Cancer incidence in immunocompromised patients: a single-center cohort study.

BACKGROUND: Diminished immune defense plays an important role in cancer development. Cancer risk in immunocompromised patients may differ. Identifying individuals with elevated cancer risk can inform strategies for routine cancer screening. This study aimed to understand and compare cancer incidence and risk in three patient groups: recipients of solid organ transplant (SOT) or hematopoietic stem cell transplant (HSCT); diagnosis of primary or secondary immunodeficiency disorder (PID/SID); and recipients of tumor necrosis factor inhibitor (TNF-i) therapy. METHODS: This retrospective cohort study used the University of Utah Health System database and Huntsman Cancer Institute tumor registry. Patients aged ≥18 years with SOT/HSCT, PID/SID or ≥ 3 months of TNF-i therapy were included. The date of transplant, diagnosis of PID/SID, or 1st TNF-i medication order date was defined as the index date. We calculated cumulative cancer incidence by Kaplan-Meier method. A Cox-proportional hazard regression model with a stepwise variable selection process was used to identify independent risk factors associated with the time to onset of a new primary cancer. RESULTS: In total, 13,887 patients were included which comprised of 2982 (21%) SOT/HSCT, 7542 (54%) PID/SID and 3363 (24%) patients receiving TNF-i. The mean (SD) age ranged from 46.8 (15) years - 50.4 (18.2) years. The proportion of white patients ranged from 72.3-84.8%. The estimated cumulative cancer incidence was 11.5% in the SOT/HSCT cohort, 14.3% in the PID/SID cohort, and 8.8% in the TNF-i cohort. The multivariable model adjusted for age, benign in-situ disease, Charlson Comorbidity Index, hypertension/cardiovascular disease/end stage renal disease, gender, race/ethnicity, and renal cyst as significant risk factors. The adjusted hazard ratios for cancer development in SOT/HSCT and PID/SID cohorts compared to the TNF-i cohort over the full follow-up period were 1.57 (95% CI: 1.16-2.13) and 2.14 (95% CI: 1.65-2.77), respectively. CONCLUSION: A significantly increased risk of cancer was observed in PID/SID patients and SOT/HSCT patients compared to TNF-i patients. Age ≥ 50 years, male gender, and clinical comorbidities were additional factors impacting cancer risk. PID/SID and SOT/HSCT patients may benefit from more intensive cancer screening.

Can Cost-effectiveness Analysis Inform Genotype-Guided Aspirin Use for Primary Colorectal Cancer Prevention?

BACKGROUND: Inherited genetic variants can modify the cancer-chemopreventive effect of aspirin. We evaluated the clinical and economic value of genotype-guided aspirin use for colorectal cancer chemoprevention in average-risk individuals. METHODS: A decision analytical model compared genotype-guided aspirin use versus no genetic testing, no aspirin. The model simulated 100,000 adults ≥50 years of age with average colorectal cancer and cardiovascular disease risk. Low-dose aspirin daily starting at age 50 years was recommended only for those with a genetic test result indicating a greater reduction in colorectal cancer risk with aspirin use. The primary outcomes were quality-adjusted life-years (QALY), costs, and incremental cost-effectiveness ratio (ICER). RESULTS: The mean cost of using genotype-guided aspirin was $187,109 with 19.922 mean QALYs compared with $186,464 with 19.912 QALYs for no genetic testing, no aspirin. Genotype-guided aspirin yielded an ICER of $66,243 per QALY gained, and was cost-effective in 58% of simulations at the $100,000 willingness-to-pay threshold. Genotype-guided aspirin was associated with 1,461 fewer polyps developed, 510 fewer colorectal cancer cases, and 181 fewer colorectal cancer-related deaths. This strategy prevented 1,078 myocardial infarctions with 1,430 gastrointestinal bleeding events, and 323 intracranial hemorrhage cases compared with no genetic testing, no aspirin. CONCLUSIONS: Genotype-guided aspirin use for colorectal cancer chemoprevention may offer a cost-effective approach for the future management of average-risk individuals. IMPACT: A genotype-guided aspirin strategy may prevent colorectal cancer, colorectal cancer-related deaths, and myocardial infarctions, while minimizing bleeding adverse events. This model establishes a framework for genetically-guided aspirin use for targeted chemoprevention of colorectal cancer with application toward commercial testing in this population.

BRCA testing and outcomes in women with breast cancer.

MAIN PURPOSE: Germline BRCA mutations (BRCAm) strongly influence the risk of developing breast cancer. This study aimed to understand the role of BRCAm testing in affected individuals and to assess its impact on the outcome of BRCAm carriers compared to non-carriers (BRCAwt) with breast cancer. RESEARCH QUESTION: The research question is "Does standard of care testing for BRCAm improve survival outcomes of breast cancer patients?" METHODS: In a single institution observational cohort study, demographic and clinical characteristics were compared between breast cancer patients with and without BRCAm. Frequency of BRCA testing was assessed. Survival outcomes were assessed by initial treatment setting stratified by BRCA status. RESULTS: Of 5712 identified women with breast cancer, 14.6% (n = 835) were tested for a BRCA mutation and had a documented result. The total number and proportion of women tested for a BRCAm increased between 2000 and 2014, resulting in an increased number of BRCAm carriers identified. However, the proportion of women who underwent testing and had a BRCAm decreased during the study period from 27.5% in 2000-2004 to 13.3% in 2010-2014. Disease-free survival was similar in the adjuvant and neoadjuvant treatment settings between BRCAm and BRCAwt patients. Progression-free survival on first line treatment and overall survival for patients with metastatic disease was also similar between BRCAm and BRCAwt patients. CONCLUSIONS: The proportion of women tested and the number of BRCAm identified increased during the study period despite a decreasing proportion of positive results among women tested.

Cost-effectiveness of early cancer surveillance for patients with Li-Fraumeni syndrome.

INTRODUCTION: Patients with germline TP53 pathogenic variants (Li-Fraumeni syndrome [LFS]) are at extremely high lifetime risk of developing cancer. Recent data suggest that tumor surveillance for patients with LFS may improve survival through early cancer detection. The objective of this study was to assess the cost-effectiveness of a cancer surveillance strategy for patients with LFS compared with those whose tumors present clinically. METHODS: A Markov decision analytic model was developed from a third-party payer perspective to estimate cost-effectiveness of routine cancer surveillance over a patient's lifetime. The model consisted of four possible health states: no cancer, cancer, post-cancer survivorship, and death. Model outcomes were costs (2015 United States Dollars [USD]), effectiveness (life years [LY] gained), and incremental cost-effectiveness ratio (ICER; change in cost/LY gained). One-way sensitivity analyses and probabilistic sensitivity analyses examined parameter uncertainty. RESULTS: The model showed a mean cost of $46 496 and $117 102 and yielded 23 and 27 LY for the nonsurveillance and surveillance strategies, respectively. The ICER for early cancer surveillance versus no surveillance was $17 125 per additional LY gained. At the commonly accepted willingness to pay threshold of $100 000/life-year gained, surveillance had a 98% probability of being the most cost-effective strategy for early cancer detection in this high-risk population. CONCLUSIONS: Presymptomatic cancer surveillance is cost-effective for patients with germline pathogenic variants in TP53. Lack of insurance coverage or reimbursement in this population may have significant consequences and leads to undetected cancers presenting in later stages of disease with worse clinical outcomes.

Immunotargeted therapy in melanoma: patient, provider preferences, and willingness to pay at an academic cancer center.

New melanoma therapies have shifted the expectations of patients and providers. Evaluating the impact of treatment characteristics may enhance shared decision making. A survey, including a discrete choice experiment, was utilized to evaluate perceived trade-offs of different melanoma treatments and to estimate out-of-pocket (OOP) willingness-to-pay (WTP) thresholds (January 2016 to March 2016). Participants included patients with melanoma at Huntsman Cancer Institute and their cancer care providers. Stakeholder focus groups were conducted to identify treatment attributes. Descriptive and comparative statistics and multinomial logit model were used to evaluate responses. Response rates were 41.9% (N = 220) for patients and 37.7% (N = 20) for providers. Immunotherapy and targeted therapy attributes considered important by participants were overall survival, immunotherapy-related side effects, and skin toxicities. Patients and providers had significantly different views of quality-of-life expectations, anxiety toward melanoma, trust to make treatment decisions, sharing concerns about treatment, time to discuss treatment, understanding OOP costs, and willingness to undergo/recommend treatment (half of the patients would undergo treatment if it was effective for > 24 months). Among patients, the average monthly OOP WTP for combination immunotherapy with nivolumab + ipilimumab was $ 2357 and for BRAF/MEK inhibitor was $1648. Among providers, these estimates were $ 2484 and $1350, respectively. Discordance existed between patients' and providers' perceptions about quality of life expectations, degree of anxiety, sharing of opinions, and progression-free survival. Our study suggests that patients and providers exhibit a higher OOP WTP for combination immunotherapy treatment compared with BRAF/MEK inhibitors, influenced predominately by overall survival expectations.

Clinical Utility of Pharmacogenetic Testing and a Clinical Decision Support Tool to Enhance the Identification of Drug Therapy Problems Through Medication Therapy Management in Polypharmacy Patients.

BACKGROUND: In polypharmacy patients, medication therapy management (MTM) services provide a comprehensive review of current medications and future treatment goals. Pharmacogenetics (PGx) may further optimize the identification of potential drug therapy problems (DTPs); however, the clinical utility of PGx information with a clinical decision support tool (CDST) in an MTM setting in identifying DTPs has not been systematically assessed. OBJECTIVE: To assess the clinical utility of an MTM service enhanced by pharmacogenetic test results and a clinical decision support tool. METHODS: This study was a post hoc analysis of the data obtained from an open-label, randomized, observational trial. Polypharmacy patients eligible for MTM service were randomly assigned to 3 intervention arms: standard MTM (SMTM), MTM incorporating CDST (CMTM), and CMTM further enhanced by PGx test results of CYP450 and VKORC1 enzymes (PGxMTM). Allocation for this post hoc analysis was based on patient adherence to the research protocol and completion of a PGx test. The number of DTPs per patient was compared across the 3 arms using analysis of variance. In addition, the frequency of serious DTPs as a categorical variable (grade 3 or above vs. lower grade) was compared across the 3 arms between PGx driven and non-PGx driven DTP recommendations. Statistical significance was tested using the chi-square test. The level of agreement between the DTP seriousness and the acceptance made by prescribers was presented as Cohen's kappa coefficient. RESULTS: Numbers of patients after cohort reallocation based on completion of PGx testing were 104, 180, and 58 for the SMTM, CMTM, and PGxMTM arms, respectively. On average, 3.08 DTPs were identified for each patient, which was nearly identical across all 3 arms. Blinded clinical pharmacists considered seriousness (grade 3 or 4) in 31% of the PGx-related DTPs in comparison with 4.9% of the non-PGx DTPs (P < 0.001). The more serious (i.e., grade 3 or above) DTP recommendations were more likely to be accepted by prescribers with the odds ratios of 1.95 (P = 0.05) and 2.39 (P = 0.15), when the analysis was performed for all DTPs and DTPs from the PGxMTM arm only, respectively. CONCLUSIONS: MTM enhanced by PGx testing and the clinical decision support tool did not increase the number of DTPs identified. However, PGx testing and the decision support software helps pharmacists determine more serious DTPs, and resulting subsequent recommendations were more readily accepted by a prescriber. Future study of the patient safety outcomes and overall health care costs associated with the utility of the decision support is warranted. DISCLOSURES: No funding was received for conducting the post hoc analysis presented in this study. Magness is employed by Magellan Health, which received funding from Genelex for costs to administrate the medication management program. The open-label randomized trial was sponsored by Genelex (Clinicaltrials.gov ID number NCT02428660). PGx tests were provided and laboratory analysis was performed by Genelex. Valerie Baron is an employee of YouScript, which created the clinical decision support tool used in this study and formerly was part of Genelex. The other authors have nothing to disclose.

Impact of a genetic counseling requirement prior to genetic testing.

BACKGROUND: Genetic counseling by a Genetic Counselor (GC) is a requirement prior to genetic testing for cancer susceptibility genes (GC-mandate policy) for some insurers. This study evaluated the impact of this policy from the patient perspective. METHODS: Surveys were sent to individuals for whom their insurer ordered genetic testing for the cancer susceptibility genes BCRA1 and BRCA2 over a 1 year time period that spanned the introduction of a GC-mandate policy. Responses were assessed by time period (before/after policy introduction) and genetic test completion. RESULTS: The surveys were completed by 1247/4950 (25.7%) eligible individuals. After policy introduction, there was no change in the proportion of respondents who completed genetic testing (p = 0.13) or had a mutation (p = 0.55). Overall decisional conflict (uncertainty or feeling uninformed) around genetic testing did not change after policy introduction (p = 0.16), but was significantly higher among respondents who did not complete genetic testing (p < 0.01). Although a larger proportion of respondents saw a GC after policy introduction (p < 0.01), fewer did so to better understand their test results (p < 0.01). The proportion of respondents who did not see a GC due to insurance issues/requirements and time restraints was higher among those tested after policy introduction or who did not complete genetic testing (p < 0.01). In multivariate analysis, respondents with a household income of $25,000 or greater were 3-times more likely to complete testing. CONCLUSIONS: A GC-mandate policy did not improve decisional conflict or increase the number of deleterious mutations identified and low-income respondents were less likely to complete testing. On the contrary, insurance requirements and time constraints may be preventing individuals at risk from receiving appropriate testing.

BRCA testing, treatment patterns and survival in platinum-sensitive recurrent ovarian cancer - an observational cohort study.

BACKGROUND: Breast cancer associated (BRCA) genes are critical for DNA repair. Mutations in BRCA1 and BRCA2 (BRCAm) result in loss of these repair mechanisms and potential carcinogenesis. Germline BRCAm are common in ovarian carcinomas, particularly in platinum-sensitive disease. The increased prevalence of BRCAm in platinum-sensitive disease is likely due to enhanced responsiveness to platinum chemotherapy from homologous recombination repair deficiency. The purpose of this study was to explore BRCA testing, treatment patterns and survival in platinum-sensitive recurrent (PSR) ovarian cancer. METHODS: This was an observational cohort analysis of PSR ovarian cancer treated at the Huntsman Cancer Institute from 1995 to 2012. Germline BRCA status was ascertained through chart review and categorized as BRCAm (BRCA1/2 positive), BRCAwt (BRCA wild type or variant of uncertain significance), and untested. Treatment patterns and survival were assessed from recurrence until death or last follow-up. The Kaplan-Meier method was used to evaluate survival from recurrence by BRCA status. Logistic regression and COX proportional hazard model was used to estimate predictors of BRCA testing and survival, respectively. RESULTS: Of the 168 PSR patients, 15 (9 %) were BRCAm, 25 (15 %) were BRCAwt, and 128 (76 %) were untested. Median age at PSR was 56 years for BRCAm and BRCAwt (p = 0.90) and 63 years for those untested (p = 0.033 vs BRCAm). Overall survival was similar between BRCAm and BRCAwt (median 50.4 vs 67.5 months, p = 0.86) and was 24.9 months in untested patients. Significant predictors for the likelihood of BRCA testing were age (OR = 0.93, 95 % CI 0.89, 0.97, p = 0.002), family history of breast or ovarian cancer (OR = 8.33, 95 % CI: 3.08, 22.59, p < 0.001), and cancer diagnosis year (OR = 10.02, 95 % CI: 3.22, 31.21, p < 0.001). BRCA-tested patients had a lower risk of death versus untested (HR 0.35, 95 % CI 0.17, 0.68, p = 0.001). CONCLUSIONS: BRCAwt patients had similar outcomes to BRCAm patients, potentially owing to similar age at diagnosis, representing a BRCA testing channeling bias. Younger patients, those with a family history of breast or ovarian cancer, and those diagnosed more recently were more likely to be BRCA tested. BRCA tested patients had a lower risk of death.

Cost-Utility of a Prognostic Test Guiding Adjuvant Chemotherapy Decisions in Early-Stage Non-Small Cell Lung Cancer.

BACKGROUND: A prognostic test was developed to guide adjuvant chemotherapy (ACT) decisions in early-stage non-small cell lung cancer (NSCLC) adenocarcinomas. The objective of this study was to compare the cost-utility of the prognostic test to the current standard of care (SoC) in patients with early-stage NSCLC. MATERIALS AND METHODS: Lifetime costs (2014 U.S. dollars) and effectiveness (quality-adjusted life-years [QALYs]) of ACT treatment decisions were examined using a Markov microsimulation model from a U.S. third-party payer perspective. Cancer stage distribution and probability of receiving ACT with the SoC were based on data from an academic cancer center. The probability of receiving ACT with the prognostic test was estimated from a physician survey. Risk classification was based on the 5-year predicted NSCLC-related mortality. Treatment benefit with ACT was based on the prognostic score. Discounting at a 3% annual rate was applied to costs and QALYs. Deterministic one-way and probabilistic sensitivity analyses examined parameter uncertainty. RESULTS: Lifetime costs and effectiveness were $137,403 and 5.45 QALYs with the prognostic test and $127,359 and 5.17 QALYs with the SoC. The resulting incremental cost-effectiveness ratio for the prognostic test versus the SoC was $35,867/QALY gained. One-way sensitivity analyses indicated the model was most sensitive to the utility of patients without recurrence after ACT and the ACT treatment benefit. Probabilistic sensitivity analysis indicated the prognostic test was cost-effective in 65.5% of simulations at a willingness to pay of $50,000/QALY. CONCLUSION: The study suggests using a prognostic test to guide ACT decisions in early-stage NSCLC is potentially cost-effective compared with using the SoC based on globally accepted willingness-to-pay thresholds. IMPLICATIONS FOR PRACTICE: Providing prognostic information to decision makers may help some patients with high-risk early stage non-small cell lung cancer receive appropriate adjuvant chemotherapy while avoiding the associated toxicities and costs in patients with low-risk disease. This study used an economic model to assess the effectiveness and costs associated with using a prognostic test to guide adjuvant chemotherapy decisions compared with the current standard of care in patients with non-small cell lung cancer. When compared with current standard care, the prognostic test was potentially cost effective at commonly accepted thresholds in the U.S. This study can be used to help inform decision makers who are considering using prognostic tests.

Assessment of HER2 testing patterns, HER2+ disease, and the utilization of HER2-directed therapy in early breast cancer.

CONTEXT: Determining human epidermal growth factor receptor 2 (HER2) status is critical for the management of early-stage breast cancer (ESBC). An understanding of HER2 testing practices can provide insight into how test results influence the use of HER2-directed therapy. OBJECTIVE: To assess HER2 testing, HER2+ disease, and HER2-directed therapy in ESBC at the Huntsman Cancer Institute before and after the 2007 American Society of Clinical Oncology and College of American Pathologist (ASCO/CAP) guidelines on HER2 testing were published. METHODS: Patients were identified from an institutional tumor registry. HER2 testing patterns and results were examined using a chart review of pathology and clinical notes. Patient characteristics, HER2+ rate, and trastuzumab use were evaluated descriptively. Discordance rate with reflex testing (immunohistochemistry [IHC]2+ retested by fluorescence in situ hybridization [FISH]) was also evaluated. RESULTS: A total of 1,459 women were included (mean age: 57 years). The rate of HER2+ disease was 17% (number [N] =245). The discordance rate between IHC2+ and FISH was 10%. After the 2007 ASCO/CAP guidelines, fewer tumors were classified as IHC3+ (16% post- versus 21.9% pre-2007), more tumors were characterized as IHC2+ (26.4% post- versus 20.7% pre-2007), and the overall HER2+ rate was decreased (18.7% versus 21.9%), but this was not statistically significant (P=0.519). Most patients with HER2+ ESBC received HER2-targeted therapy (N=185). CONCLUSION: The HER2+ rate was 17% and within the range of the reported rates in the literature. Reflex testing identified additional HER2+ tumors by approximately 10%, and should be considered a potential quality indicator. ASCO/CAP HER2 testing guidelines in 2007 appeared to impact the interpretation and classification of HER2+ tumors.

Response monitoring, tolerability, and effectiveness of imatinib treatment for chronic myeloid leukemia in a retrospective research database.

Retrospective review of imatinib monitoring through electronic health records (EHR) can provide valuable insight into the current management of chronic myelogenous leukemia (CML). This study retrospectively reviewed EHRs from 2001 to 2010 of patients with chronic phase CML (CP-CML) treated with first-line imatinib. Chart evaluations included a review of cytogenetic and molecular testing, overall survival, adverse drug events (ADEs), and therapy modifications. A total of 54 patients with CP-CML were treated with first-line imatinib and had either cytogenetic or molecular testing within 18 months of imatinib initiation. Within the first 18 months of treatment, 33 of 45 patients (73%) undergoing cytogenetic testing experienced a complete cytogenetic response (median, 241 days; range, 110-542 days) and 24 of 48 patients (50%) receiving molecular testing achieved at least a major molecular response (median, 253 days; range, 99-546 days). The average number of cytogenetic and molecular tests conducted within the first 18 months was 2.5 and 3.8, respectively. Nineteen of 54 (35%) had a dose increase of imatinib (>400 mg; median, 329 days; range, 21-1968 days). The 5-year estimated overall survival rate was 88.5%. Between 2006 and 2010 (n=30; 56%), 7 patients (23%) transitioned to dasatinib or nilotinib (median, 399 days from diagnosis; range, 180-1046 days) because of suboptimal response or treatment failure (n=5) and imatinib ADEs (n=2). Forty-six imatinib-associated ADEs occurred in 31 patients (57%), of which 10 (32%) received dose reductions (median, 52 days) and 6 (19%) had discontinuations (median, 139 days). Closely monitored patients with CML treated with imatinib at an NCCN Member Institution experienced outcomes comparable to those reported in key clinical trials.

Development of a practical screening tool to predict low muscle mass using NHANES 1999-2004.

BACKGROUND: Skeletal muscle mass declines after the age of 50. Loss of skeletal muscle mass is associated with increased morbidity and mortality. OBJECTIVE: This study aims to identify predictors of low skeletal muscle mass in older adults toward development of a practical clinical assessment tool for use by clinicians to identify patients requiring dual-energy X-ray absorptiometry (DXA) screening for muscle mass. METHODS: Data were drawn from the National Health and Nutrition Examination Surveys (NHANES) from 1999 to 2004. Appendicular skeletal mass (ASM) was calculated based on DXA scans. Skeletal muscle mass index (SMI) was defined as the ratio of ASM divided by height in square centimeters. Elderly participants were classified as having low muscle mass if the SMI was 1 standard deviation (SD) below the mean SMI of young adults (20-40 years old). Logistic regression was conducted separately in males and females age ≥65 years of age to examine the relationship between patients identified as having low muscle mass and health behavior characteristics, adjusting for comorbid conditions. The model was validated on a separate sample of 200 patients. RESULTS: Among the NHANES study population, 551 (39.7 %) males and 374 (27.5 %) females had a SMI below the 1 SD cutoff point. NHANES study subjects with a low SMI were older (mean age, 76.2 vs. 72.7 for male; 76.0 vs. 73.7 for female; and both p < 0.0001) and had a lower body mass index (mean BMI, 24.1 vs. 29.4 for male; 22.9 vs. 29.7 for female; p < 0.0001). In adjusted logistic regression analyses, age (for males) and BMI (for both males and females) remained statistically significant. A parsimonious logistic regression model adjusting for age and BMI only had a C statistic of 0.89 for both males and females. The discriminatory power of the parsimonious model increased to 0.93 for males and 0.95 for females when the cutoff defining low SMI was set to 2 SD below the SMI of young adults. In the validation sample, the sensitivity was 81.6 % for males and 90.6 % for females. The specificity was 66.2 % for males and females. CONCLUSIONS: BMI was strongly associated with a low SMI and may be an informative predictor in the primary care setting. The predictive model worked well in a validation sample.

All-cause and incremental per patient per year cost associated with chronic hepatitis C virus and associated liver complications in the United States: a managed care perspective.

BACKGROUND: Approximately 3.2-3.9 million U.S. residents are infected with the hepatitis C virus (HCV). Total annual costs (direct and indirect) in the United States for HCV were estimated to be $5.46 billion in 1997, and direct medical costs have been predicted to increase to $10.7 billion for the 10-year period from 2010 through 2019, due in part to the increasing number of HCV patients developing advanced liver disease (AdvLD). OBJECTIVE: To quantify in a sample of commercially insured enrollees (a) total per patient per year (PPPY) all-cause costs to the payer, overall and by the stage of liver disease, for patients diagnosed with HCV; and (b) incremental all-cause costs for patients diagnosed with HCV relative to a matched non-HCV cohort. METHODS: This retrospective, matched cohort study included patients aged at least 18 years and with at least 6 months of continuous enrollment in a large managed care organization (MCO) claims database from July 1, 2001, through March 31, 2010. Patients with a diagnosis of HCV (ICD-9-CM codes 070.54, 070.70) were identified and stratified into those with and without AdvLD, defined as decompensated cirrhosis (ICD-9-CM codes 070.44, 070.71, 348.3x, 456.0, 456.1, 456.2x, 572.2, 572.3, 572.4, 782.4, 789.59); hepatocellular carcinoma (HCC, ICD-9-CM code 155); or liver transplant (ICD-9-CM codes V42.7, 50.5 or CPT codes 47135, 47136). For patients without AdvLD, the index date was the first HCV diagnosis date observed at least 6 months after the first enrollment date, and at least 6 months of continuous enrollment after the index date were required. HCV patients without AdvLD were stratified into those with and without compensated cirrhosis (ICD-9-CM codes 571.2, 571.5, 571.6). For patients with AdvLD, the index date was the date of the first AdvLD diagnosis observed at least 6 months after the first enrollment date, and at least 1 day of enrollment after the index date was required. Cases were matched in an approximate 1:10 ratio to comparison patients without an HCV diagnosis or AdvLD diagnosis who met all other inclusion criteria based on gender, age, hospital referral region state, pre-index health care costs, alcoholism, human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS), and a modified Charlson Comorbidity Index. For the HCV and comparison patient cohorts, PPPY all-cause costs to the payer were calculated as total allowed charges summed across all patients divided by total patient-days of follow-up for the cohort, multiplied by 365, inflation-normalized to 2009 dollars. Because the calculation of PPPY cost generated a single value for each cohort, bootstrapping was used to generate descriptive statistics. Incremental PPPY costs for HCV patients relative to non-HCV patients were calculated as between-group differences in PPPY costs. T-tests for independent samples were used to compare costs between case and comparison cohorts. RESULTS: A total of 34,597 patients diagnosed with HCV, 78.0% with HCV without AdvLD, 4.4% with compensated cirrhosis, 12.3% with decompensated cirrhosis, 2.8% with HCC, and 2.6% with liver transplant, were matched to 330,435 comparison patients. Mean (SD) age of all HCV cases was 49.9 (8.5) years; 61.7% were male. Incremental mean (SD) PPPY costs in 2009 dollars for all HCV patients relative to comparison patients were $ 9,681 ($176) PPPY. Incremental PPPY costs were $5,870 ($157) and $5,330 ($491) for HCV patients without liver disease and with compensated cirrhosis, respectively. Incremental PPPY costs for patients with AdvLD were $27,845 ($ 965) for decompensated cirrhosis, $43,671 ($2,588) for HCC, and $ 93,609 ($4,482) for transplant. Incremental prescription drug costs, including the cost of antiviral drugs, were $2,739 ($37) for HCV patients overall, $2,659 ($41) for HCV without liver involvement, and $3,102 ($157) for HCV with compensated cirrhosis. These between-group differences were statistically significant at P<0.001. CONCLUSIONS: Based on a retrospective analysis of data from a large, MCO claims database, patients diagnosed with HCV had annual all-cause medical costs that were almost twice as high as those of enrollees without a diagnosis of HCV. Health care costs increased dramatically with AdvLD. Data from this study may help MCOs project future HCV costs and facilitate planning for HCV patient management efforts.

Contraceptive and noncontraceptive benefits of the LNG-IUS in a vertically integrated HMO.

BACKGROUND: The study was conducted to assess outcomes among women using the levonorgestrel-releasing intrauterine system (LNG-IUS). STUDY DESIGN: The data were collected via a retrospective claims database analysis of 152 women. Two nested cohorts were further distinguished based on length of follow-up: two and three continuous years (n=73 and n=29, respectively). RESULTS: Over 90% had a single insertion, and fewer than 4% experienced an LNG-IUS-related complication. Thirteen percent of women experienced menorrhagia in the year preceding insertion; this figure dropped to 12.5%, 1.2% and 0% in the 1, 2 and 3 years postinsertion. Mean number of gynecology-related visits decreased from four to two in the overall cohort, from seven to four in the cohort with 2 years of follow-up and from nine to four in the cohort with 3 years of follow-up. CONCLUSION: LNG-IUS use prevented pregnancy in all patients and was associated with decreased vaginal bleeding starting in the second year postinsertion.

Incidence and economic implications of heparin-induced thrombocytopenia in medical patients receiving prophylaxis for venous thromboembolism.

STUDY OBJECTIVES: To determine the incidence of heparin-induced thrombocytopenia (HIT) in patients admitted to a medical service who were given unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH) to prevent venous thromboembolism, the incremental cost of developing HIT, and the cost consequences of using LMWH to prevent venous thromboembolism in medical patients. DESIGN: Retrospective analysis with a nested case-control. SETTING: University-affiliated tertiary-care hospital. PATIENTS: A total of 10,121 adult medical patients admitted between August 1, 2000, and November 2, 2004, received UFH or LMWH to prevent venous thromboembolism during their admission. From these, patients with immune-mediated HIT were identified and served as case patients, and 3-5 matched control patients were identified for each case patient. MEASUREMENTS AND MAIN RESULTS: The development of HIT was determined for patients who received LMWH and for patients who received UFH. Costs were compared between the patients with HIT and the matched control patients. The cost of using LMWH to prevent venous thromboembolism was compared with the cost of using UFH. In patients receiving UFH and those receiving LMWH, the incidence of HIT was 0.51% (43/8420) and 0.084% (1/1189), respectively (p=0.037), with an overall incidence of 0.43% (44/10,121). Admissions that included development of HIT incurred an average cost of 56,364 dollars compared with 15,231 dollars (p<0.001) for admissions without HIT. Using LMWH to prevent venous thromboembolism in medical patients cost 13.88 dollars less per patient than using UFH. CONCLUSIONS: For the prophylaxis of venous thromboembolism, LMWH was associated with a lower incidence of HIT than UFH in medical patients. An admission during which the patient develops HIT costs significantly more than an admission during which the patient does not develop HIT. Low-molecular-weight heparin is cost-effective for prevention of venous thromboembolism in medical patients.

Documentation of chemotherapy infusion preparation costs in academic- and community-based oncology practices.

Significant changes in Medicare reimbursement for outpatient oncology services were proposed as part of the Medicare Modernization Act of 2003. The purpose of this study was to identify the "true cost" associated with drug-related handling for the preparation and delivery of chemotherapy doses to estimate the impact of changing reimbursement schema by Medicare. Two academic medical outpatient infusion centers and 2 community cancer centers provided data used to estimate all costs (excluding drug cost) associated with the preparation of chemotherapy doses. The data included both fixed costs (drug storage, space, equipment, and information resources) and variable costs (insurance management, inventory, waste management, pharmacy staff payroll, supplies, and shipping). The average cost for the preparation of chemotherapy doses across all sites was dollar 34.27 (range, dollar 32.08-dollar 41.23). A time-and-motion study was also performed to determine what tasks were conducted by pharmacy staff and how much time was spent in the preparation of the top 15 chemotherapeutic drugs and regimens used in the 4 sites. Data from the 4 centers was projected to show that if 3,990,495 million chemotherapy infusions were administered to a national Medicare population in 2003, when multiplied by the average cost of preparation for infusions determined by the current study (dollar 34.27), the estimated total annual cost to Medicare for chemotherapy preparation by pharmacists is dollar 136,754,263.65. The pharmacists spent most of their days (90% or more) performing tasks directly related to the preparation of these agents. These data provide scientific support for the consideration of appropriate reimbursement for chemotherapy services provided by pharmacists to Medicare beneficiaries.

Migraine matters: the role of triptans in relieving the burden in managed care.

OBJECTIVE: To provide managed care pharmacists with information regarding the prevalence and burden of migraine in the United States, approaches to diagnosing and managing migraine, and implications for managed care organizations. SUMMARY: Migraine is a common chronic condition that imparts tremendous disability to those afflicted. Economic costs associated with migraine are staggering, with the majority of costs resulting from lost workdays. Barriers to the proper management of migraine patients include misdiagnosis and a limited understanding of available pharmacological and nonpharmacological treatment options. Use of screening tools in primary care may help diagnose migraine and point to appropriate treatment plans. The use of migraine-specific therapies is discussed, with special emphasis on triptans, which have demonstrated efficacy and modest side effects. Use of triptans has been shown to reduce migraine-associated disability and overall costs associated with migraine. Studies comparing the effectiveness and costs of individual triptans are also described. CONCLUSIONS: Migraine-associated pain and disability can be significantly reduced with proper treatment. Use of diagnostic tools, such as ID Migraine, can facilitate the identification of migraine patients who need treatment. A stratified care approach with appropriate treatment can improve the lives of migraine sufferers as well as reduce migraine-associated costs for managed care organizations.