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Biomedical subjects

John D Seeger

Publications and source records attributed to John D Seeger.

13 recordsLinked to original sources

Pregnancy and pregnancy outcome among women with inflammatory skin diseases.

BACKGROUND/AIMS: The effect of inflammatory skin diseases on pregnancy has been incompletely characterized. We sought to estimate the incidence of pregnancy and pregnancy outcomes among women with inflammatory skin diseases. METHODS: Cohort study of women with atopic dermatitis (AD), psoriasis, other inflammatory skin diseases, and comparison group, followed for pregnancies and pregnancy outcomes. RESULTS: There were 3,131 pregnancies among 64,773 woman-years (4.8/100) in women with skin diseases, and 2,592 pregnancies among 59,826 woman-years (4.3/100) in the comparison group. The age-standardized incidence of pregnancy was similar to the comparison group [rate ratio (RR) = 1.2, 95% confidence interval (CI) 1.0-1.4 for AD, RR = 1.1, 95% CI 1.0-1.2 for psoriasis, and RR = 1.1, 95% CI 1.0-1.1 for other]. Spontaneous abortion was also similar to the comparison group (RR = 1.2 for AD, 95% CI 1.0-1.4, RR = 1.1, 95% CI 1.0-1.2 for psoriasis, and RR = 1.1, 95% CI 1.0-1.1 for other). CONCLUSIONS: Our results suggest little effect of skin disease on incidence or outcome of pregnancy.

Adolescent↗

Achilles tendon rupture and its association with fluoroquinolone antibiotics and other potential risk factors in a managed care population.

BACKGROUND: Case reports and observational studies have implicated fluoroquinolone antibiotic exposure as a risk factor for Achilles tendon rupture (ATR), an uncommon condition for which there are few formal studies. We sought to quantify the strength of association between exposure to fluoroquinolone antibiotics and the occurrence of ATR, accounting for other risk factors. METHODS: This was a case-control study nested within a health insurer cohort. Cases of ATR were identified and confirmed using patterns of health insurance claims that were validated through sampled medical record review. Information on risk factors, including fluoroquinolone exposure, came from health insurance claims. RESULTS: There were 947 cases of ATR and 18 940 controls. A dispensing of a fluoroquinolone antibiotic in the past 6 months was more common among ATR cases than controls, although not significantly so (odds ratio (OR) = 1.2; 95% confidence interval (CI) = 0.9-1.7), and exposure to a higher cumulative fluoroquinolone dose was more strongly associated (OR = 1.5, 95%CI = 1.0-2.3). Other risk factors for ATR were trauma (OR = 17.2, 95%CI = 14.0-20.2), male sex (OR = 3.0, 95%CI = 2.6-3.5), injected corticosteroid administration (OR = 2.2, 95%CI = 1.6-2.9), obesity (OR = 2.0, 95%CI = 1.2-3.1), rheumatoid arthritis (OR = 1.9, 95%CI = 1.0-3.7), skin or soft tissue infections (OR = 1.5, 95%CI = 0.9-2.3), oral corticosteroids (OR = 1.4, 95%CI = 1.0-1.8), and non-fluoroquinolone antibiotics (OR = 1.2, 95%CI = 1.1-1.5). CONCLUSIONS: The elevation in ATR risk associated with fluoroquinolones was similar in magnitude to that associated with oral corticosteroids or non-fluoroquinolone antibiotics. Trauma and male sex were more strongly associated with ATR, as were obesity and injected corticosteroids.

Achilles Tendon↗

The comparative safety of rosuvastatin: a retrospective matched cohort study in over 48,000 initiators of statin therapy.

PURPOSE: The purpose of this study was to compare incidence rates of hospitalization associated with rhabdomyolysis, myopathy, renal, or hepatic dysfunction, and of in-hospital death, between initiators of rosuvastatin and other statins. METHODS: This was a matched cohort study of statin initiators from the administrative database of a large health insurer in the US, during the first 6 months of rosuvastatin availability with up to 18 months of follow-up. All outcome events were verified by medical record review. Incidence rates, risk ratios, and associated 95% confidence intervals were estimated. RESULTS: From an initial pool of 12,217, 11,249 eligible rosuvastatin initiators were matched to 37,282 initiators of other statins. The incidence rate (IR) per 1000 person-years for rhabdomyolysis was 0.10 [0.00, 0.55] for rosuvastatin initiators (n = 1) and 0.06 [0.01, 0.22] for other statin initiators (n = 2), for a hazard ratio (HR) of 1.98 [0.18, 21.90]. The IR for myopathy was 0.20 [0.02, 0.71] for rosuvastatin initiators (n = 2) and 0.00 [0.00, 0.09] for other statin initiators (n = 0). The IR for renal dysfunction was 1.18 [0.61, 2.06] for rosuvastatin initiators (n = 12) and 1.26 [0.91, 1.71] for other statin initiators (n = 42), for a HR of 0.90 [0.47, 1.73]. The IR for hepatic dysfunction was 0.20 (0.02, 0.71) for rosuvastatin initiators (n = 2) and 0.24 (0.10, 0.47) for other statin initiators (n = 8), for a HR of 0.87 (0.18, 4.14). CONCLUSIONS: This study found no difference between rosuvastatin and the other statins in the incidence of hospitalizations associated with renal or hepatic events, or death. The absolute incidence rates of rhabdomyolysis and myopathy were reassuringly low among all statin initiators but remain too small for firm conclusions to be drawn on any difference between the statins.

Adolescent↗

Glucocorticoid use and serum lipid levels in US adults: the Third National Health and Nutrition Examination Survey.

OBJECTIVE: It has been generally perceived that glucocorticoids adversely affect serum lipid levels, although results of prospective studies have suggested the contrary. In this study, we sought to examine the relationship between glucocorticoid use and lipid profiles in a nationally representative sample of subjects. METHODS: Using data from 15,004 participants ages 20 years and older in The Third National Health and Nutrition Examination Survey (1988-1994), we examined the relationship between glucocorticoid use and serum lipid profiles. Glucocorticoid use was determined from the household interview regarding prescription medication use. We used multivariate linear regression to adjust for age, sex, race or ethnicity, education, smoking status, body mass index, physical activity, alcohol consumption, energy fraction from protein and carbohydrates, and total energy intake. RESULTS: Glucocorticoid use was associated with a higher serum high-density lipoprotein (HDL) cholesterol level and a lower ratio of total cholesterol-to-HDL cholesterol among subjects ages 60 years or older (multivariate difference 9.0 mg/dl [95% confidence interval (95% CI) 3.9, 14.1] and -0.6 mg/dl [95% CI -0.9, -0.3], respectively) but not among those younger than age 60 years (multivariate difference -1.5 mg/dl [95% CI -5.4, 2.5] and 0.1 mg/dl [95% CI -0.3, 0.5], respectively). Correspondingly, glucocorticoid use was associated with a higher serum apolipoprotein A-I (Apo A-I) level and a lower Apo A-I:Apo B ratio (multivariate difference 12.1 mg/dl [95% CI 2.9, 21.3] and 0.16 mg/dl [95% CI 0.03, 0.29], respectively) only among subjects ages 60 years or older. Inhalation/intranasal glucocorticoid use was also associated with a higher serum HDL cholesterol level (multivariate difference 4.9 mg/dl [95% CI 0.3, 9.5]) only among subjects ages 60 years or older. CONCLUSION: Our results suggest that glucocorticoid use is not associated with an adverse lipid profile in the US population and may be associated with a favorable lipid profile among persons ages 60 years or older, in concordance with previous prospective studies.

Adult↗

An application of propensity score matching using claims data.

BACKGROUND: Confounding by indication is a common problem in pharmacoepidemiology, where predictors of treatment also have prognostic value for the outcome of interest. The tools available to the epidemiologist that can be used to mitigate the effects of confounding by indication often have limits with respect to the number of variables that can be simultaneously incorporated as components of the confounding. This constraint becomes particularly apparent in the context of a rich data source (such as administrative claims data), applied to the study of an outcome that occurs infrequently. In such settings, there will typically be many more variables available for control as potential confounders than traditional epidemiologic techniques will allow. METHODS: One tool that can indirectly permit control of a large number of variables is the propensity score approach. This paper illustrates the application of the propensity score to a study conducted in an administrative database, and raises critical issues to be addressed in such an analysis. In this example, the effect of statin therapy on the occurrence of myocardial infarction was examined, and numerous potential confounders of this association were adjusted simultaneously using a propensity score to form matched cohorts of statin initiators and non-initiators. RESULTS: The incidence of myocardial infarction observed in the statin treated cohort was lower than the incidence in the untreated cohort, and the magnitude of this effect was consistent with results from randomized placebo controlled clinical trials of statin therapy. CONCLUSIONS: This example illustrates how confounding by indication can be mitigated by the propensity score matching technique. Concerns remain over the generalizability of estimates obtained from such a study, and how to know when propensity scores are removing bias, since apparent balance between compared groups on measured variables could leave variables not included in the propensity score unbalanced and lead to confounded effect estimates.

Cohort Studies↗

Lipid profiles among US elderly with untreated rheumatoid arthritis--the Third National Health and Nutrition Examination Survey.

OBJECTIVE: Recent studies suggest that patients with active rheumatoid arthritis (RA) have adverse serum lipid profiles. We examined lipid profiles among individuals with RA in a national sample of persons aged 60 years and older. METHODS: Using data from 4862 participants (2379 men and 2483 women) aged 60 years and older in the Third National Health and Nutrition Examination Survey (1988-94), we examined lipid profiles among participants with RA who met the American College of Rheumatology (ACR) 1987 criteria and who were not taking glucocorticoids or disease modifying antirheumatic drugs (DMARD). RESULTS: Participants with RA had lower high density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I concentrations than those without RA. After adjusting for age and sex, the differences in HDL-C level between those with and those without RA were 2.5 mg/dl (95% CI 0.8 to 4.9) using > or = 3 of the ACR criteria (n of RA cases = 104) and 8.8 mg/dl (95% CI 3.2 to 14.3) using > or = 4 criteria (n of RA cases = 26). Adjusting for age, sex, race, education, smoking status, body mass index, alcohol consumption, physical activity, dietary factors, and other potential confounders attenuated the differences slightly. The multivariate difference in serum apolipoprotein A-I levels between those with and those without RA was 4.5 mg/dl (95% CI -0.8 to 9.8) using > or = 3 ACR criteria and 13.6 mg/dl (95% CI 3.2 to 24.1) using > or = 4 criteria. All individual RA disease activity measures tended to have inverse relations with HDL-C levels, but significant inverse associations were present only with the following variables: C-reactive protein [CRP; multivariate difference per 1 mg/dl of CRP, -1.3 mg/dl (95% CI -2.0 to -0.5)], presence of hand arthritis [-2.6 mg/dl (95% CI -5.0 to -0.2)], and positive rheumatoid factor [-3.4 mg/dl (95% CI -5.5 to -1.3)]. CONCLUSION: These national survey data indicate that RA not treated with DMARD or glucocorticoids is associated with adverse lipid profiles characterized by lower HDL-C and apolipoprotein A-I levels in persons aged > or = 60 years.

Aged↗

Effects of rofecoxib and naproxen on life expectancy among patients with rheumatoid arthritis: a decision analysis.

BACKGROUND: The VIOXX Gastrointestinal Outcomes Research (VIGOR) trial showed a 53% decrease in the risk of upper gastrointestinal toxicity and a fivefold increase in the risk of myocardial infarction for rofecoxib (a selective cyclooxygenase-2 inhibitor) compared with naproxen. We examined the effects of these competing adverse events on life expectancy in patients with rheumatoid arthritis. METHODS: We used decision analysis to compare the life expectancy of a cohort of rheumatoid arthritis patients taking naproxen versus a similar cohort taking rofecoxib, using data from the VIGOR trial. We incorporated the competing risks of upper gastrointestinal toxicity and myocardial infarction, as well as their long-term health consequences, on the basis of population-based studies. RESULTS: For 58-year-old women with rheumatoid arthritis (i.e., typical of participants in the VIGOR trial), naproxen was associated with a longer life expectancy than was rofecoxib (difference = 4.4 months). This difference was larger among 58-year-old men (7.8 months). The probability that naproxen is associated with a longer life expectancy than rofecoxib among 58-year-old patients was 92% for women and 98% for men. Life expectancy became the same between the two treatments when the risk of upper gastrointestinal toxicity was 70% higher or the risk of myocardial infarction was 40% lower than that of the base case among women, and when the risk of upper gastrointestinal toxicity was 4.4-fold higher or the risk of myocardial infarction was 70% lower among men. CONCLUSION: Our analysis suggests that the competing risks of upper gastrointestinal toxicity and myocardial infarction shown in the VIGOR trial would project a longer life expectancy with naproxen than rofecoxib among patients with rheumatoid arthritis, except in those at low risk of myocardial infarction or at high risk of upper gastrointestinal toxicity.

Aged↗

Observational research in rheumatic disorders.

Observational research plays an important role in science. Much of human knowledge, including health knowledge, comes from observations, not experiments. Within medicine, observational studies cover a wide scope that ranges from case reports and case series, to descriptive studies, to analytic observational studies for causal questions. These studies often are complementary; each provides a piece of information that can be synthesized into a description and analysis of a health problem in a way that tests hypotheses and advances medical science and has the potential to lead to interventions that can improve health and quality of life. This article reviews the scope of observational studies, principles of causal inference in observational studies, and various types of observational studies with a focus of their applications in rheumatic disorders.

Causality↗

A propensity score-matched cohort study of the effect of statins, mainly fluvastatin, on the occurrence of acute myocardial infarction.

This investigation quantified the effect of statins on acute myocardial infarction (AMI) in an observational setting where fluvastatin represented most of the statin use. The study applied propensity scores to match statin initiators to statin noninitiators and followed them for the occurrence of AMI. Serum low-density lipoprotein levels were reduced by statin therapy, and there were fewer incidents of AMI in statin initiators than in noninitiators.

Cholesterol, LDL↗

Methotrexate and mortality in patients with rheumatoid arthritis: a prospective study.

BACKGROUND: Methotrexate is the most frequent choice of disease-modifying antirheumatic therapy for rheumatoid arthritis. Although results of studies have shown the efficacy of such drugs, including methotrexate, on rheumatoid arthritis morbidity measures, their effect on mortality in patients with the disease remains unknown. Our aim was to prospectively assess the effect on mortality of methotrexate in a cohort of patients with rheumatoid arthritis. METHODS: Our cohort included 1240 patients with rheumatoid arthritis seen at the Wichita Arthritis Center, an outpatient rheumatology facility. Patients' details were entered into a computerised database at the time of their first clinic visit. We also obtained and recorded demographic, clinical, laboratory, and self-reported data at each follow-up visit (average interval 3.5 months). We estimated the mortality hazard ratio of methotrexate with a marginal structural Cox proportional hazards model. FINDINGS: 191 individuals died during follow-up. Patients who began treatment with methotrexate (n=588) had worse prognostic factors for mortality. After adjustment for this confounding by indication, the mortality hazard ratio for methotrexate use compared with no methotrexate use was 0.4 (95% CI 0.2-0.8). Other conventional disease-modifying antirheumatic drugs did not have a significant effect on mortality. The hazard ratio of methotrexate use for cardiovascular death was 0.3 (0.2-0.7), whereas that for non-cardiovascular deaths was 0.6 (0.2-1.2). INTERPRETATION: Our data indicate that methotrexate may provide a substantial survival benefit, largely by reducing cardiovascular mortality. This survival benefit of methotrexate would set a standard against which new disease-modifying antirheumatic drugs could be compared.

Antirheumatic Agents↗

A cost effectiveness analysis of treatment options for methotrexate-naive rheumatoid arthritis.

OBJECTIVE: New treatment options for patients with methotrexate (MTX)-naive rheumatoid arthritis (RA) have become available. Given wide variability in efficacy and cost among different treatment options, we sought to determine their relative cost effectiveness to help guide policy in different cost constrained settings. METHODS: We performed a cost effectiveness analysis comparing 5 monotherapy options for patients with MTX-naive RA: (1) etanercept, (2) leflunomide, (3) MTX (up to 15 mg weekly), (4) sulfasalazine (SSZ), and (5) no second line agent. A decision analysis model was used with a time horizon of 6 months. We employed 2 measures of effectiveness based on published clinical trial data: American College of Rheumatology (ACR) 20% response proportion (ACR 20) and a weighted average of proportions achieving ACR 70, ACR 50, and ACR 20 (ACR 70 weighted response, ACR 70WR). Incremental cost effectiveness ratios were calculated as additional cost per patient achieving either outcome, compared with the next most expensive option. RESULTS: In both base case analyses employing ACR 20 and ACR 70WR as effectiveness measures, MTX and SSZ both cost less and were more effective (i.e., cost saving) than no second line agent. Leflunomide cost more and was less efficacious than SSZ (dominated) in analyses using either outcome. The most efficacious option, etanercept, cost US $41,900 per ACR 20 and $40,800 per ACR 70 WR compared with SSZ and MTX, respectively. When we included only direct costs in analyses, the least expensive non-dominated option was SSZ with incremental cost effectiveness ratios of US $900 per ACR 20 and $1500 per ACR 70WR compared with no second line agent. Overall, relative cost effectiveness between MTX and SSZ was sensitive to variation in relevant variables in sensitivity analyses. Otherwise, our extensive sensitivity analyses did not substantially affect the base case results. CONCLUSION: MTX is cost effective (cost saving vs the no second line agent option) for MTX-naive RA in achieving ACR 20 or ACR 70WR over a 6 month period. Based on available data, the relative cost effectiveness between SSZ and MTX cannot be determined with reasonable certainty and SSZ therapy appears to be as cost effective as MTX (cost saving) in achieving ACR outcomes over a 6 month period. The most efficacious option, etanercept, incurs much higher incremental costs per ACR 20 or ACR 70WR than other options analyzed. Whether etanercept compared with MTX is cost effective depends on whether > $40,000 per ACR 20 or ACR 70WR over a 6 month period is considered acceptable.

Analysis of Variance↗