Pre-hospital rule-out of non-ST-segment elevation acute coronary syndrome by a single troponin: final one-year outcomes of the ARTICA randomised trial.

BACKGROUND AND AIMS: The healthcare burden of acute chest pain is enormous. In the randomised ARTICA trial we showed that pre-hospital identification of low-risk patients and rule-out of non-ST-segment elevation acute coronary syndrome (NSTE-ACS) with point-of-care (POC) troponin measurement reduces 30-day healthcare costs with low major adverse cardiac events (MACE) incidence. Here we present the final one-year results of the ARTICA trial. METHODS: Low-risk patients with suspected NSTE-ACS were randomised to pre-hospital rule-out with POC troponin measurement or emergency department (ED) transfer. Primary one-year outcome was healthcare costs. Secondary outcomes were safety, quality of life (QoL) and cost-effectiveness. Safety was defined as one-year MACE, consisting of ACS, unplanned revascularisation or all-cause death. QoL was measured with EuroQol-5D-5 L questionnaires. Cost-effectiveness was defined as one-year healthcare costs difference per QoL difference. RESULTS: Follow-up was completed in all 863 patients. Healthcare costs were significantly lower in the pre-hospital strategy (€1932±€2784 vs €2649±€2750), mean difference €717 (95% confidence interval [CI] €347 to €1087; P < 0.001). In the total population, one-year MACE rate was comparable between groups (5.1% [22/434] in the pre-hospital strategy vs 4.2% [18/429] in the ED strategy; P = 0.54). In the ruled-out ACS population, one-year MACE remained low (1.7% [7/419] vs 1.4% [6/417]), risk difference 0.2% (95% CI -1.4% to 1.9%; P = 0.79). QoL showed no significant difference between strategies. CONCLUSIONS: Pre-hospital rule-out of NSTE-ACS with POC troponin testing in low-risk patients is cost-effective, expressed by a sustainable healthcare costs reduction and no significant effect on QoL. One-year MACE remained low for both strategies. Trial registration: Clinicaltrials.gov: NCT05466591, International Clinical Trials Registry Platform: NTR7346.

Differences in risk and costs between prehospital identified low-risk men and women with chest pain.

OBJECTIVE: Prehospital rule-out of non-ST-segment elevation acute coronary syndrome (NSTE-ACS) in low-risk patient with a point-of-care troponin measurement reduces healthcare costs with similar safety to standard transfer to the hospital. Risk stratification is performed identical for men and women, despite important differences in clinical presentation, risk factors and age between men and women with NSTE-ACS. Our aim was to compare safety and healthcare costs between men and women in prehospital identified low-risk patients with suspected NSTE-ACS. METHODS: In the Acute Rule-out of non-ST-segment elevation acute coronary syndrome in the (pre)hospital setting by HEART (History, ECG, Age, Risk factors and Troponin) score assessment and a single poInt of CAre troponin randomised trial, the HEAR (History, ECG, Age and Risk factors) score was assessed by ambulance paramedics in suspected NSTE-ACS patients. Low-risk patients (HEAR score ≤3) were included. In this substudy, men and women were compared. Primary endpoint was 30-day major adverse cardiac events (MACE), secondary endpoints were 30-day healthcare costs and the scores for the HEAR score components. RESULTS: A total of 863 patients were included, of which 495 (57.4%) were women. Follow-up was completed in all patients. In the total population, MACE occurred in 6.8% of the men and 1.6% of the women (risk ratio (RR) 4.2 (95% CI 1.9 to 9.2, p<0.001)). In patients with ruled-out ACS (97% of the total population), MACE occurred in 1.4% of the men and in 0.2% of the women (RR 7.0 (95% CI 2.0 to 14.2, p<0.001). Mean healthcare costs were €504.55 (95% CI €242.22 to €766.87, p<0.001) higher in men, mainly related to MACE. CONCLUSIONS: In a prehospital population of low-risk suspected NSTE-ACS patients, 30-day incidence of MACE and MACE-related healthcare costs were significantly higher in men than in women. TRIAL REGISTRATION NUMBER: NCT05466591.

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 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.

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.

Early Eculizumab Withdrawal in Patients With Atypical Hemolytic Uremic Syndrome in Native Kidneys Is Safe and Cost-Effective: Results of the CUREiHUS Study.

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

Cost-Effectiveness of Parallel Versus Sequential Testing of Genetic Aberrations for Stage IV Non-Small-Cell Lung Cancer in the Netherlands.

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.

Economic evaluation of a randomized controlled trial comparing mifepristone and misoprostol with misoprostol alone in the treatment of early pregnancy loss.

BACKGROUND: In case of early pregnancy loss (EPL) women can either choose for expectant, medical or surgical management. One week of expectant management is known to lead to spontaneous abortion in approximately 50% of women. Medical treatment with misoprostol is known to be safe and less costly than surgical management, however less effective in reaching complete evacuation of the uterus. Recently, a number of trials showed that prompt treatment with the sequential combination of mifepristone with misoprostol is superior to misoprostol alone in reaching complete evacuation. In this analysis we evaluate whether the sequential combination of mifepristone with misoprostol is cost-effective compared to misoprostol alone, in the treatment of EPL. METHODS AND FINDINGS: A cost-effectiveness analysis (CEA) from a healthcare perspective was performed alongside a randomised controlled trial (RCT) in which standard treatment with misoprostol only was compared with a combination of mifepristone and misoprostol, in women with EPL after a minimum of one week of unsuccessful management. A limited societal perspective scenario was added. This RCT, the Triple M trial, was a multicentre, randomized, double-blinded, placebo-controlled trial executed at 17 hospitals in the Netherlands. The trial started on June 27th 2018, and ended prematurely in January 2020 due to highly significant outcomes from the predefined interim-analysis. We included 351 women with a diagnosis of EPL between 6 and 14 weeks gestation after at least one week of unsuccessful expectant management. They were randomized between double blinded pre-treatment with oral mifepristone 600mg (N = 175) or placebo (N = 176) taken on day one, both followed by misoprostol orally. In both groups, an intention-to-treat analysis was performed for 172 patients, showing a significant difference in success rates between participants treated with mifepristone and misoprostol versus those treated with misoprostol alone (79.1% vs 58.7% respectively). In this cost-effective analysis we measured the direct, medical costs related to treatment (planned and unplanned hospital visits, medication, additional treatment) and indirect costs based on the IMTA Productivity Cost Questionnaire (iPCQ). Quality Adjusted Life Years (QALY's) were calculated from participants' scores on the SF-36 questionnaires sent digitally at treatment start, and one, two and six weeks later. We found medical treatment with placebo followed by misoprostol to be 26% more expensive compared to mifepristone followed by misoprostol (p = 0.001). Mean average medical costs per patient were significantly lower in the mifepristone group compared to the placebo group (€528.95 ± 328.93 vs €663.77 ± 456.03, respectively; absolute difference €134.82, 95% CI 50,46-219,18, p = 0.002). Both indirect costs and QALY's were similar between both groups. CONCLUSION: The sequential combination of mifepristone with misoprostol is cost-effective compared with misoprostol alone, for treatment of EPL after a minimum of one week of unsuccessful expectant management.

Cost Analysis From a Randomized Comparison of Immediate Versus Delayed Angiography After Cardiac Arrest.

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

Technical efficiency evaluation of colorectal cancer care for older patients in Dutch hospitals.

BACKGROUND: Preoperative colorectal cancer care pathways for older patients show considerable practice variation between Dutch hospitals due to differences in interpretation and implementation of guideline-based recommendations. This study aims to report this practice variation in preoperative care between Dutch hospitals in terms of technical efficiency and identifying associated factors. METHODS: Data on preoperative involvement of geriatricians, physical therapists and dieticians and the clinicians' judgement on prehabilitation implementation were collected using quality indicators and questionnaires among colorectal cancer surgeons and specialized nurses. These data were combined with registry-based data on postoperative outcomes obtained from the Dutch Surgical Colorectal Audit for patients aged ≥75 years. A two-stage data envelopment analysis (DEA) approach was used to calculate bias-corrected DEA technical efficiency scores, reflecting the extent to which a hospital invests in multidisciplinary preoperative care (input) in relation to postoperative outcomes (output). In the second stage, hospital care characteristics were used in a bootstrap truncated regression to explain variations in measured efficiency scores. RESULTS: Data of 25 Dutch hospitals were analyzed. There was relevant practice variation in bias-corrected technical efficiency scores (ranging from 0.416 to 0.968) regarding preoperative colorectal cancer surgery. The average efficiency score of hospitals was significantly different from the efficient frontier (p = <0.001). After case-mix correction, higher technical efficiency was associated with larger practice size (p = <0.001), surgery performed in a general hospital versus a university hospital (p = <0.001) and implementation of prehabilitation (p = <0.001). CONCLUSION: This study showed considerable variation in technical efficiency of preoperative colorectal cancer care for older patients as provided by Dutch hospitals. In addition to higher technical efficiency in high-volume hospitals and general hospitals, offering a care pathway that includes prehabilitation was positively related to technical efficiency of hospitals offering colorectal cancer care.

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 .

Telemedicine in the management of rheumatoid arthritis: maintaining disease control with less health-care utilization.

OBJECTIVES: We aimed to evaluate the use of an eHealth platform and a self-management outpatient clinic in patients with RA in a real-world setting. The effects on health-care utilization and disease activity were studied. METHODS: Using hospital data of patients with RA between 2014 and 2019, the use of an eHealth platform and participation in a self-management outpatient clinic were studied. An interrupted time series analysis compared the period before and after the introduction of the eHealth platform. The change in trend (relative to the pre-interruption trend) for the number of outpatient clinic visits and the DAS for 28 joints (DAS28) were determined for several scenarios. RESULTS: After implementation of the platform in April 2017, the percentage of patients using it was stable at ∼37%. On average, the users of the platform were younger, more highly educated and had better health outcomes than the total RA population. After implementation of the platform, the mean number of quarterly outpatient clinic visits per patient decreased by 0.027 per quarter (95% CI: -0.045, -0.08, P = 0.007). This was accompanied by a significant decrease in DAS28 of 0.056 per quarter (95% CI: -0.086, -0025, P = 0.001). On average, this resulted in 0.955 fewer visits per patient per year and a reduction of 0.503 in the DAS28. CONCLUSION: The implementation of remote patient monitoring has a positive effect on health-care utilization, while maintaining low disease activity. This should encourage the use of this type of telemedicine in the management of RA, especially while many routine outpatient clinic visits are cancelled owing to COVID-19.

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.

Does Etanercept Biosimilar Prescription in a Rheumatology Center Bend the Medication Cost Curve?

OBJECTIVE: The market entry of biosimilars is expected to bring budgetary relief. Our objective was to determine how the introduction of biosimilars influences medication costs in patients with rheumatoid arthritis (RA) and which patients gain access to biologics due to the availability of biosimilars. METHODS: Using hospital data of patients with RA between 2014 and 2018, an interrupted time series was performed. The interruption in the time series was placed at June 2016 (i.e., the introduction of the etanercept biosimilar). The changes in trends for rheumatic medication costs before and after the interruption were measured. Secondary analyses focused on explaining these trends. RESULTS: In the first quarter after the interruption, there was a decrease in total costs for biologic users of -€63,020 (95% CI -€96,487 to -€29,553, P = 0.001). The postinterruption trend did not differ from the preinterruption trend (95% CI -€6695 to €6715, P = 0.998) and after 3 quarters, the medication costs were back at the interruption level. After the interruption, the average cost per biologic user decreased by -€370 (95% CI -€602 to -€138, P = 0.005), followed by a quarterly decrease (relative to the preinterruption trend; 95% CI -€86 to -€14, P = 0.010), bending the average cost curve. The percentage of patients being treated with biologics increased in postinterruption by 0.50 percentage points quarterly (95% CI 0.38-0.62, P < 0.001). Also, the average age at the start of the first biologic increased after the interruption (P = 0.057). CONCLUSION: The average cost per patient treated with biologics decreased after the introduction of biosimilars with a persistent trend. However, the budgetary relief due to market entry of biosimilars vanished quickly due to an increase in patients treated with biologics.

One-year results after transitioning from etanercept originator to biosimilar in a setting promoting shared decision-making in rheumatology.

OBJECTIVE: The aim was to study the effect of non-mandatory transitioning from etanercept originator to etanercept biosimilar on retention rates in a setting promoting shared decision-making. METHODS: In 2016, all patients treated with etanercept originator and stable disease at the Rheumatology department in Bernhoven were offered transitioning to etanercept biosimilar by an opt-in approach. A historical cohort of patients treated with etanercept originator in 2015 was identified as the control group. Etanercept discontinuation was compared between the cohorts using Cox regression. To study the nocebo effect, reasons for discontinuation were categorized into objective reasons (e.g. laboratory abnormalities, increase in swollen joint count, allergic reaction) and subjective health complaints (symptoms perceptible only to the patient, e.g. tiredness, arthralgia). An adjusted Kaplan-Meier curve for retention of the etanercept biosimilar was made, censoring subjective health complaints as the reason for discontinuation. RESULTS: Seventy of the 79 patients eligible for transitioning agreed to transition (89%). The 1-year crude retention rate of etanercept in the transition cohort was 73% (95% CI: 0.62, 0.83), compared with a retention rate of 89% (95% CI: 0.81, 0.95) in the historical cohort (P = 0.013). This resulted in a higher risk of treatment discontinuation in the transition cohort (adjusted hazard ratio = 2.73; 95% CI: 1.23, 6.05, P = 0.01). After adjusting for the nocebo effect, the cohorts had comparable retention rates (86 vs 89%, P = 0.51). CONCLUSION: Non-mandatory transition from etanercept originator to its biosimilar using an opt-in approach in a setting promoting shared decision-making resulted in a higher discontinuation of etanercept compared with the historical cohort. This could be attributed largely to the nocebo effect.

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 .

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.

Selective Intensive Care Unit Admission After Adult Supratentorial Tumor Craniotomy: Complications, Length of Stay, and Costs.

BACKGROUND: Admitting patients to an intensive care or medium care unit (ICU/MCU) after adult supratentorial tumor craniotomy remains common practice even though some studies have suggested lower level care is sufficient for selected patients. We have introduced a "no ICU, unless" policy for tumor craniotomy patients. OBJECTIVE: To provide a quieter postoperative environment for patients, reduce the burden on the ICU department, and to evaluate whether costs can be reduced. METHODS: A cohort study was performed comparing patients that underwent tumor craniotomy for supratentorial tumors during 1 yr after introduction (n = 109) of the new policy with the year before (n = 107). Rate of complications was evaluated, as was the length of stay and patient satisfaction using qualitative evaluation. Finally, costs were evaluated comparing the situation before and after implementation of the new protocol. RESULTS: A reduction in ICU/MCU admittance from 64% to 24% of patients was found resulting in 13.3% cost reduction (€1950 per case), without increasing the length of stay at the ward. The length of stay in the hospital was similar. Complications were significantly reduced after implementing the new policy (0.98 vs 0.53 per patient, P = .003). Patients that were interviewed after the new policy reported feeling safe and at ease at the ward. CONCLUSION: Changing our policy from "ICU, unless" to "no ICU, unless" reduced complication rates and length of stay in the hospital while keeping patients satisfied. Hospital costs related to the admission have been significantly reduced by the new policy.

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.