio (ROR) can be used to estimate relative risk. Treating the data as source data for a case-control study allows for further reduction of bias by the judicious choice of controls. CONCLUSIONS: Calculating the ROR in spontaneous report databases offers advantages over the PRR. It allows for estimation of the relative risk, and focuses attention on which people or reports should be included or excluded from the control series, permitting more deliberate elimination of biases. It also highlights the inherent weaknesses in spontaneous report data, which become more evident in light of the usual principles of control selection in case-control studies.

Adverse Drug Reaction Reporting Systems↗
PubMed2004

Health outcomes among patients receiving oseltamivir.

PURPOSE: Oseltamivir was approved by the FDA for the treatment of influenza in 1999. The primary objective was to compare health outcomes among influenza patients who were treated with oseltamivir and those who were not. METHODS: The patient population included UnitedHealthcare members who received an influenza diagnosis during the 1999-2000 influenza season, divided into those who were dispensed oseltamivir on the same day (N = 3211) and those who were not dispensed oseltamivir (N = 19,985). Cardiovascular, neuropsychiatric and respiratory outcomes were assessed from medical claims for a 30-day period. RESULTS: The adjusted incidence rate ratio for major cardiac outcome was 0.56 (95%CI: 0.34-0.93) in those without a positive history of major cardiac disease, indicating that those in the oseltamivir group tended to be at lower risk of cardiac outcomes than those without oseltamivir. The adjusted incidence rate ratio for major neuropsychiatric outcome was 0.72 (95%CI: 0.53-0.97) in the negative history of neuropsychiatric disease stratum. The incidence rate ratios for respiratory events were more variable. CONCLUSIONS: There appears to be no increased risk of cardiac or neuropsychiatric outcomes among subjects with influenza who were treated with oseltamivir in comparison with those who were not.

Acetamides↗
PubMed2004

A potential bias in safety evaluation during open-label extensions of randomized clinical trials.

PURPOSE: To describe a bias that can occur in the analysis of data from certain randomized trials. METHODS AND RESULTS: Although randomized trials are effective at preventing confounding, a potentially strong confounding can arise in certain therapeutic drug trials in which follow-up is extended in an open-label phase that allows switching treatments. Many trials implement eligibility screening that excludes those at high risk of morbidity and mortality. In these trials, disease rates and death rates for the study population can rise rapidly during follow-up as the effect of screening wanes. During the open-label follow-up, a preponderance of patients may switch to the new therapy. If so, then any evaluation of the new therapy that includes follow-up from the open-label phase, as is often the case for safety evaluations, will be confounded. The confounding arises because the person-time experience of those on the new treatment will be more heavily weighted with the open-label phase experience, during which morbidity and mortality rates may be much greater than in the initial phase of follow-up. This confounding may be strong and will be in the direction of making the new treatment look worse, provided that the net switching is toward the new treatment during the open-label phase. CONCLUSIONS: The confounding described here is not prevented by randomization because it develops in a non-randomized add-on analysis to the trial. The bias can be removed, however, by controlling for time since randomization in the analysis of the data.

Bias↗
PubMed2003

Mortality of cystic fibrosis patients treated with tobramycin solution for inhalation.

BACKGROUND: Tobramycin solution for inhalation (TOBI; TSI) is indicated to treat patients with cystic fibrosis who are infected with Pseudomonas aeruginosa. Preliminary findings from a randomized trial indicate that patients who received TSI had about half the mortality rate of those assigned to placebo. METHODS: We used the Cystic Fibrosis Foundation registry data to conduct a retrospective cohort study of the risk of death among cystic fibrosis patients in 1999 according to their use of TSI during 1998. We controlled for age, lung function, height and infection with; other factors were not important confounders. RESULTS: The crude risk of death among those who received TSI therapy for 4 or more months was 3.5 times greater than that among those who received no TSI (90% confidence interval = 3.0-4.2). In general, increased TSI use was related to progressive increases in the risk of death. Such a relation is expected because TSI is used for those who are close to death, resulting in strong confounding by indication. After control of the previously mentioned confounders, the estimated risk ratio was reduced from 3.5 to 1.2. Unfortunately, it is difficult to remove confounding by indication in its entirety. Using a method that estimates the magnitude of uncontrolled confounding, we show that the actual relation between TSI and the risk of death is likely to be protective, and may well be consistent with the results from the randomized trial. CONCLUSIONS: These data illustrate strong confounding by indication and the extent to which the interpretation of data can rest on assumptions about the data and its residual biases.

Administration, Inhalation↗
PubMed2003

Seasonal variation in month of birth and diagnosis in children and adolescents with Hodgkin disease and non-Hodgkin lymphoma.

PURPOSE: Infections have been hypothesized to be a risk factor for Hodgkin disease and non-Hodgkin lymphoma. Because infections usually occur seasonally, the authors looked at the seasonal pattern of occurrence of these diseases, since seasonal variation in occurrence would lend support to the hypothesis of an etiologic link between infection and lymphoma. METHODS: The authors identified 575 patients with Hodgkin disease and 498 with non-Hodgkin lymphoma under the age of 20 years in the Danish Cancer Registry from 1943 to 1994. A periodic regression model was used to evaluate the seasonal distribution of month of diagnosis and month of birth. RESULTS: For the month of diagnosis of Hodgkin disease, the peak month of occurrence was March. The peak-to-trough ratio (the estimated incidence in the month of the peak divided by the estimated incidence in the month of the trough) was 1.57. For birth date, the ratio of case births at the peak month to case births at the trough month was 1.21, with a peak in July. There was no meaningful seasonal variation in the diagnosis or month of birth of children with non-Hodgkin lymphoma. CONCLUSIONS: These data corroborate a previously reported March peak in the diagnosis of Hodgkin disease.

Adolescent↗
PubMed2003

Folate intake and the risk of neural tube defects: an estimation of dose-response.

BACKGROUND: Studies have shown that folic acid supplementation in early pregnancy markedly reduces the risk of neural tube defects (NTDs). Investigation of the relation between relative dose of supplemental folic acid or total folate intake and NTD risk is limited. METHODS: We used data from 23,228 women, predominantly from the northeastern United States, enrolled between October 1984 and June 1987 in a prospective study of early prenatal exposures and pregnancy outcomes. Diet and vitamin intake data were gathered in the early second trimester. NTDs were ascertained through prenatal testing and by report of the delivering physician. Data analyses included multiple logistic regression and restricted spline regression modeling. RESULTS: For each additional 500 dietary folate equivalents consumed per day, the prevalence of NTDs decreased by 0.78 cases (95% confidence interval [CI] = 0.47-1.09) per 1,000 pregnancies. Compared with women having the lowest total folate intakes (0-149 folate equivalents per day), the prevalence of NTDs declined by 34%, 30%, 56% and 77% among the offspring of those women consuming 150-399, 400-799, 800-1199 and > or = 1200 folate equivalents per day, respectively (P-value for linear trend = 0.016). CONCLUSIONS: Our results suggest that NTD risk declines markedly with modest increases of total folate in early pregnancy. Total folate dose, rather than supplemental folate alone, should be considered in formulating public health guidelines for NTD prevention.

Adult↗
PubMed2003

Update on unethical use of placebos in randomised trials.

The most recent (Fifth) revision of the Declaration of Helsinki, adopted in October 2000 by the World Medical Association (WMA), reinforces the longstanding prohibition against offering placebo instead of effective therapy. The WMA left no doubt that if a beneficial treatment for a condition has already been recognised, it is unethical to offer placebo in place of such treatment to anyone in a study of the same condition. We have previously drawn attention to the discrepancy between the spirit of the Declaration and the common practice of using placebo controls in randomised trials even if effective treatment exists. Despite the mandates of the Declaration of Helsinki and concern from ethicists and scientists, the US Food and Drug Administration (FDA) continues to demand and defend placebo-controlled evidence of efficacy and safety for the development of many new pharmaceuticals, even if effective therapy exists. We suggest that the FDA's arguments defending their practice are insufficient to justify medical research that violates the Declaration of Helsinki.

Government Regulation↗
PubMed2003

Relation between serum albumin and carotid atherosclerosis: the NHLBI Family Heart Study.

BACKGROUND AND PURPOSE: Lower concentrations of albumin have been positively related to coronary disease. The aim of this project was to assess the association between serum albumin and carotid atherosclerosis. METHODS: B-mode ultrasound was used to assess carotid plaques and intima-media thickness (IMT) among white subjects from 592 randomly ascertained families in the National Heart, Lung, and Blood Institute Family Heart Study. Logistic regression was used to estimate prevalence odds ratios of any carotid plaques. RESULTS: Of the 2072 persons studied, 47% were men. Higher serum albumin was associated with younger age, lower body mass index, and lower prevalence of hypertension and coronary disease. Lower serum albumin levels were not associated with an increased odds of carotid plaques. From the lowest to the highest quartile of albumin, multivariate adjusted odds ratios for the prevalence of any carotid plaques were 1.05 (95% CI, 0.59 to 1.86), 1.34 (95% CI, 0.78 to 2.32), 1.03 (95% CI, 0.52 to 1.86), and 1.0 (reference), respectively, in men and 0.71 (95% CI, 0.40 to 1.26), 0.76 (95% CI, 0.42 to 1.36), 0.79 (95% CI, 0.46 to 1.36), and 1.0, respectively, in women. Similarly, in a linear regression model adjusted for demographic, lifestyle, and metabolic factors, serum albumin was not associated with carotid IMT. When the first 3 were compared with the highest quartile of serum albumin, regression coefficients for internal carotid IMT were 0.06458 (SE, 0.06408), 0.07205 (SE, 0.05469), and 0.000773 (SE, 0.05687), respectively, for men and -0.01795 (SE, 0.05085), -0.08501 (SE, 0.04800), and 0.009528 (SE, 0.04622), respectively, for women. CONCLUSIONS: Our data suggest that lower serum albumin levels are not associated with an increased odds of prevalent carotid atherosclerosis in either men or women.

Adult↗
PubMed2003

Randomized field trial of vaginal douching, pelvic inflammatory disease and pregnancy.

BACKGROUND: Several case-control studies have reported that women who use vaginal douche products are at increased risk for pelvic inflammatory disease. Women who douche regularly may do so for reasons related to their risk of acquiring a sexually transmitted infection, introducing confounding that is difficult to control in non-experimental studies. METHODS: We conducted a multicenter randomized field trial with a 1-year follow-up period. The study comprised 1827 women age 18-34, with no current indication of pelvic inflammatory disease, who were regular users of a douche product and who had been treated recently for a sexually transmitted bacterial infection or bacterial vaginosis. Women were randomly assigned to use either a newly designed and marketed douche product or a soft cloth towelette, and were resupplied with product at each bimonthly follow-up visit. We measured the occurrence of pelvic inflammatory disease using a combination of clinical and laboratory indicators. We also recorded pregnancy occurrence among participants. RESULTS: The risk of PID among women assigned to use the douche product, relative to that among women assigned to use the wipe product, was 1.05 (95% confidence interval = 0.57-1.9). Using an alternative, less sensitive definition of PID gave a risk ratio of 1.26 (0.62-2.6). The probability of becoming pregnant was 15% lower among women assigned to use a douche product, and 33% lower among women who douched more frequently (ratio = 0.67; 0.42-1.08). CONCLUSIONS: There was little or no indication of a greater risk of PID among women assigned to use the douche product. Douching may be related to a lower probability that a woman becomes pregnant.

Adult↗
PubMed2002

Serum albumin and risk of myocardial infarction and all-cause mortality in the Framingham Offspring Study.

BACKGROUND: Coronary disease remains the leading cause of death in the United States. The association between serum albumin and cardiovascular disease remains controversial. We used data collected prospectively from participants of the Framingham Offspring Study to assess whether a lower concentration of serum albumin was associated with an increased risk of myocardial infarction (MI) and all-cause mortality. METHODS AND RESULTS: During 21.9 years of mean follow-up, 280 cases of MI occurred. From the highest to the lowest tertile of serum albumin, crude incidence rates of MI were 26.7, 46.7, and 67.8 cases per 10 000 person-years, respectively, for men and 5.9, 15.0, and 16.8 cases per 10 000 person-years, respectively, for women. In a Mantel-Haenszel method adjusting for age, total cholesterol, and hypertension, lower serum albumin was associated with an increased risk of MI in both sexes. From the highest to the lowest tertile of albumin, the adjusted hazard ratios (95% CI) of MI were 1.0 (reference), 1.25 (0.84 to 1.84), and 1.49 (1.01 to 2.21), respectively, for men and 1.0, 1.79 (0.88 to 3.65), and 2.12 (1.06 to 4.27), respectively, for women. The albumin-MI association was stronger among hypertensive subjects in both sexes. In addition, low albumin was associated with an increased rate of all-cause mortality in women. CONCLUSIONS: Lower serum albumin concentrations appear to be associated with an increased risk of coronary disease in both sexes and with all-cause mortality in women and could help along with traditional risk factors in identifying people at risk of MI.

Adult↗