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PubMed | Clinic, Directorate, Monitoring and Evaluation and Regional Infectious Diseases Unit
Type: Journal Article | Journal: Journal of the International AIDS Society | Year: 2014

Lactic acidosis is one of the most serious side effects associated with ART, most commonly associated with stavudine. Clinical features are non-specific and specialist laboratory capabilities are essential to confirm the diagnosis, making under-diagnosis likely in resource-constrained settings. Lighthouse Trust is a tertiary referral ART centre with over 23,500 patients on ART. The adjacent University of North Carolina Project laboratory, also serving Kamuzu Central Hospital, has been the only site processing lactate tests in Central Zone for many years. Our objective was to quantify the true incidence within our cohort, and estimate the likely degree of historical missed diagnoses from less central ART clinics.All high lactate results between June 2010 and June 2013 were treated as cases, and cross referenced with the Lighthouse database. Patients transferring in to Lighthouse within one month prior to diagnosis were assumed to have been referred due to their lactic acidosis, and moved to the Central Zone cohort to avoid referral bias. Routinely collected quarterly ART cohort data for both Lighthouse and the entire Central Zone were analyzed.Over the three-year period, from within the Lighthouse cohort, there were 138 cases: 74% were female, median duration on ART was 14 months (IQR 10-26), and 98.5% were attributable to stavudine (only two cases to zidovudine). Over this period, the average number of patients taking stavudine at Lighthouse was 10,960 (3,600 on zidovudine). For the whole Central Zone (minus Lighthouse patients) there were 61,000 on stavudine (4,830 on zidovudine), yet only 124 cases of lactic acidosis were apparently diagnosed from within this cohort.Although cases may, of course, also have been missed at Lighthouse, as a tertiary referral centre the rate observed is likely to be closer to the true incidence. Over the three years, with 138 cases from the 10,960 patients taking stavudine at Lighthouse, it is likely that somewhere in the region of 700 additional cases occurred amongst the 61,000 patients elsewhere in the Central Zone. This equates to somewhere in the region of 550 missed diagnoses or 80% of all cases. Given that the clinical sequelae of undiagnosed lactic acidosis are either death or at best ART default, this provides further vindication for the decision to phase out stavudine in Malawi.


Miller R.,Directorate | Owens S.J.,Directorate | Rorslett B.,Directorate
Optics and Laser Technology | Year: 2011

While there is a range of colours found in plants the predominant colour is green. Pigments in plants have several roles e.g. photosynthesis and signalling. If colour is to be used as a signal then it must stand out from green. However, one should be aware that there are also coloured compounds where we have not yet fully investigated the role of colour in their functions - they may have roles in, for example, defence or heat exchange. In this paper, we will describe the basic chemistry of the major pigments found in plants and especially floral pigments. We will then discuss their locations in parts of the flower (such as sepals, petals, pollen and nectar), the cells in which they are found and their sub-cellular locations. Floral pigments have a large role to play in pollination of flowers by animals. They can and are modified in many ways during the development of flowers in nature, for example, at emergence and post-pollination. There are a range of biochemical mechanisms of colour change both within flowers and in isolated pigments. Some of the factors influencing colour are temperature, co-pigments, pH, metals, sugars, anthocyanin stacking and cell shape. There is a renewed interest in analysing floral pigments and how they are modified partly because of advances in recombinant DNA technologies, but also because of pollinators and their significance to biodiversity and for evolutionary studies. There is continued strong interest from the horticultural industry for the introduction of new colours e.g. the blue rose and for the exploitation of natural dyes. Funding in this area may impact future research in a potentially beneficial way but it must not deflect us from science-based conservation. Copyright © 2009 Published by Elsevier Ltd. All rights reserved.


PubMed | Clinique Medicale lActuel, Directorate, Epidemiology and Clinical Research
Type: Journal Article | Journal: Journal of the International AIDS Society | Year: 2014

In HIV+ patients exhibiting multidrug resistance (MDR), NRTIs often have little activity, increased toxicity, drug interactions and add unnecessary treatment costs. The 48 week VERITAS study demonstrated that these patients can have a safe and effective simplification of salvage regimen by removing inactive NRTIs as determined by genotypic data. Virological, immunological, clinical and financial outcomes were evaluated at an additional 96 weeks of follow-up.MDR patients with an undetectable viral load (VL) on a stable regimen containing at least four ARVs (including one inactive NRTI) were enrolled in an open-label, prospective simplification trial, where one inactive NRTI was removed at baseline (BL). A second NRTI could be removed at week 24 if the regimen contained at least five ARVs at enrolment.31 male patients participated. The mean length of treatment was 14 years, with a median CD4 count of 525. The BL regimen consisted of 4 ARVs in 22 patients (71%) and 5 ARVs in 9 patients (29%). 3TC or FTC was removed in 29 patients (94%), and either AZT or TDF was interrupted in 2 others. Four patients had a second NRTI stopped. One patient was removed at W26 as an active NRTI was removed for creatinine elevation. 30 well-controlled patients continued follow-up after W48. At W144, six patients had additional changes in their ARV regimen. Half were due to toxicity (jaundice, neuropathy and nephrotoxicity) while the other half were the result of treatment simplification. None of the patients exhibited virologic failure at the time of treatment change and maintained undetectable VLs throughout the entire follow-up. These six patients had a mean gain of 79 CD4 (p=0.17) compared to baseline. 22 of the 24 patients (92%) with no changes in ARV therapy after W48 had undetectable VLs. The other two had confirmed virologic failure, one with genotypic resistance. All 24 had elevated CD4 counts (mean +118 CD4, p<0.0001). No deaths or serious adverse events were observed. One or two ARV removals translated to a mean annual saving of $3319 CDN (11%) and $8630 (24%) respectively.Final results indicate that removing one or two inactive NRTIs from a regimen in patients taking four or more ARVs with controlled VL appears to be safe, maintains virological suppression through 144 weeks and significantly reduces treatment costs.

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