Trimethoprim-sulfonamide use during the first trimester of pregnancy and the risk of congenital anomalies.

BACKGROUND: Sulfonamide antibacterials are widely used in pregnancy, but evidence about their safety is mixed. The objective of this study was to assess the association between first-trimester sulfonamide exposure and risk of specific congenital malformations. METHODS: Mother-infant pairs were selected from a cohort of 1.2 million live-born deliveries (2001-2008) at 11 US health plans comprising the Medication Exposure in Pregnancy Risk Evaluation Program. Mothers with first-trimester trimethoprim-sulfonamide (TMP-SUL) exposures were randomly matched 1:1 to (i) a primary comparison group (mothers exposed to penicillins and/or cephalosporins) and (ii) a secondary comparison group (mothers with no dispensing of an antibacterial, antiprotozoal, or antimalarial medication during the same time period). The outcomes were cardiovascular abnormalities, cleft palate/lip, clubfoot, and urinary tract abnormalities. RESULTS: We first identified 7615 infants in the TMP-SUL exposure group, of which 7595 (99%) were exposed to a combination of TMP-SUL and the remaining 1% to sulfonamides alone. After matching (1:1) to the comparator groups and only including those with complete data on covariates, there were 20 064 (n = 6688 per group) in the primary analyses. Overall, cardiovascular defects (1.52%) were the most common and cleft lip/palate (0.10%) the least common that were evaluated. Compared with penicillin/cephalosporin exposure, and no antibacterial exposure, TMP-SUL exposure was not associated with statistically significant elevated risks for cardiovascular, cleft lip/palate, clubfoot, or urinary system defects. CONCLUSIONS: First-trimester TMP-SUL exposure was not associated with a higher risk of the congenital anomalies studied, compared with exposure to penicillins and/or cephalosporins, or no exposure to antibacterials.

Synergistic effect of statins and postmenopausal hormone therapy in the prevention of skeletal fractures in elderly women.

STUDY OBJECTIVE: To examine the role of concurrent 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) use and postmenopausal hormone therapy on osteoporosis-related fractures. DESIGN: Case-control study. Data Source. Large integrated health plan in New Mexico. Patients. Case patients were 1001 women with incident fractures of the hip, wrist, forearm, or spine that occurred between January 1, 2000, and December 31, 2005, and controls were 2607 women without fractures during the same time frame; both groups were selected from the same population of women aged 50 years or older who utilized health plan services during the study time frame. MEASUREMENTS AND MAIN RESULTS: Postmenopausal hormone therapy use was classified as "current" (12 mo before index date) or "never or past." The risk of fractures was ascertained among continuous (> or = 80% medication possession ratio during 12 mo before the index date) and current (3 mo before index date) statin users relative to patients without hyperlipidemia who did not use lipid-lowering drugs. The interaction between statins and hormone therapy was examined in multivariable logistic regression. The association between statin use and fractures was examined separately among current and never or past hormone therapy users after controlling for other risk factors. Nineteen percent of the study participants were current hormone therapy users; 9.5% were current and 4.8% were continuous statin users. No association between continuous statin use and fractures was observed among never or past hormone therapy users (odds ratio [OR] 0.80, 95% confidence interval [CI] 0.53-1.22). In contrast, a strong protective effect (OR 0.19, 95% CI 0.04-0.87) was observed among women who concurrently used statins and hormone therapy for 1 year, independent of age; corticosteroid, bisphosphonate, thiazide diuretic, calcitonin, methotrexate, or antiepileptic drug use; chronic kidney disease; and Charlson comorbidity index. CONCLUSION: Concurrent statin use and hormone therapy may have a synergistic protective effect on skeletal fractures beyond the additive effect of each individual therapy.

Impact of a seizure disorder disease management program on patient-reported quality of life.

The objective of this study was to evaluate the impact of a comprehensive, multifaceted disease management program on self-reported quality of life (QOL) for adult patients with epilepsy. The study (1996-2000) employed a quasi-experimental research design in which primary care clinics in a southwestern integrated delivery system were assigned to either the intervention or comparison group. The impact evaluation involved a comparison of responses to a validated QOL survey before and after a disease management intervention for adult health plan members with epilepsy. The intervention consisted of both formal provider training and associated tools and reinforcements as well as direct-to-patient interventions, including a comprehensive education booklet, a seizure diary, a patient education class, and a resource list. Pre-post analysis utilizing paired t-tests was conducted to identify any pre-post differences in QOL for both the intervention and comparison group patients, as measured by the seven specific domains of the epilepsy QOL instrument (QOLIE-31). The intervention group patients showed statistically significant positive changes in two QOL domains: Seizure Worry (p < 0.001) and Emotional Well-being (p < 0.05). One other domain, Overall Quality of Life, showed improvement in the intervention group that approached statistical significance (p < 0.06). There were no statistically significant changes for the comparison group. A well-designed, comprehensive disease management program can improve patient empowerment and coordination of care between the patient and provider, which resulted in an improvement in quality of life, one of the most central patient outcomes in this difficult disease.