Development of a workforce self-assessment tool for public health emergency preparedness.

BACKGROUND: In collaboration with six European public health agencies as part of the PANDEM-2 consortium, we have developed and validated a self-assessment tool that captures the workforce capacities and capabilities needed at the institutional level within National Public Health Institutes (NPHIs) to deal with public health emergencies. METHODS: The work carried out in this study included (i) a review of existing tools for workforce assessment, (ii) focus group discussions and interviews to map the experiences and needs of NPHI's, (iii) the development of a tool for NPHI's to assess their workforce capacity and capabilities in public health emergency preparedness (PHEP) and (iv) refinement of the assessment tool via a Delphi study. RESULTS: Capacity markers were identified to assess the workforce required for PHEP functions and the availability of surge capacity during a public health emergency. The tool also enables NPHIs to analyze gaps in PHEP staff competencies. The assessment scores can assist NPHI pandemic preparedness by identifying and prioritizing training and recruitment needs. CONCLUSIONS: In line with EU Regulation 2022/2371 on serious cross-border threats to health, article 11 Training of healthcare staff and public health staff, Member States (MS) are tasked with assessing current workforce capacity and capability gaps. The PANDEM-2 workforce self-assessment tool aligns with this requirement and will support effective planning and development to strengthen the public health workforce capacity in EU MS.

PANDEM-Source, a tool to collect or generate surveillance indicators for pandemic management: a use case with COVID-19 data.

Introduction: PANDEM-Source (PS) is a tool to collect and integrate openly available public health-related data from heterogeneous data sources to support the surveillance of infectious diseases for pandemic management. The tool may also be used for pandemic preparedness by generating surveillance data for training purposes. It was developed as part of the EU-funded Horizon 2020 PANDEM-2 project during the COVID-19 pandemic as a result of close collaboration in a consortium of 19 partners, including six European public health agencies, one hospital, and three first responder organizations. This manuscript describes PS's features and design to disseminate its characteristics and capabilities to strengthen pandemic preparedness and response. Methods: A requirement-gathering process with EU pandemic managers in the consortium was performed to identify and prioritize a list of variables and indicators useful for surveillance and pandemic management. Using the COVID-19 pandemic as a use case, we developed PS with the purpose of feeding all necessary data to be displayed in the PANDEM-2 dashboard. Results: PS routinely monitors, collects, and standardizes data from open or restricted heterogeneous data sources (users can upload their own data). It supports indicators and health resources related data from traditional data sources reported by national and international agencies, and indicators from non-traditional data sources such as those captured in social and mass media, participatory surveillance, and seroprevalence studies. The tool can also calculate indicators and be used to produce data for training purposes by generating synthetic data from a minimal set of indicators to simulate pandemic scenarios. PS is currently set up for COVID-19 surveillance at the European level but can be adapted to other diseases or threats and regions. Conclusion: With the lessons learnt during the COVID-19 pandemic, it is important to keep building capacity to monitor potential threats and develop tools that can facilitate training in all the necessary aspects to manage future pandemics. PS is open source and its design provides flexibility to collect heterogeneous data from open data sources or to upload end users's own data and customize surveillance indicators. PS is easily adaptable to future threats or different training scenarios. All these features make PS a unique and valuable tool for pandemic management.

Biosafety Issues in Patient Transport during COVID-19: A Case Study on the Portuguese Emergency Services.

During the COVID-19 pandemic, first responders faced significant biosafety challenges, especially while handling patient transport, potentially exposing them to infection. The PANDEM-2 (European project on pandemic preparedness and response) project, funded by the Horizon 2020 program, sought to investigate the challenges confronting Emergency Medical Systems throughout the EU. First responders from Portugal's National Institute of Medical Emergency (INEM) were considered as a representative operational model of the national first responder agencies of European member states because they played a critical role during the COVID-19 pandemic. As a result, they were asked to complete an online survey about their COVID-19 pandemic-related professional activities. The survey focused on their perspectives on current biosafety guidelines and their operational practices. It covered opinions on existing protocols, technical concerns during patient transport, and issues after the patients arrived at the hospital. The key findings revealed concerns about risk assessment, the inadequacy of guidelines, and disparities in equipment access. This survey emphasizes the importance of developing streamlined, adaptable biosafety protocols, better coordination between prehospital and in-hospital services, and the development of scalable, cost-effective biosafety solutions. Based on our findings, we propose improvements to national and European biosafety directives and advocate for streamlined adaptation during pandemics.

Diabetic Bone Fracture Repair: A Progenitor Cell-Based Paradigm.

Long bone fractures in diabetics are slower to heal, have an increased risk of developing non-union and demonstrate greater potential of infection and perioperative complications compared to non-diabetics. The causative aberrant bone mineral density and insufficient bone microstructure of diabetic patients are thought to result from altered osteoblast and osteocyte function, increased bone marrow adiposity, decreased progenitor osteo- and chondral differentiation potential and increased pro-inflammatory cytokine circulation. It is therefore reasonable to hypothesize that the root cause of faulty diabetic bone homeostasis and fracture repair is a reduced population of bone marrow progenitor cells and/or their decreased osteochondral capacity complicated by their repressed neo-vascular potential. The potential of transplanted mesenchymal stem cells with a scaffold to support callus formation through the creation of de novo bone in hyperglycemia has been reported. However, there are minimal supporting pre-clinical and clinical investigations confirming these findings. Clinical trials have instead examined mesenchymal stem cell transplantation to slow disease progression, support .-cell viability and function and restore glucose homeostasis while the direct application of allogenic non-diabetic mesenchymal stem cells at the site of orthopaedic injury remains un-investigated. Here, the literature supporting the application of mesenchymal stem cells in diabetic fracture repair is reviewed including the process of dysfunctional diabetic fracture healing, osteoblast dysregulation and the effect of the hyperglycaemic environment on progenitor cell number and performance with a view to translating the preclinical knowledge base to the administration of mesenchymal stem cells in diabetic fracture repair.

Induction of osteogenic differentiation by nanostructured alumina surfaces.

Permanent orthopedic implants are becoming increasingly important due to the demographic development. Their optimal osseointegration is key in obtaining good secondary stability. For anchorage dependent cells, topographic features of a surface play an essential role for cell adhesion, proliferation, differentiation and biomineralization. We studied the topographical effect of nanostructured alumina surfaces prepared by chemical vapor deposition on osteogenic differentiation and growth of human osteoblasts. Chemical vapor deposition of the single source precursor (tBuOAIH2)2 led to synthesis of one dimensional alumina nanostructures of high purity with a controlled stoichiometry. We fabricated different topographic features by altering the distribution density of deposited one dimensional nanostructures. Although the topography differed, all surfaces exhibited identical surface chemistry, which is the key requirement for systematically studying the effect of the topography on cells. Forty-eight hours after seeding, cell density and cell area were not affected by the nanotopography, whereas metabolic activity was reduced and formation of actin-fibres and focal adhesions was impaired compared to the uncoated control. Induction of osteogenic differentiation was demonstrated via up-regulation of alkaline phosphatase, bone sialoprotein, osteopontin and Runx2 at the mRNA level, demonstrating the potential of nanostructured surfaces to improve the osseointegration of permanent implants.

A chondromimetic microsphere for in situ spatially controlled chondrogenic differentiation of human mesenchymal stem cells.

Human mesenchymal stem cells (hMSCs) have been identified as a viable cell source for cartilage tissue engineering. However, to undergo chondrogenic differentiation hMSCs require growth factors, in particular members of the transforming growth factor beta (TGF-ß) family. While in vitro differentiation is feasible through continuous supplementation of TGF-ß3, mechanisms to control and drive hMSCs down the chondrogenic lineage in their native microenvironment remain a significant challenge. The release of TGF-ß3 from an injectable microsphere composed of the cartilage-associated extracellular matrix molecule hyaluronan represents a readily translatable approach for in situ differentiation of hMSCs for cartilage repair. In this study, chondromimetic hyaluronan microspheres were used as a growth factor delivery source for hMSC chondrogenesis. Cellular compatibility of the microspheres (1.2 and 14.1 µm) with hMSCs was shown and release of TGF-ß3 from the most promising 14.1 µm microspheres to control differentiation of hMSCs was evaluated. Enhanced accumulation of cartilage-associated glycosaminoglycans by hMSCs incubated with TGF-ß3-loaded microspheres was seen and positive staining for collagen type II and proteoglycan confirmed successful in vitro chondrogenesis. Gene expression analysis showed significantly increased expression of the chondrocyte-associated genes, collagen type II and aggrecan. This delivery platform resulted in significantly less collagen type X expression, suggesting the generation of a more stable cartilage phenotype. When evaluated in an ex vivo osteoarthritic cartilage model, implanted hMSCs with TGF-ß3-loaded HA microspheres were detected within cartilage fibrillations and increased proteoglycan staining was seen in the tissue. In summary, data presented here demonstrate that TGF-ß3-bound hyaluronan microspheres provide a suitable delivery system for induction of hMSC chondrogenesis and their use may represent a clinically feasible tissue engineering approach for the treatment of articular cartilage defects.

In vivo evaluation of defined polished titanium surfaces to prevent soft tissue adhesion.

Soft tissue-implant adhesion is often required for implant integration into the body; however, in some situations, the tissue is required to glide freely over an implant. In the case of distal radius fracture treatment, current literature describes how titanium and its alloys tend to lead to more intra-tendon inflammatory reactions compared with stainless steel. This leads to tendon-implant adhesion and damage possibly causing limited palmar flexion and even tendon rupture. The goal of this study was to analyze the effect of different surface polishings of titanium and titanium molybdenum implants on soft tissue reactions in vivo, with the aim to prevent direct soft tissue adhesion. Using a nonfracture model, to allow for study of the soft-tissue-implant surface interactions only, six surface variants of the same plate design were implanted onto the tibia of 24 New Zealand white rabbits and left in situ for 12 weeks. Results indicate that paste polished commercially pure titanium and titanium molybdenum alloy had the least soft tissue adhesion, with the concomitant development of a soft tissue capsule. Surface topography did not appear influence the thickness of the connective tissue surrounding the plate. Therefore, suitable surface polishing could be applied to plates for clinical use, where free gliding of tissues is required.

Surfaces to control tissue adhesion for osteosynthesis with metal implants: in vitro and in vivo studies to bring solutions to the patient.

For internal fracture-fixation, metal currently remains the material of choice, since it provides strength for bone fragment support, good ductility for presurgical contouring and has been shown extensively to be biopassive. For decades, the application of metal internal fixators has proven undoubtedly successful and is deemed by many as the greatest advance in orthopedic medicine to date. However, based on this unrivalled success, newer and more challenging applications for metal internal fixators have emerged. For instance, given the large increase in the occurrence of these procedures in children and the different mechanical and biological requirements based on anatomical site of implantation, the functional requirements of metal implants have become increasingly more demanding. Given this changing demand for metal internal fixators, a more pragmatic application approach is necessary. Therefore, current metal internal fixator-related orthopedic research is based on defining specific cell and tissue responses to materials both in vitro and in vivo, as well as methods to empirically facilitate implantation site-specific tissue responses. This review discusses current knowledge from both the author's as well as others' laboratories pertaining to cell- and tissue-specific responses to metal internal-fixation materials, with specific emphasis on a surface microtopographical approach to alleviating removal-related morbidity. The review also describes the 'effective roughness spectrum' hypothesis for control of cell surface integration.