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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: 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 .

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.

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.)

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.

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.

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: 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: 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.

Objectives: Experience with anti-TNF agents for a decade can be used to research the safety and effectiveness of anti-TNF agents in the long term. The objective of this article is to describe drug survival, disease activity, daily functioning, quality of life and adverse events of TNF-blocking agents in daily clinical practice after 5 years of follow-up., Methods: Data from the Dutch Rheumatoid Arthritis Monitoring (DREAM) register of 1560 RA patients were used for analyses (5-year follow-up, n=174). Drug survival and time to first serious infection or malignancy were analysed by Kaplan-Meier analysis. Several outcome measures at several follow-up moments were analysed per intention to treat and per protocol., Results: The 5-year drug survival of the first anti-TNF was 45%, and 60% for total use of TNF-blocking agents. Baseline 28-joint DAS (DAS-28) was 5.1 (s.d. 1.3). After 5 years, the mean DAS-28 was 3.2 (s.d. 1.3) in all patients who had started with TNF-blocking agents and 2.9 (s.d. 1.1) in patients who were still on TNF-blocking agents. In the latter group, the HAQ score was 0.88 (s.d. 0.7) and the EuroQol five dimensions (EQ-5D) utility score was 0.7 (s.d. 0.2). Incidence rates of serious infections and malignancies were 2.9 and 0.6 per 100 patient-years, respectively., Conclusion: Five-year follow-up of RA patients treated with TNF-blocking agents showed a 60% drug survival accompanied by sustained low disease activity, normalized function and quality of life similar to that in the general population. The benefit to risk ratio for long-term TNF-blocking therapy remains favourable.

Background: Many patients with Parkinson's disease are treated with physiotherapy. We have developed a community-based professional network (ParkinsonNet) that involves training of a selected number of expert physiotherapists to work according to evidence-based recommendations, and structured referrals to these trained physiotherapists to increase the numbers of patients they treat. We aimed to assess the efficacy of this approach for improving health-care outcomes., Methods: Between February, 2005, and August, 2007, we did a cluster-randomised trial with 16 clusters (defined as community hospitals and their catchment area). Clusters were randomly allocated by use of a variance minimisation algorithm to ParkinsonNet care (n=8) or usual care (n=8). Patients were assessed at baseline and at 8, 16, and 24 weeks of follow-up. The primary outcome was a patient preference disability score, the patient-specific index score, at 16 weeks. Health secondary outcomes were functional mobility, mobility-related quality of life, and total societal costs over 24 weeks. Analysis was by intention to treat. This trial is registered, number NCT00330694., Findings: We included 699 patients. Baseline characteristics of the patients were comparable between the ParkinsonNet clusters (n=358) and usual-care clusters (n=341). The primary endpoint was similar for patients within the ParkinsonNet clusters (mean 47.7, SD 21.9) and control clusters (48.3, 22.4). Health secondary endpoints were also similar for patients in both study groups. Total costs over 24 weeks were lower in ParkinsonNet clusters compared with usual-care clusters (difference euro727; 95% CI 56-1399)., Interpretation: Implementation of ParkinsonNet networks did not change health outcomes for patients living in ParkinsonNet clusters. However, health-care costs were reduced in ParkinsonNet clusters compared with usual-care clusters., Funding: ZonMw; Netherlands Organisation for Scientific Research; Dutch Parkinson's Disease Society; National Parkinson Foundation; Stichting Robuust., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Unlabelled: Childhood urinary tract infections (UTIs) can lead to renal scarring and ultimately to terminal renal failure, which has a high impact on quality of life, survival, and health-care costs. Variation in the treatment of UTIs between practices is high., Objective: To assess the cost-effectiveness of a maximum care model for UTIs in children, implying more testing and antibiotic treatment, compared with current practice in primary care in The Netherlands., Methods: We performed a probabilistic modeling study using Markov models. Figures used in the model were derived from a systematic review of the research literature. Multidimensional Monte Carlo simulation was used for the probabilistic analyses., Results: Maximum care gained 0.00102 (males) and 0.00219 (girls) QALYs (quality-adjusted life-years) and saved 42.70 euro (boys) and 77.81 euro (girls) in 30 years compared with current care, and was thus dominant. Net monetary benefit of maximum care ranged from 20 euro to 200 euro for a willingness to pay for a QALY ranging from 0 euro to 80,000 euro, respectively. Maximum care was also dominant over improved current care, although less dominant than to current care., Conclusions: This study suggested that maximum care for childhood UTI was dominant in the long run to current care, meaning that it delivered more quality of life at lower costs. Nevertheless, making firm conclusions is not possible, given the limitations of the input data.

Favourable cost-effectiveness of innovative technologies is more and more a necessary condition for implementation in clinical practice. But proven cost-effectiveness itself does not guarantee successful implementation. The reason for this is a potential discrepancy between long run efficiency, on which cost-effectiveness is based, and short run efficiency. Long run and short run efficiency is dependent upon economies of scale. This paper addresses the potential discrepancy between long run and short run efficiency of innovative technologies in healthcare, explores diseconomies of scale in Dutch hospitals and suggests what strategies might help to overcome hurdles to implement innovations due to that discrepancy.

Aim: to evaluate the effects of adalimumab, etanercept and infliximab on disease activity, functional ability and quality of life and the medication costs in a naturalistic design., Methods: All patients from the Dutch Rheumatoid Arthritis Monitoring (DREAM) register starting on tumour necrosis factor (TNF)alpha-blocking agents for the first time were monitored and assessed by trained research nurses every 3 months. The primary outcome was the Disease Activity Score (DAS28) course over the 12 months follow-up, analysed by linear mixed models. Secondary outcomes were the Health Assessment Questionnaire (HAQ), EuroQol five dimensions (EQ-5D) and the Short-Form 36 items (SF36) scores, and medication-related total costs., Results: The DAS28 and SF-36 physical component scale decreased in all three medication groups over 12 months, but the decrease was larger for adalimumab and etanercept in comparison to infliximab (p<0.001). The analyses of the HAQ and the EQ-5D scores showed the same (non-significant) trend, namely that at 12 months, the functionality and quality of life was better for adalimumab and etanercept patients. With regard to the medication costs, infliximab treatment resulted in significantly higher costs over the follow-up period than treatments with either adalimumab or etanercept. The comparison between adalimumab and etanercept showed a significant difference in the 12-month DAS28 course (p = 0.031). There were no additional indications for differences in effectiveness or costs between adalimumab and etanercept., Conclusion: The evaluation of the effectiveness and costs showed that adalimumab and etanercept are more or less equal and favourable compared to infliximab in the first year of treatment.

Objective: To assess the cost effectiveness of community based occupational therapy compared with usual care in older patients with dementia and their care givers from a societal viewpoint., Design: Cost effectiveness study alongside a single blind randomised controlled trial., Setting: Memory clinic, day clinic of a geriatrics department, and participants' homes. Patients 135 patients aged > or =65 with mild to moderate dementia living in the community and their primary care givers., Intervention: 10 sessions of occupational therapy over five weeks, including cognitive and behavioural interventions, to train patients in the use of aids to compensate for cognitive decline and care givers in coping behaviours and supervision., Main Outcome Measures: Incremental cost effectiveness ratio expressed as the difference in mean total care costs per successful treatment (that is, a combined patient and care giver outcome measure of clinically relevant improvement on process, performance, and competence scales) at three months after randomisation. Bootstrap methods used to determine confidence intervals for these measures., Results: The intervention cost 1183 euros (848 pounds sterling, $1738) (95% confidence interval 1128 euros (808 pounds sterling, $1657) to 1239 euros (888 pounds sterling, $1820)) per patient and primary care giver unit at three months. Visits to general practitioners and hospital doctors cost the same in both groups but total mean costs were 1748 euros (1279 pounds sterling, $2621) lower in the intervention group, with the main cost savings in informal care. There was a significant difference in proportions of successful treatments of 36% at three months. The number needed to treat for successful treatment at three months was 2.8 (2.7 to 2.9)., Conclusions: Community occupational therapy intervention for patients with dementia and their care givers is successful and cost effective, especially in terms of informal care giving.

Purpose: Current guidelines (ie, by the American Society of Clinical Oncology and the European Organisation for Research and Treatment of Cancer) do not recommend secondary infection prophylaxis, whereas, in contrast, caregivers prefer secondary prophylaxis to chemotherapy dose reduction after an episode of febrile neutropenia (FN). Because granulocyte colony-stimulating factor (G-CSF) is expensive, this study investigates the economic consequences of secondary prophylactic use of different prophylactic strategies (antibiotics, antibiotics plus G-CSF, and a combined sequential approach) in a population at risk of FN, using a Markov model., Methods: The input for the model is mainly based on the clinical outcome and patient-based cost data set (adopting the health care payer's perspective for the Netherlands) derived from a randomized study on primary prophylaxis in small-cell lung cancer (SCLC) patients; establishing mean cost of an episode FN of euro3,290 and prophylaxis of euro79 (antibiotics) +/- euro1,616 (G-CSF) per cycle. The economic analysis was analyzed probabilistically using first- and second-order Monte Carlo simulation. The incremental cost-effectiveness ratio (ICER) was defined as cost per FN-free cycle., Results: Secondary prophylaxis with antibiotics was the least expensive strategy (mean, euro4,496/patient). The strategy antibiotics plus G-CSF was most expensive (mean, euro 8,998/patient). Comparison of these two strategies resulted in an unacceptably high ICER (euro343,110 per FN-free cycle) in the Dutch context. In scenarios using higher FN-related costs (as found in the United States), the strategies are less distinct in their monetary effects, but still favor antibiotics., Conclusion: This model-based economic analysis demonstrates that in the Netherlands and most likely also in the United States, if secondary prophylaxis is preferred, the strategy with antibiotics is recommended.

Background: Cost-effectiveness remains an issue surrounding the introduction of laparoscopic donor nephrectomy (LDN)., Methods: In a randomized controlled trial the cost-effectiveness of LDN versus mini-incision open donor nephrectomy (ODN) was determined. Fifty donors were included in each group. All in-hospital costs were documented. Postoperatively, case record forms were sent to the donors during 1-year follow-up to record return-to-work and societal costs. To offset costs against quality of life, the Euroqol-5D questionnaire was administered preoperatively and 3, 7, 14, 28, 90, 180, and 365 days postoperatively., Results: Mean total costs were euro6,090 (US$7,308) after LDN and euro4,818 ($5,782) after ODN (P<0.001). Disposables influenced the cost difference most. Mean productivity loss was 68 and 75 days after LDN and ODN respectively, corresponding to euro783 ($940) gained per donor after LDN. The main gain in quality of life in the LDN group was realized within 4 weeks postoperatively. LDN resulted in a mean gain of 0.03 quality-adjusted life years at mean costs of euro1,271 ($1,525) and euro488 ($586) from a healthcare perspective and a societal perspective, respectively. This implies that one additional Quality-Adjusted Life Year after LDN costs about euro16,000 ($19,200) from a societal point of view and about euro41,000 ($49,200) from a health-care perspective. Activities other than work were resumed significantly earlier after LDN (66 vs. 91 days, P=0.01)., Conclusion: In addition to a clinically relevant donor-experienced benefit from LDN, this technique appeared, given a societal perspective, a cost-efficient procedure mainly due to less productivity losses.

Objective: The aim is to explore the preferences of female patients and physicians for IVF in three natural cycles compared to one stimulated cycle and to investigate which factors predict these preferences., Study Design: A questionnaire about IVF preference was administered initially to 105 patients between 36 and 42 years, who were on the waiting list for their first or second IVF attempt. In addition a questionnaire was sent to 56 physicians of Dutch IVF centres. The participants were asked for their preferences at different success rates based on treatment trade-off scenarios. Finally, information on demographic, psychological and other predictors for treatment choice were collected., Results: Complete data were obtained in 69 female patients (67%) and 27 physicians (49%). At a success rate for a life birth of 17% for both treatments, IVF in three natural cycles is preferred by 78% of the patients and physicians. Half of the patients and physicians still preferred natural cycle treatment at a success rate of 13%. Anxiety for hormone injections was the only significant predictor for patients' preferences., Conclusion: There seems to be a latent demand for IVF in the natural cycle related to anxiety for hormone injections.

Objective: To determine whether an investigation of microsatellite instability (MSI) in patients with colorectal carcinoma that have been selected by the pathologist could increase the number of detected families with hereditary non-polyposis colorectal carcinoma (HNPCC)., Design: Prospective inventory., Method: Pathologists selected patients with a newly diagnosed colorectal carcinoma for MSI analysis of their tumour tissue if they met one of the following four criteria: (a) colorectal carcinoma diagnosed below 50 years of age; (b) a second colorectal carcinoma; (c) a combination of colorectal carcinoma and another HNPCC-related cancer; (d) colorectal adenoma with high-grade dysplasia diagnosed below 40 years of age. Patients with a positive MSI-test were referred to a clinical geneticist. The new strategy was introduced and explored in 5 hospitals for a period of to months., Results: The new strategy was adopted and implemented successfully by pathologists and surgeons and accepted with satisfaction by the patients. Of the 55 patients included, 10 had a positive MSI-test. In 8/10 patients, DNA-mutation analysis was started by the clinical geneticist and 3 germline mutations in the MSH2-gene were detected. In 2 of 3 families with a pathogenic mutation, the family history alone did not fulfil the clinical criteria for HNPCC., Conclusion: Selection by the pathologist for MSI investigation was feasible in daily practice and identified more HNPCC patients than selection based on family history alone.

Background: Distinguishing hereditary non-polyposis colorectal cancer (HNPCC) from non-hereditary colorectal cancer (CRC) can increase the life expectancy of HNPCC patients and their close relatives., Aim: To determine the effectiveness, efficiency, and feasibility of a new strategy for the detection of HNPCC, using simple criteria for microsatellite instability (MSI) analysis of newly detected tumours that can be applied by pathologists. Criteria for MSI analysis are: (1) CRC before age 50 years; (2) second CRC; (3) CRC and HNPCC associated cancer; or (4) adenoma before age 40 years., Methods: The efficacy and cost effectiveness of the new strategy was evaluated against current practice. Decision analytic models were constructed to estimate the number of extra HNPCC mutation carriers and the costs of this strategy. The incremental costs and gain in life expectancy for a HNPCC mutation carrier were evaluated by Markov modelling. Feasibility was explored in five hospitals., Results: Using the new strategy, 2.2 times more HNPCC patients can be identified among a CRC population compared with current practice. This new strategy was found to be cost effective with an expected cost effectiveness ratio of 3801 per life year gained. When including the group of siblings and children, the cost effectiveness ratio became 2184 per life year gained. Sensitivity analysis showed these findings to be robust., Conclusions: MSI testing in a selection of newly diagnosed CRC patients was shown to be cost effective and a feasible method to identify patients at risk for HNPCC who are not recognised by family history.

The purpose was to explore the impact of response shift on quality-of-life measurement and consequently on cost-effectiveness analysis. This was done by using data from an earlier study. Adaptation to illness provides a probable explanation for the occurrence of response shift. In the case of proxy respondents, it is likely that the adaptation effect is absent. Therefore, two hypotheses were tested: 1) retrospective quality-of-life measurement does not differ from ratings given by proxies; and 2) proxy ratings differ from prospectively assessed pretreatment quality-of-life scores. Quality of life was assessed using a visual analog scale (VAS), time tradeoff (TTO), and the standard gamble (SG). Analyses revealed that neither hypothesis could be rejected, indicating that prospectively assessed pretreatment quality of life is enhanced by adaptation to the imperfect health state during the pretreatment period. Consequently, the cost-effectiveness ratio is different when using proxy measures or retrospective assessments of pretreatment quality of life, compared with using assessments of the quality of life in currently ill patients.

Background: Surgical treatment of morbid obesity is gaining in popularity, because conservative treatment is ineffective. However, a cost-effectiveness analysis has never been performed and is the main goal of the present study., Methods: 21 consecutive morbidly obese patients were tested before and after vertical banded gastroplasty (VBG). Quality of life was assessed with the Nottingham Health Profile and a visual analogue scale. A prevalence-based cost-of-illness analysis of morbid obesity was performed and the cost-effectiveness of VBG assessed., Results: VBG resulted in a significant weight loss and an improved quality of life. The improved quality of life combined with 3.6 life-years gained after VBG resulted in 12 quality adjusted life-years (QALY) gained in a lifelong scenario. Lifelong costs of illness of morbidly obese persons ranged from $8,304 to $9,367. Total direct costs of VBG were $5,865. The percentage of patients performing paid labor increased from 19% before VBG to 48% after VBG, resulting in an average productivity gain of $2,765 per year. In summary, the cost-effectiveness analysis revealed that surgical treatment of morbid obesity by means of VBG saves $4,004 to $3,928 per QALY (overall dominance)., Conclusion: Because treatment of morbid obesity with VBG results in QALYs gained and less costs, there is no doubt that this procedure should be introduced or continued from a societal point of view.

A cost-effectiveness (CE) analysis was performed of Bassini versus laparoscopic repair for primary inguinal hernia. Incremental costs per 1-year recurrence-free patient were calculated for the societal and hospital perspective. From the hospital perspective, the incremental CE ratio of laparoscopic repair is 5.348 guilders. From the societal perspective, laparoscopic repair is both less costly and more effective than Bassini repair. Results were sensitive to assumptions about recurrence rates, laparoscopic operating time, and return to work. Laparoscopic repair should replace Bassini repair in order to benefit society. From the hospital perspective, the decision to accept laparoscopic repair depends on the willingness to pay.