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Patients diagnosed with cancer have an increased risk both for myelodysplastic syndromes (MDS) and for acute myeloid leukemia (AML) following treatment.Using SEER-Medicare data, we selected patients aged 66 years and older who completed systemic therapy between 2002 and 2014 for breast (stage I-III), lung (stage I-III), or prostate (stage I-IV) cancer. For each cancer, we estimated the risk of a composite endpoint of MDS or AML in patients receiving granulocyte colony-stimulating factor (G-CSF) vs. not.The 10-year cumulative risk difference (granulocyte colony-stimulating factor [G-CSF] - no G-CSF) for MDS-AML was 0.45% (95% CI 0.13-0.77%) in breast cancer and 0.39% (95% CI 0.15-0.62%) in lung cancer. G-CSF use was associated with a hazard ratio of 1.60 (95% CI 1.07-2.40) in breast cancer and 1.50 (95% CI 0.99-2.29) in lung cancer. Filgrastim use was associated with a hazard ratio of 1.01 (95% CI 1.00-1.03) per administration in breast cancer and 1.02 (95% CI 0.99-1.05) per administration in lung cancer. Pegfilgrastim was associated with a hazard ratio of 1.08 (95% CI 1.01-1.15) per administration in breast cancer and 1.12 (95% CI 1.00-1.25) per administration in lung cancer. Analyses in prostate cancer were limited because of the low number of events.The use of G-CSF in patients diagnosed with breast and lung cancer is associated with an increased risk of MDS-AML. However, the MDS-AML absolute risk difference is very low.

Purpose Estimate effects of ranibizumab on diabetic retinopathy (DR) severity in US Hispanic and non-Hispanic white persons with center-involved diabetic macular edema (DME) causing vision impairment for whom ranibizumab treatment would be considered. Patients and methods This model simulated DR severity outcomes over 2 years in the better-seeing eye using US census, National Health and Nutrition Examination Survey, Wisconsin Epidemiologic Study of Diabetic Retinopathy, and Los Angeles Latino Eye Study data. Baseline DR severity estimated from Diabetic Retinopathy Clinical Research Network trial data. Changes in DR severity after 2 years, with/without monthly ranibizumab (0.3 or 0.5 mg), were estimated from Phase III clinical trial data (RIDE/RISE) using a 2-dimensional Monte Carlo simulation model. Number of patients over a 2-year period for whom 1) DR severity worsening was avoided, 2) DR severity improved, and 3) selected clinical events related to proliferative DR (PDR) occurred, was estimated. Results An estimated 37,274 US Hispanic and non-Hispanic white persons were projected to have DR with center-involved DME and be eligible for ranibizumab treatment. The number of persons with moderately severe non-proliferative DR (NPDR) or less severe DR at baseline who would worsen to PDR and experience a PDR complication over 2 years would be reduced from 437 with no ranibizumab to 19 with ranibizumab (95% reduction; 95% simulation interval [SI], 79-100%). The number of persons with severe NPDR or less severe DR at baseline who would be expected to improve by ≥2 DR severity levels over 2 years would increase from 1706 with no ranibizumab to 13,042 with ranibizumab (682% increase; 95% SI, 478-967%). Conclusion This model estimates that ranibizumab treatment in US Hispanic and non-Hispanic white patients with center-involved DME causing vision impairment would potentially reduce the number of patients with worsening DR and potentially increase the number with DR improvements.

Background In end-stage kidney disease, patients may undergo parathyroidectomy if secondary hyperparathyroidism cannot be managed medically. This study was designed to estimate the parathyroidectomy rate in the United States (US) and to quantify changes in costs and other outcomes after parathyroidectomy. Methods This was a retrospective observational cohort study using US Renal Data System data for 2015–2018. Parathyroidectomy rates were estimated for adult hemodialysis and peritoneal dialysis patients alive at the beginning of 2016, 2017, and 2018 who were followed for a year or until parathyroidectomy, death, or transplant. Incremental differences in economic and clinical outcomes were compared before and after parathyroidectomy in adult hemodialysis and peritoneal dialysis patients who received a parathyroidectomy in 2016 and 2017. Results The rate of parathyroidectomy per 1,000 person-years decreased from 6.5 (95% CI 6.2-6.8) in 2016 to 5.3 (95% CI 5.0-5.6) in 2018. The incremental increase in 12-month cost after versus before parathyroidectomy was $25,314 (95% CI $23,777-$27,078). By the second month after parathyroidectomy, 58% of patients had a corrected calcium level < 8.5 mg/dL. In the year after parathyroidectomy (versus before), hospitalizations increased by 1.4 per person-year (95% CI 1.3-1.5), hospital days increased by 12.1 per person-year (95% CI 11.2-13.0), dialysis visits decreased by 5.2 per person-year (95% CI 4.4-5.9), and office visits declined by 1.3 per person-year (95% CI 1.0-1.5). The incremental rate per 1,000 person years for hematoma/bleed was 224.4 (95% CI 152.5-303.1), for vocal cord paralysis was 124.6 (95% CI 59.1-232.1), and for seroma was 27.4 (95% CI 0.4-59.0). Conclusions Parathyroidectomy was a relatively uncommon event in the hemodialysis and peritoneal dialysis populations. The incremental cost of parathyroidectomy was mostly attributable to the cost of the parathyroidectomy hospitalization. Hypocalcemia occurred in over half of patients, and calcium and phosphate levels were reduced. Clinicians, payers, and patients should understand the potential clinical and economic outcomes when considering parathyroidectomy.

Background Malignant mesothelioma is a rare neoplasm associated with asbestos exposure. Characterizing treatment patterns and outcomes of older patients with advanced malignant pleural mesothelioma (MPM) is important to understand the unmet needs of this population. Aim To evaluate the demographic and clinical characteristics, treatment patterns, and outcomes among older patients diagnosed with advanced MPM in the United States between 2007 and 2013. Methods This was a retrospective cohort study using Surveillance, Epidemiology, and End Results (SEER) data linked with Medicare claims. We included patients who were age 66 or older at the time of their primary MPM diagnosis between 2007 and 2013 and followed them through 2014. Treated patients who received first-line chemotherapy with pemetrexed and platinum within 90 days of diagnosis, second-line, or third-line therapy were identified for evaluation of outcomes. Results There were 666 older patients with advanced MPM, of whom 82% were male, 87% White, 78% stage IV, and 70% had no mobility limitation indicators at diagnosis. There were 262 patients who received first-line chemotherapy for advanced MPM, most of whom (80%; n = 209) received pemetrexed-platinum. Of these 209 patients, 41% (n = 86) initiated second-line therapy, and 26% (n = 22) initiated third-line therapy. Median overall survival for the cohort of 209 patients was 7.2 months. Patients with epithelioid histology had better median overall survival (12.2 months) compared with other histologies (4.4-5.6 months). Within 90 days of diagnosis of advanced MPM, 78% of patients were hospitalized, 52% visited an emergency department, and 21% had hospice care. The 2-year cost of care was over $100 000 for all patients with advanced MPM treated with first-line pemetrexed-platinum. Conclusions Although first-line systemic anticancer treatment was generally consistent with guidelines (e.g., pemetrexed-platinum), poor patient outcomes highlight the need for effective treatment options for older patients with advanced MPM.

Background: Calcimimetics are used to treat mineral and bone disorder by reducing parathyroid hormone (PTH), calcium (Ca), and phosphorus (Phos). The study objectives were to assess the control of PTH, Ca, and Phos over time in patients receiving cinacalcet or etelcalcetide as well as dosing and time to discontinuation for etelcalcetide. Methods: This was a retrospective cohort study using electronic medical records from small and independent dialysis centers. Adults ≥18 years of age were identified as cinacalcet or etelcalcetide users based on the first calcimimetic received in 2018 (index date). Patients were followed from the index date until parathyroidectomy, kidney transplant, death, or end of data (December 31, 2018). Analyses of mean PTH, Ca, and Phos, as well as target achievement of PTH, Ca, and Phos were conducted over a 9-month period. Discontinuation with etelcalcetide was measured with the Kaplan-Meier estimator. Results: There were 1,346 cinacalcet patients (mean age 60.5 years, 43.5% female, and 47.1% Black) and 1,255 etelcalcetide patients (mean age 63.4 years, 46.6% female, and 38.5% Black). At baseline, the proportions in target were similar for etelcalcetide versus cinacalcet: 36 versus 38% for PTH, 79 versus 80% for Ca, and 43 versus 44% for Phos. Overall, 40–47% of cinacalcet users and 48–62% of etelcalcetide users were observed to be in target for PTH over 9 months. The proportion in target for Phos ranged from 41 to 46% for cinacalcet and 46–51% for etelcalcetide. The proportion in target for Ca ranged from 74 to 78% for cinacalcet and 60–73% for etelcalcetide. Etelcalcetide 12-month discontinuation was 37.4%. Conclusion: Both calcimimetics were effective in keeping PTH, Ca, and Phos levels within target. Patients receiving etelcalcetide tended to have lower laboratory values for PTH, Ca, and Phos over time, while patients receiving cinacalcet tended to be more likely to be in target for Ca over time.

Background Over time, guidelines for dyslipidemia management in patients at high risk of atherosclerotic cardiovascular disease (CVD) changed with the goal of improving patient outcomes. Guidelines have been released by the European Joint Task Force in 2007, 2012 and 2016, European Society of Cardiology in 2011, 2016 and 2019, Joint British Societies in 2014, and National Institute for Health and Care Excellence in 2014. Purpose Evaluate cardiovascular risk factors, treatment patterns, and cardiovascular outcomes over time related to dyslipidemia management. Methods Ten prevalent cohorts of patients with documented CVD receiving lipid-lowering therapy (LLT) were created using Clinical Research Practice Datalink (CPRD) records as of January 1, each year from 2008 through 2017. For each cohort, we identified CVD risk factors and LLT, and estimated the 1-year composite rate of fatal and nonfatal myocardial infarction (MI), ischemic stroke (IS), or revascularization. Patient follow-up was censored at the earliest of one year, end of data, or the outcome of interest. Patients in each cohort were required to be ≥18 years old, have ≥1 years of available medical history, and have received ≥2 LLT prescriptions in the prior year. Documented CVD was defined as MI, IS, angina, revascularization, transient ischemic attack, carotid stenosis, abdominal aortic aneurysm, or peripheral arterial disease. Patients could be in multiple cohorts. Results Annual patient counts ranged from 170,501 to 179,137 through 2013 and declined to 94,418 by 2017 (due to fewer patients in the overall CPRD data). Comparing 2008, 2011 (when ESC guidelines were revised) and 2017 showed the following for CVD risk factors: mean age was 71.6, 72.3, and 72.5 years; males were 59.9%, 61.1%, and 63.1%; current smoking was 15.1%, 15.2%, and 13.9%; type 2 diabetes was 18.4%, 20.2%, and 22.4%; stage 3–5 chronic kidney disease was 22.4%, 25.1%, and 22.8%; history of MI was 22.5%, 23.9%, and 27.4%; history of IS was 5.5%, 6.6%, and 7.9%; LDL Conclusions After 2011 in the UK, there was an increased use of high intensity statins, a greater proportion of patients with LDL levels Figure 1 Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Amgen

49 Background: Trifluridine/tipiracil (FTD/TPI) and regorafenib are among the limited treatment options in later lines of therapy for patients with advanced colorectal cancer (CRC). While these treatments have demonstrated similar efficacy, differences have been observed in tolerability and data on the impact of such differences on real-world outcomes are limited. To better understand the real world use of FTD/TPI and regorafenib in the US, we report data for adherence/persistence among patients with CRC initiating these therapies. Methods: This was a retrospective cohort study among adults with CRC identified from the IBM MarketScan Commercial Claims and Medicare Supplemental Databases, who initiated FTD/TPI or regorafenib (index) from October 2015-September 2019 and had 6 months of continuous enrollment before the index date. Follow-up was until disenrollment or end of study period. Treatment cohorts were propensity score 1:1 matched, adjusting for differences in socio-demographics, comorbidities, and other baseline characteristics. Adherence and persistence outcomes included time to discontinuation (medication gap of >45 days), medication possession ratio (MPR; number of treated days/ duration of treatment), proportion of days covered (PDC; number of treated days/ days in specified time period), and number of prescriptions received. Results: A total of 1477 patients were included: 892 initiating FTD/TPI (60%) and 585 regorafenib (40%). Demographics were similar prior to matching: mean age was 58 and 59 years, and 57% and 59% were male, in the FTD/TPI and regorafenib groups, respectively. Mean Charlson Comorbidity Index score (excluding cancer) was 0.69 for FTD/TPI initiators and 0.62 for regorafenib initiators. For the matched cohorts (n=585 in each), measures of adherence and persistence (Table) showed longer time to discontinuation (2.5 vs. 2.0 months; p

Aims: Methods for integrating external costs into clinical databases are not well-characterized. The purpose of this research was to describe and implement methods for estimating the cost of hospitalizations, prescriptions, and general practitioner and specialist visits used to manage hyperlipidemia patients experiencing cardiovascular (CV) events in the United Kingdom (UK). Methods: This study was a retrospective cohort study using the Clinical Practice Research Datalink and Hospital Episode Statistics data. Costs were incorporated based on reference costs from the National Health Service, and labor costs from the Personal Social Services Research Unit. The study population included patients seen by general practitioners in the UK from 2006–2012. Patients ≥18 years were selected at the time of their first CV-related hospitalization defined as myocardial infarction, ischemic stroke, heart failure, transient ischemic attack, unstable angina, or revascularization. To be included, patients must have received ≥2 lipid-lowering therapies. Outcome measures included healthcare utilization and direct medical costs for hospitalizations, medications, general practitioner visits, and specialist visits during the 6-month acute period, starting with the CV hospitalization, and during the subsequent 30-month long-term period. Results: There were 24,093 patients with a CV hospitalization included in the cohort. This study identified and costed 69,240 hospitalizations, 673,069 GP visits, 32,942 specialist visits, and 2,572,792 prescriptions, representing 855 unique drug and dose combinations. The mean acute period and mean annualized long-term period costs (2014£) were £4,060 and £1,433 for hospitalizations, £377 and £518 for GP visits, £59 and £103 for specialist visits, and £98 and £209 for medications. Conclusions: Hospital costs represent the largest portion of acute and long-term costs in this population. Detailed costing using utilization data is feasible and representative of UK clinical practice, but is labor intensive. The availability of a standardized coding system in the UK drug costing data would greatly facilitate drug costing.

In August 2018, the US FDA granted accelerated approval for nivolumab in small cell lung cancer (SCLC) that has progressed after platinum-based chemotherapy and at least one other line of therapy. The objective of this study was to evaluate the cost-effectiveness of nivolumab vs. usual care as third-line (3 L) therapy for patients with recurrent SCLC (rSCLC) from the health payer perspective. Given the potential for a meaningful fraction of treated patients to achieve long-term response to nivolumab, we also assessed the impact of using mixture cure modeling (MCM) vs. parametric survival modeling on survival estimates and cost-effectiveness from the US Medicare payer perspective. We created a partitioned survival decision model to assess the cost-effectiveness of 3 L nivolumab vs. usual care in rSCLC, based on observed US treatment patterns. Using this approach, we assessed the impact of extrapolating long-term survival from the CheckMate 032 trial, using both MCM and standard parametric curve fits. Nivolumab survival, resource use, and Grade 3/4 adverse event rates were derived from CheckMate 032. Usual care survival, resource use, and costs were derived from an analysis of patients receiving 3 L treatment for rSCLC in the SEER-Medicare registry. We applied 2020 Wholesale Acquisition Cost for drugs and 2020 CMS reimbursement for procedures. Utilities were derived from the literature. We estimated life years (LY), quality-adjusted life years (QALYs), and costs over a lifetime horizon. MCM and parametric survival model extrapolations resulted in 0.43 versus 0.38 more LYs, 0.34 versus 0.30 more QALYs, and $69,308 versus $61,336 more expenditure for nivolumab vs. usual care, respectively. The costs per QALY gained using mixture cure versus parametric survival modeling were $204,386 and $207,431, respectively. Mixture cure modeling was equivalent compared to parametric modeling in estimating the cost-effectiveness of nivolumab-based therapy due to the small fraction of patients achieving a long-term response with nivolumab (12.9%).

Importance Individuals with sickle cell disease (SCD) have reduced life expectancy; however, there are limited data available on lifetime income in patients with SCD. Objective To estimate life expectancy, quality-adjusted life expectancy, and income differences between a US cohort of patients with SCD and an age-, sex-, and race/ethnicity-matched cohort without SCD. Design, Setting, and Participants Cohort simulation modeling was used to (1) build a prevalent SCD cohort and a matched non-SCD cohort, (2) identify utility weights for quality-adjusted life expectancy, (3) calculate average expected annual personal income, and (4) model life expectancy, quality-adjusted life expectancy, and lifetime incomes for SCD and matched non-SCD cohorts. Data sources included the Centers for Disease Control and Prevention, National Newborn Screening Information System, and published literature. The target population was individuals with SCD, the time horizon was lifetime, and the perspective was societal. Model data were collected from November 29, 2017, to March 21, 2018, and the analysis was performed from April 28 to December 3, 2018. Main Outcomes and Measures Life expectancy, quality-adjusted life expectancy, and projected lifetime income. Results The estimated prevalent population for the SCD cohort was 87 328 (95% uncertainty interval, 79 344-101 398); 998 were male and 952 were female. Projected life expectancy for the SCD cohort was 54 years vs 76 years for the matched non-SCD cohort; quality-adjusted life expectancy was 33 years vs 67 years, respectively. Projected lifetime income was $1 227 000 for an individual with SCD and $1 922 000 for a matched individual without SCD, reflecting a lost income of $695 000 owing to the 22-year difference in life expectancy. One study limitation is that the higher estimates of life expectancy yielded conservative estimates of lost life-years and income. The analysis only considered the value of lost personal income owing to premature mortality and did not consider direct medical costs or other societal costs associated with excess morbidity (eg, lost workdays for disability, time spent in the hospital). The model was most sensitive to changes in income levels and mortality rates. Conclusions and Relevance In this simulated cohort modeling study, SCD had societal consequences beyond medical costs in terms of reduced life expectancy, quality-adjusted life expectancy, and lifetime earnings. These results underscore the need for disease-modifying therapies to improve the underlying morbidity and mortality associated with SCD.

Introduction High mortality rates in patients with chronic kidney disease-mineral and bone disorder (CKD-MBD) receiving maintenance hemodialysis are largely due to cardiovascular (CV) events. Methods We evaluated associations between MBD parameters, fibroblast growth factor 23 (FGF23) concentrations, and clinically adjudicated CV events from the Evaluation of Cinacalcet Hydrochloride Therapy to Lower Cardiovascular Events (EVOLVE) trial. Patients enrolled in EVOLVE, who had not experienced any study endpoints between randomization and week 20 with evaluable baseline and week 20 values for key laboratory parameters (parathyroid hormone, calcium, phosphate, and FGF23), were assessed. We used adjusted Cox proportional hazards regression models to estimate relative risk of outcomes (primary composite, all-cause mortality, and CV events) based on FGF23 and MBD parameters. Laboratory values were modeled with linear terms and using natural cubic splines with two degrees of freedom. Findings For the primary endpoint, patients assessed (N = 2309) were followed up over a mean duration of 3.1 years, during which 1037 CV events (497 deaths, 540 nonfatal events) occurred. Adjusted models showed an association between FGF23 and the risk of CV events. Hazard ratio per log unit of FGF23 at week 20 was 1.09 [95% CI: 1.03-1.16], and the hazard ratio per log unit change in FGF23 from week 0 to week 20 was 1.09 [95% CI: 1.00-1.17]. Discussion Our data highlight FGF23 as an independent CV risk factor and potential biomarker and therapeutic target for patients with CKD-MBD receiving maintenance hemodialysis.

Aims The aims of this study were to re-estimate the international REduction of Atherothrombosis for Continued Health (REACH) risk equation using United Kingdom data and to distinguish different relative hazards for specific atherosclerotic cardiovascular disease event histories. Methods and results Patients in the UK Clinical Research Practice Datalink (CPRD) were included as of 1 January 2005 if they were 40 years or older, had 2 or more years of prior data, received one or more moderate or high-intensity statin in the previous year, and had a history of myocardial infarction, ischemic stroke, or other atherosclerotic cardiovascular disease. Patients were followed until a composite endpoint of myocardial infarction, ischemic stroke or cardiovascular death, loss to follow-up, or end of observation. We re-estimated the REACH risk equation hazard ratios (HRs) using CPRD data (re-estimated REACH model). Our event history model replaced the REACH vascular bed variables with more specific event histories. There were 60,838 patients with 5.25 years of mean follow-up. In the validation model, HRs were in the same direction, and generally greater than REACH. In the event history model, HRs compared to other atherosclerotic cardiovascular disease alone included: recurrent myocardial infarction (HR 1.19, 95% confidence interval (CI) 1.05–1.34), recurrent ischemic stroke (HR 1.36, 95% CI 1.03–1.80), myocardial infarction and other atherosclerotic cardiovascular disease (HR 1.31, 95% CI 1.23–1.38), ischemic stroke and other atherosclerotic cardiovascular disease (HR 1.40, 95% CI 1.23–1.60), myocardial infarction and ischemic stroke (HR 1.94, 95% CI 1.23–3.04), and myocardial infarction, ischemic stroke and other atherosclerotic cardiovascular disease (HR 1.93, 95% CI 1.47–2.54). Conclusion A detailed cardiovascular event history may be useful for estimating the relative risk of future cardiovascular events.

Using SEER-Medicare linked data we identified elderly patients diagnosed with diffuse large B-cell lymphoma (DLBCL) between January 2000 and December 2007 who received second-line outpatient chemotherapy for relapsed or refractory disease. Second-line regimens were classified into three mutually exclusive groups: aggressive, conventional, and palliative. Of the 632 (426 relapsed, 206 refractory) patients in the cohort, 27.8% received aggressive second-line therapy, 39.1% received conventional therapy, and 33.1% received palliative therapy. There were no differences in survival by type of therapy received, either for relapsed or refractory patients, although the patient risk profile differed significantly. However, duration of remission, male gender, and anemia at diagnosis were important predictors in relapsed patients, and male gender, B-symptoms, comorbidity burden, and poverty status were important predictors in refractory patients. Survival in elderly patients receiving second-line therapy remains poor, and the 24-month cost of all care exceeds $97,000. Patients would benefit from improved treatment options.

Supplemental Digital Content is available in the text., Background: Rituximab was approved in 1997 and is regularly one of the largest drug expenditures for Medicare; however, its benefits and costs have not been estimated from a population perspective. Objectives: To estimate both the clinical and the economic outcomes of rituximab for its approved hematological uses at the population level. Research Design: Analyses using cancer registry incidence data from the Surveillance, Epidemiology, and End Results (SEER) program, and outcomes data from SEER data linked with Medicare administrative claims (SEER-Medicare data). These results were incorporated into an epidemiological simulation model of the population over time. Subjects: We modeled all United States patients from 1998 to 2013 diagnosed with diffuse large B-cell lymphoma, follicular lymphoma, or chronic lymphocytic leukemia. Measures: Using this model, we estimated the life-years saved, as well as their economic benefit, in the United States population. We also estimated the incremental cost of adding rituximab to chemotherapy. All economic inputs were based on Medicare reimbursed amounts inflated to 2013 dollars. Results: There were 279,704 cumulative life-years saved which were valued at $25.44 billion. The incremental direct medical cost of rituximab was estimated to be $8.92 billion, resulting in an incremental economic gain of $16.52 billion. Conclusions: These analyses, based on real-world evidence, show that the introduction of rituximab into clinical practice has produced a substantial number of incremental life-years. Importantly, the economic benefit of the life-years gained greatly exceeds the added costs of treatment.

Comorbidities are known to impact quality of life, treatment choices, and survival. Our objectives were to characterize comorbid conditions in a cohort of elderly gastric cancer patients and to determine if there is variability in the prevalence or incidence of the comorbid conditions across racial/ethnic groups. A total of 12,612 individuals, ≥66 years of age, diagnosed with gastric cancer between 2000 and 2007, and an equal number of gender- and region-matched cancer-free individuals, were identified using the National Cancer Institute’s Surveillance, Epidemiology, and End Results registry linked to Medicare claims in the United States. The prevalence (%) in the year before diagnosis and the 12-month incidence rates after diagnosis were estimated for 32 chronic and ten acute comorbid conditions for the entire cohort and by race/ethnicity (Asian, Black, Hispanic, White, and other) and Asian subgroups (e.g., Chinese, Filipino, Japanese, Pacific Islander). White and Black cases exhibited the highest prevalence of most comorbid conditions. Asian and Pacific Islander cases exhibited the lowest. There was substantial variability in the 12-month incidence of the comorbidities across the racial/ethnic groups. Electrolyte disorder was the most common incident condition among Whites and Blacks. With the exception of Whites, anemia was the most common incident condition in all racial and ethnic groups 180 days following chemotherapy. There is variability in the prevalence and incidence in comorbidities across racial/ethnic groups.

To examine utilization and outcomes in pediatric immune thrombocytopenia (ITP) hospitalizations, we used ICD-9 code 287.31 to identify hospitalizations in patients with ITP in the 2009 HCUP KID, an all-payer sample of pediatric hospitalizations from US community hospitals. Diagnosis and procedure codes were used to estimate rates of ITP-related procedures, comorbidity prevalence, costs, length of stay (LOS), and mortality. In 2009, there were an estimated 4499 hospitalizations in children aged 6 months–17 years with ITP; 43% in children aged 1–5 years; and 47% with emergency department encounters. The mean hospitalization cost was $5398, mean LOS 2.0 days, with 0.3% mortality (n = 13). With any bleeding (15.2%, including gastrointestinal 2.0%, hematuria 1.3%, intracranial hemorrhage [ICH] 0.6%), mean hospitalization cost was $7215, LOS 2.5 days, with 1.5% mortality. For ICH (0.6%, n = 27), mean cost was $40 209, LOS 8.5 days, with 21% mortality. With infections (14%, including upper respiratory 5.2%, viral 4.9%, bacterial 1.9%), the mean cost was $6928, LOS 2.9 days, with 0.9% mortality. Septic shock was reported in 0.3% of discharges. Utilization included immunoglobulin administration (37%) and splenectomies (2.3%). Factors associated with higher costs included age >6 years, ICH, hematuria, transfusion, splenectomy, and bone marrow diagnostics (p < 0.05). In conclusion, of the 4499 hospitalizations with ITP, mortality rates of 1.5%, 21%, and 0.9% were seen with any bleeding, ICH, and infection, respectively. Higher costs were associated with clinically significant bleeding and procedures. Future analyses may reveal effects of the implementation of more recent ITP guidelines and use of additional treatments.

e16598 Background: Biliary tract cancers (BTC) arise from the epithelial lining of the biliary tree and include intrahepatic and extrahepatic cholangiocarcinoma, gallbladder cancer, and sometimes cancer of the ampulla of Vater. Although this is a closely related group of diseases, comparisons of risk factors, treatment, and mortality by disease site are limited. Methods: This retrospective cohort study used Surveillance, Epidemiology, and End Results (SEER) cancer registry data linked with Medicare claims. Patients aged ≥66 years with a pathologically confirmed diagnosis of advanced (stage III or IV) BTC from 2010 to 2015 were included and followed up through 2016. Patients with any SEER-reported cancer in the prior 2 years were excluded. Any outpatient systemic treatment during follow-up was identified using Medicare claims. Patients were followed up until death, end of follow-up, subsequent primary cancer, or switch to managed care. The Kaplan-Meier estimator was used to estimate unadjusted median survival. A Cox proportional hazards model was used to identify factors associated with survival. Results: There were 2,891 patients in the cohort (Table). Factors significantly associated with worse survival included older age, presence of mobility limitations, living in an area with > 30% of the people below poverty, higher comorbidity burden, and stage IV BTC (vs stage III). Factors significantly associated with better survival included history of cancer, intrahepatic BTC (vs extrahepatic), or ampulla of Vater BTC (vs extrahepatic). Conclusions: Survival in BTC is poor and many patients do not receive outpatient systemic therapy. Patients with gallbladder and extrahepatic BTC had worse median survival and were less likely to receive systemic therapy than those with intrahepatic or ampulla of Vater BTC. Fewer ampulla of Vater patients present with Stage IV disease which could be a contributing factor to the significantly longer survival. Prior work has demonstrated an association between history of some types of cancer and survival; additional research is needed to better understand this finding. [Table: see text]

497 Background: Overall survival (OS) in advanced or metastatic BTC has not been adequately described outside the clinical trial setting. Further, real-world descriptions of OS by line of therapy, including in patients who do not receive systemic chemotherapy, are not widely available. In this study, we used data from a recent cohort of US patients available in the SEER-Medicare linked database to examine OS from diagnosis of advanced or metastatic BTC as well as from initiation of first- and second-line treatment. Methods: Patients with advanced or metastatic BTC diagnosed between 2010 and 2013 were identified in SEER-Medicare, with follow-up through 2014. Demographic and clinical characteristics were analyzed. The Kaplan-Meier estimator was used to describe OS from diagnosis among all patients, OS from diagnosis among patients who did not receive systemic treatment, and OS by line of treatment, from date of treatment initiation. The Cox proportional hazards model was used to identify demographic and clinical factors associated with survival. Results: Of the 1,461 eligible patients aged ≥66 years, 39% had gallbladder, 22% had intrahepatic, 22% had extrahepatic, and 9% had ampulla of Vater cancer. More than two-thirds of patients had stage IV disease, and 38% of patients (n = 558) received systemic chemotherapy. Systemic treatment patients were somewhat younger, more likely to be white, have stage IV cancer and less likely to have mobility limitations (24% vs. 38%) than patients who did not receive systemic treatment. Among all patients, unadjusted median OS from diagnosis was 5.6 months (95% CI 5.0-6.1). Among patients who were not treated, unadjusted median survival was 3.3 months (n = 903; 95% CI 2.8-4.0) from diagnosis. When OS was evaluated by line of treatment, median OS was 8.2 months (n = 558; 95% CI 7.6-9.0) from first-line initiation and 5.6 months (n = 220; 95% CI 4.6-6.5) from second-line initiation. Conclusions: Among newly diagnosed, older US patients, less than half receive systemic treatment for their advanced BTC, and outcomes among both treated and untreated patients remain poor. There is an immediate need for better therapies to treat patients with advanced BTC.

Background Intravenous recombinant tissue-type plasminogen activator (r-tPA) is an approved treatment for select patients with acute ischemic stroke (AIS). Data indicate r-tPA improves functional outcome three months after AIS compared with placebo. This study models the increase in quality adjusted life years (QALYs) associated with r-tPA compared with similar patients not treated with r-tPA. Methods Hospital discharge data for AIS and r-tPA were obtained from the Nationwide Inpatient Sample from 1998 to 2011. Discharge location (home, rehabilitation, long-term care, death) was mapped to modified Rankin Scale (mRS) scores based on National Institute of Neurological Disorders and Stroke (NINDS) Study Group Part 1 and 2 clinical studies. The mRS scores were mapped to relative risk of death and QALYs obtained from the literature. The model estimated expected survival and QALYs by age, gender and mRS for patients receiving r-tPA. Life expectancy and QALYs for patients not receiving r-tPA were estimated based on discharge location and mRS for placebo patients in the NINDS study. Results AIS discharges declined from over 635,000 in 1998 to over 593,000 in 2011. A total of 183,235 patients received r-tPA. Utilization of r-tPA increased from 1% of AIS patients in 1998 to over 4% in 2011. Estimated projections for QALYs gained from utilization of r-tPA to QALYS without r-tPA were just under 240,000 for the 13 years and with no discounting, and just over 165,000 assuming 3% annual discounting. In the most conservative scenario, assuming no difference in proportional discharge status (i.e. patients not treated with r-tPA are discharged in the same manner as r-tPA patients), the estimated life years gained are approximately 35,000 and QALYS gained are approximately 90,000. Conclusions r-tPA for AIS has resulted in estimated gains in quality-adjusted life years due to reduction in disability and improvement in functioning since its introduction in 1998.

Background HER2 positive (HER2+) metastatic breast cancer (MBC) is associated with high mortality. Trastuzumab was approved for use in 1998, but the life-years saved from first-line use are unknown, as are the potential US population benefits from adding pertuzumab. Objectives The first aim was to estimate the number of life-years saved by using first-line trastuzumab between 1999 and 2013 in HER2+ women with MBC. In addition, based on these estimates, the second aim was to project the life-years that could be saved by adding pertuzumab to trastuzumab in first-line therapy. Methods We constructed a simulation model accounting for incidence, testing rates, therapy utilization, and overall survival. The model was run for 1999 to 2013 (15 years) to estimate the life-years saved from using trastuzumab plus chemotherapy instead of chemotherapy alone. The model was also run from 2013 to 2027 (15 years) to project the life-years that might be saved by adding pertuzumab. Uncertainty was incorporated using Monte-Carlo methods. Results The estimated number of women with HER2+ MBC varied over time, with the peak of 9700 in 2005 and the low of 7700 in 2018. The cumulative incremental life-years saved because of first-line trastuzumab use from 1999 to 2013 was estimated to be 156,413 (95% simulation interval 114,840–195,201). The projection for pertuzumab from 2013 to 2027 was 137,959 (95% simulation interval 56,011–225,069). Exploratory analyses of value showed that pertuzumab, trastuzumab, and chemotherapy is associated with a $1.10 billion gain compared with chemotherapy alone, and adding pertuzumab is associated with a $0.06 billion gain compared with trastuzumab with chemotherapy. Conclusions This simulation model suggests that substantial progress has been made in treating HER2+ women over the past 15 years, and the future may witness similar gains with the introduction of pertuzumab.

Background It is important to identify an easily defined subset of patients at increased risk of adverse clinical outcomes associated with mineral and bone disorder (MBD) biomarkers (parathyroid hormone, calcium and phosphate). Methods Observational cohort study of 26 221 prevalent hemodialysis patients in Davita clinics as of 31 August 2005 and followed up until 31 December 2006 (16 months). Predictors were 12 possible definitions of 'clinically important' MBD based on all 3 biomarkers, and 18 alternative definitions based on only 1 or 2 biomarkers. Events were death alone and a composite of cardiovascular hospitalization or death. Excess events were calculated based on a multivariate Cox model using 5224 patients in target for all MBD biomarkers and applied to 20 997 patients out of target for at least one biomarker. Excess events attributable to MBD were estimated by subtracting the multivariate model-derived predicted number from the actual number. Outcomes were the proportion of excess events attributable to MBD captured by each definition (threshold ≥70%) and the reduction in the population size considered to have clinically important MBD (threshold ≥30%). The excess fraction was excess events divided by actual events. Results Patients with more biochemical markers out of target tended to be younger, black and have longer times since starting dialysis. The excess fraction associated with MBD ranged from ∼10 to 26% depending on the clinical endpoint and definition. The only definition to meet the thresholds required at least two of the three MBD biomarkers to be out of target (high or low). It captured 82% of excess composite endpoints and 74% of excess deaths and reduced the at-risk population by 46%. Conclusions Patients with at least two of three MBD biomarkers out of target represent a subgroup of patients at elevated risk of adverse clinical events.

Objective: To assess the prevalence of patients at very high risk of cardiovascular (CV) events in the United Kingdom (UK) and evaluate low-density lipoprotein cholesterol (LDL-C) values and treatment patterns in these patients. Methods: This cross-sectional study used primary care data from UK electronic medical records in the Clinical Practice Research Datalink (CPRD) in 2013. Very high-risk patients were defined per European Society of Cardiology guidelines as those with hyperlipidemia (assessed by co-medication) and documented cardiovascular disease (CVD) or hyperlipidemia and type 2 diabetes (DM2) without CVD (DM2w/oCVD). All analyses were descriptive. Results: Data from 4,940,226 patients were captured in the CPRD in 2013. Of these, 5% of patients had received ≥2 lipid-modifying therapy prescriptions and were at very high risk of CVD (3% [n = 138,536] had documented CVD, 2% [n = 98,743] had DM2w/oCVD). In documented CVD patients, coronary artery disease (73%) was the most frequent type of event (25% had myocardial infarction [MI]), followed by cerebrovascular disease (18%), and peripheral arterial disease (9%); 21% had experienced multiple CV events, 25% had DM2, and 3% had MI within 1 year. In documented CVD and DM2w/oCVD patients, >95% received statin treatment; 24% received high-intensity statin, and 1.5% statin plus ezetimibe. Across both populations, 64–66% had LDL-C levels ≥1.8 mmol/L, 27–28% ≥2.5 mmol/L, 6–7% ≥3.5 mmol/L, and 3% had levels ≥4.0 mmol/L, respectively. Conclusion: A well-defined proportion of patients remain at very high-risk of CVD. Statin therapy needs optimization, but, for some patients with high LDL-C levels, multiple CV events, MI within 1 year, or CVD and DM2, additional more intensive therapy may be needed.

Objectives To describe low-density lipoprotein (LDL) cholesterol management and lipid-lowering treatment patterns in patients with a cardiovascular (CV) event. Design Retrospective cohort study using Clinical Practice Research Datalink records linked with Hospital Episode Statistics data. Setting Routine clinical practice in the UK from 2006 to 2012. Participants Individuals ≥18 years were selected at their first CV-related hospitalisation (first event cohort) if they had received ≥2 lipid-lowering therapy prescriptions within 180 days beforehand. Patients were stratified into four mutually exclusive subgroups based on the presence or absence of vascular disease and of diabetes. Those with a second CV hospitalisation within 36 months were included in a separate cohort (second event cohort). Primary and secondary outcome measures LDL levels in the year prior to the CV event and 12 months later as well as measures of adherence to lipid-lowering therapy during the 12 months after the CV hospitalisation. Results There were 24 093 patients in the first event cohort, of whom 5274 were included in the second event cohort. Most received moderate intensity statins at baseline and 12 months. Among the four first event cohort subgroups at baseline, the proportions with an LDL of

e12032 Background: The study objective was to estimate the long-term consequences of recurrences following treatment with trastuzumab (TRA) among women with HER2+ early stage breast cancer (BC) in the United States (US). Methods: A simulation model was constructed to estimate the following outcomes for each combination of hormone receptor (+/-) and nodal (+/-) status: number of recurrences, direct medical cost and indirect cost attributed to recurrences. The number of women aged ≥18 years with newly diagnosed HER2+ BC between 2018 and 2037 was estimated using SEER incidence rates (assumed constant over time) and from US Census data and accounted for the proportion of women utilizing adjuvant TRA by nodal status and age (assumed constant over time). The recurrence rate to any regional, distant or contralateral site was based on the long-term follow-up of the HERceptin Adjuvant (HERA) trial (expected 20-year recurrence proportions of 27.6% for TRA and 36.7% without TRA). Medical and pharmacy costs due to a recurrence were based on a 3-year study of metastatic BC patients treated with HER2 targeted agents. Beyond year 3, cost increased by 4.5% per year. The indirect costs of recurrences included loss of income from early retirement valued at the mean hourly wage, work absenteeism ($6,960/year), and reduced productivity while at work ($3,456/year). Non-cancer related mortality was estimated using SEER data. Results: We estimated that there would be 411,373 incident cases of early stage BC who would receive adjuvant TRA treatment from 2018 to 2037. Following each annual cohort for 20 years, we estimated that there would be 112,700 recurrences after TRA treatment and 149,674 recurrences without TRA treatment. The 20-year direct medical costs of recurrences were estimated to be $28.2 and $37.5 billion with and without TRA, respectively and the indirect costs were estimated to be $4.1 and $5.6 billion with and without TRA, respectively. Conclusions: Although TRA reduced recurrences by 25% in our 20-year model, there was a substantial number of recurrences. Future research will assess the clinical and economic impact of newer HER2 directed therapies in the adjuvant (pertuzumab, T-DM1) and extended adjuvant (neratinib) setting.

e12011 Background: Long-term efficacy in the extended adjuvant setting requires a long follow-up. In the ExteNET trial, neratinib was given for a year and invasive disease-free survival (iDFS) assessed at 2 and 5 years. In women with HER2+ hormone receptor positive (HR+) cancer who initiated neratinib, the observed difference in iDFS between neratinib and placebo at 5 years (4.5%) was greater than at 2 years (3.7%). The objective of these analyses was to extrapolate the effect of neratinib on iDFS beyond 5 years in patients with HER2+/HR+ early stage breast cancer who initiated treatment after receiving adjuvant trastuzumab. Methods: We analyzed the 5-year follow-up of the ExteNET trial using flexible spline-based parametric survival models to project iDFS risk at 10 years. Analyses included only HR+ patients. Several model specifications were explored including various combinations of the following variables: treatment as a time varying covariate, nodal status (0, 1-3, ≥4 nodes), and months from last trastuzumab treatment to randomization. The regression models included different combinations of interaction terms, either a proportional hazards or a proportional odds (PO) link function, and either 2 or 6 knots. The model fit was compared using Akaike Information Criterion (AIC). Results: In general, the fit statistics among the 16 models were comparable; however, the model with the lowest AIC included no interaction terms, 2 knots, and the PO link function. The mean iDFS event rate at 10 years was estimated to be 12.2% for neratinib and 18.9% for placebo for a difference of 6.8% (range across 16 models: 6.8%-7.8%). The recurrence rate and the difference between treatment groups were largest in women with ≥4 positive nodes. Conclusions: Based on these analyses, the projected 10-year difference in iDFS between placebo and neratinib patients seems likely to persist. However, because the data was limited to 5 years, we could not include the effect of hormonal therapy cessation. Also, low event rates in the node negative group may require longer follow-up to evaluate. In absence of longer-term data for neratinib, flexible parametric survival modeling of the iDFS suggests that the effect of neratinib therapy may remain stable.

Parathyroid hormone, calcium, and phosphate have been independently associated with cardiovascular event risk. Because these parameters may be on the same causal pathway and have been proposed as quality measures, an integrated approach to estimating event risks is needed.Prevalent dialysis patients were followed from August 31, 2005 to December 31, 2006. A two-stage modeling approach was used. First, the 16-month probabilities of death and composite end point of death or cardiovascular hospitalization were estimated and adjusted for potential confounders. Second, patients were categorized into 1 of 36 possible phenotypes using average parathyroid hormone, calcium, and phosphate values over a 4-month baseline period. Associations among phenotypes and outcomes were estimated and adjusted for the underlying event risk estimated from the first model stage.Of 26,221 patients, 98.5% of patients were in 22 groups with at least 100 patients and 20% of patients were in the reference group defined using guideline-based reference ranges for parathyroid hormone, calcium, and phosphate. Within the 22 most common phenotypes, 20% of patients were in groups with significantly (P0.05) higher risk of death and 54% of patients were in groups with significantly higher risk of the composite end point relative to the in-target reference group. Increased risks ranged from 15% to 47% for death and from 8% to 55% for the composite. More than 40% of all patients were in the three largest groups with elevated composite end point risk (high parathyroid hormone, target calcium, and high phosphate; target high parathyroid hormone, target calcium, and high phosphate; and target high parathyroid hormone, target calcium, and target phosphate).After adjusting for baseline risk, phenotypes defined by categories of parathyroid hormone, calcium, and phosphate identify patients at higher risk of death and cardiovascular hospitalization. Identifying common high-risk phenotypes may inform clinical interventions and policies related to quality of care.

Aim: To estimate real-world cardiovascular disease (CVD) burden and value-based price range of evolocumab for a US-context, high-risk, secondary-prevention population. Materials and methods: Burden of CVD was assessed using the UK-based Clinical Practice Research Datalink (CPRD) in order to capture complete CV burden including CV mortality. Patients on standard of care (SOC; high-intensity statins) in CPRD were selected based on eligibility criteria of FOURIER, a phase 3 CV outcomes trial of evolocumab, and categorized into four cohorts: high-risk prevalent atherosclerotic CVD (ASCVD) cohort (n = 1448), acute coronary syndrome (ACS) (n = 602), ischemic stroke (IS) (n = 151), and heart failure (HF) (n = 291) incident cohorts. The value-based price range for evolocumab was assessed using a previously published economic model. The model incorporated CPRD CV event rates and considered CV event reduction rate ratios per 1 mmol/L reduction in low-density lipoprotein-cholesterol (LDL-C) from a meta-analysis of statin trials by the Cholesterol Treatment Trialists Collaboration (CTTC), i.e. CTTC relationship. Results: Multiple-event rates of composite CV events (ACS, IS, or coronary revascularization) per 100 patient-years were 12.3 for the high-risk prevalent ASCVD cohort, and 25.7, 13.3, and 23.3, respectively, for incident ACS, IS, and HF cohorts. Approximately one-half (42%) of the high-risk ASCVD patients with a new CV event during follow-up had a subsequent CV event. Combining these real-world event rates and the CTTC relationship in the economic model, the value-based price range (credible interval) under a willingness-to-pay threshold of $150,000/quality-adjusted life-year gained for evolocumab was $11,990 ($9,341–$14,833) to $16,856 ($12,903–$20,678) in ASCVD patients with baseline LDL-C levels ≥70 mg/dL and ≥100 mg/dL, respectively. Conclusion: Real-world CVD burden is substantial. Using the observed CVD burden in CPRD and the CTTC relationship, the cost-effectiveness analysis showed that, accounting for uncertainties, the expected value-based price for evolocumab is higher than its current annual cost, as long as the payer discount off list price is greater than 20%.

Background Patients receiving hemodialysis with values outside of target levels for parathyroid hormone (PTH: 150–600 pg/mL), calcium (Ca: 8.4–10.2 mg/dL), and phosphate (P: 3.5–5.5 mg/dL) are at elevated morbidity and mortality risk. We examined whether patients receiving care in dialysis facilities where greater proportions of patients have at least two values out of target have a higher risk of adverse clinical outcomes. Methods The study cohort consisted of 39,085 prevalent hemodialysis patients in 1298 DaVita dialysis facilities as of September 1, 2009, followed from January 1, 2010, until an outcome, a censoring event, or December 31, 2010. We determined the quintile of the distribution across facilities of the proportion of patients with at least two of three parameters out of, or above, target over a 4-month baseline period. The primary composite outcome was cardiovascular hospitalization or death. Secondary outcomes included death, cardiovascular hospitalization, and parathyroidectomy. Poisson regression models were used to estimate the association of facility quintile with outcomes. Results Facility quintile was associated with a 7 % increased risk of cardiovascular hospitalization or death (quintile 5 versus 1, RR 1.07, 95 % CI 1.01–1.13) using the out-of-target measure of exposure and a 12 % increased risk (RR 1.12, 95 % CI 1.06–1.19) using the above-target measure. No association was seen for death using either measure. Patients in facility quintiles 3–5 (versus 1) were at increased parathyroidectomy risk (RR ranged from 2.05, 95 % CI 1.10–3.82, for quintile 3 to 2.73, 95 % CI 1.50–4.98, for quintile 5). Conclusions Facility level analysis of a large prevalent sample of US patients on hemodialysis demonstrates that patients in facilities with the least control of PTH, Ca, and P had the greatest risk of parathyroidectomy or the combination of cardiovascular hospitalization or death. Electronic supplementary material The online version of this article (doi:10.1186/s12882-016-0382-8) contains supplementary material, which is available to authorized users.

Objectives To characterise the costs to the UK National Health Service of cardiovascular (CV) events among individuals receiving lipid-modifying therapy. Design Retrospective cohort study using Clinical Practice Research Datalink records from 2006 to 2012 to identify individuals with their first and second CVrelated hospitalisations (first event and second event cohorts). Within-person differences were used to estimate CV-related outcomes. Setting Patients in the UK who had their first CV event between January 2006 and March 2012. Participants Patients ≥18 years who had a CV event and received at least 2 lipid-modifying therapy prescriptions within 180 days beforehand. Primary and secondary outcome measures Direct medical costs (2014 £) were estimated in 3 periods: baseline (pre-event), acute (6 months afterwards) and long-term (subsequent 30 months). Primary outcomes included incremental costs, resource usage and total costs per period. Results There were 24 093 patients in the first event cohort of whom 5274 were included in the second event cohort. The mean incremental acute CV event costs for the first event and second event cohorts were: coronary artery bypass graft/percutaneous transluminal coronary angioplasty (CABG/PTCA) £5635 and £5823, myocardial infarction £4275 and £4301, ischaemic stroke £3512 and £4572, heart failure £2444 and £3461, unstable angina £2179 and £2489 and transient ischaemic attack £1537 and £1814. The mean incremental long-term costs were: heart failure £848 and £2829, myocardial infarction £922 and £1385, ischaemic stroke £973 and £682, transient ischaemic attack £705 and £1692, unstable angina £328 and £677, and CABG/PTCA £−368 and £599. Hospitalisation accounted for 95% of acute and 61% of long-term incremental costs. Higher comorbidity was associated with higher long-term costs. Conclusions Revascularisation and myocardial infarction were associated with the highest incremental costs following a CV event. On the basis of real-world data, the economic burden of CV events in the UK is substantial, particularly among those with greater comorbidity burden.

Septicemia is a serious problem in hemodialysis patients because it can lead to life-threatening complications and a persistently elevated risk of death. Most analyses have not examined whether there are differences in mortality risk among the organisms that cause these episodes of septicemia. This study was a retrospective cohort analysis of first septicemia hospitalizations during the first year of hemodialysis. Time to death (both in-hospital and within 12 weeks post-discharge) was compared among the different septicemia-causing organisms based on discharge diagnoses in Medicare billing data from 1996 to 2001. The effect of various complications on mortality risk was also evaluated. There were 22,130 septicemia hospitalizations identified. The most common organism identified was Staphylococcus aureus (27%), with no other organism having an incidence >10%. The overall unadjusted death rate from admission through 12 weeks of follow-up was 34%. During the first hospitalization, the death rate was 14%, and during the 12-week period after the hospitalization it was 20%. In adjusted analyses, S. aureus was associated with a 20% higher risk of death both during the in-hospital period and the 12-week post-discharge period, when compared with all other specified organisms. Hospitalizations complicated by meningitis, stroke, or endocarditis were also associated with increased risk of mortality, independent of the organism causing septicemia. Septicemia hospitalizations are associated with a high mortality rate--both during the initial hospitalization and after discharge. Meningitis, stroke, and endocarditis represent particularly serious complications. Overall, septicemia hospitalizations (especially for S. aureus) are serious events, and patients would benefit from better treatment and prevention.

At any given time, approximately 27% of patients in the United States (US) receive hemodialysis through a permanent catheter. However, this cross-sectional estimate may significantly underestimate the lifetime exposure of patients to hemodialysis catheters, and hence, to the excess risk of the adverse clinical events associated with catheter use. To further clarify catheter use in hemodialysis patients, we identified a cohort of fistula and graft patients in the US Renal Data System using Current Procedural Terminology (CPT) codes. Patients were included if their first hemodialysis was between 1 January 1996 and 31 December 2001, and Medicare was their primary payer. We identified permanent catheter insertions in these patients using CPT codes starting 6 months before their first hemodialysis session (or fistula or graft placement, if earlier), and ending 40 months afterward. Most patients (82%) were >65 years old, 57% were male, and 72% were white. The overall rate of permanent catheter insertions was 44 per 100 patient years, with 57% of patients having at least one catheter insertion. The percent of patients receiving a catheter was similar before (30%) and after (27%) the first fistula or graft placement. Cross-sectional analysis may significantly underestimate the lifetime risk of exposure to hemodialysis catheters. Because catheter use is common even in fistula and graft patients, measures used to prevent adverse events associated with catheter use are important in all patients regardless of current access type.

BACKGROUND: Estimating the incidence of medical conditions using claims data often requires constructing a prevalence period that predates an event of interest, for instance the diagnosis of cancer, to exclude those with pre-existing conditions from the incidence risk set. Those conditions missed during the prevalence period may be misclassified as incident conditions (false positives) after the event of interest.Using Medicare claims, we examined the impact of selecting shorter versus longer prevalence periods on the incidence and misclassification of 12 relatively common conditions in older persons. METHODS: The source of data for this study was the National Cancer Institute's Surveillance, Epidemiology, and End Results cancer registry linked to Medicare claims. Two cohorts of women were included: 33,731 diagnosed with breast cancer between 2000 and 2002, who had ≥ 36 months of Medicare eligibility prior to cancer, the event of interest; and 101,649 without cancer meeting the same Medicare eligibility criterion. Cancer patients were followed from 36 months before cancer diagnosis (prevalence period) up to 3 months after diagnosis (incidence period). Non-cancer patients were followed for up to 39 months after the beginning of Medicare eligibility. A sham date was inserted after 36 months to separate the prevalence and incidence periods. Using 36 months as the gold standard, the prevalence period was then shortened in 6-month increments to examine the impact on the number of conditions first detected during the incidence period. RESULTS: In the breast cancer cohort, shortening the prevalence period from 36 to 6 months increased the incidence rates (per 1,000 patients) of all conditions; for example: hypertension 196 to 243; diabetes 34 to 76; chronic obstructive pulmonary disease 29 to 46; osteoarthritis 27 to 36; congestive heart failure 20 to 36; osteoporosis 22 to 29; and cerebrovascular disease 13 to 21. Shortening the prevalence period has less impact on those without cancer. CONCLUSIONS: Selecting a short prevalence period to rule out pre-existing conditions can, through misclassification, substantially inflate estimates of incident conditions. In incidence studies based on Medicare claims, selecting a prevalence period of ≥24 months balances the need to exclude pre-existing conditions with retaining the largest possible cohort.

Background Mortality in patients with myelodysplastic syndromes (MDS) is high, and patients are likely to require hospitalizations, emergency department (ED) visits, and transfusions. The relationships between these events and the MDS complications of anemia, neutropenia, and thrombocytopenia are not well understood. Patients and methods A total of 1864 patients registered in the United States’ Surveillance Epidemiology and End Results (SEER) program and aged ≥66 years old when diagnosed with MDS in 2001 or 2002 were included. Medicare claims were used to identify MDS complications and utilization (hospitalizations, ED visits, and transfusions) until death or the end of 2005. Mortality was based on SEER data. Kaplan–Meier incidence rates were estimated and multivariable Cox models were used to study the association between complications and outcomes. Results The 3-year incidence of anemia, neutropenia, and thrombocytopenia was 81%, 25%, and 41%, and the incidence of hospitalization, ED visit, and transfusion was 62%, 42%, and 45%, respectively. Median survival time was 22 months. Cytopenia complications were significantly associated with each of these outcomes. Conclusions All types of cytopenia are common among patients with MDS and are risk factors for high rates of health care utilization and mortality. Management of the complications of MDS may improve patient outcomes.

The study goal was to characterize older chronic lymphocytic leukemia (CLL) patients and to evaluate outcomes in those patients who initiated infused therapy. Patients 66 years of age and older in the Surveillance, Epidemiology, and End Results (SEER) program with a CLL diagnosis were matched to their Medicare Part A and Part B claims for long-term follow-up. Treatment patterns, survival after initiation of infused therapy, and both hematologic and hospitalization outcomes were assessed. There were 6433 CLL patients identified, and 2040 received infused therapy. Treated patients were categorized as receiving rituximab monotherapy (16%), rituximab plus chemotherapy (14%), and chemotherapy alone (70%) based on the initial 60 days after infusion. Rituximab plus chemotherapy compared with chemotherapy alone was associated with a 25% lower risk of overall mortality (95% confidence interval, 9%-38%). Restricting to patients age 70 years and older did not change the risk reduction for rituximab plus chemotherapy. Hematologic interventions were more common with rituximab plus chemotherapy compared with chemotherapy alone, but there was no difference in all-cause hospitalizations. These analyses, based on observational data, suggest that the benefits of initial therapy with rituximab in a heterogeneous group of older CLL patients are comparable with those demonstrated in younger patients.

Background Longitudinal analyses of comorbid conditions in women with breast cancer are few. Methods Using Surveillance, Epidemiology, and End Results–Medicare data, we included 51 950 women aged ≥66 years with in situ and stage I to IV breast cancer diagnosed in 1998–2002. We identified the prevalence and incidence of 34 comorbid conditions in these women, as well as in a matched cohort without cancer whose rates were standardized to the age and race/ethnicity distribution of the cancer patients. We also estimated rates of office encounters and diagnostic or testing procedures during the 12 months before diagnosis. Results The prevalence of most conditions at diagnosis was comparable among breast cancer and noncancer patients. New conditions after diagnosis were more common in breast cancer patients, and the incidence rates increased with higher stage at diagnosis. Before diagnosis, women presenting with stage IV disease had 41% [95% confidence interval (CI) 38% to 43%] fewer physician encounters and 34% (95% CI 24% to 31%) fewer unique diagnostic tests than women diagnosed with carcinoma in situ. Conclusions Many comorbid conditions are identified as a consequence of the breast cancer diagnosis. There appears to be an important contribution from a lack of interaction with the health care system before diagnosis.