Operational research as a mechanism to improve treatment outcomes for drug-resistant TB in the WHO European Region.

In 2022, the WHO European Region accounted for 15.1% of all incident rifampicin-resistant/multidrug-resistant TB (RR/MDR-TB) cases. Most occurred in 18 high-priority countries of eastern Europe and central Asia, many of which joined an initiative led by the WHO Regional Office for Europe. The aim was to introduce three, fully oral, 9-month modified shorter treatment regimens (mSTR) to treat RR/MDR-TB under operational research conditions. The three regimens were: 1) bedaquiline + linezolid + levofloxacin + clofazimine + cycloserine (BdqLzdLfxCfzCs); 2) BdqLzdLfxCfz + delamanid (Dlm) for children over 6 years of age and adults; and 3) DlmLzdLfxCfz for children under 6 years of age. The project aimed to enhance treatment success, facilitate mSTR implementation, promote quality of care and build research capacity, while also contributing to global knowledge on all-oral mSTR use. Between April 2020 and June 2022, >2,800 patients underwent mSTR treatment in the WHO European Region. This unique experience promoted further collaboration with national tuberculosis programmes, health authorities, experts and donors within and outside Europe, with a focus on implementing operational research and improving the quality of care in high TB burden countries of the region. In the hope of encouraging others to adopt this model, we have described the principles of the initiative, its strengths and weaknesses and next steps.

En 2022, la Région européenne de l'OMS a recensé 15,1% de l'ensemble des cas de TB résistante à la rifampicine/multirésistante aux médicaments (RR/MDR-TB). La majorité de ces cas ont eu lieu dans 18 pays hautement prioritaires d'Europe orientale et d'Asie centrale, parmi lesquels de nombreux ont adhéré à une initiative dirigée par le Bureau régional de l'OMS pour l'Europe. L'objectif était de mettre en place trois schémas thérapeutiques modifiés plus courts de 9 mois, entièrement oraux, (mSTR, pour l'anglais "fully oral, 9-month modified shorter treatment regimens ¼) pour le traitement de la RR/MDR-TB dans le cadre d'une recherche opérationnelle. Ces trois schémas étaient les suivants 1) bédaquiline + linézolide + lévofloxacine + clofazimine + cyclosérine (BdqLzdLfxCfzCs) ; 2) BdqLzdLfxCfz + delamanid (Dlm) pour les enfants de plus de 6 ans et les adultes ; et 3) DlmLzdLfxCfz pour les enfants de moins de 6 ans. Le projet visait à améliorer l'efficacité des traitements, à faciliter l'application des mSTR, à promouvoir la qualité des soins et à renforcer les capacités de recherche, tout en contribuant aux connaissances mondiales sur l'utilisation des mSTR par voie orale. Entre avril 2020 et juin 2022, plus de 2 800 patients ont reçu un traitement par mSTR dans la Région Européenne de l'OMS. Cette expérience unique a encouragé la continuation de la collaboration avec les programmes nationaux de lutte contre la TB, les autorités sanitaires, les experts et les donateurs tant en Europe qu'à l'étranger. L'accent est mis sur la mise en œuvre de la recherche opérationnelle et l'amélioration de la qualité des soins dans les pays de la région où la TB est fortement prévalente. Nous avons détaillé les principes de l'initiative, ses avantages et ses inconvénients, dans l'espoir d'inciter d'autres pays à suivre cet exemple, tout en exposant les étapes à venir.

Hemostatic dressings based on poly(vinyl formal) sponges.

The development of novel hemostatic agents is related to the fact that severe blood loss due to hemorrhage continues to be the leading cause of preventable death of patients with military trauma and the second leading cause of death of civilian patients with injuries. Herein we assessed the hemostatic properties of porous sponges based on biocompatible hydrophilic polymer, poly(vinyl formal) (PVF), which meets the main requirements for the development of hemostatic materials. A series of composite hemostatic materials based on PVF sponges with different porosities and fillers were synthesized by acetalization of poly(vinyl alcohol) with formaldehyde. Nano-sized aminopropyl silica, micro-sized calcium carbonate, and chitosan hydrogel were used to modify PVF matrixes. The physicochemical properties (pore size, elemental composition, functional groups, hydrophilicity, and acetalization degree) of the synthesized composite sponges were studied by gravimetrical analysis, optical microscopy, scanning electron microscopy combined with energy dispersive x-ray spectroscopy, infrared spectroscopy, and nuclear magnetic resonance. Hemostatic properties of the materials were assessed using a model of parenchymal bleeding from the liver of white male Wistar rat with a gauze bandage as a control. All investigated PVF-based porous sponges showed high hemostatic activity: upon the application of PVF-samples the bleeding decreased within 3 min by 68.4-94.4% (р < 0.001). The bleeding time upon the application of PVF-based composites decreased by 78.3-90.4% (p < 0.001) compared to the application of well-known commercial product Celox™.

N-isopropylacrylamide-based fine-dispersed thermosensitive ferrogels obtained via in-situ technique.

Thermosensitive hydrogels with magnetic properties (ferrogels) are very promising for medical application, first of all, for the design of targeted delivery systems with controlled release of drugs and for magnetic hyperthermia and chemotherapy treatment of cancer. These magnetic hydrogels could be obtained using diverse techniques: ex- and in-situ syntheses. The present work is devoted to the study of magnetite (Fe(3)O(4)) formation inside the nanoreactors of (co)polymeric hydrogels. Polymeric templates (hydrogel films and fine-dispersed hydrogels) used for obtaining ferrogels were based on acrylic monomers: thermosensitive N-isopropylacrylamide, and hydrophilic acrylamide. Covalent cross-linking was accomplished using bifunctional monomer N,N'-methylenebisacrylamide. Influence of hydrophilic-lipophilic balance of polymeric templates and concentration of iron cations on the magnetite formation were investigated along with the development of ferrogel preparation technique. Cytotoxicity, physical and chemical properties of obtained magnetic hydrogels have been studied in this work.

Multipurpose smart hydrogel systems.

This paper represents the review of the last investigations in the field of smart polymeric hydrogels and our contribution to this matter. New hydrogel systems and nanocomposites based on acrylic monomers (acrylamide, acrylonitrile, acrylic acid, N-isopropylacrylamide etc.) with incorporated nanosized colloidal silver, hydroxyapatite and carbon nanotubes with a new set of properties have been obtained and examined. These systems can sharply change their characteristics when minor external physical (electric and magnetic fields, temperature etc.) or chemical (pH, ionic strength) stimuli are applied. Such stimulus-responsive polymeric systems are very promising from the standpoint of different medical applications, especially for the development of intelligent drug delivery systems. On the base of designed hydrogel iontophoretic transdermal therapeutic systems, endoprosthesis for the replacement of bone tissue and hydrogel burns coatings with immobilized mesenchymal cells were obtained and tested.