Real-world Data of Nivolumab for Patients With Advanced Renal Cell Carcinoma in the Netherlands:An Analysis of Toxicity, Efficacy, and Predictive Markers

Background: Nivolumab, a programmed death 1 inhibitor, has been approved as second-line treatment for advanced renal cell carcinoma (RCC) in Europe since 2016. We investigated the toxicity and efficacy of nivolumab as well as potential predictive biomarkers in the Dutch population. Patients and Methods: This was a retrospective, multicenter study of the Dutch national registry of nivolumab for the treatment of advanced RCC. The main outcome parameters included toxicity, objective response rate (ORR), overall survival (OS), progression-free survival (PFS), time to progression (TTP), and time to treatment failure (TTF). In addition, potential predictive and prognostic biomarkers for outcomes were evaluated. Results: Data on 264 patients were available, of whom 42% were International Metastatic RCC Database Consortium (IMDC) poor risk at start of nivolumab, 16% had ≥ 3 lines of previous therapy, 7% had non–clear-cell RCC, 11% had brain metastases, and 20% were previously treated with everolimus. Grade 3/4 immune-related adverse events occurred in 15% of patients. The median OS was 18.7 months (95% confidence interval, 13.7-23.7 months). Progression occurred in 170 (64.4%) of 264 patients, with a 6-and 12-months TTP of 49.8% and 31.1%, respectively. The ORR was 18.6% (49 of 264; 95% confidence interval, 14%-23%). Elevated baseline lymphocytes were associated with improved PFS (P =.038) and elevated baseline lactate dehydrogenase with poor OS, PFS, and TTF (P =.000). On-treatment increase in eosinophils by week 8 predicted improved OS (P =.003), PFS (P =.000), and TTF (P =.014), whereas a decrease of neutrophils was associated with significantly better TTF (P =.023). Conclusions: The toxicity and efficacy of nivolumab for metastatic RCC after previous lines of therapy are comparable with the results in the pivotal phase III trial and other real-world data. On-treatment increase in eosinophil count is a potential biomarker for efficacy and warrants further investigation

Estimating EQ-5D utilities based on the Short-Form Long Term Conditions Questionnaire (LTCQ-8)

Purpose: The aim of this work was to develop a mapping algorithm for estimating EuroQoL 5 Dimension (EQ-5D) utilities from responses to the Long-Term Conditions Questionnaire (LTCQ), thus increasing LTCQ’s potential as a comprehensive outcome measure for evaluating integrated care initiatives. Methods: We combined data from three studies to give a total sample of 1334 responses. In each of the three datasets, we randomly selected 75% of the sample and combined the selected random samples to generate the estimation dataset, which consisted of 1001 patients. The unselected 25% observations from each dataset were combined to generate an internal validation dataset of 333 patients. We used direct mapping models by regressing responses to the LTCQ-8 directly onto EQ-5D-5L and EQ-5D-3L utilities as well as response (or indirect) mapping to predict the response level that patients selected for each of the five EQ-5D-5L domains. Several models were proposed and compared on mean squared error and mean absolute error. Results: A two-part model with OLS was the best performing based on the mean squared error (0.038) and mean absolute error (0.147) when estimating the EQ-5D-5L utilities. A multinomial response mapping model using LTCQ-8 responses was used to predict EQ-5D-5L responses levels. Conclusions: This study provides a mapping algorithm for estimating EQ-5D utilities from LTCQ responses. The results from this study can help broaden the applicability of the LTCQ by producing utility values for use in economic analyses

Validation of the Body Concealment Scale for Scleroderma (BCSS): Replication in the Scleroderma Patient-centered Intervention Network (SPIN) Cohort

© 2016 Elsevier Ltd Body concealment is an important component of appearance distress for individuals with disfiguring conditions, including scleroderma. The objective was to replicate the validation study of the Body Concealment Scale for Scleroderma (BCSS) among 897 scleroderma patients. The factor structure of the BCSS was evaluated using confirmatory factor analysis and the Multiple-Indicator Multiple-Cause model examined differential item functioning of SWAP items for sex and age. Internal consistency reliability was assessed via Cronbach's alpha. Construct validity was assessed by comparing the BCSS with a measure of body image distress and measures of mental health and pain intensity. Results replicated the original validation study, where a bifactor model provided the best fit. The BCSS demonstrated strong internal consistency reliability and construct validity. Findings further support the BCSS as a valid measure of body concealment in scleroderma and provide new evidence that scores can be compared and combined across sexes and ages

Isolation of microsatellite loci from the coqui frog, \u3ci\u3eEleutherodactylus coqui\u3c/i\u3e

Thirteen microsatellite loci were isolated from the coqui frog (Eleutherodactylus coqui) and optimized for future research. The loci were screened across 37 individuals from two Puerto Rican populations. Loci were variable with the number of alleles per locus ranging from three to 38. Polymorphic information content ranged from 0.453 to 0.963 and observed heterozygosity for each population ranged from 0.320 to 0.920

Treatment of ulcerative compared to non-ulcerative interstitial cystitis with hyperbaric oxygen: a pilot study

Background The etiology of interstitial cystitis (IC) is often idiopathic but can be due to Hunner’s ulcers. Hyperbaric oxygen (HBO) is used to treat ulcerative disease of the superficial skin. We hypothesized that HBO can treat ulcerative IC (UIC) but would be less efficacious for non-ulcerative IC (NIC). Methods Patients with NIC and UIC enrolled in this study. Following informed consent, demographic information was collected. A visual analog pain scale and validated questionnaires were collected; each patient underwent cystoscopy prior to treatment. Each subject met with a hyperbaric specialist and after clearance underwent 30 treatments over 6 weeks. Adverse events were monitored. Patients repeated questionnaires, visual analog pain scale and global response assessment (GRA) immediately, 2 weeks, 3, 6 and 12 months after treatment. Patients also underwent cystoscopy 6 months after treatment. Differences before and after treatment were compared. Results Nine patients were recruited to this study. One was unable to participate, leaving two subjects with NIC and six with UIC. All patients completed HBO without adverse events. Three patients completed HBO but pursued other therapies 7, 8.5 and 11 months after treatment. On GRA, 83% of patients with UIC were improved. This treatment effect persisted, as 66% of UIC patients remained better at 6 months. In contrast, only one patient in the NIC group improved. Questionnaire scores improved in both groups. Pain scores improved by 2 points in the UIC group but worsened by 1.5 points in the NIC group. Two patients with ulcers resolved at 6-month cystoscopy. Conclusion HBO appeared beneficial for both UIC and NIC. Data shows slightly better benefit in patients with UIC compared to NIC; both groups showed improvement. Given the small sample size, it is difficult to draw definitive conclusions from these data. Larger studies with randomization would be beneficial to show treatment effect

Fifteen microsatellite loci for the jungle perch, Kuhlia rupestris

We developed and optimized 15 polymorphic microsatellite loci in the jungle perch, Kuhlia rupestris. Loci were screened in a single population (n = 24) from Fraser Island, Queensland, Australia. Number of alleles per locus ranged from 3 to 19 and observed heterozygosity from 0.25 to 1. No significant linkage disequilibrium was detected between any pair of loci. Genotype proportions for these loci in the population sampled were in Hardy-Weinberg equilibrium

Isolation of Microsatellite Loci from the Coqui Frog, Eleutherodactylus coqui

Thirteen microsatellite loci were isolated from the coqui frog (Eleutherodactylus coqui) and optimized for future research. The loci were screened across 37 individuals from two Puerto Rican populations. Loci were variable with the number of alleles per locus ranging from three to 38. Polymorphic information content ranged from 0.453 to 0.963 and observed heterozygosity for each population ranged from 0.320 to 0.920