Effect of silver content on the structure and antibacterial activity of silver-doped phosphate-based glasses

Staphylococcus aureus can cause a range of diseases, such as osteomyelitis, as well as colonize implanted medical devices. In most instances the organism forms biofilms that not only are resistant to the body's defense mechanisms but also display decreased susceptibilities to antibiotics. In the present study, we have examined the effect of increasing silver contents in phosphate-based glasses to prevent the formation of S. aureus biofilms. Silver was found to be an effective bactericidal agent against S. aureus biofilms, and the rate of silver ion release (0.42 to 1.22 µg·mm–2·h–1) from phosphate-based glass was found to account for the variation in its bactericidal effect. Analysis of biofilms by confocal microscopy indicated that they consisted of an upper layer of viable bacteria together with a layer (20 µm) of nonviable cells on the glass surface. Our results showed that regardless of the silver contents in these glasses (10, 15, or 20 mol%) the silver exists in its +1 oxidation state, which is known to be a highly effective bactericidal agent compared to that of silver in other oxidation states (+2 or +3). Analysis of the glasses by 31P nuclear magnetic resonance imaging and high-energy X-ray diffraction showed that it is the structural rearrangement of the phosphate network that is responsible for the variation in silver ion release and the associated bactericidal effectiveness. Thus, an understanding of the glass structure is important in interpreting the in vitro data and also has important clinical implications for the potential use of the phosphate-based glasses in orthopedic applications to deliver silver ions to combat S. aureus biofilm infections

Developing consensus of evidence to target case finding surveys for podoconiosis: a potentially forgotten disease in India.

BACKGROUND: Podoconiosis is a non-infectious geochemical lymphoedema of the lower legs associated with a significant burden of morbidity. There are historical reports of podoconiosis in India, but its current endemicity status is uncertain. In this investigation we aimed to prioritise the selection of districts for pilot mapping of podoconiosis in India. METHODS: Through a consultative workshop bringing together expert opinion on podoconiosis with public health and NTDs in India, we developed a framework for the prioritisation of pilot areas. The four criteria for prioritisation were predicted environmental suitability for podoconiosis, higher relative poverty, occurrence of lymphoedema cases detected by the state health authorities and absence of morbidity management and disability prevention (MMDP) services provided by the National Programme for Elimination of Lymphatic Filariasis. RESULTS: Environmental suitability for podoconiosis in India was predicted to be widespread, particularly in the mountainous east and hilly southwest of the country. Most of the districts with higher levels of poverty were in the central east and central west. Of 286 districts delineated by state representatives, lymphoedema was known to the health system in 189 districts and not recorded in 80. Information on MMDP services was unavailable for many districts, but 169 were known not to provide such services. We identified 35 districts across the country as high priority for mapping based on these criteria. CONCLUSIONS: Our results indicate widespread presence of conditions associated with podoconiosis in India, including areas with known lymphoedema cases and without MMDP services. This work is intended to support a rational approach to surveying for an unrecognised, geographically focal, chronic disease in India, with a view to scaling up to inform a national strategy if required

Individual Risk Factors of Mycetoma Occurrence in Eastern Sennar Locality, Sennar State, Sudan: A Case-Control Study.

Mycetoma is a serious chronic subcutaneous granulomatous inflammatory disease that is endemic in tropical and subtropical regions, where it impacts profoundly on patients, families, and communities. Individual-level risk factors for the disease are poorly understood. To address this, a case-control study was conducted based on data collected from 60 villages in Eastern Sennar Locality, Sennar State, Sudan. Based on the presence of swelling in any part of the body, or sinus formation with or without grain discharge evident from the lesion by ultrasound examination, we diagnosed 359 cases of mycetoma. For each case, we included three healthy sex-matched persons, with no evidence of mycetoma, from the same village as the control group (n = 1077). The odds for mycetoma were almost three times higher in individuals in the age group 16-30 years (Adjusted Odds Ratio (AOR) = 2.804, 95% CI = 1.424-5.523) compared to those in age group ≤ 15 years. Other factors contributing to the odds of mycetoma were history of local trauma (AOR = 1.892, 95% CI = 1.425-2.513), being unmarried (AOR = 3.179, 95% CI = 2.339-4.20) and owning livestock (AOR = 3.941, 95% CI = 2.874-5.405). In conclusion, certain factors found to be associated with mycetoma in this study could inform a high index of suspicion for mycetoma diagnosis, which would improve early case detection. Other factors found to be associated could inform the development of an interventional program for mycetoma control in Sudan, including education on healthy farming practices and the risks of puncture wounds for individuals residing in endemic areas. However, this work was conducted in one endemic state, while mycetoma cases occur in all states of Sudan. Replicating this study over a wider area would give a fuller picture of the situation, providing the control program with more comprehensive information on the risk factors for the disease

Modelling the spatial distribution of mycetoma in Sudan.

BACKGROUND: Mycetoma is a neglected tropical disease that is reported worldwide and Sudan has the highest reported number of mycetoma infections across the globe. The incidence, prevalence and burden of mycetoma globally are not precisely known and its risk factors remain largely unelucidated. METHODS: This study aimed to identify the environmental predictors of fungal and bacterial mycetoma in Sudan and to identify areas of the country where these niche predictors are met. Demographic and clinical data from confirmed mycetoma patients seen at the Mycetoma Research Centre from 1991 to 2018 were included in this study. Regression and machine learning techniques were used to model the relationships between mycetoma occurrence in Sudan and environmental predictors. RESULTS: The strongest predictors of mycetoma occurrence were aridity, proximity to water, low soil calcium and sodium concentrations and the distribution of various species of thorny trees. The models predicted the occurrence of eumycetoma and actinomycetoma in the central and southeastern states of Sudan and along the Nile river valley and its tributaries. CONCLUSION: Our results showed that the risk of mycetoma in Sudan varies geographically and is linked to identifiable environmental risk factors. Suitability maps are intended to guide health authorities, academic institutes and organisations involved in planning national scale surveys for early case detection and management, leading to better patient treatment, prevention and control of mycetoma

Mapping the global distribution of podoconiosis: applying an evidence consensus approach

Background: Podoconiosis is a type of elephantiasis characterised by swelling of the lower legs. It is often confused with other causes of tropical lymphedema and its global distribution is uncertain. Here we synthesise the available information on the presence of podoconiosis to produce evidence consensus maps of its global geographical distribution. Methods and findings: We systematically searched available data on podoconiosis in SCOPUS and MEDLINE from inception, updated to 10 May, 2019, and identified observational and population-based studies reporting podoconiosis. To establish existence of podoconiosis, we used the number of cases reported in studies and prevalence data with geographical locations. We then developed an index to assess evidence quality and reliability, assigning each country an evidence consensus score. Using these summary scores, we then developed a contemporary global map of national-level podoconiosis status. There is evidence of podoconiosis in 17 countries (12 in Africa, three in Latin America, and two in Asia) and consensus on presence in six countries (all in Africa). We have identified countries where surveillance is required to further define the presence or absence of podoconiosis. We have highlighted areas where evidence is currently insufficient or conflicting, and from which more evidence is needed. Conclusion: The global distribution of podoconiosis is not clearly known; the disease extent and limits provided here inform the best contemporary map of the distribution of podoconiosis globally from available data. These results help identify surveillance needs, direct future mapping activities, and inform prevention plans and burden estimation of podoconiosis

Current challenges and opportunities in the care of patients with fibrodysplasia ossificans progressiva (FOP): an international, multi-stakeholder perspective

Background Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare, disabling genetic disorder characterized by congenital malformations of the great toes and progressive heterotopic ossification of soft and connective tissues. Assiduous attention to the unmet needs of this patient community is crucial to prevent potential iatrogenic harm and optimize care for individuals with FOP. Objective To gather international expert opinion and real-world experience on the key challenges for individuals with FOP and their families, highlight critical gaps in care, communication, and research, and provide recommendations for improvement. Methods An international group of expert clinicians, patients and patient advocates, caregivers and representatives from the international FOP community participated in a virtual, half-day meeting on 22 March 2021 to discuss the key unmet needs of individuals with FOP. Results Individuals with FOP often face the frustration of long diagnostic journeys, the burden of self-advocacy and the navigation of novel care pathways. Globally, patients with FOP are also confronted with inequities in access to diagnosis and specialist care, and consequently, unequal access to registries, clinical trials, and essential support from patient associations. Organizations such as the International FOP Association, the International Clinical Council on FOP, and national FOP organizations work to provide information, facilitate access to expert clinical guidance, nurture patient empowerment, fund FOP research and/or foster meaningful collaborations with the research community. The non-profit Tin Soldiers Global FOP Patient Search program aims to identify and provide a pathway to diagnosis and care for individuals with FOP, particularly in underserved communities. Such global initiatives and the increasingly widespread use of telemedicine and digital platforms offer opportunities to improve vital access to care and research. Conclusions This multi-stakeholder perspective highlights some of the unmet needs of individuals with FOP and their families. Regional and international organizations play an important role in improving the quality of life of those they reach in the global FOP community. However, globally, fundamental issues remain around raising awareness of FOP among healthcare professionals, identifying individuals with FOP, reducing time to diagnosis, and ensuring access to best practice in care, support, and clinical research. Medical writing support was industry-sponsored

Predicting the environmental suitability and population at risk of podoconiosis in Africa

Podoconiosis is a type of tropical lymphedema that causes massive swelling of the lower limbs. The disease is associated with both economic insecurity, due to long-term morbidity-related loss of productivity, and intense social stigma. The geographical distribution and burden of podoconiosis in Africa are uncertain. We applied statistical modelling to the most comprehensive database compiled to date to predict the environmental suitability of podoconiosis in the African continent. By combining climate and environmental data and overlaying population figures, we predicted the environmental suitability and human population at risk of podoconiosis in Africa. Environmental suitability for podoconiosis was predicted in 29 African countries. In the year 2020, the total population in areas suitable for podoconiosis is estimated at 114.5 million people, (95% uncertainty interval: 109.4–123.9) with 16.9 million in areas suitable for both lymphatic filariasis and podoconiosis. Of the total 5,712 implementation units (typically second administrative-level units, such as districts) defined by the World Health Organization in Africa, 1,655 (29.0%) were found to be environmentally suitable for podoconiosis. The majority of implementation units with high environmental suitability are located in Angola (80, 4.8%), Cameroon (170, 10.3%), the DRC (244, 14.7%), Ethiopia (495, 29.9%), Kenya (217, 13.1%), Uganda (116, 7.0%) and Tanzania (112, 6.8%). Of the 1,655 environmentally suitable implementation units, 960 (58.0%) require more detailed community-level mapping. Our estimates provide key evidence of the population at risk and geographical extent of podoconiosis in Africa, which will help decision-makers to better plan more integrated intervention programmes

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Individual risk factors of mycetoma occurrence in eastern sennar locality, sennar state, sudan: a case-control study

Mycetoma is a serious chronic subcutaneous granulomatous inflammatory disease that is endemic in tropical and subtropical regions, where it impacts profoundly on patients, families, and communities. Individual-level risk factors for the disease are poorly understood. To address this, a case-control study was conducted based on data collected from 60 villages in Eastern Sennar Locality, Sennar State, Sudan. Based on the presence of swelling in any part of the body, or sinus formation with or without grain discharge evident from the lesion by ultrasound examination, we diagnosed 359 cases of mycetoma. For each case, we included three healthy sex-matched persons, with no evidence of mycetoma, from the same village as the control group (n = 1077). The odds for mycetoma were almost three times higher in individuals in the age group 16–30 years (Adjusted Odds Ratio (AOR) = 2.804, 95% CI = 1.424–5.523) compared to those in age group ≤ 15 years. Other factors contributing to the odds of mycetoma were history of local trauma (AOR = 1.892, 95% CI = 1.425–2.513), being unmarried (AOR = 3.179, 95% CI = 2.339–4.20) and owning livestock (AOR = 3.941, 95% CI = 2.874–5.405). In conclusion, certain factors found to be associated with mycetoma in this study could inform a high index of suspicion for mycetoma diagnosis, which would improve early case detection. Other factors found to be associated could inform the development of an interventional program for mycetoma control in Sudan, including education on healthy farming practices and the risks of puncture wounds for individuals residing in endemic areas. However, this work was conducted in one endemic state, while mycetoma cases occur in all states of Sudan. Replicating this study over a wider area would give a fuller picture of the situation, providing the control program with more comprehensive information on the risk factors for the disease