Rule-out of non-ST-segment elevation acute coronary syndrome by a single, pre-hospital troponin measurement: a randomized trial.

AIMS: Patients with suspected non-ST-segment elevation acute coronary syndrome (NSTE-ACS) are routinely transferred to the emergency department (ED). A clinical risk score with point-of-care (POC) troponin measurement might enable ambulance paramedics to identify low-risk patients in whom ED evaluation is unnecessary. The aim was to assess safety and healthcare costs of a pre-hospital rule-out strategy using a POC troponin measurement in low-risk suspected NSTE-ACS patients. METHODS AND RESULTS: This investigator-initiated, randomized clinical trial was conducted in five ambulance regions in the Netherlands. Suspected NSTE-ACS patients with HEAR (History, ECG, Age, Risk factors) score ≤3 were randomized to pre-hospital rule-out with POC troponin measurement or direct transfer to the ED. The sample size calculation was based on the primary outcome of 30-day healthcare costs. Secondary outcome was safety, defined as 30-day major adverse cardiac events (MACE), consisting of ACS, unplanned revascularization or all-cause death. : A total of 863 participants were randomized. Healthcare costs were significantly lower in the pre-hospital strategy (€1349 ± €2051 vs. €1960 ± €1808) with a mean difference of €611 [95% confidence interval (CI): 353-869; P < 0.001]. In the total population, MACE were comparable between groups [3.9% (17/434) in pre-hospital strategy vs. 3.7% (16/429) in ED strategy; P = 0.89]. In the ruled-out ACS population, MACE were very low [0.5% (2/419) vs. 1.0% (4/417)], with a risk difference of -0.5% (95% CI -1.6%-0.7%; P = 0.41) in favour of the pre-hospital strategy. CONCLUSION: Pre-hospital rule-out of ACS with a POC troponin measurement in low-risk patients significantly reduces healthcare costs while incidence of MACE was low in both strategies. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT05466591 and International Clinical Trials Registry Platform id NTR 7346.

The most efficient and effective BRCA1/2 testing strategy in epithelial ovarian cancer: Tumor-First or Germline-First?

OBJECTIVE: Genetic testing in epithelial ovarian cancer (OC) is essential to identify a hereditary cause like a germline BRCA1/2 pathogenic variant (PV). An efficient strategy for genetic testing in OC is highly desired. We evaluated costs and effects of two strategies; (i) Tumor-First strategy, using a tumor DNA test as prescreen to germline testing, and (ii) Germline-First strategy, referring all patients to the clinical geneticist for germline testing. METHODS: Tumor-First and Germline-First were compared in two scenarios; using real-world uptake of testing and setting implementation to 100%. Decision analytic models were built to analyze genetic testing costs (including counseling) per OC patient and per family as well as BRCA1/2 detection probabilities. With a Markov model, the life years gained among female relatives with a germline BRCA1/2 PV was investigated. RESULTS: Focusing on real-world uptake, with the Tumor-First strategy more OC patients and relatives with a germline BRCA1/2 PV are detected (70% versus 49%), at lower genetic testing costs (€1898 versus €2502 per patient, and €2511 versus €2930 per family). Thereby, female relatives with a germline BRCA1/2 PV can live on average 0.54 life years longer with Tumor-First compared to Germline-First. Focusing on 100% uptake, the genetic testing costs per OC patient are substantially lower in the Tumor-First strategy (€2257 versus €4986). CONCLUSIONS: The Tumor-First strategy in OC patients is more effective in identifying germline BRCA1/2 PV at lower genetic testing costs per patient and per family. Optimal implementation of Tumor-First can further improve detection of heredity in OC patients.

Manchester Procedure vs Sacrospinous Hysteropexy for Treatment of Uterine Descent: A Randomized Clinical Trial.

Importance: In many countries, sacrospinous hysteropexy is the most commonly practiced uterus-preserving technique in women undergoing a first operation for pelvic organ prolapse. However, there are no direct comparisons of outcomes after sacrospinous hysteropexy vs an older technique, the Manchester procedure. Objective: To compare success of sacrospinous hysteropexy vs the Manchester procedure for the surgical treatment of uterine descent. Design, Setting, and Participants: Multicenter, noninferiority randomized clinical trial conducted in 26 hospitals in the Netherlands among 434 adult patients undergoing a first surgical treatment for uterine descent that did not protrude beyond the hymen. Interventions: Participants were randomly assigned to undergo sacrospinous hysteropexy (n = 217) or Manchester procedure (n = 217). Main Outcomes and Measures: The primary outcome was a composite outcome of success, defined as absence of pelvic organ prolapse beyond the hymen in any compartment evaluated by a standardized vaginal support quantification system, absence of bothersome bulge symptoms, and absence of prolapse retreatment (pessary or surgery) within 2 years after the operation. The predefined noninferiority margin was 9%. Secondary outcomes were anatomical and patient-reported outcomes, perioperative parameters, and surgery-related complications. Results: Among 393 participants included in the as-randomized analysis (mean age, 61.7 years [SD, 9.1 years]), 151 of 196 (77.0%) in the sacrospinous hysteropexy group and 172 of 197 (87.3%) in the Manchester procedure group achieved the composite outcome of success. Sacrospinous hysteropexy did not meet the noninferiority criterion of -9% for the lower limit of the CI (risk difference, -10.3%; 95% CI, -17.8% to -2.8%; P = .63 for noninferiority). At 2-year follow-up, perioperative outcomes and patient-reported outcomes did not differ between the 2 groups. Conclusions: Based on the composite outcome of surgical success 2 years after primary uterus-sparing pelvic organ prolapse surgery for uterine descent, these results support a finding that sacrospinous hysteropexy is inferior to the Manchester procedure. Trial Registration: TrialRegister.nl Identifier: NTR 6978.

The Impact of Nursing Delirium Preventive Interventions in the ICU: A Multicenter Cluster-randomized Controlled Clinical Trial.

Rationale: Delirium is common in critically ill patients and is associated with deleterious outcomes. Nonpharmacological interventions are recommended in current delirium guidelines, but their effects have not been unequivocally established. Objectives: To determine the effects of a multicomponent nursing intervention program on delirium in the ICU. Methods: A stepped-wedge cluster-randomized controlled trial was conducted in ICUs of 10 centers. Adult critically ill surgical, medical, or trauma patients at high risk of developing delirium were included. A multicomponent nursing intervention program focusing on modifiable risk factors was implemented as standard of care. The primary outcome was the number of delirium-free and coma-free days alive in 28 days after ICU admission. Measurements and Main Results: A total of 1,749 patients were included. Time spent on interventions per 8-hour shift was median (interquartile range) 38 (14-116) minutes in the intervention period and median 32 (13-73) minutes in the control period (P = 0.44). Patients in the intervention period had a median of 23 (4-27) delirium-free and coma-free days alive compared with a median of 23 (5-27) days for patients in the control group (mean difference, -1.21 days; 95% confidence interval, -2.84 to 0.42 d; P = 0.15). In addition, the number of delirium days was similar: median 2 (1-4) days (ratio of medians, 0.90; 95% confidence interval, 0.75 to 1.09; P = 0.27). Conclusions: In this large randomized controlled trial in adult ICU patients, a limited increase in the use of nursing interventions was achieved, and no change in the number of delirium-free and coma-free days alive in 28 days could be determined. Clinical trial registered with www.clinicaltrials.gov (NCT03002701).

Effectiveness and cost effectiveness of interpersonal community psychiatric treatment (ICPT) for people with long-term severe non-psychotic mental disorders: a multi-Centre randomized controlled trial.

BACKGROUND: Long-term community mental health treatment for non-psychotic disorder patients with severe mental illness (SMI) who are perceived as difficult by clinicians, is poorly developed and lacks a structured, goal-centred approach. This study compares (cost-)effectiveness of Interpersonal Community Psychiatric Treatment (ICPT) with Care As Usual (CAU) on quality of life and clinician perceived difficulty in the care for non-psychotic disorder SMI-patients. A multi-centre cluster-randomized clinical tria was conducted in which Community Mental Health Nurses (Clinicians) in three large community mental health services in the Netherlands were randomly allocated to providing either ICPT or CAU to included patients. A total of 56 clinicians were randomized, who treated a total of 93 patients (59 in ICPT-group and 34 in CAU-group). METHODS: Primary outcome measure is patient-perceived quality of life as measured by the Manchester Short Assessment of Quality of Life (MANSA). Secondary outcome measures include clinician-perceived difficulty, general mental health, treatment outcomes, illness management and recovery, therapeutic relationship, care needs and social network. Patients were assessed at baseline, during treatment (6 months), after treatment (12 months) and at 6 months follow-up (18 months). Linear mixed-effects models for repeated measurements were used to compare mean changes in primary and secondary outcomes between intervention and control group of patients over time on an intention to treat basis. Potential efficiency was investigated from a societal perspective. Economic evaluation was based on general principles of a cost-effectiveness analysis. Outcome measures for health economic evaluation, were costs, and Quality Adjusted Life Years (QALYs). RESULTS: Half of the intended number of patients were recruited. There was no statistically significant treatment effect found in the MANSA (0.17, 95%-CI [- 0.058,0.431], p = 0.191). Treatment effects showed significant improvement in the Different Doctor-Patient Relationship Questionnaire-scores and a significant increase in the Illness Management and Recovery-scale Client-version scores). No effects of ICPT on societal and medical costs nor QALYs were found. CONCLUSIONS: This is the first RCT to investigate the (cost)-effectiveness of ICPT. Compared with CAU, ICPT did not improve quality of life, but significantly reduced clinician-perceived difficulty, and increased subjective illness management and recovery. No effects on costs or QALY's were found. TRIAL REGISTRATION: NTR 3988 , registered 13 May 2013.

Reducing the burden of brain tumor surgery.

BACKGROUND: Even though the need has been challenged, admitting patients to an intensive care or medium care unit (ICU/MCU) after adult supratentorial tumor craniotomy remains common practice. We have introduced a "no ICU, unless" policy for tumor craniotomy patients and evaluate costs, complications, and length of stay. METHODS: A prospective cohort study was performed comparing patients that underwent tumor craniotomy for supratentorial tumors during 2 years after introduction of the new policy with the year before. RESULTS: A reduction in ICU/MCU admittance from 88 to 23% of patients was found resulting in 13% cost reduction. Also, the new policy resulted in a 1.4-day shorter post-operative length of stay. Minor complications were reduced, while major complications remained the same. All major complications are reviewed. CONCLUSIONS: We show that routine post-operative ICU/MCU admittance after tumor craniotomy does not reduce complications, but actually interferes with recovery of our patients. Changing the paradigm results in earlier discharge and cost reduction.

Evaluation of a shared decision-making strategy with online decision aids in surgical and orthopaedic practice: study protocol for the E-valuAID, a multicentre study with a stepped-wedge design.

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 .

Decreased costs and retained QoL due to the 'PACE Steps to Success' intervention in LTCFs: cost-effectiveness analysis of a randomized controlled trial.

BACKGROUND: The number of residents in long-term care facilities (LTCFs) in need of palliative care is growing in the Western world. Therefore, it is foreseen that significantly higher percentages of budgets will be spent on palliative care. However, cost-effectiveness analyses of palliative care interventions in these settings are lacking. Therefore, the objective of this paper was to assess the cost-effectiveness of the 'PACE Steps to Success' intervention. PACE (Palliative Care for Older People) is a 1-year palliative care programme aiming at integrating general palliative care into day-to-day routines in LTCFs, throughout seven EU countries. METHODS: A cluster RCT was conducted. LTCFs were randomly assigned to intervention or usual care. LTCFs reported deaths of residents, about whom questionnaires were filled in retrospectively about resource use and quality of the last month of life. A health care perspective was adopted. Direct medical costs, QALYs based on the EQ-5D-5L and costs per quality increase measured with the QOD-LTC were outcome measures. RESULTS: Although outcomes on the EQ-5D-5L remained the same, a significant increase on the QOD-LTC (3.19 points, p value 0.00) and significant cost-savings were achieved in the intervention group (€983.28, p value 0.020). The cost reduction mainly resulted from decreased hospitalization-related costs (€919.51, p value 0.018). CONCLUSIONS: Costs decreased and QoL was retained due to the PACE Steps to Success intervention. Significant cost savings and improvement in quality of end of life (care) as measured with the QOD-LTC were achieved. A clinically relevant difference of almost 3 nights shorter hospitalizations in favour of the intervention group was found. This indicates that timely palliative care in the LTCF setting can prevent lengthy hospitalizations while retaining QoL. In line with earlier findings, we conclude that integrating general palliative care into daily routine in LTCFs can be cost-effective. TRIAL REGISTRATION: ISRCTN14741671 .

Cost-utility of individual internet-based and face-to-face Mindfulness-Based Cognitive Therapy compared with treatment as usual in reducing psychological distress in cancer patients.

OBJECTIVE: It was previously determined that group-based face-to-face Mindfulness-Based Cognitive Therapy (MBCT) and individual internet-based MBCT (eMBCT) are equally efficacious compared with treatment as usual (TAU) in reducing psychological distress. In this study, the incremental cost-utility of both interventions compared with TAU was assessed. METHODS: This cost-utility study included 245 self-referred heterogeneous cancer patients with psychological distress who were randomized to MBCT, eMBCT or TAU. Healthcare costs and (informal) work-related productivity losses were assessed by interview. Outcomes were expressed in EuroQol-5D-3L utility scores and quality-adjusted life years (QALY). An economic evaluation with a time-horizon of 3 months was conducted from the societal perspective in the intention-to-treat sample. In addition, secondary explorative analyses of costs and quality of life during the 9-month follow-up were conducted based on linear extrapolation of TAU. RESULTS: Paid work-related productivity losses and societal costs were lower in both intervention conditions compared with TAU during the 3-month intervention period. Moreover, quality of life (utility scores) improved in eMBCT versus TAU (Cohen's d: .54) and MBCT versus TAU (.53). At a willingness to pay of €20000 per QALY, the mean incremental net monetary benefit was €1916 (SD=€783) in eMBCT and €2365 (SD=€796) in MBCT versus TAU. Exploration of costs demonstrated an equal pattern of eMBCT and MBCT being superior to TAU. Quality of life at 9-month follow-up remained improved in both interventions. CONCLUSIONS: Results indicate that eMBCT and MBCT are cost-saving treatments whilst simultaneously improving quality of life for distressed cancer patients.

Cost-consequence analysis of an intervention for the management of neuropsychiatric symptoms in young-onset dementia: Results from the BEYOND-II study.

OBJECTIVE: To evaluate the cost-consequences of an intervention for the management of neuropsychiatric symptoms in nursing home residents with young-onset dementia. METHODS: A stepped wedge design was used. The intervention consisted of an educational program and a multidisciplinary care program and was implemented in 13 nursing homes from September 2015 to March 2017. Costs' outcomes included the time investment of the elderly care physician and health care psychologists regarding the management of neuropsychiatric symptoms, residents' psychotropic drug use, nursing staff absenteeism, and costs of the educational program. Composite cost measure contained the sum of costs of staff absenteeism, costs on psychotropic drugs, and costs of the educational program. Costs of time investment were investigated by comparing means. Costs of psychotropic drug use were analyzed with mixed models at resident level and as part of the composite cost measure on unit level. Staff absenteeism was also analyzed at unit level. RESULTS: Compared with care as usual, the mean costs of time invested decreased with €36.79 for the elderly care physician but increased with €46.05 for the health care psychologist in the intervention condition. Mixed model analysis showed no effect of the intervention compared with care as usual on the costs of psychotropic drug use, staff absenteeism, and the composite cost measure. The costs of the educational program were on average €174.13 per resident. CONCLUSION: The intervention did not result in increased costs compared with care as usual. Other aspects, such as the lack of a structured working method, should be taken into account when considering implementation of the intervention.

Cost-effectiveness of botulinum neurotoxin A versus surgery for drooling: a randomized clinical trial.

AIM: This study compared the cost-effectiveness of botulinum neurotoxin A (BoNT-A) injections with two-duct ligation of the submandibular glands as treatment for severe drooling after one treatment cycle. METHOD: The study was part of a larger, partly single-blinded, randomized clinical trial (trialregister.nl identifier NTR3537). Data were collected between 2012 and 2017. Evaluation was at 32 weeks after one treatment cycle. Fifty-seven patients with cerebral palsy or other neurological, non-progressive disorders and severe drooling classified as having a drooling frequency ≥3 or a drooling severity ≥2, in whom conservative treatment was deemed ineffective, were randomized to treatment by BoNT-A or two-duct ligation. An incremental cost-effectiveness ratio (ICER) was calculated using the success rates as the measure of benefit. Treatment success was defined as a decrease ≥50% from baseline to 32 weeks in the subjective visual analogue scale for the severity of drooling or the objective drooling quotient. RESULTS: Fifty-three patients were analysed (22 females, 31 males; mean age 11y, range 8-22y). Average costs for one treatment cycle, which included one BoNT-A injection, were €1929 (standard error 62) for BoNT-A and €3155 (standard error 99) for two-duct ligation. Treatment success was in favour of two-duct ligation (63% vs 27%; number needed to treat 3). The ICER was €34 per 1% gain in treatment success in favour of two-duct ligation versus BoNT-A. INTERPRETATION: The additional cost of two-duct ligation is to some extent offset by a larger treatment success rate compared with BoNT-A. WHAT THIS PAPER ADDS: Botulinum neurotoxin A (BoNT-A) is less expensive per percentage of success than two-duct ligation. The additional cost of two-duct ligation over BoNT-A is offset by greater treatment success.

Case-studies of displacement effects in Dutch hospital care.

BACKGROUND: Under a constrained health care budget, cost-increasing technologies may displace funds from existing health services. However, it is unknown what services are displaced and how such displacement takes place in practice. The aim of our study was to investigate how the Dutch hospital sector has dealt with the introduction of cost-increasing health technologies, and to present evidence of the relative importance of three main options to deal with cost-increases in health care: increased spending, increased efficiency, or displacement of other services. METHODS: We conducted six case-studies and interviewed 84 professionals with various roles and responsibilities (practitioners, heads of clinical department, board of directors, insurers, and others) to investigate how they experienced decision making in response to the cost pressure of cost-increasing health technologies. Transcripts were analyzed thematically in Atlas.ti on the basis of an item list. RESULTS: Direct displacement of high-value care due to the introduction of new technologies was not observed; respondents primarily pointed to increased spending and efficiency measures to accommodate the introduction of the cost-increasing technologies. Respondents found it difficult to identify the opportunity costs; partly due to limited transparency in the internal allocation of funds within a hospital. Furthermore, respondents experienced the entry of new technologies and cost-containment as two parallel processes that are generally not causally linked: cost containment was experienced as a permanent issue to level costs and revenues, independent from entry of new technologies. Furthermore, the way of financing was found important in displacement in the Netherlands, especially as there is a separate budget for expensive drugs. This budget pressure was found to be reallocated horizontally across departments, whereas the budget pressure of other services is primarily reallocated vertically within departments or divisions. Respondents noted that hospitals have reacted to budget pressures primarily through a narrowing in the portfolio of their services, and a range of (other) efficiency measures. The board of directors is central in these processes, insurers are involved only to a limited extent. CONCLUSIONS: Our findings indicate that new technologies were generally accommodated by greater efficiency and increased spending, and that hospitals sought savings or efficiency measures in response to cumulative cost pressures rather than in response to single cost-increasing technologies.

Cost-Effectiveness Analysis of Peripheral Nerve Field Stimulation as Add-On Therapy to Spinal Cord Stimulation in the Treatment of Chronic Low Back Pain in Failed Back Surgery Syndrome Patients.

OBJECTIVE: Presently, there is only limited evidence about the cost-effectiveness of peripheral nerve field stimulation (PNFS) and no evidence to date on the cost-effectiveness of PNFS as an add-on therapy to spinal cord stimulation (SCS). In a multicenter randomized controlled trial, PNFS as add-on therapy to SCS demonstrated clinical effectiveness in treating chronic low back pain in failed back surgery syndrome (FBSS) patients. We report here the cost-effectiveness of PNFS as additional therapy. MATERIALS AND METHODS: Cost-effectiveness analysis was performed from a health-care perspective using the general principles of cost-utility analysis, using empirical data from our multicenter randomized controlled trial on the effectiveness of hybrid SCS + PNFS on low back pain in FBSS patients, who were back pain non-responders to initial SCS-therapy, over a time-horizon of three months. Outcome measures were costs and quality-adjusted life-years (QALYs). Cost and QALYs were integrated using the net monetary benefit (NMB). Differences in costs, effects, and NMB were analyzed using multilevel regression. Uncertainty surrounding the NMB was presented by cost-effectiveness acceptability curves. RESULTS: A total of 52 patients implanted with both SCS and PNFS, randomly assigned to a group with PNFS either activated or inactive, completed the controlled part of the study. With mean total costs for the SCS + active PNFS group of €1813.86 (SD €109.78) versus €1103.64 (SD €123.43) for the SCS + inactive PNFS group at three months, we found an incremental cost-utility ratio of €25.311 per QALY gained and a probability being cost-effective of more than 80% given a willingness to pay for a QALY of about €40.000. CONCLUSIONS: From a Dutch national health-care context, when the willingness to pay threshold is up to 60.000 Euros per QALY, PNFS as an add-on therapy to SCS for the treatment of low back pain in FBSS patients has a high probability of being cost-effective.

Learning Curve and Associated Morbidity of Minimally Invasive Esophagectomy: A Retrospective Multicenter Study.

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.

The marginal benefits of healthcare spending in the Netherlands: Estimating cost-effectiveness thresholds using a translog production function.

New technologies may displace existing, higher-value care under a fixed budget. Countries aim to curtail adoption of low-value technologies, for example, by installing cost-effectiveness thresholds. Our objective is to estimate the opportunity cost of hospital care to identify a threshold value for the Netherlands. To this aim, we combine claims data, mortality data and quality of life questionnaires from 2012 to 2014 for 11,000 patient groups to obtain quality-adjusted life-year (QALY) outcomes and spending. Using a fixed effects translog model, we estimate that a 1% increase in hospital spending on average increases QALY outcomes by 0.2%. This implies a threshold of €73,600 per QALY, with 95% confidence intervals ranging from €53,000 to €94,000 per QALY. The results stipulate that new technologies with incremental cost effectiveness ratios exceeding the Dutch upper reference value of €80,000 may indeed displace more valuable care.

Evaluation of two vaginal, uterus sparing operations for pelvic organ prolapse: modified Manchester operation (MM) and sacrospinous hysteropexy (SSH), a study protocol for a multicentre randomized non-inferiority trial (the SAM study).

BACKGROUND: Pelvic organ prolapse (POP) affects up to 40% of parous women which adversely affects the quality of life. During a life time, 20% of all women will undergo an operation. In general the guidelines advise a vaginal operation in case of uterine descent: hysterectomy with uterosacral ligament plication (VH), sacrospinous hysteropexy (SSH) or a modified Manchester operation (MM). In the last decade, renewed interest in uterus sparing techniques has been observed. Previous studies have shown non-inferiority between SSH and VH. Whether or not SSH and MM are comparable concerning anatomical and functional outcome is still unknown. The practical application of both operations is at least in The Netherlands a known cause of practice pattern variation (PPV). To reveal any difference between both techniques the SAM-study was designed. METHODS: The SAM-study is a randomized controlled multicentre non-inferiority study which compares SSH and MM. Women with symptomatic POP in any stage, uterine descent and POP-Quantification (POP-Q) point D at ≤ minus 1 cm are eligible. The primary outcome is the composite outcome at two years of absence of prolapse beyond the hymen in any compartment, the absence of bulge symptoms and absence of reoperation for pelvic organ prolapse. Secondary outcomes are hospital parameters, surgery related morbidity/complications, pain perception, further treatments for prolapse or urinary incontinence, POP-Q anatomy in all compartments, quality-of-life, sexual function, and cost-effectiveness. Follow-up takes place at 6 weeks, 12 and 24 months. Additionally at 12 weeks, 6 and 9 months cost-effectiveness will be assessed. Validated questionnaires will be used and gynaecological examination will be performed. Analysis will be performed following the intention-to-treat and per protocol principle. With a non-inferiority margin of 9% and an expected loss to follow-up of 10%, 424 women will be needed to prove non-inferiority with a confidence interval of 95%. DISCUSSION: This study will evaluate the effectiveness and costs of SSH versus MM in women with primary POP. The evidence will show whether the existing PPV is detrimental and a de-implementation process regarding one of the operations is needed. TRIAL REGISTRATION: Dutch Trial Register (NTR 6978, http://www.trialregister.nl ). Date of registration: 29 January 2018. Prospectively registered.

Discontinuation of antidepressant medication in primary care supported by monitoring plus mindfulness-based cognitive therapy versus monitoring alone: design and protocol of a cluster randomized controlled trial.

BACKGROUND: Antidepressant use continues to rise, mainly explained by an increase in the proportion of patients receiving long term treatment. Although treatment guidelines recommend discontinuation after sustained remission, discontinuing antidepressants appears to be challenging for both patients and general practitioners (GPs). Mindfulness-Based Cognitive Therapy (MBCT) is an effective intervention that reduces the risk of relapse in recurrent depression and might facilitate discontinuation by teaching patients to cope with withdrawal symptoms and fear of relapse. The current study aims to investigate the effectiveness of the combination of Supported Protocolized Discontinuation (SPD) and MBCT in comparison with SPD alone in successful discontinuation of long-term use of antidepressants in primary care. METHODS: This study involves a cluster-randomized controlled trial conducted in primary care patients with long-term use antidepressants with baseline and 6, 9 and 12 months follow-up assessments. Patients choosing to discontinue their medication will be offered a combination of SPD and MBCT or SPD alone. Our primary outcome will be full discontinuation of antidepressant medication (= 0 mg) within 6 months after baseline assessment. Secondary outcome measures will be the severity of withdrawal symptoms, symptoms of depression and anxiety, psychological well-being, quality of life and medical and societal costs. DISCUSSION: In theory, stopping antidepressant medication seems straightforward. In practice however, patients and their GPs appear reluctant to initiate and accomplish this process. Both patients and professionals are in need of appropriate tools and information to better support the process of discontinuing antidepressant medication. TRIAL REGISTRATION: ClinicalTrials.gov PRS ID: NCT03361514 retrospectively registered October 2017.

Pain Exposure Physical Therapy versus conventional treatment in complex regional pain syndrome type 1-a cost-effectiveness analysis alongside a randomized controlled trial.

OBJECTIVE: To analyze cost-effectiveness of Pain Exposure Physical Therapy compared to conventional treatment alongside a randomized controlled trial (NCT00817128) in patients with complex regional pain syndrome type 1, where no clinical difference was shown between the two groups in an intention-to-treat analysis. DESIGN: Randomized controlled trial with 9 months follow-up. SETTING: Patients were recruited from hospitals and general practitioners in the region around a university hospital. SUBJECTS: A total of 56 patients, 45 (80.4%) female, were randomized. About 4 patients in the intervention and 11 patients in the conventional group switched groups. The mean (SD) age was 44.3 (16.6) years, and in 37 (66.1%) patients, the upper extremity was affected. INTERVENTIONS: Patients received either Pain Exposure Physical Therapy (maximum of five sessions), or conventional treatment conforming with the Dutch multidisciplinary guideline. MAIN MEASURES: For the economic evaluation difference between the groups in health-related quality of life (quality-adjusted life years (QALYs)), and the clinical outcomes Impairment level Sum Score-Restricted Version and Pain Disability was determined based on the intention-to-treat analysis as well as differences in both healthcare-related costs and travel expenses. Cost-effectiveness planes were constructed using bootstrapping to compare effects and costs. RESULTS: No significant effects were found for QALYs (mean difference = -0.02; 95% confidence interval (CI) -0.10 to 0.04) and clinical outcomes. A cost minimization analysis showed a significant difference in costs between groups. The conventional treatment was 64% more expensive than the Pain Exposure Physical Therapy. CONCLUSION: This economic analysis shows that Pain Exposure Physical Therapy compared to conventional treatment is cost-effective.

Early treatment versus expectative management of patent ductus arteriosus in preterm infants: a multicentre, randomised, non-inferiority trial in Europe (BeNeDuctus trial).

BACKGROUND: Much controversy exists about the optimal management of a patent ductus arteriosus (PDA) in preterm infants, especially in those born at a gestational age (GA) less than 28 weeks. No causal relationship has been proven between a (haemodynamically significant) PDA and neonatal complications related to pulmonary hyperperfusion and/or systemic hypoperfusion. Although studies show conflicting results, a common understanding is that medical or surgical treatment of a PDA does not seem to reduce the risk of major neonatal morbidities and mortality. As the PDA might have closed spontaneously, treated children are potentially exposed to iatrogenic adverse effects. A conservative approach is gaining interest worldwide, although convincing evidence to support its use is lacking. METHODS: This multicentre, randomised, non-inferiority trial is conducted in neonatal intensive care units. The study population consists of preterm infants (GA < 28 weeks) with an echocardiographic-confirmed PDA with a transductal diameter > 1.5 mm. Early treatment (between 24 and 72 h postnatal age) with the cyclooxygenase inhibitor (COXi) ibuprofen (IBU) is compared with an expectative management (no intervention intended to close a PDA). The primary outcome is the composite of mortality, and/or necrotising enterocolitis (NEC) Bell stage ≥ IIa, and/or bronchopulmonary dysplasia (BPD) defined as the need for supplemental oxygen, all at a postmenstrual age (PMA) of 36 weeks. Secondary outcome parameters are short term sequelae of cardiovascular failure, comorbidity and adverse events assessed during hospitalization and long-term neurodevelopmental outcome assessed at a corrected age of 2 years. Consequences regarding health economics are evaluated by cost effectiveness analysis and budget impact analysis. DISCUSSION: As a conservative approach is gaining interest, we investigate whether in preterm infants, born at a GA less than 28 weeks, with a PDA an expectative management is non-inferior to early treatment with IBU regarding to the composite outcome of mortality and/or NEC and/or BPD at a PMA of 36 weeks. TRIAL REGISTRATION: This trial is registered with the Dutch Trial Register NTR5479 (registered on 19 October 2015), the registry sponsored by the United States National Library of Medicine Clinicaltrials.gov NCT02884219 (registered May 2016) and the European Clinical Trials Database EudraCT 2017-001376-28 .

Cost-effectiveness of a multicomponent primary care program targeting frail elderly people.

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.