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Introduction: The introduction of eculizumab has improved the outcome in patients with atypical hemolytic uremic syndrome (aHUS). The optimal treatment strategy is debated. Here, we report the results of the CUREiHUS study, a 4-year prospective, observational study monitoring unbiased eculizumab discontinuation in Dutch patients with aHUS after 3 months of therapy., Methods: All pediatric and adult patients with aHUS in native kidneys and a first-time eculizumab treatment were evaluated. In addition, an extensive cost-consequence analysis was conducted., Results: A total of 21 patients were included in the study from January 2016 to October 2020. In 17 patients (81%), a complement genetic variant or antibodies against factor H were identified. All patients showed full recovery of hematological thrombotic microangiopathy (TMA) parameters after the start of eculizumab. A renal response was noted in 18 patients. After a median treatment duration of 13.6 weeks (range 2.1-43.9), eculizumab was withdrawn in all patients. During follow-up (80.7 weeks [0.0-236.9]), relapses occurred in 4 patients. Median time to first relapse was 19.5 (14.3-53.6) weeks. Eculizumab was reinitiated within 24 hours in all relapsing patients. At last follow-up, there were no chronic sequelae, i.e., no clinically relevant increase in serum creatinine (sCr), proteinuria, and/or hypertension in relapsing patients. The low sample size and event rate did not allow to determine predictors of relapse. However, relapses only occurred in patients with a likely pathogenic variant. The cost-effectiveness analysis revealed that the total medical expenses of our population were only 30% of the fictive expenses that would have been made when patients received eculizumab every fortnight., Conclusion: It is safe and cost-effective to discontinue eculizumab after 3 months of therapy in patients with aHUS in native kidneys. Larger data registries are needed to determine factors associated with suboptimal kidney function recovery during eculizumab treatment, factors to predict relapses, and long-term outcomes of eculizumab discontinuation., (© 2022 Published by Elsevier Inc. on behalf of the International Society of Nephrology.)

Purpose: A large number of targeted treatment options for stage IV nonsquamous non-small-cell lung cancer with specific genetic aberrations in tumor DNA is available. It is therefore important to optimize diagnostic testing strategies, such that patients receive adequate personalized treatment that improves survival and quality of life. The aim of this study is to assess the efficacy (including diagnostic costs, turnaround time (TAT), unsuccessful tests, percentages of correct findings, therapeutic costs, and therapeutic effectiveness) of parallel next generation sequencing (NGS)-based versus sequential single-gene-based testing strategies routinely used in patients with metastasized non-small-cell lung cancer in the Netherlands., Methods: A diagnostic microsimulation model was developed to simulate 100,000 patients with prevalence of genetic aberrations, extracted from real-world data from the Dutch Pathology Registry. These simulated patients were modeled to undergo different testing strategies composed of multiple tests with different test characteristics including single-gene and panel tests, test accuracy, the probability of an unsuccessful test, and TAT. Diagnostic outcomes were linked to a previously developed treatment model, to predict average long-term survival, quality-adjusted life-years (QALYs), costs, and cost-effectiveness of parallel versus sequential testing., Results: NGS-based parallel testing for all actionable genetic aberrations is on average €266 cheaper than single-gene-based sequential testing, and detects additional relevant targetable genetic aberrations in 20.5% of the cases, given a TAT of maximally 2 weeks. Therapeutic costs increased by €8,358, and 0.12 QALYs were gained, leading to an incremental cost-effectiveness ratio of €69,614/QALY for parallel versus sequential testing., Conclusion: NGS-based parallel testing is diagnostically superior over single-gene-based sequential testing, as it is cheaper and more effective than sequential testing. Parallel testing remains cost-effective with an incremental cost-effectiveness ratio of 69,614 €/QALY upon inclusion of therapeutic costs and long-term outcomes.

Background In patients with out-of-hospital cardiac arrest without ST-segment elevation, immediate coronary angiography did not improve clinical outcomes when compared with delayed angiography in the COACT (Coronary Angiography After Cardiac Arrest) trial. Whether 1 of the 2 strategies has benefits in terms of health care resource use and costs is currently unknown. We assess the health care resource use and costs in patients with out-of-hospital cardiac arrest. Methods and Results A total of 538 patients were randomly assigned to a strategy of either immediate or delayed coronary angiography. Detailed health care resource use and cost-prices were collected from the initial hospital episode. A generalized linear model and a gamma distribution were performed. Generic quality of life was measured with the RAND-36 and collected at 12-month follow-up. Overall total mean costs were similar between both groups (EUR 33 575±19 612 versus EUR 33 880±21 044; P =0.86). Generalized linear model: (β, 0.991; 95% CI, 0.894-1.099; P =0.86). Mean procedural costs (coronary angiography and percutaneous coronary intervention, coronary artery bypass graft) were higher in the immediate angiography group (EUR 4384±3447 versus EUR 3028±4220; P <0.001). Costs concerning intensive care unit and ward stay did not show any significant difference. The RAND-36 questionnaire did not differ between both groups. Conclusions The mean total costs between patients with out-of-hospital cardiac arrest randomly assigned to an immediate angiography or a delayed invasive strategy were similar during the initial hospital stay. With respect to the higher invasive procedure costs in the immediate group, a strategy awaiting neurological recovery followed by coronary angiography and planned revascularization may be considered. Registration URL: https://trialregister.nl; Unique identifier: NL4857.

Background: Inguinal hernia repair, gallbladder removal, and knee- and hip replacements are the most commonly performed surgical procedures, but all are subject to practice variation and variable patient-reported outcomes. Shared decision-making (SDM) has the potential to reduce surgery rates and increase patient satisfaction. This study aims to evaluate the effectiveness of an SDM strategy with online decision aids for surgical and orthopaedic practice in terms of impact on surgery rates, patient-reported outcomes, and cost-effectiveness., Methods: The E-valuAID-study is designed as a multicentre, non-randomized stepped-wedge study in patients with an inguinal hernia, gallstones, knee or hip osteoarthritis in six surgical and six orthopaedic departments. The primary outcome is the surgery rate before and after implementation of the SDM strategy. Secondary outcomes are patient-reported outcomes and cost-effectiveness. Patients in the usual care cluster prior to implementation of the SDM strategy will be treated in accordance with the best available clinical evidence, physician's knowledge and preference and the patient's preference. The intervention consists of the implementation of the SDM strategy and provision of disease-specific online decision aids. Decision aids will be provided to the patients before the consultation in which treatment decision is made. During this consultation, treatment preferences are discussed, and the final treatment decision is confirmed. Surgery rates will be extracted from hospital files. Secondary outcomes will be evaluated using questionnaires, at baseline, 3 and 6 months., Discussion: The E-valuAID-study will examine the cost-effectiveness of an SDM strategy with online decision aids in patients with an inguinal hernia, gallstones, knee or hip osteoarthritis. This study will show whether decision aids reduce operation rates while improving patient-reported outcomes. We hypothesize that the SDM strategy will lead to lower surgery rates, better patient-reported outcomes, and be cost-effective., Trial Registration: The Netherlands Trial Register, Trial NL8318, registered 22 January 2020. URL: https://www.trialregister.nl/trial/8318 .

Background: Platinum-based chemoradiotherapy for locally advanced head and neck cancer (LAHNC) induces a high rate of acute toxicity, including dysphagia and aspiration pneumonia. We hypothesised that prophylactic antibiotics can prevent pneumonia and hospitalisations and can be cost-effective., Patient and Methods: In this multicentre randomised trial, patients with LAHNC treated with chemoradiotherapy received prophylactic amoxicillin/clavulanic acid from day 29 after the start of treatment until 14 days after completion of chemoradiotherapy or standard care without prophylaxis. The primary objective was to observe a reduction in pneumonias. Secondary objectives were to evaluate the hospitalisation rate, adverse events, costs and health-related quality of life., Results: One hundred six patients were included; of which, 95 were randomised: 48 patients were allocated to the standard group and 47 patients to the prophylaxis group. A pneumonia during chemoradiotherapy and follow-up until 3.5 months was observed in 22 (45.8%) of 48 patients in the standard group and in 22 (46.8%) of 47 patients in the prophylaxis group (p = 0.54). Hospitalisation rate was significantly higher in the standard group versus the prophylaxis group, 19 of 48 pts (39.6%) versus 9 of 47 pts (19.1%), respectively (p = 0.03). Significantly more episodes with fever of any grade were observed in the standard group (29.2% vs 10.2%, p = 0.028). A significant difference in costs was found, with an average reduction of €1425 per patient in favour of the prophylaxis group., Conclusion: Although prophylactic antibiotics during chemoradiotherapy for patients with LAHNC did not reduce the incidence of pneumonias, it did reduce hospitalisation rates and episodes with fever significantly and consequently tended to be cost-effective., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: To investigate the morbidity that is associated with the learning curve of minimally invasive esophagectomy., Background: Although learning curves have been described, it is currently unknown how much extra morbidity is associated with the learning curve of technically challenging surgical procedures., Methods: Prospectively collected data were retrospectively analyzed of all consecutive patients undergoing minimally invasive Ivor Lewis esophagectomy in 4 European expert centers. The primary outcome parameter was anastomotic leakage. Secondary outcome parameters were operative time and textbook outcome ("optimal outcome"). Learning curves were plotted using weighted moving average and CUSUM analysis was used to determine after how many cases the plateau was reached. Learning associated morbidity was calculated with area under the curve analysis., Results: This study included 646 patients. Three of the 4 hospitals reached the plateau of 8% anastomotic leakage. The length of the learning curve was 119 cases. The mean incidence of anastomotic leakage decreased from 18.8% during the learning phase to 4.5% after the plateau had been reached (P < 0.001). Thirty-six extra patients (10.1% of all patients operated on during the learning curve) experienced learning associated anastomotic leakage, that could have been avoided if patients were operated by surgeons who had completed the learning curve. The incidence of textbook outcome increased from 28% to 53% and the mean operative time decreased from 344 minutes to 270 minutes., Conclusions: A considerable number of 36 extra patients (10.1%) experienced learning associated anastomotic leakage. More research is urgently needed to investigate how learning associated morbidity can be reduced to increase patient safety during learning curves.

Background: Over the last 20 years, integrated care programs for frail elderly people aimed to prevent functional dependence and reduce hospitalization and institutionalization. However, results have been inconsistent and merely modest. To date, evidence on the cost-effectiveness of these programs is scarce. We evaluated the cost-effectiveness of the CareWell program, a multicomponent integrated care program for frail elderly people., Methods: Economic evaluation from a healthcare perspective embedded in a cluster controlled trial of 12 months in 12 general practices in (the region of) Nijmegen. Two hundred and four frail elderly from 6 general practices in the intervention group received care according to the CareWell program, consisting of multidisciplinary team meetings, proactive care planning, case management, and medication reviews; 165 frail elderly from 6 general practices in the control group received usual care. In cost-effectiveness analyses, we related costs to daily functioning (Katz-15 change score i.e. follow up score minus baseline score) and quality adjusted life years (EQ-5D-3 L)., Results: Adjusted mean costs directly related to the intervention were €456 per person. Adjusted mean total costs, i.e. intervention costs plus healthcare utilization costs, were €1583 (95% CI -4647 to 1481) higher in the intervention group than in the control group. Incremental Net Monetary Benefits did not show significant differences between groups, but on average tended to favour usual care., Conclusions: The CareWell primary program was not cost-effective after 12 months. From a cost-effectiveness perspective, widespread implementation of the program in its current form cannot be recommended., Trial Registration: The study was registered in the ClinicalTrials.govProtocol Registration System: ( NCT01499797 ; December 26, 2011). Retrospectively registered.

European countries have enhanced the scope of private provision within their health care systems. Privatizing services have been suggested as a means to improve access, quality, and efficiency in health care. This raises questions about the relative performance of private hospitals compared with public hospitals. Most systematic reviews that scrutinize the performance of the private hospitals originate from the United States. A systematic overview for Europe is nonexisting. We fill this gap with a systematic realist review comparing the performance of public hospitals to private hospitals on efficiency, accessibility, and quality of care in the European Union. This review synthesizes evidence from Italy, Germany, the United Kingdom, France, Greece, Austria, Spain, and Portugal. Most evidence suggests that public hospitals are at least as efficient as or are more efficient than private hospitals. Accessibility to broader populations is often a matter of concern in private provision: Patients with higher social-economic backgrounds hold better access to private hospital provision, especially in private parallel systems such as the United Kingdom and Greece. The existing evidence on quality of care is often too diverse to make a conclusive statement. In conclusion, the growth in private hospital provision seems not related to improvements in performance in Europe. Our evidence further suggests that the private (for-profit) hospital sector seems to react more strongly to (financial) incentives than other provider types. In such cases, policymakers either should very carefully develop adequate incentive structures or be hesitant to accommodate the growth of the private hospital sector., (Copyright © 2018 John Wiley & Sons, Ltd.)

Objectives: The aim of this study was to compare costs and clinical outcomes of two protocols for implant placement in edentulous oral cancer patients: implant placement during ablative surgery and postponed implant placement., Material and Methods: All edentulous patients who underwent curative tumor surgery between 2007 and 2009 at the Radboud university medical center (Radboudumc) and UMC Utrecht, both in the Netherlands, were included retrospectively. At the Radboudumc, 79 of 98 patients received implants during ablative surgery. At the UMC Utrecht, 18 of 95 patients received implants after a disease-free period of at least 6 months, because satisfying conventional dentures could not be made. Costs, implant details and clinical outcomes were recorded retrospectively up to 5 years after tumor surgery., Results: Individual costs of implant placement were lower in the during-ablative-surgery protocol (€2235 vs. €4152), while implant failure and loading were comparable to the postponed-placement protocol. In the during-ablative-surgery protocol, more patients received implant-retained overdentures (62% vs. 17%) and more patients had functioning dentures (65% vs. 47%), which were placed at an earlier stage (291 vs. 389 days after surgery). Overall costs of the during-ablative-surgery protocol were higher, as more patients received implants and functioning implant-retained dentures, which were more expensive than conventional dentures., Conclusions: Placing implants during ablative surgery lowered the individual costs of implant placement and led to more patients with functioning dentures, while implant failure and loading were comparable to postponed placement., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Consultation of a nephrologist is important in aligning care for patients with chronic kidney disease (CKD) at the primary-secondary care interface. However, current consultation methods come with practical difficulties that can lead to postponed consultation or patient referral instead., Objective: This study aimed to investigate whether a web-based consultation platform, telenephrology, led to a lower referral rate of indicated patients. Furthermore, we assessed consultation rate, quality of care, costs and general practitioner (GPs') experiences with telenephrology., Methods: Cluster randomized controlled trial with 47 general practices in the Netherlands was randomized to access to telenephrology or to enhanced usual care. A total of 3004 CKD patients aged 18 years or older who were under primary care were included (intervention group n = 1277, control group n = 1727) and 2693 completed the trial. All practices participated in a CKD management course and were given an overview of their CKD patients., Results: The referral rates amounted to 2.3% (n = 29) in the intervention group and 3.0% (n = 52) in the control group, which was a non-significant difference, OR 0.61; 95% CI 0.31 to 1.23. The intervention group's consultation rate was 6.3% (n = 81) against 5.0% (n = 87) (OR 2.00; 95% CI 0.75-5.33). We found no difference in quality of care or costs. The majority of GPs had a positive opinion about telenephrology., Conclusion: The data in our study do not allow for conclusions on the effect of telenephrology on the rate of patient referrals and provider-to-provider consultations, compared to conventional methods. It was positively evaluated by GPs and was non-inferior in terms of quality of care and costs., (© The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: In cost-effectiveness analyses in healthcare, Quality-Adjusted Life Years are often used as outcome measure of effectiveness. However, there is an ongoing debate concerning the appropriateness of its use for decision-making in palliative care., Aim: To systematically map pros and cons of using the Quality-Adjusted Life Year to inform decisions on resource allocation among palliative care interventions, as brought forward in the debate, and to discuss the Quality-Adjusted Life Year's value for palliative care., Design: The integrative review method of Whittemore and Knafl was followed. Theoretical arguments and empirical findings were mapped., Data Sources: A literature search was conducted in PubMed, EMBASE, and CINAHL, in which MeSH (Medical Subject Headings) terms were Palliative Care, Cost-Benefit Analysis, Quality of Life, and Quality-Adjusted Life Years., Findings: Three themes regarding the pros and cons were identified: (1) restrictions in life years gained, (2) conceptualization of quality of life and its measurement, including suggestions to adapt this, and (3) valuation and additivity of time, referring to changing valuation of time. The debate is recognized in empirical studies, but alternatives not yet applied., Conclusion: The Quality-Adjusted Life Year might be more valuable for palliative care if specific issues are taken into account. Despite restrictions in life years gained, Quality-Adjusted Life Years can be achieved in palliative care. However, in measuring quality of life, we recommend to-in addition to the EQ-5D- make use of quality of life or capability instruments specifically for palliative care. Also, we suggest exploring the possibility of integrating valuation of time in a non-linear way in the Quality-Adjusted Life Year.

Background: Kidney transplantation in patients with atypical haemolytic uraemic syndrome (aHUS) is frequently complicated by recurrence of aHUS, often resulting in graft loss. Eculizumab prophylaxis prevents recurrence, improving graft survival. An alternative treatment strategy has been proposed where eculizumab is administered upon recurrence. We combined available evidence and performed a cost-effectiveness analysis of these competing strategies., Methods: A cost-effectiveness analysis using a decision analytical approach with Markov chain analyses was used to compare alternatives for aHUS patients with end-stage renal disease (ESRD): (i) dialysis treatment, (ii) kidney transplantation, (iii) kidney transplantation with eculizumab therapy upon recurrence of aHUS, (iv) kidney transplantation with eculizumab induction consisting of 12 months of prophylaxis and (v) kidney transplantation with lifelong eculizumab prophylaxis. We assumed that all patients received a graft from a living donor and that recurrence probability was 28.4% within the first year of transplantation., Results: At 8.34 quality-adjusted life years (QALYs) gained and a cost of €402 412, kidney transplantation without eculizumab was the least costly alternative. By comparison, dialysis was more costly and resulted in fewer QALYs gained. Eculizumab upon recurrence resulted in 9.55 QALYs gained at a cost of €425 097. The incremental cost-effectiveness ratio (ICER) was €18 748 per QALY. Both eculizumab induction and lifelong eculizumab were inferior to eculizumab upon recurrence, as both resulted in fewer QALYs gained and higher costs., Conclusions: Kidney transplantation is more cost effective than dialysis to treat ESRD due to aHUS. Adding eculizumab treatment results in a substantial gain in QALYs. When compared with eculizumab upon recurrence, neither eculizumab induction nor lifelong eculizumab prophylaxis resulted in more QALYs, but did yield far higher costs. Therefore, eculizumab upon recurrence of aHUS is more acceptable., (© The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Background: Despite the well-known health benefits of physical activity, it is a great challenge to stay physically active for frail-older adults with mobility limitations. The aim of this study was to test the (cost-) effectiveness of a patient-centred physical therapy strategy (Coach2Move) in which individualized treatment (motivational interviewing, physical examination, individualized goal setting, coaching and advice on self management, and physical training) is combined to increase physical activity level and physical fitness and, thereby, to decrease the level of frailty., Methods: A randomized controlled trial was performed in 13 physical therapy practices with measurements at 3 and 6 months. Eligible patients were aged 70 years or over and had mobility problems (i.e. difficulties with walking, moving, getting up and changing position from bed or chair to standing, or stair climbing). The primary outcome was physical activity (total and moderate intensity) in minutes per day. Secondary outcomes were as follows: frailty, walking speed and distance, mobility, and quality of life. Data were analysed using linear mixed models for repeated measurements. Healthcare costs and quality-adjusted life years (QALYs) were computed and combined using net monetary benefit (NMB) for different willingness to pay thresholds. Data on costs, QALYs, and NMBs were analysed using linear mixed models., Results: One hundred and thirty patients participated in this study. At 6 months, the between-group difference was significant for moderate-intensity physical activity in favour of the Coach2Move group [mean difference: 17.9 min per day; 95% confidence interval (CI) 4.0 to 34.9; P = 0.012]. The between-group difference for total physical activity was 14.1 min per day (95% CI -6.6 to 34.9; P = 0.182). Frailty decreased more in the Coach2Move group compared with usual care [mean difference: -0.03 (95% CI: -0.06 to -0.00; P = 0.027)]. Compared with usual treatment, the Coach2Move strategy resulted in cost savings (€849.8; 95% CI: 1607 to 90; P = 0.028), an improvement in QALYs, (0.02; 95% CI: 0.00 to 0.03; P = 0.03), and a higher NMB at every willingness to pay threshold., Conclusions: Older adults with mobility problems are able to safely increase physical activity in their own environment and reduce frailty. This study emphasizes both the potential cost-effectiveness of a patient-centred approach in the frail elderly and the importance of physical activity promotion in older adults with mobility limitations.

Background: Skin cancer, including basal cell carcinoma (BCC), has become a major health care problem. The limitations of a punch biopsy (at present the gold standard) as diagnostic method together with the increasing incidence of skin cancer point out the need for more accurate, cost-effective, and patient friendly diagnostic tools. In vivo reflectance confocal microscopy (RCM) is a noninvasive imaging technique that has great potential for skin cancer diagnosis., Objective: To investigate whether in vivo RCM can correctly identify the subtype of BCC and to determine the cost-effectiveness of RCM compared with punch biopsy (usual care)., Study Design: Randomized controlled multicenter trial., Methods: On the basis of 80% power and an alpha of 0.05, 329 patients with lesions clinically suspicious for BCC will be included in this study. Patients will be randomized for RCM or for a punch biopsy (usual care). When a BCC is diagnosed, surgical excision will follow and a follow-up visit will be planned 3 months later. Several questionnaires will be filled in (EQ-5D, EQ-5D VAS, iMTA PCQ, and TSQM-9). We will perform statistical analysis, cost-effectiveness, and patient outcome analysis after data collection., Results: This research started in January 2016 and is ethically approved. We expect to finish this study at the end of 2018., Conclusions: In this study, we will investigate whether RCM is at least as good in identifying BCC subtypes as conventional pathological investigation of skin biopsies. Anticipating that RCM is found to be a cost-effective alternative, it saves on direct medical consumption like labor of the pathologist and other medical personnel as well as materials related to treatment failure with at least equal effectiveness., Trial Registration: Clinicaltrials.gov NCT02623101; https://clinicaltrials.gov/ct2/show/NCT02623101 (Archived by WebCite at http://www.webcitation.org/6id54WQa2).

Background: This study aimed to document the variation in technical efficiency of primary care (PC) practices in delivering evidence-based cardiovascular risk management (CVRM) and to identify associated factors., Methods: This observational study was based on the follow-up measurements in a cluster randomized trial. Patients were recruited from 41 general practices in the Netherlands, involving 106 GPs and 1671 patients. Data on clinical performance were collected from patient records. The analysis focused on PC practices and used a two-stage data envelopment analysis (DEA) approach. Bias-corrected DEA technical efficiency scores for each PC practice were generated, followed by regression analysis with practice efficiency as outcomes and organizational features of general practice as predictors., Results: Not all PC practices delivered recommended CVRM with the same technical efficiency; a significant difference from the efficient frontier was found (p < .000; 95 % CI 1.018-1.041). The variation in technical efficiency between PC practices was associated with training practice status (p = .026). Whether CVRM clinical tasks were performed by a practice nurse or a GP did not influence technical efficiency in a statistical significant way neither did practice size., Conclusions: Technical efficiency in delivering evidence-based CVRM increased with having a training practice status. Nurse involvement and practice size showed no statistical impact.

Purpose: Acetabular deficiencies in young patients can be restored in several ways during total hip arthroplasty. Currently, cementless cups are most frequently used. Impaction bone grafting of acetabular defects is a more biological approach, but is it cost-effective in young patients on the long term?, Methods: We designed a decision model for a cost-utility analysis of a cemented cup with acetabular impaction bone grafting versus an uncemented cup, in terms of cost per quality-adjusted life year (QALY) for the young adult with acetabular bone deficiency, in need for a primary total hip arthroplasty. Outcome probabilities and effectiveness were derived from the Radboud University Nijmegen Medical Centre and the Norwegian Hip Register. Multiple sensitivity analyses were used to assess the contribution of the included variables in the model's outcome., Results: Cemented cups with impaction bone grafting were more cost-effective compared to the uncemented option in terms of costs per QALY. A scenario suggesting equal primary survival rates of both cemented and uncemented cups still showed an effect gain of the cemented cup with impaction bone grafting, but at higher costs., Conclusions: Based on this model, the first choice of treatment of the acetabular bone deficient osteoarthritic hip in a young patient is reconstruction with impaction bone grafting and a cemented cup.

Background: Risk-reducing salpingo-oophorectomy (RRSO) around the age of 40 is currently recommended to BRCA1/2 mutation carriers. This procedure decreases the elevated ovarian cancer risk by 80-96% but it initiates premature menopause as well. The latter is associated with short-term and long-term morbidity, potentially affecting quality of life (QoL). Based on recent insights into the Fallopian tube as possible site of origin of serous ovarian carcinomas, an alternative preventive strategy has been put forward: early risk-reducing salpingectomy (RRS) and delayed oophorectomy (RRO). However, efficacy and safety of this alternative strategy have to be investigated., Methods: A multicentre non-randomised trial in 11 Dutch centres for hereditary cancer will be conducted. Eligible patients are premenopausal BRCA1/2 mutation carriers after completing childbearing without (a history of) ovarian carcinoma. Participants choose between standard RRSO at age 35-40 (BRCA1) or 40-45 (BRCA2) and the alternative strategy (RRS upon completion of childbearing and RRO at age 40-45 (BRCA1) or 45-50 (BRCA2)). Women who opt for RRS but do not want to postpone RRO beyond the currently recommended age are included as well. Primary outcome measure is menopause-related QoL. Secondary outcome measures are ovarian/breast cancer incidence, surgery-related morbidity, histopathology, cardiovascular risk factors and diseases, and cost-effectiveness. Mixed model data analysis will be performed., Discussion: The exact role of the Fallopian tube in ovarian carcinogenesis is still unclear. It is not expected that further fundamental research will elucidate this role in the near future. Therefore, this clinical trial is essential to investigate RRS with delayed RRO as alternative risk-reducing strategy in order to improve QoL., Trial Registration: ClinicalTrials.gov ( NCT02321228 ).

Background: Mindfulness-based interventions have shown to reduce psychological distress in cancer patients. The accessibility of mindfulness-based interventions for cancer patients could be further improved by providing mindfulness using an individual internet-based format. The aim of this study is to test the effectiveness of a Mindfulness-Based Cognitive Therapy (MBCT) group intervention for cancer patients in comparison with individual internet-based MBCT and treatment as usual (TAU)., Methods/design: A three-armed multicenter randomized controlled trial comparing group-based MBCT to individual internet-based MBCT and TAU in cancer patients who suffer from at least mild psychological distress (Hospital Anxiety and Depression Scale (HADS) ≥ 11). Measurements will be conducted prior to randomization (baseline), post-treatment and at 3 months and 9 months post-treatment. Participants initially allocated to TAU are subsequently randomized to either group- or individual internet-based MBCT and will receive a second baseline measurement after 3 months. Thus, the three-armed comparison will have a time span of approximately 3 months. The two-armed intervention comparison includes a 9-month follow-up and will also consist of participants randomized to the intervention after TAU. Primary outcome will be post-treatment psychological distress (HADS). Secondary outcomes are fear of cancer recurrence (Fear of Cancer Recurrence Inventory), rumination (Rumination and Reflection Questionnaire), positive mental health (Mental Health Continuum - Short Form), and cost-effectiveness (health-related quality of life (EuroQol -5D and Short Form-12) and health care usage (Trimbos and iMTA questionnaire on Costs associated with Psychiatric illness). Potential predictors: DSM-IV-TR mood/anxiety disorders (SCID-I) and neuroticism (NEO-Five Factor Inventory) will be measured. Mediators of treatment effect: mindfulness skills, (Five-Facets of Mindfulness Questionnaire- Short Form), working alliance (Working Alliance Inventory) and group cohesion (Group Cohesion Questionnaire) will also be measured., Discussion: This trial will provide valuable information on the clinical and cost-effectiveness of group versus internet-based MBCT versus TAU for distressed cancer patients., Trial Registration: Clinicaltrials.gov NCT02138513. Registered 6 May 2014.

Background: A large randomized clinical trial (the Occupational Therapy in Parkinson's Disease [OTiP] study) recently demonstrated that home-based occupational therapy improves perceived performance in daily activities of people with Parkinson's disease (PD). The aim of the current study was to evaluate the cost-effectiveness of this intervention., Methods: We performed an economic evaluation over a 6-month period for both arms of the OTiP study. Participants were 191 community-dwelling PD patients and 180 primary caregivers. The intervention group (n = 124 patients) received 10 weeks of home-based occupational therapy; the control group (n = 67 patients) received usual care (no occupational therapy). Costs were assessed from a societal perspective including healthcare use, absence from work, informal care, and intervention costs. Health utilities were evaluated using EuroQol-5d. We estimated cost differences and cost utility using linear mixed models and presented the net monetary benefit at different values for willingness to pay per quality-adjusted life-year gained., Results: In our primary analysis, we excluded informal care hours because of substantial missing data for this item. The estimated mean total costs for the intervention group compared with controls were €125 lower for patients, €29 lower for caregivers, and €122 higher for patient-caregiver pairs (differences not significant). At a value of €40,000 per quality-adjusted life-year gained (reported threshold for PD), the net monetary benefit of the intervention per patient was €305 (P = 0.74), per caregiver €866 (P = 0.01) and per patient-caregiver pair €845 (P = 0.24)., Conclusion: In conclusion, occupational therapy did not significantly impact on total costs compared with usual care. Positive cost-effectiveness of the intervention was only significant for caregivers., (© 2015 International Parkinson and Movement Disorder Society.)

Question: What is the effect of a multifaceted intervention with participation of patients on improvement of patient-centredness in fertility care?, Summary Answer: A multifaceted intervention with participation of patients did not improve total patient-centredness scores provided by women in fertility care., What Is Known Already: We should provide care that takes into account the preferences and needs of patients, i.e. patient-centred care. Especially infertile patients who suffer from a high emotional burden of treatment could benefit from a more patient-centred approach in healthcare. However, the improvement of patient-centred care is still needed, because effective strategies to come to improvement are lacking., Study Design, Size and Duration: A cluster RCT was performed within 32 Dutch fertility clinics, covering about one-third of all Dutch hospitals. After randomization, 16 clinics in the intervention group were exposed to a multifaceted improvement strategy for patient-centred fertility care for 1 year. This strategy comprised audit and feedback, educational outreach visits and patient-mediated interventions. The remaining 16 clinics in the control group performed care as usual., Participants/materials, Setting and Methods: The clinics' levels of patient-centredness were measured, using the validated Patient-centredness Questionnaire-Infertility (PCQ-Infertility). At baseline measurement, a total of 1620 women in couples undergoing fertility care (this included both male, female, mixed infertility and infertility of unknown cause) in one of the participating clinics were randomly selected to participate in the study and complete the questionnaire. For the after measurement, we randomly selected a comparable sample of 1565 women in infertile couples. Both women who had already started their treatment before the start of the study (67%) and women who started their treatment after the start of this study (33%) were included. To avoid bias, we only included the responses of non-pregnant respondents., Main Results and Role of Chance: The final analysis involved 30 clinics. A total of 946 women (response 58.4%) completed their questionnaire at baseline measurement and also a total of 946 women (response 60.4%) at after measurement. After excluding the pregnant patients, respectively 696 and 730 questionnaires were eligible for analysis at baseline and after measurement. The total score of case-mix adjusted PCQ-Infertility at after measurement did not differ significantly between the intervention and control group (B = 0.06; 95% confidence interval (CI) = -0.04-0.15; P = 0.25). However, scores on the continuity of care subscale were significantly higher in the intervention group compared with the control group (B = 0.20; 95% CI = 0.00-0.40; P < 0.05). The addition of three interaction terms to the model had a significant impact: (i) being younger than 36 years, (ii) beginning treatment after the study had started and (iii) using complementary and alternative medicine. If women met all three conditions, the scores in the intervention group were on average 0.31 points higher compared with the control group (95% CI = 0.14-0.48; P = <0.001)., Limitations, Reasons for Caution: Our response rates are sufficient, but the responses of many women are still lacking which might have biased our results. Furthermore, the PCQ-Infertility scores at baseline measurement were already reasonably high, which could have limited the effect of the multifaceted improvement strategy. Because we only included women in infertile couples in our study, we cannot draw conclusions on the effect of an improvement strategy for patient-centred fertility care for partners., Wider Implication of the Findings: A multifaceted intervention with participation of patients did not improve total patient-centredness scores, although some effect could be observed in specific groups of women and in specific dimensions of patient-centredness. These results can guide future research, in which we should focus more on personalized strategies and outcome measures., Study Funding/competing Interests: This work was supported by Merck Sharp & Dohme (MSD), The Netherlands. There are no competing interests., Trial Registration: Clinical Trials NCT01481064., (© The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Chronic fatigue is present in more than 60% of the patients with a neuromuscular disease and can be their most disabling symptom. In combination with other impairments, fatigue often results in low levels of physical activity and decreased social participation, leading to high societal costs. 'Energetic' is a self-management group program aimed at improving social participation, physical endurance and alleviating fatigue in these patients. The primary aim of this study is to evaluate the effectiveness and cost-effectiveness of the Energetic program., Methods/design: A multicentered, assessor-blinded, two-armed randomized controlled trial is conducted with evaluations at inclusion and four, seven and fifteen months later. The study includes patients with a neuromuscular disease and chronic fatigue and, when present, their caregivers. The participants are randomized (ratio 1:1) to either an intervention group, receiving the Energetic program, or a control group, receiving usual care (i.e., no specific intervention). The Energetic program covers four months and includes four modules: 1) individually tailored aerobic exercise training; 2) education about aerobic exercise; 3) self-management training in applying energy conservation strategies; and 4) implementation and relapse prevention in daily life. Two months after cessation of the program a booster session is provided. The primary outcome is the perceived performance score of the Canadian Occupational Performance Measure (COPM). Secondary outcomes include the COPM-satisfaction score, and measures of fatigue, physical endurance, activity engagement, mood, and self-efficacy. Caregiver burden is also evaluated as a secondary outcome. Health-related quality of life and medical and societal costs are assessed to estimate cost-effectiveness of the program., Discussion: The Energetic study is the first randomized controlled trial to evaluate the effectiveness and cost-effectiveness of a combined physical and self-management group training program for improving social participation, physical endurance and alleviating fatigue in patients with neuromuscular diseases. It will generate new insights in (cost-)effective rehabilitation strategies for these incurable conditions., Trial Registration: Clinicaltrials.gov NCT02208687 .

Background: Lyme borreliosis, a potentially severe tick-borne infection caused by Borrelia burgdorferi, can cause multi-system inflammatory disease. The incidence has been increasing, as has the number of patients with persistent symptoms attributed to Borrelia. These symptoms, also referred to as post-Lyme disease syndrome, may follow an erythema migrans or other Lyme manifestations, and include pain, fatigue, and cognitive disturbances. The optimal duration of treatment for these symptoms is a subject of controversy. The PLEASE study is designed to determine whether prolonged antibiotic treatment leads to better patient outcome than standard treatment., Methods/design: The PLEASE study is a double-blind, randomized, placebo-controlled trial. Based on power analysis and compensating for possible loss to follow-up, a minimum of 255 patients with borreliosis-attributed persistent symptoms are included. These symptoms are either (a) temporally related to an erythema migrans or otherwise proven symptomatic borreliosis, or (b) accompanied by a positive B. burgdorferi IgG or IgM immunoblot. All patients receive open-label ceftriaxone for two weeks. Patients are then randomized (ratio 1:1:1) to blinded oral follow-up treatment for 12 weeks with (I) doxycycline, (II) clarithromycin combined with hydroxychloroquine, or (III) placebo. The primary outcome is the physical component summary score (PCS) of the RAND-36 Health Status Inventory (RAND SF-36) at week 14. Secondary outcomes include physical and mental aspects of health-related quality of life (assessed by the subscales of the RAND SF-36), fatigue, neuropsychological evaluation, physical activity, and cost-effectiveness., Discussion: This article describes the background and design issues of the PLEASE study protocol. The results of this study may provide evidence for prescribing or withholding prolonged antibiotic treatment., Trial Registration: ClinicalTrials.gov: NCT01207739 , Netherlands Trial Register: NTR2469.

Context: Patients with thyroid nodules of indeterminate cytology undergo diagnostic surgery according to current guidelines. In 75% of patients, the nodule is benign. In these patients, surgery was unnecessary and unbeneficial because complications may occur. Preoperative fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) was found to have a very high negative predictive value (96%) and might therefore avoid futile surgery, complications, and costs. In the United States, two molecular tests of cytology material are routinely used for this purpose., Objective: Five-year cost-effectiveness for routine implementation of FDG-PET/CT was evaluated in adult patients with indeterminate fine-needle aspiration cytology and compared with surgery in all patients and both molecular tests., Design: A Markov decision model was developed to synthesize the evidence on cost-effectiveness about the four alternative strategies. The model was probabilistically analyzed. One-way sensitivity analyses of deterministic input variables likely to influence outcome were performed., Setting and Subjects: The model was representative for adult patients with cytologically indeterminate thyroid nodules., Main Outcome Measures: The discounted incremental net monetary benefit (iNMB), the efficiency decision rule containing outcomes as quality-adjusted life-years and (direct) medical cost, of implementation of FDG-PET/CT is displayed., Results: Full implementation of FDG-PET/CT resulted in 40% surgery for benign nodules, compared with 75% in the conventional approach, without a difference in recurrence free and overall survival. The FDG-PET/CT modality is the more efficient technology, with a mean iNMB of €3684 compared with surgery in all. Also, compared with a gene expression classifier test and a molecular marker panel, the mean iNMB of FDG-PET/CT was €1030 and €3851, respectively, and consequently the more efficient alternative., Conclusion: Full implementation of preoperative FDG-PET/CT in patients with indeterminate thyroid nodules could prevent up to 47% of current unnecessary surgery leading to lower costs and a modest increase of health-related quality of life. Compared with an approach with diagnostic surgery in all patients and both molecular tests, it is the least expensive alternative with similar effectiveness as the gene-expression classifier.

Study Question: What are patients and insurers willing to pay for different aspects of fertility care, with a particular focus on patient-centredness?, Summary Answer: In fertility care, both patients and health insurers place a high value on patient-centred factors, also when taking into account the effectiveness of fertility care. WHAT IS KNOWN ALREADY?: The benefit patients derive from fertility treatment may arise from several aspects of their care, such as the effectiveness, safety or patient-centred factors. Patient-centredness is recognized as an important, multi-dimensional concept, including domains on the organizational level (e.g. information provision) and on the human level (e.g. patient involvement)., Study Design, Size, and Duration: We performed a discrete choice experiment (DCE) within 32 Dutch fertility clinics and five large health insurance companies in the Netherlands. A total of 996 infertile patients who underwent at least one treatment cycle for their fertility problem and 84 healthcare insurers participated in the study which was executed in the summer of 2012., Participants/materials, Setting, Methods: All participating patients and health insurers completed a DCE about their preferences in fertility care regarding the effectiveness, patient-centredness of care and additional costs. Logistic regression analysis was subsequently used to determine what both patients and health insurers were willing to pay for a one-step increase in patient-centred care and 1% higher pregnancy rates., Main Results and the Role of Chance: Five hundred and fifty patients (55.2%) and 45 healthcare insurers (53.6%) completed the DCE questionnaire. Patients were willing to pay a median amount of €463 for a relevant one-step increase in patient-centred care and €107 for 1% increase in pregnancy rates. Healthcare insurers' valuations were lower: €191 for more patient-centred care and €60 for 1% increase in pregnancy rates. The willingness-to-pay values depended on patients' age, patients' ethnicity, income, and treatment type and on health insurers' age., Limitations, Reasons for Caution: An important limitation of a DCE study is that other attributes, that were not included in our study, are relevant as well. Therefore, our study participants might make other choices in real life compared with our hypothetical DCE scenarios. We tried to prevent this potential bias by selecting the most important attributes from the literature, using the input of an expert panel and performing a pilot study to test the validity of our questionnaire., Wider Implications of the Findings: This study emphasizes the importance of patient-centredness aspects of care for both infertile patients and their insurers. Therefore, efforts by policymakers and clinicians to improve these aspects of care would increase the overall value patients derive from their fertility treatment. Moreover, although insurers placed a lower monetary value on patient-centredness aspects than patients, it is arguable that insurers' purchasing decisions should be guided by patient rather than insurer preferences. Finally, given the relatively high monetary value patients place on patient-centred aspects of their fertility care, there may be a willingness to allow for some optional co-payments for this quality of care dimension., Study Funding/competing Interests: This work was supported by Merck Sharp and Dohme, the Netherlands. No competing interests declared., Trial Registration Number: Clinical Trials NCT01834313., (© The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objective: Increased recall rates in the Dutch breast cancer screening program call for a new assessment strategy aiming to reduce unnecessary costs and anxiety. Diagnostic work-up (usual care) includes multidisciplinary hospital assessment and is similar for all recalled women, regardless of the radiologist's suspicion of breast cancer. This is similar in many Canadian settings. We developed a novel assessment strategy that offers women with a low suspicion of breast cancer a quick and non-invasive assessment by a screening radiologist (intervention). We compared these two strategies in a cost-effectiveness analysis based on a randomized controlled trial: multicentre randomized controlled trial (MASS trial, Netherlands National Trial Register: NTR1480)., Methods: Participants were enrolled between August 2010 and December 2012 and were randomly assigned to either the intervention or control group (allocation ratio 2:1). Fourteen assessment centres participated in the study. Questionnaires were used to record quality of life (EuroQol-5D), health care use and costs after recall., Results: Our study comprised 366 women, of whom 288 were randomly assigned to the intervention group and 88 to the control group. The mean difference in cost was €153/CAD $226 (95% confidence interval €107-199/CAD $158-294, p&lt;0.001). We found no significant differences in quality of life. The bootstrapped incremental cost-effectiveness ratios in the cost-effectiveness plane showed that the intervention was the efficient, cost-saving modality., Conclusion: Our data show the benefits of tailoring diagnostic assessment to the screening radiologist's suspicion of breast cancer. Scenarios of implementing such a strategy in the Dutch screening or health care system are currently being discussed with various stakeholders.

Cost-effectiveness analysis has become a widely accepted tool for decision making in health care. The standard textbook cost-effectiveness analysis focuses on whether to make the switch from an old or common practice technology to an innovative technology, and in doing so, it takes a global perspective. In this article, we are interested in a local perspective, and we look at the questions of whether and when the switch from old to new should be made. A new approach to cost-effectiveness from a local (e.g., a hospital) perspective, by means of a mathematical model for cost-effectiveness that explicitly incorporates time, is proposed. A decision rule is derived for establishing whether a new technology should be adopted, as well as a general rule for establishing when it pays to postpone adoption by 1 more period, and a set of decision rules that can be used to determine the optimal timing of adoption. Finally, a simple example is presented to illustrate our model and how it leads to optimal decision making in a number of cases.

Background: Dementia-care mapping (DCM) is a cyclic intervention aiming at reducing neuropsychiatric symptoms in people with dementia in nursing homes. Alongside an 18-month cluster-randomized controlled trial in which we studied the effectiveness of DCM on residents and staff outcomes, we investigated differences in costs of care between DCM and usual care in nursing homes., Methods: Dementia special care units were randomly assigned to DCM or usual care. Nurses from the intervention care homes received DCM training, a DCM organizational briefing day and conducted the 4-months DCM-intervention twice during the study. A single DCM cycle consists of observation, feedback to the staff, and action plans for the residents. We measured costs related to health care consumption, falls and psychotropic drug use at the resident level and absenteeism at the staff level. Data were extracted from resident files and the nursing home records. Prizes were determined using the Dutch manual of health care cost and the cost prices delivered by a pharmacy and a nursing home. Total costs were evaluated by means of linear mixed-effect models for longitudinal data, with the unit as a random effect to correct for dependencies within units., Results: 34 units from 11 nursing homes, including 318 residents and 376 nursing staff members participated in the cost analyses. Analyses showed no difference in total costs. However certain changes within costs could be noticed. The intervention group showed lower costs associated with outpatient hospital appointments over time (p = 0.05) than the control group. In both groups, the number of falls, costs associated with the elderly-care physician and nurse practitioner increased equally during the study (p<0.02)., Conclusions: DCM is a cost-neutral intervention. It effectively reduces outpatient hospital appointments compared to usual care. Other considerations than costs, such as nursing homes' preferences, may determine whether they adopt the DCM method., Trial Registration: Dutch Trials Registry NTR2314.

Background: Older adults can benefit from physical activity in numerous ways. Physical activity is considered to be one of the few ways to influence the level of frailty. Standardized exercise programs do not necessarily lead to more physical activity in daily life, however, and a more personalized approach seems appropriate. The main objective of this study is to investigate whether a focused, problem-oriented coaching intervention ('Coach2Move') delivered by a physiotherapist specializing in geriatrics is more effective for improving physical activity, mobility and health status in community-dwelling older adults than usual physiotherapy care. In addition, cost-effectiveness will be determined., Methods/design: The design of this study is a single-blind randomized controlled trial in thirteen physiotherapy practices. Randomization will take place at the individual patient level. The study population consists of older adults, ≥70 years of age, with decreased physical functioning and mobility and/or a physically inactive lifestyle. The intervention group will receive geriatric physiotherapy according to the Coach2Move strategy. The control group will receive the usual physiotherapy care. Measurements will be performed by research assistants not aware of group assignment. The results will be evaluated on the amount of physical activity (LASA Physical Activity Questionnaire), mobility (modified 'get up and go' test, walking speed and six-minute walking test), quality of life (SF-36), degree of frailty (Evaluative Frailty Index for Physical Activity), fatigue (NRS-fatigue), perceived effect (Global Perceived Effect and Patient Specific Complaints questionnaire) and health care costs., Discussion: Most studies on the effect of exercise or physical activity consist of standardized programs. In this study, a personalized approach is evaluated within a group of frail older adults, many of whom suffer from multiple and complex diseases and problems. A complicating factor in evaluating a new approach is that it may not be automatically adopted by clinicians. Specific actions are undertaken to optimize implementation of the Coach2Move strategy during the trial. Whether or not these will be sufficient is a matter we will consider subsequently, using quality indicators and process analysis., Trial Registration: The Netherlands National Trial Register: NTR3527.

This paper examines the short run inefficiencies that arise during gradual implementation of a new cost-effective technology in healthcare. These inefficiencies arise when health gains associated with the new technology cannot be obtained immediately because the new technology does not yet supply all patients, and when there is overcapacity for the old technology in the short run because the supply of care is divided among two mutually exclusive technologies. Such efficiency losses are not taken into account in standard textbook cost-effectiveness analysis in which a steady state is presented where costs and effects are assumed to be unchanging over time. A model is constructed to quantify such short run inefficiencies as well as to inform the decision maker about the optimal implementation pattern for the new technology. The model operates by integrating the incremental net benefit equations for both the period of co-existence of mutually exclusive technologies and the period after complete substitution of the old technology. It takes into account the rate of implementation of the new technology, depreciation of capital of the old technology as well as the demand curves for both technologies. The model is applied to the real world case of converting from screen film to digital mammography in the Netherlands.

The transinguinal preperitoneal (TIPP) technique using a soft mesh with a memory ring was developed recently for inguinal hernia repair. To compare TIPP with the Lichtenstein method, a randomised trial was conducted (ISRCTN93798494). The aim of this study was to perform an economic evaluation of the TIPP modality compared to the Lichtenstein modality from both a hospital and societal perspective alongside the clinical trial. The TULIP study was a double-blind randomised clinical trial comparing two techniques for inguinal hernia repair (TIPP and Lichtenstein). Correct generation of the allocation sequence, allocation concealment, blinding, and follow-up were used/applied according to the recommendations of the Cochrane Handbook. Next to the cost drivers, the short-form-36 health survey (SF-36) data from the TULIP trial was used to determine utility. The SF-36 data from the TULIP trial were revised using the SF-6D algorithm according to Brazier. Two scenarios-a hospital and a societal perspective-were presented. If the analyses showed no difference in effects (on the SF-6D) the cost effectiveness decision rule to cost minimisation was altered. No significant difference in SF-6D utility between both modalities was found (mean difference: 0.888, 95% CI -1.02 to 1.23); consequently, the economic decision rule became cost minimisation. For the hospital perspective no significant differences in costs were found (mean difference: euro -13, 95% CI euro -130 to euro 104). However, when including productivity gains in the analysis, significant differences (P = 0.037) in costs favouring the TIPP modality (mean saving: euro 1,472, 95% CI euro 463- euro 2,714) were found. The results show that TIPP is a cost-saving inguinal hernia repair technique compared to the Lichtenstein modality against equal effectiveness expressed as quality adjusted life week at 1 year given a societal perspective. In the trial, TIPP patients showed on average a quicker recovery of 6.5 days compared to Lichtenstein patients.

Background: Live kidney donation has a clear economical benefit over dialysis and deceased-donor transplantation. Compared with mini-incision open donor nephrectomy, laparoscopic donor nephrectomy (LDN) is considered cost-effective. However, little is known on the cost-effectiveness of hand-assisted retroperitoneoscopic donor nephrectomy (HARP). This study evaluated the cost-effectiveness of HARP versus LDN., Methods: Alongside a randomized controlled trial, the cost-effectiveness of HARP versus LDN was assessed. Eighty-six donors were included in the LDN group and 82 in the HARP group. All in-hospital costs were recorded. During follow-up, return-to-work and other societal costs were documented up to 1 year. The EuroQol-5D questionnaire was administered up to 1 year postoperatively to calculate quality-adjusted life years (QALYs)., Results: Mean total costs from a healthcare perspective were $8935 for HARP and $8650 for LDN (P = 0.25). Mean total costs from a societal perspective were $16,357 for HARP and $16,286 for LDN (P = 0.79). On average, donors completely resumed their daytime jobs on day 54 in the HARP group and on day 52 in the LDN group (P = 0.65). LDN resulted in a gain of 0.005 QALYs., Conclusions: Absolute costs of both procedures are very low and the differences in costs and QALYs between LDN and HARP are very small. Other arguments, such as donor safety and pain, should determine the choice between HARP and LDN.

Background: Malignant lymphomas constitute a diverse group of cancers of lymphocytes. One well-known disease is Hodgkin's lymphoma; the others are classified as non-Hodgkin's lymphoma (NHL). NHLs are the most common hematologic neoplasms in adults worldwide, and in 2012 over 170,000 new cases were estimated in the United States and Europe.In previous studies, several practice gaps in hospital care for patients with NHL have been identified. To decrease this variation in care, the present study aims to perform a problem analysis in which barriers to and facilitators for optimal NHL care will be identified and, based on these findings, to develop (tailored) improvement strategies. Subsequently, we will assess the effectiveness, feasibility and costs of the improvement strategies., Methods/design: Barriers and facilitators will be explored using the literature, using interviews and questionnaires among physicians involved in NHL care, and patients diagnosed with NHL. The results will be used to develop a tailored improvement strategy. A cluster randomized controlled trial involving 19 Dutch hospitals will be conducted. Hospitals will be randomized to receive either an improvement strategy tailored to the barriers and facilitators found or, a standard strategy of audit and feedback.The effects of both strategies will be evaluated using previously developed quality indicators. Adherence to the indicators will be measured before and after the intervention period based on medical records from newly diagnosed NHL patients. To study the feasibility of both strategies, a process evaluation will be additionally performed. Data about exposure to the different elements of the strategies will be collected using questionnaires. Economic evaluation from a healthcare perspective will compare the two implementation strategies, where the costs of the implementation strategy and changes in healthcare consumption will be assessed., Discussion: The presence of variation in the use of diagnostic tests, treatment, and follow-up between different physicians in different hospitals in the Netherlands is important for patients. To reduce the existing variation in care, implementation of tailored interventions to improve NHL care is necessary., Trial Registration: This trial is registered at ClinicalTrial.gov as the PEARL study, registration number NCT01562509.

Background: The effectiveness of dementia-care mapping (DCM) for institutionalised people with dementia has been demonstrated in an explanatory cluster-randomised controlled trial (cRCT) with two DCM researchers carrying out the DCM intervention. In order to be able to inform daily practice, we studied DCM effectiveness in a pragmatic cRCT involving a wide range of care homes with trained nursing staff carrying out the intervention., Methods: Dementia special care units were randomly assigned to DCM or usual care. Nurses from the intervention care homes received DCM training and conducted the 4-months DCM-intervention twice during the study. The primary outcome was agitation, measured with the Cohen-Mansfield agitation inventory (CMAI). The secondary outcomes included residents' neuropsychiatric symptoms (NPSs) and quality of life, and staff stress and job satisfaction. The nursing staff made all measurements at baseline and two follow-ups at 4-month intervals. We used linear mixed-effect models to test treatment and time effects., Results: 34 units from 11 care homes, including 434 residents and 382 nursing staff members, were randomly assigned. Ten nurses from the intervention units completed the basic and advanced DCM training. Intention-to-treat analysis showed no statistically significant effect on the CMAI (mean difference between groups 2·4, 95% CI -2·7 to 7·6; p = 0·34). More NPSs were reported in the intervention group than in usual care (p = 0·02). Intervention staff reported fewer negative and more positive emotional reactions during work (p = 0·02). There were no other significant effects., Conclusions: Our pragmatic findings did not confirm the effect on the primary outcome of agitation in the explanatory study. Perhaps the variability of the extent of implementation of DCM may explain the lack of effect., Trial Registration: Dutch Trials Registry NTR2314.

Background: Visual analogue scales (VAS) are often used to measure health-related quality of life (HRQoL). However, when such scales contain ambiguous anchors like "best imaginable health state," they produce answers that are difficult to interpret, as such anchors are interpreted differently by respondents of different age. This phenomenon that people's interpretation of subjective response scales changes in response to changing circumstances is known as scale recalibration. The current study attempts to investigate whether scale recalibration in a patient sample with cognitive limitations and proxies differs from the general population., Methods: The participants in the current study were 151 pairs of community-dwelling patients with dementia and their proxies. They were administered three VASs with different upper anchors; (A) "best imaginable health state," (B) "best imaginable health state for someone your age," and (C) "best imaginable health state for a 25-year-old." From literature, we inferred a conceptual model for the general population that predicts the ordinal relationship of the VASs to be B ≥ A ≥ C. This rank order is tested by repeated measure ANOVA's in the aforementioned populations., Results: VAS scores of patients with dementia were in line with the conceptual model. Proxy VAS scores for assessing patient HRQoL were not in line with the model: A > B > C. In addition, proxy VAS scores for assessing their own health were not in line with the model: A > B > C., Conclusion: Patients with dementia use the VAS in a similar way to the general population. Proxies assessing either patients or themselves differ from the general population.

Background: Occupational therapists may have an added value in the care of patients with Parkinson's disease whose daily functioning is compromised, as well as for their immediate caregivers. Evidence for this added value is inconclusive due to a lack of rigorous studies. The aim of this trial is to evaluate the (cost) effectiveness of occupational therapy in improving daily functioning of patients with Parkinson's disease., Methods/design: A multicenter, assessor-blinded, two-armed randomized controlled clinical trial will be conducted, with evaluations at three and six months. One hundred ninety-two home-dwelling patients with Parkinson's disease and with an occupational therapy indication will be assigned to the experimental group or to the control group (2:1). Patients and their caregivers in the experimental group will receive ten weeks of home-based occupational therapy according to recent Dutch guidelines. The intervention will be delivered by occupational therapists who have been specifically trained to treat patients according to these guidelines. Participants in the control group will not receive occupational therapy during the study period. The primary outcome for the patient is self-perceived daily functioning at three months, assessed with the Canadian Occupational Performance Measure. Secondary patient-related outcomes include: objective performance of daily activities, self-perceived satisfaction with performance in daily activities, participation, impact of fatigue, proactive coping skills, health-related quality of life, overall quality of life, health-related costs, and effectiveness at six months. All outcomes at the caregiver level will be secondary and will include self-perceived burden of care, objective burden of care, proactive coping skills, overall quality of life, and care-related costs. Effectiveness will be evaluated using a covariance analysis of the difference in outcome at three months. An economic evaluation from a societal perspective will be conducted, as well as a process evaluation., Discussion: This is the first large-scale trial specifically evaluating occupational therapy in Parkinson's disease. It is expected to generate important new information about the possible added value of occupational therapy on daily functioning of patients with Parkinson's disease., Trial Registration: Clinicaltrials.gov: NCT01336127.

Background: In comparison to other European population-based breast cancer screening programmes, the Dutch programme has a low referral rate, similar breast cancer detection and a high breast cancer mortality reduction. The referral rate in the Netherlands has increased over time and is expected to rise further, mainly following nationwide introduction of digital mammography, completed in 2010. This study explores the consequences of the introduction of digital mammography on the balance between referral rate, detection of breast cancer, diagnostic work-up and associated costs., Methods: Detailed information on diagnostic work-up (chart review) was obtained from referred women (n = 988) in 2000-06 (100% analogue mammography) and 2007 (75% digital mammography) in Nijmegen, the Netherlands., Results: The average referral rate increased from 15 (2000-06) to 34 (2007) per 1000 women screened. The number of breast cancers detected increased from 5.5 to 7.8 per 1000 screens, whereas the positive predictive value fell from 37% to 23%. A sharp rise in diagnostic work-up procedures and total diagnostic costs was seen. On the other hand, costs of a single work-up slightly decreased, as less surgical biopsies were performed., Conclusion: Our study shows that a low referral rate in combination with the introduction of digital mammography affects the balance between referral rate and detection rate and can substantially influence breast cancer care and associated costs. Referral rates in the Netherlands are now more comparable to other countries. This effect is therefore of value in countries where implementation of digital breast cancer screening has just started or is still under discussion.

Objective: The clinical benefit of routine follow-up in patients treated for ovarian cancer is subject to debate. In this study, the magnitude of the potential survival benefit of routine examinations was evaluated by Markov modeling., Methods: The clinical course of ovarian cancer was simulated using a 4-state nonstationary Markov model. Risk of recurrence and mortality probabilities were derived from individual patient data and Statistics Netherlands. The life expectancy was simulated for 3 follow-up scenarios: a current, withholding (all recurrences detected symptomatically), and perfect follow-up program (all recurrences detected asymptomatically). The impact of effective recurrence treatment in the future was modeled by varying the mortality ratio between patients with asymptomatically versus symptomatically detected recurrences. The model was validated using empirical data., Results: The mean life expectancy of patients, aged 58 years and in complete clinical remission after primary treatment, was 10.8 years. Varying the transition probabilities with ±25% changed the life expectancy by up to 1.1 years. The modeled life expectancy for the withholding and perfect follow-up scenarios was also 10.8 years and insensitive to model assumptions. In patients with stages IIB to IV, the life expectancy was 7.0 years, irrespective of follow-up strategy. A mortality ratio of 0.8 for patients with asymptomatically versus symptomatically detected recurrences resulted in a gain in life expectancy of 5 months for withholding versus perfect follow-up., Conclusions: Routine follow-up in ovarian cancer patients is not expected to improve the life expectancy. The timing of detection of recurrent ovarian cancer is immaterial until markedly improved treatment options become available.

Objective: To examine the effectiveness of post-diagnosis dementia treatment and coordination of care by memory clinics compared with general practitioners., Design: Multicentre randomised controlled trial., Setting: Nine memory clinics and 159 general practitioners in the Netherlands., Participants: 175 patients with a new diagnosis of mild to moderate dementia living in the community and their informal caregivers., Interventions: Usual care provided by memory clinic or general practitioner., Main Outcome Measures: Caregiver rated quality of life of the patient measured with the quality of life in Alzheimer's disease instrument and self perceived burden of the informal caregiver measured with the sense of competence questionnaire (intention to treat analysis)., Results: The quality of life of the patients in the memory clinic group was 0.5 (95% confidence interval -0.7 to 1.6) points higher than in the general practitioner group. Caregivers' burden was 2.4 (-5.8 to 1.0) points lower in the memory clinic group than in the general practitioner group., Conclusion: No evidence was found that memory clinics were more effective than general practitioners with regard to post-diagnosis treatment and coordination care for patients with dementia. Without further evidence on the effectiveness of these modalities, other arguments, such as cost minimisation, patients' preferences, or regional health service planning, can determine which type of dementia care is offered., Trial Registration: Clinical trials NCT00554047.

Important assumptions that underlie cost-effectiveness analysis (CEA) are that production technologies are convex and that production processes always perform at constant returns to scale. However, in the short run these assumptions are likely to be violated. Therefore, CEAs might overestimate cost-effectiveness in the short run. To come up with a more precise cost-effectiveness outcome, we present a model that is able to correct the long-run incremental net benefit (INB) for short-run inefficiencies. This provides decision makers with a more realistic view of the expected efficiency gains. This model starts by determining the initial efficiency losses inflicted by inflexible resources. Then the model is made dynamic in order to adjust the efficiency losses by allowing for refilling and writing off freed capacity. Finally, the model calculates the length of the short-run time frame in which such efficiency losses exist, and a correction term with which the usual long-run INB should be adjusted to account for short-run inefficiencies. The model is applied to two cases: dialysis and digitizing a radiography department. The dialysis case shows moderate short-run efficiency losses while in the radiography case short-run efficiency losses are sufficiently large to cause a switch in cost-effectiveness from favorable to inefficient in the short run., (Copyright © 2011 John Wiley & Sons, Ltd.)

Background: The effectiveness and efficiency of nursing-home dementia care are suboptimal: there are high rates of neuropsychiatric symptoms among the residents and work-related stress among the staff. Dementia-care mapping is a person-centred care method that may alleviate both the resident and the staff problems. The main objective of this study is to evaluate the effectiveness and cost-effectiveness of dementia-care mapping in nursing-home dementia care., Methods/design: The study is a cluster-randomised controlled trial, with nursing homes grouped in clusters. Studywise minimisation is the allocation method. Nursing homes in the intervention group will receive a dementia-care-mapping intervention, while the control group will receive usual care. The primary outcome measure is resident agitation, to be assessed with the Cohen-Mansfield Agitation Inventory. The secondary outcomes are resident neuropsychiatric symptoms, assessed with the Neuropsychiatric Inventory--Nursing Homes and quality of life, assessed with Qualidem and the EQ-5D. The staff outcomes are stress reactions, job satisfaction and job-stress-related absenteeism, and staff turnover rate, assessed with the Questionnaire about Experience and Assessment of Work, the General Health Questionnaire-12, and the Maastricht Job Satisfaction Scale for Health Care, respectively. We will collect the data from the questionnaires and electronic registration systems. We will employ linear mixed-effect models and cost-effectiveness analyses to evaluate the outcomes. We will use structural equation modelling in the secondary analysis to evaluate the plausibility of a theoretical model regarding the effectiveness of the dementia-care mapping intervention. We will set up process analyses, including focus groups with staff, to determine the relevant facilitators of and barriers to implementing dementia-care mapping broadly., Discussion: A novelty of dementia-care mapping is that it offers an integral person-centred approach to dementia care in nursing homes. The major strengths of the study design are the large sample size, the cluster-randomisation, and the one-year follow-up. The generalisability of the implementation strategies may be questionable because the motivation for person-centred care in both the intervention and control nursing homes is above average. The results of this study may be useful in improving the quality of care and are relevant for policymakers., Trial Registration: The trial is registered in the Netherlands National Trial Register: NTR2314., (© 2012 van de Ven et al; licensee BioMed Central Ltd.)

In breast cancer, it has been shown that pN0(i+) and pN1mi have a comparable negative impact on disease-free survival, compared with pN0. However, pN0(i+) is considered to be a heterogeneous group. We determined the effect of metastatic size and microanatomic location within the pN0(i+) group on breast cancer recurrence. We included all Dutch breast cancer patients diagnosed in 1998-2005 with favorable primary tumor characteristics and a final nodal status of pN0(i+). For this analysis, only patients without adjuvant systemic therapy were eligible (n = 513). Presence of single tumor cells versus cell clusters, metastatic size and microanatomic location were recorded. Primary endpoint was disease-free survival. Analyses were adjusted for age at diagnosis, tumor size, tumor grade, axillary treatment and hormone receptor status. The 5-year disease-free survival of patients with single tumor cell(s) (n = 93) was 78.6% and with tumor cell cluster(s) (n = 404) 77.1%. The hazard ratio for disease events was 1.05 (95% CI 0.63-1.76) for cell cluster(s) compared with single cell(s). In a Cox regression model, doubling of metastatic tumor size corresponded to a hazard ratio of 1.21 (95% CI 1.02-1.43). The adjusted hazard ratio was 0.90 (95% CI 0.54-1.50) for parenchymal (n = 112) versus sinusoidal location (n = 395). Single tumor cells bear similar prognostic information as small tumor cell clusters, even though results do suggest that within the pN0(i+) group, increasing size of nodal involvement is associated with reduced survival. Microanatomic location does not seem to have prognostic relevance.

Unlabelled: Gram-positive bacteremia has a high morbidity and mortality rate of approximately 30%. Delayed diagnosis of clinically silent metastatic infectious foci is an important indicator for a complicated outcome. (18)F-FDG PET/CT allows detection of focal infection, resulting in lower relapse rates and mortality. Here, we present a cost-effectiveness analysis associated with introduction of (18)F-FDG PET/CT for patients with gram-positive bacteremia., Methods: A cost-effectiveness analysis in a prospective (18)F-FDG PET/CT group (n = 115) and matched control group (n = 230) was performed alongside a clinical study, the results of which were previously published. Mortality at 6 mo was considered the final effect outcome and was used in the denominator of the incremental cost-effectiveness ratio., Results: Mortality in the (18)F-FDG PET/CT group was 19%, compared with 32% in the control group (P < 0.01). Incremental costs of (18)F-FDG PET/CT were $9,454 (95% confidence interval [CI], $3,963-$14,947), mainly because of admission (mean, $6,631; 95% CI, $1,449-$11,814). Additional costs were related to echocardiography (P < 0.01), not to (18)F-FDG PET/CT (P = 0.8). The mean incremental costs of the (18)F-FDG PET/CT strategy estimated by stratification for endocarditis were $5,277 per patient (95% CI, $429-$10,123; P = 0.03). The point estimate of the incremental cost-effectiveness ratio is $72,487 per prevented death (95% CI, $11,388-$323,379)., Conclusion: Introduction of a diagnostic regimen including routine (18)F-FDG PET/CT decreases morbidity and mortality. The cost increase is due to in-hospital treatment of metastatic infectious foci. Costs per prevented death, $72,487, are within the range that is considered to be efficient by Dutch guidelines. Patients with high-risk gram-positive bacteremia therefore should have easy access to (18)F-FDG PET/CT to enable early detection of metastatic infectious disease.

Objective: To perform a modelling study on the cost-effectiveness of three outcome-directed strategies in early RA patients: Strategy 1: starting MTX monotherapy, followed by the addition of LEF, followed by MTX with addition of anti-TNF; Strategy 2: start with MTX and LEF combination followed by MTX with anti-TNF; and Strategy 3: immediate start with MTX and anti-TNF., Methods: A validated Markov model was used to evaluate the cost-effectiveness of the three strategies. Effectiveness of the strategies was determined using daily practice data from two cohorts and used as input parameter in the model. Patients treated according to the strategies were matched for baseline 28-joint DAS (DAS-28). Using Monte Carlo simulation, expected costs, quality-adjusted life-years (QALYs) and incremental cost per QALY gained for a 5-year time horizon were calculated following both a health-care and a societal perspective., Results: The percentage of patients in remission and number of QALYs were comparable between the three strategies. Starting with a combination (MTX plus LEF or anti-TNF) was more costly than starting with MTX alone. This resulted in an unfavourable incremental cost-effectiveness ratio for starting on anti-TNF vs initially MTX: health-care perspective of €138,028 and from a societal perspective of €136,150 per QALY gained over 5 years., Conclusion: In this modelling study, starting with MTX or anti-TNF has comparable effectiveness. However, initial anti-TNF was far more expensive than starting with MTX monotherapy. Therefore, based on this study, a treatment strategy starting with MTX monotherapy is favoured over a strategy with MTX and anti-TNF right away in early RA patients.

Background: The aim of this study is evaluating the (cost-) effectiveness of a multidisciplinary, evidence based care program to improve the management of depression in nursing home residents of somatic and dementia special care units. The care program is an evidence based standardization of the management of depression, including standardized use of measurement instruments and diagnostical methods, and protocolized psychosocial, psychological and pharmacological treatment., Methods/design: In a 19-month longitudinal controlled study using a stepped wedge design, 14 somatic and 14 dementia special care units will implement the care program. All residents who give informed consent on the participating units will be included. Primary outcomes are the frequency of depression on the units and quality of life of residents on the units. The effect of the care program will be estimated using multilevel regression analysis. Secondary outcomes include accuracy of depression-detection in usual care, prevalence of depression-diagnosis in the intervention group, and response to treatment of depressed residents. An economic evaluation from a health care perspective will also be carried out., Discussion: The care program is expected to be effective in reducing the frequency of depression and in increasing the quality of life of residents. The study will further provide insight in the cost-effectiveness of the care program., Trial Registration: Netherlands Trial Register (NTR): NTR1477.

Comparability of cost-effectiveness of colorectal cancer (CRC) screening strategies is limited if heterogeneous study data are combined. We analyzed prospective empirical data from a randomized-controlled trial to compare cost-effectiveness of screening with either one round of immunochemical fecal occult blood testing (I-FOBT; OC-Sensor®), one round of guaiac FOBT (G-FOBT; Hemoccult-II®) or no screening in Dutch aged 50 to 75 years, completed with cancer registry and literature data, from a third-party payer perspective in a Markov model with first- and second-order Monte Carlo simulation. Costs were measured in Euros (€), effects in life-years gained, and both were discounted with 3%. Uncertainty surrounding important parameters was analyzed. I-FOBT dominated the alternatives: after one round of I-FOBT screening, a hypothetical person would on average gain 0.003 life-years and save the health care system €27 compared with G-FOBT and 0.003 life years and €72 compared with no screening. Overall, in 4,460,265 Dutch aged 50-75 years, after one round I-FOBT screening, 13,400 life-years and €320 million would have been saved compared with no screening. I-FOBT also dominated in sensitivity analyses, varying uncertainty surrounding important effect and cost parameters. CRC screening with I-FOBT dominated G-FOBT and no screening with or without accounting for uncertainty., (Copyright © 2010 UICC.)

Background: Surgical treatment of colorectal liver metastases has become increasingly aggressive. The influence of this more active surgical approach on patients' health-related quality of life (HRQoL) has hardly been evaluated. This study investigated the impact of surgical and systemic treatment on HRQoL in patients undergoing hepatic resection for colorectal metastases., Methods: A total of 145 patients with colorectal liver metastases were entered prospectively into the study. Based on HRQoL values derived from the EuroQol-5D, health summary measures were calculated to express the overall impact on four distinct clinical states. The HRQoL instrument was used at baseline, 3 and 6 weeks after surgery, and every 3 months thereafter for up to 3 years., Results: Patients showed a clear deterioration in HRQoL in the first weeks after surgery, followed by a recovery to baseline levels at 3 months after potentially curative surgery. In contrast, a sustained decline was noted when initial surgery for colorectal liver metastases was considered futile and palliative chemotherapy was started immediately. Three years after initial surgery, there were distinct differences in HRQoL between patients with or without recurrence. The latter group still had HRQoL scores at baseline levels, whereas patients with tumour recurrence showed a significant deterioration in HRQoL. Remarkably, there was no decline in HRQoL in patients with recurrent disease who could be treated by secondary surgical intervention., Conclusion: Superior overall HRQoL in the first 3 years after initial successful surgical intervention merits an aggressive surgical approach and intensive follow-up to detect recurrence early., (Copyright © 2010 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.)