Management of multidrug-resistant tuberculosis (MDR-TB) is a significant challenge to the global healthcare system due to the complexity and long duration of the MDR-TB treatment. This study analyzed ...the safety of patients on longer injectable-based MDR-TB treatment regimens using active pharmacovigilance data.
We conducted an observational, prospective study based on active pharmacovigilance within the national TB program. A total of 659 MDR-TB patients were enrolled and followed up at 9 TB- hospitals in 9 provinces of all 3 regions in Vietnam between 2014 and 2016. Patients received a treatment regimen (standardized or individualized) based on their drug susceptibility test result and their treatment history. Baseline and follow-up information was collected at the start and during treatment. Adverse events (AE) were defined and classified as serious adverse events (SAEs) or otherwise. Multivariate Cox regression following the Iterative Bayesian Model Averaging algorithm was performed to identify factors associated with AE occurrence.
Out of 659 patients assessed, 71.3% experienced at least one AE, and 17.5% suffered at least one SAE. The most common AEs were gastrointestinal disorders (38.5%), arthralgia (34.7%), and psychiatric disorders (30.0%). The proportion of patients with nephrotoxicity and hearing loss or vestibular disorders were 7.4% and 15.2%, respectively. 13.1% of patients required modifications or interruption of one or more drugs. In 77.7% of patients, treatment was completed successfully, while 9.3% lost to follow-up, in 3.0% treatment failed, and 7.4% died. Some significant risk factors for nephrotoxicity included diabetes mellitus (HR = 8.46 1.91-37.42), renal dysfunction (HR = 8.46 1.91-37.42), alcoholism (HR = 13.28 5.04-34.99), and a higher average daily dose of injectable drugs (HR = 1.28 1.14-1.43).
While a majority of patients on the longer injectable-based regimens experienced non-serious AEs during MDR-TB treatment, one in six patients experienced at least an SAE. Active TB drug-safety monitoring is useful to understand the safety of MDR-TB treatment and explore the risk factors for toxicity. All-oral, shorter MDR-TB regimens might be able to reduce the inconvenience, discomfort, and toxicity of such regimens and increase adherence and likelihood of successful completion.
The selective detection and classification of NH3 and H2S gases with H2S gas interference based on conventional SnO2 thin film sensors is still the main problem. In this work, three layers of ...SnO2/Pt/WO3 nanofilms with different WO3 thicknesses (50, 80, 140, and 260 nm) were fabricated using the sputtering technique. The WO3 top layer were used as a gas filter to further improve the selectivity of sensors. The effect of WO3 thickness on the (NH3, H2, and H2S) gas-sensing properties of the sensors was investigated. At the optimal WO3 thickness of 140 nm, the gas responses of SnO2/Pt/WO3 sensors toward NH3 and H2 gases were slightly lower than those of Pt/SnO2 sensor film, and the gas response of SnO2/Pt/WO3 sensor films to H2S gas was almost negligible. The calcification of NH3 and H2 gases was effectively conducted by machine learning algorithms. These evidences manifested that SnO2/Pt/WO3 sensor films are suitable for the actual NH3 detection of NH3 and H2S gases.
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•The three layers of the SnO2/Pt/WO3 nanofilms based-gas sensor have been developed.•The SnO2/Pt/WO3 nanofilms can detect NH3 and H2 gases at low concentrations.•The classification of NH3 and H2 gases is made by machine learning algorithms.•The cross-response of sensors to interfering gas such as H2S were almost eliminated.•The gas filter mechanism was explained by the molecular size of the tested gases.
The irrational overuse of antibiotics should be minimized as it drives the development of antibiotic resistance, but changing these practices is challenging. A better understanding is needed of ...practices and economic incentives for antibiotic dispensing in order to design effective interventions to reduce inappropriate antibiotic use. Here we report on both quantitative and qualitative aspects of antibiotic sales in private pharmacies in northern Vietnam.
A cross-sectional study was conducted in which all drug sales were observed and recorded for three consecutive days at thirty private pharmacies, 15 urban and 15 rural, in the Hanoi region in 2010. The proportion of antibiotics to total drug sales was assessed and the revenue was calculated for rural and urban settings. Pharmacists and drug sellers were interviewed by a semi-structured questionnaire and in-depth interviews to understand the incentive structure of antibiotic dispensing.
In total 2953 drug sale transactions (2083 urban and 870 rural) were observed. Antibiotics contributed 24% and 18% to the total revenue of pharmacies in urban and rural, respectively. Most antibiotics were sold without a prescription: 88% in urban and 91% in rural pharmacies. The most frequent reported reason for buying antibiotics was cough in the urban setting (32%) and fever in the rural area (22%). Consumers commonly requested antibiotics without having a prescription: 50% in urban and 28% in rural area. The qualitative data revealed that drug sellers and customer's knowledge of antibiotics and antibiotic resistance were low, particularly in rural area.
Over the counter sales of antibiotic without a prescription remains a major problem in Vietnam. Suggested areas of improvement are enforcement of regulations and pricing policies and educational programs to increase the knowledge of drug sellers as well as to increase community awareness to reduce demand-side pressure for drug sellers to dispense antibiotics inappropriately.
Hospital effluents represent an important source for the release of antibiotics and antibiotic resistant bacteria into the environment. This study aims to determine concentrations of various ...antibiotics in wastewater before and after wastewater treatment in a rural hospital (60 km from the center of Hanoi) and in an urban hospital (in the center of Hanoi) in Vietnam, and it aims to explore the relationship between antibiotic concentrations in wastewater before wastewater treatment and quantities of antibiotics used in the rural hospital, over a period of one year in 2013. Water samples were collected using continuous sampling for 24 h in the last week of every month. The data on quantities of antibiotics delivered to all inpatient wards were collected from the Pharmacy department in the rural hospital. Solid-phase extraction and high performance liquid chromatography-tandem mass spectrometry were used for chemical analysis. Significant concentrations of antibiotics were present in the wastewater both before and after wastewater treatment of both the rural and the urban hospital. Ciprofloxacin was detected at the highest concentrations in the rural hospital's wastewater (before treatment: mean = 42.8 µg/L; after treatment: mean = 21.5 µg/L). Metronidazole was detected at the highest concentrations in the urban hospital's wastewater (before treatment: mean = 36.5 µg/L; after treatment: mean = 14.8 µg/L). A significant correlation between antibiotic concentrations in wastewater before treatment and quantities of antibiotics used in the rural hospital was found for ciprofloxacin (r = 0.78; p = 0.01) and metronidazole (r = 0.99; p < 0.001).
Abstract
Rationale:
Congenital bile acid synthesis defect (BASD) is a rare disease caused by mutations in the aldo-keto reductase 1D1 gene, which encodes the primary Δ4-3-oxosteroid 5β-reductase ...enzyme. Early disease diagnosis is critical for early treatment with bile acid replacement therapy, with an excellent chance for recovery. In contrast, protracted diagnosis and treatment may lead to poor outcomes, including decompensated hepatic cirrhosis, liver transplant, and even death.
Patient concerns:
Three clinical congenital bile acid synthesis defect cases in the Vietnamese population are herein reported. These pediatric patients presented with symptoms of prolonged postpartum jaundice and abnormal loose stool (mucus, lipids, and white). The clinical examinations showed hepatosplenomegaly. Urinalysis showed a very low fraction of primary bile acids and atypical 3-oxo-Δ4- bile acids in all three patients.
Diagnoses:
The patients were diagnosed with primary Δ4-3-oxosteroid 5β-reductase deficiency. Next-generation gene sequencing revealed two homozygous mutations in the aldo-keto reductase family 1 member D1 gene. The first is a documented variant, c.797G>A (p.Arg266Gln), and the second is a novel mutation at c.155T>C (p.Ile52Thr).
Interventions:
Immediately after diagnosis, patients were treated with oral chenodeoxycholate 5 mg/kg/d.
Outcomes:
The patients’ symptoms, signs, and primary bile acids levels improved significantly.
Lessons:
Clinicians should consider genetic disorders related to cholestasis for effective and life-saving treatment. A prompt genetic analysis by next-generation gene sequencing enables patients to access bile acid replacement therapy earlier, significantly improving short- and long-term outcomes.
It is unclear why the severity of influenza varies in healthy adults or why the burden of severe influenza shifts to young adults when pandemic strains emerge. One possibility is that ...cross-protective T cell responses wane in this age group in the absence of recent infection. We therefore compared the acute cellular immune response in previously healthy adults with severe versus mild pandemic H1N1 infection.
49 previously healthy adults admitted to the National Hospital of Tropical Diseases, Viet Nam with RT-PCR-confirmed 2009 H1N1 infection were prospectively enrolled. 39 recovered quickly whereas 10 developed severe symptoms requiring supplemental oxygen and prolonged hospitalization. Peripheral blood lymphocyte subset counts and activation (HLADR, CD38) and differentiation (CD27, CD28) marker expression were determined on days 0, 2, 5, 10, 14 and 28 by flow cytometry. NK, CD4 and CD8 lymphopenia developed in 100%, 90% and 60% of severe cases versus 13% (p<0.001), 28%, (p = 0.001) and 18% (p = 0.014) of mild cases. CD4 and NK counts normalized following recovery. B cell counts were not significantly associated with severity. CD8 activation peaked 6-8 days after mild influenza onset, when 13% (6-22%) were HLADR+CD38+, and was accompanied by a significant loss of resting/CD27+CD28+ cells without accumulation of CD27+CD28- or CD27-CD28- cells. In severe influenza CD8 activation peaked more than 9 days post-onset, and/or was excessive (30-90% HLADR+CD38+) in association with accumulation of CD27+CD28- cells and maintenance of CD8 counts.
Severe influenza is associated with transient T and NK cell deficiency. CD8 phenotype changes during mild influenza are consistent with a rapidly resolving memory response whereas in severe influenza activation is either delayed or excessive, and partially differentiated cells accumulate within blood indicating that recruitment of effector cells to the lung could be impaired.
The environmental spread of antibiotic-resistant bacteria has been recognised as a growing public health threat for which hospitals play a significant role. The aims of this study were to investigate ...the prevalence of antibiotic resistance and antibiotic resistance genes (ARGs) in
isolates from hospital wastewater in Vietnam. Wastewater samples before and after treatment were collected using continuous sampling every month over a year. Standard disk diffusion and E-test were used for antibiotic susceptibility testing. Extended-spectrum beta-lactamase (ESBL) production was tested using combined disk diffusion. ARGs were detected by polymerase chain reactions. Resistance to at least one antibiotic was detected in 83% of isolates; multidrug resistance was found in 32%. The highest resistance prevalence was found for co-trimoxazole (70%) and the lowest for imipenem (1%). Forty-three percent of isolates were ESBL-producing, with the
gene being more common than
Co-harbouring of the
,
and
genes was found in 46% of isolates resistant to ciprofloxacin. The large presence of antibiotic-resistant
isolates combined with ARGs in hospital wastewater, even post-treatment, poses a threat to public health. It highlights the need to develop effective processes for hospital wastewater treatment plants to eliminate antibiotic resistant bacteria and ARGs.
•The goals of economic efficiency and social equity are conflicting features of Vietnam’s rice policies.•Rice profit has markedly fallen during Vietnam’s high economic growth period despite the ...country’s effort to reverse it.•The terms of trade in rice production during Vietnam’s transition have deteriorated due to increasingly high labor costs.•Little investment in R&D and policy restricting farmers’ production choices have curbed technical change in rice production.•Government equity-targeting measures and increasingly aging farm workers have hindered the farm amalgamation process.
Increasing agricultural productivity is often deemed necessary to enhance rural income and ultimately narrow the urban–rural disparity in transitional economies. However, the objectives of social equity and economic efficiency can contradict each other, especially in the context of fierce competition for resources between agriculture and non-agricultural sectors and given the inherently and largely redundant and unskilled aging rural population that often occurs during the economic transition to a market economy. We investigate the case of Vietnam during its high growth period (2000–2016), over which the country introduced policies to increase efficiency in rice production and income for farmers. Contrary to expectations, we find a substantial fall in the terms of trade for rice, indicating a regression in farm income. This fall in the terms of trade did not enhance technical change, as seen in other countries, and only marginally improved technical efficiency in most regions. The reason stems from Vietnam’s limited investment in scientific research and development and policies that restrict farmers’ decision-making power in production, among others. We further examine the causes of inefficiency using data from two household surveys in 2004 and 2014 (with plot-level information) and semi-structured interviews with farmers in 2016–2017. The high ratio of aging farmworkers who are unable to find alternative employment during the transition emerges as an essential impediment to increases in rice productivity, in addition to previously documented land-use-related issues. This demographic feature, along with government equity-targeting measures, hinders the farm amalgamation progress, further limiting efforts to enhance efficiency. Thus, the goals of economic efficiency and social equity do indeed appear to be contradictory features of Vietnam’s rice policies, posing a significant development challenge for the country’s current and likely future progress.
A second cluster of COVID-19 cases imported from Europe occured in Vietnam from early March 2020. We describe 44 SARS-CoV-2 RT-PCR positive patients (cycle threshold value <30) admitted to the ...National Hospital for Tropical Diseases in Hanoi between March 6 and April 15 2020. Whole SARS-CoV-2 genomes from these patients were sequenced using Illumina Miseq and analysed for common genetic variants and relationships to local and globally circulating strains. Results showed that 32 cases were Vietnamese with a median age of 37 years (range 15-74 years), and 23 were male. Most cases were acquired outside Vietnam, mainly from the UK (n = 15), other European countries (n = 14), Russia (n = 6) and countries in Asia (n = 3). No cases had travelled from China. Forty-one cases had symptoms at admission, typically dry cough (n = 36), fever (n = 20), sore throat (n = 14) and diarrhoea (n = 12). Hospitalisation was long with a median of 25 days, most commonly from 20-29 days. All SARS-CoV-2 genomes were similar (92-100% sequence homology) to the reference sequence Wuhan_1 (NC_045512), and 32 strains belonged to the B.1.1 lineage. The three most common variants were linked, and included C3037T, C14408T (nsp12: P323L) and A23403G (S: D614G) mutations. This group of mutations often accompanied variant C241T (39/44 genomes) or GGG 28881..28883 AAC (33/44 genomes). The prevalence of the former reflected probable European origin of viruses, and the transition D614G was dominant in Vietnam. New variants were identified; however, none could be associated with disease severity.
•Characterization of eighty coffee bacterial endophytes.•Twelve bacterial genera described for the first time as coffee endophytes.•Wide range of plant growth promoting and biocontrol ...activities.•Antifungal activity on Fusarium oxysporum.•Nematicidal activity on Radopholus duriophilus and Pratylenchus coffeae.
The endophytic bacteria were isolated from coffee roots and seeds in Vietnam and identified with 16S rDNA sequencing as belonging to the Actinobacteria, Firmicutes and Proteobacteria phyla with the Nocardia, Bacillus and Burkholderia as dominant genera, respectively. Out of the thirty genera recovered from Coffea canephora and Coffea liberica, twelve were reported for the first time in endophytic association with coffee including members of the genera Brachybacterium, Caballeronia, Kitasatospora, Lechevalieria, Leifsonia, Luteibacter, Lysinibacillus, Mycolicibacterium, Nakamurella, Paracoccus, Sinomonas and Sphingobium. A total of eighty bacterial endophytes were characterized in vitro for several plant growth promoting and biocontrol traits including: the phosphate solubilization, the indolic compounds, siderophores, HCN, esterase, lipase, gelatinase and chitinase production. A subset of fifty selected bacteria were tested for their potential as biocontrol agents with in vitro confrontations with the fungal pathogen Fusarium oxysporum as well as the coffee parasitic nematodes Radopholus duriophilus and Pratylenchus coffeae. The three most efficient isolates on F. oxysporum belonging to the Bacillus, Burkholderia, and Streptomyces genera displayed a growth inhibition rate higher than 40%. Finally, five isolates from the Bacillus genus were able to lead to 100% of mortality in 24 h on both R. duriophilus and P. coffeae.
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