Coen Bernaards

Fatigue in long-term breast carcinoma survivors: a longitudinal investigation.

A longitudinal study was designed to evaluate the prevalence, persistence, and predictors of posttreatment fatigue in breast carcinoma survivors.

Gradient Projection Algorithms and Software for Arbitrary Rotation Criteria in Factor Analysis

Almost all modern rotation of factor loadings is based on optimizing a criterion, for example, the quartimax criterion for quartimax rotation. Recent advancements in numerical methods have led to general orthogonal and oblique algorithms for optimizing essentially any rotation criterion. All that is required for a specific application is a definition of the criterion and its gradient. The authors present the implementations of gradient projection algorithms, both orthogonal and oblique, as well as a catalogue of rotation criteria and corresponding gradients. Software for these is downloadable and free; a specific version is given for each of the computing environments used most by statisticians. Examples of rotation methods are presented by applying them to a loading matrix from Wehmeyer and Palmer.

Mericitabine and ritonavir-boosted danoprevir with or without ribavirin in treatment-naive HCV genotype 1 patients: INFORM-SVR study.

Safety and tolerability of peginterferon‐based hepatitis C virus (HCV) infection therapy remains suboptimal, even when direct‐acting antiviral agents are added. This study assessed the efficacy, safety and tolerability of mericitabine combined with ritonavir‐boosted danoprevir (danoprevir/r) ± ribavirin for up to 24 weeks in treatment‐naïve HCV genotype (G)1 infected patients.

Pharmacokinetic analysis of irinotecan plus bevacizumab in patients with advanced solid tumors

PurposeThe purpose of this study was to evaluate the effect of bevacizumab on the pharmacokinetics (PK) of irinotecan and its active metabolite. Exploratory analyses of the impact of variability in uridine diphosphate glucuronosyltransferase 1A (UGT1A) genes on irinotecan metabolism and toxicity were conducted.MethodsThis was an open-labeled, fixed-sequence study of bevacizumab with FOLFIRI (irinotecan, leucovorin, and infusional 5-fluorouracil). Pharmacokinetic assessments were conducted in cycles 1 and 3.ResultsForty-five subjects were enrolled. No difference in dose-normalized AUC0–last for irinotecan and SN-38 between irinotecan administered alone or in combination with bevacizumab was identified. Leukopenia was associated with higher exposure to both irinotecan and SN-38. UGT1A1 polymorphisms were associated with variability in irinotecan PK. Gastrointestinal toxicity was associated with UGT1A6 genotype. No other associations between UGT1A genotypes and toxicity were detected.ConclusionBevacizumab does not affect irinotecan PK when administered concurrently. A variety of pharmacogenetic relationships may influence the pharmacokinetics of irinotecan and its toxicity.

Evaluation of pharmacokinetics, user handling, and tolerability of peginterferon alfa-2a (40 kDa) delivered via a disposable autoinjector device.

Background Peginterferon alfa-2a (40 kDa) is currently administered using a prefilled syringe. The peginterferon alfa-2a disposable autoinjector is a new safety-engineered device designed to facilitate injection and reduce the risk of needlestick injuries. The analysis of two open-label Phase I trials evaluated the pharmacokinetics, successful administration, and tolerability of peginterferon alfa-2a when using the autoinjector. The studies were performed to support the filing and registration of the autoinjector device. Methods In trial 1, 50 healthy adult subjects received one 180 μg dose of peginterferon alfa-2a via the autoinjector. Serial blood samples were collected predose, up to 336 hours following drug administration, and at follow-up (28 ± 3 days post-dosing) for noncompartmental pharmacokinetic analysis. Trial 2 randomized 60 adult patients with chronic hepatitis C to 180 μg peginterferon alfa-2a once weekly by the autoinjector or prefilled syringe for 3 weeks followed by the alternative device (prefilled syringe or autoinjector, respectively) for 3 weeks. Patients also received ribavirin. Administration by the devices was evaluated under direct observation by a study staff member and by patient subjective assessment. Results In trial 1, following a single dose of peginterferon alfa-2a, the maximum plasma concentration was 16.1 ± 5.3 ng/mL (mean ± standard deviation), and area under the concentration time curve (0–168 hours) was 1996 ± 613 ng · hour/mL, similar to that reported using a vial/syringe or prefilled syringe. In trial 2, few patients showed handling difficulties with either device. Generally, patients were observed to be more satisfied and confident, followed instructions better, and successfully initiated injection with the autoinjector versus the prefilled syringe. Patients reported the autoinjector to be more convenient and easier to use. No pain or discomfort was experienced using the autoinjector. The autoinjector safety profile was consistent with that known for peginterferon alfa-2a/ribavirin. Conclusion These results indicate that peginterferon alfa-2a can be successfully and safely delivered via the autoinjector and that the device is easy to handle.

Cost-effectiveness of obinutuzumab plus bendamustine followed by obinutuzumab monotherapy for the treatment of follicular lymphoma patients who relapse after or are refractory to a rituximab-containing regimen in the US

Abstract Aims: Obinutuzumab (GA101, G) was approved in February 2016 by the US Food and Drug Administration to treat follicular lymphoma (FL) patients who relapsed after, or are refractory to (R/R), a rituximab-containing regimen (R/R-rituximab). In the GADOLIN trial, R/R-rituximab patients who received G plus bendamustine (B) followed by G-monotherapy (G + B) for up to 2 years had significantly improved progression-free survival and overall survival compared to patients receiving B-monotherapy. This study estimated the cost-effectiveness of G + B vs B-monotherapy for R/R-rituximab FL patients from a US payer perspective. Materials and methods: Patient outcomes were simulated using a 3-state area under the curve model including progression-free survival, progressive disease, and death. This study used R/R-rituximab data from the National LymphoCare Study to extrapolate the GADOLIN trial’s refractory FL progression-free and overall survival data to a R/R-rituximab FL population. Drug utilization and adverse events were based on trial data, and costs were based on Medicare reimbursements and drug wholesale acquisition costs in 2016. Utility estimates were derived from published literature. Post-progression treatment costs were based on observed post-progression therapies in GADOLIN. Sensitivity analyses were conducted to assess model uncertainty. Results: G + B resulted in an increase in quality-adjusted life years relative to B-monotherapy of 1.24 (95% CR = 0.61–1.87); the incremental total cost was

Understanding the effect of the HCV polymerase inhibitor mericitabine on early viral kinetics in the phase 2 JUMP‐C and PROPEL studies

58,100 (95% CR = 

Perceptions of positive meaning and vulnerability following breast cancer: Predictors and outcomes among long-term breast cancer survivors

54,500–

Robustness of a multivariate normal approximation for imputation of incomplete binary data.

61,500). The incremental cost-effectiveness ratio was

The BCPT Symptom Scales: A Measure of Physical Symptoms for Women Diagnosed With or at Risk for Breast Cancer

47,000 per QALY gained, and, based on probabilistic simulations, there was a 98% probability that G + B was cost-effective at the