Stereotactic Body radiotherapy and pedicLE screw fixatioN During one hospital visit for patients with symptomatic unstable spinal metastases: a randomized trial (BLEND RCT) using the Trials within Cohorts (TwiCs) design.

BACKGROUND: Spinal metastases can lead to unremitting pain and neurological deficits, which substantially impair daily functioning and quality of life. Patients with unstable spinal metastases receive surgical stabilization followed by palliative radiotherapy as soon as wound healing allows. The time between surgery and radiotherapy delays improvement of mobility, radiotherapy-induced pain relief, local tumor control, and restart of systemic oncological therapy. Stereotactic body radiotherapy (SBRT) enables delivery of preoperative high-dose radiotherapy while dose-sparing the surgical field, allowing stabilizing surgery within only hours. Patients may experience earlier recovery of mobility, regression of pain, and return to systemic oncological therapy. The BLEND RCT evaluates the effectiveness of SBRT followed by surgery within 24 h for the treatment of symptomatic, unstable spinal metastases. METHODS: This phase III randomized controlled trial is embedded within the PRospective Evaluation of interventional StudiEs on boNe meTastases (PRESENT) cohort. Patients with symptomatic, unstable spinal metastases requiring stabilizing surgery and radiotherapy will be randomized (1:1). The intervention group (n = 50) will be offered same-day SBRT and surgery, which they can accept or refuse. According to the Trial within Cohorts (TwiCs) design, the control group (n = 50) will not be informed and receive standard treatment (surgery followed by conventional radiotherapy after 1-2 weeks when wound healing allows). Baseline characteristics and outcome measures will be captured within PRESENT. The primary outcome is physical functioning (EORTC-QLQ-C15-PAL) 4 weeks after start of treatment. Secondary endpoints include pain response, time until return to systemic oncological therapy, quality of life, local tumor control, and adverse events up to 3 months post-treatment. DISCUSSION: The BLEND RCT evaluates the effect of same-day SBRT and stabilizing surgery for the treatment of symptomatic, unstable spinal metastases compared with standard of care. We expect better functional outcomes, faster pain relief, and continuation of systemic oncological therapy. The TwiCs design enables efficient recruitment within an ongoing cohort, as well as prevention of disappointment bias and drop-out as control patients will not be informed about the trial. TRIAL REGISTRATION: ClinicalTrials.gov NCT05575323. Registered on October 11, 2022.

Plugging membranes after fetoscopy in congenital diaphragmatic hernia: early cost-effectiveness analysis.

OBJECTIVES: Fetal endoscopic tracheal occlusion (FETO) improves neonatal survival of fetuses with congenital diaphragmatic hernia (CDH). However, FETO also increases the risk of preterm prelabor rupture of membranes (PPROM) and preterm delivery (PTD), as fetal membrane defects after fetoscopy do not heal. To solve this issue, an advanced sealing plug for closing the membrane defect is being developed. Using early-stage health economic modeling, we aimed to estimate the potential value of this innovative plug in terms of costs and effects, and to determine the properties required for it to become cost-effective. METHODS: Early-stage health economic modeling was applied to the case of performing FETO in women with a singleton pregnancy whose fetus is diagnosed prenatally with CDH. We simulated a cohort of patients using a state-transition model over a 45-year time horizon. In our best-case-scenario analysis, we compared the current-care strategy with the perfect-plug strategy, which reduces the risk of PPROM and PTD by 100%, to determine the maximum quality-adjusted life years (QALYs) gained and costs saved. Using threshold analysis, we determined the minimum percentage reduction in the risk of PPROM and PTD required for the plug to be considered cost-effective. The impact of model parameters on outcome was investigated using a sensitivity analysis. RESULTS: Our model indicated that a perfect-plug strategy would yield on average an additional 1.94 QALYs at a cost decrease of €2554 per patient. These values were influenced strongly by the percentage of cases with early PTD (27-34 weeks). Threshold analysis showed that, for €500 per plug, the plug strategy needs a minimum percentage reduction of 1.83% in the risk of PPROM and PTD (i.e. reduction in the risk from 47.50% to 46.63% for PPROM and from 71.50% to 70.19% for PTD) to be cost-effective. CONCLUSIONS: Our model-based approach showed clear potential of the plug strategy when applied in the context of FETO for CDH fetuses, as only a minor reduction in the risk of PPROM and PTD is needed for the plug to be cost-effective. Its value is expected to be even higher when used in conditions associated with a higher rate of early PTD. Continued investment in research and development of the plug strategy appears to provide value for money. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Septoplasty versus non-surgical management for nasal obstruction in adults with a deviated septum: economic evaluation alongside a randomized controlled trial.

BACKGROUND: For years, the benefits of septoplasty have been questioned. Due to the scarce and inconclusive literature, several National Health Service (NHS) Clinical Commissioning Groups in England decided to add septal surgery to their list of restricted procedures with low clinical value. Recently, evidence was obtained that septoplasty is actually more effective than non-surgical management for nasal obstruction in adults with a deviated septum. However, the relation between costs and effects of septoplasty remains unknown. METHODS: We conducted an economic evaluation alongside an open, multicenter, pragmatic randomized controlled trial in two tertiary and 16 secondary referral hospitals in the Netherlands. Adults with nasal obstruction and a deviated septum were randomized to (1) septoplasty with or without concurrent turbinate surgery or (2) non-surgical management consisting of (a combination of) medical treatment and watchful waiting. Analyses were performed on an intention-to-treat basis. Single imputation nested in the bootstrap percentile method (using 5000 bootstrap replications) was performed to assess the effect of missing data. After 12 and 24 months, we assessed the incremental costs per quality-adjusted life year (QALY) gained from a healthcare and a societal perspective. RESULTS: A total of 203 adults were randomly assigned to septoplasty (N = 102) or non-surgical management (N = 101). After 12 months, the mean cost difference between septoplasty and non-surgical management using a healthcare or societal perspective was €1181 (95%CI €1038 to €1323) or €2192 per patient (95%CI €1714 to €2670), respectively. The mean QALY difference was 0.03 per patient (95%CI - 0.01 to 0.07). Incremental costs per QALY gained from a healthcare or societal perspective were €41,763 or €77,525, respectively. After 24 months, the mean cost difference between the two groups using a healthcare or societal perspective decreased to €936 (95%CI €719 to €1153) or €1671 per patient (95%CI €952 to €2390), respectively. The mean QALY difference increased to 0.05 per patient (95%CI - 0.03 to 0.14). Incremental costs per QALY gained from a healthcare or societal perspective became €17,374 or €31,024, respectively. Analyses of imputed data did not alter our findings. CONCLUSIONS: Depending on the selected perspective, cost-effectiveness threshold, and time horizon, septoplasty has the potential to be cost-effective. Despite considerable uncertainty, septoplasty seems to be cost-effective from a healthcare perspective, after 24 months against a threshold of €20,000 per QALY. From a societal perspective, septoplasty is not yet cost-effective after 24 months, but it comes closer to the cost-effectiveness threshold as time passes by. TRIAL REGISTRATION: Nederlands Trial Register, NTR3868 (https://www.trialregister.nl/trial/3698). Prospectively registered on February 21, 2013.

Robot assisted radical cystectomy versus open radical cystectomy in bladder cancer (RACE): study protocol of a non-randomized comparative effectiveness study.

BACKGROUND: Despite the fact that the cost-effectiveness of robot-assisted radical cystectomy (RARC) is not yet proven, and open radical (ORC) cystectomy is recommended as the standard of care in patients with high-risk non-muscle-invasive and muscle-invasive bladder cancer, the use of RARC is still increasing. The objective of the current ongoing comparative effectiveness trial therefore is to study the (cost-)effectiveness of RARC compared to ORC, both in terms of objective (complication rates, oncological outcomes) and patient-reported (health-related quality of life) outcome measures. METHODS: This study is designed as a non-randomized, multicentre comparative effectiveness trial. Centres with an annual caseload of > 20 radical cystectomies can include patients after informed consent has been given. Centres that perform RARC must have passed the (initial) learning curve of 40 cases. A total of 338 (2 × 169) patients will be enrolled from 23 participating centres (12 ORC, 10 RARC and 1 LRC). Follow-up visits will be scheduled at 1, 3, 6 and 12 months. During each follow-up visit, clinical data and health-related quality of life questionnaires will be administered. Costs will be studied using a monthly resource usage questionnaire. Impact on complications and quality of life will be calculated as the average difference between the groups with 95% confidence intervals, adjusted for potential baseline differences by means of propensity score matching. DISCUSSION: This study aims to contribute to the development of evidence-based guidelines regarding the most cost-effective surgical technique for radical cystectomy. TRIAL REGISTRATION: Nederlands Trial Register/Dutch Trial Registry, trial identifying number: NTR5362. Registered on 14 August 2015. ( http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=5362 ).

Potential savings in the diagnosis of vestibular schwannoma.

INTRODUCTION: Magnetic resonance imaging (MRI) is used to screen patients at risk for vestibular schwannoma (VS). These MRIs are costly and have an extremely low yield; only 3% of patients in the screening population has an actual VS. It might be worthwhile to develop a test to predict VS and refer only a subset of all patients for MRI. OBJECTIVE: To examine the potential savings of such a hypothetical diagnostic test before MRI. DESIGN: We built a decision analytical model of the diagnostic strategy of VS. Input was derived from literature and key opinion leaders. The current strategy was compared to hypothetical new strategies, assigning MRI to the following: (i) all patients with pathology, (ii) all patients with important pathology and (iii) only patients with VS. This resulted in potential cost savings for each strategy. We conducted a budget impact analysis to predict nationwide savings for the Netherlands and the United Kingdom (UK), and a probabilistic sensitivity analysis to address uncertainty. RESULTS: Mean savings ranged from €256 (95%CI €250 - €262) or approximately US$284 (95%CI US$277 - US$291) per patient for strategy 1 to €293 (95%CI €290 - €296) or approximately US$325 (95%CI US$322 - US$328) per patient for strategy 3. Future diagnostic strategies can cost up to these amounts per patient and still be cost saving. Annually, for the Netherlands, €2.8 to €3.2 million could be saved and €10.8 to €12.3 million for the UK. CONCLUSIONS: The model shows that substantial savings could be generated if it is possible to further optimise the diagnosis of VS.

The merits of decision modelling in the earliest stages of the IDEAL framework: An innovative case in DIEP flap breast reconstructions.

BACKGROUND: The IDEAL framework aims at improving the evidence base of available surgical innovations. However, the development of such innovations and collection of evidence is costly. Surgical innovation can provide more value for money if innovations are evaluated at an early stage, where evaluations can inform the decision whether to stop or to further develop an innovation. We illustrate how decision modelling can be readily adopted at the earliest stages (0-1) of the IDEAL framework, using an innovation in bilateral DIEP flap breast reconstruction as an example. METHODS: We quantified expected costs and quality-adjusted life years (QALYs) of the current treatment and compared them with an innovation aimed at reducing complications and surgery time. The maximum effect of eliminating all complications (headroom analysis) was explored. Moreover, three scenarios with varying complications and surgery time reductions were modelled. Furthermore, the maximum price of the innovation was estimated in a threshold analysis according to its impact and societal willingness to pay. RESULTS: The headroom analysis showed that when all complications associated with the current treatment are prevented, up to €889 per patient is saved. Scenario analysis showed cost savings between €256 and €828 per patient. When surgery time is reduced by 15 min and complications by 50%, the innovation will remain cost-effective at €671 per patient. CONCLUSION: In a field struggling with cost containment, decision modelling can help to separate promising innovations from costly failures at an early stage. In this example, decision modelling showed that it seems worthwhile to further develop the innovation.

Parental quality of life in complex paediatric neurologic disorders of unknown aetiology.

Complex paediatric neurology (CPN) patients generally present with non-specific symptoms, such as developmental delay, impaired movement and epilepsy. The diagnostic trajectory in these disorders is usually complicated and long-lasting, and may be burdensome to the patients and their parents. Additionally, as caring for a chronically ill child can be stressful and demanding, parents of these patients may experience impaired health-related quality of life (HRQoL). This study aims to assess parental HRQoL and factors related to it in CPN. Physical and mental HRQoL of 120 parents was measured and compared to the general population using the SF-12 questionnaire. Parents also completed this questionnaire for the measurement of patient HRQoL. Additional questionnaires were used to measure parental uncertainty (Visual Analogue Scale) and worry phenomena (Penn State Worry Questionnaire), and to obtain socio-demographic data. A linear mixed model with random effect was used to investigate which of these variables were associated with parental HRQoL. As compared to the general population, HRQoL of these parents appeared diminished. Fathers showed both lowered physical (51.76, p < 0.05) and mental (49.41, p < 0.01) HRQoL, whereas mothers only showed diminished mental (46.46, p < 0.01) HRQoL. Patient HRQoL and parental worry phenomena were significantly correlated with overall and mental parental HRQoL. The reduction in parental mental HRQoL is alarming, also because children strongly rely on their parents and parental mental health is known to influence children's health. Awareness of these problems among clinicians, and supportive care if needed are important to prevent exacerbation of the problems.

Quality of life after different procedures for regional control in oral cancer patients: cross-sectional survey.

OBJECTIVES: To examine health utilities in patients with cT1-2 oral cavity squamous cell carcinoma following different diagnostic and treatment modalities for the neck and to investigate the relation between shoulder morbidity and health utility. DESIGN: Cross-sectional survey. SETTING: Two Dutch hospitals. PARTICIPANTS: Four subgroups of patients with oral cavity cancer who underwent watchful waiting, sentinel lymph node biopsy, elective supraomohyoid neck dissection or therapeutic modified radical neck dissection. MAIN OUTCOME MEASURES: Patients received the EuroQol-5D-3L questionnaire and the shoulder disability questionnaire. Mean health utility, visual analogue scale and shoulder disability scores were calculated. RESULTS: A total of 181 patients (62%) returned the questionnaires. Mean health utilities, adjusted for age, gender and time since treatment were 0.804, 0.863, 0.834 and 0.794 for the watchful waiting, sentinel lymph node biopsy, supraomohyoid neck dissection and modified radical neck dissection subgroups, respectively. Mean shoulder disability scores (higher score means more shoulder complaints) for these subgroups were 8.64, 10.57, 18.92 and 33.66. Patients with shoulder complaints had a mean utility of 0.78 while patients without shoulder complaints had a mean utility of 0.90. CONCLUSIONS: This study shows that more invasive procedures appear to result in lower health utility. The high health utility for patients after sentinel lymph node biopsy supports a role for this procedure in patients with oral cancer.

Yearly hypertension screening in women with a history of pre-eclampsia: a cost-effectiveness analysis.

BACKGROUND: Women with a history of preeclampsia are at increased risk for future hypertension and cardiovascular disease (CVD); until now it is not clear whether preventive measures are needed. METHODS: A decision-analytic Markov model was constructed to evaluate healthcare costs and effects of screening and treatment (100 % compliance) for hypertension post preeclampsia based on the available literature. Cardiovascular events and CVD mortality were defined as health states. Outcomes were measured in absolute costs, events, life-years and quality-adjusted life-years (QALYs). Sensitivity and threshold analyses were performed to address uncertainty. RESULTS: Over a 20-year time horizon, events occurred in 7.2 % of the population after screening, and in 8.5 % of the population without screening. QALYs increased from 16.37 (no screening strategy) to 16.40 (screening strategy), an increment of 0.03 (95 % CI 0.01;0.05) QALYs. Total expected costs were € 8016 in the screening strategy, and € 9087 in the none screening strategy (expected saving of € 1071 (95 % CI - 3146;-87) per person). CONCLUSION: Annual hypertension screening and treatment in women with a history of preeclampsia may save costs, for at least a similar quality of life and survival due to prevented CVD compared with standard care.

The diagnostic pathway in complex paediatric neurology: a cost analysis.

BACKGROUND: The diagnostic trajectory of complex paediatric neurology may be long, burdensome, and expensive while its diagnostic yield is frequently modest. Improvement in this trajectory is desirable and might be achieved by innovations such as whole exome sequencing. In order to explore the consequences of implementing them, it is important to map the current pathway. To that end, this study assessed the healthcare resource use and associated costs in this diagnostic trajectory in the Netherlands. METHODS: Fifty patients presenting with complex paediatric neurological disorders of a suspected genetic origin were included between September 2011 and March 2012. Data on their healthcare resource utilization were collected from the hospital medical charts. Unit prices were obtained from the Dutch Healthcare Authority, the Dutch Healthcare Insurance Board, and the financial administration of the hospital. Bootstrap simulations were performed to determine mean quantities and costs. RESULTS: The mean duration of the diagnostic trajectory was 40 months. A diagnosis was established in 6% of the patients. On average, patients made 16 physician visits, underwent four imaging and two neurophysiologic tests, and had eight genetic and 16 other tests. Mean bootstrapped costs per patient amounted to €12,475, of which 43% was for genetic tests (€5,321) and 25% for hospital visits (€3,112). CONCLUSION: Currently, the diagnostic trajectories of paediatric patients who have complex neurological disease with a strong suspected genetic component are lengthy, resource-intensive, and low-yield. The data from this study provide a backdrop against which the introduction of novel techniques such as whole exome sequencing should be evaluated.