Menin Inhibition With Revumenib for KMT2A-Rearranged Relapsed or Refractory Acute Leukemia (AUGMENT-101).

PURPOSE: Revumenib, an oral, small molecule inhibitor of the menin-lysine methyltransferase 2A (KMT2A) interaction, showed promising efficacy and safety in a phase I study of heavily pretreated patients with KMT2A-rearranged (KMT2Ar) acute leukemia. Here, we evaluated the activity of revumenib in individuals with relapsed/refractory (R/R) KMT2Ar acute leukemia. METHODS: AUGMENT-101 is a phase I/II, open-label, dose-escalation and expansion study of revumenib conducted across 22 clinical sites in five countries (ClinicalTrials.gov identifier: NCT04065399). We report results from the phase II, registration-enabling portion. Individuals age ≥30 days with R/R KMT2Ar acute leukemia or with AML and nucleophosmin 1 (NPM1) mutation were enrolled. Revumenib was administered once every 12 hours, at 163 mg (95 mg/m2 if weight <40 kg) with a strong cytochrome P450 inhibitor, in 28-day cycles. The primary end points were the rate of complete remission (CR) or CR with partial hematologic recovery (CR + CRh) and safety. At a prespecified interim analysis, safety was assessed in all KMT2Ar treated patients; efficacy was assessed in those with centrally confirmed KMT2Ar. The separate NPM1 cohort of the trial is ongoing. RESULTS: From October 1, 2021, to July 24, 2023, N = 94 patients (median [range] age, 37 [1.3-75] years) were treated. Grade ≥3 adverse events included febrile neutropenia (37.2%), differentiation syndrome (16.0%), and QTc prolongation (13.8%). In the efficacy-evaluable patients (n = 57), the CR + CRh rate was 22.8% (95% CI, 12.7 to 35.8), exceeding the null hypothesis of 10% (P = .0036). Overall response rate was 63.2% (95% CI, 49.3 to 75.6), with 15 of 22 patients (68.2%) having no detectable residual disease. CONCLUSION: Revumenib led to high remission rates with a predictable safety profile in R/R KMT2Ar acute leukemia. To our knowledge, this trial represents the largest evaluation of a targeted therapy for these patients.

FAS and SREBP-1c Inhibition via AMPK Activation in HepG2 Cells by Biovip, Tox-off, and Traphanoside GO1 from Glinus oppositifolius.

Glinus oppositifolius is an endemic herbaceous plant found in tropical Asian countries and is native in Vietnam. It is used in traditional folk medicine because of its flavor and antiseptic and laxative effects. In the current research, the effects of Tox-off, Biovip, and the purified compounds isolated from G. oppositifolius in the previous study were evaluated on the activation of adenosine 5'-monophosphate-activated protein kinase (AMPK)-activated protein kinase (AMPK) and acetyl-coenzyme A carboxylase (ACC) in C2C12 myoblasts. In addition, the most potent active compounds, traphanoside-GO1 (TRA-GO1) and TRA-GO5 have validated the reduction of fatty acid synthase (FAS) and sterol regulatory element binding protein (SREBP)-1c in HepG2 cells. We found that Tox-off and Biovip significantly increased the phosphorylation of AMPK and ACC in C2C12 myoblasts. Furthermore, TRA-GO1 and TRA-GO5 significantly increased the AMPK activation and phosphorylation of its downstream substrate ACC in a concentration-dependent way compared to the dimethyl sulfoxide (DMSO) control. Besides, the protein level of FAS and SREBP-1c decreased by TRA-GO1 and TRA-GO5 in a concentration-dependent manner. Taken together, our results showed that the increased AMPK and ACC phosphorylation by active components of G. oppositifolius may activate the AMPK signaling pathways, which are useful for the anti-obesity and its related metabolic disorders.

Pairwise approach for analysis and reporting of child's free sugars intake from a birth cohort study.

OBJECTIVES: The prospective cohort design is an important research design, but a common challenge is missing data. The purpose of this study is to compare three approaches to managing missing data, the pairwise (n = 1386 children), the partial or modified pairwise (n = 1019) and the listwise (n = 546), to characterize the trajectories of children's free sugars intake (FSI) across early childhood. METHODS: By applying the Group-based Trajectory Model Technique to three waves of data collected from a prospective cohort study of South Australian children, this study examined the three approaches in managing missing data to validate and discuss children's FSI trajectories. RESULTS: Each approach identified three distinct trajectories of child's FSI from 1 to 5 years of age: (1) 'low and fast increasing', (2) 'moderate and increasing' and (3) 'high and increasing'. The trajectory memberships were consistent across the three approaches, and were for the pairwise scenario (1) 15.1%, (2) 68.3% and (3) 16.6%; the partial or modified pairwise (1) 15.9%, (2) 64.1% and (3) 20.0%; and the listwise (1) 14.9%, (2) 64.9% and (3) 20.2% of children. CONCLUSIONS: Given the comparability of the findings across the analytical approaches and the samples' characteristics between baseline and across different data collection waves, it is recommended that the pairwise approach be used in future analyses to optimize the sample size and statistical power when examining the relationship between FSI in the first years of life and health outcome such as dental caries.

Trends in, projections of, and inequalities in non-communicable disease management indicators in Vietnam 2010-2030 and progress toward universal health coverage: A Bayesian analysis at national and sub-national levels.

Background: Movement towards Universal Health Coverage (UHC) can improve health services, risk factor management, and inequality in non-communicable diseases (NCD); conversely, prioritizing and monitoring NCD management can support pathways to UHC in resource-limited settings. We aimed to estimate trends in NCD management indicators in Vietnam from 2010, and projections to 2030 at national and sub-national levels; compute the probability of reaching UHC targets; and measure inequalities in NCD management indicators at demographic, geographic, and socio-economic levels. Methods: We included data of 37,595 households from four nationally representative surveys from 2010. We selected and estimated the coverage of NCD health service and risk management indicators nationally and by six sub-national groups. Using Bayesian models, we provided trends and projections and calculated the probability of reaching UHC targets of 80% coverage by 2030. We estimated multiple inequality indices including the relative index of inequality, slope index of inequality, and concentration index of inequality, and provided an assessment of improvement in inequalities over the study period. Findings: Nationally, all indicators showed a low probability of achieving 2030 targets except sufficient use of fruit and vegetables (SUFV) and non-use of tobacco (NUT). We observed declining trends in national coverage of non-harmful use of alcohol (NHUA), sufficient physical activity (SPA), non-overweight (NOW), and treatment of diabetes (TOD). Except for SPA, no indicator showed the likelihood of achieving 2030 targets at any regional level. Our model suggested a non-achievement of 2030 targets for all indicators in any wealth quintile and educational level, except for SUFV and NUT. There were diversities in tendency and magnitude of inequalities with widening gaps between genders (SPA, TOD), ethnic groups (SUFV), urban-rural areas (TOH), wealth quintiles, and educational levels (TOD, NUT, NHUA). Interpretation: Our study suggested slow progress in NCD management at the national level and among key sub-populations in Vietnam, together with existing and increasing inequalities between genders, ethnicities, geographic areas, and socioeconomic groups. We emphasised the necessity of continuously improving the healthcare system and facilities, distributing resources between geographic areas, and simultaneously integrating economic, education, and gender intervention and programs. Funding: None.

Suicidality among older Australian adults.

Background: Vulnerability to suicidality is a concern among older adults, particularly as this proportion of the population is growing. Determining what factors contribute to suicidality will help to create a framework for understanding and assessing suicidal risk among older adults and developing effective treatments. This study examined suicidality among older Australian adults. Methods: This study forms part of a larger study to trial a survey to collect cross-sectional data on the mental and physical health of older Australian adults across time. One hundred and fourteen Australian residents aged 65 years and over completed an anonymous survey online or by returning a paper-and-pencil version of the survey by post. The survey took approximately 25 min to complete and comprised of (1) sociodemographic questions (e.g., age, gender, education), (2) validated questionnaires measuring depression, general anxiety, psychological distress, insomnia, substance dependence, problem gambling, and stress, and (3) mental and physical health and wellbeing items (e.g., religiosity, assistance with daily tasks, and mental health service usage in the last 12-months). The dependent variable, suicidality, was measured by asking participants whether they had ever seriously thought about committing suicide. Results: Associations with suicidality were analyzed using Chi-squares and independent samples t-tests. The results found suicidality to be significantly associated with lower levels of satisfaction with the frequency of seeing and/or communicating with friends, and inadequate levels of community engagement. Conclusion: The results of this survey reinforce the importance of social connectedness as a central and significant protective factor against suicidality among older adults.

Trends in, projections of, and inequalities in reproductive, maternal, newborn and child health service coverage in Vietnam 2000-2030: A Bayesian analysis at national and sub-national levels.

BACKGROUND: To assess the reproductive, maternal, newborn and child health (RMNCH) service coverage in Vietnam with trends in 2000-2014, projections and probability of achieving targets in 2030 at national and sub-national levels; and to analyze the socioeconomic, regional and urban-rural inequalities in RMNCH service indicators. METHODS: We used national population-based datasets of 44,624 households in Vietnam from 2000 to 2014. We applied Bayesian regression models to estimate the trends in and projections of RMNCH indicators and the probabilities of achieving the 2030 targets. Using the relative index, slope index, and concentration index of inequality, we examined the patterns and trends in RMNCH coverage inequality. FINDINGS: We projected that 9 out of 17 health service indicators (53%) would likely achieve the 2030 targets at the national level, including at least one and four ANC visits, BCG immunization, access to improved water and adequate sanitation, institutional delivery, skilled birth attendance, care-seeking for pneumonia, and ARI treatment. We observed very low coverages and zero chance of achieving the 2030 targets at national and sub-national levels in early initiation and exclusive breastfeeding, family planning needs satisfied, and oral rehydration therapy. The most deprived households living in rural areas and the Northwest, Northeast, North Central, Central Highlands, and Mekong River Delta regions would not reach the 80% immunization coverage of DPT3, Polio3, Measles and full immunization. We found socioeconomic, regional, and urban-rural inequalities in all RMNCH indicators in 2014 and no change in inequalities over 15 years in the lowest-coverage indicators. INTERPRETATION: Vietnam has made substantial progress toward UHC. By improving the government's health system reform efforts, re-allocating resources focusing on people in the most impoverished rural regions, and restructuring and enhancing current health programs, Vietnam can achieve the UHC targets and other health-related SDGs. FUNDING: The authors did not receive any funds for conducting this study.

Spatial distribution of Culex mosquito abundance and associated risk factors in Hanoi, Vietnam.

Japanese encephalitis (JE) is the major cause of viral encephalitis (VE) in most Asian-Pacific countries. In Vietnam, there is no nationwide surveillance system for JE due to lack of medical facilities and diagnoses. Culex tritaeniorhynchus, Culex vishnui, and Culex quinquefasciatus have been identified as the major JE vectors in Vietnam. The main objective of this study was to forecast a risk map of Culex mosquitoes in Hanoi, which is one of the most densely populated cities in Vietnam. A total of 10,775 female adult Culex mosquitoes were collected from 513 trapping locations. We collected temperature and precipitation information during the study period and its preceding month. In addition, the other predictor variables (e.g., normalized difference vegetation index [NDVI], land use/land cover and human population density), were collected for our analysis. The final model selected for estimating the Culex mosquito abundance included centered rainfall, quadratic term rainfall, rice cover ratio, forest cover ratio, and human population density variables. The estimated spatial distribution of Culex mosquito abundance ranged from 0 to more than 150 mosquitoes per 900m2. Our model estimated that 87% of the Hanoi area had an abundance of mosquitoes from 0 to 50, whereas approximately 1.2% of the area showed more than 100 mosquitoes, which was mostly in the rural/peri-urban districts. Our findings provide better insight into understanding the spatial distribution of Culex mosquitoes and its associated environmental risk factors. Such information can assist local clinicians and public health policymakers to identify potential areas of risk for JE virus. Risk maps can be an efficient way of raising public awareness about the virus and further preventive measures need to be considered in order to prevent outbreaks and onwards transmission of JE virus.

Factors associated with high-risk behaviors of people newly diagnosed with HIV/AIDS: results from a cross-sectional study in Vietnam.

Towards the elimination of this global epidemic, understanding the high-risk behaviors of people newly diagnosed with HIV/AIDS (PNDWH) is essential. This study aimed to describe the general characteristics and high-risk behaviors of PNDWH and identify associated factors for adopting high-risk behaviors. A cross-sectional survey was conducted in Vietnam to explore the high-risk behaviors of 506 PNDWH. Associated factors were identified using multivariable logistic regressions. 83.2% of participants had sex without using a condom, and 27.9% had more than two sex partners. Among injected drug users, 44% had shared needles with an average number of 2.1 shared partners. Male, Kinh ethnicity (Vietnamese), high income, and high educational level were risk factors for high-risk behaviors. Our findings revealed the first time a comprehensive picture of PNDWH and emphasized the high prevalence of STIs, including untreated STIs and the long delay since the early HIV diagnosis. Also, our model found much higher risk behaviors among participants who were non-adherent to ART and those currently enrolled in ART. By better managing newly-diagnosed cases, better integrating STI management services and prevention consultants, as well as improving ART adherence programs, Vietnam can make better progress towards the complete control of HIV for its most vulnerable populations.

Healthcare Workers' Knowledge and Attitudes Regarding the World Health Organization's "My 5 Moments for Hand Hygiene": Evidence From a Vietnamese Central General Hospital.

OBJECTIVES: Although the World Health Organization (WHO) initiative "My 5 Moments for Hand Hygiene" has been lauded as effective in preventing hospital-associated infections, little is known about healthcare workers (HCWs)' hand hygiene behavior. In this study, we sought to assess knowledge and attitudes towards the concepts in this initiative, as well as associated factors, among Vietnamese HCWs at a general hospital. METHODS: A structured questionnaire was administered to HCWs at a central Vietnamese general hospital in 2015. Multiple logistic regression analysis was used to identify factors associated with HCWs' knowledge and attitudes towards hand hygiene. RESULTS: Of 120 respondents, 65.8% and 67.5% demonstrated appropriate knowledge and a positive attitude, respectively, regarding all 5 hand hygiene moments. Logistic regression indicated better knowledge of hand hygiene in workers who were over 30 years old, who were direct HCWs (rather than managers), who had frequent access to clinical information, and who received their clinical information from training. Those who worked in infectious and tropical disease wards, who had frequent access to clinical information, and who received information from training were more likely to have a positive attitude towards hand hygiene than their counterparts. CONCLUSIONS: Although many Vietnamese HCWs displayed moderate knowledge and positive attitudes towards the WHO hand hygiene guidelines, a key gap remained. Regular education and training programs are needed to increase knowledge and to improve attitudes and practices towards hand hygiene. Furthermore, a combination of multimodal strategies and locally-adapted interventions is needed for sustainable hand hygiene adherence.

Discovery of Highly Selective Inhibitors of Calmodulin-Dependent Kinases That Restore Insulin Sensitivity in the Diet-Induced Obesity in Vivo Mouse Model.

Polymorphisms in the region of the calmodulin-dependent kinase isoform D (CaMK1D) gene are associated with increased incidence of diabetes, with the most common polymorphism resulting in increased recognition by transcription factors and increased protein expression. While reducing CaMK1D expression has a potentially beneficial effect on glucose processing in human hepatocytes, there are no known selective inhibitors of CaMK1 kinases that can be used to validate or translate these findings. Here we describe the development of a series of potent, selective, and drug-like CaMK1 inhibitors that are able to provide significant free target cover in mouse models and are therefore useful as in vivo tool compounds. Our results show that a lead compound from this series improves insulin sensitivity and glucose control in the diet-induced obesity mouse model after both acute and chronic administration, providing the first in vivo validation of CaMK1D as a target for diabetes therapeutics.

Factors associated with job satisfaction among district hospital health workers in Northern Vietnam: a cross-sectional study.

BACKGROUND: In many developing countries, including Vietnam, little is known about job satisfaction among lower level-health staff. The purpose of this study was to assess job satisfaction and its determinants among district hospital health staff. METHODS: In a cross-sectional quantitative study, 128 health staff from a rural district hospital in Northern Vietnam were approached for data collection. Regression techniques were adopted to assess factors associated with several types of job satisfaction. RESULTS: Overall job satisfaction was moderately high, ranging from 69% to 91%. Across all dimensions, health workers showed their highest satisfaction with co-worker relationships, while, in comparison, it was much lower for their supervisor's style and relationship. However, they claimed their lowest satisfaction with compensation and benefits. In final multivariate models, females and those satisfied with knowledge, skills and job performance were most likely to be satisfied with relationships with co-workers. Staff who were married, received a low pay, who were not satisfied with supervisor style and relationships and who were not satisfied with staff training, development opportunities were least likely to be satisfied with compensation and benefits. CONCLUSIONS: The study findings highlight an important need for designing an intervention program that considers organizational factors. Copyright © 2016 John Wiley & Sons, Ltd.

Removal of phosphorus from water by using volcanic ash soil (VAS): batch and column experiments.

Using low-cost and naturally available materials is considered an optimal adsorbent for removing phosphorus (P) from water due to its simplicity and economic efficiency. This study examined the removal of P from water using volcanic ash soil (VAS) by batch and column experiments. The maximum adsorption capacity of P was 2.94 mg g-1, estimated from the batch experiment according to a Langmuir isotherm. The column study showed a higher adsorption capacity of 5.57 mg g-1. The breakthrough curve showed that influent water containing 2 mg L-1 P was completely purified by VAS within 1,230 pore volumes (PV). The breakthrough and saturation points of the curves were 3,100 PV and 14,875 PV, respectively. After an adsorption column was loaded with 20,508 PV, a regeneration procedure was developed to determine whether an ion exchange of P with chloride occurred or adsorbed P in the columns could be eluted. Approximately 20% of P was recovered from columns by desorption tests, regardless of NaCl solution or deionized water. Specific surface area and mineral concentrations are both important characteristics that improve the adsorption capacity of VAS. The present study suggests that VAS is a promising adsorbent to remove P in water.

Factors associated with self-medication among medicine sellers in urban Vietnam.

In Vietnam, many medicine sellers serving pharmacies and retail outlets do not have adequate professional qualifications, and there has been a limited institutional control. The objective of this cross-sectional study was to examine the prevalence and determinants of self-medication among medicine sellers in Hanoi, Vietnam. Although 96.55% of medicine sellers had relatively serious health problems, only 61.21% visited a healthcare facility, though self-medication was moderately high (approximately 39%). Adopting Andersen's conceptual model, it was identified that medicine sellers who reported higher professional education, had low confidence in healthcare services, had not received any professional in-service during the prior year, had less serious health problems and who perceived the current costs of healthcare as too high were more likely to report self-medication. The findings have public health policy implications for these healthcare providers in urban Vietnam and other similar developing countries.

Factors associated with drug use among male motorbike taxi drivers in urban Vietnam.

A cross-sectional study was conducted on a sample of 291 male motorbike taxi drivers (MMTDs) recruited through social mapping technique in Hanoi, Vietnam, for face-to-face interviews to examine factors associated with drug use among MMTDs using Information-Motivation-Behavioral skills (IMB) model. Among 291 MMTDs, 17.18% reported drug use sometime in their lives, 96% of whom were drug injectors. Being depressed, being originally borne in urban cities, currently residing in rural areas, having a longer time living apart from their wives/lovers, using alcohol, following Buddhism, and reporting lower motivation of HIV prevention predict significantly higher odds of uptaking drugs.

Gender difference in academic planning activity among medical students.

BACKGROUND: In Vietnam, as doctor of medicine is socially considered a special career, both men and women who are enrolled in medical universities often study topics of medicine seriously. However, as culturally expected, women often perform better than men. Because of this, teaching leadership and management skill (LMS) to develop academic planning activity (APA) for female medical students would also be expected to be more effective than male counterparts. This research aimed to compare by gender the effect of teaching LMS on increasing APA, using propensity score matching (PSM). METHODS: In a cross-sectional survey utilizing a self-reported structured questionnaire on a systematic random sample of 421 male and female medical students in Hanoi Medical University, this study adopted first regression techniques to construct a fit model, then PSM to create a matched control group in order to allow for evaluating the effect of LMS education. RESULTS: There were several interesting gender differences. First, while for females LMS education had both direct and indirect effects on APA, it had only direct effect on males' APA. Second, after PSM to adjust for the possible confounders to balance statistically two groups - with and without LMS education, there is statistically a significant difference in APA between male and female students, making a net difference of 11% (p<.01), equivalent to 173 students. The difference in APA between exposed and matched control group in males and females was 9% and 20%, respectively. These estimates of 9.0 and 20.0 percentage point increase can be translated into the practice of APA by 142 males and 315 females, respectively, in the population. These numbers of APA among male and female students can be explained by LMS education. CONCLUSIONS: Gender appears to be a factor explaining in part academic planning activity.