Community-level consumption of antibiotics according to the AWaRe (Access, Watch, Reserve) classification in rural Vietnam

Objectives To review community-level consumption of antibiotics in rural Vietnam, according to the WHO Access, Watch, Reserve (AWaRe) classification of 2019, and identify factors associated with the choice of these antibiotics. Methods In this cross-sectional study, data on antibiotic purchases were collected through a customer exit survey of 20 community antibiotic suppliers in Ba Vi District, Hanoi, between September 2017 and July 2018. Antibiotic consumption was estimated through the number of antibiotic encounters, the number of DDDs supplied and the number of treatment days (DOTs) with antibiotics, and analysed according to the AWaRe classification. The factors associated with watch-group antibiotic supply were identified through multivariable logistic regression analysis. Results In total, there were 1342 antibiotic encounters, with access-group antibiotics supplied in 792 encounters (59.0%), watch-group antibiotics supplied in 527 encounters (39.3%) and not-recommended antibiotics supplied in 23 encounters (1.7%). No reserve-group antibiotics were supplied. In children, the consumption of watch-group antibiotics dominated in all three measures (54.8% of encounters, 53.0% of DOTs and 53.6% of DDDs). Factors associated with a higher likelihood of watch-group antibiotic supply were: private pharmacy (OR, 4.23; 95% CI, 2.8–6.38; P < 0.001), non-prescription antibiotic sale (OR, 2.62; 95% CI, 1.78–3.87; P < 0.001) and children (OR, 2.56; 95% CI, 1.84–3.55; P < 0.001). Conclusions High consumption of watch-group antibiotics was observed, especially for use in children. The frequent supply of watch-group antibiotics at private pharmacies reconfirms the need for implementing pharmacy-targeted interventions in Vietnam

Pharmacogenomic Analysis of CYP3A5&ast;3 and Tacrolimus Trough Concentrations in Vietnamese Renal Transplant Outcomes

Thi Van Anh Nguyen,1,&ast; Ba Hai Le,2,&ast; Minh Thanh Nguyen,2,&ast; Viet Thang Le,3,&ast; Viet Tien Tran,4,&ast; Dinh Tuan Le,5,&ast; Duong Anh Minh Vu,2,&ast; Quy Kien Truong,3,&ast; Trong Hieu Le,2,&ast; Huong Thi Lien Nguyen2,&ast; 1Department of Pharmacy, 103 Military Hospital, Hanoi, Vietnam; 2Department of Clinical Pharmacy, Hanoi University of Pharmacy, Hanoi, Vietnam; 3Department of Nephrology and Dialysis, 103 Military Hospital, Hanoi, Vietnam; 4Department of Infectious Diseases, 103 Military Hospital, Hanoi, Vietnam; 5Department of Rheumatology and Endocrinology, 103 Military Hospital, Hanoi, Vietnam&ast;These authors contributed equally to this workCorrespondence: Huong Thi Lien Nguyen, Department of Clinical Pharmacy, Hanoi University of Pharmacy, 13-15 Le Thanh Tong, Hoan Kiem, Hanoi, Vietnam, Tel +84904308406, Email [email protected]: CYP3A5 polymorphisms have been associated with variations in the pharmacokinetics of tacrolimus (Tac) in kidney transplant patients. Our study aims to quantify how the CYP3A5 genotype influences tacrolimus trough concentrations (C0) in a Vietnamese outpatient population by selecting an appropriate population pharmacokinetic model of Tac for our patients.Patients and Methods: The external dataset was obtained prospectively from 54 data of adult kidney transplant recipients treated at the 103 Military Hospital. All published Tac population pharmacokinetic models were systematically screened from PubMed and Scopus databases and were selected based on our patient’s available characteristics. Mean absolute prediction error (MAPE), mean prediction error, and goodness-of-fit plots were used to identify the appropriate model for finding the formula that identifies the influence of CYP3A5 genotype on the pharmacokinetic data of Vietnamese patients.Results: The model of Zhu et al had a good predictive ability with MAPE of 19.29%. The influence of CYP3A5 genotype on tacrolimus clearance was expressed by the following formulas: . The simulation result showed that Tac C0 was significantly higher in patients not expressing CYP3A5 (p< 0.001).Conclusion: The incorporation of the CYP3A5 phenotype into Zhu’s structural model has significantly enhanced our ability to predict Tacrolimus trough levels in the Vietnamese population. This study’s results underscore the valuable role of CYP3A5 phenotype in optimizing the forecast of Tac concentrations, offering a promising avenue to assist health-care practitioners in their clinical decision-making and ultimately advance patient care outcomes.Keywords: tacrolimus, population pharmacokinetic, CYP3A5, Vietna

OCIAD1 is a host mitochondrial substrate of the hepatitis C virus NS3-4A protease.

The hepatitis C virus (HCV) nonstructural protein 3-4A (NS3-4A) protease is a key component of the viral replication complex and the target of protease inhibitors used in current clinical practice. By cleaving and thereby inactivating selected host factors it also plays a role in the persistence and pathogenesis of hepatitis C. Here, we describe ovarian cancer immunoreactive antigen domain containing protein 1 (OCIAD1) as a novel cellular substrate of the HCV NS3-4A protease. OCIAD1 was identified by quantitative proteomics involving stable isotopic labeling using amino acids in cell culture coupled with mass spectrometry. It is a poorly characterized membrane protein believed to be involved in cancer development. OCIAD1 is cleaved by the NS3-4A protease at Cys 38, close to a predicted transmembrane segment. Cleavage was observed in heterologous expression systems, the replicon and cell culture-derived HCV systems, as well as in liver biopsies from patients with chronic hepatitis C. NS3-4A proteases from diverse hepacivirus species efficiently cleaved OCIAD1. The subcellular localization of OCIAD1 on mitochondria was not altered by NS3-4A-mediated cleavage. Interestingly, OCIAD2, a homolog of OCIAD1 with a cysteine residue in a similar position and identical subcellular localization, was not cleaved by NS3-4A. Domain swapping experiments revealed that the sequence surrounding the cleavage site as well as the predicted transmembrane segment contribute to substrate selectivity. Overexpression as well as knock down and rescue experiments did not affect the HCV life cycle in vitro, raising the possibility that OCIAD1 may be involved in the pathogenesis of hepatitis C in vivo

Community-based antibiotic access and use in six low-income and middle-income countries: a mixed-method approach

Background Antimicrobial misuse is common in low-income and middle-income countries (LMICs), and this practice is a driver of antibiotic resistance. We compared community-based antibiotic access and use practices across communities in LMICs to identify contextually specific targets for interventions to improve antibiotic use practices. Methods We did quantitative and qualitative assessments of antibiotic access and use in six LMICs across Africa (Mozambique, Ghana, and South Africa) and Asia (Bangladesh, Vietnam, and Thailand) over a 2·5-year study period (July 1, 2016–Dec 31, 2018). We did quantitative assessments of community antibiotic access and use through supplier mapping, customer exit interviews, and household surveys. These quantitative assessments were triangulated with qualitative drug supplier and consumer interviews and discussions. Findings Vietnam and Bangladesh had the largest proportions of non-licensed antibiotic dispensing points. For mild illness, drug stores were the most common point of contact when seeking antibiotics in most countries, except South Africa and Mozambique, where public facilities were most common. Self-medication with antibiotics was found to be widespread in Vietnam (55·2% of antibiotics dispensed without prescription), Bangladesh (45·7%), and Ghana (36·1%), but less so in Mozambique (8·0%), South Africa (1·2%), and Thailand (3·9%). Self-medication was considered to be less time consuming, cheaper, and overall, more convenient than accessing them through health-care facilities. Factors determining where treatment was sought often involved relevant policies, trust in the supplier and the drug, disease severity, and whether the antibiotic was intended for a child. Confusion regarding how to identify oral antibiotics was revealed in both Africa and Asia. Interpretation Contextual complexities and differences between countries with different incomes, policy frameworks, and cultural norms were revealed. These contextual differences render a single strategy inadequate and instead necessitate context-tailored, integrated intervention packages to improve antibiotic use in LMICs as part of global efforts to combat antibiotic resistance. Funding Wellcome Trust and Volkswagen Foundation