Efficacy of a nurse-led sexual rehabilitation intervention for women with gynaecological cancers receiving radiotherapy: results of a randomised trial.

BACKGROUND: The multicentre randomised SPARC trial evaluated the efficacy of a nurse-led sexual rehabilitation intervention on sexual functioning, distress, dilator use, and vaginal symptoms after radiotherapy for gynaecological cancers. METHODS: Eligible women were randomised to the rehabilitation intervention or care-as-usual. Four intervention sessions were scheduled over 12 months, with concurrent validated questionnaires and clinical assessments. Primary outcome was the Female Sexual Function Index (FSFI). A generalised-mixed-effects model compared groups over time. RESULTS: In total, 229 women were included (n = 112 intervention; n = 117 care-as-usual). No differences in FSFI total scores were found between groups at any timepoint (P = 0.37), with 12-month scores of 22.57 (intervention) versus 21.76 (care-as-usual). The intervention did not significantly improve dilator use, reduce sexual distress or vaginal symptoms compared to care-as-usual. At 12 months, both groups had minimal physician-reported vaginal stenosis; 70% of women were sexually active and reported no or mild vaginal symptoms. After radiotherapy and brachytherapy, 85% (intervention) versus 75% (care-as-usual) of participants reported dilation twice weekly. DISCUSSION: Sexual rehabilitation for women treated with combined (chemo)radiotherapy and brachytherapy improved before and during the SPARC trial, which likely contributed to comparable study groups. Best practice involves a sexual rehabilitation appointment 1 month post-radiotherapy, including patient information, with dilator guidance, preferably by a trained nurse, and follow-up during the first year after treatment. CLINICAL TRIAL REGISTRATION: NCT03611517.

Effectiveness of longstanding exercise therapy compared with usual care for people with rheumatoid arthritis and severe functional limitations: a randomised controlled trial.

OBJECTIVES: To compare the effectiveness of longstanding (>52 weeks), supervised exercise therapy with usual care in adults with rheumatoid arthritis (RA) and severe functional limitations. METHODS: Participants were randomised 1:1 to the intervention (individualised goal-setting, active exercises, education and self-management regarding physical activity) or usual care. Primary endpoint was the change in the Patient-Specific Complaints activity ranked 1 (PSC1, 0-10) at 52 weeks. Secondary endpoints included the PSC activities ranked 2 and 3 (PSC2, PSC3), Health Assessment Questionnaire-Disability Index (HAQ-DI), Rheumatoid Arthritis Quality of Life Questionnaire (RAQoL), 6-minute walk test (6MWT), Patient Reported Outcome Measurement Information System Physical Function-10 (PROMIS PF-10) and the Short Form-36 Physical and Mental Component Summary Scales (SF-36 PCS and MCS). (Serious) Adverse events (AEs) were recorded. Measurements were done by blinded assessors. Analyses at 52 weeks were based on the intention-to-treat principle. RESULTS: In total, 217 people (90% female, age 58.8 (SD 12.9) years) were randomised (n=104 intervention, n=98 usual care available for analyses). At 52 weeks, the improvement of the PSC1 was significantly larger in the intervention group (mean difference (95% CI) -1.7 (-2.4, -1.0)). Except for the SF-36 MCS, all secondary outcomes showed significantly greater improvements favouring the intervention (PSC2 -1.8 (-2.4, -1.1), PSC3 -1.7 (-2.4, -1.0), PROMIS PF-10 +3.09 (1.80, 4.38), HAQ-DI -0.17 (-0.29, -0.06), RAQoL -2.03 (-3.39, -0.69), SF-36 PCS +3.83 (1.49, 6.17) and 6MWT +56 (38, 75) m). One mild, transient AE occurred in the intervention group. CONCLUSION: Longstanding, supervised exercise therapy was more effective than usual care in people with RA and severe functional limitations. TRIAL REGISTRATION NUMBER: Netherlands Trial Register (NL8235), included in the International Clinical Trial Registry Platform (https://trialsearch.who.int/Trial2.aspx?TrialID=NL8235).

One-year effectiveness of long-term exercise therapy in people with axial spondyloarthritis and severe functional limitations.

OBJECTIVE: To evaluate the effectiveness of long-term, personalized, supervised exercise therapy on functional ability compared with usual care in people with axial spondyloarthritis (axSpA) and severe functional limitations. METHODS: Participants were randomly 1:1 assigned to the intervention(maximal 64 sessions, with 14 additional optional sessions of supervised active exercise therapy(e.g. aerobic and muscle strengthening) with individualized goal-setting, education and self-management regarding physical activity) or usual care(care determined by clinician(s) and participants themselves). Primary end point was the change in the Patient-Specific Complaints activity ranked 1 (PSC1 (0-10)) at 52 weeks. Secondary endpoints were the PSC activities ranked 2 and 3, the Bath Ankylosing Spondylitis Functional Index, 6-min walk test, Patient Reported Outcome Measurement Information System-Physical Function-10 and the Short Form-36 Physical and Mental Component Summary Score (SF-36 PCS and MCS). Statistical comparisons comprised independent student t-tests and linear mixed models, based on intention-to-treat. RESULTS: 214 participants(49% female, age 52 (SD 12) years), were randomized to the intervention (n = 110) or usual care (N = 104) group. In the intervention group 93% started treatment, using on average 40.5 sessions (SD 15.1). At 52 weeks, the difference in change in PSC1 between groups favored the intervention group (mean difference [95% CI]; -1.8 [-2.4 to -1.2]). additionally, all secondary outcomes, except the SF-36 MSC, showed significantly greater improvements in the intervention group with effect sizes ranging from 0.4-0.7. CONCLUSION: Long-term, supervised exercise therapy proved more effective than usual care in improving functional disability and physical quality of life in people with axSpA and severe functional limitations. CLINICAL TRIAL REGISTER NUMBER: Netherlands Trial Register NL8238, included in the International Clinical Trial Registry Platform (ICTRP) (https://trialsearch.who.int/Trial2.aspx?TrialID=NL8238).

How to Use Costs in Value-Based Healthcare: Learning from Real-life Examples.

BACKGROUND: Healthcare organizations measure costs for business operations but do not routinely incorporate costs in decision-making on the value of care. AIM: Provide guidance on how to use costs in value-based healthcare (VBHC) delivery at different levels of the healthcare system. SETTING AND PARTICIPANTS: Integrated practice units (IPUs) for diabetes mellitus (DM) and for acute myocardial infarction (AMI) at the Leiden University Medical Center and a collaboration of seven breast cancer IPUs of the Santeon group, all in the Netherlands. PROGRAM DESCRIPTION AND EVALUATION: VBHC aims to optimize care delivery to the patient by understanding how costs relate to outcomes. At the level of shared decision-making between patient and clinician, yearly check-up consultations for DM type I were analyzed for patient-relevant costs. In benchmarking among providers, quantities of cost drivers for breast cancer care were assessed in scorecards. In continuous learning, cost-effectiveness analysis was compared with radar chart analysis to assess the value of telemonitoring in outpatient follow-up. DISCUSSION: Costs vary among providers in healthcare, but also between provider and patient. The joint analysis of outcomes and costs using appropriate methods helps identify and optimize the aspects of care that drive desired outcomes and value.

FDG-PET/CT in indeterminate thyroid nodules: cost-utility analysis alongside a randomised controlled trial.

PURPOSE: To evaluate cost-effectiveness of an [18F]FDG-PET/CT-driven diagnostic workup as compared to diagnostic surgery, for thyroid nodules with Bethesda III/IV cytology. [18F]FDG-PET/CT avoids 40% of futile diagnostic surgeries for benign Bethesda III/IV nodules. METHODS: Lifelong societal costs and quality-adjusted life years (QALYs) were assessed for 132 patients participating in a randomised controlled multicentre trial comparing [18F]FDG-PET/CT to diagnostic surgery. The observed 1-year trial results were extrapolated using a Markov model. The probability of cost-effectiveness was estimated using cost-effectiveness acceptability curves, taking uncertainty about sampling, imputation, and parameters into account. RESULTS: The observed 1-year cost difference of [18F]FDG-PET/CT as compared to diagnostic surgery was - €1000 (95% CI: - €2100 to €0) for thyroid nodule-related care (p = 0.06). From the broader societal perspective, the 1-year difference in total societal costs was - €4500 (- €9200 to €150) (p = 0.06). Over the modelled lifelong period, the cost difference was - €9900 (- €23,100 to €3200) (p = 0.14). The difference in QALYs was 0.019 (- 0.045 to 0.083) at 1 year (p = 0.57) and 0.402 (- 0.581 to 1.385) over the lifelong period (p = 0.42). For a willingness to pay of €50,000 per QALY, an [18F]FDG-PET/CT-driven work-up was the cost-effective strategy with 84% certainty. CONCLUSION: Following the observed reduction in diagnostic surgery, an [18F]FDG-PET/CT-driven diagnostic workup reduced the 1-year thyroid nodule-related and societal costs while sustaining quality of life. It is very likely cost-effective as compared to diagnostic surgery for Bethesda III/IV nodules. TRIAL REGISTRATION NUMBER: This trial is registered with ClinicalTrials.gov: NCT02208544 (5 August 2014), https://clinicaltrials.gov/ct2/show/NCT02208544 .

[18F]FDG-PET/CT to prevent futile surgery in indeterminate thyroid nodules: a blinded, randomised controlled multicentre trial.

PURPOSE: To assess the impact of an [18F]FDG-PET/CT-driven diagnostic workup to rule out malignancy, avoid futile diagnostic surgeries, and improve patient outcomes in thyroid nodules with indeterminate cytology. METHODS: In this double-blinded, randomised controlled multicentre trial, 132 adult euthyroid patients with scheduled diagnostic surgery for a Bethesda III or IV thyroid nodule underwent [18F]FDG-PET/CT and were randomised to an [18F]FDG-PET/CT-driven or diagnostic surgery group. In the [18F]FDG-PET/CT-driven group, management was based on the [18F]FDG-PET/CT result: when the index nodule was visually [18F]FDG-positive, diagnostic surgery was advised; when [18F]FDG-negative, active surveillance was recommended. The nodule was presumed benign when it remained unchanged on ultrasound surveillance. In the diagnostic surgery group, all patients were advised to proceed to the scheduled surgery, according to current guidelines. The primary outcome was the fraction of unbeneficial patient management in one year, i.e., diagnostic surgery for benign nodules and active surveillance for malignant/borderline nodules. Intention-to-treat analysis was performed. Subgroup analyses were performed for non-Hürthle cell and Hürthle cell nodules. RESULTS: Patient management was unbeneficial in 42% (38/91 [95% confidence interval [CI], 32-53%]) of patients in the [18F]FDG-PET/CT-driven group, as compared to 83% (34/41 [95% CI, 68-93%]) in the diagnostic surgery group (p < 0.001). [18F]FDG-PET/CT-driven management avoided 40% (25/63 [95% CI, 28-53%]) diagnostic surgeries for benign nodules: 48% (23/48 [95% CI, 33-63%]) in non-Hürthle cell and 13% (2/15 [95% CI, 2-40%]) in Hürthle cell nodules (p = 0.02). No malignant or borderline tumours were observed in patients under surveillance. Sensitivity, specificity, negative and positive predictive value, and benign call rate (95% CI) of [18F]FDG-PET/CT were 94.1% (80.3-99.3%), 39.8% (30.0-50.2%), 95.1% (83.5-99.4%), 35.2% (25.4-45.9%), and 31.1% (23.3-39.7%), respectively. CONCLUSION: An [18F]FDG-PET/CT-driven diagnostic workup of indeterminate thyroid nodules leads to practice changing management, accurately and oncologically safely reducing futile surgeries by 40%. For optimal therapeutic yield, application should be limited to non-Hürthle cell nodules. TRIAL REGISTRATION NUMBER: This trial is registered with ClinicalTrials.gov: NCT02208544 (5 August 2014), https://clinicaltrials.gov/ct2/show/NCT02208544 .

A sexual rehabilitation intervention for women with gynaecological cancer receiving radiotherapy (SPARC study): design of a multicentre randomized controlled trial.

BACKGROUND: Sexual problems are frequently reported after treatment with radiotherapy (RT) for gynaecological cancer (GC), in particular after combined external beam radiotherapy and brachytherapy (EBRT+BT). Studies demonstrate that psychosexual support should include cognitive behavioural interventions and involvement of the patient's partner, if available. Therefore, we developed a nurse-led sexual rehabilitation intervention, including these key components. The intervention was previously pilot-tested and results demonstrated that this intervention improves women's sexual functioning and increases dilator compliance. The objective of the current study is to investigate the (cost-)effectiveness of the intervention compared to optimal care as usual (CAU). We expect that women who receive the intervention will report a statistically significant greater improvement in sexual functioning and - for women who receive EBRT+BT - higher compliance with dilator use, from baseline to 12 months post-RT than women who receive optimal care as usual (CAU). METHODS/DESIGN: The intervention is evaluated in the SPARC (Sexual rehabilitation Programme After Radiotherapy for gynaecological Cancer) study, a multicentre, randomized controlled trial (RCT). The primary endpoint is sexual functioning. Secondary outcomes include body image, fear of sexual activity, sexual-, treatment-related- and psychological distress, health-related quality of life and relationship satisfaction. A cost-effectiveness analysis (CEA) will be conducted in which the costs of the intervention will be related to shifts in other health care costs and the impact on patient outcome. The study sample will consist of 220 women with GC treated with RT in specialized GC treatment centres (N = 10). Participants are randomized to either the intervention- or CAU control group (1:1), and within each centre stratified by type of radiotherapy (EBRT+BT vs. EBRT only) and having a partner (yes/no). All women complete questionnaires at baseline (T1) and at 1, 3, 6, and 12 months post-RT (T2, T3, T4 and T5, respectively). DISCUSSION: There is a need to improve sexual functioning after RT for GC. This RCT will provide evidence about the (cost-)effectiveness of a nurse-led sexual rehabilitation intervention. If proven effective, the intervention will be a much needed addition to care offered to GC survivors and will result in improved quality of life. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03611517 . Registered 2 August 2018.

Cost-benefit Analysis of Cochlear Implants: A Societal Perspective.

OBJECTIVES: While the costs and outcomes of cochlear implantation (CI) have been widely assessed, most of these analyses were solely performed from the perspective of healthcare costs. This study assesses the costs and benefits of CI in the Netherlands from a broader societal perspective, including health outcomes, healthcare cost, educational cost, and productivity losses and gains. DESIGN: The cost and benefits of CI were analyzed in this cost-benefit analysis, in which a monetary value is put on both the resources needed and the outcomes of CI. The costs and benefits were analyzed by prototypical instances of three groups, representing the majority of cochlear implant patients: prelingually deaf children implanted at the age of 1, adults with progressive profound hearing loss implanted at the age of 40 and seniors implanted at the age of 70 with progressive profound hearing loss. Costs and benefits were estimated over the expected lifetimes of the members of each group, using a Markov state transition model. Model parameters and assumptions were based on published literature. Probabilistic and one-way sensitivity analyses were performed. RESULTS: In all three patient groups, the total benefits of CI exceeded the total cost, leading to a net benefit of CI. Prelingually deaf children with a bilateral CI had a lifetime positive outcome net benefit of €433,000. Adults and seniors with progressive profound hearing loss and a unilateral CI had a total net benefit of €275,000 and €76,000, respectively. These results ensue from health outcomes expressed in monetary terms, reduced educational cost, and increased productivity. CONCLUSIONS: Based on estimates from modeling, the increased healthcare costs due to CI were more than compensated by the value of the health benefits and by savings in educational and productivity costs. In particular, for children and working adults, the societal benefit was positive even without taking health benefits into account. Therefore, CI generates an advantage for both patients and society.

Implications of response shift for micro-, meso-, and macro-level healthcare decision-making using results of patient-reported outcome measures.

PURPOSE: Results of patient-reported outcome measures (PROMs) are increasingly used to inform healthcare decision-making. Research has shown that response shift can impact PROM results. As part of an international collaboration, our goal is to provide a framework regarding the implications of response shift at the level of patient care (micro), healthcare institute (meso), and healthcare policy (macro). METHODS: Empirical evidence of response shift that can influence patients' self-reported health and preferences provided the foundation for development of the framework. Measurement validity theory, hermeneutic philosophy, and micro-, meso-, and macro-level healthcare decision-making informed our theoretical analysis. RESULTS: At the micro-level, patients' self-reported health needs to be interpreted via dialogue with the clinician to avoid misinterpretation of PROM data due to response shift. It is also important to consider the potential impact of response shift on study results, when these are used to support decisions. At the meso-level, individual-level data should be examined for response shift before aggregating PROM data for decision-making related to quality improvement, performance monitoring, and accreditation. At the macro-level, critical reflection on the conceptualization of health is required to know whether response shift needs to be controlled for when PROM data are used to inform healthcare coverage. CONCLUSION: Given empirical evidence of response shift, there is a critical need for guidelines and knowledge translation to avoid potential misinterpretations of PROM results and consequential biases in decision-making. Our framework with guiding questions provides a structure for developing strategies to address potential impacts of response shift at micro-, meso-, and macro-levels.

Healthcare utilization and costs among prolactinoma patients: a cross-sectional study and analysis of determinants.

PURPOSE: Prolactinomas are the most prevalent functioning pituitary adenomas. They affect gonadal function as well as health-related quality of life (HRQoL). This study aimed to report healthcare utilization and costs, including their determinants, for prolactinoma patients. METHODS: Cross-sectional study of 116 adult prolactinoma patients in chronic care in a Dutch tertiary referral center. Patients completed four validated questionnaires, assessing healthcare utilization and costs over the previous 12 months (Medical Consumption Questionnaire), disease bother and needs (Leiden Bother and Needs Questionnaire Pituitary), HRQoL (Short Form-36), and self-reported health status (EuroQol 5D). Regression analyses were used to assess associations between disease-related characteristics and healthcare utilization and costs. RESULTS: Mean age was 52.0 years (SD 13.7) and median follow-up was 15.0 years (IQR 7.6-26.1). Patients visited the endocrinologist (86.2%), general practitioner (37.9%), and ophthalmologist (25.0%) most frequently. Psychological care was used by 12.9% of patients and 5% were admitted to hospital. Mean annual healthcare costs were €1928 (SD 3319), mainly for pituitary-specific medication (37.6% of total costs), hospitalization (19.4%) and specialist care (16.1%). Determinants for higher healthcare utilization and costs were greater disease bother and needs for support, lower HRQoL, elevated prolactin, and longer disease duration, while tumor size, hypopituitarism and adrenal insufficiency were not significantly associated with healthcare utilization and costs. CONCLUSION: Healthcare utilization and costs of prolactinoma patients are related to patient-reported HRQoL, bother by disease and needs for support. Therefore, addressing patients' HRQoL and needs is a way forward to improve efficiency of care and patients' health status.

Changes in healthcare utilisation for paediatric tonsillectomy and adenoidectomy in the Netherlands: a population-based study.

OBJECTIVES: Tonsillectomy and adenoidectomy in children are controversial subjects with large regional variation in surgical rates, partly explained by cultural differences and lack of high-quality evidence on indications for surgery. A quality of care cycle was executed on this topic in the Netherlands. The objective of this study was to estimate changes in healthcare utilisation for paediatric tonsil surgery in the Netherlands. METHODS: Population-based data on tonsillectomies and adenoidectomies in children up to age 10 were retrieved retrospectively from Dutch administrative databases between 2005 and 2018. A change point analysis was performed to detect the most pivotal change point in surgical rates. We performed univariate analyses to compare surgical patients' characteristics before and after the pivotalpoint . Impact on healthcare budget and societal costs were estimated using current prices and data from cost-effectiveness analyses. RESULTS: The annual number of adenotonsillectomies reduced by 10 952 procedures (-39%; from 129 per 10 000 children to 87 per 10 000 children) between 2005 and 2018, and the number of adenoidectomies by 14 757 procedures (-49%; from 138 per 10 000 children to 78 per 10 000 children). The most pivotal change point was observed around 2012, accompanied by small changes in patient selection for surgery before and after 2012. An estimated €5.3 million per year was saved on the healthcare budget and €10.4 million per year on societal costs. CONCLUSION: The quality of care cycle resulted in fewer operations, with a concomitant reduction of costs. We suggest that part of these savings be invested in new research to maintain the quality of care cycle.

The incidence and economic impact of aggression in closed long-stay psychiatric wards.

OBJECTIVE: Aggressive behaviour is highly prevalent in long-term psychiatric inpatient care. We aimed to estimate the overall incidence of aggression, the time staff took to handle aggression incidents, and the weighted average financial costs thereof. METHODS: A random sampling procedure was conducted at long-term psychiatric inpatient care facilities. Nurses were asked to recall all incidents (i.e., verbal, physical towards objects, self, or others) of their shift. For the time spent on each type of incident, staff were monitored in real-time. Estimated costs were calculated by the time spent multiplied by hourly wages in addition to material-related costs. RESULTS: Incidence rates were 90 incidents per patient year. The average time spent per incident was 125 min but differed for each type of incident. Almost 80% of this time was consumed by nursing staff. The average cost per aggression incident was €78; extrapolated per patient year, the total costs were approximately €7000. CONCLUSIONS: The current study found a high rate of aggression incidents in closed long-stay psychiatric wards. Reports of aggression on these types of wards are scarce. Nevertheless, aggression seems to have a severe impact on invested time and related costs, which suggests a need for aggression-prevention and de-escalating programs.Key pointsAggression incidents are highly prevalent and are accompanied by high costs.The effect of aggression incidents on the workload for staff members is high, especially for nursing staff.Studies across countries on the incidence and the costs of aggression among psychiatric inpatients are needed to help model the effects of (new) strategies for aggression reduction.

Editor's Choice - A Systemic Evaluation of the Costs of Elective EVAR and Open Abdominal Aortic Aneurysm Repair Implies Cost Equivalence.

OBJECTIVE: The suggested high costs of endovascular aneurysm repair (EVAR) hamper the choice of insurance companies and financial regulators for EVAR as the primary option for elective abdominal aortic aneurysm (AAA) repair. However, arguments used in this debate are impeded by time related aspects such as effect modification and the introduction of confounding by indication, and by asymmetric evaluation of outcomes. Therefore, a re-evaluation minimising the impact of these interferences was considered. METHODS: A comparative analysis was performed evaluating a period of exclusive open repair (OR; 1998-2000) and a period of established EVAR (2010-2012). Data from four hospitals in The Netherlands were collected to estimate resource use. Actual costs were estimated by benchmark cost prices and a literature review. Costs are reported at 2019 prices. A break even approach, defining the costs for an endovascular device at which cost equivalence for EVAR and OR is achieved, was applied to cope with the large variation in endovascular device costs. RESULTS: One hundred and eighty-six patients who underwent elective AAA repair between 1998 and 2000 (OR period) and 195 patients between 2010 and 2012 (EVAR period) were compared. Cost equivalence for OR and EVAR was reached at a break even price for an endovascular device of €13 190. The main cost difference reflected the longer duration of hospital stay (ward and Intensive Care Unit) of OR (€11 644). Re-intervention rates were similar for OR (24.2%) and EVAR (24.6%) (p = .92). CONCLUSION: Cost equivalence for EVAR and OR occurs at a device cost of €13 000 for EVAR. Hence, for most routine repairs, EVAR is not costlier than OR until at least the five year follow up.

Transanal minimally invasive surgery (TAMIS) versus endoscopic submucosal dissection (ESD) for resection of non-pedunculated rectal lesions (TRIASSIC study): study protocol of a European multicenter randomised controlled trial.

BACKGROUND: In the recent years two innovative approaches have become available for minimally invasive en bloc resections of large non-pedunculated rectal lesions (polyps and early cancers). One is Transanal Minimally Invasive Surgery (TAMIS), the other is Endoscopic Submucosal Dissection (ESD). Both techniques are standard of care, but a direct randomised comparison is lacking. The choice between either of these procedures is dependent on local expertise or availability rather than evidence-based. The European Society for Endoscopy has recommended that a comparison between ESD and local surgical resection is needed to guide decision making for the optimal approach for the removal of large rectal lesions in Western countries. The aim of this study is to directly compare both procedures in a randomised setting with regard to effectiveness, safety and perceived patient burden. METHODS: Multicenter randomised trial in 15 hospitals in the Netherlands. Patients with non-pedunculated lesions > 2 cm, where the bulk of the lesion is below 15 cm from the anal verge, will be randomised between either a TAMIS or an ESD procedure. Lesions judged to be deeply invasive by an expert panel will be excluded. The primary endpoint is the cumulative local recurrence rate at follow-up rectoscopy at 12 months. Secondary endpoints are: 1) Radical (R0-) resection rate; 2) Perceived burden and quality of life; 3) Cost effectiveness at 12 months; 4) Surgical referral rate at 12 months; 5) Complication rate; 6) Local recurrence rate at 6 months. For this non-inferiority trial, the total sample size of 198 is based on an expected local recurrence rate of 3% in the ESD group, 6% in the TAMIS group and considering a difference of less than 6% to be non-inferior. DISCUSSION: This is the first European randomised controlled trial comparing the effectiveness and safety of TAMIS and ESD for the en bloc resection of large non-pedunculated rectal lesions. This is important as the detection rate of these adenomas is expected to further increase with the introduction of colorectal screening programs throughout Europe. This study will therefore support an optimal use of healthcare resources in the future. TRIAL REGISTRATION: Netherlands Trial Register, NL7083 , 06 July 2018.

PORTEC-4a: international randomized trial of molecular profile-based adjuvant treatment for women with high-intermediate risk endometrial cancer.

BACKGROUND: Vaginal brachytherapy is currently recommended as adjuvant treatment in patients with high-intermediate risk endometrial cancer to maximize local control and has only mild side effects and no or limited impact on quality of life. However, there is still considerable overtreatment and also some undertreatment, which may be reduced by tailoring adjuvant treatment to the patients' risk of recurrence based on molecular tumor characteristics. PRIMARY OBJECTIVES: To compare the rates of vaginal recurrence in women with high-intermediate risk endometrial cancer, treated after surgery with molecular-integrated risk profile-based recommendations for either observation, vaginal brachytherapy or external pelvic beam radiotherapy or with standard adjuvant vaginal brachytherapy STUDY HYPOTHESIS: Adjuvant treatment based on a molecular-integrated risk profile provides similar local control and recurrence-free survival as current standard adjuvant brachytherapy in patients with high-intermediate risk endometrial cancer, while sparing many patients the morbidity of adjuvant treatment and reducing healthcare costs. TRIAL DESIGN: A multicenter, international phase III randomized trial (2:1) of molecular-integrated risk profile-based adjuvant treatment (experimental arm) or adjuvant vaginal brachytherapy (standard arm). MAJOR INCLUSION/EXCLUSION CRITERIA: Women aged 18 years and over with a histological diagnosis of high-intermediate risk endometrioid endometrial cancer after total abdominal or laparoscopic hysterectomy and bilateral salpingo-oophorectomy. High-intermediate risk factors are defined as: (i) International Federation of Gynecology and Obstetrics stage IA (with invasion) and grade 3; (ii) stage IB grade 1 or 2 with age ≥60 and/or lymph-vascular space invasion; (iii) stage IB, grade 3 without lymph-vascular space invasion; or (iv) stage II (microscopic and grade 1). ENDPOINTS: The primary endpoint is vaginal recurrence. Secondary endpoints are recurrence-free and overall survival; pelvic and distant recurrence; 5-year vaginal control (including treatment for relapse); adverse events and patient-reported symptoms and quality of life; and endometrial cancer-related healthcare costs. SAMPLE SIZE: 500 eligible and evaluable patients. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: Estimated date for completing accrual will be late 2021. Estimated date for presentation of (first) results is expected in 2023. TRIAL REGISTRATION: The trial is registered at clinicaltrials.gov (NCT03469674) and ISRCTN (11659025).

Rationale and design of the PaTIO study: PhysiotherApeutic Treat-to-target Intervention after Orthopaedic surgery.

BACKGROUND: Physiotherapy is a proven effective treatment strategy after total knee and hip arthroplasty (TKA/THA), however there is considerable practice variation regarding its timing, content and duration. This study aims to compare the (cost-) effectiveness of a standardized, treat-to-target postoperative physiotherapy strategy with usual postoperative care. METHODS: Using a cluster randomized study design, consecutive patients scheduled for a primary TKA/THA in 18 hospitals in the Netherlands will be assigned to the treat-to-target physio therapy strategy or usual postoperative care. With the treat-to-target strategy a standardized, individually tailored, exercise program is aimed at the attainment of specific functional milestones. Assessments are done at baseline, 6 weeks and 3, 6, 9 and 12 months follow up. The primary outcome will be the Knee injury / Hip disability and Osteoarthritis Outcome Score - Physical Function Short Form (KOOS-PS / HOOS-PS) at 3 months follow up. Secondary outcomes are the numeric rating scale for pain, the Oxford Knee and Hip Scores, performance-based test and the EuroQol 5D-5L for quality of life. Healthcare use, productivity and satisfaction with postoperative care are measured by means of questionnaires. In total, 624 patients will be needed of which 312 TKA and 312 THA patients. DISCUSSION: The study will provide evidence concerning the (cost-) effectiveness of the treat-to-target postoperative physiotherapy treatment compared to usual postoperative care. The results of this study will address an important evidence gap and will have a significant impact in daily practice of the physio therapist. TRIAL REGISTRATION: Registered in the Dutch Trial Registry on April 15, 2018. Registration number: NTR7129 .

Combining multiple imputation and bootstrap in the analysis of cost-effectiveness trial data.

In healthcare cost-effectiveness analysis, probability distributions are typically skewed and missing data are frequent. Bootstrap and multiple imputation are well-established resampling methods for handling skewed and missing data. However, it is not clear how these techniques should be combined. This paper addresses combining multiple imputation and bootstrap to obtain confidence intervals of the mean difference in outcome for two independent treatment groups. We assessed statistical validity and efficiency of 10 candidate methods and applied these methods to a clinical data set. Single imputation nested in the bootstrap percentile method (with added noise to reflect the uncertainty of the imputation) emerged as the method with the best statistical properties. However, this method can require extensive computation times and the lack of standard software makes this method not accessible for a larger group of researchers. Using a standard unpaired t-test with standard multiple imputation without bootstrap appears to be a robust alternative with acceptable statistical performance for which standard multiple imputation software is available.

Transforaminal epidural injection versus continued conservative care in acute sciatica (TEIAS trial): study protocol for a randomized controlled trial.

BACKGROUND: Sciatica is a condition that is characterised by radicular pain in the leg and primarily caused by a herniated lumbar intervertebral disk. In addition to leg pain, patients can experience back pain, leg numbness and leg weakness resulting in decreased productivity and social activity. The majority of sciatica cases recovers spontaneously and therefore patients are initially treated conservatively with oral pain medication. However, some patients experience intractable pain that severely impedes them and no consensus exists on the optimal conservative treatment to reduce this discomfort in the acute phase of sciatica. The aim of the TEIAS trial is to assess the effectiveness, cost-effectiveness and predictive capability on patient outcome of transforaminal epidural injection (TEI) compared to treatment with standard pain medication. METHODS: This study is designed as a prospective, open-label, mono-centered, randomized controlled trial. Patients that visit their general practitioner with complaints of radicular leg pain and meet the selection criteria are asked to participate in this study. Eligible patients will be randomized to treatment with TEI or to treatment with standard oral pain medication. Treatment of TEI will comprise lidocaine with methylprednisolone acetate for L3 and below and lidocaine with dexamethasone above L3. A total of 142 patients will be recruited and follow-up will occur after 1, 2, 4, 10 and 21 weeks for assessment of pain, functionality, patient received recovery and cost-effectiveness. The primary outcome will be the average score for leg pain at 2 weeks. For this outcome we defined a clinically relevant difference as 1.5 on the 11-point NRS scale. DISCUSSION: Adequate conservative treatment in the acute phase of sciatica is lacking, particularly for patients with severe symptoms. Focusing on effectiveness, cost-effectiveness and predictive capability on patient outcome of TEI will produce useful information allowing for more lucid decision making in the conservative treatment of sciatica in the acute phase. TRIAL REGISTRATION: This trial is registered in the ClinicalTrials.gov database under registry number NCT03924791 on April 23, 2019.

Patient explicit consideration of tradeoffs in decision making about rectal cancer treatment: benefits for decision process and quality of life.

Introduction: Patient preferences are often not discussed in treatment decisions in oncology. We introduced an online values clarification method (VCM) to help newly diagnosed rectal cancer patients participate in shared decision making about short-course preoperative radiotherapy. Material and Methods: We offered a link to the VCM to a subset of consecutive patients before the pretreatment consultation with the radiation oncologist. Consultations were audiotaped and coded for expressions of patient preferences. Patients were asked to complete pre- and post-consultation questionnaires. Questionnaires assessed values clarity, decision regret and presence and impact of fecal incontinence and sexual problems. Results: Of 135 patients who had their consultation audiotaped and completed questionnaires, 35 received and accessed the VCM-link. Patients in the VCM-group slightly more often expressed preferences during consultations. Questionnaire data showed that patients in the VCM-group did not differ in how clear their values were, but experienced lower regret and less impact of treatment harms at 6 months follow-up; differences were non-significant but in the same direction at 12 months. Discussion: This is the first study to assess the effect of an adaptive conjoint analysis-based VCM on actual patient-clinician communication, and long-term decision regret and impact of treatment harms. Being explicitly invited to think about treatment benefits and harms seems to help patients to live with treatment consequences.

Influence of response shift and disposition on patient-reported outcomes may lead to suboptimal medical decisions: a medical ethics perspective.

BACKGROUND: Patient-reported outcomes (PROs) are frequently used for medical decision making, at the levels of both individual patient care and healthcare policy. Evidence increasingly shows that PROs may be influenced by patients' response shifts (changes in interpretation) and dispositions (stable characteristics). MAIN TEXT: We identify how response shifts and dispositions may influence medical decisions on both the levels of individual patient care and health policy. We provide examples of these influences and analyse the consequences from the perspectives of ethical principles and theories of just distribution. CONCLUSION: If influences of response shift and disposition on PROs and consequently medical decision making are not considered, patients may not receive optimal treatment and health insurance packages may include treatments that are not the most effective or cost-effective. We call on healthcare practitioners, researchers, policy makers, health insurers, and other stakeholders to critically reflect on why and how such patient reports are used.