[Economic evaluation of porous metal cones in total knee arthroplasty]. / Étude de l'impact économique des cônes en métal poreux dans les arthroplasties totales du genou.

INTRODUCTION: The use of porous metal cones (PMC) to fill bone loss during knee replacements is increasing, but these medical devices are not reimbursed in addition to diagnosis related tariffs (DRTs). The economic impact of PMC may be significant for hospitals. MATERIAL AND METHODS: This multicenter observational study includes all patients who benefited of a total knee prosthesis, with reconstruction by PMC, between June 2014 and June 2019, in two French university hospitals. The costs of each diagnosis related group (DRG) was evaluated using the "étude nationale des coûts à méthodologie commune (ENC)". The PMC costs were compared with the amounts of DRG and with the fares perceived by the hospital from the French sickness fund (DRTs). RESULTS: 96 patients (103 stays) benefited from the implantation of 195 cones. The hospital incomes were 10,970±1401€ /stay. Spending associated with PMC represented 35% of DRGs and 44% of DRTs. The average additional cost related to the cones was 2709±1138€ /stay. If the reconstructions had been performed by allograft, the average gain for hospitals would have been 108€ /stay. CONCLUSION: If PMC have clinical benefits for surgeons in reducing the incidence of revision, this study shows the inadequacy of the funding of these devices for French hospitals. This suggests the need to expand the possibilities of supporting innovative technologies.

Cost-effectiveness of stent-retriever thrombectomy in large vessel occlusion strokes of the anterior circulation: Analysis from the French societal perspective.

OBJECTIVES: To determine the cost-effectiveness of stent retriever thrombectomy (SRT) added to standard of care (SOC) in large vessel occlusion (LVO) strokes, adopting the French societal perspective given the lack of published studies with such perspective. METHODS: We developed an hybrid model (decision tree until one year post-stroke followed by a Markov model from one year onward). The time horizon was 20 years. We calculated transition probabilities across the modified Rankin Scale (mRS) based on a published meta-analysis. The main outcome measure was quality adjusted life-years (QALYs) gained. Resources and input costs were derived from a literature search. We calculated the incremental cost-effectiveness ratio (ICER) expressed as cost/QALY. We used 1-way deterministic and probabilistic sensitivity analysis (PSA) to evaluate the model uncertainty. RESULTS: In the base-case, adding SRT to SOC resulted in increased effectiveness of 0.73 QALY while total costs were reduced by 3,874€ (ICER of -5,400€/QALY). In the scenario analysis adopting the French healthcare system perspective, the ICER was 4,901€/QALY. Parameters the most influential were the relative risks of SRT over SOC for 90-days mortality and for 90-days mRS 0-2, and the time horizon. PSA showed the 95% confidence interval of the ICER was -21,324 to 4,591€/QALY, with SRT having 85.5% chance to be dominant and 100% to be cost-effective at a threshold of 50,000€/QALY. CONCLUSION: SRT was dominant from a French societal perspective, from 9 years post-stroke onwards. Cost-effectiveness of SRT added to SOC becomes undisputable with evidences from payer and societal viewpoints.

Optimization of high-grade glioma resection using 5-ALA fluorescence-guided surgery: A literature review and practical recommendations from the neuro-oncology club of the French society of neurosurgery.

BACKGROUND: When feasible, the surgical resection is the standard first step of the management of high-grade gliomas. 5-ALA fluorescence-guided-surgery (5-ALA-FGS) was developed to ease the intra-operative delineation of tumor borders in order to maximize the extent of resection. METHODS: A Medline electronic database search was conducted. English language studies from January 1998 until July 2018 were included, following the PRISMA guidelines. RESULTS: 5-ALA can be considered as a specific tool for the detection of tumor remnant but has a weaker sensibility (level 2). 5-ALA-FGS is associated with a significant increase in the rate of gross total resection reaching more than 90% in some series (level 1). Consistently, 5-ALAFGS improves progression-free survival (level 1). However, the gain in overall survival is more debated. The use of 5-ALA-FGS in eloquent areas is feasible but requires simultaneous intraoperative electrophysiologic functional brain monitoring to precisely locate and preserve eloquent areas (level 2). 5-ALA is usable during the first resection of a glioma but also at recurrence (level 2). From a practical standpoint, 5-ALA is orally administered 3 hours before the induction of anesthesia, the recommended dose being 20 mg/kg. Intra-operatively, the procedure is performed as usually with a central debulking and a peripheral dissection during which the surgeon switches from white to blue light. Provided that some precautions are observed, the technique does not expose the patient to particular complications. CONCLUSION: Although 5-ALA-FGS contributes to improve gliomas management, there are still some limitations. Future methods will be developed to improve the sensibility of 5-ALA-FGS.

Is fluorescence-guided surgery with 5-ala in eloquent areas for malignant gliomas a reasonable and useful technique?

INTRODUCTION: High-grade gliomas surgery in eloquent areas must achieve two pivotal aims: oncological efficacy and preservation of unimpaired neurological functions or improvement of impaired neurological functions. Here, we evaluated the safety and the usefulness of 5-ALA fluorescence-guided surgery in eloquent areas. MATERIAL AND METHODS: Single center, retrospective and consecutive series of adult patients operated on for a supratentorial glioblastoma between November 2012 and November 2015. RESULTS: Fifty-one patients with a glioblastoma located within an eloquent area were included: 24 patients operated on with 5-ALA (5-ALA group), and 27 patients operated on under white light (control group). Preoperative motor and language deficits were similar in the 5-ALA group (50%, 37.5%) as in the control group (59.3%, 55.6%) (P=0.510; P=0.200). Three-month postoperative motor and language deficits rates were similar in the 5-ALA group (12.5%, 12.5%) as in the control group (29.6%, 14.8%) (P=0.180; P=0.990). The extent of resection did not significantly vary between groups (P=0.280). The overall survival did not significantly vary between groups (P=0.080) but the progression-free survival was significantly higher in the 5-ALA group than in the control group (P=0.020). The 12-month progression-free survival was significantly higher in 5-ALA group (60%) than in control group (21%; P=0.006). In multivariate analysis, the 5-ALA was an independent prognostic factor associated with progression-free survival (P=0.030). CONCLUSION: 5-ALA fluorescence-guided surgery for glioblastoma located in eloquent areas is effective to improve progression-free survival. To preserve functional outcomes, it requires the routine use of intraoperative functional mapping to respect functional boundaries.

[Economic evaluation of medical devices not included in the French list of products and services qualifying for reimbursement: Example of biologic meshes]. / Impact économique à l'hôpital de dispositifs médicaux non remboursés en sus des GHS : exemple des prothèses de renfort biologiques.

OBJECTIVES: To present a method aimed to evaluate the economic impact associated with the use of medical devices (DM) not reimbursed in addition to diagnosis related groups (DRGs) tariffs using the example of biological meshes for parietal reinforcement. METHODS: In this multicenter retrospective cohort study, we included all patients who received a biological mesh between January 2010-April 2014 (University hospitals of Saint-Étienne, France) or between January 2010-March 2015 (Lyon University hospitals, France). Measured costs associated with biologic meshes were compared to those of the "Étude nationale des coûts à méthodologie commune" (2012) to weigh the economic impact of biologic meshes with the French DRGs costs. We also compared these costs to the fares perceived by the hospital from the French sickness fund (GHS). RESULTS: Thirty-six patients received a biological mesh and were treated by a total of 38 biological meshes. Of these, the implant was Protexa®, Permacol® and Strattice® in 66%, 29% and 5% of cases respectively. The hospitals incomes were 10,496±5562€ per stay. Meshes-related expenditures represented in average 28% of DRGs costs and 38% of GHS tariffs. The mean additional cost for biological meshes was 3793±2292 euros compared to the mean cost on implantable medical devices in the French DRGs. CONCLUSION: Given their currently restricted use, the hospital budget impact of biological meshes remains limited although the incremental cost per patient is substantial. Analytic costs data can be useful within the scope of decision-making related to DM not refunded by the French health system.

Xenograft biologic mesh in parietal and general surgery: Technical assessment and review of clinical effectiveness and safety data.

STUDY AIM: To describe the main technical characteristics of biologic prostheses used for parietal reinforcement and to present the state of the art on their risk/benefit ratio. METHODS: We conducted a technical analysis of manufacturer specifications of the biologic prostheses that are currently available in France accompanied by a literature review by selecting meta-analyses and systematic reviews, randomized controlled trials and publications of health technology rating agencies. RESULTS: Biological implants for parietal reinforcement are mainly intended for use in a contaminated environment where the use of synthetic prostheses is contra-indicated. We identified fourteen systematic reviews and meta-analyses and one randomized controlled trial. Six ongoing clinical trials were identified as well as two clinical trials that had been interrupted. In the current state of knowledge, there are no high-level evidence data on the therapeutic contribution of biologic prostheses that allow prioritization of the various biologic prostheses according to their characteristics or their different manufacturing processes. CONCLUSION: Pending the results of current randomized controlled trials to validate the indications and an eventual specific reimbursement, indications for the use of biologic parietal reinforcement prostheses seems to be limited to rare clinical situations and only after collegial discussion.

The cost-effectiveness of tumor-treating fields therapy in patients with newly diagnosed glioblastoma.

BACKGROUND: There is strong concern about the costs associated with adding tumor-treating fields (TTF) therapy to standard first-line treatment for glioblastoma (GBM). Hence, we aimed to determine the cost-effectiveness of TTF therapy for the treatment of newly diagnosed patients with GBM. METHODS: We developed a 3-health-state Markov model. The perspective was that of the French Health Insurance, and the horizon was lifetime. We calculated the transition probabilities from the survival parameters reported in the EF-14 trial. The main outcome measure was incremental effectiveness expressed as life-years gained (LYG). Input costs were derived from the literature. We calculated the incremental cost-effectiveness ratio (ICER) expressed as cost/LYG. We used 1-way deterministic and probabilistic sensitivity analysis to evaluate the model uncertainty. RESULTS: In the base-case analysis, adding TTF therapy to standard of care resulted in increases of life expectancy of 4.08 months (0.34 LYG) and €185 476 per patient. The ICER was €549 909/LYG. The discounted ICER was €596 411/LYG. Parameters with the most influence on ICER were the cost of TTF therapy, followed equally by overall survival and progression-free survival in both arms. The probabilistic sensitivity analysis showed a 95% confidence interval of the ICER of €447 017/LYG to €745 805/LYG with 0% chance to be cost-effective at a threshold of €100 000/LYG. CONCLUSION: The ICER of TTF therapy at first-line treatment is far beyond conventional thresholds due to the prohibitive announced cost of the device. Strong price regulation by health authorities could make this technology more affordable and consequently accessible to patients.

Current trends in the management of glioblastoma in a French University Hospital and associated direct costs.

WHAT IS NEW AND OBJECTIVES: Trends in the care of glioblastoma in actual practice settings are poorly described. In a previous pharmacoepidemiologic study, we highlighted changes in the management of patients with glioblastoma (GBM) newly diagnosed between 2004 and 2008. Our aim was to complete and to extend the previous report with a study of a cohort of patients diagnosed in 2011 to emphasize the trends in the pharmacotherapy of GBM over the last decade. METHODS: A single-centre study was undertaken of three historic cohorts of GBM patients newly diagnosed during years 2004, 2008 and 2011 (corresponding to groups 1, 2 and 3, respectively) but limited to patients eligible for radiotherapy after initial diagnosis. The type of medical management was described and compared, as well as overall survival and total cost from diagnosis to death or the last follow-up date. Cost analysis was performed from the French sickness fund perspective using tariffs from 2014. RESULTS: Two hundred and seventeen patients (49 in Group 1, 73 in Group 2, 95 in Group 3) were selected with similar baseline characteristics. Fluorescence-guided surgery using 5-ALA was increasingly used over the three periods. There was a strong trend towards broader use of temozolomide radiochemotherapy (39%, 73% and 83% of patients, respectively) as first-line treatment as well as bevacizumab regimen at recurrence (6%, 48% and 58% of patients, respectively). The increase in overall survival between Group 2 and Group 1 was confirmed for patients in Group 3 (17·5 months vs. 10 months in Group 1). The mean total cost per patient was 53368 € in Group 1, 70 201 € in Group 2 and 78355 € in Group 3. Hospital care represented the largest expenditure (75%, 59% and 60% in groups 1, 2 and 3, respectively) followed by chemotherapy drug costs (11%, 30% and 29%, respectively). WHAT IS NEW AND CONCLUSION: This is the first study to report on changes in the management of GBM in real-life practice. The ten-year study indicates an improvement in overall survival but also an increase in total cost of care. The data should be useful for informing the care of GBM patients in settings similar to ours.

Direct costs associated with the management of progressive early onset scoliosis: estimations based on gold standard technique or with magnetically controlled growing rods.

BACKGROUND: The main disadvantage of the surgical management of early onset scoliosis (EOS) using conventional growing rods is the need for iterative surgical procedures during childhood. The emergence of an innovative device using distraction-based magnetically controlled growing rods (MCGR) provides the opportunity to avoid such surgeries and therefore to improve the patient's quality of life. HYPOTHESIS: Despite the high cost of MCGR and considering its potential impact in reducing hospital stays, the use of MCGR could reduce medical resource consumption in a long-term view in comparison to traditional growing rod (TGR). MATERIALS AND METHODS: A cost-simulation model was constructed to assess the incremental cost between the two strategies. The cost for each strategy was estimated based on probability of medical resource consumption determined from literature search as well as data from EOS patients treated in our centre. Some medical expenses were also estimated from expert interviews. The time horizon chosen was 4 years as from first surgical implantation. Costs were calculated in the perspective of the French sickness fund (using rates from year 2013) and were discounted by an annual rate of 4%. Sensitivity analyses were conducted to test model strength to various parameters. RESULTS: With a time horizon of 4 years, the estimated direct costs of TGR and MCGR strategies were 49,067 € and 42,752 €, respectively leading to an incremental costs of 6135 € in favour of MCGR strategy. In the first case, costs were mainly represented by hospital stays expenses (83.9%) whereas in the other the cost of MCGR contributed to 59.5% of the total amount. In the univariate sensitivity analysis, the tariffs of hospital stays, the tariffs of the MCG, and the frequency of distraction surgeries were the parameters with the most important impact on incremental cost. DISCUSSION: MCGR is a recent and promising innovation in the management of severe EOS. Besides improving the quality of life, its use in the treatment of severe EOS is likely to be offset by lower costs of hospital stays. LEVEL OF EVIDENCE (WITH STUDY DESIGN): Level IV, economic and decision analyses, retrospective study.

Management of glioblastoma: comparison of clinical practices and cost-effectiveness in two cohorts of patients (2008 versus 2004) diagnosed in a French university hospital.

WHAT IS KNOWN AND OBJECTIVE: Therapeutic options for the management of glioblastoma (GBM) have greatly evolved over the last decade with the emergence of new regimens combining radiotherapy plus temozolomide and the use of bevacizumab at recurrence. Our aim was to assess the clinical and economic impacts of those novel strategies in our center. METHODS: A single-center retrospective chart review was conducted on patients newly diagnosed with a GBM over two periods (year 2004, group 1 or year 2008, group 2) with limitations to those eligible to radiotherapy after initial diagnosis. The type of medical management was described and compared, as well as overall survival and total costs from diagnosis to death or the last follow-up date. Cost analysis was performed under the French Sickness Fund perspective using tariffs from 2012. RESULTS: One hundred twenty-two patients were selected (49 in group 1 and 73 in group 2) with similar baseline characteristics within the two groups. Patients from group 2 received more frequently temozolomide radiochemotherapy (71% vs. 39%, P < 0·05) as first-line treatment as well as bevacizumab regimen at recurrence (48% vs. 6%, P < 0·05); the median overall survival was increased between the two periods (respectively 17 vs. 10 months, P < 0·05). The mean total cost per patient was 54,388 € in group 1 and 71,148 € in group 2 (P < 0·05). Hospital care represented the largest expenditure (76% and 58% in groups 1 and 2 respectively) followed by chemotherapy drugs costs (11% and 30% respectively). The total cost difference between the two groups was explained by the increasing use of temozolomide and bevacizumab. The incremental cost-effectiveness ratio was estimated at 54,355 € per life-year gained. WHAT IS NEW AND CONCLUSION: As far as we know, this is the first study reporting the total cost of GBM management based on the French perspective, as well as the cost-effectiveness of clinical practices in term of cost per life-year gained. Those novel strategies have contributed to improve overall survival while inducing a substantial, but acceptable, increase of total costs.

[Impact of sugammadex on neuromuscular blocking agents use: a multicentric, pharmaco-epidemiologic study in French university hospitals and military hospitals]. / Impact du sugammadex sur les consommations de curares : étude pharmaco-épidémiologique multicentrique dans les centres hospitalo-universitaires et hôpitaux d'instructions des armées français.

INTRODUCTION: Seven Neuromuscular Blocking Agents (NMBA) are commercialized in France. Four of them have an intermediate duration of action. Sugammadex required the use of NMBA slightly employed in clinical practice in France. Its introduction in routine practice could have an impact on NMBA use in clinical practice. This study was then conducted to assess and compare NMBA use before and after the commercialization of sugammadex. MATERIALS AND METHODS: A longitudinal, retrospective, observational study was conducted between 2008 and 2011 in French university hospitals and military hospitals. The consumption data for sugammadex and NMBA were collected using a collection grid which was filled by pharmacists or anesthesiologists. Drug use was measured by the number of vials used divided by the annual number of hospitalizations in surgery and obstetrics (HSO). An overall analysis of the annual frequency of NMBA use was firstly performed, then individual data of each hospital were analyzed. Descriptive statistical analysis including mean, standard deviation, median, minimum and maximum was achieved. RESULTS: Thirty-four out of 39 hospitals participated in the study (87%) and analysis was performed on 26 of them (7%). The data of eight institutions were excluded due to missing values or because of the non-admission of sugammadex in their formulary. The NMBA mostly used were non-steroidal NMBA (75% of market share) with an increased use between 2008 and 2011 concerning atracurium (from 41 to 51 vials of 50mg atracurium used per 100 HSO). The overall analysis revealed an increase of the occurrence of rocuronium (between 2008 and 2011: from 1 to 4.8 vials of 50mg rocuronium used per 100 HSO). Individual analyses on each hospital showed a possible effect of sugammadex introduction on NMBA use in nine hospitals. DISCUSSION AND CONCLUSIONS: The commercialization of sugammadex seems to have induced a discrete increase of steroidal NMBA but non-steroidal NMBA remain the leading agent in France. A long-term follow-up is deserved.

[Economic and organizational impact of the use of a disposable sheath with a flexible cystoscope]. / Cystoscope flexible à gaine stérile à usage unique: impact organisationnel et économique et sécurité bactériologique.

PURPOSE: To assess both economical and organizational impact as well as bacteriologic safety of a flexible cystoscope with sterile disposable sheath (FCSDS) compared to standard flexible cystoscopy (SFC) in two French urologic academic units. PATIENTS: Two-center prospective study, comparing the use of the FCSDS to the SFC on two consecutive periods of time. Two hundred and five patients were included and divided into each group. Duration procedures and costs were analysed in the two techniques. The urinary tract infection rate was also described. A dedicated sheaths leaks test after use was performed systematically. RESULTS: The preparation time of the fibroscope was longer for the sheathed cystoscopy group: 16.2 minutes versus 10.9 minutes for the standard group. The mean duration of disinfection was significantly shorter for the sheathed cystoscopy group: 53.8 minutes saved compared to the standard group; 99.01% of the tested sheaths, after their use, had no breaches. Urinary tract infections rate were similar in the two groups. The average cost of a sheathed cystoscopy compared to the standard was significantly cheaper in Lyon and almost equivalent in Marseille. CONCLUSION: The FCSDS allows significant saving over the disinfection duration, consumable costs and staff costs, while ensuring patient bacteriologic safety similar to SFC.

[Surgery of high-grade gliomas guided by fluorescence: a retrospective study of 22 patients]. / Exérèse neurochirurgicale optimale des gliomes de haut grade guidée par fluorescence : mise au point à partir d'une série rétrospective de 22 patients.

BACKGROUND AND PURPOSE: Optimal surgical resection improves the prognosis of glioblastomas. However, this goal is far from being achieved due to its invasive nature. Several studies have already shown the efficacy of fluorescence-guided surgery, in improving the quality of resection of glioblastoma. We report herein our experience through a retrospective serie and describe the principles, limitations and advantages of this technique. METHODS: Between 2006 and 2009, 22 patients underwent resection of a glioblastoma guided by fluorescence. Following operations, all patients underwent sequential clinical examination and radiological monitoring using multimodal MRI. The extent of resection was assessed by the surgeon during the procedure and by the radiologist on MRI. The curves of progression-free clinical survival (SSP) and overall survival (SG) were analyzed. The prognostic value of the extent of resection was studied. RESULTS: We obtained 68.2% of complete resection according to the absence of residual fluorescence as assessed by the surgeon, and 75% according to the absence of residual tumor on early MRI. The median SSP was 10.75 months and the median SG was 17 months. Complete tumoral resection confirmed by loss of fluorescence significatively increases the median SSP of 6.7 months to 12.9 months (p=0.001559) and the median SG of 12.3 months to 20.9 months (p=0.000559). After 1 year, 81.8% of patients were still alive. CONCLUSIONS: Our study confirms the use of fluorescence as an effective method to allow optimal resection of glioblastoma. In addition to neuronavigation, surgical experience, vision and proprioception, fluorescence contributes to achieve a complete tumor resection.

Management of relapsed or refractory multiple myeloma in French hospitals and estimation of associated direct costs: a multi-centre retrospective cohort study.

WHAT IS KNOWN AND BACKGROUND: For relapsed or refractory multiple myeloma (RRMM), a series of novel agents (thalidomide, bortezomib and lenalidomide) has emerged during the latest decade, but their use in routine clinical practice is not well documented as well as the cost of RRMM. OBJECTIVE: Our aim is to review the therapeutic management of such patients in France and to estimate the associated costs. METHODS: A retrospective cohort study, based on chart reviews, was conducted in French Haematology Departments over the period 2004-2007 and the associated direct costs estimated. RESULTS: One hundred and two patients with a relapse after first-line therapy were selected from five centres. The average follow-up from diagnosis or the date of first relapse to death or to the latest news was respectively 56.25 and 23.53 months. Novel agents were used in 73% of all cases, and in all cases of first relapse. Thalidomide and bortezomib were respectively the most frequently used second-line (57%) and third-line treatments (44%). The average number of lines of treatment received per patient as from first relapse was 2.75 (min 1; max 8) and the mean direct cost per month was estimated at 3130 € after the first relapse. This cost was represented in greater part by the cost of chemotherapy drugs (66%). WHAT IS NEW AND CONCLUSION: The use of novel agents such as thalidomide, bortezomib and lenalidomide for RRMM is highly prevalent in France from the first relapse. The associated medical cost is substantial mainly due to the cost of the new agents.

Lenalidomide in the treatment of multiple myeloma: a review.

Lenalidomide is an immunomodulatory drug derived from thalidomide. It was developed to maximize the anti-inflammatory and anti-neoplasic properties of thalidomide and to reduce its toxicity. The molecular mechanism of action of lenalidomide is unclear, but its therapeutic activity is mainly due to its well defined anti-inflammatory, immunomodulatory, anti-proliferative and anti-angiogenic properties. In relapsed or refractory multiple myeloma (MM), lenalidomide, combined with standard dose dexamethasone, is superior to dexamethasone alone in terms of time to progression, response rate and overall survival. The most commonly reported adverse events include haematological toxicity with manageable neutropenia and thrombopenia. Lenalidomide does not trigger the limiting toxicities of thalidomide: somnolence, neuropathy and constipation. Lenalidomide, in combination with dexamethasone, is indicated for the treatment of MM patients who have received at least one prior therapy and is administered orally at the dose of 25 mg q.d. for 21 days of 28-day cycles. The drug is being investigated for the treatment of newly diagnosed MM. In this review, we summarize the pharmacokinetic, pharmacodynamic and clinical trial data on lenalidomide.