Public healthcare system utilization for chronic hepatitis C infection in Vietnam.

BACKGROUND: Healthcare utilization is typically adversely affected when the treatment is expensive and requires multiple visits. We examined the determinants of healthcare-seeking for Hepatitis C virus (HCV) infection which is asymptomatic, chronic, and requires costly treatment in an urban tertiary care referral hospital in Vietnam. METHODS: We conducted a secondary analysis of hospital data for patients attending the Hospital for Tropical Diseases in Ho Chi Minh City, Vietnam between 2017 and 2020 specifically for HCV infection treatment. Poisson regression was used to determine the effect of personal factors (age, sex, comorbidities) and structural factors (health insurance, proximity to the facility, seasonality, year of visit) on the number of hospital visits. RESULTS: From 2017 to 2020 a total of 22,052 eligible patients sought treatment in the hospital. Among the patients, 50.4% were males and 58.7% were > 50 years of age. The mean number of visits per person was 2.17. In the multivariate analysis compared to 2017, the number of hospital visits increased by 4% in 2018 and then significantly decreased in 2019 and 2020. Visit numbers were significantly lower (6%) among South East region residents compared to those from Central Highlands and for those who lived further away from the hospital. The visit numbers were significantly higher among older age groups (5-11%), those with health insurance (6%), and those with comorbidities (5%) compared to others. Although the number of hospital visits by females was higher (7%) than males in 2017, it significantly decreased in subsequent years. CONCLUSIONS: Our study indicated that there are both structural and individual factors affecting the number of visits for HCV treatment. To meet the global strategy for elimination of HCV, Vietnam Government needs to address the structural and personal barriers to healthcare seeking, with a special focus on women.

Nobiletin Enhances Chemosensitivity to Adriamycin through Modulation of the Akt/GSK3ß/ß⁻Catenin/MYCN/MRP1 Signaling Pathway in A549 Human Non-Small-Cell Lung Cancer Cells.

Drug resistance is a major problem in the treatment of non-small-cell lung cancer (NSCLC). In this study, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was performed to identify the differentially expressed genes in Adriamycin (ADR)-resistant NSCLC A549/ADR cells compared with parental A549 cells. Among the tested phytochemicals, nobiletin (NBT) is able to overcome the ADR resistance of A549/ADR cells. NBT treatment decreased the expression of a neuroblastoma-derived MYC (MYCN) and multidrug resistance-associated protein 1 (MRP1) as well as downregulating Akt, GSK3ß, and ß-catenin. Consistent with these results, NBT treatment resulted in the accumulation of intracellular ADR. A combination index (CI) assay confirmed the synergistic effect of combined treatment with NBT and ADR in reducing the viability of A549/ADR cells (CI = 0.152). Combined treatment with NBT and ADR enhanced apoptosis in A549/ADR cells, as evidenced by increased caspase-3 activation, poly (ADP-ribose) polymerase (PARP) cleavage, and sub-G1 population compared to treatment with ADR alone. In vivo experiments using a mouse xenograft model revealed that combination therapy with NBT and ADR significantly reduced tumor volume by 84.15%. These data suggest that NBT can sensitize ADR-induced cytotoxicity against A549/ADR cells by inhibiting MRP1 expression, indicating that NBT could serve as an effective adjuvant agent for ADR-based chemotherapy in lung cancer.

Effects of the Combination of Gliotoxin and Adriamycin on the Adriamycin-Resistant Non-Small-Cell Lung Cancer A549 Cell Line.

Acquired drug resistance constitutes an enormous hurdle in cancer treatment, and the search for effective compounds against resistant cancer is still advancing. Marine organisms are a promising natural resource for the discovery and development of anticancer agents. In this study, we examined whether gliotoxin (GTX), a secondary metabolite isolated from marine-derived Aspergillus fumigatus, inhibits the growth of adriamycin (ADR)-resistant non-small-cell lung cancer (NSCLC) cell lines A549/ADR. We investigated the effects of GTX on A549/ADR cell viability with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and the induction of apoptosis in A549/ADR cells treated with GTX via fluorescence-activated cell sorting analysis, Hoechst staining, annexin V/propidium iodide staining, tetraethylbenzimidazolylcarbocyanine iodide (JC-1) staining, and western blotting. We found that GTX induced apoptosis in A549/ADR cells through the mitochondria-dependent pathway by disrupting mitochondrial membrane potential and activating p53, thereby increasing the expression levels of p21, p53 upregulated modulator of apoptosis (PUMA), Bax, cleaved poly (ADP-ribose) polymerase (PARP), and cleaved caspase-9. More importantly, we discovered that GTX works in conjunction with ADR to exert combinational effects on A549/ADR cells. In conclusion, our results suggest that GTX may have promising effects on ADR-resistant NSCLC cells by inducing mitochondria-dependent apoptosis and through the combined effects of sequential treatment with ADR.