Impact of clinical pharmacist-led interventions on switching from intravenous-to-oral antibiotics in patients with infectious diseases at a Vietnamese hospital.

OBJECTIVES: To evaluate the impact of clinical pharmacist-led interventions on the switch from intravenous (IV) to oral (PO) antibiotics among inpatients with infectious diseases. METHODS: A before-and-after study was conducted among inpatients aged 18 or older who were diagnosed with infectious diseases and received IV antibiotics for at least 24 h at the Thong Nhat Hospital during the pre-intervention (between January 2021 and June 2021) and intervention (between January 2022 and June 2022) periods. Information on patient characteristics, antibiotic usage, length of hospital stay and treatment outcomes was obtained from medical records. The interventions included introducing IV-to-PO switch guidelines to physicians and clinical pharmacists' feedback on eligible cases. The impact of the pharmacists' interventions was evaluated by comparing primary outcomes (switch rate and appropriateness of switching) and secondary outcomes (duration of IV therapy, length of hospital stay and treatment outcomes) between the two study periods. RESULTS: We included 99 patients in the pre-intervention and 80 patients in the intervention period. The proportion of patients who switched from IV-to-PO antibiotics increased from 44.4% in the pre-intervention period to 67.8% in the intervention period (p = 0.008). The overall rate of appropriate conversion increased significantly from 43.8% to 67.5% (p = 0.043). There were no statistically significant differences between the two periods with respect to the median duration of IV therapy (9 days vs. 8 days), length of hospital stay (10 days vs. 9 days) and treatment outcomes. Logistic regression analysis showed that the interventions resulted in a higher switch rate, whereas age was negatively associated with the switching rate. CONCLUSIONS: The implementation of clinical pharmacist-led interventions was effective in promoting IV-to-PO antibiotic conversion.

Vitamin E intake and paraoxonase 1 (PON1) rs662 genetic polymorphism are associated with colorectal cancer risk in a Korean population.

Vitamin E and paraoxonase 1 (PON1) are associated with cancer development. However, their interactive effect on colorectal cancer (CRC) risk is inconclusive. We conducted a case-control study including 1,351 CRC patients and 2,670 controls at the Korean National Cancer Centre (KNCC). There was an inverse association between vitamin E intake and CRC risk (odds ratio (OR) = 0.31; 95% confidence interval (CI) = 0.22-0.42). We identified a reduced CRC risk among individuals with CC genotype of PON1 rs662 polymorphism compared with subjects carrying the T allele (OR = 0.74; 95% CI = 0.61-0.90). The highest interaction between vitamin E intake and PON1 rs662 variants was significant for the subjects carrying the CC genotype (p-interaction = 0.014). This study provided further supporting evidence that vitamin E intake is associated with lower odds of CRC. Furthermore, the activity of vitamin E is strengthened among individuals carrying C allele of the PON1 rs662 polymorphism.

Unveiling the genomic structures and evolutionary events of the saxitoxin biosynthetic gene sxtA in the marine toxic dinoflagellate Alexandrium.

Marine dinoflagellates Alexandriumare known to produce saxitoxin (STX) and cause paralytic shellfish poisoning (PSP) which can result in mortality in human. SxtA is considered a core gene for the biosynthesis of STX. However, its gene coding structure and evolutionary history have yet to be fully elucidated. Here, we determined the full-length sequences of sxtA cDNA and genomic coding regions from two toxic dinoflagellates, Alexandrium catenella (LIMS-PS-2645 and LIMS-PS-2647) andA. pacificum (LMBE-C4), characterised their domain structures, and resolved evolutionary events. The sxtA gene was encoded on the genome without introns, and was identical in length (4002 bp) between two A. catenella strains, but their sequences differed from A. pacificum (5031 bp). SxtA consists of four domains, sxtA1, sxtA2, sxtA3, and sxtA4; however, A. pacificum has an extra domain TauD near sxtA1. Each domain had >64.4% GC content, with the highest being 71.6% in sxtA3. Molecular divergence was found to be significantly higher in sxtA4 than in the other domains. Phylogenetic trees of sxtA and separate domains showed that bacteria diverged earliest, followed by non-toxic, toxic cyanobacteria, toxic dinoflagellates. While sxtA domains in Alexandrium were similar to the PKS-like structure with the conserved sxtA1, sxtA2, and sxtA3. PKS_KS may be replaced by sxtA4 in toxic Alexandrium. These suggest that sxtA in Alexandrium may have evolved by acquiring specific domains, whose modification and complexity markedly affect toxin biosynthesis.

Quality of life assessment in patients on chronic dialysis: Comparison between haemodialysis and peritoneal dialysis at a national hospital in Vietnam.

OBJECTIVES: End-stage renal disease (ESRD) is a chronic disease that can adversely affect the patient's quality of life (QoL) in terms of functional limitation and cognitive impairment. This study aimed to identify the factors associated with QoL in patients with ESRD undergoing dialysis at a national hospital in Vietnam. METHODS: A descriptive cross-sectional study was conducted among outpatients aged ≥18 years who underwent haemodialysis (HD) or peritoneal dialysis (PD) for at least 3 months at Thong Nhat Hospital, Ho Chi Minh City, Vietnam from May 2020 to July 2021. QoL was measured using the validated Vietnamese version of the EuroQol-5 Dimensional-5 Level (EQ-5D-5L). The factors associated with the QoL of patients with ESRD undergoing dialysis were identified using multiple linear regression analysis. RESULTS: In total, 131 (73.6%) and 47 (26.4%) patients underwent HD and PD, respectively. Overall, 178 (55.6%) patients were men (median age, 66 [56-79] years). The mean EQ-5D-5L score was significantly higher in patients undergoing PD than in those undergoing HD (0.848 ± 0.183 vs. 0.766 ± 0.231; p = 0.030). Older age (ß = -0.006; p < 0.001) and peptic ulcer disease (ß = -0.083; p = 0.029) were associated with lower QoL scores. PD treatment was associated with higher QoL scores (ß = 0.065; p = 0.046). CONCLUSIONS: It is necessary to improve the QoL of patients undergoing dialysis, especially of elderly patients and patients with peptic ulcer disease. PD may be a better method for maintenance dialysis, if applicable, in terms of QoL.

Impact of antimicrobial stewardship intervention in clean and clean-contaminated surgical procedures at a Vietnamese national hospital.

OBJECTIVES: We investigated the characteristics of prophylactic antimicrobial use in clean and clean-contaminated surgical procedures and assessed the efficacy of a prophylactic antimicrobial stewardship intervention at Thong Nhat Hospital, Ho Chi Minh City, Vietnam. METHODS: A cross-sectional study was conducted on 354 patients who underwent either clean or clean-contaminated surgical procedures at Thong Nhat Hospital. Eligible patients were classified with respect to three periods of intervention from 2017 to 2020. Data collection included surgical procedures, patient characteristics, and prophylactic antimicrobial usage. We determined the efficacy of antimicrobial stewardship intervention based on comparisons among the primary outcome (the appropriateness of prophylactic antimicrobials) and secondary outcomes (postoperative antimicrobial prophylaxis (AP) prolongation, length of postoperative hospital stay, and cost of antimicrobials). RESULTS: The mean age of patients in periods 1, 2, and 3 was 54.5 ± 16.6, 50.2 ± 16.5, and 52.8 ± 17.3 years, respectively, with an overall male/female ratio of 1.1/1. No significant differences were detected in basic patient characteristics during the three periods. Majority of the surgical procedures were clean (56%-59%) and scheduled (85%-86%). Prophylactic antimicrobial stewardship intervention enhanced AP appropriateness (by 12.7%, 12.7%, and 39.0% in periods 1, 2, and 3, respectively, p < 0.001), decreased postoperative prophylactic antimicrobial duration [3.0 (0-6), 1.5 (0-5), and 0.0 (0-1) days, respectively, p < 0.001], and reduced average antimicrobial expenses (p < 0.001). CONCLUSIONS: The prophylactic antimicrobial stewardship interventions introduced at Thong Nhat Hospital had several positive impacts on the appropriateness of prophylactic antimicrobial use and treatment costs.

Antibiotic use in gastrointestinal surgery patients at a Vietnamese national hospital.

BACKGROUND: Invasive gastrointestinal surgery may be performed as an open or endoscopic procedure, such as laparoscopic semi-colon surgery, laparoscopic appendectomy, laparoscopic gastrectomy, and anal surgery, among other such operations. Regardless of the approach, the operative procedure interferes with the patient's gastrointestinal tract, necessitating the rational use of prophylactic antibiotics to improve treatment outcomes and minimize postoperative infections. OBJECTIVE: To investigate the prophylactic and postoperative antibiotic usage in patients who underwent invasive gastrointestinal surgery, and to identify factors associated with postoperative infection. DESIGN: This descriptive, cross-sectional study included 112 patients who underwent invasive gastrointestinal surgery at the Department of Gastroenterology, Thong Nhat Hospital. We conducted a cross-sectional study in all inpatients aged 18 years and older, who underwent invasive gastrointestinal surgery between January 2020 and December 2020. We recorded patient characteristics, the administration and appropriateness of antibiotics, as well as treatment outcomes. The appropriateness of prophylactic and postoperative antibiotic usage was assessed based on 2015 Vietnamese national guideline for antibiotic use. Multivariable logistic regression analysis was used to determine the factors associated with postoperative infection. RESULTS: Patients' mean age was 59.7 ± 17.2 years. Most surgeries (89.3%) were clean-contaminated procedures. The rates of appropriate types of antibiotics selected, doses, and overall rates of appropriateness of antibiotic prophylaxis were 68.0%, 76.4% and 54.7%, respectively. Of the patients investigated, 34.8% had at least one sign of postoperative infection; the overall appropriate rate of postoperative antibiotic was 38.5%. Old age was associated with postoperative infection and longer length of hospitalization. CONCLUSION: Implementation of the guidelines recommended for the prophylactic and therapeutic use of antibiotics is essential to improve treatment outcomes.

Flood risk mapping and analysis using an integrated framework of machine learning models and analytic hierarchy process.

In this study, a new approach of machine learning (ML) models integrated with the analytic hierarchy process (AHP) method was proposed to develop a holistic flood risk assessment map. Flood susceptibility maps were created using ML techniques. AHP was utilized to combine flood vulnerability and exposure criteria. We selected Quang Binh province of Vietnam as a case study and collected available data, including 696 flooding locations of historical flooding events in 2007, 2010, 2016, and 2020; and flood influencing factors of elevation, slope, curvature, flow direction, flow accumulation, distance from river, river density, land cover, geology, and rainfall. These data were used to construct training and testing datasets. The susceptibility models were validated and compared using statistical techniques. An integrated flood risk assessment framework was proposed to incorporate flood hazard (flood susceptibility), flood exposure (distance from river, land use, population density, and rainfall), and flood vulnerability (poverty rate, number of freshwater stations, road density, number of schools, and healthcare facilities). Model validation suggested that deep learning has the best performance of AUC = 0.984 compared with other ensemble models of MultiBoostAB Ensemble (0.958), Random SubSpace Ensemble (0.962), and credal decision tree (AUC = 0.918). The final flood risk map shows 5075 ha (0.63%) in extremely high risk, 47,955 ha (5.95%) in high-risk, 40,460 ha (5.02%) in medium risk, 431,908 ha (53.55%) in low risk areas, and 281,127 ha (34.86%) in very low risk. The present study highlights that the integration of ML models and AHP is a promising framework for mapping flood risks in flood-prone areas.

The Cost-Effectiveness of Adapting and Implementing a Brief Intervention to Target Frequent Alcohol Use Among Persons with HIV in Vietnam.

Brief interventions to reduce frequent alcohol use among persons with HIV (PWH) are evidence-based, but resource-constrained settings must contend with competition for health resources. We evaluated the cost-effectiveness of two intervention arms compared to the standard of care (SOC) in a three-arm randomized control trial targeting frequent alcohol use in PWH through increasing the percent days abstinent from alcohol and viral suppression. We estimated incremental cost per quality-adjusted life year (QALY) gained from a modified societal perspective and a 1-year time horizon using a Markov model of health outcomes. The two-session brief intervention (BI), relative to the six-session combined intervention (CoI), was more effective and less costly; the estimated incremental cost-effectiveness of the BI relative to the SOC, was $525 per QALY gained. The BI may be cost-effective for the HIV treatment setting; the health utility gained from viral suppression requires further exploration.

Validation of screening tools for common mental health disorders in the methadone maintenance population in Hanoi, Vietnam.

BACKGROUND: Common mental health disorders (CMDs), including depression, anxiety and post-traumatic stress disorder (PTSD) may worsen both HIV and drug use outcomes, yet feasible tools to accurately identify CMDs have received limited study in this population. We aimed to validate the Patient Health Questionnaire (PHQ-9), Generalized Anxiety Disorder screen (GAD-7) and Primary Care PTSD screen for DSM-5 (PC-PTSD-5) in a methadone maintenance therapy (MMT) patient population in Hanoi, Vietnam. METHODS: We conducted a cross-sectional survey. The PHQ-9, GAD-7, and PC-PTSD-5 were administered to MMT patients. A blinded interviewer administered the Mini-International Neuropsychiatric Interview (MINI) as the reference gold standard. Total scores of each tool were compared with the MINI diagnoses using a receiver operating characteristic curves, and we identified the optimal respective cut-off scores using the Youden's Index. RESULTS: We enrolled 400 MMT patients. Approximately 99.3% were male (n = 397) and 21.8% (n = 87) were HIV positive. The prevalence of major depressive disorder, generalized anxiety disorder and PTSD, respectively, was 10.5, 4 and 2%. Optimal cut-off scores for the PHQ-9, GAD-7 and PC-PTSD were ≥ 5, ≥3, and ≥ 4 with a sensitivity/specificity of 95.2%/91.9, 93.8%/87.5, and 62.5%/95.2%. CONCLUSIONS: The prevalence of CMDs in the MMT population was lower than expected. A lower cut-off score may be considered when screening for CMDs in this population. Further research should investigate the validity of somatic symptom-based screening tools among other drug-using or MMT populations.

Examining common mental health disorders in people living with HIV on methadone maintenance therapy in Hanoi, Vietnam.

BACKGROUND: Injection drug use drives HIV transmission in Southeast Asia, where around a quarter of users are living with HIV. Vietnam developed Methadone Maintenance Therapy (MMT) programs to reduce unsafe drug abuse. Common mental health disorders (CMD), including depression, anxiety and post-traumatic stress disorder (PTSD), can worsen MMT outcomes and are highly prevalent among people living with HIV (PLH). We aimed to characterize HIV and CMD among MMT patients and assess the impact of HIV and CMD on MMT engagement outcomes in Hanoi, Vietnam. METHODS: This cross-sectional study was conducted at an urban MMT clinic in Hanoi. Participants were screened for CMD with the relevant sections of the Mini International Neuropsychiatric Interview (MINI). Tabular comparisons and regression models were used to understand the association of HIV and CMD with substance use and methadone compliance. RESULTS: Of the 400 MMT participants, 22% were living with HIV, 11% a CMD, 27% reported injection drug use, and 27% reported methadone noncompliance. Around 17% of those with HIV also had a CMD. Reporting non injection and injection drug use were each higher among those with CMD regardless of HIV status. In addition, reporting any drug use was much higher among those with both HIV and CMD than among those with neither (73% vs 31%, p value 0.001). While methadone noncompliance was lower among PLH than among those without HIV (16.3% vs 30.1%, p value 0.010), noncompliance was higher among those with CMD than among those without (40.5% vs 25.6%, p value 0.045). Among those without HIV, noncompliance was higher among those with CMD than among those without, but among those with HIV, the opposite relationship was observed. CONCLUSION: There is complex overlap between substance use and methadone noncompliance among MMT patients living with HIV, CMD or both. In this population, we found a high prevalence of CMD and substance use among PLH, and a high prevalence of substance use and methadone noncompliance among those with CMD. Prioritizing provision of mental health care services to MMT patients living with HIV can help improve engagement with substance use disorder treatment and reduce the risk of HIV transmission.

Evaluation of a Liquid Biopsy Protocol using Ultra-Deep Massive Parallel Sequencing for Detecting and Quantifying Circulation Tumor DNA in Colorectal Cancer Patients.

The identification and quantification of actionable mutations are critical for guiding targeted therapy and monitoring drug response in colorectal cancer. Liquid biopsy (LB) based on plasma cell-free DNA analysis has emerged as a noninvasive approach with many clinical advantages over conventional tissue sampling. Here, we developed a LB protocol using ultra-deep massive parallel sequencing and validated its clinical performance for detection and quantification of actionable mutations in three major driver genes (KRAS, NRAS and BRAF). The assay showed a 92% concordance for mutation detection between plasma and paired tissues and great reliability in quantification of variant allele frequency.

Perpetration of Intimate Partner Violence Among Men Living with HIV in Northern Vietnam.

We examined the prevalence of intimate partner violence (IPV) perpetration and characteristics of HIV-infected male perpetrators. The cross-sectional study was conducted in Vietnam with male antiretroviral treatment clients (N = 1099; mean age = 40.2 years). Bivariable associations were tested between psychological or physical/sexual IPV perpetration in the last 12 months and sociodemographic, psychosocial, and sexual behavioral factors using prevalence ratios. Factors significant at p < 0.10 were entered in multivariable models for each IPV outcome using a modified Poisson approach. Results showed 15.6% (N = 171/1099) reported perpetrating psychological IPV and 7.6% (N = 84/1099) perpetrating physical/sexual IPV in the last 12 months. HIV risk behaviors, including hazardous drinking and multiple sexual partners, having witnessed interparental violence as a child, and depressive symptoms were associated with perpetrating IPV. HIV interventions targeting HIV-infected men in Vietnam should intervene on IPV perpetration by addressing the co-occurring factors of sexual risk, depression, alcohol use, and child maltreatment that are correlated with IPV.

Perspectives of clients and providers on factors influencing opioid agonist treatment uptake among HIV-positive people who use drugs in Indonesia, Ukraine, and Vietnam: HPTN 074 study.

BACKGROUND: Opioid agonist treatment (OAT) is an effective method of addiction treatment and HIV prevention. However, globally, people who inject drugs (PWID) have insufficient OAT uptake. To expand OAT access and uptake, policymakers, program developers and healthcare providers should be aware of barriers to and facilitators of OAT uptake among PWID. METHODS: As a part of the HPTN 074 study, which assessed the feasibility of an intervention to facilitate HIV treatment and OAT in PWID living with HIV in Indonesia, Ukraine, and Vietnam, we conducted in-depth interviews with 37 HIV-positive PWID and 25 healthcare providers to explore barriers to and facilitators of OAT uptake. All interviews were audio-recorded, transcribed, translated into English, and coded in NVivo for analysis. We developed matrices to identify emergent themes and patterns. RESULTS: Despite some reported country-specific factors, PWID and healthcare providers at all geographic locations reported similar barriers to OAT initiation, such as complicated procedures to initiate OAT, problematic clinic access, lack of information on OAT, misconceptions about methadone, financial burden, and stigma toward PWID. However, while PWID reported fear of drug interaction (OAT and antiretroviral therapy), providers perceived that PWID prioritized drug use over caring for their health and hence were less motivated to take up ART and OAT. Motivation for a life change and social support were reported to be facilitators. CONCLUSION: These results highlight a need for support for PWID to initiate and retain in drug treatment. To expand OAT in all three countries, it is necessary to facilitate access and ensure low-threshold, financially affordable OAT programs for PWID, accompanied with supporting interventions. PWID attitudes and beliefs about OAT indicate the need for informational campaigns to counter misinformation and stigma associated with addiction and OAT (especially methadone).

Client and Provider Perspectives on Antiretroviral Treatment Uptake and Adherence Among People Who Inject Drugs in Indonesia, Ukraine and Vietnam: HPTN 074.

HIV-infected people who inject drugs (PWID) have low uptake of HIV services, increasing the risk of transmission to uninfected injection or sexual partners and the likelihood of AIDS-related deaths. HPTN 074 is a vanguard study assessing the feasibility of an integrated intervention to facilitate treatment as prevention to PWID in Indonesia, Ukraine, and Vietnam. We describe barriers to and facilitators of ART uptake and adherence among PWID. We conducted in-depth interviews with 62 participants, including 25 providers and 37 PWID at baseline across all sites. All interviews were recorded, transcribed, translated into English and coded in NVivo for analysis. Matrices were developed to identify emergent themes and patterns. Overall, differences between provider and PWID perspectives were greater than differences in cross-site perspectives. Providers and PWID recognized clinic access, financial barriers, side effects, and lack of information about HIV testing and ART enrollment as barriers to ART. However, providers tended to emphasize individual level barriers to ART, such as lack of motivation due to drug use, whereas PWID highlighted health systems barriers, such as clinic hours and financial burden, fears, and side effects. Providers did not mention stigma as a barrier though their language reflected stereotypes about drug users. The differences between provider and PWID perspectives suggest a gap in providers' understanding of PWID. This misunderstanding has implications for patient-provider interactions that may affect PWID willingness to access care or adhere to ART. Lessons learned from this study will be important as countries with a significant HIV burden among PWID design and implement programs to engage HIV-infected PWID in care and treatment.

Perceived need, barriers to and facilitators of mental health care among HIV-infected PWID in Hanoi, Vietnam: a qualitative study.

BACKGROUND: The HIV epidemic in Vietnam has been primarily driven by injection drug use. HIV-infected people who inject drugs (PWID) in Vietnam have very high rates of mental health problems, which can accelerate progression to AIDS and increase mortality rates. No research has explored the barriers and facilitators of mental health care for HIV-infected PWID in Vietnam. METHODS: We conducted 28 in-depth interviews among HIV-infected PWID (n = 16), HIV and MMT (methadone maintenance treatment) providers (n = 8), and health officials (n = 4) in Hanoi. We explored participants' perceptions of mental health disorders, and barriers and facilitators to seeking and receiving mental health care. RESULTS: HIV-infected PWID were perceived by both PWID, HIV/MMT providers, and health officials to be vulnerable to mental health problems and to have great need for mental health care. Perceived social, physical, and economical barriers included stigma towards HIV, injection drug use, and mental illnesses; lack of awareness around mental health issues; lack of human resources, facilities and information on mental health services; and limited affordability of mental health services. Social support from family and healthcare providers was a perceived facilitator of mental health care. CONCLUSIONS: Interventions should raise self-awareness of HIV-infected PWID about common mental health problems; address social, physical, economic barriers to seeking mental health services; and increase social support for patients.

Application of response surface methodology to optimize the fabrication of ZnCl2-activated carbon from sugarcane bagasse for the removal of Cu2.

The present study focused on the application of response surface methodology to optimize the fabrication of activated carbon (AC) from sugarcane bagasse for adsorption of Cu2+ ion. The AC was synthesized via chemical activation with ZnCl2 as the activating agent. The central composite design based experiments were performed to assess the individual and interactive effect of influential parameters, including activation temperature, ZnCl2 impregnation ratio and activation time on the AC yield and removal of Cu2+ ion from the aqueous environment. The statistically significant, well-fitting quadratic regression models were successfully developed as confirmed by high F- and low P-values (<0.0001), high correlation coefficients and lack-of-fit tests. Accordingly, the optimum AC yield and removal efficiency of Cu2+ were predicted, respectively, as 48.8% and 92.7% which were approximate to the actual values. By applying the predicted optimal parameters, the AC shows a surprisingly high surface area of around 1,500 m2/g accompanied by large pore volume and narrow micropore size at low fabrication temperature.

Environmental Factors Modulate Saxitoxins (STXs) Production in Toxic Dinoflagellate Alexandrium: An Updated Review of STXs and Synthesis Gene Aspects.

The marine dinoflagellate Alexandrium is known to form harmful algal blooms (HABs) and produces saxitoxin (STX) and its derivatives (STXs) that cause paralytic shellfish poisoning (PSP) in humans. Cell growth and cellular metabolism are affected by environmental conditions, including nutrients, temperature, light, and the salinity of aquatic systems. Abiotic factors not only engage in photosynthesis, but also modulate the production of toxic secondary metabolites, such as STXs, in dinoflagellates. STXs production is influenced by a variety of abiotic factors; however, the relationship between the regulation of these abiotic variables and STXs accumulation seems not to be consistent, and sometimes it is controversial. Few studies have suggested that abiotic factors may influence toxicity and STXs-biosynthesis gene (sxt) regulation in toxic Alexandrium, particularly in A. catenella, A. minutum, and A. pacificum. Hence, in this review, we focused on STXs production in toxic Alexandrium with respect to the major abiotic factors, such as temperature, salinity, nutrients, and light intensity. This review informs future research on more sxt genes involved in STXs production in relation to the abiotic factors in toxic dinoflagellates.

Clinical Efficacy And Safety of Long-Term Treatment Of Tenofovir Alafenamide Vs Tenofovir Disoproxil Fumarate for Chronic Hepatitis B in Vietnam.

INTRODUCTION: Hepatitis B virus (HBV) infection is a contagious condition posing a major public health risk in various nations including Vietnam. In 2019, the Ministry of Health introduced tenofovir alafenamide (TAF) to treat patients with chronic HBV infection and reduce the long-term toxicity of tenofovir disoproxil fumarate (TDF). This study aimed to assess the effectiveness and safety of these two medications in individuals with HBeAg-positive chronic HBV. METHODS: This retrospective cohort study included data collected from the medical records of patients with chronic HBV who visited the Liver Clinic at University Medical Center HCMC between 2018 and 2020. RESULTS: After two years of treatment, the proportion of HBeAg loss in the TAF group was twice that of the TDF group (22.4% vs. 11.2%), indicating a statistically significant difference in the probability of HBeAg loss (adjusted hazard ratio = 2.22; 95% CI 1.43 to 3.42; p < 0.01). Additionally, there was a statistically significant difference in the rate and ability of antiviral response between patients treated with TAF and TDF (65% vs. 54.5%, respectively; adjusted hazard ratio = 1.34; 95% CI 1.08 to 1.69; p < 0.01). 93.9% of patients achieved the goal of restoring ALT to normal, a higher percentage compared to the 81.2% in the TDF group, and the likelihood of achieving normal ALT levels with TAF was greater compared to those on TDF (adjusted hazard ratio = 1.67; 95% CI 1.38 to 2.01; p < 0.01). Moreover, there was a statistically significant difference in the variation in renal function between the TAF and TDF groups. Serum creatinine levels in the TAF group increased less than those in the TDF group by 0.03 mg/dL every 6 months (95% CI -0.04 to -0.01, p < 0.01), and the eGFR in the TAF group was higher than that in the TDF group every 6 months by 2.78 mL/min/1.73 m2 (95% CI 0.98 to 4.57, p < 0.01). However, there was no statistically significant difference in the likelihood of HBeAg seroconversion between chronic hepatitis B patients treated with TAF or TDF (adjusted hazard ratio = 1.79; 95% CI 0.91 to 3.53; p = 0.09), nor in the risk of adverse events between the two groups (adjusted odds ratio = 1.34; 95% CI 0.88 to 2.05; p = 0.17). Additionally, although the HBsAg concentration in the TAF group was lower than in the TDF group by an average of 0.05 log10 IU/mL every 6 months (95% CI -0.15 to 0.05), this difference also did not reach statistical significance (p = 0.35). DISCUSSION: TAF has been demonstrated to achieve some therapeutic efficacy goals and reduce nephrotoxicity better than TDF. However, no differences were found in seroconversion or adverse events between the patient groups.

Polyphyletic origin of saxitoxin biosynthesis genes in the marine dinoflagellate Alexandrium revealed by comparative transcriptomics.

The marine dinoflagellate Alexandrium is known to form harmful algal blooms, and at least 14 species within the genus can produce saxitoxins (STXs). STX biosynthesis genes (sxt) are individually revealed in toxic dinoflagellates; however, the evolutionary history remains controversial. Herein, we determined the transcriptome sequences of toxic Alexandrium (A. catenella and A. pacificum) and non-toxic Alexandrium (A. fraterculus and A. fragae) and characterized their sxt by focusing on evolutionary events and STX production. Comparative transcriptome analysis revealed higher homology of the sxt in toxic Alexandrium than in non-toxic species. Notably, non-toxic Alexandrium spp. were found to have lost two sxt core genes, namely sxtA4 and sxtG. Expression levels of 28 transcripts related to eight sxt core genes showed that sxtA, sxtG, and sxtI were relatively high (>1.5) in the toxic group compared to the non-toxic group. In contrast, the non-toxic group showed high expression levels in sxtU (1.9) and sxtD (1.7). Phylogenetic tree comparisons revealed distinct evolutionary patterns between 28S rDNA and sxtA, sxtB, sxtI, sxtD, and sxtU. However, similar topology was observed between 28S rDNA, sxtS, and sxtH/T. In the sxtB and sxtI phylogeny trees, toxic Alexandrium and cyanobacteria were clustered together, separating from non-toxic species. These suggest that Alexandrium may acquire sxt genes independently via horizontal gene transfer from toxic cyanobacteria and other multiple sources, demonstrating monocistronic transcripts of sxt in dinoflagellates.

Two novel glutathione S-transferase (GST) genes in the toxic marine dinoflagellate Alexandrium pacificum and their transcriptional responses to environmental contaminants.

The present study identified two novel glutathione S-transferase (GST) genes from the toxic dinoflagellate Alexandrium pacificum and examined their molecular characteristics and transcriptional responses to algicides and environmental contaminants. Bioinformatic analysis revealed that both ApGSTs are cytosolic, belonging to the chi-like class (ApGST1) and an undefined class (ApGST2). The overall expression of ApGSTs showed similar patterns depending on the exposed contaminants, while they were differently regulated by polychlorinated biphenyl (PCB). Copper treatments (CuCl2 and CuSO4) did not significantly induce the expression of ApGSTs. The highest up-regulations of ApGST1 and ApGST2 were under 6-h treatments of 0.10 and 0.50 mg L-1 NaOCl. Interestingly, only ApGST1 increased significantly after 0.10, 0.50, and 1.00 mg L-1 of PCB exposure (6 h). Intracellular reactive oxygen species (ROS) increased considerably under NaOCl; however, it was not significantly higher in the PCB-treated cells. GST activity was increased by NaOCl and PCB treatments, but only PCB caused apoptosis. These results suggest that GSTs are involved in the first line of phase II detoxification, protecting dinoflagellate cells against oxidative damage.