Expert Assessments for Off-Label Medicine useMedications are subject to tight regulation in most parts of the world whereby a particular drug, the group of patients it is used on and they way it is administered must be approved by a governing body prior to its marketing for use. Once authorised the specifics of its use (age group, dose, route of administration etc.) are written into the pack notes for reference by doctors and these form a useful check for the doctor that he is using the drug correctly. In a field of rare diseases such as aspergillosis there is often a serious lack of fully tested and authorised medications for use by doctors. This leads directly to the use of medications which are not authorised to treat the disease, or are not authorised for use in a particular patient group or for use in a particular way - this is referred to as off-label use. This is completely legal in many countries as long as it is carried out by doctors as physicians have the legal power to do so - they are however doing so without the authorised guidelines and must use their own experience and judgement. This situation is less than ideal and the UK NHS have decided to begin providing expert assessments for off-lable drug use via the National Institute for Clinical Excellence (NICE). The principle will be to provide a summary based on current available evidence which doesn't replace formal guidence but will support local decision making. Read more here. Latest News and ArticlesPCR-based diagnostics kit MycAssay recently had a positive outcome from an evaluation comparing it with other assays when attempting to detect Aspergillus infection in bronchoalveolar lavage samples taken from 158 patients suffering with haemotological or critical illness. MycAssay was found to be comparable to a galactomannan - based assay in terms of specificity and sensitivity and is of course a very rapid way to test for aspergillosis. The lack of a publicly-funded collection of strains for many micro-organisms is bemoaned in an article by Dugan et.al Attention Clinicians!AspICU2 is a web-based multicentre observational survey to assess the burden of aspergillosis and other fungi in critically ill patients. AspICU2 is the follow up of the original study AspICU project where emphasis was given to Aspergillus-positive cultures in critically ill patients. AspICU2 has a broadened scope to include other fungal disease with the accent on epidemiology, especially incidence and risk factor identification.
Selected articles: (38 new articles added, 17 of which are reviews)Rapid induction of multiple resistance mechanisms in Aspergillus fumigatus during azole therapy: a case study and review of the literature The authors detect and review multiple mechanisms of azole resistance (CYP51 and non-CYP51-related) arising in patients undergoing azole therapy. The generation of resistance is rapid, with 4 months being the average amount of time taken with a range from 3 weeks to 23 months. In Vitro Acquisition of Secondary Azole Resistance in Aspergillus fumigatus Isolates After Prolonged Exposure to Itraconazole: Presence of Heteroresistant Populations Slowly increasing the exposure of Aspergillus fumigatus isolates to itraconazole increases resistance (Minimal Inhibitory Concentration levels) to itraconazole and posaconazole (using a CPY51-independant mechanism) but not voriconazole. Inoculating large numbers of conidia onto medium containing 4 microgramme per ml itraconazole reproducably caused the isolation of strains resistant to both itraconazole & posaconazole all of which harboured a well documented azole resistant CYP51 mutation. New resources for functional analysis of omics data for the genus Aspergillus Once we have the DNA sequence of the entire genome of an organism we can start to identify the genes stored on that DNA - a process known as DNA annotation. Up until now only one Aspergillus species (fumigatus) had been annotated, now seven more Aspergillus species have been annotated by comparing their genes with those identified on A. fumigatus. 97% of all genes have been mapped. Molecular Diagnosis and Species-specific Identification of Medically Important Aspergillus species by Real Time PCR in Experimental Invasive Pulmonary Aspergillosis Rapid identification of the species of an infecting Aspergillus is potentially useful to guide diagnosis and treatment. This group have developed a TaqMan-based assay that can sensitively (comparable to current Galactomannan based tests) and specifically detect species in bronchoalveolar (BAL) samples from a mouse model for invasive aspergillosis. Pharmacokinetics and safety of intravenous voriconazole to oral switch in immunocompromised children compared to adults Overall, voriconazole IV doses higher than 7 mg/kg are needed in children to closely match adult exposures, and a weight-based oral dose may be more appropriate for children than a fixed dose. Safety of voriconazole in children was consistent with the known safety profile of voriconazole. ReviewsProtein Glycosylation in Aspergillus fumigatus Is Essential for Cell Wall Synthesis and Serves as a Promising Model of Multicellular Eukaryotic Development Glycosylation is a conserved posttranslational modification that is found in all eukaryotes, which helps generate proteins with multiple functions. This paper implies that the investigation of glycosylation in A. fumigatus is not only vital for elucidating the mechanism of fungal cell wall synthesis, which will benefit the design of new antifungal therapies, but also helps to understand the role of protein glycosylation in the development of multicellular eukaryotes. This paper describes the advances in functional analysis of protein glycosylation in A. fumigatus. Invasive fungal infections following liver transplantation - risk factors, incidence and outcome. The incidence of invasive fungal infections (IFIs), particularly candidiasis and aspergillosis, following solid organ transplantation vary from 1.4% to 42%. IFIs most commonly occur after orthotropic liver transplantation (OLT), lung/heart and pancreas transplantation. Mortality related to IFIs depends on the type of transplant and vary from 3% to 100% of cases. CONCLUSIONS: Early diagnosis and prompt treatment is fundamental for patient survival. Immunopathology and immunogenetics of allergic bronchopulmonary aspergillosis Allergic bronchopulmonary aspergillosis (ABPA) is a Th2 hypersensitivity lung disease in response to Aspergillus fumigatus that affects asthmatic and cystic fibrosis (CF) patients. A number of genetic risks have recently been identified in the development of ABPA. These include HLA-DR and HLA-DQ, IL-4 receptor alpha chain (IL-4RA) polymorphisms, IL-10 -1082GA promoter polymorphisms, surfactant protein A2 (SP-A2) polymorphisms, and cystic fibrosis transmembrane conductance regulator gene (CFTR) mutations. These genetic risk studies and their consequences of elevated biologic markers may aid in identifying asthmatic and CF patients who are at risk to the development of ABPA. Furthermore, these studies suggest that immune modulation with medications such as anti-IgE, anti-IL-4, and/or IL-13 monoclonal antibodies may be helpful in the treatment of ABPA. Drug InteractionsSeveral updates have been added by referring to Triazole antifungal agents drug-drug interactions involving hepatic cytochrome P450. The web address for this database is now www.antifungalinteractions.org Hall of Fame2 additions to Hall of Fame for scientists who have made outstanding contributions to our scientific understanding of Aspergillus: John Fincham FRS and John Pateman FRS Patients WebsiteHimalayan 100 mile challengeLewis has successfully completed the challenge and has written about his experiences in his blog at http://everestendurance.blogspot.com/2011/11/race-starts-here.html To date the magnificant total of £9,136 has been donated - many thanks to everyone who has contributed and it is not too late to donate now. Get INVOLVEDINVOLVE is a UK organisation dedicated to public involvment in the NHS, public health and social care research. They are currently looking for new members from the public rather than the professional world. For more information go here.
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