1,721,033 research outputs found
Switching to boosted protease inhibitor plus a second antiretroviral drug (dual therapy) for treatment simplification: a multicenter analysis
No full textTo assess the role of drugs used in dual therapy (DT), as cART simplification, over the risk of treatment failure
Interpretation systems for genotypic drug resistance of HIV-1
No full textGenotypic assays are widely used tools for determining human immunodeficiency virus type 1 (HIV-1) drug resistance and for guiding treatment changes in patients failing antiretroviral therapy. Several systems have been developed to interpret the complex influence of key amino acid substitutions of the enzymes targeted by therapy on the phenotypic susceptibility or clinical response to available antiretroviral agents. This overview identifies 21 systems giving an interpretation on how amino acid substitutions affect phenotypic drug susceptibility or clinical activity of anti-HIV-1 agents. There was substantial variability in the mechanisms underlying the interpretations, the nature of the systems, their intended use, the source type of their knowledge base, and their update and output. Most of the systems could be accessed for free on the internet, functioned as rule-based algorithms updated by experts and at least partially based on literature evidence, and offered an automated report through a software. Nevertheless, the rule base was not always clarified. An update of the rules and the clinical validation of the systems are presented to help in the critical evaluation of their possible use. Importantly, only 8 systems were intended for clinical use and 5 of these had at least partially undergone clinical validation
Increased ophthalmic artery resistance index is associated with cognitive impairment in HIV-infected patients.
No full textOBJECTIVES:
Despite the introduction of combined antiretroviral therapy (cART), the prevalence of HIV-associated neurocognitive disorders (HANDs) remains high. Aim of the study was to investigate the potential relationship between ophthalmic artery resistance index (OARI), a marker of subclinical cerebrovascular disease, and cognitive performance.
METHODS:
We performed a cross-sectional cohort study by consecutively enrolling HIV-infected patients during routine outpatient visits. All subjects underwent a comprehensive neuropsycological battery and ultrasonographic assessment of OARI. Patients were classified as cognitively impaired if they showed decreased cognitive function involving at least two ability domains. OARI was considered abnormal if above 0.72 at left or right side. Factors associated with cognitive performance were evaluated by linear and logistic regression analysis.
RESULTS:
A total of 116 patients [78.4% males, median age 44 years (IQR 37-49), 13.8% with past AIDS-defining events, median CD4 482 cells/μL (IQR 352-690), 79.3% with HIV RNA <20 copies/mL] were enrolled. A hundred-thirteen (97.4%) subjects were on cART of which 88.5% on current regimen from one year. Fifty-four (46.6%) patients were classified as cognitively impaired. ROC curves indicated that the most discriminant left and right OARI values for predicting a mild cognitive impairment were >0.72 (AUC = 0.73, sensitivity 61.8%, specificity 81.4%, p < 0.001) and >0.71 (AUC = 0.72, sensitivity 69.1%, specificity 71.2%, p < 0.001), respectively. Multivariate analysis showed that OARI >0.72 (OR 4.7, p = 0.001) was independently associated with increased risk of cognitive impairment. Moreover, education (β = -0.18, p = 0.005), Zung depression score (β = +0.05, p = 0.021) and an abnormal OARI (β = +1.46, p = 0.002) were independently associated with an increased number of pathological performances. Evaluating separately each cognitive domain, an abnormal OARI confirmed an independent association with lower performance in attention and executive functions (p = 0.003) and in psychomotor speed (p = 0.010).
CONCLUSIONS:
Increased OARI was associated with lower cognitive performance in HIV-infected patients. These findings suggest a potential role of subclinical cerebrovascular disease in the pathogenesis of HAND
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Declining prevalence of HIV-1 drug resistance in treatment-failing patients: a clinical cohort study.
No full textOBJECTIVES: A major barrier to successful viral suppression in HIV type 1 (HIV-1)-infected individuals is the emergence of virus resistant to antiretroviral drugs. We explored the evolution of genotypic drug resistance prevalence in treatment-failing patients from 1999 to 2005 in a clinical cohort. PATIENTS AND METHODS: Prevalence of major International AIDS Society-USA HIV-1 drug resistance mutations was measured over calendar years in a population with treatment failure and undergoing resistance testing. Predictors of the presence of resistance mutations were analysed by logistic regression. RESULTS: Significant reductions of the prevalence of resistance to all three drug classes examined were observed. This was accompanied by a reduction in the proportion of treatment-failing patients. Independent predictors of drug resistance were the earlier calendar year, prior use of suboptimal nucleoside analogue therapy, male sex and higher CD4 levels at testing. CONCLUSIONS: In a single clinical cohort, we observed a decrease in the prevalence of resistance to all three examined antiretroviral drug classes over time. If this finding is confirmed in multicentre cohorts it may translate into reduced transmission of drug-resistant virus from treated patients
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Predictors of successful genotype-guided antiretroviral therapy in treatment-experienced individuals over calendar year: a cohort study
No full textBACKGROUND: The continuous development of new drugs for use in triple-drug combination antiretroviral therapy (cART) has dramatically decreased morbidity and mortality in HIV-1 infected individuals. However, increasing drug resistance could be associated with a poor outcome. OBJECTIVES: To determine the efficacy of resistance genotype-guided antiretroviral regimens in combination antiretroviral therapy (cART)-failing patients over calendar years and its predictors. STUDY DESIGN: Patients, with an available resistance genotype performed between 1999 and 2008, who failed a highly active antiretroviral therapy (HAART) regimen, changed therapy within 6 months from genotype and maintained the same salvage regimen, were selected from a clinical cohort database. Virologic efficacy was analyzed using time-to virologic suppression (VS, HIV-1 RNA<50 copies/ml). RESULTS: In 270 sequences analyzed from 212 patients, after a median follow-up of 23 weeks, there were 160 patients with VS (59.3%). Mean regimens' genotypic sensitivity score (GSS) increased from 1.86 (SD+/-0.92) in 1999-2001, to 2.29 (SD+/-0.96) in 2005-2008 (p=0.001 for trend). VS was achieved in 39% of those patients genotyped in 1999-2001, and increased to 69% for patients with genotyping performed between 2005 and 2008 (p<0.001). More recent calendar year, younger age and less use of suboptimal therapy were predictors of more effective HAART regimens but only more recent calendar year maintained a trend toward significance in a multivariable model. More recent genotyping calendar year, younger age, lower number of HAART regimens experienced, lower HIV-1 RNA and higher GSS independently conveyed and increased the probability of VS. CONCLUSIONS: Resistance-guided salvage antiretroviral therapy was more effective during more recent calendar years, independent from other measurable confounders, including the GSS of the employed regimen. Convenience and tolerability of newer agents should account for the observed effect
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