Explore the vast range of titles available.

Background Blended cognitive behaviour therapy (bCBT) is an effective treatment for fear of cancer recurrence (FCR) in curatively-treated breast, colorectal and prostate cancer survivors with high FCR. However, long-term outcomes are unknown. This study investigated the long-term efficacy and cost-effectiveness of bCBT compared with care as usual (CAU). Methods Eighty-eight cancer survivors with high FCR (Cancer Worry Scale ≥14) were randomly assigned to bCBT ( n  = 45) or CAU ( n  = 43). Data were collected at baseline and at three, nine and fifteen months from baseline and analysed by modified intention-to-treat. Efficacy was investigated with linear mixed-effects models. Cost-effectiveness was investigated from a societal perspective by comparing costs with quality-adjusted life-years (QALYs). Results Participants who received bCBT reported significantly lower FCR compared with CAU (mean difference of − 1.787 [95% CI -3.251 to − 0.323, p  = 0.017] at 15 months follow-up), and proportionally greater self-rated and clinically significant improvement at each follow-up measurement. Total QALYs were non-significantly different between conditions when adjusted for utility score baseline differences (0.984 compared to 0.957, p  = 0.385), while total costs were €631 lower (95% CI -1737 to 2794, p  = 0.587). Intervention costs of bCBT were €466. The incremental cost-effectiveness ratio amounted to an additional €2049 per QALY gained, with a 62% probability that bCBT is cost-effective at a willingness to pay (WTP) threshold of €20,000 per QALY. Results were confirmed in sensitivity analyses. Conclusions bCBT for cancer survivors with FCR is clinically and statistically more effective than CAU on the long-term. In addition, bCBT is a relatively inexpensive intervention with similar costs and QALYs as CAU. Trial registration The RCT was registered in the Dutch National Trial Register ( NTR4423 ) on 12-Feb-2014. This abstract was previously presented at the International Psycho-Oncology Society conference of 2018 and published online. (Psycho-oncology, 27(S3):8-55; 2018)

BackgroundPromising genetic therapies are being investigated in facioscapulohumeral muscular dystrophy (FSHD). However, the current cost of illness is largely unknown.ObjectiveThis study aimed at determining the socioeconomic burden of FSHD.MethodsAdult patients with FSHD from the Dutch FSHD registry were invited to complete a questionnaire on medical consumption, work productivity and health-related quality of life (HR-QoL) using the EQ-5D-5L. Associated costs were calculated from a societal perspective. A generalized linear model was fitted to the data to investigate whether level of mobility was related to annual costs of illness.Results172 patients with FSHD completed the questionnaire (response rate 65%). The per-patient annual direct medical costs of FSHD were estimated at €12,077, direct non-medical costs at €9179 and indirect costs at €5066, adding up to a total cost of illness of €26,322 per patient per year. The direct costs of illness were €21,256, approximately five times higher than the mean per-capita health expenditures in the Netherlands. Major cost-driving factors were formal home care and informal care. A decreased level of mobility was associated with higher direct costs of illness. HR-QoL was significantly reduced in patients with FSHD with a median health utility value of 0.63.ConclusionsWe show that FSHD is associated with substantial direct and indirect socioeconomic costs as well as a reduction in HR-QoL. These findings are important for health care decision makers and aids in allocation of research funds and evaluation of the cost-effectiveness of novel therapies.

Patients on home parenteral nutrition (HPN) are at risk for catheter-related complications; mainly infections and occlusions. We have previously shown in HPN patients presenting with catheter sepsis that catheter locking with taurolidine dramatically reduced re-infections when compared with heparin. Our HPN population therefore switched from heparin to taurolidine in 2008. The aim of the present study was to compare long-term effects of this catheter lock strategy on the occurrence of catheter-related bloodstream infections and occlusions in HPN patients. Data of catheter-related complications were retrospectively collected from 212 patients who received HPN between January 2000 and November 2011, comprising 545 and 200 catheters during catheter lock therapy with heparin and taurolidine, respectively. We evaluated catheter-related bloodstream infection and occlusion incidence rates using Poisson-normal regression analysis. Incidence rate ratios were calculated by dividing incidence rates of heparin by those of taurolidine, adjusting for underlying disease, use of anticoagulants or immune suppressives, frequency of HPN/fluid administration, composition of infusion fluids, and duration of HPN/fluid use before catheter creation. Bloodstream infection incidence rates were 1.1/year for heparin and 0.2/year for taurolidine locked catheters. Occlusion incidence rates were 0.2/year for heparin and 0.1/year for taurolidine locked catheters. Adjusted incidence ratios of heparin compared to taurolidine were 5.9 (95% confidence interval, 3.9-8.7) for bloodstream infections and 1.9 (95% confidence interval, 1.1-3.1) for occlusions. Given that no other procedural changes than the catheter lock strategy were implemented during the observation period, these data strongly suggest that taurolidine decreases catheter-related bloodstream infections and occlusions in HPN patients compared with heparin.

Background This paper describes the rationale and design of the RECOVER study. Currently, there is no consensus regarding the optimal treatment for high-risk, non-metastatic prostate cancer (PCa). The study primarily aims to evaluate and compare the impact of treatment with robot-assisted radical prostatectomy (RP) versus external beam radiation therapy (EBRT) with androgen deprivation therapy (ADT) for men with high-risk, non-metastatic PCa regarding health-related quality of life (HRQoL) and functional outcomes. Secondary objectives are progression-free survival (PFS), distant metastasis-free survival (DMFS), costs and cost-effectiveness. Methods The RECOVER study is a comparative effectiveness study that prospectively includes newly diagnosed high-risk (cT3a-bN0M0, ISUP-grade ≥ 4 and/or PSA > 20 ng/mL), non-metastatic PCa patients. Four Dutch prostate cancer networks, comprising 29 hospitals, are currently participating in the study. Patient reported outcomes are collected before treatment initiation, 12 months and 36 months after treatment initiation and include the EORTC-QLQ-C30, the EPIC-26, an adapted version of the SCQ, an adapted version of the iMTA Productivity Cost Questionnaire and several specific questions regarding patient characteristics, treatment of PCa specific complaints and health resources used. Clinical data regarding patient-, tumor- and treatment characteristics and oncological outcomes are collected up to 5 years after diagnosis. For sufficient power, patient reported outcomes of 471 patients must be collected 36 months after treatment initiation. Descriptive statistics and mixed-effects models are used to assess differences in HRQoL and functional outcomes over time between the patients treated with radical prostatectomy versus EBRT (+ ADT). Inverse probability of treatment weighting or the g-formula are used to adjust for confounding covariates associated with treatment. Secondary endpoints PFS and DMFS are evaluated using a competing risk analysis and cost-utility and budget-impact analyses will be performed to determine cost and cost-effectiveness. Discussion An observational prospective design was chosen since a randomized controlled trial comparing surgery and radiotherapy was not deemed feasible. This study evaluates effectiveness of treatment in a routine clinical setting (with adjustment for confounding) and its findings will enhance patients’ and healthcare professionals’ awareness for the impact of both treatment modalities on (long-term) daily functioning and HRQoL and aid treatment decision making. Trial registration This study is registered at ClinicalTrials.gov (NCT05931419).

Background: The androgen receptor pathway inhibitors (ARPI), abiraterone acetate and enzalutamide, are commonly used in first-line treatment of patients with metastatic castration-resistant prostate cancer (mCRPC). However, early resistance to ARPI treatment occurs frequently. Traditionally, the response is evaluated 3–6 months after the start of treatment. However, recent findings indicate that by detecting circulating tumor DNA (ctDNA) at baseline and 4 weeks after ARPI treatment initiation, patients with a nondurable response can be identified after 4 weeks of treatment, enabling an early switch to alternative treatments. Objective: This study aims to evaluate the cost-effectiveness of ctDNA-guided treatment switch after 4 weeks of ARPI therapy in mCRPC patients compared to standard of care. Design: A cost-effectiveness analysis. Methods: A cost-effectiveness analysis was conducted by creating a Markov state transition model to simulate progression, mortality, and treatment costs over a 5-year time horizon comparing ctDNA-guided care versus standard of care. The outcomes measured were incremental treatment costs per life-years and quality-adjusted life-years (QALYs) gained. Results: The analysis showed an incremental cost-effectiveness ratio of €65,400.86 per QALY gained and an incremental net monetary benefit of €2716.62. Thereby, the use of ctDNA-guided treatment was cost-effective in comparison to standard care in 74% of the simulations using a willingness-to-pay threshold of €80,000 per QALY gained. Conclusion: Our study demonstrated the cost-effectiveness of using a ctDNA-guided early therapy switch in non-responders after only 4 weeks of first-line ARPI therapy in mCRPC patients. This paves the way for implementing ctDNA-guided treatment decisions in clinical practice.

The pharmacokinetics of many antidepressants (tricyclic antidepressants (TCA) or selective serotonin re-uptake inhibitors (SSRI)) are influenced by the highly polymorphic CYP2D6 enzyme. Therefore, pharmacogenetics could play an important role in the treatment of depressive patients. The potential cost-utility of screening patients is however still unknown. Therefore, a Markov model was developed to compare the strategy of screening for CYP2D6 and subsequently adjust antidepressant treatment according to a patient’s metabolizer profile of poor, extensive, or ultra metabolizer, with the strategy of no screening (‘one size fits all’ principle). Each week a patient had a probability of side effects, which was followed by dosage titration or treatment switching. After 6 weeks treatment effect was evaluated followed by treatment adjustments if necessary, with a total time horizon of the model of 12 weeks. The analysis was performed from a societal perspective. The strategy of screening compared with no screening resulted in incremental costs of €91 (95 percentiles: €39; €152) more expensive but also more effect with 0.001 quality adjusted life years (QALYs) (95 percentiles: 0.001; 0.002) gain. The incremental cost-effectiveness ratio (ICER) was therefore €77,406 per QALY gained, but varied between €22,500 and €377,500 depending on the price of screening and productivity losses. According to our model, we cannot unequivocally conclude that screening for CYP2D6 in primary care patients using antidepressants is be cost-effective, as the results are surrounded by large uncertainty. Therefore, information from ongoing studies should be used to reduce these uncertainties.

IntroductionOsteoarthritis (OA) is a multifactorial disease in which low-grade inflammation is considered to play a pivotal role. Although colchicine is a widely used anti-inflammatory drug in the treatment of gout, its effect in OA is still disputed due to inconsistent results of short-term clinical trials. Therefore, we aim to evaluate the effect of long-term colchicine 0.5 mg once daily on the incidence of knee or hip replacements in patients with knee or hip OA.Methods and analysisThe ECHO trial is a prospective, multicentre, randomised, double-blind, placebo-controlled, phase III trial in which 1200 participants with knee or hip OA tolerant to colchicine during a 30-day run-in period will be 1:1 randomised to colchicine 0.5 mg once daily or matching placebo using concealed allocation. The primary endpoint is the time from randomisation to the first knee or hip replacement assessed up to 4.5 years. Secondary endpoints include course of pain, physical function, joint space narrowing, low-grade inflammation, quality of life, clinical or radiological onset of OA in a new joint group other than present at baseline, number of participants using pain medication during the study, onset of new cardiovascular events (ie, myocardial infarction, ischaemia-driven coronary revascularisation, ischaemic stroke, peripheral artery disease or cardiovascular death) and direct and indirect costs related to treatment and disease burden due to OA. Harm-related endpoints include the number of (serious) adverse events, the number of withdrawals due to (serious) adverse events and changes in laboratory data (ie, serum creatinine, estimated glomerular filtration rate and alanine transferase) throughout the study. The primary analysis will be performed according to the intention-to-treat principle.Ethics and disseminationThis trial has been approved by the Medical Ethics Review Committee East-Netherlands. Findings will be presented at scientific meetings and published in a peer-reviewed scientific journal.Trial registration numberNCT06578182.

Background Psoriasis is a chronic immune-mediated inflammatory skin disease for which biologics are effective treatments. Dose reduction (DR) of the first generation biologics seems a promising way for more efficient use of expensive biologics. A substantial part of patients on tumor necrosis factor (TNF)-alfa inhibitors and ustekinumab could successfully lower their dose, after following a tightly controlled DR strategy. The objective of this study is to assess whether controlled DR of interleukin (IL)-17 and IL-23 inhibitors in psoriasis patients with low disease activity is non-inferior (NI) to usual care (UC). Methods This is an international, prospective, multicenter, pragmatic, randomized, non-inferiority trial. A total of 244 patients with stable low disease activity (Psoriasis Area and Severity Index (PASI) ≤ 5) for at least 6 months and using secukinumab, ixekizumab, brodalumab, guselkumab, risankizumab, or tildrakizumab in the standard dose, together with stable low disease activity, defined as a PASI ≤ 5 and Dermatology Life Quality Index (DLQI) ≤ 5 at the moment of inclusion, will be randomized 2:1 to DR or UC. In the DR group, dosing intervals will be prolonged stepwise to achieve 66% and 50% of the original dose. Disease activity is monitored every 3 months by PASI and DLQI. In case of disease flare (i.e., PASI and/or DLQI increase), treatment is adjusted to the previous effective dose. The primary outcome is the incidence proportion of persistent flares (PASI > 5 for ≥ 3 months), which will be compared between arms. Secondary outcomes include proportion of patients with successful DR, (course of) PASI and DLQI, serious adverse events (SAEs), health-related quality of life, costs, and pharmacokinetic profile. Outcomes of DR will be compared to UC. Discussion With this study, we aim to assess whether DR of IL-17 and IL-23 inhibiting biologics can be achieved for psoriasis patients with low disease activity, without losing disease control. Reducing the dose may lead to more efficient use of biologics. Trial registration ClinicalTrials.gov NCT04340076 . Registered on April 9 2020.

In the extension phase, both groups were treated according to a treat-to-target protocol: tapering was recommended in case of a stable low disease activity, at the discretion of the rheumatologist in both groups.1 3 Quality-adjusted life years (QALYs) were determined by trapezoid method based on the EuroQol-5D5L measured quality of life. Since medication costs were the main cost drivers in the DRESS study, only medication costs were recorded from 18 to 36 months. Because comparisons within one group are paired observations, we bootstrapped within-patient differences in QALY and costs instead of group-level differences for these comparisons for a more efficient analysis. [...]the cost-effectiveness of protocolised tapering was maintained from 18 to 36 months, although medication costs rose slightly (but non-significantly), possibly because a subset of patients returned to a higher dose during follow-up.

Background The importance of respecting patients’ preferences when making treatment decisions is increasingly recognized. Efficiently retrieving papers from the scientific literature reporting on the presence and nature of such preferences can help to achieve this goal. The objective of this study was to create a search filter for PubMed to help retrieve evidence on patient preferences for treatment outcomes. Methods A total of 27 journals were hand-searched for articles on patient preferences for treatment outcomes published in 2011. Selected articles served as a reference set. To develop optimal search strategies to retrieve this set, all articles in the reference set were randomly split into a development and a validation set. MeSH-terms and keywords retrieved using PubReMiner were tested individually and as combinations in PubMed and evaluated for retrieval performance (e.g. sensitivity (Se) and specificity (Sp)). Results Of 8238 articles, 22 were considered to report empirical evidence on patient preferences for specific treatment outcomes. The best search filters reached Se of 100 % [95 % CI 100-100] with Sp of 95 % [94–95 %] and Sp of 97 % [97–98 %] with 75 % Se [74–76 %]. In the validation set these queries reached values of Se of 90 % [89–91 %] with Sp 94 % [93–95 %] and Se of 80 % [79–81 %] with Sp of 97 % [96–96 %], respectively. Conclusions Narrow and broad search queries were developed which can help in retrieving literature on patient preferences for treatment outcomes. Identifying such evidence may in turn enhance the incorporation of patient preferences in clinical decision making and health technology assessment.