Diane L. McNally

Prevalence of Thyrotoxicosis, Antithyroid Medication Use, and Complications Among Pregnant Women in the United States

BACKGROUND Population-based estimates of the prevalence of thyrotoxicosis (TTX), the frequency of antithyroid drug (ATD) use, and risk of adverse events in pregnant women and their infants are lacking. Therefore, our objective was to obtain epidemiologic estimates of these parameters within a large population-based sample of pregnant women with TTX. METHODS A retrospective claims analysis was performed from the MarketScan Commercial Claims and Encounters health insurance database for the period 2005-2009. Women aged 15-44 years, enrolled for at least 2 years, and who had a pregnancy during the study period were included. Diagnosis of TTX was based on International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes using narrow (TTX-1=ICD 242.0) and broad (TTX-2=ICD 242.0 or 242.9) definitions. ATD use was based on prescriptions filled for propylthiouracil (PTU) or methimazole (MMI). Adverse events in mothers and infants were determined from the ICD-9-CM diagnosis codes recorded on submitted claims. RESULTS The database contained 904,497 eligible women. The average yearly prevalence per 1000 pregnant women was 2.46 for TTX-1 and 5.88 for TTX-2. Thirty-nine percent used ATD at any time during the study period. Compared to women without a TTX diagnosis, there was more than a twofold increase for liver disease among women with TTX (odds ratio [OR]=2.08, p<0.001) and a 13% increased risk for congenital anomalies (OR=1.13, p=0.014), but no association was observed with ATD use. The rates of congenital defects (per 1000 infants) associated with ATD use were 55.6 for MMI, 72.1 for PTU, and 65.8 for untreated women with TTX, compared to 58.8 among women without TTX. CONCLUSIONS There was some indication of an elevated risk of liver disease and congenital anomalies in women with TTX, but the risk did not appear to be related to the ATD use. There seems to be a higher pregnancy termination rate for women with TTX on MMI, which likely reflects elective pregnancy terminations.

Erythropoiesis-stimulating agents are not associated with increased risk of thrombosis in patients with myelodysplastic syndromes

Background There are limited reports of thrombosis among myelodysplastic syndrome patients exposed to erythropoiesis stimulating agents. It is not clear whether erythropoiesis stimulating agents are associated with an increased risk of thrombosis in myelodysplastic syndromes, as they are among patients with solid tumors. Design and Methods The association between use of erythropoiesis stimulating agent and transient thrombosis risk in patients with myelodysplastic syndromes was assessed in a case-crossover study nested within a cohort of incident myelodysplastic syndrome patients. Using the US Surveillance, Epidemiology, and End Results Medicare-linked database, cases with an incident diagnosis of deep vein thrombosis were identified. Using conditional logistical regression, the odds of exposure to erythropoiesis stimulating agents in the 12 weeks prior to the incident deep vein thrombosis (hazard period) was compared to the exposure odds in a prior 12-week comparison period. Results Within the cohort of eligibles with myelodysplastic syndromes (n=5,673) there were 212 incident cases of deep vein thrombosis events. Mean age was 76.2 (standard deviation=±8.6) years. Use of erythropoiesis stimulating agents was not associated with deep vein thrombosis in the crude nor the adjusted models (OR=1.21, 95% CI: 0.60, 2.43). Central venous catheter placement (OR=6.47, 95% CI: 2.37, 17.62) and red blood cell transfusion (OR=4.60, 95% CI: 2.29, 9.23) were associated with deep vein thrombosis. Conclusions Despite the link between use of erythropoiesis stimulating agents and thrombosis among patients with solid tumors, this study provides evidence that their safety profile may be different among patients with myelodysplastic syndromes.

Lenalidomide performance in the real world: patterns of use and effectiveness in a Medicare population with myelodysplastic syndromes.

Lenalidomide is approved for the treatment of anemia with transfusion dependence (TD) in patients with lower‐risk myelodysplastic syndrome (MDS) with 5q deletion (del5q‐MDS), but its “real‐life” use and effect on transfusion needs are unclear. In the current study, the authors examined its use in the Medicare population.

Skeletal-related events and mortality among older men with advanced prostate cancer

OBJECTIVE Skeletal-related events (SREs) are defined as a cluster of events including clinical diagnoses and treatment. Using claims data, the burden of SREs as a group has been reported among patients with cancer. We investigate the mortality impact of subcomponents of SREs, a topic that has received limited attention among older men. MATERIALS AND METHODS We analyzed prostate cancer (PCa) and all-cause mortality among men diagnosed with metastatic PCa from 2000 to 2007 using Surveillance, Epidemiology, and End Results data linked with 1999-2009 Medicare data. We created three measures of pathological fracture (PF), spinal cord compression (SCC), and bone surgery (BS) that differed in the use of claims-based bone metastasis information. We reported covariate-adjusted hazard ratios (HRs) using the full sample and a propensity score-matched sample (PSMS). RESULTS Application of inclusion/exclusion criteria resulted in 7062 men in the full sample (1776 in the PSMS). PCa-specific (all-cause mortality) was 54% (80%) at a median follow-up of 609days. SRE prevalence ranged from 9.7% to 17.1% across the measures. In a PCa mortality model, the HR associated with an SRE ranged from 1.07 (0.98-1.16) to 1.31 (1.18-1.45). The HRs for SCC and PF were statistically significant and positively associated with PCa-specific mortality. The results for BS depended on the measure. Results for SCC and BS, but not for PF, were preserved using a PSMS. CONCLUSIONS The relationship between SREs and mortality among older men with metastatic PCa was driven by SCC and depended on the definition used to measure SREs.

Patient and physician characteristics associated with erythropoiesis-stimulating agent use in patients with myelodysplastic syndromes

Patient and physician characteristics associated with use of erythropoiesis-stimulating agents in myelodysplastic syndrome patients have not yet been described. Myelodysplastic syndrome patients diagnosed from 2001 to 2005 were identified from the Surveillance Epidemiology and End Results-Medicare database. Multivariate regressions examined the association between patient and physician characteristics and the probability of receiving any erythropoiesis-stimulating agents, and of receiving therapeutic-length (≥8 week) treatment episodes. Among the 6,588 myelodysplastic syndrome patients studied, 65% received erythropoiesis-stimulating agents. Use of erythropoiesis-stimulating agents was lower for blacks compared to whites (OR 0.78; 95% CI:0.61–0.99), single persons compared to married (OR 0.77; 95% CI:0.62–0.97), Medicaid recipients (OR 0.66; 95% CI:0.55–0.79), and those living in census tracts with lower educational attainment. Patients who did not consult a hematology-oncology specialist were less likely to receive erythropoiesis-stimulating agents. Specialist access, financial resources and mobility are key determinants of receipt of erythropoiesis-stimulating agents among myelodysplastic syndrome patients.

Asthma-related medication use among children in the United States

BACKGROUND Asthma is one of the most common chronic conditions in children and has a major impact on health care use and quality of life. The Best Pharmaceuticals for Children Act mandates the federal government to sponsor pediatric studies of drugs approved for use in the United States but lacking evaluation in the pediatric population and lacking interest of commercial sponsors. As input into the drug selection and prioritization process, information is needed on the percentage of children who receive asthma-related medications. OBJECTIVE To estimate the percentage of children who receive asthma-related medications. METHODS Retrospective analysis of outpatient medical and drug claims from members of commercial health care insurance plans enrolled any time from January 1, 2004, through December 31, 2005. The study population included 4,259,103 children throughout the United States aged birth through 17 years. RESULTS Fifteen percent of all children were dispensed an asthma-related medication. Among 218,943 children with an asthma diagnosis, 188,286 (86%) had a dispensed asthma-related medication at any time during the 2-year study period. Among children without any asthma diagnoses, 398,880 (10%) had a dispensed medication. Fifty-nine percent of children with an asthma diagnosis were dispensed an anti-inflammatory medication within 90 days after a claim with a diagnosis of asthma. CONCLUSIONS Asthma-related medications are dispensed to a large percentage of the pediatric population, including many who do not have claims with asthma diagnoses listed. Data on the pharmacokinetics and safety of these drugs in children are largely unknown and difficult to obtain. Clinical studies that use new tools and approaches are needed to resolve this information gap.

43 The broad use of erythropoietic stimulating agents (ESA) for myelodysplastic syndromes (MDS) in the U.S. is not consistent with guidelines

3. We developed a novel epigenetic profiling-based flow cytometry to measure expressions of nuclear factors at the single cell level. Conclusion: Epigenetic regulatory mechanisms including DNA and histone methylations are important for regulating expression of RUNX1 and PU.1. Identification of epigenetic alterations on these factor encoding genes indicates the importance of epigenetic disregulation in the pathogenesis of MDS.

Chemotherapy Treatment and Survival in Estrogen Receptor Negative Metastatic Breast Cancer: A Population-Based Analysis.

Introduction: Although controlled clinical trials have demonstrated a beneficial effect of various chemotherapy regimens on survival in breast cancer (BC), little is known about treatment patterns and survival benefit in the “real world” population of elderly women with metastatic BC. Methods: We identified female Medicare beneficiaries aged ≥66 years with metastatic BC diagnosed from 1999 to 2005 in the Surveillance, Epidemiology and End Results cancer registries (SEER). Patients with a prior history of any cancer were excluded. Treatment-related data were abstracted from linked Medicare claims. Since Medicare claims have incomplete information on oral selective estrogen receptor modulators, we limited our study cohort to estrogen receptor negative (ER-) women. Chemotherapy was defined as the receipt of any chemotherapeutic regimen within 6 months after diagnosis. Initial regimens were characterized based on drugs given during the first 30 days of chemotherapy. We used a continuous-time interval-censored survival analysis to determine the effect of chemotherapy on hazard of any-cause death, controlling for sociodemographic and clinical factors, including proxy measures for performance status. Results: We identified 1518 ER(-) women diagnosed with metastatic BC in SEER. Mean age was 77.6 (SD 7.6) years, 84% were white race and 27% were married at the time of diagnosis. Of the 1518 metastatic ER(-) BC patients, 493 (32%) received chemotherapy. As compared to women who did not receive chemotherapy, women who received chemotherapy were more likely to be younger, married, have lower pre-cancer comorbidity as measured by the Charlson comorbidity index, have seen an oncology specialist and have cancer-directed surgery or radiation prior to chemotherapy. Initial regimens comprised predominantly one (31%) or two (46%) drug classes. The most common regimens were taxanes only (18%), anthracycline+alkylating agents (17%) and antimetabolite+alkylating agent (9%). Overall median followup time was 7 months; 1223 women (81%) died during followup. Median survival time was 5 months among women who did not receive chemotherapy and 15 months among women who received chemotherapy. Chemotherapy was associated with a statistically significant survival benefit (adjusted Hazard Ratio 0.61, 95% confidence interval 0.54, 0.70). Conclusion: In this population-based study of older women, there was a variety of chemotherapy regimens used for metastatic ER(-) BC. Chemotherapy received within 6 months after diagnosis was associated with a 39% reduction in hazard of death. These findings reflect chemotherapy use outside of the clinical trial setting and have important clinical and policy implications for the study of treatments among older women with advanced BC. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2064.