Use of Antidiabetic drugs during pregnancy among U.S. women with Livebirth deliveries in the Mini-Sentinel system.

BACKGROUND: As the prevalence of diabetes mellitus increases in the population, the exposure to antidiabetic drugs (ADDs) during pregnancies is expected to grow, as has been seen over the last decade. The objective of this study was to estimate the prevalence of ADD use during pregnancy among women in the Mini-Sentinel Distributed Database (MSDD) who delivered a liveborn infant. METHODS: We identified qualifying livebirth pregnancies among women aged 10 to 54 years in the MSDD from 2001 to 2013. ADD use was estimated using outpatient pharmacy dispensing claims and days-supplied among three cohorts: all livebirth pregnancies, pregnancies among women with pre-existing diabetes, and pregnancies among women without prior ADD use. RESULTS: Among the 1.9 million pregnancies in the MSDD that resulted in a livebirth from 2001 to 2013, 4.4% were exposed to an ADD. Of the 15,606 pregnancies (0.8%) with pre-existing diabetes, 92.8% were also exposed during the pregnancy period. The most commonly used product in these pregnancies was insulin (75.6% of pregnancies). In contrast, in pregnancies of women without prior ADD use, the most commonly used products were glyburide and insulin, and most of these users were diagnosed with gestational diabetes. CONCLUSIONS: Patterns of ADD use during pregnancy described here, along with changes in disease incidence and management, highlight the importance of continuing surveillance of ADD utilization patterns and examining the safety and effectiveness of these products in pregnancy.

Comparative Stroke, Bleeding, and Mortality Risks in Older Medicare Patients Treated with Oral Anticoagulants for Nonvalvular Atrial Fibrillation.

BACKGROUND: Nonvitamin K antagonist oral anticoagulants (NOACs) are alternatives to warfarin in patients with nonvalvular atrial fibrillation. Randomized trials compared NOACs with warfarin, but none have compared individual NOACs against each other for safety and effectiveness. METHODS: We performed a retrospective new-user cohort study of patients with nonvalvular atrial fibrillation enrolled in US Medicare who initiated warfarin (n = 183,318), or a standard dose of dabigatran (150 mg twice daily; n = 86,198), rivaroxaban (20 mg once daily; n = 106,389), or apixaban (5 mg twice daily; n = 73,039) between October 2010 and September 2015. Propensity score-adjusted Cox proportional hazards regression was used to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CI) for the outcomes of thromboembolic stroke, intracranial hemorrhage, major extracranial bleeding, and all-cause mortality, comparing each NOAC with warfarin, and with each other NOAC. RESULTS: Compared with warfarin, each NOAC was associated with reduced risks of thromboembolic stroke (20%-29% reduction; P = .002 [dabigatran], P < 0.001 [rivaroxaban, apixaban]), intracranial hemorrhage (35%-62% reduction; P < 0.001 [each NOAC]), and mortality (19%-34% reduction; P < .001 [each NOAC]). The NOACs were similar for thromboembolic stroke but rivaroxaban was associated with increased risks of intracranial hemorrhage (vs dabigatran: HR = 1.71; 95% CI, 1.35-2.17), major extracranial bleeding (vs dabigatran: HR = 1.32; 95% CI, 1.21-1.45; vs apixaban: HR = 2.70; 95% CI, 2.38-3.05), and death (vs dabigatran: HR = 1.12; 95% CI, 1.01-1.24; vs apixaban: HR = 1.23; 95% CI, 1.09-1.38). Dabigatran was associated with reduced risk of intracranial hemorrhage (HR = 0.70; 95% CI ,0.53-0.94) and increased risk of major extracranial bleeding (HR = 2.04; 95% CI, 1.78-2.32) compared with apixaban. CONCLUSIONS: Among patients treated with standard-dose NOAC for nonvalvular atrial fibrillation and warfarin users with similar baseline characteristics, dabigatran, rivaroxaban, and apixaban were associated with a more favorable benefit-harm profile than warfarin. Among NOAC users, dabigatran and apixaban were associated with a more favorable benefit-harm profile than rivaroxaban.

Safety assessment of niacin in the US Food and Drug Administration's mini-sentinel system.

PURPOSE: The Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events (HPS2-THRIVE) trial found higher incidence rates of adverse reactions, including bleeding, in patients receiving the combination of extended-release niacin and laropiprant versus placebo. It is not known whether these adverse events are attributable to laropiprant, not approved in the USA, or to extended-release niacin. We compared rates of major gastrointestinal bleeding and intracranial hemorrhage among initiators of extended-release niacin and initiators of fenofibrate. METHODS: We used Mini-Sentinel (now Sentinel) to conduct an observational, new user cohort analysis. We included data from 5 Data Partners covering the period from January 1, 2007 to August 31, 2013. Individuals who initiated extended-release niacin were propensity score-matched to individuals who initiated fenofibrate. Within the matched cohorts, we used Cox proportional hazards models to compare rates of hospitalization for major gastrointestinal bleeding events and intracranial hemorrhage assessed using validated claims-based algorithms. RESULTS: A total of 234 242 eligible extended-release niacin initiators were identified, of whom 210 389 (90%) were 1:1 propensity score-matched to eligible fenofibrate initiators. In propensity score-matched analyses, no differences were observed between exposure groups in rates of major gastrointestinal bleeding (hazard ratio [HR], 0.98; 95% confidence interval [CI], 0.82 to 1.18) or intracranial hemorrhage (HR, 1.21; 95% CI, 0.66 to 2.22). Results were similar in pre-specified sensitivity and subgroup analyses. CONCLUSIONS: We did not observe evidence for an association between extended-release niacin versus fenofibrate and rates of major gastrointestinal bleeding or intracranial hemorrhage.

Stroke, Bleeding, and Mortality Risks in Elderly Medicare Beneficiaries Treated With Dabigatran or Rivaroxaban for Nonvalvular Atrial Fibrillation.

Importance: Dabigatran and rivaroxaban are non-vitamin K oral anticoagulants approved for stroke prevention in patients with nonvalvular atrial fibrillation (AF). There are no randomized head-to-head comparisons of these drugs for stroke, bleeding, or mortality outcomes. Objective: To compare risks of thromboembolic stroke, intracranial hemorrhage (ICH), major extracranial bleeding including major gastrointestinal bleeding, and mortality in patients with nonvalvular AF who initiated dabigatran or rivaroxaban treatment for stroke prevention. Design, Setting, and Participants: Retrospective new-user cohort study of 118 891 patients with nonvalvular AF who were 65 years or older, enrolled in fee-for-service Medicare, and who initiated treatment with dabigatran or rivaroxaban from November 4, 2011, through June 30, 2014. Differences in baseline characteristics were adjusted using stabilized inverse probability of treatment weights based on propensity scores. The data analysis was performed from May 7, 2015, through June 30, 2016. Exposures: Dabigatran, 150 mg, twice daily; rivaroxaban, 20 mg, once daily. Main Outcomes and Measures: Adjusted hazard ratios (HRs) for the primary outcomes of thromboembolic stroke, ICH, major extracranial bleeding including major gastrointestinal bleeding, and mortality, with dabigatran as reference. Adjusted incidence rate differences (AIRDs) were also estimated. Results: A total of 52 240 dabigatran-treated and 66 651 rivaroxaban-treated patients (47% female) contributed 15 524 and 20 199 person-years of on-treatment follow-up, respectively, during which 2537 primary outcome events occurred. Rivaroxaban use was associated with a statistically nonsignificant reduction in thromboembolic stroke (HR, 0.81; 95% CI, 0.65-1.01; P = .07; AIRD = 1.8 fewer cases/1000 person-years), statistically significant increases in ICH (HR, 1.65; 95% CI, 1.20-2.26; P = .002; AIRD = 2.3 excess cases/1000 person-years) and major extracranial bleeding (HR, 1.48; 95% CI, 1.32-1.67; P < .001; AIRD = 13.0 excess cases/1000 person-years), including major gastrointestinal bleeding (HR, 1.40; 95% CI, 1.23-1.59; P < .001; AIRD = 9.4 excess cases/1000 person-years), and with a statistically nonsignificant increase in mortality (HR, 1.15; 95% CI, 1.00-1.32; P = .051; AIRD = 3.1 excess cases/1000 person-years). In patients 75 years or older or with CHADS2 score greater than 2, rivaroxaban use was associated with significantly increased mortality compared with dabigatran use. The excess rate of ICH with rivaroxaban use exceeded its reduced rate of thromboembolic stroke. Conclusions and Relevance: Treatment with rivaroxaban 20 mg once daily was associated with statistically significant increases in ICH and major extracranial bleeding, including major gastrointestinal bleeding, compared with dabigatran 150 mg twice daily.

Comparative Risk of Anaphylactic Reactions Associated With Intravenous Iron Products.

IMPORTANCE: All intravenous (IV) iron products are associated with anaphylaxis, but the comparative safety of each product has not been well established. OBJECTIVE: To compare the risk of anaphylaxis among marketed IV iron products. DESIGN, SETTING, AND PARTICIPANTS: Retrospective new user cohort study of IV iron recipients (n = 688,183) enrolled in the US fee-for-service Medicare program from January 2003 to December 2013. Analyses involving ferumoxytol were limited to the period January 2010 to December 2013. EXPOSURES: Administrations of IV iron dextran, gluconate, sucrose, or ferumoxytol as reported in outpatient Medicare claims data. MAIN OUTCOMES AND MEASURES: Anaphylaxis was identified using a prespecified and validated algorithm defined with standard diagnosis and procedure codes and applied to both inpatient and outpatient Medicare claims. The absolute and relative risks of anaphylaxis were estimated, adjusting for imbalances among treatment groups. RESULTS: A total of 274 anaphylaxis cases were identified at first exposure, with an additional 170 incident anaphylaxis cases identified during subsequent IV iron administrations. The risk for anaphylaxis at first exposure was 68 per 100,000 persons for iron dextran (95% CI, 57.8-78.7 per 100,000) and 24 per 100,000 persons for all nondextran IV iron products combined (iron sucrose, gluconate, and ferumoxytol) (95% CI, 20.0-29.5 per 100,000) , with an adjusted odds ratio (OR) of 2.6 (95% CI, 2.0-3.3; P < .001). At first exposure, when compared with iron sucrose, the adjusted OR of anaphylaxis for iron dextran was 3.6 (95% CI, 2.4-5.4); for iron gluconate, 2.0 (95% CI 1.2, 3.5); and for ferumoxytol, 2.2 (95% CI, 1.1-4.3). The estimated cumulative anaphylaxis risk following total iron repletion of 1000 mg administered within a 12-week period was highest with iron dextran (82 per 100,000 persons, 95% CI, 70.5- 93.1) and lowest with iron sucrose (21 per 100,000 persons, 95% CI, 15.3- 26.4). CONCLUSIONS AND RELEVANCE: Among patients in the US Medicare nondialysis population with first exposure to IV iron, the risk of anaphylaxis was highest for iron dextran and lowest for iron sucrose.

Cardiovascular, bleeding, and mortality risks in elderly Medicare patients treated with dabigatran or warfarin for nonvalvular atrial fibrillation.

BACKGROUND: The comparative safety of dabigatran versus warfarin for treatment of nonvalvular atrial fibrillation in general practice settings has not been established. METHODS AND RESULTS: We formed new-user cohorts of propensity score-matched elderly patients enrolled in Medicare who initiated dabigatran or warfarin for treatment of nonvalvular atrial fibrillation between October 2010 and December 2012. Among 134 414 patients with 37 587 person-years of follow-up, there were 2715 primary outcome events. The hazard ratios (95% confidence intervals) comparing dabigatran with warfarin (reference) were as follows: ischemic stroke, 0.80 (0.67-0.96); intracranial hemorrhage, 0.34 (0.26-0.46); major gastrointestinal bleeding, 1.28 (1.14-1.44); acute myocardial infarction, 0.92 (0.78-1.08); and death, 0.86 (0.77-0.96). In the subgroup treated with dabigatran 75 mg twice daily, there was no difference in risk compared with warfarin for any outcome except intracranial hemorrhage, in which case dabigatran risk was reduced. Most patients treated with dabigatran 75 mg twice daily appeared not to have severe renal impairment, the intended population for this dose. In the dabigatran 150-mg twice daily subgroup, the magnitude of effect for each outcome was greater than in the combined-dose analysis. CONCLUSIONS: In general practice settings, dabigatran was associated with reduced risk of ischemic stroke, intracranial hemorrhage, and death and increased risk of major gastrointestinal hemorrhage compared with warfarin in elderly patients with nonvalvular atrial fibrillation. These associations were most pronounced in patients treated with dabigatran 150 mg twice daily, whereas the association of 75 mg twice daily with study outcomes was indistinguishable from warfarin except for a lower risk of intracranial hemorrhage with dabigatran.

Use of an active surveillance system by the FDA to observe patterns of quinine sulfate use and adverse hematologic outcomes in CMS Medicare data.

PURPOSE: In 2005, the Food and Drug Administration approved Qualaquin (quinine) for treatment of malaria and later ordered unapproved quinine formulations off the market. In 2009, labeling for Qualaquin added a warning for use for leg cramps, as serious hematologic reactions could occur. We examined quinine use trends among Medicare beneficiaries focusing on indications for use and associations with adverse hematologic outcomes. METHODS: Medicare beneficiaries, aged 65 years and older, in 2006-2012, were included in incident quinine or comparator, diltiazem, cohorts if 183 days prior to dispensing, they were enrolled in Medicare, had no dispensing of quinine, diltiazem, ticlodipine, clopidogrel, and sulfonamide drugs, and had no diagnoses of thrombocytopenia, immune thrombocytopenic purpura (ITP), thrombotic microangiopathy (TMA), or hemolytic-uremic syndrome (HUS). Diagnoses of malaria or leg cramps were observed during 183 days prior to index dispensing. Outcomes of ITP, TMA, or HUS in inpatient or emergency room settings were then observed during drug use. RESULTS: Prevalent use of quinine decreased by 99%, from 419 675 to 6036 users during 2006-2012. Of 88 066 quinine users, 9 had diagnoses of malaria and 36 218 had leg cramps. Incidence rates (per 1000 person-years) for ITP were quinine 1.67 and diltiazem 0.40 [incidence rate ratio 4.2 (95% confidence interval 2.5, 6.5)], for TMA were quinine 0.23 and diltiazem 0.03 [incidence rate ratio 6.9 (95% confidence interval 1.3, 24.0)], and for HUS were quinine 0 and diltiazem 0.01. CONCLUSIONS: Use of quinine decreased substantially, although diagnoses of leg cramps persist. To our knowledge, this is the first demonstration of an association for quinine and ITP and TMA in claims data.

Implicit value judgments in the measurement of health inequalities.

CONTEXT: Quantitative estimates of the magnitude, direction, and rate of change of health inequalities play a crucial role in creating and assessing policies aimed at eliminating the disproportionate burden of disease in disadvantaged populations. It is generally assumed that the measurement of health inequalities is a value-neutral process, providing objective data that are then interpreted using normative judgments about whether a particular distribution of health is just, fair, or socially acceptable. METHODS: We discuss five examples in which normative judgments play a role in the measurement process itself, through either the selection of one measurement strategy to the exclusion of others or the selection of the type, significance, or weight assigned to the variables being measured. FINDINGS: Overall, we find that many commonly used measures of inequality are value laden and that the normative judgments implicit in these measures have important consequences for interpreting and responding to health inequalities. CONCLUSIONS: Because values implicit in the generation of health inequality measures may lead to radically different interpretations of the same underlying data, we urge researchers to explicitly consider and transparently discuss the normative judgments underlying their measures. We also urge policymakers and other consumers of health inequalities data to pay close attention to the measures on which they base their assessments of current and future health policies.

Impact of socioeconomic status on cancer incidence and stage at diagnosis: selected findings from the surveillance, epidemiology, and end results: National Longitudinal Mortality Study.

BACKGROUND: Population-based cancer registry data from the Surveillance, Epidemiology, and End Results (SEER) Program at the National Cancer Institute (NCI) are mainly based on medical records and administrative information. Individual-level socioeconomic data are not routinely reported by cancer registries in the United States because they are not available in patient hospital records. The U.S. representative National Longitudinal Mortality Study (NLMS) data provide self-reported, detailed demographic and socioeconomic data from the Social and Economic Supplement to the Census Bureau's Current Population Survey (CPS). In 1999, the NCI initiated the SEER-NLMS study, linking the population-based SEER cancer registry data to NLMS data. The SEER-NLMS data provide a new unique research resource that is valuable for health disparity research on cancer burden. We describe the design, methods, and limitations of this data set. We also present findings on cancer-related health disparities according to individual-level socioeconomic status (SES) and demographic characteristics for all cancers combined and for cancers of the lung, breast, prostate, cervix, and melanoma. METHODS: Records of cancer patients diagnosed in 1973-2001 when residing 1 of 11 SEER registries were linked with 26 NLMS cohorts. The total number of SEER matched cancer patients that were also members of an NLMS cohort was 26,844. Of these 26,844 matched patients, 11,464 were included in the incidence analyses and 15,357 in the late-stage diagnosis analyses. Matched patients (used in the incidence analyses) and unmatched patients were compared by age group, sex, race, ethnicity, residence area, year of diagnosis, and cancer anatomic site. Cohort-based age-adjusted cancer incidence rates were computed. The impact of socioeconomic status on cancer incidence and stage of diagnosis was evaluated. RESULTS: Men and women with less than a high school education had elevated lung cancer rate ratios of 3.01 and 2.02, respectively, relative to their college educated counterparts. Those with family annual incomes less than $12,500 had incidence rates that were more than 1.7 times the lung cancer incidence rate of those with incomes $50,000 or higher. Lower income was also associated with a statistically significantly increased risk of distant-stage breast cancer among women and distant-stage prostate cancer among men. CONCLUSIONS: Socioeconomic patterns in incidence varied for specific cancers, while such patterns for stage were generally consistent across cancers, with late-stage diagnoses being associated with lower SES. These findings illustrate the potential for analyzing disparities in cancer outcomes according to a variety of individual-level socioeconomic, demographic, and health care characteristics, as well as by area measures available in the linked database.

An overview of methods for monitoring social disparities in cancer with an example using trends in lung cancer incidence by area-socioeconomic position and race-ethnicity, 1992-2004.

The authors provide an overview of methods for summarizing social disparities in health using the example of lung cancer. They apply four measures of relative disparity and three measures of absolute disparity to trends in US lung cancer incidence by area-socioeconomic position and race-ethnicity from 1992 to 2004. Among females, measures of absolute and relative disparity suggested that area-socioeconomic and race-ethnic disparities increased over these 12 years but differed widely with respect to the magnitude of the change. Among males, the authors found substantial disagreement among summary measures of relative disparity with respect to the magnitude and the direction of change in disparities. Among area-socioeconomic groups, the index of disparity increased by 47% and the relative concentration index decreased by 116%, while for race-ethnicity the index of disparity increased by 36% and the Theil index increased by 13%. The choice of a summary measure of disparity may affect the interpretation of changes in health disparities. Important issues to consider are the reference point from which differences are measured, whether to measure disparity on the absolute or relative scale, and whether to weight disparity measures by population size. A suite of indicators is needed to provide a clear picture of health disparity change.

Dental insurance and clinical dental outcomes in NHANES III.

OBJECTIVES: The National Health and Nutrition Examination Survey (NHANES III) 1988-1994 is one of the few nationally representative data sets with information on both private dental insurance and a clinical dental exam. The objective of this analysis was to examine the possible associations between private dental insurance and clinical exam outcomes, demographic variables, and dental visits. METHODS: Using NHANES III data, analysis was limited to persons aged 20 years or older who had a dental exam and reported on their private dental insurance status. Initial analyses were based on comparisons between those with and without private dental insurance. Propensity scoring method was used to examine the effects of dental insurance on clinical exam variables. RESULTS: The percentage of individuals with private dental insurance was significantly greater among non-Hispanic blacks, those with higher educational attainment, those living at/above the federal poverty level, and those with a dental visit in the past year compared to their respective counterparts. Those with untreated caries, those with a loss of attachment of greater than 4 mm, and those with 12-27 missing teeth were significantly less likely to have dental insurance (p < 0.05) than their respective counterparts. CONCLUSIONS: These results suggest that having private dental insurance is associated with better clinical oral health status.