Diagnostic capacities and treatment practices on implantation mycoses: Results from the 2022 WHO global online survey.

Between January and March 2022, WHO conducted a global online survey to collect data on diagnostic capacities and treatment practices in different settings for four implantation mycoses: eumycetoma, actinomycetoma, cutaneous sporotrichosis and chromoblastomycosis. The survey investigated the type of diagnostic methods available in countries at various health system levels (tertiary, secondary, primary level) and the medicines used to treat implantation mycoses, with a view to understanding the level of drug repurposing for treatment of these diseases. 142 respondents from 47 countries, including all continents, contributed data: 60% were from middle-income countries, with 59% working at the tertiary level of the health system and 30% at the secondary level. The results presented in this article provide information on the current diagnostic capacity and treatment trends for both pharmacological and non-pharmacological interventions. In addition, the survey provides insight on refractory case rates, as well as other challenges, such as availability and affordability of medicines, especially in middle-income countries. Although the study has limitations, the survey-collected data confirms that drug repurposing is occurring for all four surveyed implantation mycoses. The implementation of an openly accessible global and/or a national treatment registry for implantation mycoses could contribute to address the gaps in epidemiological information and collect valuable observational data to inform treatment guidelines and clinical research

Improving access to quality-assured and safe medicines and diagnostics for Neglected Tropical Diseases ― through coordinated procurement mechanisms and development of a strategy for regulatory pathways

Access to quality-assured, efficacious and safe health products is critical to ensure that the 2021–2030 neglected tropical disease (NTD) road map targets can be achieved. However, it is challenging due to various factors such as lack of funding, little interest from the pharmaceutical industry, limited regulatory oversight and few quality assurance mechanisms and uncoordinated procurement with uncertain forecasting. Aiming to shed light on the current market landscape for leishmaniasis, one of NTDs, and develop a regulatory framework for NTD diagnostics, we conducted an analysis of 1) global procurement of leishmaniasis medicines for the past 5 years and 2) the availability of commercially available NTD diagnostics. For historical procurement analysis, we estimated the global demand of each leishmaniasis medicines based on the number of cases reported to WHO and the treatment regimen used in each country. Procurement data were obtained from procurement agencies, international organizations, WHO, national leishmaniasis programmes and manufacturers. Expert interviews were conducted to have a better understanding of how medicines were procured and used. For the development of a strategy for regulatory pathways for NTD diagnostics, the list of commercially available diagnostics was compiled from various sources and the inventory was analyzed according to diagnostic type, intended use, regulatory status, and risk classification. To estimate the global need and size of the market for each type of diagnostic, annual procurement data were collected from procurement agencies. The comparison of estimated need and procurement data indicated discrepancies in supply and demand at global level as well as in the leishmaniasis endemic countries. The extent of the gap in supply was up to 80% of the needs for one of the leishmaniasis medicines. Mismatch between supply and demand was much wider for cutaneous leishmaniasis than visceral leishmaniasis. Of 125 diagnostic tools included in this analysis, rapid diagnostic tools accounted for 33% of diagnostics used for NTDs and very few diagnostics had been subjected to regulatory assessment. The number of tests needed for each disease was less than 1 million units per annum, except in the case of two diseases, suggesting limited commercial value. Addressing improved access and supply and regulatory barriers requires multidimensional, collaborative and concerted efforts at the global and national levels. Priority actions proposed to improve access to leishmaniasis medicines include (i) setting up the procurement coordination mechanism with major partners for the development of joint forecasting and market shaping interventions, (ii) proactive engagement of manufacturers to secure uninterrupted supply of quality-assured medicines and (iii) promoting high-level advocacy. Despite the nature of the market, and presumed insufficient return on commercial investment, acceptable levels of assurance on performance, quality and safety of NTD diagnostics are still required. Priority actions include setting up an agile, interim, stepwise risk assessment mechanism, in particular for diagnostics of lower risk, in order to support national NTD programmes and their partners with the selection and procurement of the diagnostics needed to control, eliminate and eradicate NTDs. </p

The global procurement landscape of leishmaniasis medicines.

Ensuring access to essential medicines for leishmaniasis control is challenging, as leishmaniasis is a very small and unattractive market for pharmaceutical industry. Furthermore, control programmes are severely underfunded. We conducted an analysis of global procurement of leishmaniasis medicines for the past 5 years in order to shed light on the current leishmaniasis market landscape and supply and demand dynamics. We estimated global demand of each leishmaniasis medicines, the amount of each medicine required to treat all reported cases, based on the number of cases reported to WHO and the first-line treatment regimen used in each country. Procurement data were obtained from procurement agencies, international organizations, WHO, national leishmaniasis programmes and manufacturers. Expert interviews were conducted to have a better understanding of how medicines were procured and used. The comparison of estimated need and procurement data indicated discrepancies in supply and demand at global level as well as in the most endemic countries. The extent of the gap in supply was up to 80% of the needs for one of the leishmaniasis medicines. Mismatch between supply and demand was much wider for cutaneous leishmaniasis than visceral leishmaniasis. This study presents a current picture of procurement patterns and imbalance in global supply and demand. Addressing improved access and supply barriers requires concerted and coordinated efforts at the global and national levels. Priority actions include setting up a procurement coordination mechanism among major procurers, partners and national programmes where forecasting and supply planning is jointly developed and communicated with manufacturers. In addition, continuous engagement of manufacturers and advocacy is critical to diversify the supplier base and ensure quality-assured and affordable generic medicines for leishmaniasis

Analysis of Outcomes in Ischemic vs Nonischemic Cardiomyopathy in Patients With Atrial Fibrillation A Report From the GARFIELD-AF Registry

IMPORTANCE Congestive heart failure (CHF) is commonly associated with nonvalvular atrial fibrillation (AF), and their combination may affect treatment strategies and outcomes

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field