Cell-type-specific tumour sensitivity identified with a bromodomain targeting PROTAC in adenoid cystic carcinoma.

Salivary gland adenoid cystic carcinoma (ACC) is a rare malignancy with limited treatment options. The development of novel therapies is hindered by a lack of preclinical models. We have generated ACC patient-derived xenograft (PDX) lines that retain the physical and genetic properties of the original tumours, including the presence of the common MYB::NFIB or MYBL1::NFIB translocations. We have developed the conditions for the generation of both 2D and 3D tumour organoid patient-derived ACC models that retain MYB expression and can be used for drug studies. Using these models, we show in vitro and in vivo sensitivity of ACC cells to the bromodomain degrader, dBET6. Molecular studies show a decrease in BRD4 and MYB protein levels and target gene expression with treatment. The most prominent effect of dBET6 on tumours in vivo was a change in the relative composition of ACC cell types expressing either myoepithelial or ductal markers. We show that dBET6 inhibits the progenitor function of ACC cells, particularly in the myoepithelial marker-expressing population, revealing a cell-type-specific sensitivity. These studies uncover a novel mechanistic effect of bromodomain inhibitors on tumours and highlight the need to impact both cell-type populations for more effective treatments in ACC patients. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

HIV knowledge and risk behaviors among drug users in three Vietnamese mountainous provinces.

BACKGROUND: Globally, people who inject drugs are highly vulnerable to HIV transmission. Methadone maintenance treatment (MMT) programs are one of the most cost-effective mechanisms to substitute opioid use and improve the quality of life of patients. Since the coverage of MMT is still limited and even for those patients who are treated, improving their knowledge on HIV and maintaining healthy behaviors are key to maximizing the outcomes of HIV harm reduction programs. This study examined the knowledge on HIV, perceived risk and HIV testing among drug users accessing methadone maintenance services in three Vietnamese mountainous areas. METHODS: A cross-sectional study of 300 people enrolling for MMT services in three provinces in Vietnam was conducted. The factors associated with the knowledge, attitudes, and practices of respondents about HIV/AIDS were exploited using multivariable logistic model. RESULTS: Of the 300-people surveyed, 99% knew of HIV and 60.6% were identified as having good knowledge. While 75.2% identified that injecting drugs was a risk factor for HIV, 52.2% thought they were not at risk of HIV mainly as they did not share needles. 92.6% had undergone HIV testing with 17.4% being positive, a number which was significantly lower than Vietnam's national average for people who inject drugs. Age, ethnicity and education were associated with knowledge of HIV while ART treatment was linked to self-assessed HIV status. CONCLUSIONS: This study sheds new light on the knowledge attitudes and practices of people who inject drugs, particularly males in mountainous areas of Vietnam regarding HIV prevention. Overall, knowledge was good with most conducting safe practices towards transmission. Enhanced education and targeting of minority groups could help in increasing the numbers receiving MMT and HIV services.

Factors Associated with Substance Use and Sexual Behavior among Drug Users in Three Mountainous Provinces of Vietnam.

Due to their geographical characteristics, the mountainous areas of Vietnam are particularly vulnerable to illicit drug use. Drug users in remote areas are also more likely to engage in risky sexual behaviors. This study aimed to describe the prevalence and characteristics of substance use and sexual behaviors and explored their related factors among newly admitted drug users in three mountainous provinces of Vietnam. A cross-sectional study was conducted on 300 newly-admitted drug users registering for Methadone Maintenance Treatment (MMT) at 6 clinics in three provinces: Dien Bien, Lai Chau and Yen Bai from October 2014 to December 2015. Information about the socio-demographic characteristics, history of substance use, and sexual behaviors were collected. The multivariate logistic regression model was used to identify potential predictors of four outcomes, which included: drug injection, re-use of needles, using condoms during the last time of having sex, and having sexual intercourse with female sex workers. The proportion of injecting drug users was 68.3%; of those 9% never re-used needles. Of note, 69% of those who reported having sex with female sex workers in the last month did not use condoms. Regression models showed that those who injected drugs and had health problems in last 30 days had greater odds of having sex with female sex workers. Drug users in mountainous settings acknowledged the high prevalence of human immunodeficiency virus (HIV)-related risk behaviors and a demand for physical and psychological care. Scaling up MMT services is key to approaching this high-risk group; however, at the same time, comprehensive harm-reduction interventions, counseling, and health care services should also be made accessible and effective in this setting.

Workability of patients with HIV/AIDS in Northern Vietnam: a societal perspective on the impact of treatment program.

In Vietnam, the antiretroviral therapy (ART) program has been widely scaled up across the country since 2005, and now covers treatment for about half the HIV population. However, limited data exist about the workability and productivity outcome of ART in Vietnam. We aim to assess the employment status and work productivity among HIV patients taking ART in Northern Vietnam. A cross-sectional study was conducted in Hanoi and Nam Dinh with 1133 participants taking ART at the selected clinics. The Work Productivity and Activity Impairment Questionnaire: General Health (WPAI-GH) was applied. We found that 23% of patients with HIV/AIDS reported overall work productivity loss, and 12% had activity impairment. Among those having a job, their monthly income, however, was significantly lower than national averages 2806 thousand VND vs. 4120 thousand VND). The average education level of participants was low, with only 41.61% having greater than secondary education. Health problems and lower CD4 cell counts decreased workability of the patients while having a more dependent family, being a smoker or having a later HIV stage was associated with being less likely to have a job. The rate of employment among HIV/AIDS patients in this study was high however incomes were substantially lower than average. This could be due to low education levels or social stigma regarding these patients. Vocational education programs and public awareness could empower the patients economically. Similarly, a number of social and behavioral problems were associated with decreasing the working rate and productivity. Addressing these health issues may improve productivity among patients.

Quality of life improvement, social stigma and antiretroviral treatment adherence: implications for long-term HIV/AIDS care.

By 2020, the Vietnamese government has committed to having 90% of patients receiving ART as well as 90% of those on ART having successful viral suppression. Factors that influence adherence to ART among patients are essential to allowing the adequate care. This study was conducted across 8 outpatient clinics in Hanoi and Nam Dinh province and included 1133 patients living with HIV. Socioeconomic factors such as marital status, education, employment as well as health-related quality of life improvements were investigated as potentially being associated with adherence rates of ART patients. Through multivariate logistic regression analysis with self-reported ART adherence and VAS scores, this study was able to identify marital status and employment as two factors associated with positive adherence scores. Similarly, health problems, stigmatization, and duration on ART were associated negatively with ART adherence. Knowing that these factors may be linked to adherence rates, they can be preemptively managed with patients to enhance adherence rates and achieve successful viral suppression.

Financial mobilization for antiretroviral therapy program: multi-level predictors of willingness to pay among patients with HIV/AIDS in Vietnam.

In Vietnam, significant progress has been made in increasing the number of patients receiving antiretroviral therapy (ART) in the last number of years. As this number increases and international aid and funding for HIV services declines, a greater proportion of ART funding will need to be provided by the government budget, health insurance or by the patients themselves. This study aims to evaluate the willingness of HIV patients to pay for ART. A cross-sectional study which included 1133 HIV-positive patients was conducted across 8 outpatient centers in Hanoi and Nam Binh in Northern Vietnam in 2013. Contingent valuation method was used to assess the willingness to pay (WTP) of patient for ART. Over 90% of the patients were willing to pay for ART for an average amount of 19.7 USD per month. Regression models showed that the willingness of patients to pay for ART was influenced by factors such as employment, income, quality of life and social factors. The amount patients were willing to pay was also associated with gender, living place and level of HIV service administration. By establishing these factors which influence the amount of WTP for ART, plans for the future can be effectively designed and patient groups at risk can be appropriately managed.

Customers' Perceptions of Compliance with a Tobacco Control Law in Restaurants in Hanoi, Vietnam: A Cross-Sectional Study.

The Tobacco Harm Prevention Law has been promulgated in 2012 in Vietnam, prohibiting smoking in public places such as restaurants except for designated smoking areas. However, currently, evidence about Vietnamese customers’ and restaurants’ compliance with the Law is constrained. This study aimed to explore customers’ perceptions; attitudes and practices towards the compliance with tobacco control regulations in the restaurants in Hanoi, Vietnam. A cross-sectional study was performed in October 2015 with 1746 customers in 176 communes in Hanoi, Vietnam. Data about customers’ perceptions on how restaurants comply with the smoking control law and whether customers smoking actively or experienced SHS in restaurants in the last 30 days were collected. Multivariable mixed effects logistic regression model was used to determine the factors related to smoking in the restaurant. Most customers were aware of the law on Tobacco Harm Prevention (79%; n = 1320) and regulations that prohibited smoking in restaurants (78.4%; n = 1137). While 75.8% (n = 1285) of customers perceived that they did not see or rarely saw no-smoking signs, 17.7% (n = 481) of customers reported that they frequently saw direct marketing of tobacco in visited restaurants. About one-fourth of customers witnessed that the staff reminded customers not to smoke inside restaurants (28.8%; n = 313), and 65% (n = 1135) sometimes or always were exposed to secondhand smoke in their visited restaurants. People who were female (OR = 0.02, 95% CI = 0.01⁻0.05) were less likely to report their smoking in the restaurant than their counterparts. Those having higher age (OR = 1.03; 95% CI = 1.01⁻1.06), high school education (OR = 2.14, 95% CI = 1.07⁻4.26), being office workers (OR = 3.24, 95% CI = 1.33⁻7.92) or unemployed (OR = 4.45; 95% CI = 1.09⁻18.15) had a higher likelihood of reporting to be restaurant smokers than those having lower high education or students, respectively. This study highlighted a low level of perceived compliance with the smoke-free law in Vietnamese restaurants. Improving the monitoring systems for the enforcement of the smoking law in restaurants should be prioritized; restaurant owners should implement 100% smoke-free environments as following the best practice towards the tobacco control law along with educational campaigns to promote the awareness of restaurant owners and customers about the tobacco control law.