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Objective:. Guidelines advise to perform endoscopic surveillance following ileocolic resection (ICR) in Crohn disease (CD) for timely diagnosis of recurrence. This study aims to assess the variation in endoscopic recurrence (ER) rates in patients after ICR for CD using the most commonly used classification systems, the Rutgeerts score (RS) and modified Rutgeerts score (mRS) classifications. Methods:. A systematic literature search using MEDLINE, Embase, and the Cochrane Library was performed. Randomized controlled trials and cohort studies describing ER < 12 months after an ICR for CD were included. Animal studies, reviews, case reports (

We used Surveillance, Epidemiology, and End Results-Medicare data (2000-2006) to describe treatment and survival in women diagnosed with metastatic breast cancer (MBC) who received trastuzumab. There were 610 patients with a mean age of 74 years. Overall, 32% received trastuzumab alone and 47% received trastuzumab plus a taxane. In multivariate analysis, trastuzumab plus chemotherapy was associated with a lower adjusted cancer mortality rate (Hazard Ratio [HR] 0.54; 95% Confidence Interval [CI] 0.39-0.74; p < .001) than trastuzumab alone among patients who received trastuzumab as part of first-line therapy. Adding chemotherapy to first-line trastuzumab for metastatic breast cancer is associated with improved cancer survival. [ABSTRACT FROM AUTHOR]

Background: Surgery with both neoadjuvant and adjuvant chemotherapy represents the standard of care for extremity osteosarcoma despite a lack of high-quality evidence for its use, and trial evidence that suggests that up-front surgery may result in better outcomes. This study estimated the difference in overall survival for the standard of care ("Neoadjuvant First") vs upfront surgery first followed by adjuvant chemotherapy ("Surgery First")., Patients and Methods: Using Surveillance, Epidemiology, and End Results data, we identified patients age 5-29, diagnosed with a primary cancer of upper or lower extremity osteosarcoma between 2007 and 2019 who received surgery and chemotherapy. Our primary endpoint was the 5-year survival difference between the Surgery First and Neoadjuvant First groups., Results: Adjusted 5-year survival was 74% for Surgery First patients and 67% for Neoadjuvant First patients, with a survival difference of 6.9% (95% CI -4.2% - 16.1%). In sensitivity analyses of 5-year survival, the results were consistent, showing a 6.8% to 13.7% higher 5-year survival in Surgery First patients. Significant mortality risk factors included older age, larger tumor size, the type of resection (salvage vs amputation), and stage 3-4 disease (vs stage 1-2 disease)., Conclusion: The evidence supporting neoadjuvant therapy in osteosarcoma care is weak. However, there is evidence that pausing chemotherapy in the peri-surgical period might affect outcomes. Consequently, this study, and its consistency with the results from the only randomized trial, suggests that there is reason to revisit a prospective, randomized trial of osteosarcoma treatment regarding the timing of surgery and chemotherapy., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction: The treatment landscape of small cell lung cancer (SCLC) is evolving. Evidence generated from administrative claims is needed to characterize real-world SCLC patients. However, the current ICD-10 coding system cannot distinguish SCLC from non-small cell lung cancer (NSCLC). We developed and estimated the accuracy of an algorithm to identify SCLC in claims-only databases., Methods: We performed a cross-sectional study of lung cancer patients diagnosed from 2016-2017 using the Surveillance, Epidemiology and End Results (SEER), linked with Medicare database. The analysis included two phases - data exploration (utilizing a 25% random sample) and data validation (remaining 75% sample). The SEER definition of SCLC and NSCLC were used as the gold standard. Claims-based algorithms were identified and evaluated for their sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV)., Results: The eligible cohort included 31,912 lung cancer patients. The mean age was 76.3 years, 44.6% were male, with 9.4% having SCLC and 90.6% identified as NSCLC using SEER. The exploration analysis identified potential algorithms based on treatment data. In the validation analysis of 7,438 lung cancer patients who received systemic treatment in the outpatient setting, an etoposide-based algorithm (etoposide use in 180 days following lung cancer diagnosis) to identify SCLC showed: sensitivity 95%, specificity 95%, PPV 82% and NPV 99%., Discussion: An etoposide treatment-based algorithm showed good accuracy in identifying SCLC patients. Such algorithms can facilitate analyses of treatment patterns, outcomes, healthcare resource and costs among treated SCLC patients, thereby bolstering the evidence-base for best patient care., Competing Interests: AB and XP are employees and shareholders of Amgen Inc. DB is a former employee of Amgen Inc. MD is an employee and owner of Outcomes Insights and received funding from Amgen, Inc. to conduct this research. This study was funded by Amgen, Inc. Amgen manufactures and sells products for use in patients with lung cancer. Amgen approved both the study protocol and the decision to publish prior to the research being initiated., (Copyright © 2024 Danese, Balasubramanian, Bebb and Pundole.)

Competing Interests: The authors declare no conflicts of interest.

Background and Aims: Biliary tract cancer (BTC) is a rare, lethal, heterogeneous group of cancers often diagnosed at an advanced stage. While gemcitabine plus cisplatin is the standard of care for first-line treatment of locally advanced or metastatic BTC, no globally accepted standard of care currently exists for second-line treatment of BTC following chemotherapy. However, the treatment landscape is evolving with approvals for therapies targeting actionable mutations. This study aimed to characterize treatment patterns and survival in patients with locally advanced or metastatic BTC., Methods: Patients with advanced or metastatic BTC in the Surveillance, Epidemiology, and End Results Medicare database between 2010 and 2015 (N = 2063) were included; patients with nonprimary BTC were excluded. Patient and clinical characteristics, line and type of therapy, and overall survival of patients were analyzed., Results: Only 45.5% (n = 938) of patients initiated systemic therapy within 90 days of diagnosis. The most common event following diagnosis was initiation of first-line therapy, and the most common event following first-line treatment was death. Median survival ranged from 5.0 months for patients receiving second-line fluoropyrimidine to 9.7 months for patients receiving second-line gemcitabine. Duration of therapy ranged from 0.7 months for patients receiving second-line fluoropyrimidine to 3.7 months for patients receiving first-line gemcitabine plus cisplatin therapy., Conclusion: Overall survival from diagnosis was poor and influenced by age, sex, stage, mobility limitations, comorbidity burden, poverty, and previous cancer. Treatment patterns varied for patients who progressed following first-line therapy, as there was no consensus second-line treatment for locally advanced or metastatic BTC without clinically targetable mutations., (© 2023 The Authors.)

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., (© 2021 The Authors. Cancer Reports published by Wiley Periodicals LLC.)

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., (© 2022. The Author(s).)

Introduction: Patients diagnosed with cancer have an increased risk both for myelodysplastic syndromes (MDS) and for acute myeloid leukemia (AML) following treatment., Methods: 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., Results: 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., Conclusions: 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., (© 2022. The Author(s), under exclusive licence to Springer Healthcare Ltd., part of Springer Nature.)

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., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

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., (© 2020 International Society for Hemodialysis.)

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., (© 2020 S. Karger AG, Basel.)

There is little evidence about whether additional risk stratification for adult patients with acute lymphoblastic leukemia age 65 and older is warranted. Using the Surveillance, Epidemiology, and End Results data linked to Medicare claims, we examined the effects of age, comorbid conditions, and mobility limitations on treatment and survival in a cohort of 795 patients diagnosed with ALL between 1 January 2000 and 31 December 2009. In the cohort, 54% received chemotherapy within the first 90 days, of whom 74% were hospitalized during the first chemotherapy administration. Unadjusted median survival was 172 days (95% CI = 244-379) for the overall cohort, 325 days (95% CI = 244-379) for those age 65-69, but only 59 days (95% CI = 45-76) for those age ≥80. In multivariate analyses, older age groups (70-74, 75-79, and ≥80) and comorbidity score ≥2 were independently associated with poorer survival. Treatment and outcomes vary considerably among subgroups of older patients suggesting that further risk stratification may be useful.

Background: Most healthcare data sources store information within their own unique schemas, making reliable and reproducible research challenging. Consequently, researchers have adopted various data models to improve the efficiency of research. Transforming and loading data into these models is a labor-intensive process that can alter the semantics of the original data. Therefore, we created a data model with a hierarchical structure that simplifies the transformation process and minimizes data alteration., Methods: There were two design goals in constructing the tables and table relationships for the Generalized Data Model (GDM). The first was to focus on clinical codes in their original vocabularies to retain the original semantic representation of the data. The second was to retain hierarchical information present in the original data while retaining provenance. The model was tested by transforming synthetic Medicare data; Surveillance, Epidemiology, and End Results data linked to Medicare claims; and electronic health records from the Clinical Practice Research Datalink. We also tested a subsequent transformation from the GDM into the Sentinel data model., Results: The resulting data model contains 19 tables, with the Clinical Codes, Contexts, and Collections tables serving as the core of the model, and containing most of the clinical, provenance, and hierarchical information. In addition, a Mapping table allows users to apply an arbitrarily complex set of relationships among vocabulary elements to facilitate automated analyses., Conclusions: The GDM offers researchers a simpler process for transforming data, clear data provenance, and a path for users to transform their data into other data models. The GDM is designed to retain hierarchical relationships among data elements as well as the original semantic representation of the data, ensuring consistency in protocol implementation as part of a complete data pipeline for researchers.

Importance: Both adherence and treatment intensity can alter the effectiveness of lipid-lowering therapy in routine clinical practice., Objective: To evaluate the association of adherence and treatment intensity with cardiovascular outcomes in patients with documented cardiovascular disease (CVD), type 2 diabetes without CVD or chronic kidney disease (CKD), and CKD without CVD., Design, Setting, and Participants: Retrospective cohort study using the Clinical Practice Research Datalink from January 2010 through February 2016. United Kingdom primary care was the setting. Participants were newly treated patients who received their first statin and/or ezetimibe prescription between January 1, 2010, and December 31, 2013, plus an additional prescription for statins and/or ezetimibe during the following year., Exposures: Adherence was assessed annually using the proportion of days covered, with adherent defined as a proportion of days covered of 80% or higher. Treatment intensity was classified according to guidelines based on the expected percentage of low-density lipoprotein cholesterol (LDL-C) reduction as low (<30% reduction), moderate (30% to <50% reduction), or high (≥50% reduction). Adherence and treatment intensity were multiplied to create a combined measure, reflecting treatment intensity after accounting for adherence., Main Outcomes and Measures: Composite end point of cardiovascular death or hospitalization for myocardial infarction, unstable angina, ischemic stroke, heart failure, or revascularization. Hazard ratios (HRs) were estimated against patients not treated for 1 year or longer., Results: Among a total of 29 797 newly treated patients, there were 16 701, 12 422, and 674 patients with documented CVD, type 2 diabetes without CVD or CKD, and CKD without CVD, respectively; mean (SD) ages were 68.3 (13.2), 59.3 (12.4), and 67.3 (15.1) years, and male proportions were 60.6%, 55.0%, and 47.0%. In the documented CVD cohort, patients receiving high-intensity therapy were more likely to be adherent over time (84.1% in year 1 and 72.3% in year 6) than patients receiving low-intensity therapy (57.4% in year 1 and 48.4% in year 6). Using a combined measure of adherence and treatment intensity, a graded association was observed with both LDL-C reduction and CVD outcomes: each 10% increase in the combined measure was associated with a 10% lower risk (HR, 0.90; 95% CI, 0.86-0.94). Adherent patients receiving a high-intensity regimen had the lowest risk (HR, 0.60; 95% CI, 0.54-0.68) vs patients untreated for 1 year or longer. Findings in the other 2 cohorts were similar., Conclusions and Relevance: Results of this study demonstrate that the lowest cardiovascular risk was observed among adherent patients receiving high-intensity therapy, and the highest cardiovascular risk was observed among nonadherent patients receiving low-intensity therapy. Strategies that improve adherence and greater use of intensive therapies could substantially improve cardiovascular risk.

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.

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.

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 <1.8 mmol/L was similar between the two diabetic cohorts (36% to 38%) and were higher than those in the two non-diabetic cohorts (17% to 22%) and in the second event cohort (31%). An incremental 5% to 9% had an LDL below 1.8 mmol/L at 12 months, suggesting intensification of therapy. The proportion of adherent patients (medication possession ratio of≥0.8) was highest for statins, ranging from 68% to 72%. For ezetimibe, the range was 65% to 70%, and for fibrates, it was 48% to 62%., Conclusions: Despite the existence of effective therapies for lowering cholesterol, patients do not reach achievable LDL targets., Competing Interests: Competing interests: MD, MG, and RG work with Outcomes Insights, Inc., which was funded to conduct this study. LK is an employee of Amgen, Inc. KK has acted as a consultant and speaker for Novartis, Novo Nordisk, Sanofi-Aventis, Lilly, Merck Sharp & Dohme, Janssen, Astra Zeneca and Boehringer Ingelheim. He has received grants in support of investigator and investigator-initiated trials from Novartis, Novo Nordisk, Sanofi-Aventis, Lilly, Pfizer, Boehringer Ingelheim, Merck Sharp & Dohme, Janssen and Roche and has served on advisory boards for Lilly, Sanofi-Aventis, Merck Sharp & Dohme, Novo Nordisk, Boehringer Ingelheim, Janssen and Astra Zeneca. SRKS has provided consulting to Amgen and received grants from Kowa and Sanofi. KKR has provided consultancy to Amgen, Sanofi, Pfizer, Regeneron, Astra Zeneca, Kowa, Aegerion, Merck Sharp & Dohme, Lilly and ISIS, and received grants from Sanofi, Regeneron, Amgen, Pfizer and Merck Sharp & Dohme through his institution., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

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.

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.

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 CV-related 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., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Purpose: 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., Methods: 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)., Results: 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., Conclusions: There is variability in the prevalence and incidence in comorbidities across racial/ethnic groups.

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.

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., (© 2016 World Stroke Organization.)

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., (Copyright © 2015. Published by Elsevier Inc.)

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., (© The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA.)

Our study describes the incidence and risk factors for undiagnosed diabetes in elderly cancer patients. Using Surveillance, Epidemiology, and End Results-Medicare data, we followed patients with breast, colorectal, lung, or prostate cancer from 24 months before to 3 months after cancer diagnosis. Medicare claims were used to exclude patients with diabetes 24 to 4 months before cancer (look-back period), identify those with diabetes undiagnosed until cancer, and construct indicators of preventive services, physician contact, and comorbidity during the look-back period. Logistic regression analyses were performed to identify factors associated with undiagnosed diabetes. Overall, 2,678 patients had diabetes undiagnosed until cancer. Rates were the highest in patients with both advanced-stage cancer and low prior primary care/medical specialist contact (breast 8.2%, colorectal 5.9%, lung 4.4%). Nonwhite race/ethnicity, living in a census tract with a higher percent of the population in poverty and a lower percent college educated, lower prior preventive services use, and lack of primary care and/or medical specialist care prior to cancer all were associated with higher (P ≤ 0.05) adjusted odds of undiagnosed diabetes. Undiagnosed diabetes is relatively common in selected subgroups of cancer patients, including those already at high risk of poor outcomes due to advanced cancer stage.

Preexisting comorbidity adversely impacts breast cancer treatment and outcomes. We examined the incremental impact of comorbidity undetected until cancer. We followed breast cancer patients in SEER-Medicare from 12 months before to 84 months after diagnosis. Two comorbidity indices were constructed: the National Cancer Institute index, using 12 months of claims before cancer, and a second index for previously undetected conditions, using three months after cancer. Conditions present in the first were excluded from the second. Overall, 6,184 (10.1%) had ≥1 undetected comorbidity. Chronic obstructive pulmonary disease (38%) was the most common undetected condition. In multivariable analyses that adjusted for comorbidity detected before cancer, older age, later stage, higher grade, and poor performance status all were associated with higher odds of ≥1 undetected comorbidity. In stage I-III cancer, undetected comorbidity was associated with lower adjusted odds of receiving adjuvant chemotherapy (Odds Ratio (OR) = 0.81, 95% Confidence Interval (CI) 0.73-0.90, P < 0.0001; OR = 0.38, 95% CI 0.30-0.49, P < 0.0001; index score 1 or ≥2, respectively), and with increased mortality (Hazard Ratio (HR) = 1.45, 95% CI 1.38-1.53, P < 0.0001; HR = 2.38, 95% CI 2.18-2.60, P < 0.0001; index score 1 or ≥2). Undetected comorbidity is associated with less aggressive treatment and higher mortality in breast cancer.

Background and Objectives: 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., Design, Setting, Participants, & Measurements: 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., Results: 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 (P<0.05) 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)., Conclusion: 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.

Objective: Studies suggest comorbidity plays an important role in ovarian cancer. We characterized the epidemiology of comorbid conditions in elderly U.S. women with ovarian cancer., Methods: Women with ovarian cancer age ≥66 years, and matched cancer-free women, were identified using the National Cancer Institute's Surveillance, Epidemiology, and End Results registry linked to Medicare claims. Prevalence before diagnosis/index date and 3- and 12-month incidence rates (per 1000 person-years) after diagnosis/index date were estimated for 34 chronic and acute conditions across a broad range of diagnostic categories., Results: There were 5087 each of women with ovarian cancer and cancer-free women. The prevalence of most conditions was similar between cancer and cancer-free patients, but exceptions included hypertension (51.8% and 43.5%, respectively), osteoarthritis (13.4% and 17.3%, respectively), and cerebrovascular disease (8.0% and 9.8%, respectively). In contrast, 3- and 12-month incidence rates (per 1000 person years) of most conditions were significantly higher in cancer than in cancer-free patients: hypertension (177.3 and 47.4, respectively); thromboembolic event (145.3 and 5.5, respectively); congestive heart failure (113.3 and 28.6, respectively); infection (664.4 and 55.2, respectively); and anemia (408.3 and 33.1, respectively) at 12 months., Conclusions: Comorbidities were common among elderly women. After cancer diagnosis, women with ovarian cancer had a much higher incidence of comorbidities than cancer-free women. The high incidence of some of these comorbidities may be related to the cancer or its treatment, but others may have been prevalent but undiagnosed until the cancer diagnosis. The presence of comorbidities may affect treatment decisions., (Copyright © 2013 Elsevier Inc. All rights reserved.)

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: In breast cancer, diabetes diagnosed prior to cancer (previously diagnosed) is associated with advanced cancer stage and increased mortality. However, in the general population, 40% of diabetes is undiagnosed until glucose testing, and evidence suggests one consequence of increased evaluation and management around breast cancer diagnosis is the increased detection of previously undiagnosed diabetes. Biological factors - for instance, higher insulin levels due to untreated disease - and others underlying the association between previously diagnosed diabetes and breast cancer could differ in those whose diabetes remains undiagnosed until cancer. Our objectives were to identify factors associated with previously undiagnosed diabetes in breast cancer, and to examine associations between previously undiagnosed diabetes and cancer stage, treatment patterns, and mortality., Methods: Using Surveillance, Epidemiology, and End Results-Medicare, we identified women diagnosed with breast cancer and diabetes between 01/2001 and 12/2005. Diabetes was classified as previously diagnosed if it was identified within Medicare claims between 24 and 4 months before cancer diagnosis, and previously undiagnosed if it was identified from 3 months before to ≤ 3 months after cancer. Patients were followed until 12/2007 or death, whichever came first. Multivariate analyses were performed to examine risk factors for previously undiagnosed diabetes and associations between undiagnosed (compared to previously diagnosed) diabetes, cancer stage, treatment, and mortality., Results: Of 2,418 patients, 634 (26%) had previously undiagnosed diabetes; the remainder had previously diagnosed diabetes. The mean age was 77.8 years, and 49.4% were diagnosed with in situ or stage I disease. Age > 80 years (40% of the cohort) and limited health system contact (primary care physician and/or preventive services) prior to cancer were associated with higher adjusted odds of previously undiagnosed diabetes. Previously undiagnosed diabetes was associated with higher adjusted odds of advanced stage (III/IV) cancer (Odds Ratio = 1.37: 95% Confidence Interval (CI) 1.05 - 1.80; P = 0.02), and a higher adjusted mortality rate due to causes other than cancer (Hazard Ratio = 1.29; 95% CI 1.02 - 1.63; P = 0.03)., Conclusions: In breast cancer, previously undiagnosed diabetes is associated with advanced stage cancer and increased mortality. Identifying biological factors would require further investigation.

Romiplostim increases platelet counts and reduces the risk of bleeding in patients with immune thrombocytopenia (ITP). This post hoc analysis compared the effect of romiplostim versus medical standard of care (SOC) on clinically relevant bleeding-related episodes (BREs) in a 52-week open-label study of patients with ITP. BREs were defined as actual bleeding events and/or use of rescue medication. Nonsplenectomized adult patients with ITP were randomized to receive weekly subcutaneous injections of romiplostim (n = 157) or SOC (n = 77). The rate of all BREs (per 100 patient-weeks) was lower in patients treated with romiplostim (3.1) than in those treated with SOC (9.4); the relative rate (romiplostim/SOC) was 0.33 (95 % CI 0.27-0.40). The rate of BREs associated with immunoglobulin (Ig) rescue medication was also lower for romiplostim (0.2) than SOC (4.8); the relative rate (romiplostim/SOC) was 0.05 (95 % CI 0.03-0.08). BRE rates were lower in patients with platelet counts ≥50 × 10(9)/L, and patients treated with romiplostim spent more time with platelet counts ≥50 × 10(9)/L than did patients treated with SOC. Bleeding-related hospitalizations were rare in both groups. Thus, romiplostim treatment provided greater reductions in all BREs, as well as BREs involving Ig rescue medications, than did SOC.

Objectives: To assess the accuracy and precision of inverse probability weighted (IPW) least squares regression analysis for censored cost data., Methods: By using Surveillance, Epidemiology, and End Results-Medicare, we identified 1500 breast cancer patients who died and had complete cost information within the database. Patients were followed for up to 48 months (partitions) after diagnosis, and their actual total cost was calculated in each partition. We then simulated patterns of administrative and dropout censoring and also added censoring to patients receiving chemotherapy to simulate comparing a newer to older intervention. For each censoring simulation, we performed 1000 IPW regression analyses (bootstrap, sampling with replacement), calculated the average value of each coefficient in each partition, and summed the coefficients for each regression parameter to obtain the cumulative values from 1 to 48 months., Results: The cumulative, 48-month, average cost was $67,796 (95% confidence interval [CI] $58,454-$78,291) with no censoring, $66,313 (95% CI $54,975-$80,074) with administrative censoring, and $66,765 (95% CI $54,510-$81,843) with administrative plus dropout censoring. In multivariate analysis, chemotherapy was associated with increased cost of $25,325 (95% CI $17,549-$32,827) compared with $28,937 (95% CI $20,510-$37,088) with administrative censoring and $29,593 ($20,564-$39,399) with administrative plus dropout censoring. Adding censoring to the chemotherapy group resulted in less accurate IPW estimates. This was ameliorated, however, by applying IPW within treatment groups., Conclusion: IPW is a consistent estimator of population mean costs if the weight is correctly specified. If the censoring distribution depends on some covariates, a model that accommodates this dependency must be correctly specified in IPW to obtain accurate estimates., (Copyright © 2012 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

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.

Background: Granulocyte-colony stimulating factor (G-CSF) reduces the risk of severe neutropenia associated with chemotherapy, but its cost implications following chemotherapy are unknown., Objective: Our objective was to examine associations between G-CSF use and medical costs after initial adjuvant chemotherapy in early-stage (stage I-III) breast cancer (ESBC)., Methods: Women diagnosed with ESBC from 1999 to 2005, who had an initial course of chemotherapy beginning within 180 days of diagnosis and including ≥1 highly myelosuppressive agent, were identified from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. Medicare claims were used to describe the initial chemotherapy regimen according to the classes of agents used: anthracycline ([A]: doxorubicin or epirubicin); cyclophosphamide (C); taxane ([T]: paclitaxel or docetaxel); and fluorouracil (F). Patients were classified into four study groups according to their G-CSF use: (i) primary prophylaxis, if the first G-CSF claim was within 5 days of the start of the first chemotherapy cycle; (ii) secondary prophylaxis, if the first claim was within 5 days of the start of the second or subsequent cycles; (iii) G-CSF treatment, if the first claim occurred outside of prophylactic use; and (iv) no G-CSF. Patients were described by age, race, year of diagnosis, stage, grade, estrogen (ER) and progesterone (PR) receptor status, National Cancer Institute (NCI) Co-morbidity Index, chemotherapy regimen and G-CSF use. Total direct medical costs ($US, year 2009 values) to Medicare were estimated from 4 weeks after the last chemotherapy administration up to 48 months. Medical costs included those for ESBC treatment and all other medical services received after chemotherapy. Least squares regression, using inverse probability weighting (IPW) to account for censoring within the cohort, was used to evaluate adjusted associations between G-CSF use and costs., Results: A total of 7026 patients were identified, with an average age of 72 years, of which 63% had stage II disease, and 59% were ER and/or PR positive. Compared with no G-CSF, those receiving G-CSF primary prophylaxis were more likely to have stage III disease (30% vs. 16%; p < 0.0001), to be diagnosed in 2003-5 (87% vs. 26%; p < 0.0001), and to receive dose-dense AC-T (26% vs. 1%; p < 0.0001), while they were less likely to receive an F-based regimen (12% vs. 42%; p < 0.0001). Overall, the estimated average direct medical cost over 48 months after initial chemotherapy was $US 42,628. In multivariate analysis, stage II or III diagnosis (compared with stage I), NCI Co-morbidity Index score 1 or ≥2 (compared with 0), or FAC or standard AC-T (each compared with AC) were associated with significantly higher IPW 48-month costs. Adjusting for patient demographic and clinical factors, costs in the G-CSF primary prophylaxis group were not significantly different from those not receiving primary prophylaxis (the other three study groups combined). In an analysis that included four separate study groups, G-CSF treatment was associated with significantly greater costs (incremental cost = $US 2938; 95% CI 285, 5590) than no G-CSF., Conclusions: Direct medical costs after initial chemotherapy were not statistically different between those receiving G-CSF primary prophylaxis and those receiving no G-CSF, after adjusting for potential confounders.

Background. Trastuzumab improves survival in HER2-positive women with metastatic breast cancer (MBC). The consequences of longer survival include a higher likelihood of additional metastases, including those in the central nervous system (CNS). The effect of CNS metastases on both trastuzumab discontinuation and survival in older patients has not been described. Patients and Methods. We used the Surveillance Epidemiology and End Results (SEER) Medicare data to identify a cohort of 562 women age 66 or older with MBC who were diagnosed between January 1, 2000 and December 31, 2005, free of CNS metastases, and initiated trastuzumab after MBC diagnosis. Time to discontinuation and time to death were analyzed using proportional hazards models. Results. Newly diagnosed CNS metastases were associated with both higher risk of trastuzumab discontinuation (relative hazard [RH] = 1.78, 95% CI 1.11-2.87) and higher risk of death (RH = 2.49, 95% CI 1.84-3.37). The incidence rate of new CNS metastases was comparable among various sites of metastasis (10.7 to 14.7 per 1,000 patient-months), except for bone which was higher (24.1 per 1,000). Conclusion. The diagnosis of CNS metastases was associated with an increase in both the likelihood of discontinuing trastuzumab therapy as well as the risk of death.

Practice guidelines define hemodialysis catheter dysfunction as blood flow rate (BFR) <300 mL/min. We conducted a study using data from DaVita and the United States Renal Data System to evaluate the impact of catheter dysfunction on dialysis and other medical services. Patients were included if they had ≥8 consecutive weeks of catheter dialysis between 8/2004 and 12/2006. Actual BFR <300 mL/min despite planned BFR ≥300 mL/min was used to define catheter dysfunction during each dialysis session. Among 9,707 patients, the average age was 62,53% were female, and 40% were black. The median duration of catheter dialysis was 190 days, and the cohort accounted for 1,075,701 catheter dialysis sessions. There were 70,361 sessions with catheter dysfunction, and 6,33 1 (65.2%) patients had at least one session with catheter dysfunction. In multivariate repeated measures analysis, catheter dysfunction was associated with increased odds of missing a dialysis session due to access problems (Odds ratio [OR] 2.50; P < 0.001), having an access-related procedure (OR 2.10; P < 0.001), and being hospitalized (OR 1.10; P = 0.001). Catheter dysfunction defined according to NKF vascular access guidelines results in disruptions of dialysis treatment and increased use of other medical services.

Rituximab improves survival in follicular lymphoma (FL), but is considerably more expensive than conventional chemotherapy. We estimated the total direct medical costs, cumulative survival, and cost-effectiveness of adding rituximab to first-line chemotherapy for FL, based on a single source of data representing routine practice in the elderly. Using surveillance, epidemiology, and end results (SEER) registry data plus Medicare claims, we identified 1,117 FL patients who received first-line CHOP (cyclophosphamide (C), doxorubicin, vincristine (V), and prednisone (P)) or CVP +/- rituximab. Multivariate regression was used to estimate adjusted cumulative cost and survival differences between the two groups over four years after beginning treatment. The median age was 73 years (minimum 66 years), 56% had stage III-IV disease, and 67% received rituximab. Adding rituximab to first-line chemotherapy was associated with higher adjusted incremental total cost ($18,695; 95% Confidence Interval (CI) $9,302-$28,643) and longer adjusted cumulative survival (0.18 years; 95% CI 0.10-0.27) over four years of followup. The expected cost-effectiveness was $102,142 (95% CI $34,531-296,337) per life-year gained. In routine clinical practice, adding rituximab to first-line chemotherapy for elderly patients with FL results in higher direct medical costs to Medicare and longer cumulative survival after four years.

Purpose: Elevated levels of phosphorus (P) and calcium (Ca) have been shown in observational studies to be associated with an increased risk of adverse clinical outcomes including mortality. Vitamin D sterols have been shown to increase the risk of hypercalcemia and hyperphosphatemia in clinical trials. We sought to explore these risks in real-world clinical practice., Methods: We employed a case-crossover design, which eliminates confounding by non-time-varying patient characteristics by comparing, within each patient, vitamin D doses before the event with those at an earlier period. Using this method, we estimated the risk of hypercalcemic (Ca ≥ 11 g/dL) and hyperphosphatemic (P ≥ 8 g/dL) events for patients at different dose quartiles of vitamin D relative to patients not on a vitamin D sterol., Results: There was a dose-dependent association between vitamin D dose quartile and risk of hypercalcemia or hyperphosphatemia. In adjusted analyses, each increase in vitamin D quartile was associated with a multiple of hypercalcemia risk between 1.7 and 19 times compared with those not on vitamin D and a multiple of hyperphosphatemia risk between 1.8 and 4., Conclusion: Use of vitamin D sterols is associated with an increased risk of hypercalcemic and hyperphosphatemic events in real-world clinical practice. Other potential predictors of these events, such as phosphate binder use and dialysate Ca levels, were not examined in this analysis., (Copyright © 2011 John Wiley & Sons, Ltd.)

Objective: To estimate the number of non-Hispanic white individuals in the United States avoiding legal blindness and visual impairment from neovascular age-related macular degeneration (AMD) with ranibizumab availability., Methods: Modeling of visual acuity outcomes from phase 3 ranibizumab trials to incidence rates of neovascular AMD from population-based studies., Results: If no treatment were given, of the 103 582 individuals developing neovascular AMD for which ranibizumab would be indicated and available, 16 268 would become legally blind in 2 years. Monthly ranibizumab would reduce the incidence of legal blindness in 2 years by 72% (95% confidence interval [CI], 70% to 74%) to 4484 individuals. If no treatment were given, 34 702 would become visually impaired. Monthly ranibizumab would reduce the incidence of visual impairment in 2 years by 37% (95% CI, 35% to 39%) to 21 919 cases., Conclusions: Ranibizumab should have a substantial effect on reducing the magnitude of legal blindness and visual impairment within 2 years after diagnosis of neovascular AMD among non-Hispanic white individuals in the United States. Although racial subgroups other than non-Hispanic whites were not considered (because there is limited information in the literature regarding incidence rates of choroidal neovascularization in other populations) and although these results assume access to and application of monthly ranibizumab for 2 years, the number of individuals developing legal blindness or vision impairment from neovascular AMD should be reduced dramatically if monthly ranibizumab is applied when indicated.

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.