An Analysis of Dasatinib Treatment Patterns in Patients with Chronic Myeloid Leukemia after Experiencing Pleural Effusion during Dasatinib Therapy.

INTRODUCTION: Treatment with dasatinib for chronic myeloid leukemia (CML) has been associated with development of pleural effusion; however, data regarding its optimal management are limited. We examined treatment patterns and healthcare resource utilization (HCRU) and costs among patients with CML treated with dasatinib who experienced a subsequent pleural effusion. METHODS: Adults with CML and ≥1 pharmacy claim for dasatinib in 2015-2018 who experienced pleural effusion after dasatinib were identified using data from claims databases. RESULTS: Overall, 123 patients were eligible. After 1 year, of the 38.2% of patients with a dose modification, 72.3% did not switch treatment; among these patients, 70.6% continued treatment. Among patients with a stable dose after pleural effusion (61.8%), 57.9% later switched to another TKI. The mean (SD) duration of dasatinib treatment after pleural effusion was 262.0 (124.0) days for patients with a dose modification versus 149.1 (155.2) days for those with a stable dose (p < 0.001). HCRU and costs were similar between groups. CONCLUSION: Dasatinib dose modification after pleural effusion was not always required; however, patients with dose modifications continued therapy for a longer duration with a lower rate of switching to another TKI versus patients who remained on a stable dose.

Epidemiology of Huntington's Disease in the United States Medicare and Medicaid Populations.

INTRODUCTION: Huntington's disease (HD) is a rare, genetic, and ultimately fatal neurodegenerative disease, with a devastating impact on individuals and families across generations. Few estimates of HD epidemiology in the United States (US) exist. METHODS: This study employed a retrospective cross-sectional design to examine the epidemiology of HD in the US Medicare and Medicaid beneficiary populations using 2016-2017 claims data from the Medicare 100% Research Identifiable Files (RIFs) and 2014 claims data from the Medicaid Analytic eXtract (MAX) files for 17 states. Medicare beneficiaries ≥65 years with a diagnosis of HD (≥1 claim with ICD-10-CM code G10) in 2017 and Medicaid beneficiaries <65 years with a diagnosis of HD (≥1 claim with ICD-9-CM code 333.4) in 2014 were identified. The study outcomes included the 2017 prevalence proportion and incidence rate of HD in the Medicare population and the 2014 prevalence proportion of HD in the Medicaid population. RESULTS: In the Medicare population, 1,941 prevalent and 819 incident cases of HD were identified in 2017, corresponding to a prevalence proportion of 13.1 per 100,000 persons and incidence rate of 6.1 per 100,000 person-years. In the Medicaid population, 353 prevalent cases of HD were identified in 2014, corresponding to a prevalence proportion of 15.2 per 100,000 persons. CONCLUSION: This study suggests that prevalence and incidence of HD in the US may be higher than previously estimated. This has important implications in raising awareness of HD among providers and payers and ensuring availability of and access to services for HD patients and care partners in the Medicare and Medicaid populations.

Transcriptional Regulation of the Synaptic Vesicle Protein Synaptogyrin-3 (SYNGR3) Gene: The Effects of NURR1 on Its Expression.

Synaptogyrin-3 (SYNGR3) is a synaptic vesicular membrane protein. Amongst four homologues (SYNGR1 to 4), SYNGR1 and 3 are especially abundant in the brain. SYNGR3 interacts with the dopamine transporter (DAT) to facilitate dopamine (DA) uptake and synaptic DA turnover in dopaminergic transmission. Perturbed SYNGR3 expression is observed in Parkinson's disease (PD). The regulatory elements which affect SYNGR3 expression are unknown. Nuclear-receptor-related-1 protein (NURR1) can regulate dopaminergic neuronal differentiation and maintenance via binding to NGFI-B response elements (NBRE). We explored whether NURR1 can regulate SYNGR3 expression using an in silico analysis of the 5'-flanking region of the human SYNGR3 gene, reporter gene activity and an electrophoretic mobility shift assay (EMSA) of potential cis-acting sites. In silico analysis of two genomic DNA segments (1870 bp 5'-flanking region and 1870 + 159 bp of first exon) revealed one X Core Promoter Element 1 (XCPE1), two SP1, and three potential non-canonical NBRE response elements (ncNBRE) but no CAAT or TATA box. The longer segment exhibited gene promoter activity in luciferase reporter assays. Site-directed mutagenesis of XCPE1 decreased promoter activity in human neuroblastoma SH-SY5Y (↓43.2%) and human embryonic kidney HEK293 cells (↓39.7%). EMSA demonstrated NURR1 binding to these three ncNBRE. Site-directed mutagenesis of these ncNBRE reduced promoter activity by 11-17% in SH-SY5Y (neuronal) but not in HEK293 (non-neuronal) cells. C-DIM12 (Nurr1 activator) increased SYNGR3 protein expression in SH-SY5Y cells and its promoter activity using a real-time luciferase assay. As perturbed vesicular function is a feature of major neurodegenerative diseases, inducing SYNGR3 expression by NURR1 activators may be a potential therapeutic target to attenuate synaptic dysfunction in PD.

Real-World Treatment Patterns for Lung Neuroendocrine Tumors: A Claims Database Analysis.

OBJECTIVE: The aim of this study was to describe real-world lung neuroendocrine tumor (NET) treatment patterns. METHODS: This study examined cytotoxic chemotherapy (CC), somatostatin analogues (SSA), targeted therapy (TT), interferon, and liver-directed therapies in 2 US claims databases. Patients ≥18 years with ≥1 inpatient or ≥2 outpatient claims for lung NET, initiating pharmacologic treatment between July 1, 2009, and June 30, 2014, were identified and followed until the end of enrollment or study end, whichever occurred first. RESULTS: A total of 785 newly pharmacologically treated lung NET patients were identified: mean (SD) age was 58.6 (9.1) years; 54.0% were female; 78.2% started first-line therapy with CC, 18.1% with SSA, and 1.1% with TT. Mean duration of first-line treatment was 397 days for SSA, 142 days for CC, and 135 days for TT. 74.1% of patients received no pharmacological treatment beyond first-line. The most common second-line treatment was SSA. CONCLUSIONS: Most patients received CC as first-line treatment, with SSA being less common. SSA-treated patients remained on therapy for > 1 year, compared to < 5 months for CC. The high proportion of patients using chemotherapy and the low proportion receiving second-line treatment seems consistent with treatment guidelines for small cell lung cancer rather than for NET. Future studies are warranted to describe reasons for treatment choice, discontinuation, and switching.

Incidence and prevalence of neuroendocrine tumors of the lung: analysis of a US commercial insurance claims database.

BACKGROUND: As reported in Surveillance, Epidemiology, and End Results (SEER) data, US incidence and prevalence of neuroendocrine tumors (NET) has increased over recent years. The study objective was to update incidence and prevalence information for lung NET using administrative claims. METHODS: This descriptive epidemiological study used 2009-2014 data from 2 US claims databases: MarketScan and PharMetrics. Patients (18-64 years old) had ≥1 inpatient or ≥ 2 outpatient claims with NET of bronchus or lung, identified by International Classification of Diseases, 9th Revision, Clinical Modification diagnosis codes. Prevalence was number of lung NET patients divided by number of enrollees/year. Incidence was number of patients with a first observed NET diagnosis who were disease-free for 2 years prior, divided by number of enrollees. Age and gender adjustments performed. RESULTS: The annual number of patients with lung NET identified from 2009 to 2014 ranged from 435 to 796 (MarketScan) and 419-648 (PharMetrics). In MarketScan, there was a 7.4% (95%CI 2.1-13.0; p = 0.027) annual percent change (APC) in the age-adjusted incidence for males and 6.8% (- 0.2-14.3; 0.052) for females. In PharMetrics, APC was - 2.9% (- 13.8-9.4; 0.395) for males; 14.7% (- 12.9-51.2; 0.165) for females. In MarketScan, APC in age-adjusted prevalence for males was 9.9% (4.7-15.3; 0.006); 16.2% (11.4-21.1; <.001) for females. For PharMetrics, APCs were 9.5% (2.3-17.2; 0.021) for males; 16.3% (9.6-23.5; 0.002) for females. CONCLUSIONS: From 2009 to 2014 there was a statistically significant increase in age-adjusted lung NET incidence for males in MarketScan, and a statistically significant increase in age-adjusted prevalence for both genders in PharMetrics. Incidence and prevalence changes, to the extent they exist, may be due to better diagnostic methods, increased awareness of NET among clinicians and pathologists, and/or an actual increase in US disease occurrence. Differences in rates across databases are difficult to explain. These results suggest the need for awareness of the clinically effective and safe treatment options available for lung NET patients among healthcare providers.

The Incidence and Health Care Resource Burden of the Myelodysplastic Syndromes in Patients in Whom First-Line Hypomethylating Agents Fail.

BACKGROUND: Although hypomethylating agents (HMAs) are effective and approved therapies for patients with myelodysplastic syndromes (MDS), many patients do not benefit from treatment, and nearly all ultimately stop responding to HMAs. The incidence and cost burden of HMA failure are unknown yet needed to appreciate the magnitude and significance of such failure. METHODS: We analyzed a de-identified dataset of over 5 million individuals with private health insurance in the U.S. to estimate MDS incidence, prevalence, and treatments. Based on MDS provider interviews, a conceptual model of MDS patient management was constructed to create a new, claims-relevant and drug development-relevant definition of HMA treatment failure. This algorithm was used to define resource encumbrance of MDS patients in whom HMA treatment failed. RESULTS: We estimated an MDS incidence rate of ∼70 cases per 100,000 enrollees per year and a prevalence of 155 cases per 100,000 enrollees. The proportion of MDS patients receiving HMA treatment was low (∼3%), and treatment was typically initiated within 1 year of the first MDS claim. Notably, HMA-treated individuals were older and had more comorbidities than the overall MDS cohort. Total health care costs of managing MDS patients after HMA failure were high (∼$77,000 during the first 6 months) and were driven primarily by non-pharmacy costs. CONCLUSION: This study quantifies for the first time the burden of significant unmet need in caring for MDS patients following HMA treatment failure. The Oncologist 2017;22:379-385Implications for Practice: U.S.-based treatment patterns among MDS patients demonstrate the significant clinical, financial, and health care burden associated with HMA failure and call for active therapies for this patient population.

Tolerability of central nervous system symptoms among HIV-1 infected efavirenz users: analysis of patient electronic medical record data.

Efavirenz (EFV) is a non-nucleoside reverse transcriptase inhibitor indicated for treatment of HIV-1 infection. Despite concern over EFV tolerability in clinical trials and practice, particularly related to central nervous system (CNS) adverse events, some observational studies have shown high rates of EFV continuation at one year and low rates of CNS-related EFV substitution. The objective of this study was to further examine the real-world rate of CNS-related EFV discontinuation in antiretroviral therapy naïve HIV-1 patients. This retrospective cohort study used a nationally representative electronic medical records database to identify HIV-1 patients ≥12 years old, treated with a 1st-line EFV-based regimen (single or combination antiretroviral tablet) from 1 January 2009 to 30 June 2013. Patients without prior record of EFV use during 6-month baseline (i.e., antiretroviral therapy naïve) were followed 12 months post-medication initiation. CNS-related EFV discontinuation was defined as evidence of a switch to a replacement antiretroviral coupled with record of a CNS symptom within 30 days prior, absent lab evidence of virologic failure. We identified 1742 1st-line EFV patients. Mean age was 48 years, 22.7% were female, and 8.1% had a prior report of CNS symptoms. The first year, overall discontinuation rate among new users of EFV was 16.2%. Ten percent of patients (n = 174) reported a CNS symptom and 1.1% (n = 19) discontinued EFV due to CNS symptoms: insomnia (n = 12), headache (n = 5), impaired concentration (n = 1), and somnolence (n = 1). The frequency of CNS symptoms was similar for patients who discontinued EFV compared to those who did not (10.3 vs. 9.9%; P = .86). Our study found that EFV discontinuation due to CNS symptoms was low, consistent with prior reports.

Long-term treatment outcomes of acromegaly patients presenting biochemically-uncontrolled at a tertiary pituitary center.

BACKGROUND: Acromegaly is a rare, slowly progressive disorder resulting from excessive growth hormone (GH) production by a pituitary somatotroph tumor. The objective of this study was to examine acromegaly treatment outcomes during long-term care at a specialized pituitary center in patients presenting with lack of biochemical control. METHODS: Data came from an acromegaly registry at the Cedars-Sinai Medical Center Pituitary Center (center). Acromegaly patients included in this study were those who presented biochemically-uncontrolled for care at the center. Biochemical control status, based on serum insulin-like growth factor-1 values, was determined at presentation and at study end. Patient characteristics and acromegaly treatments were reported before and after presentation by presenting treatment status and final biochemical control status. Data on long-term follow-up were recorded from 1985 through June 2013. RESULTS: Seventy-four patients presented uncontrolled: 40 untreated (54.1%) and 34 (45.9%) previously-treated. Mean (SD) age at diagnosis was 43.2 (14.7); 32 (43.2%) were female patients. Of 65 patients with tumor size information, 59 (90.8%) had macroadenomas. Prior treatments among the 34 previously-treated patients were pituitary surgery alone (47.1%), surgery and medication (41.2%), and medication alone (11.8%). Of the 40 patients without prior treatment, 82.5% achieved control by study end. Of the 34 with prior treatment, 50% achieved control by study end. CONCLUSIONS: This observational study shows that treatment outcomes of biochemically-uncontrolled acromegaly patients improve with directed care, particularly for those that initially present untreated. Patients often require multiple modalities of treatment, many of which are offered with the highest quality at specialized pituitary centers. Despite specialized care, some patients were not able to achieve biochemical control with methods of treatment that were available at the time of their treatment, showing the need for additional treatment options.

The association between biochemical control and cardiovascular risk factors in acromegaly.

BACKGROUND: The study aim was to estimate the proportion of acromegaly patients with various comorbidities and to determine if biochemical control was associated with reduced proportion of cardiovascular risk factors. METHODS: Data were from a single-center acromegaly registry. Study patients were followed for ≥12 months after initial treatment. Study period was from first to last insulin-like growth factor-I and growth hormone tests. RESULTS: Of 121 patients, 55% were female. Mean age at diagnosis was 42.4 (SD: 15.0). Mean study period was 8.8 (SD: 7.2) years. Macroadenomas were observed in 93 of 106 patients (87.7%), and microadenomas in 13 (12.3%). Initial treatment was surgery in 104 patients (86%), pharmacotherapy in 16 (13.2%), and radiation therapy in 1 (0.8%). Of 120 patients, 79 (65.8%) achieved control during the study period. New onset comorbidities (reported 6 months after study start) were uncommon (<10%). Comorbidities were typically more prevalent in uncontrolled versus controlled patients-24 (58.5%) vs. 33 (41.8%) had hypertension, 17 (41.5%) vs. 20 (25.3%) had diabetes, 11 (26.8%) vs. 16 (20.3%) had sleep apnea, and 3 (7.3%) vs. 3 (3.8%) had cardiomyopathy-except for colon polyps or cancer (19.5% vs. 20.3%), left ventricular hypertrophy (9.8% vs. 11.4%), and visual defects (14.6% vs. 17.7%). CONCLUSIONS: A greater number of comorbidities were observed in biochemically uncontrolled patients with acromegaly compared to their controlled counterparts in this single-center registry. About a third of the patients remained uncontrolled after a mean of >8 years of treatment, demonstrating the difficulty of achieving control in some patients.

EPIDEMIOLOGY OF GASTROINTESTINAL NEUROENDOCRINE TUMORS IN A U.S. COMMERCIALLY INSURED POPULATION.

OBJECTIVE: To estimate incidence and prevalence of gastrointestinal neuroendocrine tumors (GI NETs) in U.S. commercially insured patients. METHODS: This was a retrospective, cross-sectional study using 2009 to 2014 data from MarketScan and PharMetrics commercial claims databases. Patients were 18 to 64 years old, and had 1 inpatient or 2 outpatient claims with GI NET, identified by International Classification of Diseases, 9th Revision, Clinical Modification codes. Incidence was calculated as number of patients with NET who were disease-free for 2 years prior, divided by number of enrollees and reported as per million person-years (PMPY). Prevalence was calculated as the number of GI NET patients divided by the number of enrollees per year. RESULTS: The annual number of patients with GI NET ranged from 2,014 to 3,413 in MarketScan and 1,436 to 2,336 in PharMetrics. Incidence increased from 2011 to 2014: 67.0 to 79.1 PMPY in MarketScan and 47.4 to 58.2 PMPY in PharMetrics. Incidence increased by 24.3% in females and 10.7% in males in MarketScan, and by 17.6% in females and 29.3% in males in PharMetrics. Incidence increased with age and was highest in the 45 to 54 and 55 to 64 age groups. Prevalence increased from 77.9 to 131.2 per million per year (MarketScan) and 50.8 to 108.9 (PharMetrics) from 2009 to 2014. Prevalence was generally higher in females than males and highest in 55 to 64 year olds. These increases may be due to better diagnostics, increased awareness of NET among clinicians and pathologists, and/or actual increase in disease. CONCLUSION: Clinicians may see GI NET with increasing frequency and should become more familiar with its presentation and treatment. ABBREVIATIONS: GI = gastrointestinal; ICD-9-CM = International Classification of Diseases, 9th Revision, Clinical Modification; NET = neuroendocrine tumor; PMPY = per million person-years; SEER = Surveillance, Epidemiology, and End Results.

AN APPROACH TO USING DATA MINING TO SUPPORT EARLY IDENTIFICATION OF ACROMEGALY.

OBJECTIVE: Data mining using insurance claims presents an opportunity to incorporate new analytic techniques in identifying rare conditions. This study aims to identify dyads of clinical conditions associated with acromegaly that may, with further validation and testing, be used to initially identify and diagnose this rare disease more accurately and efficiently. METHODS: This case-control study used two claims databases to identify acromegaly patients (cases) (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM]: 253.0) from 2008-2013. Each case was assigned two nonacromegaly controls (same age, gender, and region). Matched patients were randomly split into development and validation datasets. With expert clinician input, we isolated common associated conditions using ICD-9-CM codes. We identified all 2-way combinations of these conditions (dyads) and calculated the rate and risk relative (RR) to controls. Dyads meeting certain criteria (case rate ≥5% [or ≥1% if RR ≥5] or observed RR > expected) were replicated in the validation dataset to confirm results. RESULTS: We identified 3,731 cases and 7,462 controls: mean age 41.8 (SD, 16.1) years, 51.8% female. A total of 32 and 38 dyads, reduced from 630, met study criteria. Among replicated dyads, case rates varied -15.9% (hypertension and metabolic disorder) to 0.6% (arthritis and menstrual abnormalities). The highest RRs (e.g., valvular insufficiency and colon polyps [RR, 13.5; rate, 0.7%]) also exceeded expected values. Replication showed similar RR direction and size. CONCLUSION: This novel analytic approach revealed several dyads that were significantly associated with an acromegaly diagnosis. Presence of high-risk condition pairs, if verified by a detailed data source (e.g., medical charts), may be incorporated into screening tools or serve as potential markers for physicians to consider an acromegaly diagnosis. ABBREVIATIONS: ICD-9-CM = International Classification of Diseases, Ninth Revision, Clinical Modification ID = identification RR = relative risk.

Mechanical ventilation in idiopathic pulmonary fibrosis: a nationwide analysis of ventilator use, outcomes, and resource burden.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is associated with increased risk of respiratory-related hospitalizations. Studies suggest mechanical ventilation (MV) use in IPF does not improve outcomes and guidelines recommend against its general use. Our objective was to investigate MV use and association with cost and mortality in IPF. METHODS: This retrospective study, using a nationwide sample, included claims with IPF (ICD-9-CM: 516.3) in 2009-2011 and principal respiratory disease diagnosis (ICD-9-CM: 460-519); excluding lung transplant. Regression models were used to determine predictors of MV and association with cost, LOS, and mortality. Domain analysis was used to account for use of subpopulation. Costs were adjusted to 2011. Data on patient severity not available. RESULTS: Twenty two thousand three hundred fifty non-transplant IPF patients were admitted with principal respiratory disease diagnosis: Mean age 70.0 (SD 13.9), 49.1% female, mean LOS 7.4 (SD 8.2). MV was used in 11.4% of patients with a non-significant decline over time. In regression models, MV was associated with an increased stay of 9.78 days (95% CI 8.38-11.18) and increased cost of $36,583 (95% CI $32,021-41,147). MV users had significantly increased mortality (OR 15.55, 95% CI 12.13-19.95) versus nonusers. CONCLUSIONS: Mechanical ventilation use has not significantly changed over time and is mostly used in younger patients and those admitted for non-IPF respiratory conditions. MV was associated with a 4-fold admission cost increase ($49,924 versus $11,742) and a 7-fold mortality increase (56% versus 7.5%), although patients who receive MV may differ from those who do not. Advances in treatment and decision aids are needed to improve outcomes in IPF.

IDENTIFICATION OF POTENTIAL MARKERS FOR CUSHING DISEASE.

OBJECTIVE: Cushing disease (CD) causes a wide variety of nonspecific symptoms, which may result in delayed diagnosis. It may be possible to uncover unusual combinations of otherwise common symptoms using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes. Our aim was to identify and evaluate dyads of clinical symptoms or conditions associated with CD. METHODS: We conducted a matched case-control study using a commercial healthcare insurance claims database designed to compare the relative risk (RR) of individual conditions and dyad combinations of conditions among patients with CD versus matched non-CD controls. RESULTS: With expert endocrinologist input, we isolated 10 key conditions (localized adiposity, hirsutism, facial plethora, polycystic ovary syndrome, abnormal weight gain, hypokalemia, deep venous thrombosis, muscle weakness, female balding, osteoporosis) with RRs varying from 5.3 for osteoporosis to 61.0 for hirsutism (and infinite RR for localized adiposity). The RRs of dyads of these conditions ranged from 4.1 for psychiatric disorders/serious infections to 128.0 for hirsutism/fatigue in patients with versus without CD. Construction of uncommon dyads resulted in further increases in RRs beyond single condition analyses; for example, osteoporosis alone had an RR of 5.3, which increased to 8.3 with serious infections and to 52.0 with obesity. CONCLUSION: This study demonstrated that RR of any one of 10 key conditions selected by expert opinion was ≥5 times greater in CD compared to non-CD, and nearly all dyads had RR≥5. An uncommon dyad of osteoporosis and obesity had an RR of 52.0. If clinicians consider the diagnosis of CD when the highest-risk conditions are seen, identification of this rare disease may improve.

INCIDENCE AND PREVALENCE OF ACROMEGALY IN THE UNITED STATES: A CLAIMS-BASED ANALYSIS.

OBJECTIVE: Acromegaly, a rare endocrine disorder, results from excessive growth hormone secretion, leading to multisystem-associated morbidities. Using 2 large nationwide databases, we estimated the annual incidence and prevalence of acromegaly in the U.S. METHODS: We used 2008 to 2013 data from the Truven Health MarketScan® Commercial Claims and Encounters Database and IMS Health PharMetrics healthcare insurance claims databases, with health plan enrollees <65 years of age. Study patients had ≥2 claims with acromegaly (International Classification of Diseases, 9th Revision, Clinical Modification Code [ICD-9CM] 253.0), or 1 claim with acromegaly and 1 claim for pituitary tumor, pituitary surgery, or cranial stereotactic radiosurgery. Annual incidence was calculated for each year from 2009 to 2013, and prevalence in 2013. Estimates were stratified by age and sex. RESULTS: Incidence was up to 11.7 cases per million person-years (PMPY) in MarketScan and 9.6 cases PMPY in PharMetrics. Rates were similar by sex but typically lowest in ≤17 year olds and higher in >24 year olds. The prevalence estimates were 87.8 and 71.0 per million per year in MarketScan and PharMetrics, respectively. Prevalence consistently increased with age but was similar by sex in each database. CONCLUSION: The current U.S. incidence of acromegaly may be up to 4 times higher and prevalence may be up to 50% higher than previously reported in European studies. Our findings correspond with the estimates reported by a recent U.S. study that used a single managed care database, supporting the robustness of these estimates in this population. Our study indicates there are approximately 3,000 new cases of acromegaly per year, with a prevalence of about 25,000 acromegaly patients in the U.S. ABBREVIATIONS: CT = computed tomography GH = growth hormone IGF-1 = insulin-like growth factor 1 ICD-9-CM Code = International Classification of Diseases, 9th Revision, Clinical Modification Codes MRI = magnetic resonance imaging PMPY = per million person-years.

Clinical and economic burden of idiopathic pulmonary fibrosis: a retrospective cohort study.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a devastating condition with a variable course. Not uncommonly, IPF patients are hospitalized for respiratory-related causes, including disease worsening. This study aimed to characterize the prevalence, and economic and health care burden of IPF. METHODS: Retrospective insurance claims data collected yearly between January 1, 2009 and December 31, 2011, were used to determine prevalence and calculate all-cause and respiratory-related resource utilization and costs. Patients had at least one inpatient claim or two outpatient claims for IPF (ICD-9-CM code 516.3). Results for health care burden are reported for the 2011 cohort (similar findings in 2009-2010). Costs are reported in 2011 US dollars ($). RESULTS: Patients with IPF had a mean age of 69.8-71.3 years. Overall prevalence for IPF was 28.8, 28.1 and 19.8 per 100,000 insured persons in 2009, 2010 and 2011. In each year, prevalence increased with age. In 2011, 37.7% of patients were hospitalized at least once for any cause; 19.5% for respiratory-related reasons. Also in 2011, the mean number of all-cause outpatient visits and respiratory-related office visits was 18.5 and 5.7 per patient, respectively. All-cause health care costs in 2011 were $59,379 per patient; 36.6% of costs ($21,732) were respiratory related. CONCLUSIONS: The prevalence of IPF in this claims database increased with age, with a notable increase in those over 65 years. IPF is associated with a large economic and health care burden. Additional research is needed to determine how such burden might be reduced.

Corticosteroid-related toxicity in patients with chronic idiopathic urticariachronic spontaneous urticaria.

BACKGROUND: Treatments for patients with chronic idiopathic urticaria (CIU)chronic spontaneous urticaria (CSU) who were unresponsive to antihistamines include oral corticosteroids (OCS). Risks of OCS-related side effects in these patients have not been described quantitatively. OBJECTIVE: To investigate the relationship between OCS use and the risk of developing side effects possibly attributable to OCS and associated health care costs in privately insured patients with CIU/CSU. METHODS: This retrospective cohort study analyzed a commercial claims data base from January 1, 2008, to December 31, 2012. Patients with CIU/CSU were identified by International Classification of Diseases, Ninth Revision, Clinical Modification codes via a validated algorithm. Possible OCS-related side effects included the following: diabetes mellitus, hypertension, lipid disorders, cataracts, depression or mania, osteoporosis or fractures, and infectious diseases. A time-dependent Cox regression (adjusted for age, sex, Charlson Comorbidity Index, and immunomodulator use) was used to separately model cumulative oral prednisone-equivalent exposure and the risk of side effects. Incremental total adjusted health care costs were compared in patients with versus patients without possible OCS-related side effects. RESULTS: Among 12,647 patients with CIU/CSU, 55.4% used OCS. An additional 1 g of prednisone-equivalent exposure was associated with a 7% increase in the likelihood of developing a possible side effect (hazard ratio, 1.07 [95% confidence interval, 1.051.08]). From the period before to the period after OCS initiation, the total mean adjusted annual health care costs increased by 1833 in users of OCS with new possible side effects and decreased by 2183 in patients without new possible side effects (p 0.001). CONCLUSION: Patients with CIU/CSU who were treated with OCS had an increased risk of possible OCS-related side effects and higher total health care costs than their counterparts not treated with OCS.

The impact of genomic testing on the recommendation for radiation therapy in patients with ductal carcinoma in situ: A prospective clinical utility assessment of the 12-gene DCIS score™ result.

BACKGROUND AND OBJECTIVES: Twenty percent of breast cancers are ductal carcinoma in situ (DCIS), with 15-60% having a local recurrence (LR) after surgery. Radiotherapy reduces LR by 50% but has not impacted survival. The validated Oncotype DX(®) 12-gene assay (DCIS Score) provides individualized 10-year LR estimates. This is the first study to assess whether DCIS Score impacts physicians' recommendations for radiation. METHODS: Ten sites enrolled women (9/2012-2/2014) with DCIS eligible for breast-conserving therapy, excluding patients with invasive carcinoma and planned mastectomy. Prospective data collected included clinicopathologic factors, DCIS Score assay, and treatment recommendation before and after the assay result was known. RESULTS: In 115 patients (median age: 61 years; 74.8% postmenopausal), median DCIS size was 8 mm; 20% were nuclear grade 1, 46.1% grade 2; 64.4% reported necrosis. 86.1% were ER+, 79.1% PR+ (immunohistochemistry assay). Median DCIS Score: 29 (range: 0-85). Pre-assay, 73% (95%CI: 64.0-80.9%) had radiotherapy recommendations vs. 59.1% (95%CI: 49.6-68.2%) post-assay (P= 0.008). Physicians rated DCIS Score as the most impactful factor in planning treatment. CONCLUSIONS: The radiotherapy recommendation changed from pre-assay to post-assay 31.3% (95%CI: 23.0-40.6%) of the time--a clinically significant change. This study supports the clinical utility of the DCIS Score and indicates that the test provides additional, individualized information on LR risk.

Validation of an ICD-9-based claims algorithm for identifying patients with chronic idiopathic/spontaneous urticaria.

BACKGROUND: There is no specific International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code for chronic idiopathic urticaria or spontaneous urticaria (CIU/CSU), a skin condition characterized by hives and angioedema lasting at least 6 weeks with no known cause. OBJECTIVE: To validate an ICD-9-CM-based algorithm for identification of patients with CIU/CSU and thus facilitate claims-based research. METHODS: Patient records were reviewed at 4 US practices. Patients included in the study were from a random sample of those identified by their physician as having CIU/CSU or because they met the following diagnosis-based algorithm: (1) at least 2 outpatient ICD-9-CM diagnosis codes 708.1, 708.8, or 708.9 at least 6 weeks apart or (2) 1 outpatient diagnosis of 708.1, 708.8, or 708.9 and 1 diagnosis of 995.1 at least 6 weeks apart. Data collected included ICD-9-CM codes, diagnoses of urticaria and allergy-related conditions, and medication use. Sensitivity and positive predictive value were calculated. The study was approved by the Western Institutional Review Board. RESULTS: One hundred forty-nine patient records were reviewed (mean age 41.1 years; 73.8% were women; 69.1% were white): 115 were identified with the diagnosis-based algorithm, 90 were patients with "known CIU/CSU", and 56 were in the 2 groups. The mean duration of CIU/CSU was 2.9 to 3.1 years. The 2 cohorts most frequently had diagnoses of idiopathic urticaria, unspecified urticaria, and other specified urticaria. The diagnosis-based algorithm had a positive predictive value of 90.4% and a sensitivity of 71.1%. CONCLUSION: The high positive predictive value suggests that patients identified using the algorithm are highly likely to have CIU/CSU. The 71.1% sensitivity suggests that most patients with CIU/CSU will be identified. The validation statistics support the use of the diagnosis-based algorithm in claims-based research, although future studies could refine the algorithm further.

Health-care costs and utilization related to long- or short-acting antiepileptic monotherapy use.

PURPOSE: This study aimed to compare health-care utilization and costs in patients treated with long-acting (LA) vs. short-acting (SA) antiepileptic drug (AED) monotherapy. METHODS: We conducted a cross-sectional study of claims from the OptumInsight™ database. Our analysis was restricted to adults diagnosed with epilepsy and who used AED monotherapy. Patients were excluded if they used >1 type of AED, had <9months of treatment, or had a treatment gap of >60days. Antiepileptic drugs were classified as LA or SA based on published data and expert opinion. Medical and pharmacy claims were used to estimate health-care utilization and costs, and baseline group differences were adjusted using multivariate analyses. RESULTS: There were 4058 (49.6%) LA AED users and 4122 (50.4%) SA AED users. Medication possession ratios (MPRs) were not significantly different between LA AED users and SA AED users (P=0.125). Long-acting AED users had lower mean overall health-care costs ($9757 vs. $12,689), lower epilepsy-related costs ($3539 vs. $5279), and lower rate of overall (8.8% vs. 10.9%) and epilepsy-related hospitalizations (5.7% vs. 7.6%) compared with SA AED users (all P<0.01). After adjusting for demographics and clinical characteristics, mean overall costs were lower by $686 and the mean epilepsy-related costs were lower by $894 in LA AED users. CONCLUSION: Although MPRs were similar in LA AED and SA AED groups, patients treated with LA monotherapy had a lower economic burden compared with those treated with SA monotherapy, indicating that using AEDs with extended duration of action is associated with decreased health-care use and lower health-care costs.

Incremental healthcare resource utilization and costs in US patients with Cushing's disease compared with diabetes mellitus and population controls.

PURPOSE: Resource utilization and costs in Cushing's disease (CD) patients have not been studied extensively. We compared CD patients with diabetes mellitus (DM) patients and population-based controls to characterize differences in utilization and costs. METHODS: Using 2008-2012 MarketScan® database, we identified three patient groups: (1) CD patients; (2) DM patients; and (3) population-based control patients without CD. DM and control patients were matched to CD patients by age, gender, region, and review year in a 2:1 ratio. Outcomes included annual healthcare resource utilization and costs. RESULTS: There were 1852 CD patients, 3704 DM patients and 3704 controls. Mean age was 42.9 years; 78.2 % were female. CD patients were hospitalized more frequently (19.3 %) than DM patients (11.0 %, p < .001) or controls (5.6 %, p < .001). CD patients visited the ED more frequently (25.4 %) than DM patients (21.1 %, p < .001) or controls (14.3 %, p < .001). CD patients had more office visits than DM patients (19.1 vs. 10.7, p < .001) or controls (7.1, p < .001). CD patients on average filled more prescriptions than DM patients (51.7 vs. 42.7, p < .001) or controls (20.5, p < .001). Mean total healthcare costs for CD patients were $26,269 versus $12,282 for DM patients (p < .001) and $5869 for controls (p < .001). CONCLUSIONS: CD patients had significantly higher annual rates of healthcare resource utilization compared to matched DM patients and population controls without CD. CD patient costs were double DM costs and quadruple control costs. This study puts into context the additional burdens of CD over DM, a common, chronic endocrine condition affecting multiple organ systems, and population controls.