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INTRIGUE was an open-label, phase 3 study in adult patients with advanced gastrointestinal stromal tumor who had disease progression on or intolerance to imatinib and who were randomized to once-daily ripretinib 150 mg or sunitinib 50 mg. In the primary analysis, progression-free survival (PFS) with ripretinib was not superior to sunitinib. In clinical and nonclinical studies, ripretinib and sunitinib have demonstrated differential activity based on the exon location of KITmutations. Therefore, we hypothesized that mutational analysis using circulating tumor DNA (ctDNA) might provide further insight. In this exploratory analysis (N= 362), baseline peripheral whole blood was analyzed by a 74-gene ctDNA next-generation sequencing–based assay. ctDNA was detected in 280/362 (77%) samples with KITmutations in 213/362 patients (59%). Imatinib-resistant mutations were found in the KIT ATP-binding pocket (exons 13/14) and activation loop (exons 17/18). Mutational subgroup assessment showed 2 mutually exclusive populations with differential treatment effects. Patients with only KITexon 11 + 13/14 mutations (ripretinib, n= 21; sunitinib, n= 20) had better PFS with sunitinib versus ripretinib (median, 15.0 versus 4.0 months). Patients with only KITexon 11 + 17/18 mutations (ripretinib, n= 27; sunitinib, n= 25) had better PFS with ripretinib versus sunitinib (median, 14.2 versus 1.5 months). The results of this exploratory analysis suggest ctDNA sequencing may improve the prediction of the efficacy of single-drug therapies and support further evaluation of ripretinib in patients with KITexon 11 + 17/18 mutations. ClinicalTrials.gov identifier: NCT03673501.

Background: Expanded HIV screening efforts in the United States have increased the use of rapid HIV tests in emergency departments. The reported sensitivity and specificity of rapid HIV tests exceed 99%. Objective: To assess whether a reactive rapid oral HIV test result correctly identifies adults with HIV infection in the emergency department. Design: Diagnostic test performance assessment within the framework of a randomized, clinical trial. Setting: Brigham and Women's Hospital emergency department (Boston, Massachusetts) from 7 February to 1 October 2007. Patients: 849 adults with valid rapid oral HIV test results. Intervention: Rapid HIV testing with the OraQuick ADVANCE Rapid HIV-1/2 Antibody Test (OraSure Technologies, Bethlehem, Pennsylvania). Patients with reactive rapid test results were offered enzyme-linked immunoassay, Western blot, and plasma HIV-1 RNA testing for confirmation. Measurements: Specificity and positive likelihood ratio. Results: 39 patients had reactive results (4.6% [95% CI, 3.2% to 6.0%]). On confirmation, 5 patients were HIV-infected (prevalence, 0.6% [CI, 0.1% to 1.1%]) and 26 were non-HIV-infected (8 patients declined confirmation). The estimated rapid test specificity was 96.9% (CI, 95.7% to 98.1%). Sensitivity analyses of the true HIV status of unconfirmed cases and test sensitivity resulted in a positive likelihood ratio of 8 to 32. Western blot alone as a confirmation test provided conclusive HIV status in only 50.0% (CI, 30.8% to 69.2%) of patients at first follow-up. The addition of HIV-1 RNA testing to the confirmation protocol improved this rate to 96.2% (CI, 88.8% to 100.0%). Limitation: Test sensitivity cannot be assessed because nonreactive OraQuick test results were not confirmed. Conclusion: Although patients with a reactive oral OraQuick HIV screening test in the emergency department had an 8- to 32-fold increased odds of HIV infection compared with the pretest odds, the specificity of the test was lower than anticipated.

AbstractAims:To compare healthcare resource utilization and costs between patients aged 18–64 years with osteoarthritis (OA) and matched controls without OA in a privately insured population.Methods:Patients with OA were selected from de-identified US-based employer claims (Q1:1999–Q3:2011). The index date was defined as the first OA diagnosis indicated by ICD-9-CM codes. One year before and after the index date were defined as the baseline and study periods, respectively. A second OA diagnosis during the study period was also required. Patients with OA were matched one-to-one on age, gender, index date, and minimum length of follow-up to controls without OA. Baseline characteristics and study period resource utilization and costs (2016 USD) were compared between cohorts.Results:This study identified 199,539 patients with OA (knee: 87,271, hip: 19,953, hand: 15,670, spine: 12,496). The average age was 54 years, and 58% were female. OA patients had higher healthcare resource utilization than matched controls in inpatient, emergency room, and outpatient settings (p < .001 for all). Further, patients with OA had 4-times the excess total medical costs of their matched controls ($14,521 vs $3,629; p < .001). Patients with hip OA had the highest medical costs among all joint locations. Outpatient and pharmacy costs were similar among patients with knee, hip, and hand OA, but higher in patients with spine OA. In sub-group analyses, older patients (45–64 years old) had higher costs.Limitations:This sample, obtained using claims data, only includes patients who were actively seeking care for OA and were likely symptomatic. Asymptomatic patients would likely not be captured in this analysis.Conclusions:Patients with OA incur greater healthcare resource utilization and costs than patients without OA, with substantial variation by joint location.

AbstractObjective:To describe dosing patterns and to compare the drug costs per month spent in progression-free survival (PFS) among patients with advanced renal cell carcinoma (aRCC) treated with everolimus or axitinib following a first tyrosine kinase inhibitor (TKI).Methods:A medical record retrospective review was conducted among medical oncologists and hematologists/oncologists in the US. Patient eligibility criteria included: (1) age ≥18 years; (2) discontinuation of first TKI (sunitinib, sorafenib, or pazopanib) for medical reasons; (3) initiation of axitinib or everolimus as a second targeted therapy during February 2012–January 2013. Real-world dosing patterns were summarized. Dose-specific drug costs (as of October 2014) were based on wholesale acquisition costs from RED BOOK Online. PFS was compared between everolimus and axitinib using a multivariable Cox proportion hazards model. Everolimus and axitinib drug costs per month of PFS were compared using multivariable gamma regression models.Results:A total of 325 patients received everolimus and 127 patients received axitinib as second targeted therapy. Higher proportions of patients treated with axitinib vs everolimus started on a higher than label-recommended starting dose (14% vs 2%) or experienced dose escalation (11% vs 1%) on second targeted therapy. The PFS did not differ significantly between patients receiving everolimus or axitinib (adjusted hazard ratio (HR) = 1.16; 95% confidence interval [CI] = 0.73–1.82). After baseline characteristics adjustment, axitinib was associated with 17% ($1830) higher drug costs per month of PFS compared to everolimus ($12,467 vs $10,637; p < 0.001).Limitations:Retrospective observational study design and only drug acquisition costs considered in drug costs estimates.Conclusions:Patients with aRCC receiving axitinib as second targeted therapy were more likely to initiate at a higher than label-recommended dose and were more likely to dose escalate than patients receiving everolimus. With similar observed durations of PFS, drug costs were significantly higher—by 17% per month of PFS—with axitinib than with everolimus.

The rates of total joint arthroplasty (TJA) of the hip and knee have increased in North America over the last decade. While initially designed for elderly patients (70 years of age), several reports suggest that an increasing number of younger patients are undergoing joint replacements. This suggests that more people are meeting the indication for TJA earlier in their lives. Alternatively, it might indicate a broadening of the indications for TJA.

The US Centers for Disease Control and Prevention (CDC) guidelines and the World Health Organization (WHO) both recommend HIV testing in health-care settings. However, neither organization provides prescriptive details regarding how these recommendations should be adapted into clinical practice in an emergency department. We have implemented an HIV-testing program in the ED of a major academic medical center within the scope of the Universal Screening for HIV Infection in the Emergency Room (USHER) Trial—a randomized clinical trial evaluating the feasibility and cost-effectiveness of HIV screening in this setting. Drawing on our collective experiences in establishing programs domestically and internationally, we offer a practical framework of lessons learned so that others poised to embark on such HIV testing programs may benefit from our experiences.

ObjectiveKnee osteoarthritis OA is highly prevalent and disabling. Patients with radiographic knee OA may experience pain and functional impairment, which can diminish their health status. Our objective was to determine factors associated with selfreported health status in a national populationbased sample with radiographic knee OA.MethodsOur sample included all of the Third National Health and Nutrition Examination Survey NHANESIII participants who underwent a knee radiograph and were found to have radiographic OA defined as KellgrenLawrence grade 2 or higher. Selfreported health status was determined by asking the participant to rate their overall health as excellent, very good, good, fair, or poor. Selfreported health status was analyzed as an ordinal variable using cumulative logit regression, as a dichotomous variable excellentvery goodgood versus fairpoor using logistic regression, and as a continuous variable after transformation using linear regression.ResultsA total of 1,021 42 of NHANESIII participants with a knee radiograph were included in this analysis. The multivariable analyses were performed on 1,009 99 of the eligible participants with complete data. We found that nonwhite race, lower income, more comorbidities, and greater functional limitation were associated with worse selfreported health status in all 3 multivariable analyses.ConclusionThis study has quantified the role of clinical, radiographic, and socioeconomic factors associated with selfreported health status in a populationbased sample of patients with knee OA. Selfreported health status in patients with knee OA was associated with functional status and comorbidity.

This study examines the effect of first targeted therapy on outcomes with everolimus as second targeted therapy in patients with metastatic renal cell carcinoma. Overall survival, treatment failure, and discontinuation are analyzed in 3 chart reviews, and results are synthesized in a meta-analysis. Results indicate that first targeted therapy does not significantly affect outcomes of patients using everolimus as second targeted therapy.

Leptin has been suspected to contribute to the development of osteoarthritis (OA). However, this hypothesis has not been tested in large-scale hand OA cohorts. Our study aimed to determine whether there is a cross-sectional relationship between serum leptin levels and hand OA in a population-based sample of US adults.