Direct identification of microorganisms from positive blood cultures using the lysis-filtration technique and matrix assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS): a multicentre study.

Microbial identification from blood cultures is essential to institute optimal antibiotic therapy and improve survival possibilities. Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) has been successfully applied to identify bacteria and yeasts from positive blood cultures broths. The aim of this multicentre study was to evaluate the reliability of the lysis-filtration technique associated with MALDI-TOF MS to directly identify microorganisms from 765 positive blood cultures collected in six Italian hospitals. Overall, 675/765 (78.1%) blood isolates were correctly identified at the species level, with significant differences between Gram-negative and Gram-positive bacteria (92.6%, and 69.8%, respectively). Some difficulties arise in identifying Streptococcus pneumoniae, Staphylococcus aureus, yeasts and anaerobes. The lysis-filtration protocol is a suitable procedure in terms of performance in identifying microorganisms, but it is quite expensive and technically time-consuming since the time of filtration is not regular for all the samples. The application of the MALDI-TOF MS technique to the direct microbial identification from positive blood cultures is a very promising approach, even if more experience must be gained to minimize errors and costs.

IL-21 is associated with natural resistance to HIV-1 infection in a Colombian HIV exposed seronegative cohort.

Higher IL-21 levels were associated with natural resistance to HIV infection in an Italian cohort. Thus we wanted to confirm such association in HIV exposed seronegative individuals (HESN) from Colombia. Cells from HESN were less susceptible to infection and expressed higher IL-21 mRNA levels than healthy controls at both baseline and 7-days post-infection; similar results were observed for IL-6, perforin, and granzyme. These results suggest that IL-21/IL-6 increase may be a distinctive quality in the profile of HIV-1 resistance, at least during sexual exposure. However, further studies are necessary to confirm the specific protective mechanisms of these cytokines.

NRTI Sparing Therapy in Virologically Controlled HIV-1 Infected Subjects: Results of a Controlled, Randomized Trial (Probe).

Dual treatments could help clinicians to avoid drawbacks and toxicities due to the nucleosidic backbone, while maintaining the efficacy and convenience of robust combination antiretroviral therapy (cART). We explored the combination of rilpivirine plus boosted darunavir (DRV) as an option when switching from standard cART in patients who are virologically suppressed. In this randomized, open-label, proof-of-concept, noninferiority trial, we recruited patients aged 18 years or older with chronic HIV-1 infection and on a stable, effective (>6 months) protease inhibitor-based cART including a nucleosidic backbone. The primary endpoint was noninferiority of the virological response between treatment groups, according to FDA snapshot approach. Sixty patients were randomly allocated to dual treatment with rilpivirine plus boosted DRV or to continue their ongoing triple treatment. Noninferiority was shown at the prespecified level of -12% both at 24 and 48 weeks. At week 24, 100% of patients in the dual arm presented a blood HIV-RNA level <50 copies per milliliter compared with 90.1% in the triple drug arm (difference 9.9%, 95% CI: -0.7 to 20.7), whereas, at 48 weeks, the same proportions were 96.7% and 93.4%, respectively (difference 3.3%, 95% CI: -7.15 to 13.5). The mean change in CD4 cell count from baseline was 6.0 cells per microliter (SD, 184) for dual treatment and 16.5 cells per microliter (SD, 142) for triple treatment. A relevant decrement in CD838HLADR cells was observed in both arms. The reduction was, however, significantly more pronounced in the dual-therapy arm. At week 48, the CD838HLADR cell count was 3.4% (SD, 2.2) in the dual-therapy arm and 5.2% (SD, 3.1) in the triple arm (P = 0.018). None of the patients developed severe adverse events nor had to stop treatment because of adverse events or presented grade 3-4 laboratory abnormalities. A greater reduction of bone stiffness (-2.25; SD, 7.1) was observed in patients randomized to continue triple therapy compared with patients switched to dual therapy (-0.32; SD, 8.8). Finally, baseline HIV-DNA content directly correlated with pre-cART viral load of patients (P = 0.021), but not with time on cART or time with HIV-RNA below 50 copies per milliliter. Independently of the study arm, patients with a n HIV-RNA level constantly above 3 copies per milliliter or showing viral blips had baseline HIV-DNA levels significantly higher (64,656 copies per 10 cells; SD, 93057) compared with patients who constantly presented a HIV-RNA level below the detection limit of 3 copies per milliliter (14,457 copies per 10 cells; SD, 14098) (P = 0.001). A rilpivirine-boosted plus ritonavir-boosted DRV therapy was not inferior over 48 weeks to a standard boosted protease inhibitor-based triple cART. The dual therapy did not negatively affect lipid profile and renal function and was more friendly on bone metabolism. This approach constitutes an alternative for patients experiencing nucleoside reverse transcriptase inhibitor-related toxicities.

Clinical and Epidemiological Characteristics of Suicides Committed in Medellin, Colombia.

BACKGROUND: The purpose of this study was to identify the characteristics of individuals who committed suicide in Medellín between 2008 and 2010, and to identify variables related to the type of events. METHODS: A retrospective and descriptive analysis was conducted on data provided by the National Institute of Legal Medicine and Forensic Sciences. In addition, a univariate and bivariate analysis was used to identify the sociodemographic and medical-legal characteristics of the deceased. Multiple correspondence analysis was also used in order to establish typologies. The information was analyzed using STATA 11.0. RESULTS: Of the 389 cases occurring between 2008 and 2010, 84.6% (n=329) were men. The male to female ratio was 5:1; 64% of the cases occurred in people aged 18-45 years; 6.7% occurred in children under 18, with hanging being the method most chosen by the victims (48.3%). Exploratory analysis was used to identify a possible association between the use of violent methods and events occurring in the housing and social strata 1, 2 and 3. CONCLUSIONS: Some factors could be associated with suicide, providing data that could consolidate health intervention strategies in our population.

Early clinical response and presence of viral resistant minority variants: a proof of concept study.

INTRODUCTION: Traditional genotyping assays detect viral variants present in at least 15-25% of the entire virus population. We tested the Next generation GS Junior System (NGS) setted with a detection limit of 0.05% and evaluated the clinical relevance of low prevalent mutations. METHODS: NGS was performed on the plasma of 26 infected individuals who started a TDF/FTC/RPV (15 subjects) or TDF/FTC/EFV (11 subjects) cART after a routine HIV-1 drug-resistance negative test by Viroseq HIV-1 Genotyping System. Amplicon Sequencing of HIV-1 RT and PR Plate (Roche) was performed following the manufacturer's instructions. HIV-1 variants were analyzed by a specific HIV-1 tool by AVA software v. 2.7. The updated IAS resistance mutations list (March 2013) was considered for the analysis of resistance positions. Patients were followed testing viral load and immunologic parameters. RESULTS: Twenty four males and two females with a mean age of 43 years were included. Twenty-one were nave for cART. At baseline, median HIV-RNA was 4.57 log copies/mL (range 2.15-6.57) and CD4 count 315 cells/mcL (range 16-648). In 18 patients, NGS did not detect any additional variant relevant for the selected cART compared to population genotyping. In the remaining eight patients resistance conferring mutations to part of the ongoing regimen were detected. Single mutations E138K (two cases) and M184V in three distinct patients and V90I+G190E; M184V+A98S; Y215F+V118I+T215I; L210S+T215I+F227L; and A62V+D67G+K70N+188H in the remaining five subjects. In all cases, the mutation prevalence was inferior to 5%. The mean daily reduction of VL was -3759 copies/mL in patients without NGS detected mutations and -1045 copies/mL in those with mutations. The median KM estimates for reaching an HIV-RNA blood level <50 copies/mL were 127 days and 161 days, respectively. One patient without baseline resistance selected for M184I+E138K+T215I (NGS) after four months of TDF/FTC/RPV therapy. CONCLUSIONS: NGS detected low-frequency HIV-1 variants harbouring RT drug resistance mutations that could have affected the therapy outcome. However, viral decay in an early cART phase was not affected by the presence of resistant minority variants. The low prevalence of the detected mutation, the limited effect on the combination regimen and the potency of cART components could be possible explanations of our findings. Longer follow-up and larger casuistries are needed to determine the clinical relevance of NGS in routine clinical practice and eventually define a clinically relevant mutations' prevalence.

Clinical and Epidemiological Characteristics of Suicides Committed in Medellin, Colombia / Características clínicas y epidemiológicas del suicidio consumado en Medellín, Colombia

Background: The purpose of this study was to identify the characteristics of individuals who committed suicide in Medellín between 2008 and 2010, and to identify variables related to the type of events. Methods: A retrospective and descriptive analysis was conducted on data provided by the National Institute of Legal Medicine and Forensic Sciences. In addition, a univariate and bivariate analysis was used to identify the sociodemographic and medical-legal characteristics of the deceased. Multiple correspondence analysis was also used in order to establish typologies. The information was analyzed using STATA 11.0. Results: Of the 389 cases occurring between 2008 and 2010, 84.6% (n = 329) were men. The male to female ratio was 5:1; 64% of the cases occurred in people aged 18-45 years; 6.7% occurred in children under 18, with hanging being the method most chosen by the victims (48.3%). Exploratory analysis was used to identify a possible association between the use of violent methods and events occurring in the housing and social strata 1, 2 and 3. Conclusions: Some factors could be associated with suicide, providing data that could consolidate health intervention strategies in our population.

Antecedentes: El propósito del estudio es identificar las características de los individuos que cometieron suicidio en la ciudad de Medellín entre 2008 y 2010, además de identificar variables relacionadas con la tipología de los eventos. Métodos: Análisis descriptivo retrospectivo de los datos suministrados por el Instituto Nacional de Medicina Legal y Ciencias Forenses. Además, análisis univariable y bivariable para identificar las características sociodemográficas y médico-legales de los fallecidos. Para establecer posibles tipologías, se utilizó el análisis de correspondencias múltiples. La información se analizó utilizando el programa STATA 11.0. Resultados: De los 389 casos ocurridos entre 2008 y 2010, el 84,6% (n = 329) correspondió a varones. La razón varones:mujeres es 5:1. El 64% de los casos ocurrió en personas de 18-45 anños y el 6,7%, en menores de 18 años. El ahorcamiento fue el método más elegido por las víctimas (48,3%). El análisis exploratorio permitió identificar una posible asociación entre el uso de métodos violentos con los eventos que ocurren en la vivienda y los estratos sociales 1, 2 y 3. Conclusiones: Se pudo delinear algunos factores asociados al suicidio consumado, aportando elementos que pueden consolidar estrategias de intervención en la salud de nuestra población.