Selection of prosthetic aortic valves in the United States among elderly Medicare patients from 2006 to 2015.

BACKGROUND: Both biological and mechanical prosthetic valves are treatment choices for aortic valve replacement. We aimed to characterize the selection of prosthetic aortic valves among elderly Medicare patients. METHODS: This was a retrospective analysis of patients aged 65 years or older who underwent aortic valve replacement alone or in combination with other procedures in the 2006-2015 Medicare databases. Patients were continuously enrolled in Medicare Part A and B. We characterized the trends and regional variation of the selection of prosthetic valves. Multivariable logistic regression was used to evaluate the determinants that influenced the selection of prosthetic valves. RESULTS: During the study period, there were 272,921 Medicare patients aged 65 years or older who underwent aortic valve replacement and met the inclusion and exclusion criteria. The selection of mechanical aortic valves decreased from 32.0% in 2006 to 24.3% in 2015 (P < .01). In comparison with 18.5% from northeastern states, 34.6% of patients from southern states selected mechanical valves (P < .01). Major determinants of the selection of prosthetic valves include age, gender, region, hospital characteristics, and physician experience. Patients being older, male, living in the northeast region, operated on in a high-volume hospital, and by more experienced physicians were more likely to receive biological valves. CONCLUSIONS: A 24.1% decrease in the selection of mechanical aortic valves was observed among elderly Medicare patients from 2006 to 2015. A dramatic regional difference was observed in the choice of prosthetic valves across the nation.

Idelalisib for Treatment of Relapsed Follicular Lymphoma and Chronic Lymphocytic Leukemia: A Comparison of Treatment Outcomes in Clinical Trial Participants vs Medicare Beneficiaries.

Importance: Idelalisib (IDEL) is approved as monotherapy in relapsed follicular lymphoma (FL) and with rituximab (IDEL+R) for relapsed chronic lymphocytic leukemia (CLL). Toxic effects can be severe and treatment-limiting. Outcomes in a real-world population are not yet characterized. Objective: We compared IDEL treatment outcomes in the clinical setting with outcomes in clinical trial data. Design, Setting, and Participants: This cohort study compared clinical trial participants treated with IDEL, aged 65 years or older, in studies 101-09 and 312-0116 with Medicare beneficiaries treated with IDEL of the same disease state and treatment regimen. Study 101-09 was a phase 2, single-group, open-label trial supporting accelerated approval of IDEL for relapsed or refractory FL. Study 312-0116 was a phase 3, multicenter, randomized, double-blind trial supporting approval of IDEL+R for relapsed CLL. Analyses were conducted between February and December 2018. Main Outcomes and Measures: Treatment duration, on-treatment and overall mortality, and serious and fatal infections were compared between trial participants and Medicare beneficiaries. Cox proportional hazards models quantified differences by cohort. Results: We identified 26 trial participants (mean [SD] age, 73 [4.9] years; 12 [46.2%] women) and 305 Medicare beneficiaries (mean [SD] age, 76 [6.9] years; 103 [54.8%] women) receiving IDEL for FL and 89 trial participants (mean [SD] age, 74 [6.0] years; 30 [33.7%] women) and 294 Medicare beneficiaries (mean age, 76 [6.3] years; 111 [37.8%] women) receiving IDEL+R for CLL. Medicare beneficiaries were older with higher comorbidity; had a shorter median treatment duration for CLL (173 days vs 473 days, P < .001) but not FL (114, days vs 160 days, P = .38); a numerically higher mortality rate (CLL: HR, 1.40; 95% CI, 0.93-2.11; FL: HR, 1.39; 95% CI, 0.69-2.78); and a significantly higher fatal infection rate per 100 person-years for CLL (18.4 vs 9.8, P = .04) and a numerically higher rate for FL (27.6 vs 18.6, P = .54), compared with trial participants. Trial participants had approximately twice as many dose reductions (CLL: 32.6% vs 18.0%; P = .003; FL: 38.5% vs 16.1%; P = .02). Among Medicare beneficiaries, a hospitalized infection within 6 months prior to IDEL initiation was associated with a 2.11-fold increased risk for on-treatment fatal infections (95% CI, 1.44-3.10). Despite a March 2016 recommendation for Pneumocystis jirovecii pneumonia prophylaxis in patients treated with IDEL, prophylaxis rates were low after March 2016 (FL: 25%, CLL: 37%). Conclusions and Relevance: We observed substantial imbalances in baseline comorbidities and treatment outcomes between Medicare beneficiaries and trial participants aged 65 years or older. Immunosuppression-related toxic effects, including infections, may have been somewhat reduced in trials by more frequent dose reductions and exclusion of patients with ongoing infections. Selective eligibility criteria and closer monitoring of trial patients may be responsible for limited generalizability of trial data to clinical practice.

Healthy User Bias in Comparative Safety Studies for Brand-Name vs. Generic Products: The Example of Warfarin.

Warfarin was selected as a case study to examine confounding when comparing a product across different manufacturers because it is a narrow therapeutic index drug with prevalent beliefs for brand-name superiority. Medicare beneficiaries aged ≥65 years with atrial fibrillation and an incident outpatient warfarin prescription from July 2006 through July 2015 were included in the study population (N = 746,098). Substantial imbalances were observed between brand-name warfarin and generics for (i) clinical comorbidity, (ii) socioeconomic status, (iii) prescriber specialty, (iv) recent ambulatory and emergent care, (v) drug adherence, (vi) pharmacy setting (e.g., retail, mail-order), and (vii) risk scores for bleeding and thrombosis. Patients receiving brand-name warfarin were healthier than patients receiving generic manufactured warfarin. Utilization of generic warfarin products also differed by geographic region and pharmacy setting. Manufacturer-level comparative-safety studies for causal inference should carefully consider the presence of these imbalances and their potential for introducing healthy user bias.

Influenza vaccination coverage estimates in the fee-for service Medicare beneficiary population 2006 - 2016: Using population-based administrative data to support a geographic based near real-time tool.

Older adults are at great risk of developing serious complications from seasonal influenza. We explore vaccination coverage estimates in the Medicare population through the use of administrative claims data and describe a tool designed to help shape outreach efforts and inform strategies to help raise influenza vaccination rates. This interactive mapping tool uses claims data to compare vaccination levels between geographic (i.e., state, county, zip code) and demographic (i.e., race, age) groups at different points in a season. Trends can also be compared across seasons. Utilization of this tool can assist key actors interested in prevention - medical groups, health plans, hospitals, and state and local public health authorities - in supporting strategies for reaching pools of unvaccinated beneficiaries where general national population estimates of coverage are less informative. Implementing evidence-based tools can be used to address persistent racial and ethnic disparities and prevent a substantial number of influenza cases and hospitalizations.

Beneficiary characteristics and vaccinations in the end-stage renal disease Medicare beneficiary population, an analysis of claims data 2006-2015.

BACKGROUND: The Advisory Committee on Immunization Practices (ACIP) routinely recommends three vaccines - influenza, hepatitis B, and pneumococcal vaccines - for End-Stage Renal Disease (ESRD) dialysis patients. METHODS: We sought to assess vaccination coverage among fee-for-service (FFS) Medicare beneficiaries with ESRD who received Part B dialysis services at any point from January 1, 2006 through December 31, 2015 (through June 30, 2016 for influenza). To assess influenza vaccination rates in a given influenza season, we restricted the population to beneficiaries who were continuously enrolled in Medicare Parts A and B throughout all twelve months of that season. To assess hepatitis B and pneumococcal vaccine coverage following dialysis initiation, we developed a Kaplan-Meier curve for all patients who began dialysis between 2006 and 2015. RESULTS: For influenza vaccination, we identified an average of approximately 325,000 ESRD dialysis beneficiaries enrolled through each influenza season from 2006-2015. Seasonal influenza vaccination rates steadily increased during the 10-year period, from 52% in 2006-2007 to 71% in 2015-2016. The greatest increases in influenza vaccination appear in non-white beneficiaries with overall utilization in non-whites higher than in whites (p < .001). For the hepatitis B and pneumococcal vaccinations, we identified over 350,000 ESRD dialysis beneficiaries who began dialysis over the 10-year study window. The probability of receiving a hepatitis B vaccine within the first three years of entering into the ESRD program was higher (77%) than the probability of receiving any pneumococcal vaccine (53%). 45% of ESRD patients completed at least one dose of the two hepatitis B series (three-dose or four-dose) at any time during the study period. CONCLUSIONS: Opportunities exist at regional and facility levels to improve vaccination coverage. Compliance to ACIP recommendations may directly affect risk for ESRD dialysis patients for complications from diseases that can be mitigated by vaccination.

Modeling the potential impact on the US blood supply of transfusing critically ill patients with fresher stored red blood cells.

BACKGROUND: Although some studies have suggested that transfusion recipients may have better medical outcomes if transfused with red blood cell units stored for a short time, the overall body of evidence shows mixed results. It is important to understand how using fresher stored red blood cell units for certain patient groups may affect blood availability. METHODS: Based on the Stock-and-Flow simulation model of the US blood supply developed by Simonetti et al. 2014, we evaluated a newly implemented allocation method of preferentially transfusing fresher stored red blood cell units to a subset of high-risk group of critically ill patients and its potential impact on supply. RESULTS: Simulation results showed that, depending on the scenario, the US blood total supply might be reduced between 2-42%, when compared to the standard of care in transfusion medicine practice. Among our simulated scenarios, we observed that the number of expired red blood cell units modulated the supply levels. The age threshold of the required red blood cell units was inversely correlated with both the supply levels and the number of transfused units that failed to meet that age threshold. CONCLUSION: To our knowledge, this study represents the first attempt to develop a comprehensive framework to evaluate the impact of preferentially transfusing fresher stored red blood cells to the higher-risk critically ill patients on supply. Model results show the difficulties to identify an optimal scenario.

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.

Prenatal mercury exposure, autism, and developmental delay, using pharmacokinetic combination of newborn blood concentrations and questionnaire data: a case control study.

BACKGROUND: Methylmercury (MeHg), known for well over a century as a neurotoxin in adults, has more recently been studied for potential detrimental effects during early brain development. While several studies have estimated mercury exposure, they usually rely on either a single biomarker or questionnaire data, each of which has limitations. The goal of this paper was to develop a toxicokinetic model that incorporates both biomarker and questionnaire data to estimate the cumulative exposure to MeHg through seafood consumption using data collected from the Childhood Autism Risks from Genetics and the Environment (CHARGE) study. METHODS: We utilized a previously described discrete-time model that estimates blood MeHg concentration given a piecewise-constant ingestion rate and single-compartment pharmacokinetics. We measured newborn bloodspot Hg concentrations and obtained information pertaining to maternal fish consumption using a questionnaire. Using MeHg concentration estimates from the toxicokinetic model, cumulative MeHg exposure was estimated in children with autism, children with developmental delay, and typically developing children. Median estimated cumulative MeHg was compared among diagnostic groups using the Kruskal-Wallis Test. Multinomial logistic regression models were constructed to assess the association between cumulative MeHg concentration and the risk of autism and developmental delay (vs. typical development). RESULTS: The estimated average MeHg concentration of for all fish species consumed by mothers was 42 ppb. Median cumulative MeHg over gestation was similar across diagnostic groups (p-values raged from 0.91 to 0.98). After adjusting for potential confounding, we found no association between cumulative MeHg exposure and the risk of autism (OR = 0.95, 95% CI: 0.95, 1.12) or developmental delay (OR = 1.00, 95% CI: 0.89, 1.13). CONCLUSIONS: The toxicokinetic model described in this paper yielded fish MeHg concentration estimates that are consistent with fish species containing lower levels of MeHg. Overall, cumulative MeHg exposure does not appear to detectably elevate the risk of autism or developmental delay. Based on the regression standard error for the association between ASD and TD, we would have reported statistical significance for an adjusted odds ratio of 1.09 or larger. This method can easily be extended to other epidemiologic studies in which there is a biomarker measurement and questionnaire data regarding exposure.

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.

Early mortality after aortic valve replacement with mechanical prosthetic vs bioprosthetic valves among Medicare beneficiaries: a population-based cohort study.

IMPORTANCE: Early mortality for patients who undergo aortic valve replacement (AVR) may differ between mechanical and biological prosthetic (hereinafter referred to as bioprosthetic) valves. Clinical trials may have difficulty addressing this issue owing to limited sample sizes and low mortality rates. OBJECTIVE: To compare early mortality after AVR between the recipients of mechanical and bioprosthetic aortic valves. DESIGN, SETTING, AND PARTICIPANTS: A retrospective analysis of patients 65 years or older in the Medicare databases who underwent AVR from July 1, 2006, through December 31, 2011. In the mixed-effects models adjusting for physician and hospital random effects, we estimated odds ratios (OR) of early mortality to compare mechanical vs bioprosthetic valves. EXPOSURES: Mechanical or bioprostheticaortic valve replacement. MAIN OUTCOMES AND MEASURES: Early mortality was measured as death on the date of surgery, death within 1 to 30 or 31 to 365 days after the date of surgery, death within 30 days after the date of hospital discharge, and operative mortality (death within 30 days after surgery or at discharge, whichever is longer). RESULTS: Of the 66 453 Medicare beneficiaries who met inclusion criteria, 19 190 (28.88%) received a mechanical valve and 47 263 (71.12%) received a bioprosthetic valve. The risk for death on the date of surgery was 60% higher for recipients of mechanical valves than recipients of bioprosthetic valves (OR, 1.61 [95% CI, 1.27-2.04; P < .001]; risk ratio [RR], 1.60). The risk difference decreased to 16% during the 30 days after the date of surgery (OR, 1.18 [95% CI, 1.09-1.28; P < .001]; RR, 1.16). We found no differences within 31 to 365 days after the date of surgery and within the 30 days after discharge. The risk for operative mortality was 19% higher for recipients of mechanical compared with bioprosthetic valves (OR, 1.21 [95% CI, 1.13-1.30; P < .001]; RR, 1.19). The number needed to treat with mechanical valves to observe 1 additional death on the surgery date was 290; to observe 1 additional death within 30 days of surgery, 121. Consistent findings were observed in subgroup analyses of patients who underwent concurrent AVR and coronary artery bypass graft, but not in the subgroup undergoing isolated AVR. CONCLUSIONS AND RELEVANCE: In this cohort analysis of Medicare beneficiaries, use of mechanical aortic valves was associated with a higher risk for death on the date of surgery and within the 30 days after surgery compared with bioprosthetic aortic valves among patients who underwent concurrent AVR and coronary artery bypass graft but not isolated AVR.

Cardiovascular and mortality risks in older Medicare patients treated with varenicline or bupropion for smoking cessation: an observational cohort study.

PURPOSE: To compare cardiovascular and mortality risks in elderly patients treated with varenicline or bupropion for smoking cessation. METHODS: Elderly Medicare beneficiaries were entered into new-user cohorts of varenicline or bupropion for smoking cessation and followed on therapy for primary outcomes of acute myocardial infarction (AMI), stroke, mortality, and a composite of any of these events. Secondary outcomes were unstable angina, coronary revascularization, and a composite of any primary or secondary outcome event. Propensity score stratification was used to adjust for baseline differences in potential confounding factors. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using Cox proportional hazards, with bupropion as reference. RESULTS: In cohorts of 74 824 varenicline and 14 133 bupropion users, there were 164 AMI, 96 stroke, 87 death, 317 primary composite, and 814 secondary composite events while on therapy. The HRs (95%CI) were 0.79 (0.50-1.24) for AMI, 1.27 (0.63-2.55) for stroke, 0.58 (0.30-1.13) for death, 0.84 (0.58-1.23) for the primary composite, and 0.92 (0.73-1.14) for the secondary composite. The risk of AMI or the primary composite outcome did not differ in subgroups defined by age, diabetes status, or presence of underlying ischemic heart disease. Only 30% of patients remained on either study drug beyond their first prescription. CONCLUSION: Cardiovascular and mortality risks were not increased in older patients treated with varenicline compared with bupropion for smoking cessation. A potential increase in the risk of stroke with varenicline could not be excluded. Treatment persistence with either drug was low. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

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.

Cardiovascular and mortality risk in elderly Medicare beneficiaries treated with olmesartan versus other angiotensin receptor blockers.

PURPOSE: In the randomized trial, Randomized Olmesartan and Diabetes Microalbuminuria Prevention, acute cardiovascular death was increased nearly fivefold in diabetic patients treated with high-dose olmesartan, an angiotensin receptor blocker (ARB), compared with placebo. METHODS: Medicare beneficiaries were entered into new-user cohorts of olmesartan or other ARBs and followed on therapy for occurrence of acute myocardial infarction, stroke, or death. Analyses focused on specific subgroups defined by diabetes status, ARB dose, and duration of therapy. Hazard ratios (HR) with 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression, with other ARBs as reference. RESULTS: A total of 158,054 olmesartan and 724,673 other ARB users were followed for 54,285 and 260,390 person-years, respectively, during which 9237 endpoint events occurred. Lower-dose olmesartan was not associated with increased risk for any endpoint, regardless of duration of use. High-dose olmesartan for 6 months or longer was associated with increased risk of death in patients with diabetes (HR 2.03, 95%CI 1.09-3.75, p = 0.02) and with reduced risk in nondiabetic patients (HR 0.46, 95%CI 0.24-0.86, p = 0.01). Some, but not all, sensitivity analyses suggested that selective prescribing of olmesartan to healthier patients (channeling bias) may have accounted for the reduced risk in nondiabetic patients. CONCLUSIONS: High-dose olmesartan was associated with an increased risk of death in diabetic patients treated for 6 months or longer and with a reduced risk of death in nondiabetic patients, when compared with use of other ARBs. This latter effect was probably because of selective prescribing of olmesartan to healthier patients, although effect modification cannot be excluded. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.