Arturo Viniegra-Osorio

Survey on physicians' knowledge and attitudes towards clinical practice guidelines at the Mexican Institute of Social Security

OBJECTIVE A survey was organized to determine the general level of knowledge and attitudes of medical personnel towards clinical practice guidelines (CPG). METHODS A questionnaire modified from two validated instruments was used. Multi-stratified sampling was applied, and 1782 questionnaires were completed. RESULTS A total of 80.4% of physicians had regular employment contract, 8.6% managerial post and 9.3% temporary work contract. Average age and working time were 43.7 and 15 years respectively; 64.3% were male. It was reported that 47.9% participated in academic activities, 70.8% belonged to a medical association, 40.3% identified CPG as steps towards arriving at a diagnosis and/or treatment and 14.9% thought that CPG were norms. A total of 10.7% of the physicians believed that guidelines are based on scientific evidence, 10% perceived them as supporting tools, 10.8% had no knowledge of them, 65% said that they used them, 76.7% thought that personal experience was as important as CPG recommendations and 57.4% thought that CPG were necessary for good medical practice. Physicians preferred that CPG be produced by personnel from outside the Mexican Institute of Social Security, or who had followed validity criteria. CONCLUSIONS The majority of physicians considered CPG to be useful tools. It was evident that few knew where to acquire CPG, and this would lead to their limited use. Findings from this study enabled procuring a broader idea of the level of knowledge and attitudes of Mexican Institute of Social Security physicians towards CPG. This information is relevant when planning strategies for the purpose of sharing and implementing CPG.

Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis

BackgroundThe correlations of genotypic and phenotypic tests with treatment, clinical history and the significance of mutations in viruses of HIV-infected patients are used to establish resistance mutations to protease inhibitors (PIs). Emerging mutations in human immunodeficiency virus type 1 (HIV-1) protease confer resistance to PIs by inducing structural changes at the ligand interaction site. The aim of this study was to establish an in silico structural relationship between natural HIV-1 polymorphisms and unusual HIV-1 mutations that confer resistance to PIs.ResultsProtease sequences isolated from 151 Mexican HIV-1 patients that were naïve to, or subjected to antiretroviral therapy, were examined. We identified 41 unrelated resistance mutations with a prevalence greater than 1%. Among these mutations, nine exhibited positive selection, three were natural polymorphisms (L63S/V/H) in a codon associated with drug resistance, and six were unusual mutations (L5F, D29V, L63R/G, P79L and T91V). The D29V mutation, with a prevalence of 1.32% in the studied population, was only found in patients treated with antiretroviral drugs. Using in silico modelling, we observed that D29V formed unstable protease complexes when were docked with lopinavir, saquinavir, darunavir, tipranavir, indinavir and atazanavir.ConclusionsThe structural correlation of natural polymorphisms and unusual mutations with drug resistance is useful for the identification of HIV-1 variants with potential resistance to PIs. The D29V mutation likely confers a selection advantage in viruses; however, in silico, presence of this mutation results in unstable enzyme/PI complexes, that possibly induce resistance to PIs.