Cost-effectiveness of a bone substitute delivering gentamicin in the treatment of chronic osteomyelitis of long bones: Protocol for the CONVICTION randomized multicenter study

IntroductionChronic osteomyelitis is a serious osteoarticular infection that most often occurs in the long bones, responsible for significant morbidity with the risk of fracture and amputation. Despite advances in both antibiotics and surgical treatment, the probability of recurrence of infection remains at around 20%. Cerament-G (BONESUPPORT AB, Sweden) is a synthetic bone substitute that fills the bone void left by surgery, prevents infection and promotes bone regeneration within this space. Cerament-G also provides the local delivery of high doses of gentamicin over several weeks. Two prospective observational studies described a number of infectious recurrences of 4 and 5% after the use of Cerament-G. Although available in France, Cerament-G is currently not reimbursed and its high cost constitutes a barrier to its use. We hypothesize that the use of Cerament-G will lead to fewer costs to the collectivity while improving patient utility and, as an innovative strategy, will be superior to standard of care on recurrence of infection.Methods and analysisThe Conviction Study is a prospective, multicenter, randomized, single blind study conducted in 14 French Reference Centers for Complex Osteoarticular infections. The main objective is to evaluate the cost-effectiveness of using Cerament-G in the treatment of chronic long bone osteomyelitis by comparing this innovative strategy to standard of care. A cost-utility analysis from the collective perspective will be conducted over a 24-month time horizon after the initial surgery. The outcome for the main medico-economic evaluation will be Quality Adjusted Life Years (QALYs).DiscussionThe study is being conducted throughout the CRIOAc network in France, in referral centers for the management of complex infections which will facilitate patient recruitment. This study has several limitations: the investigators have to be trained to handle the device, and it was impossible to blind the surgeon.ConclusionIf the use of Cerament-G is demonstrated to be superior to leaving the dead space empty during surgery for patients with stage III chronic long bone osteomyelitis, its use will be recommended to improve the prognosis of such patients, and this device may eventually qualify for reimbursement through the French Health Insurance scheme.Ethics and disseminationThis protocol received authorization from the Ethics Committee CPP Sud Méditerranée V on April 27, 2021 (21.03.10.77652) and the French National Agency for Medicines and Health Products on May 6, 2021 (2020-A02299-30). Results will be disseminated to the scientific community through congresses and publication in peer-reviewed journals

Case report: Continuous infusions of ceftazidime-avibactam and aztreonam in combination through elastomeric infusors for 12 weeks for the treatment of bone and joint infections due to metallo-β-lactamase producing Enterobacterales

Among carbapenem-resistant Enterobacterales, metallo-beta-lactamase producing strains represent a growing therapeutic challenge. While the association of aztreonam and ceftazidime-avibactam has been investigated in recent years for the treatment of infections involving these strains, little to no clinical data support the use of this association for the treatment of bone and joint infections. We report two cases of complex bone and joint infections involving metallo-beta-lactamase-producing Enterobacterales, successfully treated at our referral center with aztreonam and ceftazidime-avibactam for 12 weeks in continuous infusions through elastomeric infusors

La santé connectée et "son" droit : approches de droit européen et de droit français

International audienceLa montée en puissance d'acteurs au sein des processus décisionnels a souvent provoqué de la défiance dans la doctrine notamment juridique, comme en attestent les débats autour de l'avènement d'un apparent « gouvernement des juges » 2 ou encore d'un prétendu « gouvernement des experts ». A l'heure actuelle, la crainte d'une confiscation du pouvoir décisionnel ne découle plus du rôle joué par une catégorie d'acteurs mais du progrès technique et des nouvelles technologies qui en résultent. L'heure est au « gouvernement de la technologie ». Les réflexions engagées sur l'avenir d'une justice prédictive, le développement de technologies persuasives ou encore la prolifération des objets connectés mettent toutes l'accent sur le bouleversement opéré par les mutations technologiques sur nos processus décisionnels, nos habitudes, nos modes de vie et peut-être même nos modes de raisonnement. Le domaine de la santé n'a pas été épargné par cette colonisation technologique, la santé devient elle aussi connectée. Le développement de la santé connectée est prolifique et bénéfique. La santé connectée permet des avancées en matière de qualité de la santé, de qualité des soins, d'accès aux soins et, dans le même temps, est une source de réduction des dépenses de santé 3. La santé connectée offre, en d'autres termes, tout à la fois des perspectives pour le renforcement de la qualité de la santé et pour l'assainissement des finances des systèmes de santé. Si les progrès, dont la santé connectée est porteuse, ne doivent pas être minimisés, les risques inhérents à cette dernière ne peuvent pas non plus l'être. En premier lieu, la santé connectée modifie la relation médecin-patient traditionnelle. Dans le cadre de la relation de santé, un certain nombre de données sont produites : certaines sont issues des examens médicaux ; d'autres du patient lui-même. Or, si la relation patient-médecin est majoritairement dématérialisée, les données produites par le patient lui même telles que son ressenti, son émotionnel peuvent échapper au médecin. Est-ce alors un problème pour la qualité des soins ? Dans la mesure où ces informations peuvent permettre de réfléchir sur les causes d'une maladie, d'une épidémie, elles sont nécessaires pour assurer une meilleure prise en charge du patient mais aussi pour améliorer la prévention médicale. Un raisonnement quasi mathématique priverait alors peut-être le corps médical d'informations fondamentales pour penser les causes de certaines affections. En deuxième lieu, la santé connectée tend à priver l'individu de son droit de ne pas savoir. En effet, un certain nombre d'applications, sans forcément être des dispositifs médicaux, indiquent, par exemple, aux individus les risques pour leur santé en fonction de leur activité physique, de leur âge ou encore de leur poids. A travers ces informations, ces technologies prédéfinissent ainsi le comportement à venir de l'individu et le prive alors d'une part de son libre arbitre. Il s'agit là surement davantage d'une question éthique que d'une question juridique qu'il ne fera ainsi pas partie de nos développements. Enfin, un autre risque 1 Cette recherche a été menée dans la cadre du projet APPRISE financé par la Fondation universitaire A*MIDEX. 2 L'expression « gouvernement des juges » est apparue sous la plume d'Edouard Lambert en 1921. Edouard LAMBERT, Le gouvernement des juges et la lutte contre la législation sociale aux Etats-Unis. L'expérience américaine du contrôle judiciaire de la constitutionnalité des lois, Paris, Giard, 1921, rééd, Préface F. Moderne, Paris, Dalloz, 2015, 276 p. 3 Pierre SIMON et Dominique ACKER, « La place de la télémédecine dans l'organisation des soins », Rapport Mission thématique n° 7/PS/DA, Ministèr

Cost-effectiveness of a bone substitute delivering gentamicin in the treatment of chronic osteomyelitis of long bones: Protocol for the CONVICTION randomized multicenter study

International audienceIntroduction Chronic osteomyelitis is a serious osteoarticular infection that most often occurs in the long bones, responsible for significant morbidity with the risk of fracture and amputation. Despite advances in both antibiotics and surgical treatment, the probability of recurrence of infection remains at around 20%. Cerament-G (BONESUPPORT AB, Sweden) is a synthetic bone substitute that fills the bone void left by surgery, prevents infection and promotes bone regeneration within this space. Cerament-G also provides the local delivery of high doses of gentamicin over several weeks. Two prospective observational studies described a number of infectious recurrences of 4 and 5% after the use of Cerament-G. Although available in France, Cerament-G is currently not reimbursed and its high cost constitutes a barrier to its use. We hypothesize that the use of Cerament-G will lead to fewer costs to the collectivity while improving patient utility and, as an innovative strategy, will be superior to standard of care on recurrence of infection. Methods and analysis The Conviction Study is a prospective, multicenter, randomized, single blind study conducted in 14 French Reference Centers for Complex Osteoarticular infections. The main objective is to evaluate the cost-effectiveness of using Cerament-G in the treatment of chronic long bone osteomyelitis by comparing this innovative strategy to standard of care. A cost-utility analysis from the collective perspective will be conducted over a 24-month time horizon after the initial surgery. The outcome for the main medico-economic evaluation will be Quality Adjusted Life Years (QALYs). Discussion The study is being conducted throughout the CRIOAc network in France, in referral centers for the management of complex infections which will facilitate patient recruitment. This study has several limitations: the investigators have to be trained to handle the device, and it was impossible to blind the surgeon. Conclusion If the use of Cerament-G is demonstrated to be superior to leaving the dead space empty during surgery for patients with stage III chronic long bone osteomyelitis, its use will be recommended to improve the prognosis of such patients, and this device may eventually qualify for reimbursement through the French Health Insurance scheme. Ethics and dissemination This protocol received authorization from the Ethics Committee CPP Sud Méditerranée V on April 27, 2021 (21.03.10.77652) and the French National Agency for Medicines and Health Products on May 6, 2021 (2020-A02299-30). Results will be disseminated to the scientific community through congresses and publication in peer-reviewed journals

Case report: Continuous infusions of ceftazidime-avibactam and aztreonam in combination through elastomeric infusors for 12 weeks for the treatment of bone and joint infections due to metallo-β-lactamase producing Enterobacterales

Among carbapenem-resistant Enterobacterales , metallo-beta-lactamase producing strains represent a growing therapeutic challenge. While the association of aztreonam and ceftazidime-avibactam has been investigated in recent years for the treatment of infections involving these strains, little to no clinical data support the use of this association for the treatment of bone and joint infections. We report two cases of complex bone and joint infections involving metallo-beta-lactamase-producing Enterobacterales , successfully treated at our referral center with aztreonam and ceftazidime-avibactam for 12 weeks in continuous infusions through elastomeric infusors

Direct genotyping of cytomegalovirus envelope glycoproteins from toddler's saliva samples

Centre Hospitalier Universitaire (CHU) Limoges, Centre National de Reference du CMV, Laboratoire de Bactériologie-Virologie-Hygiène, Limoges, FranceInternational audienceBACKGROUND: The polymorphism of genes encoding CMV envelope protein is used for strain classification and may influence pathogenesis and/or infectivity. CMV genotyping is usually based on sequencing or acrylamide gel-RFLP, but these methods are not suited to rapid screening of large populations. OBJECTIVES: We developed a high-throughput method to analyze CMV strains diversity and to detect multiple-strain infection in a large population of toddlers (six daycare centers (DCC) and an emergency unit (EU)). METHODS: We developed a new PCR-RFLP method coupled with capillary electrophoresis fragment detection for UL55-gB, UL75-gH and UL73-gN genotyping. To detect gB recombinants, gpUL55 typing was applied to two variable zones (NTerminal and central). We applied this method to 212 CMV-positive saliva samples and controlled the results by direct sequencing of PCR products. RESULTS: We identified 112 strains, that fell into eight groups in UL55-gB, two groups in UL75-gH, and seven groups in UL73-gN. The 79 samples from the emergency unit contained 30 strains, 28 children harboring 2 strains. The samples (n=133) from the six daycare centers contained respectively 4, 1, 6, 1 and 11 strains. Fifteen percent of strains were UL55-gB recombinants. CONCLUSION: Our new method can simultaneously determine gB, gH and gN genotypes and offers more precise classification of CMV strains than previous RFLP-based methods. This could constitute the basis for a new classification, particularly in UL55-gB. Easy direct identification of multiple strains and recombinants in pathological samples could facilitate large epidemiologic studies

A preliminary study for an intraoperative 3D bioprinting treatment of severe burn injuries.

Abstract Background : Intraoperative three-dimensional (3D) fabrication of living tissues could be the next biomedical revolution in patient treatment. Approach : We developed a surgery-ready robotic 3D bioprinter and demonstrated that a bioprinting procedure using medical grade hydrogel could be performed using a 6-axis robotic arm in vivo for treating burn injuries. Results : We conducted a pilot swine animal study on a deep third-degree severe burn model. We observed that the use of cell-laden bioink as treatment substantially affects skin regeneration, producing in situ fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF), necessary for tissue regeneration and re-epidermalization of the wound. Innovation and Conclusion: We described an animal study of intraoperative 3D bioprinting living tissue. This emerging technology brings the first proof of in vivo skin printing feasibility using a surgery-ready robotic arm-based bioprinter. Our positive outcome in skin regeneration, joined with this procedure's feasibility, allow us to envision the possibility of using this innovative approach in a human clinical trial in the near future