From electrophysiological exploration to management of heart arrhythmias: Economic analysis of practices in a high-volume French hospital over two different time periods.

BACKGROUND: Medical devices (MD) used to treat arrhythmias range from electrophysiological exploration catheters to intracardiac ablation catheters, and they are continuously undergoing optimization. The inclusion of innovative MD in Diagnosis Related Groups (DRG) of the French healthcare economic system can lead to financial imbalance for health institutions. The objective of this study was to compare cost-revenue analyses for interventional heart rhythm management in a high-volume French hospital between two time periods. METHODS: For 3 months in 2014 and 3 months in 2017, all of the patients admitted to the interventional rhythmic unit with arrhythmia were included retrospectively in this monocenter study. All arrhythmias were considered. The primary clinical endpoint was the difference between the expenses and incomes, calculated for each patient. The secondary endpoint was the breakdown of costs. RESULTS: 217 patients were included. In 2014 period, the analysis revealed a deficit of 409±1717 euros per patient and an overall deficit for the hospital of 44,635 euros. In 2017 period, the same evaluation indicated a deficit of 446±1316 euros per patient and an overall deficit for the hospital of 48,210 euros. The cost of MD accounts for a significant share of total expenses. CONCLUSION: The profitability for the cardiac rhythm activity at our facility was optimized between 2014 and 2017. The reliance on ambulatory care increased. However, the reduction in the expenses incurred did not increase the profitability for the facility. It was offset by a decrease in DRG tariffs. A flowchart-type structure based on these practices analyses for rhythmic disorder treatments was developed.

Economic challenges of using innovative medical devices in major public health pathologies: Example of acute ischemic stroke management by mechanical thrombectomy.

BACKGROUND: Activity-based Funding can induce financial imbalances for health institutions if innovative medical devices (MD) used to perform acts are included in Diagnosis Related Groups (DRG) tariff. To be reimbursed in addition to the DRG tariff, innovative MD must have received a favorable evaluation by the French National Authority for Health (Haute Autorité de Santé) and be registered on the positive list. The aim of this study was to evaluate the expenses and incomes generated by each scenario (before and after the reimbursement of MD), and the financial reports. This study concerned the management of ischemic stroke by mechanical thrombectomy devices, in high-volume French hospital. METHODS: All patients who have had an acute ischemic stroke and admitted to the interventional neuroradiology unit between January 2016 and December 2017 were included retrospectively in this monocentric study. They were divided into four subgroups based on the severity of the DRG. The cost study was carried out using the French National Cost Study Methodology adjusted for the duration of the stays and by micro-costing on MD. RESULTS: A total of 267 patients were included. Over the study period, the average cost of the hospital stay was €10,492±6364 for a refund of €9838±6749 per patient. The acts performed became profitable once the MD were registered on the positive list (€-1017±3551 vs. €560±2671; P<0.05). Despite this reimbursement, this activity remained in deficit for DRG lowest severity (level 1) patients (€-492±1244). Specific MD used for mechanical thrombectomy represented 37% of the total cost of stay. CONCLUSION: The time required to evaluate MD reimbursement files is too long compared to their development. As a result, practitioners are in difficulty to be able to carry out acts according to the consensual practices of their learned societies, without causing any financial deficit of their institutions.

[The roles and the impacts of pharmacists in the management of medical devices at the hospital: A literature review]. / Rôles et retombées des pharmaciens dans la gestion des dispositifs médicaux en établissement de santé : une revue de littérature.

OBJECTIVES: Identify the training profile and the published evidences about the roles and the impacts of hospital pharmacists in medical devices. METHODS: A literature review was conducted using Google, Google Scholar and Pubmed for 1990-2016 associated with a manual search conducted in three non-indexed pharmaceutical journals for 2000-2016. RESULTS: The analysis of training programs available did not allow us to identify a specific training profile. A total of 72 articles related to the roles and the impacts of the pharmacist were identified, 52 of which came from non-indexed journals. Those articles did not deal specifically about the roles and the impacts of pharmacist; however, articles were analyses for three spheres including the referencing of medical devices (n=36), the evaluation (n=19) and the distribution system (n=13). CONCLUSIONS: French pharmacists have many theoretical and practical training opportunities. There are a few articles describing precisely the roles and the impacts of hospital pharmacists in medical device. It appears urgent to better document this activity in professional and indexed literature.

Medico-economic study of the management of hepatocellular carcinoma by chemo-embolization.

PURPOSE: This study has two aims. The first is to compare conventional lipiodol chemo-embolization (Trans Arterial Chemo-Embolization - TACE) to one using pre-loaded particles (Trans Arterial Chemo-Embolisation-Drug Eluted Bead - TACE-DEB) using a cost minimization study. The second is to define the fundable nature of TACE-DEB and the conditions under which it is cost-effective. MATERIALS AND METHODS: Retrospective study of patients treated by chemo-embolization (n=31: TACE; n=32: TACE-DEB) during the year 2010. The cost minimization study was conducted from the hospital perspective. Direct medical costs were calculated and compared using the readjusted ENCC (National Studies of Costs by Common Methodology) method. The affordability of the two techniques and definition of a cost-effective hypothesis (break-even point) were also established. RESULTS: All DRGs combined, lengths of stay (TACE: 4.90 ± 3.36; TACE-DEB: 5.03 ± 3.36) does not change significantly. An average upper mean cost for TACE-DEB is described (TACE: 2869.05 €; TACE-DEB: 3960.10 €). The affordability calculations in the study show that, overall, TACE-DEB can be funded regardless of DRG. A ratio of 1.3 procedures using the conventional (TACE) method would enable TACE-DEB procedures to be funded. CONCLUSION: This medico-economic analysis demonstrates that the TACE-DEB procedure is fundable.

[Cost-effectiveness analysis of vacuum-assisted closure in the surgical wound bed preparation of soft tissue injuries]. / Evaluation coût-efficacité de la thérapie par pression négative dans la préparation chirurgicale des pertes de substance cutanée.

This work proposes, from the point of view of the University Hospital Center of Nantes (acute care), a cost-effectiveness assessment of negative pressure wound therapy (NPWT), in comparison with moist wound therapy, in the surgical preparation of cutaneous defects requiring reconstructive surgery. This retrospective study was realized after data collection from patient files with hospitalization for the management of open-leg fractures with a view to reconstructive surgery by graft or flap (Cauchoix II or III). Effectiveness criteria, after debridement and NWPT initiation, was the time period required for preparing the wound for definitive reconstructive surgery closure by flap or graft. NWPT is compared, over the same 2000 to 2006 period, to the only existing therapeutic alternative, that is to say moist wound therapy. Only direct costs in relation with consumed resources dedicated to each medical strategy were taken into account. A Mann-Whitney U nonparametric test and boostrap technique have been used for statistical and sensitivity analysis. Twenty-five patients were recruited for the two medical strategies. Wound preparation time is significantly shorter for patient treated with NPWT (p=0.026 Mann-Whitney U-test) and is equal to 20 days less on average for time period required for preparing the wound for reconstructive surgery. Hospitalization costs is very significantly lower for patients being treated with NPWT (p=0.02). In absolute value, this cost is reduced on the average by 6000 euro per patient (i.e. by more than 60%). The incremental cost-effectiveness ratio is of the order of 164 euro per day of wound preparation for surgery gained.

[Biomaterials for reconstruction and bone substitution in otorhinolaryngology and head and neck surgery]. / Biomatériaux de reconstruction et de comblement osseux en ORL et chirurgie cervicofaciale.

INTRODUCTION: Position of medical devices has increased for last 30 years in otorhinolaryngology. Legal directive of use, main indications and perspectives are presented. RESULTS AND DISCUSSION: Biomaterials are medical devices planned for tissue reconstruction or substitution. The approval labelling are planned in Europe by the European Community certification (marquage CE) and overseen by a postmarket medical device safety (matériovigilance), that are completely independent from the Food and Drug Administration certification. Indications of biomaterials are likely competitive to those of autografts; their advantage is to limit the morbidity due to autograft harvesting. Benefits are aesthetics, functional or complementary. Main indications are presented in otology, rhinology, face traumatology, laryngology, anti-aging surgery, implants and epithesis. Research fields are scanned (increased therapeutic properties, drug delivery systems, tissue engineering...). CONCLUSION: Biomaterials are increasingly implanted in ENT surgery. The surgical success of their use require a strict legal label and well-defined indications.

Injectable bone substitute to preserve alveolar ridge resorption after tooth extraction: a study in dog.

The aim of the present study was to assess the efficacy of a ready-to-use injectable bone substitute on the prevention of alveolar ridge resorption after tooth extraction. Maxillary and mandibular premolars were extracted from 3 Beagle dogs with preservation of alveolar bone. Thereafter, distal sockets were filled with an injectable bone substitute (IBS), obtained by combining a polymer solution and granules of a biphasic calcium phosphate (BCP) ceramic. As a control, the mesial sockets were left unfilled. After a 3 months healing period, specimens were removed and prepared for histomorphometric evaluation with image analysis. Histomorphometric study allowed to measure the mean and the maximal heights of alveolar crest modifications. Results always showed an alveolar bone resorption in unfilled sockets. Resorption in filled maxillary sites was significantly lower than in control sites. Interestingly, an alveolar ridge augmentation was measured in mandibular filled sockets including 30% of newly-formed bone. It was concluded that an injectable bone substitute composed of a polymeric carrier and calcium phosphate can significantly increase alveolar ridge preservation after tooth extraction.

Neointimal hyperplasia after stenting in a human mammary artery organ culture.

Although the use of stents has limited the incidence of restenosis, in-stent restenosis remains an important problem. In-stent restenosis is the result of a healing process that induced neointimal hyperplasia through mechanisms that are still not understood. The aim of this study was to analyze the histological consequences of the healing process following stent implantation. Internal mammary arteries from atheroslerotic patients undergoing coronary artery bypass surgery were stented and maintained in culture for 0-28 days. Stent implantation after predilatation induced an extensive loss of endothelial cells whereas direct stenting preserved endothelium between the struts. Morphometric analysis shows that stent placement induced neointimal thickening. Smooth muscle alpha-actin labeling indicates that neo-intimal formation was mainly due to proliferation and migration of smooth muscle cells. Smooth muscle cell proliferation, assessed by MIB-1 staining, was maximal at day 14 after stent insertion. Human mammary artery organ culture thus provides valuable information on histological consequences of stent implantation with or without predilatation regarding endothelial cell disappearance and neointimal hyperplasia. These data also demonstrate that neointimal thickening induced by stent implantation comprises an intrinsic component resulting from the vessel wall response to stent insertion and suggest that blood factors could play an amplifying but not necessary role.

Vancomycin encapsulation in biodegradable poly(epsilon-caprolactone) microparticles for bone implantation. Influence of the formulation process on size, drug loading, in vitro release and cytocompatibility.

Vancomycin encapsulation in biodegradable poly(epsilon-caprolactone) microparticles (200 microm mean diameter) was most efficient with a simple emulsion technique that dispersed 122.5 mg/g of polymer. Scanning electron micrographs showed smooth or pitted particles. Dissolution studies were correlated with microparticle morphology, indicating higher release with pitted particles when vancomycin was encapsulated in a dissolved state. The cytocompatibility of these poly(epsilon-caprolactone) microparticles was demonstrated by a direct contact cytotoxic assay. This material can be considered as an efficient drug delivery system for bone implantation.

A new injectable bone substitute combining poly(epsilon-caprolactone) microparticles with biphasic calcium phosphate granules.

Previous studies have shown the effectiveness of an injectable bone substitute (IBS) composed of biphasic calcium phosphate in 2% hydroxypropyl methylcellulose gel (50/50 w/w). A therapeutic agent in the form of a drug can be added to the biomaterial by encapsulation into microparticles to protect the active agent, control its release and preserve the material rheological properties. Poly(epsilon-caprolactone) was used in this study because of its biocompatibility and resorbability, as tested in orthopaedic implants and surgical sutures. Particles (80-200 microm) were manufactured by a solvent evaporation-extraction process (1 g of polymer, 11-15 ml methylene chloride, with a stirring speed of 400-600 rpm) and introduced into the IBS in a 5-50% (V/V) range. Injectability was evaluated by texture analysis. With less than 45% of particles, the material had rheological properties similar to those of the reference IBS, whereas injectability decreased markedly with more than 45% of particles. A preliminary in vitro release study showed that this type of triphasic IBS could be efficient for drug delivery systems with osteoconduction properties.

Injectable bone substitute using a hydrophilic polymer.

We studied a new injectable biomaterial for bone and dental surgery consisting of a hydrophilic polymer as matrix and bioactive calcium phosphate (CaP) ceramics as fillers. This material is composed of complex fluids whose flow is determined by the laws of rheology. We investigated the macromolecular effects on this composite in a tube. The stability of the polymer and the mixture is essential to the production of a ready-to-use injectable biomaterial. These flow properties are necessary to obtain CaP bioactivity in a dental canal or bone defect during percutaneous surgery. Macromolecules provide spaces between CaP ceramic granules and facilitate the role of the biological agents of bone substitution.

A new injectable calcium phosphate biomaterial for immediate bone filling of extraction sockets: a preliminary study in dogs.

BACKGROUND: Many different bone substitutes, such as autografts, allografts or synthetic biomaterials have been proposed to restore alveolar bone loss and support efficient placement of dental implants. This experimental study evaluated the osteoconductive properties of an injectable bone substitute (IBS) composed of a polymeric carrier and a calcium phosphate mineral phase, used to fill mandibular and maxillary canine extraction sockets. METHODS: The polymer was a cellulose derivative (methyl-hydroxy-propyl-cellulose, MHPC), and the mineral phase consisted of granules of biphasic calcium phosphate (BCP) ceramics 200 to 500 microm in diameter. Mandibular and maxillary premolars extracted from 3 dogs (a total of 60 extraction sites) were immediately treated with the IBS or left unfilled as control sites. Animals were sacrificed 3 months after implantation and all extraction sockets were prepared for histological evaluation. RESULTS: Qualitative histological studies showed that the IBS was able to support the extensive apposition of well-mineralized newly formed lamellar bone over the entire socket surface and appeared to prevent alveolar ridge bone loss in treated extraction sites. Quantitative evaluation showed that the amount of newly formed bone was significantly higher in mandibular than maxillary extraction sockets for both treated and control sites. CONCLUSIONS: An injectable bone substitute composed of a polymeric carrier and calcium phosphate was effective in enhancing the bone fill of extraction sockets. This approach may prove promising for periodontal lesions. The material expressed osteoconductive capacities, and the biological properties of the mineral phase were conserved.

In vitro influence of apatite-granule-specific area on human growth hormone loading and release.

Although calcium phosphate biomaterials often are used as drug delivery systems (DDS) at bone sites, the conditions affecting the loading of the therapeutic agent (TA) have not been well documented. A human growth hormone (hGH) adsorption method was used in this study to investigate the influence of the formulated apatite (AP)-specific area on loading and release. AP powders were formulated with a 200-500 microm granulometry and various specific areas. Two milligrams of hGH in solution were deposited for 24 h at 37 degrees C on 100 mg of AP with different specific areas. The amount of hGH loaded was determined by immunoradiometric assay (IRMA) and eluted stain bioassay (ESTA) using Nb2 lymphoma rat cells. Although loading was not greatly influenced by a specific area between 3 and 25 m2/g, dependency was noted for higher specific areas. Human GH release was measured by IRMA and ESTA over a 33-day period, with half-time release between 25 and 79 h. Comparison of IRMA and ESTA measurements for the hGH amounts loaded showed that hGH biologic activity was conserved. Results indicate that it is feasible to control the quantity of TA loading on AP by modifying specific areas for in vivo applications.

In vitro evaluation of a new injectable calcium phosphate material.

The purpose of this study was to develop an injectable bone substitute (IBS) for percutaneous orthopedic surgery. The multiphasic material used was composed of a 2% aqueous solution of methylhydroxypropylcellulose (MHPC) and biphasic calcium phosphate (BCP, 60% hydroxyapatite and 40% beta-tricalcium phosphate) in which MHPC served as the carrier for 80-200 microm of BCP granules. The best BCP/polymer ratio was determined by the rheological properties and higher BCP content of the material. Steam sterilization was more effective than gamma irradiation in maintaining the stability of the mixture and conserving its physiochemical and mechanical properties. The in vitro biocompatibility of the composite was checked by direct-contact cytotoxicity and cell-proliferation assays. A preliminary in vivo test was performed in the rabbit using intraosseous implantations in the femoral epiphysis. Histological analysis was done after 1, 2, 4, and 10 weeks. Bone ingrowth into the IBS, in close association with BCP granules, was observed after 1 week and increased regularly from the surface inward at 2, 4, and 10 weeks. At the same time, smaller BCP granules (less than 80 microns in diameter) were degraded and resorbed. This injectable biomaterial proved suitable for cavity filling. The water solubility and viscosity of the polymer allow cells to recolonize, with in situ bonding of the mineral phase.

Apatite as carrier for growth hormone: in vitro characterization of loading and release.

Previous studies concerning bone drug delivery systems have provided little data about the amount of drug loaded, one of the essential factors for determining the dose/effect relationship. To investigate this factor, an adsorption method involving a therapeutic agent was tested in vitro on an apatitic calcium phosphate (AP). One milligram of human growth hormone (hGH) was deposited onto 0.1, 0.15, and 0.2 g of AP powder over a period of 24 h at 37 degrees C. The amount of hGH loaded was determined by subtracting the dose recovered from that applied on AP. The results show that 1 g of AP absorbed 9.48 mg of hGH. From 0.1 and 0.15 g of hGH-loaded AP, hGH was released in vitro for 2 and 3 weeks, respectively, with a 50% time release (T1/2) at 30 h and 72 h, respectively, for the two quantities. The amount of drug loaded and the determined release kinetics were compatible with the action pattern of hGH, indicating that hGH-loaded calcium phosphate supports are suitable for bone-growth promotion.

Dynamic compaction: a new process to compact therapeutic agent-loaded calcium phosphates.

The sintering stage in the classical process of preparing bone substitution materials prevents therapeutic agents from being loaded into calcium phosphate powder. However, dynamic compaction, a new process, requires no external heat, allowing the therapeutic agent to be incorporated into ceramics. This report presents the results of an in vitro study of therapeutic agents associated with calcium phosphate powder and involving this new process. A mixture of vancomycin lyophilized powder (0.15 g) and biphasic calcium phosphate (BCP) powder (1.85 g) was compacted. In addition, 2 ml of human growth hormone (1 mg ml-1) were associated with BCP powder by physical adsorption on bead surfaces before compaction. Detection by monoclonal antibodies and sodium dodecyl sulphate polyacrylamide gel electrophoresis demonstrated the structural integrity of the two therapeutic agents after consolidation. This new compaction process should be useful in developing ceramics that contain a therapeutic agent.

Risks of reusing coronary angioplasty catheters: results of an experimental study.

This experimental study was conducted to evaluate the microbiological and mechanical risks of reusing angioplasty catheters after decontamination and resterilization. The catheters studied were decontaminated in an ultrasound chamber, rinsed, dried, wrapped, and resterilized at 25 or 35 Kgray. Sterility checks performed on catheters cut into three segments concerned bacteria, mushrooms, yeasts, and pyrogens. The surface condition of the balloons was studied by scanning electron microscopy. The mechanical properties analyzed were balloon diameter and bursting pressure and the mean resistance of the catheter body to breakage. Seventy angioplasty catheters of three different types (rapid exchange, coaxial, and on-wire balloon catheter) were tested. Decontamination proved insufficient owing to the persistence of cellular elements on the balloon surface and the presence of pyrogens. Sterility of the material was not ensured with an irradiation of 25 Kgray. It was probable but not certain with 35 Kgray, since an inhibitory effect on micro-organism growth was noted. Mechanical properties were not modified significantly. Our results do not favor the reuse of coronary angioplasty catheters. Better decontamination is desirable but difficult to obtain because of the adhesion of cellular elements to the polymers composing the catheters. Although our results are not necessarily applicable to all resterilization protocols, they indicate that teams desiring to reuse angioplasty material should first test the validity of their procedure for decontamination and resterilization.