Resective Epilepsy Surgery, QUality of life and Economic evaluation (RESQUE): the change in quality of life after resective epilepsy surgery-protocol for a multicentre, prospective cohort study.

INTRODUCTION: Resective epilepsy surgery is often seen as a last resort when treating drug-resistant epilepsy. Positive results on quality of life (QoL) and economic benefits after surgery argue for a less restrictive attitude towards epilepsy surgery for drug-resistant epilepsy. QoL and economic benefits are country-dependent. The objective of the Resective Epilepsy Surgery, QUality of life and Economic evaluation (RESQUE) trial is to evaluate the change in QoL before and after epilepsy surgery in Dutch people with drug-resistant epilepsy. The results will form part of an economic evaluation of epilepsy surgery in people with epilepsy (PWE) in The Netherlands. METHODS AND ANALYSIS: A longitudinal prospective multicentre cohort study involving 100 PWE undergoing epilepsy surgery between 2019 and 2025 is being performed in three Dutch academic hospitals. Excluded are PWE who have a lower level of intelligence (TIQ<70) or who do not master the Dutch language. Before surgery and 3, 6, 12 and 24 months after surgery, PWE receive validated online questionnaires (QOLIE-31, EQ-5D, iMCQ and iPCQ) on QoL, cost of care, expectations and satisfaction. Primary outcome is the change in QoL. Secondary outcomes are change in generic QoL, seizure reduction (International League Against Epilepsy Outcome Classification), medical consumption, productivity, the correlation between QoL and seizure reduction and expectation of and satisfaction with the surgery. ETHICS AND DISSEMINATION: The study design has been approved by the Medical Ethics Review Committee (METC) of Maastricht UMC+ (2019-1134) and the Amsterdam UMC (vu). At the time of writing, UMC Utrecht is in the process of considering approval. The study will be conducted according to the Dutch Medical Research Involving Human Subjects Act and the Declaration of Helsinki. The results will be publicly disclosed and submitted for publication in international peer-reviewed scientific journals. There is no veto on publication by the involved parties. TRIAL REGISTRATION: NL8278; Pre-results.

QUality of life and Economic evaluation after neuroSTimulation for Epilepsy (QUESTE) in adolescents and adults with drug-resistant epilepsy: protocol for a multicentre, prospective observational cohort study in The Netherlands.

INTRODUCTION: Epilepsy is one of the most common chronic neurological disorders. Antiseizure medication (ASM) is the first choice of treatment, however, 30% of epilepsy patients are drug-resistant. For these patients, neuromodulation can be an option, especially when epilepsy surgery is not possible or did not lead to seizure freedom. Epilepsy is associated with reduced quality of life (QoL), which heavily depends on seizure control.The most recent Cochrane reviews have shown that vagus nerve stimulation and deep brain stimulation of the anterior nucleus of the thalamus, lead to a responder rate OR of, respectively, 1.93 and 1.20. The question arises if neuromodulation for drug-resistant epilepsy (DRE) will be more cost-effective than sole treatment with ASM. The current study aims to determine the change in QoL after neuromodulation. Secondarily, we will aim to study the cost-effectiveness of these treatments. METHODS AND ANALYSIS: This prospective cohort study aims at including 100 patients aged 16 or above who will be referred for neuromodulation, from January 2021 to January 2026. After informed consent, QoL and other relevant parameters will be assessed at baseline, 6 months, 1, 2 and 5 years after surgery. Data on seizure frequency will be derived from patient charts. We expect that DRE patients will report better QoL after neuromodulation. Even if they would still report seizures, the treatment can be seen as useful. This is especially true when patients can participate in society again to a greater extent than before treatment. ETHICS AND DISSEMINATION: The board of directors of participating centres all gave permission for this study to commence. The medical ethics committees decided that this study does not fall under the Medical Research Involving Human Subjects Act (WMO). The findings of this study will be presented at (inter)national conferences and in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NL9033.

A systematic review of economic evaluations of treatments for patients with epilepsy.

The increasing number of treatment options and the high costs associated with epilepsy have fostered the development of economic evaluations in epilepsy. It is important to examine the availability and quality of these economic evaluations and to identify potential research gaps. As well as looking at both pharmacologic (antiepileptic drugs [AEDs]) and nonpharmacologic (e.g., epilepsy surgery, ketogenic diet, vagus nerve stimulation) therapies, this review examines the methodologic quality of the full economic evaluations included. Literature search was performed in MEDLINE, EMBASE, NHS Economic Evaluation Database (NHS EED), Econlit, Web of Science, and CEA Registry. In addition, Cochrane Reviews, Cochrane DARE and Cochrane Health Technology Assessment Databases were used. To identify relevant studies, predefined clinical search strategies were combined with a search filter designed to identify health economic studies. Specific search strategies were devised for the following topics: (1) AEDs, (2) patients with cognitive deficits, (3) elderly patients, (4) epilepsy surgery, (5) ketogenic diet, (6) vagus nerve stimulation, and (7) treatment of (non)convulsive status epilepticus. A total of 40 publications were included in this review, 29 (73%) of which were articles about pharmacologic interventions. Mean quality score of all articles on the Consensus Health Economic Criteria (CHEC)-extended was 81.8%, the lowest quality score being 21.05%, whereas five studies had a score of 100%. Looking at the Consolidated Health Economic Evaluation Reporting Standards (CHEERS), the average quality score was 77.0%, the lowest being 22.7%, and four studies rated as 100%. There was a substantial difference in methodology in all included articles, which hampered the attempt to combine information meaningfully. Overall, the methodologic quality was acceptable; however, some studies performed significantly worse than others. The heterogeneity between the studies stresses the need to define a reference case (e.g., how should an economic evaluation within epilepsy be performed) and to derive consensus on what constitutes "standard optimal care."

Does sinus rhythm conversion after cardiac surgery affect postoperative health- related quality of life?

BACKGROUND: We investigated the impact and the predictive value of sinus rhythm at 12 months (SR12) on subscales of three different HrQoL questionnaires: SF-36., EuroQoL and MFI 20. METHODS: Data of 125 cardiac surgery patients with pre-operative AF from our previous randomized trial were used. Based on their rhythm outcome patients were divided in two groups: SR12 or AF at 12 months follow up (non-SR12). All questionnaires were self-administered pre-operatively and at 3 months, 6 months and 12 months after surgery. RESULTS: Synus rhytm at 12 months was predictive of improvement of SF36- mental score (MS, p = 0.021), Euro-QoL-MS (p = 0.009), VAS (p = 0.006), and MFI 20-MS (p = 0.009). We failed to find any significant interactions between SR12 and any of the other significant risk factors: age <65 years, paroxysmal type of AF and preoperative AF duration <12 months. In contrast, SR12 was not significant in predicting physical score (PS) subscales of any of the questionnaires (all, p > 0.05) which were predicted by age <65 years (SF36-PS, p = 0.029) by paroxysmal type of AF and age <65 years (Euro-QoL-PS, p = 0.017 and p = 0.04, respectively) and by AF duration <12 months, paroxysmal type of AF and age < 65 years (MFI 20-PS, p = 0.019, p = 0.020 and p = 0.015, respectively). CONCLUSIONS: Specific mental-related HrQoL scales are much more sensitive to sinus rhythm conversion. Sinus rithm mantainance shows significant effects on mental scores independently of other cofactors. Successful conversion to sinus rhythm after surgical ablation during cardiac surgery does not significantly affect phisical health related quality of life during 1 year follow up.

Health-related quality of life after fast-track treatment results from a randomized controlled clinical equivalence trial.

PURPOSE: This randomized clinical equivalence trial was designed to evaluate health-related quality of life (HRQoL) after fast-track treatment for low-risk coronary artery bypass (CABG) patients. METHODS: Four hundred and ten CABG patients were randomly assigned to undergo either short-stay intensive care treatment (SSIC, 8 h of intensive care stay) or control treatment (care as usual, overnight intensive care stay). HRQoL was measured at baseline and 1 month, and one year after surgery using the multidimensional index of life quality (MILQ), the EQ-5D, the Beck Depression Inventory and the State-Trait Anxiety Inventory. RESULTS: At one month after surgery, no statistically significant difference in overall HRQoL was found (MILQ-score P-value=.508, overall MILQ-index P-value=.543, EQ-5D VAS P-value=.593). The scores on the MILQ-domains, physical, and social functioning were significantly higher at one month postoperatively in the SSIC group compared to the control group (P-value=.049; 95%CI: 0.01-2.50 and P-value=.014, 95% CI: 0.24-2.06, respectively). However, these differences were no longer observed at long-term follow-up. CONCLUSIONS: According to our definition of clinical equivalence, the HRQoL of SSIC patients is similar to patients receiving care as usual. Since safety and the financial benefits of this intervention were demonstrated in a previously reported analysis, SSIC can be considered as an adequate fast-track intensive care treatment option for low-risk CABG patients.

Erythropoietin as an adjuvant treatment with (chemo) radiation therapy for head and neck cancer.

BACKGROUND: Tumour hypoxia increases tumour invasiveness and has a negative impact on response to therapy. Hypoxic tumours are also associated with severely anaemic individuals. It has therefore been hypothesised that correcting anaemia, by increasing haemoglobin levels using erythropoietin, improves tumour oxygenation and consequently the patient's prognosis. OBJECTIVES: To assess whether combined treatment with radiotherapy and erythropoietin (RT plus EPO) is better than standard radiotherapy (RT alone) for the treatment of head and neck cancer patients. SEARCH STRATEGY: We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; CINAHL; Web of Science; BIOSIS Previews; Cambridge Scientific Abstracts; mRCT and additional sources for published and unpublished trials. The date of the most recent search was 24 February 2009. SELECTION CRITERIA: Two independent authors assessed identified studies according to the eligibility criteria: RCTs which delivered radiotherapy combined with or without erythropoietin, in patients of any age with head and neck cancer of any stage or type. In addition, trials administering concomitant iron therapy among one or both arms were also eligible. DATA COLLECTION AND ANALYSIS: For statistical analysis of survival data, we computed a weighted estimate of the typical treatment effect across studies. We used Chi(2) heterogeneity tests to test for statistical heterogeneity among trials and performed the statistical analyses using Review Manager 5.0. MAIN RESULTS: Five RCTs with a total of 1397 patients were included. Pooled data yielded a significantly worse overall survival (OS) for RT plus EPO as compared to RT alone (Peto odds ratio 0.73; 95% confidence interval (CI) 0.58 to 0.91; P = 0.005, five trials). For local regional tumour control (LRTC) analyses resulted in a small but non-significant difference between the RT alone group and the RT plus EPO group (RR 0.92; 95% CI 0.81 to 1.03; P = 0.15, four trials). In addition, the local regional progression free survival (LRPFS) measured in four studies was significantly different between groups (Peto odds ratio 0.63; 95% CI 0.49 to 0.80; P = 0.0002, four trials), in favour of the RT alone group. Two studies used supplemental iron in the RT plus EPO group and not in the RT alone group. When excluding these studies from the analyses, the statistically (non-) significant differences in OS, LRTC and LRPFS are maintained. AUTHORS' CONCLUSIONS: There are strong suggestions that RT plus EPO has a negative influence on outcome as opposed to RT alone. However, the target haemoglobin concentration, which was higher than recommended in four of the five included RCTs, may have had a significant role. Nevertheless, based on these findings EPO should not be administered as an addition to RT outside the experimental setting for patients with head and neck cancer.

Concomitant hyperthermia and radiation therapy for treating locally advanced rectal cancer.

BACKGROUND: Surgery has been the treatment of choice for patients with rectal cancer. For locally advanced cancer results were poor, with high rates of locoregional recurrences and poor overall survival data. Adding (chemo)radiotherapy upfront improved results mainly in locoregional control. Adding hyperthermia to radiotherapy preoperatively might have an equivalent beneficial effect. OBJECTIVES: To quantify the potential beneficial effect of thermo radiation compared to chemo-radiation with respect to pathological complete responses, overall survival and toxicity in rectal cancer therapy. SEARCH STRATEGY: We identified the relevant phase II and III randomised controlled trials in any language trough electronic searches May 2007 of the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2007), the Cochrane Colorectal Cancer Groups Specialised Register, MEDLINE (from 1966), EMBASE (from 1974), CINAHL (from 1982). Furthermore, various trial databases were searched for the identification of recent completed and ongoing trials (metaRegister of Controlled Trials, Cancer Research UK, Cancer.gov, The Eastern Cooperative Oncology Group Trials Database). All studies identified until May 2007 were considered for inclusion in the present study. SELECTION CRITERIA: Only phase II and III randomised controlled clinical trials were included in the analysis. DATA COLLECTION AND ANALYSIS: All identified studies were assessed by two independent reviewers. A weighted estimate of the treatment effect was computed for 2, 3, 4 and 5-year survival, for local tumour recurrence, severe acute and late toxicity and complete tumour response (CR). CR was defined either clinically by disappearance of all pretreatment signs of local tumour or pathologically by microscopically free margins. The risk ratio (RR) and hazard ratio (HR) were used. Analyses were performed with the Reference Manager (RevMan). MAIN RESULTS: Six RCTs published between 1990 and 2007 were identified. A total number of 520 patients was treated, 258 in the radiotherapy only arm (RT) and 262 in the radiotherapy-hyperthermia arm (RHT). Four studies (424 patients) reported overall survival (OS) rates. After 2 years, OS was significantly better in the RHT group (HR 2.06; 95% CI 1.33-3.17; p=.001), but this difference disappeared after a longer period (3, 4 and 5 year OS). All but one studies reported CR rates. A significant higher CR rate was observed in the RHT group (RR 2.81; 95% CI 1.22-6.45; p=.01). Only 2 studies reported on acute toxicity. In these 2 studies no significant differences were observed between the RT and the RHT group. Late toxicity data were not reported. AUTHORS' CONCLUSIONS: Further studies are needed to compare chemoradiation versus thermoradiation versus chemoradiation plus hyperthermia in well selected/conducted and quality controlled randomised trials.

Does fast-track treatment lead to a decrease of intensive care unit and hospital length of stay in coronary artery bypass patients? A meta-regression of randomized clinical trials.

OBJECTIVE: Evaluation of randomized, controlled clinical trials studying fast-track treatment in low-risk coronary artery bypass grafting patients. DESIGN: Meta-regression. PATIENTS: Low-risk coronary artery bypass grafting patients. INTERVENTIONS: Fast-track treatments including (high or low) anesthetic dose, normothermia vs. hypothermia, and extubation protocol (within or after 8 hrs). MEASUREMENTS: Number of hours of intensive care unit stay, number of days of hospital stay, prevalence of myocardial infarction, and death. Furthermore, quality of life and cost evaluations were evaluated. The epidemiologic and economic qualities of the different trials were also assessed. MAIN RESULTS: A total of 27 studies evaluating fast-track treatment were identified, of which 12 studies were with major and 15 were without major differences in extubation protocol or anesthetic treatment or both. The use of an early extubation protocol (p=.000) but not the use of a low anesthetic dose (p=.394) or normothermic temperature management (p=.552) resulted in a decrease of the total intensive care unit stay of low-risk coronary artery bypass grafting patients. Early extubation was found to be an important determinant of the total hospital stay for these patients. An influence of the type of fast-track treatment on mortality or the prevalence of postoperative myocardial infarction was not observed. In general, the epidemiologic and economic qualities of included studies were moderate. CONCLUSIONS: Although fast-track anesthetics and normothermic temperature management facilitate early extubation, the introduction of an early extubation protocol seems essential to decrease intensive care unit and hospital stay in low-risk coronary artery bypass grafting patients.

One-year cost-effectiveness of surgical treatment of morbid obesity: vertical banded gastroplasty versus Lap-Band.

BACKGROUND: This study was designed as an economic evaluation alongside a randomized clinical trial. The object of this study was to evaluate the 1-year cost-effectiveness of surgical treatment of morbid obesity comparing two operations. METHODS: 100 patients were assigned randomly to vertical banded gastroplasty (VBG) or Lap-Band surgery. Both medical and non-medical costs were identified and measured. Costs data were combined with percentage Excess Weight Loss (%EWL) and with Quality Adjusted Life Years (QALYs) to obtain cost per %EWL and cost per QALY ratios. RESULTS: At 1 year, the total costs were not significantly different between both groups (95% confidence interval E5,999-E1,765). Also, the QALY gain after surgery was not significantly different between the two groups. However, %EWL was significantly higher in the VBG group compared to the Lap-Band group, P-value .0001. The estimated incremental cost per %EWL was E105.83 (E1,885.91/-17.82). For the costs per QALY, the estimated ratio was dominant. The overall mortality in this study was 2%. 2 patients in the VBG group died within 30 days after surgery; 1 of these deaths was possibly related to the VBG procedure. CONCLUSION: At 1 year after surgery, the costs and QoL of the two treatment modalities were found to be equal. Therefore, the selection of the procedure can be based on the clinical aspects, effectivity and safety at 1 year. In addition, the results of a long-term cost-effectiveness analysis (e.g. with a follow-up of 36 months) planned in the future can also be helpful in the selection of the preferred treatment.

Short-stay intensive care after coronary artery bypass surgery: randomized clinical trial on safety and cost-effectiveness.

OBJECTIVE: To evaluate the safety and cost-effectiveness of short-stay intensive care (SSIC) treatment for low-risk coronary artery bypass patients. DESIGN: Randomized clinical equivalence trial. SETTING: University Hospital Maastricht, the Netherlands. PATIENTS: Low-risk coronary artery bypass patients. INTERVENTIONS: A total of 600 patients were randomly assigned to undergo either SSIC treatment (8 hrs of intensive care treatment) or control treatment (care as usual, overnight intensive care treatment). MEASUREMENTS: The primary outcome measures were intensive care readmissions and total hospital stay. The secondary outcome measures were total hospital costs, quality of life, postoperative morbidity, and mortality. Hospital costs consisted of the cost of hospital admission or admissions and outpatient costs. MAIN RESULTS: The difference in intensive care readmission between the two groups of 1.13% was very small and not significantly different (p = .241; 95% confidence interval, -0.9% to 2.9%). The total hospital stay (p = .807; 95% confidence interval, 1.2 to -0.4) and postoperative morbidity were comparable between the groups. The SSIC group's quality of life improved more compared with the control group's quality of life (p = .0238; 95% confidence interval, 0.0012 to 0.0464). The total hospital costs for SSIC were significantly lower (95% confidence interval, -1,581 to -174) compared with those for the control group (4,625 and 5,441, respectively). The estimated incremental cost-effectiveness ratio (cost/delta quality-adjusted life months) thus showed the dominance of SSIC. Bootstrap and sensitivity analyses confirm the robustness of the study findings. CONCLUSIONS: Compared with usual care, SSIC is a safe and cost-effective approach. SSIC can be considered as an alternative for conventional postoperative intensive care treatment for low-risk coronary artery bypass graft patients.