Real-World Therapy Management and Outcomes of First-Line Axitinib Plus Pembrolizumab in Patients With Advanced Renal Cell Carcinoma in the United States.

Background: Combination axitinib plus pembrolizumab is a standard of care in the first-line treatment of patients with advanced clear cell renal cell carcinoma (RCC). This analysis describes the clinical characteristics, treatment management and outcomes of patients receiving first-line (1L) axitinib plus pembrolizumab in a real-world US setting. Methods: Electronic health record (EHR)-derived data from the Flatiron Health Database, which includes ~280 cancer clinics across 800 sites in the US, were used. Patients had confirmed Stage IV or metastatic RCC and initiated 1L axitinib plus pembrolizumab on or after 1/1/2018 to 3/31/2021. Outcomes were best overall response rate; real-world progression-free survival (rwPFS) and overall survival (OS) at landmark time periods (3, 6, 9, and 12 months). Therapy management (TM) included dose hold, dose change and discontinuation. Data are reported as medians (IQR) unless otherwise noted. Results: 355 patients received 1L axitinib plus pembrolizumab, with median follow-up of 9.7 (0.1-24.3) months. IMDC Risk Score was favorable, intermediate, and poor in 27 (7.6%), 126 (35.5%), and 76 (21.4%) patients, respectively (23.4% intermediate/poor, 12.1% unknown). 270 patients (76.1%) received only 1L axitinib plus pembrolizumab and 85 patients (24.3%) received ≥1 subsequent line of treatment; cabozantinib was the most frequent subsequent line of treatment (47.9%). rwPFS at 3 months and 1 year was 77.2% and 39.3%, respectively. OS ranged from 90.8% at 3 months to 73.5% at 1 year. Best overall response rate was 47.9%. Toxicity was the most common reason for first TM events of dose hold, change and discontinuation at, 58.6%, 58.5%, and 45.8%, respectively. Over 80% of patients with TM were able to continue with 1L axitinib plus pembrolizumab. Conclusions: In a real-world setting, axitinib plus pembrolizumab was effective as a 1L treatment for patients with advanced RCC. Dose holds, changes and discontinuation were driven by treatment-related toxicity. Dose holds may represent an effective TM strategy to toxicity.

Treatment patterns and overall survival in HER2+ metastatic breast cancer at US community oncology practices.

Aim: To describe real-world treatment patterns/outcomes among patients with HER2+ metastatic breast cancer (MBC). Materials & methods: Real-world treatments and overall survival (OS) were evaluated among adult women diagnosed with HER2+ MBC, with and without brain metastases (BMs), between 1 June 2012 and  31 May 2018 using electronic medical records from the Definitive Oncology Dataset. Results: Among 372 patients, 69% initiated first-line trastuzumab plus pertuzumab-based therapy; many therapy combinations were utilized in the second- to fourth-line. During follow-up (median 24.8 months), 18% of patients died (22% with and 16% without BMs). Mean OS was shortest among patients with BMs at MBC diagnosis in the third- and fourth-line. Conclusion: OS was poor, and no clear standard of care was observed among patients with HER2+ MBC progressing on trastuzumab-based therapies.

Contemporary treatment utilization among women diagnosed with symptomatic uterine fibroids in the United States.

BACKGROUND: This study evaluated treatment patterns among women diagnosed with symptomatic uterine fibroids (UF) in the United States. Data were retrospectively extracted from the IBM Watson Health MarketScan® Commercial Claims and Encounters and Medicaid Multi-State databases. METHODS: Women aged 18-64 years with ≥1 medical claim with a UF diagnosis (primary position, or secondary position plus ≥1 associated symptom) from January 2010 to June 2015 (Commercial) and January 2009 to December 2014 (Medicaid) were eligible; the first UF claim during these time periods was designated the index date. Data collected 12 months pre- and 12 and 60 months post-diagnosis included clinical/demographic characteristics, pharmacologic/surgical treatments, and surgical complications. Prevalence (2015) and cumulative incidence (Commercial, 2010-2015; Medicaid, 2009-2015) of symptomatic UF were estimated. RESULTS: 225,737 (Commercial) and 19,062 (Medicaid) women had a minimum of 12 months post-index continuous enrollment and were eligible for study. Symptomatic UF prevalence and cumulative incidence were: 0.57, 1.23% (Commercial) and 0.46, 0.64% (Medicaid). Initial treatments within 12 months post-diagnosis were surgical (Commercial, 36.7%; Medicaid, 28.7%), pharmacologic (31.7%; 53.0%), or none (31.6%; 18.3%). Pharmacologic treatments were most commonly non-steroidal anti-inflammatory drugs and oral contraceptives; hysterectomy was the most common surgical treatment. Of procedures of abdominal hysterectomy, abdominal myomectomy, uterine artery embolization, and ablation in the first 12 months post-index, 14.9% (Commercial) and 24.9% (Medicaid) resulted in a treatment-associated complication. Abdominal hysterectomy had the highest complication rates (Commercial, 18.5%; Medicaid, 31.0%). CONCLUSIONS: Off-label use of pharmacologic therapies and hysterectomy for treatment of symptomatic UF suggests a need for indicated non-invasive treatments for symptomatic UF.

Commercial claims costs related to health care resource use associated with a diagnosis of peanut allergy.

BACKGROUND: Peanut allergy (PA) affects approximately 1.6 million US children. The current standard of care is strict avoidance and prompt reaction treatment. Peanut allergy health care costs and health care resource utilization (HCRU) are poorly understood. OBJECTIVE: To estimate PA health care costs and HCRU using a nationally representative commercial payer database. METHODS: The IBM MarketScan Commercial Claims and Encounters Database was examined for PA diagnosis/reaction codes between January 2010 and October 2016 in patients 64 years of age or younger, with age cohort-matched controls. Outcomes were measured 12 months before and after the first claim date. Health care costs and HCRU were compared using Student's t tests and χ2 tests. RESULTS: Patients with a PA-related diagnostic code (n = 41,675) incurred almost double all-cause health care costs vs controls ($6436 vs $3493, P < .001), mainly from inpatient and outpatient medical costs ($5002 vs $2832, P < .001). More than one third of the PA group patients (36%) had a code indicative of an anaphylactic reaction during follow-up. Mean PA or reaction-related code costs per visit totaled $7921 for hospitalizations and $1115 for emergency department (ED) visits. Costs were 30% lower in patients with asthma codes without PA codes vs those with both codes ($5678 vs $8112, P < .001); all-cause ED costs were more than double in patients with atopic dermatitis codes with PA codes vs those without PA codes ($654 vs $308, P < .001). CONCLUSION: National commercial payer claims data indicate a significant health care burden associated with a PA-related code, including over $6400/patient in annual all-cause costs and increased health care utilization.

Association Between Switching to a High-Deductible Health Plan and Discontinuation of Type 2 Diabetes Treatment.

Importance: High-deductible health plans (HDHPs) are a common cost-savings option for employers but may lead to underuse of necessary treatments because beneficiaries bear the full cost of health care, including medications, until a deductible is met. Objectives: To evaluate the association between switching from a non-HDHP to an HDHP and discontinuation of antihyperglycemic medication and to assess whether the association differs in patients using branded vs generic antihyperglycemic medications. Design, Setting, and Participants: This retrospective matched cohort study used administrative claims from MarketScan databases to identify commercially insured adult patients with type 2 diabetes who used at least 1 antihyperglycemic medication in 2013. Patients in the HDHP cohort (n = 1490) were matched by propensity scores to a non-HDPH control cohort (n = 1490). Data were collected and analyzed from January 1, 2013, through December 31, 2014. Exposures: Switching from a non-HDHP in 2013 to a full replacement HDHP in 2014 (no non-HDHP option offered) vs staying on a non-HDHP. Main Outcomes and Measures: Difference-in-differences models estimated discontinuation of branded and generic antihyperglycemic medications. Results: Among the 2980 patients included in the analysis (1932 men [64.8%]; mean [SD] age, HDHP cohort: 52.6 [6.9] years; non-HDHP cohort: 52.7 [7.3] years), no difference between the HDHP and non-HDHP cohorts was found in unadjusted follow-up discontinuation rates for all antihyperglycemic medications (255 [22.7%] vs 255 [23.3%]; P = .72); however, among patients using branded medication, a significantly greater proportion of patients in the HDHP group did not refill branded medications (81 of 396 [20.5%] vs 61 of 437 [14.0%]; P = .009). Difference-in-differences models were not statistically significant. Conclusions and Relevance: These findings suggest switching to an HDHP is associated with discontinuation specifically of branded medications. Unintended health consequences may result and should be considered by employers making health care benefit decisions.

Disease burden and cost of hidradenitis suppurativa: a retrospective examination of US administrative claims data.

OBJECTIVES: Hidradenitis suppurativa (HS) causes substantial morbidity and quality-of-life impairment. We examined demographic/clinical characteristics of patients with HS and treatment patterns, prevalence and healthcare resource utilisation/expenditures related to HS in the real-world. DESIGN: Retrospective claims data of MarketScan Commercial, Medicare Supplemental and Medicaid databases (2009-2014). SETTING: USA. PARTICIPANTS: Patients aged ≥12 years with ≥3 non-diagnostic outpatient or inpatient claims with an HS diagnosis code and ≥12 months continuous enrolment with medical and pharmacy benefits before (preindex) and after (postindex) the earliest diagnosis of HS (index) were included. RESULTS: There were 11 325 Commercial/Medicare patients (mean age 37.4 years) and 5164 Medicaid patients (mean age 28.3 years). HS was more common in Medicaid than Commercial/Medicare patients (0.301% and 0.098%, respectively, in 2014). Cellulitis and psychiatric disorders were the most common comorbidities and oral antibiotics and narcotics were the most frequently prescribed drugs preindex, with ≥10% increase postindex in both populations. HS-related inpatient costs decreased while outpatient costs increased from preindex to postindex. Medicaid patients had several risk factors that may be associated with poor outcomes (eg, high rates of prescription pain medication use, comorbidities, drug discontinuation/interruption/holiday, emergency department (ED) visits and hospitalisation). CONCLUSIONS: Commercial/Medicare and Medicaid HS beneficiaries experience high comorbidity burden but use different treatment modalities to manage HS. Results suggest a substantial unmet need exists among this patient population, with Medicaid patients experiencing a particularly high burden of disease and expensive healthcare resource utilisation.

A comparison of treatment patterns, healthcare resource utilization, and costs among young adult Medicaid beneficiaries with schizophrenia treated with paliperidone palmitate or oral atypical antipsychotics in the US.

BACKGROUND: Much of the burden associated with schizophrenia is attributed to its early onset and chronic nature. Treatment with once monthly paliperidone palmitate (PP1M) is associated with lower healthcare utilization and better adherence as compared to oral atypical antipsychotics (OAAs). This study aimed to evaluate real-world effectiveness of PP1M and OAA therapies among US-based adult Medicaid patients with schizophrenia, overall and among young adults aged 18-35 years. METHODS: Adult patients with a diagnosis of schizophrenia and at least two claims for PP1M or OAA between January 1, 2010 and December 31, 2014 were selected from the IBM Watson Health MarketScan Medicaid Database. Treatment patterns and healthcare resource utilization and costs were compared between PP1M and OAA treatment groups following inverse probability of treatment (IPT) weighting to adjust for potential differences. Utilization and cost outcomes were estimated using OLS and weighted Poisson regression models. RESULTS: After IPT weighting, the young adult PP1M and OAA cohorts were comprised of 3,095 and 3,155 patients, respectively. PP1M patients had a higher duration of continuous treatment exposure (168.2 vs 132.5 days, p = .004) and better adherence on the index medication (proportion of days covered ≥80%: 19.0% vs 17.1%, p < .049). Young adults treated with PP1M were 37% less likely to have an all-cause inpatient admission (odds ratio [OR] = 0.63, 95% confidence interval [CI] = 0.53-0.74) and 33% less likely to have an ER visit (OR = 0.67, 95% CI = 0.55-0.81) compared to OAA young adult patients, but 27% more likely to have an all-cause outpatient office visit (OR = 1.27, 95% CI = 1.02-1.56). PP1M patients incurred significantly lower medical costs as compared to OAA patients. CONCLUSIONS: Medicaid patients with schizophrenia treated with PP1M have higher medication adherence and have fewer hospitalizations as compared to patients treated with OAAs. PP1M may lead to reduced healthcare utilization and improved clinical outcomes.

Cost sharing and branded antidepressant initiation among patients treated with generics.

OBJECTIVES: To determine the relationship between consumer cost sharing for branded antidepressants and the initiation of branded therapy among patients with major depressive disorder (MDD) filling a prescription for generic MDD medication. STUDY DESIGN: Retrospective cross-sectional analyses. METHODS: Patients aged 18 to 64 years with MDD who filled a generic antidepressant were identified in commercial claims data for 2012 to 2014. For each year-specific analysis, an average cost-sharing index for branded antidepressants at the level of the plan was computed. Multivariable models were used to estimate the relationship between plan-level cost sharing for branded antidepressant medications and the filling of branded prescriptions, with demographic and clinical variables as covariates. RESULTS: For patients with MDD filling a generic prescription, increases in branded cost sharing were associated with significant decreases in the likelihood of filling a branded antidepressant in each year (P <.001). Results in 2012 imply that a shift from the 0th to 90th percentile in the branded cost-sharing index corresponded with a 9.5% decrease in the relative likelihood of a branded fill among patients receiving a generic antidepressant. The corresponding figures for 2013 and 2014 were 9.3% and 3.5%, respectively. CONCLUSIONS: In MDD, patients and clinicians who dutifully adhere to guidelines requiring a trial of first-line medication may ultimately require therapy with alternate agents to achieve adequate disease control. A "reward the good soldier" benefit design would lower cost sharing for higher-tier evidence-based therapies when clinically indicated. Results suggest that narrowing the gap in cost sharing between branded and generic medications following a trial of a generic agent might improve access to second-line treatment in MDD.

Analysis of utilization patterns and associated costs of the breast imaging and diagnostic procedures after screening mammography.

BACKGROUND: Little data exist on real-world patterns and associated costs of downstream breast diagnostic procedures following an abnormal screening mammography or clinical exam. OBJECTIVES: To analyze the utilization patterns in real-world clinical settings for breast imaging and diagnostic procedures, including the frequency and volume of patients and procedures, procedure sequencing, and associated health care expenditures. MATERIALS AND METHODS: Using medical claims from 2011 to 2015 MarketScan Commercial and Medicare Databases, adult females with breast imaging/diagnostic procedures (diagnostic mammography, ultrasound, molecular breast imaging, tomosynthesis, magnetic resonance imaging, or biopsy) other than screening mammography were selected. Continuous health plan coverage without breast diagnostic procedures was required for ≥13 months before the first found breast diagnostic procedure (index event), with a 13-month post-index follow-up period. Key outcomes included diagnostic procedure volumes, sequences, and payments. Results reported descriptively were projected to provide US national patient and procedure volumes. RESULTS: The final sample of 875,526 patients was nationally projected to 12,394,432 patients annually receiving 8,732,909 diagnostic mammograms (53.3% of patients), 6,987,399 breast ultrasounds (42.4% of patients), and 1,585,856 biopsies (10.3% of patients). Following initial diagnostic procedures, 49.4% had second procedures, 20.1% followed with third procedures, and 10.0% had a fourth procedure. Mean (SD) costs for diagnostic mammograms of US$349 ($493), ultrasounds US$132 ($134), and biopsies US$1,938 ($2,343) contributed US$3.05 billion, US$0.92 billion, and US$3.07 billion, respectively, to annual diagnostic breast expenditures estimated at US$7.91 billion. CONCLUSION: The volume and expense of additional breast diagnostic testing, estimated at US$7.91 billion annually, underscores the need for technological improvements in the breast diagnostic landscape.

The effect of DPP-4 inhibitors on asthma control: an administrative database study to evaluate a potential pathophysiological relationship.

RATIONALE: DPP-4 may regulate immunological pathways implicated in asthma. Assessing whether DPP-4 inhibitor (DPP-4i) use might affect asthma control is clinically important because DPP-4i use in type 2 diabetes mellitus management (T2DM) is increasing. This study evaluated associations between DPP-4i use and asthma control. METHODS: This was a retrospective, observational, matched cohort study using administrative claims in the MarketScan® Commercial Claims and Encounters (Commercial) and Medicare Supplemental and Coordination of Benefits (Medicare Supplemental) databases. Adult asthma patients initiating an oral DPP-4i or a non-DPP-4i between November 1, 2006 and March 31, 2014 were included. Patients were followed for asthma-related outcomes for 12 months after initiation of the antidiabetes medication. Outcomes included risk-domain asthma control (RDAC), defined as no asthma hospitalizations, no lower respiratory tract infections, and no oral corticosteroid (OCS) prescriptions; overall asthma control (RDAC criteria plus limited short-acting beta agonist use); treatment stability (RDAC criteria plus no increase of ≥50% in inhaled corticosteroid dose or addition of other asthma therapy); and severe asthma exacerbation rates (asthma-related hospitalizations, emergency room visits, or acute treatments with OCS). Comparisons were made between two matched cohorts (DPP-4i vs. non-DPP-4i initiators) using multivariable logistic regression and generalized linear modeling. Covariates included baseline demographic and clinical characteristics related to asthma and T2DM. RESULTS: The adjusted odds of achieving RDAC (odds ratio [OR]: 1.05; 95% CI: 0.964 to 1.147), overall asthma control (OR: 1.04; 95% CI: 0.956 to 1.135), and treatment stability (OR: 1.04; 95% CI: 0.949 to 1.115) did not differ between the DPP-4i and non-DPP-4i cohorts. A difference was not found between cohorts in severe asthma exacerbation rates during the 12 months following initiation of antidiabetes treatment (mean = 0.32 vs. 0.34 exacerbations per subject-year, respectively; p=0.064). CONCLUSION: Asthma control was similar between patients initiating DPP-4i and non-DPP-4i antidiabetes medications, suggesting no association between DPP-4i use and asthma control.

Discontinuation rates and health care costs in adult patients starting generic versus brand SSRI or SNRI antidepressants in commercial health plans.

BACKGROUND: Generic antidepressants offer significant prescription drug cost savings compared with brand-name antidepressants, but critics of managed care interventions promoting generic medication use suggest that some generic antidepressants are not as safe or effective as the brand alternatives. OBJECTIVE: To assess (a) rates of discontinuation of the initially dispensed medication and (b) disease-specific and total health care costs and pharmacy costs, comparing patients who initiated therapy with brand versus generic selective serotonin reuptake inhibitors (SSRI) or selective norepinephrine reuptake inhibitors (SNRI). METHODS: Antidepressant users aged 18 to 64 years with no pharmacy claims for an SSRI/SNRI in the 180 days prior to the start of SSRI/SNRI therapy (baseline) were identified in the MarketScan database between July 1, 2005, and June 30, 2007, and were followed for 180 days (followup). All study patients met the following criteria: (a) continuously eligible from baseline through follow-up; (b) at least 1 medical claim with a primary or secondary diagnosis of major depressive disorder (ICD-9-CM codes 296.2 or 296.3) in either the baseline or follow-up period; and (c) no pharmacy claims for antipsychotic medications in the baseline period. For brand versus generic antidepressant initiators, logistic regression was used to determine the odds of 6-month therapy discontinuation, defined as no medication refills or absence of a refill for the initially dispensed medication within 1.5 times the days supply dispensed, adjusted for important covariates. Costs were measured as total plan allowed charges including member cost share. Adjusted mean (least squares means holding covariates at mean values) all-cause medical costs, disease-specific (claims with a ICD-9-CM diagnosis code for major depressive disorder in the primary or secondary diagnosis field) medical costs, all-cause pharmacy costs, and SSRI/SNRI antidepressant costs were compared for brand versus generic initiators using generalized linear regression models, also adjusted for baseline covariates. RESULTS: Of 16,659 new SSRI/SNRI users, 47.8% (n=7,955) initiated a brand-name medication and 52.2% (n=8,704) initiated a generic product. Of the 7,955 who initiated a brand-name antidepressant, 46.8% (n=3,723) discontinued the initially dispensed drug within 180 days, compared with 44.2% (n=3,843) of the 8,704 who initiated a generic. The adjusted odds of discontinuation among generic and brand drug users did not significantly differ (odds ratio [OR]=1.09, 95% CI=0.98-1.22). Adjusted all-cause 6-month average health care costs in patients initiating therapy on a generic antidepressant were $3,660 (95% CI=$3,538-$3,787) compared with $4,587 (95% CI=$4,422-$4,757) for patients initiating on a brand-name antidepressant. Adjusted average 6-month SSRI/SNRI antidepressant costs were 43.7% lower in patients initiating on a generic drug ($174 vs. $309). CONCLUSIONS: The likelihood of discontinuation was similar for patients who initiated therapy with brand or generic antidepressants, and shortterm health care costs and pharmacy costs were lower in patients starting a generic SSRI/SNRI. The results suggest that the use of generic antidepressants as first-line agents in the treatment of major depressive disorder is associated with continuation rates similar to initiation with brand antidepressants but with lower health care costs.

The Benefit of Adjuvant Chemotherapy in Elderly Patients with Stage III Colorectal Cancer is Independent of Age and Comorbidity.

OBJECTIVES: To determine the combined effect of age and comorbidity on receipt of chemotherapy and its impact on survival in elderly patients with stage III colorectal cancer (CRC). MATERIALS AND METHODS: All patients over age 65 with Stage III CRC diagnosed 1996-2006 were identified from the Barnes-Jewish Hospital Oncology Data Services registry. An age/comorbidity staging system was created using the ACE-27 comorbidity index and data from both Stage II and III CRC. The staging system was then applied to patients with Stage III CRC. Odds of receiving chemotherapy were calculated, and survival analyses determined the impact of chemotherapy on overall survival in each age/comorbidity stage. RESULTS: 435 patients with Stage III CRC were evaluated [median age 75 years (range 65-99)]. Advancing age/comorbidity stage (Alpha, Beta, Gamma) was associated with decreasing odds of receiving chemotherapy for Stage III CRC [Odds Ratio 0.83 (95% CI, 0.51-1.35) for Beta and 0.14 (95% CI, 0.08-0.24) for Gamma, compared to Alpha]. Chemotherapy was associated with lower risk of death in each of the age/comorbidity stages, compared to those who underwent surgery only. The hazard ratio for death in patients who did not receive chemotherapy, relative to those who did, within each age/comorbidity stage was 1.8 [95%CI 1.06-3.06] for Alpha, 2.24 [95%CI 1.38-3.63] for Beta and 2.10 [95% CI 1.23-3.57] for Gamma. CONCLUSION: While stage III CRC patients with increasing age and comorbidity are less likely to receive chemotherapy, receipt of chemotherapy is associated with a lower risk of death.

Gender differences in self-reported symptom awareness and perceived ability to manage therapy with disease-modifying medication among commercially insured multiple sclerosis patients.

BACKGROUND: Multiple sclerosis (MS) is a chronic, neurodegenerative inflammatory disease that affects approximately 400,000 Americans, the majority of whom are female. Although MS prevalence is higher among females, males are more likely to have a more progressive clinical course. For both genders, use of disease-modifying medications (DMMs) in the clinical management of MS is pivotal in altering the natural course and diminishing progressive disability over time. OBJECTIVES: To evaluate gender differences in self-reported symptom awareness and perceived ability to manage therapy among MS patients taking a DMM. METHODS: During February 2008, a self-administered, 42-item survey was mailed to 4,700 commercially insured patients taking a DMM to treat MS. Survey items measured self-reported clinical characteristics, symptom awareness, and perceived ability to manage therapy. Bivariate analyses assessed associations of gender with other predictor and outcome variables, including demographic characteristics, clinical disease characteristics, specific DMM used at the time of the survey, self-reported symptom awareness, and perceived ability to manage therapy. Logistic regression analyses further assessed the associations of gender with symptom awareness and perceived ability to manage MS after adjustment for relevant covariates (age at diagnosis, educational level, income, current DMM, type of pharmacy where drug was dispensed, frequency of flare-ups, and clinical course of disease). RESULTS: The response rate was 44.1% (n = 2,074). Of the 2,022 respondents with useable surveys, 80.6% were female; 82.3% had relapsing remitting MS; and 83.1% were taking one of the most commonly used DMMs (intramuscular interferon beta-1a 33.4%, subcutaneous interferon beta-1a 15.9%, and glatiramer acetate 33.8%). Compared with female patients, males were older and a greater proportion had a more progressive clinical course of disease. In multivariate models, female patients were more likely than males to report recognition of a relapse/exacerbation (odds ratio [OR] = 1.37, 95% CI = 1.03-1.82) and to report knowing what to do when experiencing a relapse/exacerbation (OR = 1.34, 95% CI = 1.01- 1.77) or if they missed a dose of medication (OR = 1.78, 95% CI = 1.08-2.43). Females were also more likely to report awareness of treatment options (OR = 1.48, 95% CI = 1.07-2.07) and to think that DMMs were helping their MS (OR = 1.32, 95% CI = 1.02-1.77). CONCLUSIONS: Female MS patients report better awareness of disease symptoms and have more positive perceptions of their ability to manage therapy with DMMs than male MS patients. These findings suggest that male MS patients may require additional education and support to manage their disease and therapy needs. Knowledge of these gender differences potentially could help managed care organizations to improve therapy adherence by guiding gender-specific patient support programs.

A comparison of diabetes medication adherence and healthcare costs in patients using mail order pharmacy and retail pharmacy.

OBJECTIVE: To compare long-term diabetes medication adherence and healthcare costs in patients using mail order pharmacy versus retail pharmacy. METHODS: The MarketScan database was used to identify patients who filled prescriptions for oral anti-diabetes medications in a retail pharmacy for at least 6 months before switching to mail order pharmacy for at least 12 months. These patients were matched to others who used retail pharmacy continuously for at least 18 months. A propensity score was used to create matched groups of patients comparable on probability of switching to mail order, weighted Poisson regression was used to analyze differences in medication adherence, and Tobit regression was used to compare costs. RESULTS: A total of 14,600 patients who switched to mail order were matched to 43,800 patients who used retail pharmacy continuously. The average adjusted adherence in retail pharmacy was 63.4% compared to 84.8% after switching to mail order. Per-member-per-month total healthcare and total medical costs were on average $34.32 and $37.54 lower in the mail order group, respectively. Diabetes-related medical costs were on average $19.14 lower in the mail order group, while pharmacy costs were $14.13 higher. LIMITATIONS: Limitations include a patient population under the age of 65, no information on pharmacy benefit design, and limited follow-up time relative to that necessary to identify long-term diabetes complications. CONCLUSIONS: After adjusting for measured confounders of medication adherence and disease severity, individuals who switched to mail order pharmacy had higher medication possession ratios and trended toward lower total and diabetes-related medical costs over time.

The effect of nasally administered budesonide respules on adrenal cortex function in patients with chronic rhinosinusitis.

OBJECTIVES: To evaluate whether nasal administration of budesonide in adults with chronic rhinosinusitis for 30 days suppresses adrenal function and to assess its clinical efficacy. DESIGN: An open-label prospective study. SETTING: Academic medical center. PATIENTS: We assessed adrenal function in 9 patients using the cosyntropin test before and after budesonide therapy. INTERVENTION: Budesonide respule therapy. MAIN OUTCOME MEASURE: Scores from the Sino-Nasal Outcome Test-20 (SNOT-20), a tool for assessing rhinosinusitis health and quality of life, were used to assess efficacy of budesonide treatment. RESULTS: All of our patients showed adequate adrenal response to cosyntropin stimulation before and after the budesonide trial. The mean difference in SNOT-20 scores was -1 (95% confidence interval, -1.77 to -0.23; P = .02), indicating clinically significant improvement after therapy. CONCLUSION: Our findings suggest that using budesonide nasal wash may be clinically effective in decreasing the symptoms of chronic rhinosinusitis and does so without suppression of the hypothalamic-pituitary-adrenal axis in patients with chronic rhinosinusitis.

Impact of comorbidity on overall survival in patients surgically treated for renal cell carcinoma.

OBJECTIVES: Although the classification of cancer has traditionally focused on the gross and microscopic characteristics of the tumor, the overall health of patients can affect their survival. Because patients with renal cell carcinoma often have other medical conditions, we explored the effect of preexisting medical disease on survival after radical and partial nephrectomy. METHODS: From January 1995 to August 2003, the comorbidity status of 697 patients with nonmetastatic renal cell carcinoma who had undergone radical or partial nephrectomy was prospectively coded using the Adult Comorbidity Evaluation-27. Histopathologic review of all slides was performed according to the 2004 World Health Organization scheme. Other variables analyzed included age, sex, ethnicity, pathologic stage, Fuhrman grade, and tumor size. The effect of these factors on overall survival (OS) was analyzed using Cox proportional hazards regression model. RESULTS: The median follow-up was 32.2 months for survivors and 36.5 months for all patients. The OS rate at 1, 3, and 5 years was 92.0% (641 patients), 75.3% (525 patients), and 52.7% (367 patients), respectively. Univariate analyses demonstrated that age, comorbidity, tumor size, Fuhrman grade, and pathologic stage were significant predictors of OS. Multivariate analysis revealed that age (hazard ratio [HR] 1.42, 95% confidence interval [CI] 1.10 to 1.82, P = .0067), comorbidity (HR 1.37, 95% CI 1.16 to 1.63, P = .0002), pathologic stage (HR 1.97, 95% CI 1.60 to 2.41, P < .0001), and grade (HR 1.83, 95% CI 1.28 to 2.59, P = .0008) predicted for OS. CONCLUSIONS: The results of this study have demonstrated that comorbidity is an independent prognostic factor for OS in patients with renal cell carcinoma. Capturing the comorbidity information using validated instruments can improve the preoperative evaluation of patients by providing more accurate prognostic information.

The changing prevalence of comorbidity across the age spectrum.

The purpose of the research was to demonstrate that comorbid health conditions disproportionately affect elderly cancer patients. Descriptive analyses and stacked area charts were used to examine the prevalence and severity of comorbid ailments by age of 27,506 newly diagnosed patients treated at one of eight cancer centers between 1998 and 2003. Hypertension was the most common ailment in all patients, diabetes was the second most prevalent ailment in middle-aged patients, and previous solid tumor(s) were the second most prevalent ailment in patients aged 74 and older. Although the prevalence and severity of comorbid ailments including dementia and congestive heart failure increased with age, some comorbidities such as HIV/AIDS and obesity decreased. Advances in cancer interventions have increased survivorship, but the impact of the changing prevalence and severity of comorbidities at different ages has implications for targeted research into targeted clinical and psychosocial interventions.

HLA alleles determine differences in human natural killer cell responsiveness and potency.

Epidemiological studies have associated certain human disease outcomes with particular killer cell Ig-like receptor (KIR) and HLA genotypes. However, the functional explanation for these associations is poorly understood, because the KIRs were initially described as natural killer (NK) cell inhibitory receptors with specificity for HLA molecules on their cellular targets. Yet resolution of infections is often associated with genotypic pairing of inhibitory KIRs with their cognate HLA ligands. Recent studies in mice indicate a second role for MHC-specific inhibitory receptors, i.e., self-MHC recognition confers functional competence on the NK cell to be triggered through their activation receptors, a process termed licensing. As a result, licensed NK cells with self-MHC-specific receptors are more readily activated as compared with unlicensed NK cells without self-MHC-specific receptors. Such results predict that human NK cells may undergo a similar process. Here, we examined the human NK cell subset expressing KIR3DL1, the only known KIR specific for HLA-Bw4 alleles. The KIR3DL1(+) subset in normal donors with two HLA-B-Bw4 genes displayed increased responsiveness to tumor stimulation compared with the KIR3DL1(+) subset from individuals with only one or no Bw4 genes. By contrast, NK cells lacking KIR3DL1 showed no differences. Therefore, these data indicate that particular KIR and HLA alleles are associated with more responsive NK cells, strongly suggesting that human NK cells are also subjected to NK cell licensing, and providing a potential functional explanation for the influence of KIR and HLA genes in disease as well as interindividual differences in NK cell potency.

Prognostic impact of comorbidity in patients with bladder cancer.

OBJECTIVE: To determine the impact of comorbidity on survival of bladder cancer patients. METHODS: The population included 675 patients with newly diagnosed bladder cancer whose medical information was abstracted from a hospital cancer registry. Adult Comorbidity Evaluation-27, a validated instrument, was used to prospectively categorize comorbidity. Independent variables assessed include comorbidity, American Joint Committee on Cancer (AJCC) stage, grade, age, gender, and race. Outcome measure was overall survival. We analyzed the entire cohort, patients with noninvasive disease, and patients requiring cystectomy. Cox proportional hazards analysis was used to assess impact of independent variables on survival. RESULTS: Median age at diagnosis for the entire cohort was 71 yr and median follow-up was 45 mo. Of 675 patients, 446 had at least one comorbid condition and 301 died during follow-up. On multivariable analysis for the entire cohort, comorbidity (p=0.0001), AJCC stage (p=0.0001), age (p=0.0001), and race (p=0.0045) significantly predicted overall survival. On subset analysis of noninvasive bladder cancer patients, comorbidity (p=0.0001) and age (p=0.0001) independently predicted overall survival, whereas stage, grade, race, and gender did not. On subset analysis of cystectomy patients, comorbidity (p=0.0053), stage (p=0.0001), and race (p=0.0449) significantly predicted overall survival. CONCLUSIONS: Comorbidity is an independent predictor of overall survival in the entire cohort of bladder cancer patients, the subset with noninvasive disease, and the subset treated with cystectomy.

Relief of idiopathic subjective tinnitus: is gabapentin effective?

OBJECTIVE: To assess the therapeutic benefit of gabapentin (Neurontin) for subjective idiopathic troublesome tinnitus. DESIGN: An 8-week, double-blind, randomized clinical trial. SETTING: Academic otolaryngology clinic in St Louis, Mo. SUBJECTS: One hundred thirty-five subjects with severe idiopathic subjective tinnitus of 6 months' duration or longer. INTERVENTION: Gabapentin, at a maintenance dosage of 900 to 3600 mg/d for 8 weeks, or lactose placebo. MAIN OUTCOME MEASURE: Change in the Tinnitus Handicap Inventory score from baseline to the study end point. RESULTS: The overall change in the Tinnitus Handicap Inventory score for the entire cohort from baseline to week 8 was 11.2; the change among the 59 subjects randomized to the gabapentin arm was 11.3 and the change among the 56 subjects in the placebo arm was 11.0. The difference was 0.03 (95% confidence interval, -5.5 to 6.2; P = .91). CONCLUSION: Gabapentin is no more effective than placebo for the relief of idiopathic subjective tinnitus. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00317850.