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.

Cost Effectiveness of Rectal Culture-based Antibiotic Prophylaxis in Transrectal Prostate Biopsy: The Results from a Randomized, Nonblinded, Multicenter Trial.

Background: Culture-based antibiotic prophylaxis is a plausible strategy to reduce infections after transrectal prostate biopsy (PB) related to fluoroquinolone-resistant pathogens. Objective: To assess the cost effectiveness of rectal culture-based prophylaxis compared with empirical ciprofloxacin prophylaxis. Design setting and participants: The study was performed alongside a trial in 11 Dutch hospitals investigating the effectiveness of culture-based prophylaxis in transrectal PB between April 2018 and July 2021 (trial registration number: NCT03228108). Intervention: Patients were 1:1 randomized for empirical ciprofloxacin prophylaxis (oral) or culture-based prophylaxis. Costs for both prophylactic strategies were determined for two scenarios: (1) all infectious complications within 7 d after biopsy and (2) culture-proven Gram-negative infections within 30 d after biopsy. Outcome measurements and statistical analysis: Differences in costs and effects (quality-adjusted life-years [QALYs]) were analyzed from a healthcare and societal perspective (including productivity losses, and travel and parking costs) using a bootstrap procedure presenting uncertainty surrounding the incremental cost-effectiveness ratio in a cost-effectiveness plane and acceptability curve. Results and limitations: For the 7-d follow-up period, culture-based prophylaxis (n = 636) was €51.57 (95% confidence interval [CI] 6.52-96.63) more expensive from a healthcare perspective and €16.95 (95% CI -54.29 to 88.18) from a societal perspective than empirical ciprofloxacin prophylaxis (n = 652). Ciprofloxacin-resistant bacteria were detected in 15.4%. Extrapolating our data, from a healthcare perspective, 40% ciprofloxacin resistance would lead to equal cost for both strategies. Results were similar for the 30-d follow-up period. No significant differences in QALYs were observed. Conclusions: Our results should be interpreted in the context of local ciprofloxacin resistance rates. In our setting, from a healthcare perspective, culture-based prophylaxis was significantly more expensive than empirical ciprofloxacin prophylaxis. From a societal perspective, culture-based prophylaxis was somewhat more cost effective against the threshold value customary for the Netherlands (€80.000). Patient summary: Culture-based prophylaxis in transrectal prostate biopsy was not associated with reduced costs compared with empirical ciprofloxacin prophylaxis.

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.

Implementing a Personalized Physical Therapy Approach (Coach2Move) Is Effective in Increasing Physical Activity and Improving Functional Mobility in Older Adults: A Cluster-Randomized, Stepped Wedge Trial.

OBJECTIVE: The purpose of this study was to assess whether the superior cost-effectiveness of a personalized physical therapy approach (Coach2Move)-which was demonstrated in a previous trial compared with usual care physical therapy (UCP)-can be replicated in daily clinical practice. METHODS: A multicenter, cluster-randomized, stepped wedge trial with 4 clusters consisting of 4 physical therapist practices in the Netherlands was used to compare a personalized physical therapy approach to elicit physical activity (Coach2Move) versus care as usual. Multilevel analyses for effectiveness were conducted for the amount of physical activity (Longitudinal Aging Study Amsterdam Physical Activity Questionnaire) and functional mobility (Timed "Up & Go" Test) at 3, 6 (primary outcome), and 12 months' follow-up. Secondary outcomes were level of frailty (Evaluative Frailty Index for Physical Activity), perceived effect (Global Perceived Effect and Patient-Specific Complaints Questionnaires), quality of life (Euro Quality of Life-5 Dimensions-5 Levels [EQ-5D-5L]), and health care expenditures. RESULTS: The 292 community-dwelling older adults with mobility problems visiting physical therapists were included in either the Coach2Move (n = 112; mean [SD] age = 82 [5] years; 60% female) or UCP (n = 180; mean [SD] age = 81 (6) years; 62% female) section of the trial. At baseline, Coach2Move participants were less physically active compared with UCP participants (mean difference = -198; 95% CI = -90 to -306 active minutes). At 6 months, between-group mean differences [95% CI] favored Coach2Move participants on physical activity levels (297 [83 to 512] active minutes), functional mobility (-14.2 [-21 to -8]) seconds), and frailty levels (-5 [-8 to -1] points). At 12 months, the physical activity levels of Coach2Move participants further increased, and frailty levels and secondary outcomes remained stable, whereas outcomes of UCP participants decreased. After the Coach2Move implementation strategy, physical therapists utilized significantly fewer treatment sessions compared with before the implementation (15 vs 22). Anticipated cost savings were not observed. CONCLUSION: This study replicated the results of an earlier trial and shows that Coach2Move leads to better mid- and long-term outcomes (physical activity, functional mobility, level of frailty) in fewer therapy sessions compared with UCP. Based on these and earlier findings, the implementation of Coach2Move in physical therapist practice is recommended. IMPACT: This article describes the implementation of the Coach2Move approach, a treatment strategy that has proven to be cost-effective in a previously conducted randomized controlled trial. Implementation of Coach2Move in a real-life setting allowed an evaluation of the effects in a clinically relevant population. Coach2Move has been shown to increase physical activity, improve functional mobility, and reduce frailty more effectively compared with UCP therapy and therefore has application for physical therapists working with older adults in daily clinical practice. LAY SUMMARY: Coach2Move is a new physical therapy approach for older adults. Implementation of Coach2Move in daily clinical practice can help people better outcomes over a longer period of time against similar costs compared with regular physical therapy.

MiCare study, an evaluation of structured, multidisciplinary and personalised post-ICU care on physical and psychological functioning, and quality of life of former ICU patients: a study protocol of a stepped-wedge cluster randomised controlled trial.

INTRODUCTION: Over 70% of the intensive care unit (ICU) survivors suffer from long-lasting physical, mental and cognitive problems after hospital discharge. Post-ICU care is recommended by international guidelines, but evidence for cost-effectiveness lacks. The aim of this study is to evaluate the clinical effectiveness and cost-effectiveness of structured, multidisciplinary and personalised post-ICU care versus usual care on physical and psychological functioning and health-related quality of life (HRQoL) of ICU survivors, 1- and 2-year post-ICU discharge. METHODS AND ANALYSIS: The MONITOR-IC post-ICU care study (MiCare study) is a multicentre stepped-wedge randomised controlled trial conducted in five hospitals. Adult patients at high risk for critical illness-associated morbidity post-ICU will be selected and receive post-ICU care, including an invitation to the post-ICU clinic 3 months after ICU discharge. A personalised long-term recovery plan tailored to patients' reported outcome measures will be made. 770 (intervention) and 1480 (control) patients will be included. Outcomes are 1- and 2-year HRQoL (EuroQol Instrument (EQ-5D-5L)), physical (fatigue and new physical problems), mental (anxiety, depression and post-traumatic stress disorder), and cognitive symptoms and cost-effectiveness. Medical data will be retrieved from patient records and cost data from health insurance companies. ETHICS AND DISSEMINATION: Due to the lack of evidence, Dutch healthcare insurers do not reimburse post-ICU care. Therefore, evaluation of cost-effectiveness and integration in guidelines supports the evidence. Participation of several societies for physicians, nurses, paramedics, and patients and relatives in the project team increases the support for implementation of the intervention in clinical practice. Patients and relatives will be informed by the patient associations, hospitals and professional associations. Informing healthcare insurers about this project's results is important for the consideration for inclusion of post-ICU care in Dutch standard health insurance. The study is approved by the Radboud University Medical Centre research ethics committee (2021-13125). TRIAL REGISTRATION NUMBER: NCT05066984.

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.

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.

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.

What is the evidence base of used aggregated antibiotic resistance percentages to change empirical antibiotic treatment? A scoping review.

OBJECTIVES: Antibiotic resistance requires continuous monitoring by experts to decide whether empirical antibiotic therapies (EATs) should be replaced by alternative antibiotics. The exact moment and criteria for this change are unclear and generally based on consensus between experts. This scoping review aims to identify from the literature the resistance thresholds used for a change in EAT and the criteria on which they are based. METHODS: Scoping review for which a comprehensive structured literature search was conducted. Rayyan, software for systematic reviews, was used for the screening of abstracts and titles. Data sources were Pubmed and a hand-search of reference lists and grey literature. Papers were eligible if they concerned any type of bacterial infectious disease and mentioned or defined antibiotic resistance thresholds for decision-making purposes for EAT. The inclusion and analysis of articles was done by two researchers; any conflicts were resolved through discussion or by consulting a third reviewer. RESULTS: We identified 3146 unique papers. Following title/abstract screening, 125 papers were comprehensively read, and 16 papers were included. The included papers gave thresholds for urinary tract infections, respiratory tract infections, meningitis, skin and soft tissue infections, gonorrhoea, and bone and joint infections. Six criteria were found that were commonly used to base the thresholds on. These were: disease severity, efficacy of treatment, adverse drug events, risk of Clostridioides difficile infection, costs, and increased resistance. The number of criteria used to define each threshold varied from one to six between papers. CONCLUSIONS: The thresholds used for EATs are few, commonly based on expert opinion estimates, and can therefore have broad ranges. Used criteria underlying reported thresholds are heterogenous and require standardization. Considering the rising trend in resistance, there is a clear need for rigid tools to determine thresholds in order to support guideline development with the best and timely evidence.

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.

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.

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.

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 .

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.