Outcomes of Antiretroviral Therapy in Vietnam: Results From a National Evaluation.

Outcomes of antiretroviral therapy in Vietnam: results from a national evaluation.

PLoS One. 2013; 8(2): e55750
Nguyen DB, Do NT, Shiraishi RW, Le YN, Tran QH, Huu Nguyen H, Medland N, Nguyen LT, Struminger BB

Vietnam has significantly scaled up its national antiretroviral therapy (ART) program since 2005. With the aim of improving Vietnam’s national ART program, we conducted an outcome evaluation of the first five years of the program in this concentrated HIV epidemic where the majority of persons enrolled in HIV care and treatment services are people who inject drugs (PWID). The results of this evaluation may have relevance for other national ART programs with significant PWID populations.Retrospective cohort analysis of patients at 30 clinics randomly selected with probability proportional to size among 120 clinics with at least 50 patients on ART.Charts of patients whose ART initiation was at least 6 months prior to the study date were abstracted. Depending on clinic size, either all charts or a random sample of 300 charts were selected. Analyses were limited to treatment-naïve patients. Multiple imputations were used for missing data.Of 7,587 patient charts sampled, 6,875 were those of treatment-naïve patients (74.4% male, 95% confidence interval [CI]: 72.4-76.5, median age 30, interquartile range [IQR]: 26-34, 62.0% reported a history of intravenous drug use, CI: 58.6-65.3). Median baseline CD4 cell count was 78 cells/mm (IQR: 30-162) and 30.4% (CI: 25.8-35.1) of patients were at WHO stage IV. The majority of patients started d4T/3TC/NVP (74.3%) or d4T/3TC/EFV (18.6%). Retention rates after 6, 12, 24, and 36 months were 88.4% (CI: 86.8-89.9), 84.0% (CI: 81.8-86.0), 78.8% (CI: 75.7-81.6), and 74.6% (CI: 69.6-79.0). Median CD4 cell count gains after 6, 12, 24, and 36 months were 94 (IQR: 45-153), 142 (IQR: 78-217), 213 (IQR: 120-329), and 254 (IQR: 135-391) cells/mm. Patients who were PWID showed significantly poorer retention.The study showed good retention and immunological response to ART among a predominantly PWID group of patients despite advanced HIV infections at baseline. HubMed – drug

In silico analysis of putative paralytic shellfish poisoning toxins export proteins in cyanobacteria.

PLoS One. 2013; 8(2): e55664
Soto-Liebe K, López-Cortés XA, Fuentes-Valdes JJ, Stucken K, Gonzalez-Nilo F, Vásquez M

Paralytic shellfish poisoning toxins (PSTs) are a family of more than 30 natural alkaloids synthesized by dinoflagellates and cyanobacteria whose toxicity in animals is mediated by voltage-gated Na channel blocking. The export of PST analogues may be through SxtF and SxtM, two putative MATE (multidrug and toxic compound extrusion) family transporters encoded in PSTs biosynthetic gene cluster (). is present in every cluster analyzed; however, is only present in the clade. These transporters are energetically coupled with an electrochemical gradient of proton (H) or sodium (Na) ions across membranes. Because the functional role of PSTs remains unknown and methods for genetic manipulation in PST-producing organisms have not yet been developed, protein structure analyses will allow us to understand their function. By analyzing the cluster of eight PST-producing cyanobacteria, we found no correlation between the presence of or and a specific PSTs profile. Phylogenetic analyses of SxtF/M showed a high conservation of SxtF in the clade, suggesting conserved substrate affinity. Two domains involved in Na and drug recognition from NorM proteins (MATE family) of and are present in SxtF/M. The Na recognition domain was conserved in both SxtF/M, indicating that Na can maintain the role as a cation anti-transporter. Consensus motifs for toxin binding differed between SxtF and SxtM implying differential substrate binding. Through protein modeling and docking analysis, we found that there is no marked affinity between the recognition domain and a specific PST analogue. This agrees with our previous results of PST export in D9, where we observed that the response to Na incubation was similar to different analogues. These results reassert the hypothesis regarding the involvement of Na in toxin export, as well as the motifs LXGLQD (SxtM) and LVGLRD (SxtF) in toxin recognition. HubMed – drug

Biologic drug access and juvenile idiopathic arthritis in Canada: improving collaboration between clinician experts and funders.

J Rheumatol. 2013 Mar; 40(3): 338
Cohen E, Grill A, Coyle D

HubMed – drug

Longterm Safety and Efficacy of Tocilizumab in Patients with Rheumatoid Arthritis: A Cumulative Analysis of Up to 4.6 Years of Exposure.

J Rheumatol. 2013 Mar 1;
Genovese MC, Rubbert-Roth A, Smolen JS, Kremer J, Khraishi M, Gómez-Reino J, Sebba A, Pilson R, Williams S, van Vollenhoven R

OBJECTIVE: To assess the longterm safety and efficacy of tocilizumab (TCZ) in patients with moderate to severe rheumatoid arthritis (RA). METHODS: Patient data were from 5 randomized controlled TCZ trials (n = 4211), their open-label extension phases (n = 3512), and a drug interaction study (n = 23). All randomly assigned patients, regardless of previous RA treatment, were analyzed. Measures of safety included number of adverse events (AE), serious AE (SAE), AE leading to treatment discontinuation, laboratory tests, and deaths. Efficacy measures included American College of Rheumatology (ACR) 20/50/70 responses, tender joint count (TJC), swollen joint count (SJC), ACR core set components, and low disease activity (LDA) or Disease Activity Score in 28 joints (DAS28) remission. ACR/European League Against Rheumatism (EULAR) disease remission was a posthoc exploratory analysis. RESULTS: Total duration of observation was 12,293 patient-years (PY). No new safety signals were identified; infections were the most common AE and SAE. The rate of serious infections was 4.5/100 PY. Improvements from baseline in clinical efficacy, measured as ACR20/50/70 responses, TJC, SJC, ACR core set components, and LDA and DAS28 remission, were generally sustained through at least 216 weeks of followup. ACR/EULAR disease remission was attained by 16.5% (Boolean) and 22.7% (index) of patients at Week 216. CONCLUSION: TCZ has to date been studied for up to 4.6 years (240 weeks) of treatment in patients with RA. Our analysis reveals a longer-term safety profile consistent with previous observations, no new safety signals, and durable efficacy of TCZ in a large clinical trial program. HubMed – drug