Near real-time surveillance for Guillain-Barré syndrome after influenza vaccination among the Medicare population, 2010/11 to 2013/14.

BACKGROUND: Guillain-Barré syndrome (GBS) is a serious acute demyelinating disease that causes weakness and paralysis. The Food and Drug Administration (FDA) began collaborating with the Centers for Medicare and Medicaid Services (CMS) to develop near real-time vaccine safety surveillance capabilities in 2006 and has been monitoring for the risk of GBS after influenza vaccination for every influenza season since 2008. METHODS: We present results from the 2010/11 to 2013/14 influenza seasons using the Updating Sequential Probability Ratio Test (USPRT), with an overall 1-sided α of 0.05 apportioned equally using a constant alpha-spending plan among 20 consecutive weekly tests, 5 ad hoc tests, and a 26th final end of season test. Observed signals were investigated using the self-controlled risk interval (SCRI) design. RESULTS: Over 15 million people were vaccinated in each influenza season. In the 2010/11 influenza season, we observed an elevated GBS risk during the season, with an end of season SCRI analysis finding a nonsignificant increased risk (RR=1.25, 95% CI: 0.96-1.63). A sensitivity analysis applying the positive predictive value of the ICD-9 code for GBS from the 2009/10 season estimated a RR=1.98 (95% CI: 1.42-2.76). Although the 2010/11 influenza vaccine suggested an increased GBS risk, surveillance of the identical vaccine in the 2011/12 influenza season did not find an increased GBS risk after vaccination. No signal was observed in the subsequent three influenza seasons. CONCLUSIONS: Conducting near real-time surveillance using USPRT has proven to be an excellent method for near real-time GBS surveillance after influenza vaccination, as demonstrated by our surveillance efforts during the 2010/11-2013/14 influenza seasons. In the 2010/2011 influenza season, in addition to the 2009 H1N1 influenza pandemic, using near real-time surveillance we were able to observe a signal early in the influenza season and the method has now become routine.

Babesiosis Occurrence among the Elderly in the United States, as Recorded in Large Medicare Databases during 2006-2013.

BACKGROUND: Human babesiosis, caused by intraerythrocytic protozoan parasites, can be an asymptomatic or mild-to-severe disease that may be fatal. The study objective was to assess babesiosis occurrence among the U.S. elderly Medicare beneficiaries, ages 65 and older, during 2006-2013. METHODS: Our retrospective claims-based study utilized large Medicare administrative databases. Babesiosis occurrence was ascertained by recorded ICD-9-CM diagnosis code. The study assessed babesiosis occurrence rates (per 100,000 elderly Medicare beneficiaries) overall and by year, age, gender, race, state of residence, and diagnosis months. RESULTS: A total of 10,305 elderly Medicare beneficiaries had a recorded babesiosis diagnosis during the eight-year study period, for an overall rate of about 5 per 100,000 persons. Study results showed a significant increase in babesiosis occurrence over time (p<0.05), with the largest number of cases recorded in 2013 (N = 1,848) and the highest rates (per 100,000) in five Northeastern states: Connecticut (46), Massachusetts (45), Rhode Island (42), New York (27), and New Jersey (14). About 75% of all cases were diagnosed from May through October. Babesiosis occurrence was significantly higher among males vs. females and whites vs. non-whites. CONCLUSION: Our study reveals increasing babesiosis occurrence among the U.S. elderly during 2006-2013, with highest rates in the babesiosis-endemic states. The study also shows variation in babesiosis occurrence by age, gender, race, state of residence, and diagnosis months. Overall, our study highlights the importance of large administrative databases in assessing the occurrence of emerging infections in the United States.

Comparative Effectiveness of Cardiac Resynchronization Therapy Defibrillators Versus Standard Implantable Defibrillators in Medicare Patients.

Previous analyses have shown that there is lower mortality with cardiac resynchronization therapy defibrillators (CRT-D) in patients with left bundle branch block (LBBB) but demonstrated mixed results in patients without LBBB. We evaluated the comparative effectiveness of CRT-D versus standard implantable defibrillators (ICDs) separately in patients with LBBB and right bundle branch block (RBBB) using Medicare claims data. Medicare records from CRT-D and ICD recipients from 2002 to 2009 that were followed up for up to 48 months were analyzed. We used propensity scores to match patients with ICD to those with CRT-D. In LBBB, 1:1 matching with replacement resulted in 54,218 patients with CRT-D and 20,763 with ICD, and in RBBB, 1:1 matching resulted in 7,298 patients with CRT-D and 7,298 with ICD. In LBBB, CRT-D had a 12% lower risk of heart failure hospitalization or death (hazard ratio [HR] 0.88, 95% confidence interval 0.86 to 0.90) and 5% lower death risk (HR 0.95, 0.92 to 0.97) compared with ICD. In RBBB, CRT-D had a 15% higher risk of heart failure hospitalization or death (HR 1.15, 1.10 to 1.20) and 13% higher death risk (HR 1.13, 1.07 to 1.18). Sensitivity analysis revealed that accounting for covariates not captured in the Medicare database may lead to increased benefit with CRT-D in LBBB and no difference in RBBB. In conclusion, in a large Medicare population, CRT-D was associated with lower mortality in LBBB but higher mortality in RBBB. The absence of certain covariates, in particular those that determine treatment selection, may affect the results of comparative effectiveness studies using claims data.

Posttransfusion purpura occurrence and potential risk factors among the inpatient US elderly, as recorded in large Medicare databases during 2011 through 2012.

BACKGROUND: Posttransfusion purpura (PTP) is a serious transfusion complication resulting in sudden thrombocytopenia with bleeding. The study's objective was to assess PTP occurrence and potential risk factors among the inpatient US elderly, ages 65 and older, during 2011 through 2012. STUDY DESIGN AND METHODS: This retrospective claims-based study utilized large Medicare databases for calendar years 2011 and 2012. Transfusions of blood and blood components were identified by recorded ICD-9-CM procedure codes and revenue center codes, and PTP was ascertained via ICD-9-CM diagnosis code. Our study evaluated PTP rates (per 100,000 inpatient transfusion stays) among elderly Medicare beneficiaries, overall and by age, sex, race, number of units, and blood components transfused. Multivariate regression analyses were used to assess potential risk factors. RESULTS: Among 4,336,338 inpatient transfusion stays for elderly beneficiaries during the study period, 78 had a PTP diagnosis code recorded, an overall rate of 1.8 per 100,000 stays. PTP occurrence varied by the blood components, units transfused, and other characteristics. Significantly higher odds of PTP were found for platelet (PLT)-containing transfusions, with greater number of units transfused, as well as for elderly with histories of cardiac arrhythmias (odds ratio [OR], 2.65; 95% confidence interval [CI], 1.43-4.93), coagulopathy (OR, 1.79; 95% CI, 1.01-3.21), leukemia (OR, 2.37; 95% CI, 1.07-5.26), transplant (OR, 2.68; 95% CI, 1.41-5.09), and other conditions. CONCLUSION: Our population-based study suggests a substantially higher PTP risk with PLT-containing transfusions. The study also suggests increased PTP risk with greater number of units transfused as well as the importance of underlying health conditions and prior recipient alloimmunization for PTP occurrence among the elderly.

Transfusion-related acute lung injury and potential risk factors among the inpatient US elderly as recorded in Medicare claims data, during 2007 through 2011.

BACKGROUND: Transfusion-related acute lung injury (TRALI) is a serious complication leading to pulmonary edema and respiratory failure. This study's objective was to assess TRALI occurrence and potential risk factors among inpatient US elderly Medicare beneficiaries, ages 65 and older, during 2007 through 2011. STUDY DESIGN AND METHODS: This retrospective claims-based study utilized large Medicare administrative databases. Transfusions were identified by recorded procedure and revenue center codes. TRALI was ascertained via ICD-9-CM diagnosis code. The study evaluated TRALI rates among the inpatient elderly overall and by calendar year, age, sex, race, blood components, and units transfused. Logistic regression analyses were used to assess potential risk factors. RESULTS: Of 11,378,264 inpatient transfusion stays for elderly Medicare beneficiaries, 2556 had a recorded TRALI diagnosis code, an overall rate of 22.46 per 100,000 stays. TRALI rates were higher for platelet (PLT)- and plasma-containing transfusions and increased by year and number of units transfused (p < 0.0001). Significantly higher odds of TRALI were also found for persons ages 65 to 79 years versus more than 79 years (OR, 1.19; 95% confidence interval CI, 1.09-1.29), females versus males (OR, 1.26; 95% CI, 1.16-1.38), white versus nonwhite (OR, 1.43; 95% CI, 1.27-1.66), and with 6-month histories of postinflammatory pulmonary fibrosis (OR, 1.89; 95% CI, 1.52-2.20), tobacco use (OR, 1.16; 95% CI, 1.00-1.26), and other diseases. CONCLUSION: Our study among the elderly suggests TRALI to be a severe event and identifies a substantially increased TRALI occurrence with greater number of units and with PLT- or plasma-containing transfusions. The study also suggests importance of underlying health conditions, prior recipient alloimmunization, and nonimmune mechanism in TRALI development among the elderly.

Chart-confirmed guillain-barre syndrome after 2009 H1N1 influenza vaccination among the Medicare population, 2009-2010.

Given the increased risk of Guillain-Barré Syndrome (GBS) found with the 1976 swine influenza vaccine, both active surveillance and end-of-season analyses on chart-confirmed cases were performed across multiple US vaccine safety monitoring systems, including the Medicare system, to evaluate the association of GBS after 2009 monovalent H1N1 influenza vaccination. Medically reviewed cases consisted of H1N1-vaccinated Medicare beneficiaries who were hospitalized for GBS. These cases were then classified by using Brighton Collaboration diagnostic criteria. Thirty-one persons had Brighton level 1, 2, or 3 GBS or Fisher Syndrome, with symptom onset 1-119 days after vaccination. Self-controlled risk interval analyses estimated GBS risk within the 6-week period immediately following H1N1 vaccination compared with a later control period, with additional adjustment for seasonality. Our results showed an elevated risk of GBS with 2009 monovalent H1N1 vaccination (incidence rate ratio = 2.41, 95% confidence interval: 1.14, 5.11; attributable risk = 2.84 per million doses administered, 95% confidence interval: 0.21, 5.48). This observed risk was slightly higher than that seen with previous seasonal influenza vaccines; however, additional results that used a stricter case definition (Brighton level 1 or 2) were not statistically significant, and our ability to account for preceding respiratory/gastrointestinal illness was limited. Furthermore, the observed risk was substantially lower than that seen with the 1976 swine influenza vaccine.

Left bundle branch block predicts better survival in women than men receiving cardiac resynchronization therapy: long-term follow-up of ∼ 145,000 patients.

OBJECTIVES: The goal of this study was to test the hypothesis that in recipients of cardiac resynchronization therapy defibrillators (CRT-D), conventional left bundle branch block (LBBB) diagnosis predicts better survival in women than in men. BACKGROUND: New York Heart Association class I and II patients without LBBB do not benefit from CRT-D, and women have better survival after CRT-D than men. Separate analysis suggests that QRS duration thresholds for LBBB diagnosis differ according to sex, and conventional LBBB electrocardiographic criteria are falsely positive in men more frequently than in women. METHODS: We analyzed Medicare records from 144,642 CRT-D recipients between 2002 and 2008 that were followed up for up to 90 months. Medicare billing data were used to determine age, sex, race, and comorbidities. Hazard ratios (HRs) were calculated to assess if conventional LBBB diagnosis had different prognostic significance according to sex. RESULTS: In univariate analysis, LBBB was associated with a 31% reduction in death in women (HR: 0.69 [95% confidence interval (CI): 0.67 to 0.71]) but only a 16% reduction in death in men (HR: 0.84 [95% CI: 0.82 to 0.85]). In multivariable analyses controlling for comorbidities, LBBB was associated with a 26% reduction in death in women (HR: 0.74 [95% CI: 0.71 to 0.77]) and a 15% reduction in death in men (HR: 0.85 [95% CI: 0.83 to 0.87]). A significant interaction (p < 0.0001) between sex and LBBB was seen. CONCLUSIONS: LBBB diagnosis is associated with greater survival in women than in men receiving CRT-D, and this discrepancy is not explained by differences in measured comorbidities. Possible explanations for this difference include that LBBB may have different prognostic significance according to sex or that LBBB diagnosis is more often false-positive in men compared with women.

Outpatient transfusions and occurrence of serious noninfectious transfusion-related complications among US elderly, 2007-2008: utility of large administrative databases in blood safety research.

BACKGROUND: Transfusion-related acute lung injury (TRALI) and hemolytic transfusion reactions account for significant transfusion-related morbidity and mortality in the United States. Our study evaluated types and quantities of transfused components as well as occurrence of TRALI, ABO, and Rh incompatibilities among the US elderly in the institutional outpatient setting during 2007 to 2008. STUDY DESIGN AND METHODS: This retrospective claims-based study utilized the Centers for Medicare & Medicaid Services' large administrative databases. Transfusions were identified by recorded procedure and revenue center codes, while complications were ascertained via ICD-9-CM diagnosis codes. The study quantified blood use based on revenue center units. RESULTS: Among 26,054,242 and 25,662,864 Medicare elderly in 2007 and 2008, a total of 241,055 (0.9%) and 251,284 (1.0%) had outpatient transfusions. Leukoreduced red blood cells (LR-RBCs) was the most frequently transfused single blood component (60.1 and 61.3%, respectively) each year. Likewise, LR-RBCs and LR pheresis platelets (LR-PLTs) was the most frequent component combination (2.4 and 2.6%, respectively). TRALI rate comparison for RBCs and PLTs versus RBCs only showed higher rate for RBCs and PLTs (p = 0.033). In 2007 and 2008, ABO incompatibility rate comparison for irradiated (IR) LR-RBCs versus LR-RBCs showed higher rates for IR LR-RBCs (rate ratio [RR] 37.4, 95% confidence interval [CI] 10.6-132.6; and RR 31.3, 95% CI 11.6-84.4, respectively). CONCLUSION: This study shows potential usefulness of Medicare databases in assessment of blood utilization, transfusion-related complications, and risk factors among US elderly in the outpatient setting. It suggests limitations (e.g., need for several years of data to better assess rare complications) and importance of databases as hypothesis-generating tool to supplement blood safety research.

Babesiosis among elderly Medicare beneficiaries, United States, 2006-2008.

We used administrative databases to assess babesiosis among elderly persons in the United States by year, sex, age, race, state of residence, and diagnosis months during 2006-2008. The highest babesiosis rates were in Connecticut, Rhode Island, New York, and Massachusetts, and findings suggested babesiosis expansion to other states.