Towards safer and efficient formulations: Machine learning approaches to predict drug-excipient compatibility.

Predicting drug-excipient compatibility is a critical aspect of pharmaceutical formulation design. In this study, we introduced an innovative approach that leverages machine learning techniques to improve the accuracy of drug-excipient compatibility predictions. Mol2vec and 2D molecular descriptors combined with the stacking technique were used to improve the performance of the model. This approach achieved a significant advancement in the predictive capacity as demonstrated by the accuracy, precision, recall, AUC, and MCC of 0.98, 0.87, 0.88, 0.93 and 0.86, respectively. Using the DE-INTERACT model as the benchmark, our stacking model could remarkably detect drug-excipient incompatibility in 10/12 tested cases, while DE-INTERACT managed to recognize only 3 out of 12 incompatibility cases in the validation experiments. To ensure user accessibility, the trained model was deployed to a user-friendly web platform (URL: https://decompatibility.streamlit.app/). This interactive interface accommodated inputs through various types, including names, PubChem CID, or SMILES strings. It promptly generated compatibility predictions alongside corresponding probability scores. However, the continual refinement of model performance is crucial before applying this model in practice.

Diagnostic Value in Screening Severe Depression of the Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, Beck Depression Inventory Scale, and Zung's Self-Rating Anxiety Scale Among Patients with Recurrent Depression Disorder.

Background: Depression is a widespread and incapacitating mental health disorder that impacts millions of people worldwide, playing a substantial role in the overall global health challenges. Depression has a big impact on a person's quality of life, cognitive and social functioning, risk of suicide, risk of heart disease and other illnesses, as well as death from all causes. Objective: It may be challenging to choose the best tools to screen for severe depression in patients with recurrent depression disorder (PRD) considering the diversity of psychological scales in Vietnam. The aim of this study was to evaluate diagnostic value for detect severe depression of four psychological scales including Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A), Beck Depression Inventory Scale (BECK), and Zung's Self-Rating Anxiety Scale (SAS) by genders and age groups among PRD in Vietnam. Methods: This study was conducted at National Institute of Mental Health, Bach Mai Hospital, Vietnam, from 2020 to 2021. There were 109 PRD evaluated with HAM-D, HAM-A, BECK, and SAS by qualified psychiatrists. By analysing Area Under the Curve (AUC) of Receiver Operating Characteristic (ROC) curve, we determined sensitivity, specificity and cut points of four above scales. Results: Among four scales, the BECK scale had the best diagnostic effect with the most optimal sensitivity and specificity (61.64% and 75%, respectively). We proposed the new cut-off of HAM-D, HAM-A, BECK, and SAS for detecting severe depression among PRD were 20, 34, 30, and 45, respectively. By genders, the cut points for the HAM-D, HAM-A, BECK, and SAS in males were 20, 27, 34, and 44, respectively, while those figure in females were 14, 34, 30, and 46, respectively. By age groups, adults had cut values for four above scales of 20, 34, 27, and 45, respectively, whereas those for the elderly were 16, 17, 35, and 44, respectively. Conclusion: We highly recommended that BECK is the most optimal method to screen severe depression in PRD in Vietnam. It is essential to utilize varied cut values of HAM-D, HAM-A, BECK, and SAS for different genders and age groups.

The Production of Standardized Samples with Known Concentrations for Severe Acute Respiratory Syndrome Coronavirus 2 RT-qPCR Testing Validation for Developing Countries in the Period of the Pandemic Era.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic of pneumonia spreading around the world, leading to serious threats to public health and attracting enormous attention. There is an urgent need for sensitive diagnostic testing implementation to control and manage SARS-CoV-2 in public health laboratories. The quantitative reverse transcription PCR (RT-qPCR) assay is the gold standard method, but the sensitivity and specificity of SARS-CoV-2 testing are dependent on a number of factors. METHODS: We synthesized RNA based on the genes published to estimate the concentration of inactivated virus samples in a biosafety level 3 laboratory. The limit of detection (LOD), linearity, accuracy, and precision were evaluated according to the bioanalytical method validation guidelines. RESULTS: We found that the LOD reached around 3 copies/reaction. Furthermore, intra-assay precision, accuracy, and linearity met the accepted criterion with an RSD for copies of less than 25%, and linear regression met the accepted R 2 of 0.98. CONCLUSIONS: We suggest that synthesized RNA based on the database of the NCBI gene bank for estimating the concentration of inactivated virus samples provides a potential opportunity for reliable testing to diagnose coronavirus disease 2019 (COVID-19) as well as limit the spread of the disease. This method may be relatively quick and inexpensive, and it may be useful for developing countries during the pandemic era. In the long term, it is also applicable for evaluation, verification, validation, and external quality assessment.

Radiation Degradation of ß-Glucan with a Potential for Reduction of Lipids and Glucose in the Blood of Mice.

: Water-soluble and low molecular weight (Mw) ß-glucans were successfully prepared by γ-irradiation of water-insoluble yeast ß-glucans. The radiation dose used for the degradation of yeast ß-glucan was remarkably reduced by increasing the pH of the sample or combining with hydrogen peroxide treatment. Radiation-degraded ß-glucans with molecular weights in the range of 11-48 kDa reduced the total cholesterol, triglyceride, low density lipoprotein (LDL) cholesterol, and glucose levels in the blood of administered mice. The decreasing levels of both lipid and glucose indexes in the blood of tested mice strongly depended on the molecular weight of the ß-glucan, and the radiation-degraded ß-glucan with a molecular weight of about 25 kDa was found to be the most effective for the reduction of blood lipid and glucose levels. Particularly, the oral administration of 25 kDa ß-glucan, with a daily dose of about 2 mg per head, reduced the total cholesterol, triglyceride, LDL-cholesterol, and glucose levels in the blood of tested mice to about 47.4%, 48.5%, 45.7%, and 47.2%, respectively. The effects on the reduction of blood lipid and glucose levels were also found to be stable after 20 days of stopping administration. These results indicate that the degraded ß-glucan with a molecular weight of about 25 kDa prepared by γ-ray irradiation is a very promising ingredient that can be used in nutraceutical food for therapeutics of diabetic and dyslipidemia.

Clinical characteristics, organ failure, inflammatory markers and prediction of mortality in patients with community acquired bloodstream infection.

BACKGROUND: Community acquired bloodstream infection (CABSI) in low- and middle income countries is associated with a high mortality. This study describes the clinical manifestations, laboratory findings and correlation of SOFA and qSOFA with mortality in patients with CABSI in northern Vietnam. METHODS: This was a retrospective study of 393 patients with at least one positive blood culture with not more than one bacterium taken within 48 h of hospitalisation. Clinical characteristic and laboratory results from the first 24 h in hospital were collected. SOFA and qSOFA scores were calculated and their validity in this setting was evaluated. RESULTS: Among 393 patients with bacterial CABSI, approximately 80% (307/393) of patients had dysfunction of one or more organ on admission to the study hospital with the most common being that of coagulation (57.1% or 226/393). SOFA performed well in prediction of mortality in those patients initially admitted to the critical care unit (AUC 0.858, 95%CI 0.793-0.922) but poor in those admitted to medical wards (AUC 0.667, 95%CI 0.577-0.758). In contrast qSOFA had poor predictive validity in both settings (AUC 0.692, 95%CI 0.605-0.780 and AUC 0.527, 95%CI 0.424-0.630, respectively). The overall case fatality rate was 28%. HIV infection (HR = 3.145, p = 0.001), neutropenia (HR = 2.442, p = 0.002), SOFA score 1-point increment (HR = 1.19, p < 0.001) and infection with Enterobacteriaceae (HR = 1.722, p = 0.037) were independent risk factors for in-hospital mortality. CONCLUSIONS: Organ dysfunction was common among Vietnamese patients with CABSI and associated with high case fatality. SOFA and qSOFA both need to be further validated in this setting.

Healthcare infrastructure capacity to respond to severe acute respiratory infection (SARI) and sepsis in Vietnam: A low-middle income country.

PURPOSE: This study investigated the availability of relevant structural and human resources needed for the clinical management of patients with severe acute respiratory infections and sepsis in critical care units in Vietnam. MATERIAL AND METHODS: A questionnaire survey was conducted by purposive sampling of 128 hospitals (36% of total hospitals in surveyed provinces), including 25 provincial and 103 district level hospitals, from 20 provinces in Vietnam. Data on availability of hospital characteristics, structural resources and health care workers was then analyzed. RESULTS: Most hospitals (>80%) reported having 60% of the relevant structural resources. Significant differences were observed between provincial hospitals when compared to district hospitals in regards to availability of central oxygen piping system (78.3% vs 38.7%, p=0.001) mechanical ventilation (100.0% vs 73.6%, p=0.003), mobile x-rays (80.0% vs 29.8%, p<0.001), carbapenem antibiotic (73.9% vs 17.4%, p<0.001) and norepinephrine (95.8% vs 56.3%, p<0.001). There was a limited availability of arterial blood gas analyzers (13.7%), oseltamivir (42.2%) and N95 respirators (54.6%) across all hospitals surveyed. CONCLUSIONS: The limited availability of relevant structural and human resources in critical care units around Vietnam makes the implementation of quality critical care to patients with SARI and sepsis, according international guidelines, not universally possible.

Detection and Characterization of Clade 1 Reassortant H5N1 Viruses Isolated from Human Cases in Vietnam during 2013.

Highly pathogenic avian influenza (HPAI) H5N1 is endemic in Vietnamese poultry and has caused sporadic human infection in Vietnam since 2003. Human infections with HPAI H5N1 are of concern due to a high mortality rate and the potential for the emergence of pandemic viruses with sustained human-to-human transmission. Viruses isolated from humans in southern Vietnam have been classified as clade 1 with a single genome constellation (VN3) since their earliest detection in 2003. This is consistent with detection of this clade/genotype in poultry viruses endemic to the Mekong River Delta and surrounding regions. Comparison of H5N1 viruses detected in humans from southern Vietnamese provinces during 2012 and 2013 revealed the emergence of a 2013 reassortant virus with clade 1.1.2 hemagglutinin (HA) and neuraminidase (NA) surface protein genes but internal genes derived from clade 2.3.2.1a viruses (A/Hubei/1/2010-like; VN12). Closer analysis revealed mutations in multiple genes of this novel genotype (referred to as VN49) previously associated with increased virulence in animal models and other markers of adaptation to mammalian hosts. Despite the changes identified between the 2012 and 2013 genotypes analyzed, their virulence in a ferret model was similar. Antigenically, the 2013 viruses were less cross-reactive with ferret antiserum produced to the clade 1 progenitor virus, A/Vietnam/1203/2004, but reacted with antiserum produced against a new clade 1.1.2 WHO candidate vaccine virus (A/Cambodia/W0526301/2012) with comparable hemagglutination inhibition titers as the homologous antigen. Together, these results indicate changes to both surface and internal protein genes of H5N1 viruses circulating in southern Vietnam compared to 2012 and earlier viruses.

HIV risk behaviours and determinants among people living with HIV/AIDS in Vietnam.

There is a potentially high risk of HIV spreading from people living with HIV/AIDS. We conducted a cross-sectional study to examine HIV risk behaviours and their determinants among people living with HIV/AIDS. Eighty-two percent had been sexually active. Sex with multiple partners was reported by 20% and consistent condom use by about one third. More than half of the participants (52%) reported having injected drugs during the previous month, and 35% of those had shared needles and syringes. Voluntary HIV testing and having received condoms or injection equipment from the local HIV prevention program, were found to be significantly associated with fewer HIV risk behaviours. Having learned recently about personal HIV status, multiple sex partners, low educational attainment and young age were found to be associated with higher HIV risk behaviours. Giving high priority to targeted preventive and support programmes is likely to be a highly cost-effective strategy.

Household survey in two provinces in Viet Nam estimates HIV prevalence in an urban and a rural population.

A household-based population study interviewed 2,553 women and 1,984 men aged 15-49 years in urban (Ho Chi Minh City) and rural (Thai Binh) provinces in Viet Nam between July and August 2005. The survey response rate was high--approximately 97% of households and 93% of adults overall, with a >92% acceptance of HIV testing among eligible adults. The unadjusted estimated population HIV prevalence was 0.3% (confidence interval [CI]: 0.1-0.6%) in Thai Binh and 0.7% (CI: 0.3-1.3) in Ho Chi Minh City (HCMC), compared with the national estimates and projections of 0.352% and 1.250%, respectively, for 2005. The ratio of male-to-female prevalence was 10.5:1 in Thai Binh and 1.3:1 in HCMC. A low level of men reported purchasing sex in the last 12 months (2.4%) and there were low self-reports of sexually transmitted infections in all adults (5%). A correct knowledge of HIV/AIDS prevention methods was high in both provinces (83%), although only 24.8% of women knew of the use of antiretroviral therapy to prevent vertical transmission of HIV. The observed population prevalence was consistent with recent projections in Thai Binh, although lower than expected in HCMC, indicating the substantial downward revisions of projected population HIV prevalence may need to be extended. The unequal sex prevalence ratio is consistent with the projected trends of increasing male-to-female sexual transmission in urban areas. The results and experience of this study will inform future population based surveys in Viet Nam and the broader Asian region.

Human immunodeficiency virus (HIV) infection patterns and risk behaviours in different population groups and provinces in Viet Nam.

OBJECTIVE: To study patterns and determinants of HIV prevalence and risk-behaviour characteristics in different population groups in four border provinces of Viet Nam. METHODS: We surveyed four population groups during April-June 2002. We used stratified random-cluster sampling and collected data concomitantly on HIV status and risk behaviours. The groups included were female sex workers (n = 2023), injecting drug users (n = 1391), unmarried males aged 15-24 years (n = 1885) and different categories of mobile groups (n = 1923). FINDINGS: We found marked geographical contrasts in HIV prevalence, particularly among female sex workers (range 0-24%). The HIV prevalence among injecting drug users varied at high levels in all provinces (range 4-36%), whereas lower prevalences were found among both unmarried young men (range 0-1.3%) and mobile groups (range 0-2.5%). All groups reported sex with female sex workers. Less than 40% of the female sex workers had used condoms consistently. The strongest determinants of HIV infection among female sex workers were inconsistent condom use (adjusted odds ratio [OR], 5.3; 95% confidence interval [CI], 2.4-11.8), history of injecting drug use and mobility, and, among injecting drug users, sharing of injection equipment (adjusted OR, 7.3; 95% CI, 2.3-24.0) and sex with non-regular partners (adjusted OR 3.4; 95% CI 1.4-8.5). CONCLUSION: The finding of marked geographical variation in HIV prevalence underscores the value of understanding local contexts in the prevention of HIV infection. Although lacking support from data from all provinces, there would appear to be a potential for sex work to drive a self-sustaining heterosexual epidemic. That the close links to serious injecting drug use epidemics can have an accelerating effect in increasing the spread of HIV merits further study.

HSV-2 antibodies in female sex workers in Vietnam.

Little information is available on the prevalence of herpes simplex type-2 (HSV-2) antibodies among groups at potential high risk of HIV in Asia. This study was carried out to determine the prevalence of HSV-2 antibodies and correlates of HSV-2 infection in female sex workers (FSWs) in border provinces of Vietnam. Nine hundred and four FSWs in five border provinces of Vietnam were interviewed about selected sociodemographic and behavioural characteristics, and information about partners by a standard interview schedule. Serological samples were collected for HSV-2 antibodies, syphilis and HIV. The overall prevalence of HSV-2 antibodies was 27.7% (95% confidence interval [CI]: 24.8-30.7%). The prevalence of HSV-2 in southern provinces (Dong Thap 32.3%, An Giang 33.3% and Kien Giang 29.9%) was higher than that in the central (Quang Tri 20.8%) and northern border areas (Lai Chau 5.0%). In multivariate analysis, Kinh ethnicity (odds ratio [OR] = 2.59, P = 0.02), direct sex work (OR = 1.61, P = 0.01), >/=9 clients/week (OR = 2.11, P = <0.001), ever worked outside Vietnam (OR = 2.12, P = 0.05), >1 pregnancy termination (OR = 1.58, P = 0.05), syphilis (OR = 5.19, P = <0.001) and HIV (OR = 2.68,P = 0.01) were associated with HSV-2. Age

Epidemiological profile and burden of rotavirus diarrhea in Vietnam: 5 years of sentinel hospital surveillance, 1998-2003.

For 5 years, we have conducted sentinel surveillance for rotavirus at 6 hospitals in 4 cities in Vietnam. Stool samples obtained from >10,000 children <5 years old who were admitted to the hospital with diarrhea have been screened for rotavirus. Overall, 55% of samples were positive, and there was little variability in rates of detection of rotavirus between sites (44%-62%). In Vietnam, the characteristics of rotavirus infection more closely resemble those seen in developed countries, rather than those seen in developing countries: children become infected at an older age, the percentage of stool samples in which rotavirus is detected is extremely high, and the rotavirus strains appear to be the common types, with fewer mixed infections occurring. It is estimated that 5300-6800 children <5 years old die of rotavirus infection each year in Vietnam, representing 8%-11% of all deaths in this age group (cumulative risk per child by age 5 years, 1 in 200 to 1 in 285). Additional studies are ongoing to document the economic cost of the disease and to assess the burden of both fatal cases and milder cases of disease. Study outcomes will provide information for future testing and potential use of a rotavirus vaccine.