A Mouse Model of X-Linked Chronic Granulomatous Disease for the Development of CRISPR/Cas9 Gene Therapy.

Chronic granulomatous disease (CGD) is an inherited immunodeficiency disease mainly caused by mutations in the X-linked CYBB gene that abrogate reactive oxygen species (ROS) production in phagocytes and microbial defense. Gene repair using the CRISPR/Cas9 system in hematopoietic stem and progenitor cells (HSPCs) is a promising technology for therapy for CGD. To support the establishment of efficient and safe gene therapies for CGD, we generated a mouse model harboring a patient-derived mutation in the CYBB gene. Our CybbC517del mouse line shows the hallmarks of CGD and provides a source for Cybb-deficient HSPCs that can be used to evaluate gene-therapy approaches in vitro and in vivo. In a setup using Cas9 RNPs and an AAV repair vector in HSPCs, we show that the mutation can be repaired in 19% of treated cells and that treatment restores ROS production by macrophages. In conclusion, our CybbC517del mouse line provides a new platform for refining and evaluating novel gene therapies and studying X-CGD pathophysiology.

Impact of COVID-19 on patterns of drug utilization: A case study at national hospital.

BACKGROUND: The Coronavirus disease of 2019 (COVID-19) pandemic and the corresponding mitigation measures have had a discernible impact on drug utilization among outpatients. However, limited research exists on the prescription trends in the elderly population during the pandemic period in Viet Nam. OBJECTIVES: This study aims to analyze the effects of COVID-19 on outpatient drug utilization patterns at a national geriatric hospital in Ho Chi Minh City before and after the early onset of the pandemic. METHODS: Data was collected from the prescriptions and administration claims, encompassing the period from January 2016 to December 2022. The dataset was divided into two periods: Period 1: January 2016 to December 2020 and Period 2: January 2021 to December 2022. The drug utilization was measured using DDD/1000P (defined daily doses-DDD per 1000 prescriptions) on a monthly basis. The analysis employed interrupted time series using Autoregressive Integrated Moving Average (ARIMA) to detect changes in drug use levels and rates. RESULTS: A total of 1,060,507 and 644,944 outpatient prescriptions from Thong Nhat Hospital were included in Period 1 and Period 2, respectively. The median age of the patients were 58 in Period 1 and 67 years old in Period 2. The most common comorbidities were dyslipidemia, hypertension, and diabetes mellitus. In terms of medication utilization, cardiovascular drugs were the most frequently prescribed, followed by drugs active on the digestive and hormonal systems. The study observed significant surges in the number of prescriptions and the average number of drugs per prescription. However, there were no significant changes in the overall consumption of all drugs. Among the drug groups related to the cardiovascular system, three subgroups experienced a sudden and significant increase: cardiac therapy, beta-blocking agents, and antihypertensives, with increasing consumption levels of 1,177.73 [CI 95%: 79.29; 2,276.16], 73.32 [CI 95%: 28.18; 118.46], and 36.70 [CI 95%: 6.74; 66.66] DDD/1000P, respectively. On the other hand, there was a significant monthly decrease of -31.36 [CI 95%: -57.02; -5.70] DDD/1000P in the consumption of anti-inflammatory and antirheumatic products. Interestingly, there was a significant increase of 74.62 [CI 95%: -0.36; 149.60] DDD/1000P in the use of antigout preparations. CONCLUSION: COVID-19 resulted in a sudden, non-significant increase in overall drug consumption levels among outpatients. Notably, our findings highlight significant increases in the utilization of three drug groups related to the cardiovascular system, specifically cardiac therapy, beta-blocking agents, and antihypertensives. Intriguingly, there was a statistically significant increase in the consumption of antigout preparations, despite a decline in the monthly consumption rate of non-steroidal anti-flammatory drugs (NSAIDs). Further studies in the following years are necessary to provide a more comprehensive understanding of the impact of COVID-19 on outpatient drug utilization patterns.

Evaluation of the impact before and after the application of an antimicrobial stewardship program at Dong Thap General Hospital, Vietnam, from 2017 to 2021.

Background: Vietnam has one of the highest rates of antibiotic resistance in Asia. In 2020, the Vietnam Minister of Health introduced new legislation for the implementation of an antimicrobial stewardship program (ASP). The evidence for the effectiveness of ASP in small hospitals and hospitals located in provinces was limited compared with larger-scale and central city hospitals. Aim: Evaluation of the impact before and after the introduction of an antimicrobial stewardship program at Dong Thap General Hospital, from 2017 to 2021. Methods: Retrospective data was collected from June 2017 to June 2021. The impact of the ASP on changes in antibiotic use and the clinical outcome associated with the implementation of the ASP was evaluated using autoregressive integrated moving average modelling of controlled interrupted time-series analysis. Results: There was a significant and sustained decrease in antibiotic consumption level (step change) in 2 indicators, DOT/1000PD (129.55; P<0.01) and LOT/1000PD (99.95, P<0.01), immediately after the ASP intervention. There were no statistically significant changes identified in terms of consumption with DDD/1000PD, or in the clinical outcomes. The results showed no statistically significant change in consumption trend (ramps) in all evaluated indicators. No statistically significant changes in consumption levels and trends were observed in the control group. Conclusion: The ASP implemented in Dong Thap General Hospital from 2017 to 2021 showed a considerable influence on antibiotic consumption as indicated by the DOT/1000 PD and LOT/1000 PD during the initial stages. Moreover, controlling antibiotic consumption did not negatively impact patient outcomes.

Cytotoxic and Apoptotic Effects of Pinostilbene and Bortezomib Combination Treatment on Human Multiple Myeloma Cells.

Multiple myeloma (MM) is a cancer of plasma cells in the bone marrow characterized by bone lesions, hypercalcemia, anemia, and renal failure. Bortezomib (BTZ), a common treatment for MM, is a proteasome inhibitor that induces apoptosis in MM cells. However, high doses of BTZ can be very toxic, signifying a need for a synergistic drug combination to improve treatment efficacy. Resveratrol (RES), a phenolic compound found in grapes, has been shown to inhibit MM cell growth. We sought to identify a synergistic combination of BTZ with a RES derivative and analyze the effects on reducing viability and inducing apoptosis in human MM cells. BTZ as well as RES and its derivatives pinostilbene (PIN) and piceatannol (PIC) decreased MM cell viability in a dose- and time-dependent manner and increased expression of cleaved proapoptotic proteins poly(ADP-ribose) polymerase 1 (PARP1) and caspase-3 in a dose-dependent manner. The combination of 5 nM BTZ and 5 µM PIN was identified to have synergistic cytotoxic effects in MM RPMI 8226 cells. MM RPMI 8226 cells treated with this combination for 24 h showed increased cleaved PARP1 and caspase-3 expression and higher percentages of apoptotic cells versus cells treated with the individual compounds alone. The treatment also showed increased apoptosis induction in MM RPMI 8226 cells co-cultured with human bone marrow stromal HS-5 cells in a Transwell model used to mimic the bone marrow microenvironment. Expression of oxidative stress defense proteins (catalase, thioredoxin, and superoxide dismutase) in RPMI 8226 cells were reduced after 24 h treatment, and cytotoxic effects of the treatment were ameliorated by antioxidant N-acetylcysteine (NAC), suggesting the treatment impacts antioxidant levels in RPMI 8226 cells. Our results suggest that this combination of BTZ and PIN decreases MM cell viability synergistically by inducing apoptosis and oxidative stress in MM cells.

Identification of a Novel Renal Metastasis Associated CpG-Based DNA Methylation Signature (RMAMS).

Approximately 21% of patients with renal cell cancer (RCC) present with synchronous metastatic disease at the time of diagnosis, and metachronous metastatic disease occurs in 20-50% of cases within 5 years. Recent advances in adjuvant treatment of aggressive RCC following surgery suggest that biomarker-based prediction of risk for distant metastasis could improve patient selection. Biometrical analysis of TCGA-KIRC data identified candidate loci in the NK6 homeobox 2 gene (NKX6-2) that are hypermethylated in primary metastatic RCC. Analyses of NKX6-2 DNA methylation in three gene regions including a total of 16 CpG sites in 154 tumor-adjacent normal tissue, 189 RCC, and 194 metastatic tissue samples from 95 metastasized RCC patients revealed highly significant tumor-specific, primary metastatic-specific, and metastatic tissue-specific hypermethylation of NKX6-2. Combined CpG site methylation data for NKX6-2 and metastasis-associated genes (INA, NHLH2, and THBS4) demonstrated similarity between metastatic tissues and metastatic primary RCC tissues. The random forest method and evaluation of an unknown test cohort of tissues using receiver operator characteristic curve analysis revealed that metastatic tissues can be differentiated by a median area under the curve of 0.86 (p = 1.7 × 10-8-7.5 × 10-3) in 1000 random runs. Analysis of variable importance demonstrated an above median contribution for decision-making of at least one CpG site in each of the genes, suggesting superior informativity for sites annotated to NHLH2 and NKX6-2. Thus, DNA methylation of NKX6-2 is associated with the metastatic state of RCC tissues and contributes to a four-gene-based statistical predictor of tumoral and metastatic renal tissues.

Assessment of Knowledge, Attitude, and Practice in Adverse Drug Reaction Reporting of Healthcare Professionals in Vietnam: A Cross-Sectional Study.

Background: Under-reporting is a major issue of ADR spontaneous reporting system. This study assesses the knowledge, attitude, and practice of healthcare professionals in Children's Hospital in Vietnam and suggests solutions to enhance ADR reporting rate based on findings. Methods: A cross-sectional study was conducted and 397 self-administered structured questionnaires were distributed to all potential HCPs working in surveyed hospital within 2 weeks from June 03 to June 20, 2020. Results: Overall response rate was 97% with 384 responses. A majority answered correctly ADRs' knowledge apart from form supplier (1.6%) and possible causes (2.6%). The need to focus on patient care (33.3%) and the trivia of reaction (31.5%) reduced HCPs' attention. About 61.7% reported once in their career, 49.7% had training. Having trained group had numbers of practice significantly higher than their counterparts. Major reason for not reporting was lack of information and instruction. Preferred solutions were regularly training, updating, and collaboration of HCPs in reporting ADR. Conclusion: Healthcare professionals had adequate knowledge, positive attitude, and moderate practice. Training significantly raised the number of practices in reporting ADR. Preferred solutions were regular training, updating, and collaboration of healthcare professionals in ADR reporting.

Targeted Delivery of DNA Topoisomerase Inhibitor SN38 to Intracranial Tumors of Glioblastoma Using Sub-5 Ultrafine Iron Oxide Nanoparticles.

Effectively delivering therapeutics for treating brain tumors is hindered by the physical and biological barriers in the brain. Even with the compromised blood-brain barrier and highly angiogenic blood-tumor barrier seen in glioblastoma (GBM), most drugs, including nanomaterial-based formulations, hardly reach intracranial tumors. This work investigates sub-5 nm ultrafine iron oxide nanoparticles (uIONP) with 3.5 nm core diameter as a carrier for delivering DNA topoisomerase inhibitor 7-ethyl-10-hydroxyl camptothecin (SN38) to treat GBM. Given a higher surface-to-volume ratio, uIONP shows one- or three-folds higher SN38 loading efficiency (48.3 ± 6.1%, mg/mg Fe) than those with core sizes of 10 or 20 nm. SN38 encapsulated in the coating polymer exhibits pH sensitive release with <10% over 48 h at pH 7.4, but 86% at pH 5, thus being protected from converting to inactive glucuronide by UDP-glucuronosyltransferase 1A1. Conjugating αv ß3 -integrin-targeted cyclo(Arg-Gly-Asp-D-Phe-Cys) (RGD) as ligands, RGD-uIONP/SN38 demonstrates targeted cytotoxicity to αv ß3 -integrin-overexpressed U87MG GBM cells with a half-maximal inhibitory concentration (IC50 ) of 30.9 ± 2.2 nm. The efficacy study using an orthotopic mouse model of GBM reveals tumor-specific delivery of 11.5% injected RGD-uIONP/SN38 (10 mg Fe kg-1 ), significantly prolonging the survival in mice by 41%, comparing to those treated with SN38 alone (p < 0.001).

The Economic Burden of Chronic Kidney Disease in Vietnam.

Our objective is to analyze the economic burden of chronic kidney disease (CKD) in Vietnam, particularly in District 2 Hospital at Ho Chi Minh City in 2019. This is a descriptive cross-sectional study. The data source is the medical records of the patients. Encoding the data, analyzing treatment cost, regression modeling, and verification were performed using Stata 15 software. Patients with stage 3 CKD account for the highest proportion of the CKD patient population. CKD comorbidities include hypertension, diabetes, cardiovascular disease, and anemia, which increase the treatment fees of patients. Approximately half of the patients with CKD have diabetes or cardiovascular disease. Treatment costs increase as the condition of the patient worsens (except for stage 1 and 2 CKD). The total expenses of all CKD patients in District 2 Hospital were USD 916 423 988.60. Five main factors that affect the treatment fee of a patient: CKD stage, age, gender, and the presence of diabetes, cardiovascular disease, and anemia. The regression model correctly predicts 96% of cases and can explain 64.15% of the fluctuations in costs. The cost of CKD treatment was higher than Vietnam's per capita GDP in 2019, and the primary factors affecting costs are comorbidities and dialysis.

Impact of Antimicrobial Stewardship Program on Vancomycin Usage: Costs and Outcomes at Hospital for Tropical Diseases in Ho Chi Minh City, Vietnam.

BACKGROUND: Nowadays, with the emergence of vancomycin-resistant strains, the clinical use of vancomycin has been followed closely by applying the antimicrobial stewardship program (ASP) to enhance effectiveness in treatment and reduce cost burden for patients. METHODS: A descriptive cross-sectional study at the Hospital for Tropical Diseases was conducted to assess the inpatient status assigned to intravenous vancomycin and factors associated with the cost of treatment during two periods of implementing ASP, which were i) from April 1, 2016 to March 31, 2018 (previous ASP-pASP) and ii) from June 1, 2018 to March 31, 2020 (new ASP-nASP). RESULTS: Among 1375 patients who met the sampling criteria, there were 601 and 774 patients in pASP and nASP, respectively. The rate of no improvement/mortality in the pASP was higher than that in nASP (37.10% vs 25.98%, p <0.05). The proportion of patients with two or more infection episodes in nASP is lower than that in pASP (9.83% vs 18.64%, p<0.05). Besides, nASP has higher length of therapy (LOT) and higher day of therapy (DOT). The average treatment cost in the pASP is higher than that in the nASP, 1891.22 (95% CI, 1713.46-2068.98) USD vs 1775.55 (95% CI, 1576.22-1974.88) USD. There are seven factors (p<0.05) that associate with the total cost of treatment (age, number of infection episodes, length of stay, discharge status, clinical department, LOT, DOT) in pASP. On the other hand, the nASP has five factors (p<0.001), in which the log(LOT) and age are not as statistically significant (p=0.5127 and 0.3852, respectively) as in the pASP model. CONCLUSION: The implementation and improvement of the ASP at the Hospital for Tropical Diseases have initially shown benefits for patients using intravenous vancomycin. Specifically, the ASP helps to reduce treatment costs, improve patient outcomes, reduce length of stay and decrease the average daily dose of vancomycin.

Assessment of Job Stress of Clinical Pharmacists in Ho Chi Minh City, Vietnam: A Cross-Sectional Study.

Objectives: The official implementation of clinical pharmacy in Vietnam has arrived relatively late, resulting in various stressors. This study aims to evaluate job stress level and suggest viable solutions. Methods: A cross-sectional study was conducted on clinical pharmacists (CPs) in 128 hospitals in Ho Chi Minh City (HCMC). Job stress questions were derived from the Healthcare Profession Stress Inventory (HPSI). Results: A total of 197 CPs participated, giving a response rate of 82.4%. Participants were found to have moderate job stress with an overall mean stress score of 1.5 (0.4) and stress rate of 52.8%. The sample size was statistically adequate and the HPSI was valid and reliable. Patient care responsibility was the main stressor, especially in public hospitals, followed by job conflicts. Lack of experience, low income, and inability to participate in clinical ward rounds caused significant stress to CPs regarding job recognition and job uncertainty. More practice-oriented training programs in bachelor curricula and clinical practice should be applied to help CPs gain more experience, self-confidence, and diminish job stress. Conclusion: CPs in HCMC have moderate stress. More practice-oriented training programs should be prioritized to lessen stress for CPs.

Optimization of Procedure for Determining Dissolved Oxygen in Surface Water and Seawater Exploiting the UV-vis Absorption of Mn(III) Species.

We present an analytical method for dissolved oxygen based on the quantification of Mn(III) absorbance in a water sample. After Mn(II) reacts with the oxygen molecules in water, Mn(III) is formed and stabilized by hexa-metaphosphate under acidic conditions. The UV visible absorbance of Mn(III) is proportional to the oxygen concentration in the water sample. Compared to the Winkler method, the proposed method has the same accuracy (R = 0.9992 at 0 - 52 mg dm-3) but requires fewer reagents; furthermore, it does not involve titration. Interferences from nitrite and iodate were not observed. This procedure can be used to accurately and quickly determine the oxygen concentrations in different natural water sources, including seawater.

Job satisfaction of clinical pharmacists and clinical pharmacy activities implemented at Ho Chi Minh city, Vietnam.

Ho Chi Minh City (HCMC) in Vietnam pioneered the practice of clinical pharmacy; however, hospitals in HCMC have faced numerous challenges that might influence the job satisfaction of clinical pharmacists (CPs). Additionally, there have been no official statistics about clinical pharmacy activities that have been reported so far. Therefore, this study was conducted to examine the current status of the clinical pharmacy profession and to analyze the key factors affecting job satisfaction of CPs in HCMC. This was a cross-sectional study. Self-administered questionnaires were distributed to all the CPs in all the 128 hospitals in HCMC via an online survey tool from May to June 2020. Only about 30% of the respondents were full-time CPs. The percentage of CPs participating in clinical wards was relatively low (52.79%). "Provide drug information for patients and medical employees" was the most common clinical pharmacy activity, with the percentage of CPs participating in it being nearly 90%. Overall, 74.1% of the 197 CPs surveyed were satisfied with their current job. The factors that they were satisfied with the most and the least were "Inter & Intra professional relationships" (95.9%) and "Income" (59.9%), respectively. The only demographic and work-related characteristic that had a statistically significant association with overall job satisfaction was "Ward round participation". Most clinical pharmacy tasks noted a high rate of participation from the CPs. Nevertheless, hospitals in HCMC was found to be experiencing a shortage of CPs and low levels of participation of CPs in ward rounds, and most CPs were unable to completely focus on clinical pharmacy tasks. Regarding CPs' job satisfaction-related aspects, income and ward round participation appear to be the two factors that should be increased, in order to enhance CPs' job satisfaction.

Development of a Photometric Method to Measure Molecular Oxygen in Water.

A photometric method to determine molecular oxygen in water was developed. When manganese(II) is oxidized by oxygen under alkaline conditions, the presence of polyphosphate can prevent precipitation due to a coacervate reaction. The oxidized manganese later dissolves in acid to form a pink Mn(III) species, which has a stable UV/vis spectrum. Monitoring of the oxygen concentration based on the absorbance of the pink Mn(III) species at 517 nm showed a strong correlation with both the Winkler method and an optical sensor. As a result, the present method can measure not only dissolved oxygen, but also fine bubbles oxygen in in the water sample with high reliability (0 - 26 mg dm-3, r2 = 0.9995). During this process, no significant interference from nitrite or metal ions was observed. The accuracy of the measurement was steady at high temperatures of the water samples (≤ 363 K).

Macrophages expedite cell proliferation of prostate intraepithelial neoplasia through their downstream target ERK.

The risk factors for prostate cancer include a high-fat diet and obesity, both of which are associated with an altered cell environment including increased inflammation. It has been shown that chronic inflammation due to a high-fat diet or bacterial infection has the potential to accelerate prostate cancer as well as its precursor, prostatic intraepithelial neoplasia (PIN), development. However, the underlying mechanism of how chronic inflammation promotes prostate cancer development, especially PIN, remains unclear. In this study, we showed that more macrophages were present in PIN areas as compared to the normal areas of human prostate. When co-culturing PIN cells with macrophages in 3D, more PIN cells had nuclear localized cyclin D1, indicating that macrophages enhanced PIN cell proliferation. We identified ICAM-1 and CCL2 as chemoattractants expressed by PIN cells to recruit macrophages. Furthermore, we discovered that macrophage-secreted cytokines including C5a, CXCL1, and CCL2 were responsible for increased PIN cell proliferation. These three cytokines activated ERK and JNK signaling in PIN cells through a ligand-receptor interaction. However, only blockade of ERK abolished macrophage cytokines-induced cell proliferation of PIN. Overall, our results provide a mechanistic view on how macrophages activated through chronic inflammation can expedite PIN progression during prostate cancer development. The information from our work can facilitate a comprehensive understanding of prostate cancer development, which is required for improvement of current strategies for prostate cancer therapy.

Cost-Effectiveness of Gliclazide-Based Intensive Glucose Control vs. Standard Glucose Control in Type 2 Diabetes Mellitus. An Economic Analysis of the ADVANCE Trial in Vietnam.

Introduction: ADVANCE was a large, multinational clinical study conducted over 5 years in type 2 diabetes mellitus (T2DM). In all, 11,140 patients were randomly assigned to receive gliclazide-based intensive glucose control (IGC) or standard glucose control (SGC). IGC was shown to significantly reduce the incidence of major macrovascular and microvascular events (composite endpoint) or major microvascular events compared with SGC, primarily by enhancing renal protection. We assessed the cost-effectiveness of IGC vs. SGC, based on the ADVANCE results, from a Vietnamese healthcare payer perspective. Materials and Methods: A partitioned survival times model across five health states (no complications, myocardial infarction, stroke, end-stage renal disease [ESRD], and diabetes-related eye-disease) was designed. Time-to-event curves were informed by the cumulative incidence of events and corresponding hazard ratios from the ADVANCE study. Health outcomes were expressed in terms of ESRD avoided and quality-adjusted life years (QALYs). Costs (in US $) comprised treatment costs and health state costs. Utility weights and costs were documented from literature reporting Vietnamese estimates. For sensitivity analyses, all parameters were individually varied within their 95% confidence interval bounds (when available) or within a ±30% range. Results: Over a 5-year horizon, IGC avoided 6.5 additional ESRD events per 1,000 patients treated compared with SGC (IGC, 3.5 events vs. SGC, 10.0 events) and provided 0.016 additional QALYs (IGC, 3.570 QALYs vs. SGC, 3.555 QALYs). Total costs were similar for the two strategies (IGC, $3,786 vs. SGC, $3,757). Although the total drug costs were markedly higher for IGC compared with SGC ($1,703 vs. $873), this was largely offset by the savings from better renal protection with IGC (IGC, $577 vs. SGC, $1,508). The incremental cost-effectiveness ratio (ICER) of IGC vs. SGC was $1,878/QALY gained, far below the threshold recommended by the World Health Organization (i.e., 1-3 × gross domestic product per inhabitant ≈$7,500 in Vietnam). The ICER of IGC vs. SGC per ESRD event avoided was $4,559/event. The findings were robust to sensitivity analysis. Conclusion: In Vietnam, gliclazide-based IGC was shown to be cost-effective compared with SGC from a healthcare payer perspective, as defined in the ADVANCE study.

Enhancement of CRISPR-Cas9 induced precise gene editing by targeting histone H2A-K15 ubiquitination.

BACKGROUND: Precise genetic modifications are preferred products of CRISPR-Cas9 mediated gene editing in mammalian cells but require the repair of induced double-strand breaks (DSB) through homology directed repair (HDR). Since HDR competes with the prevailing non-homologous end joining (NHEJ) pathway and depends on the presence of repair templates its efficiency is often limited and demands optimized methodology. RESULTS: For the enhancement of HDR we redirect the DSB repair pathway choice by targeting the Ubiquitin mark for damaged chromatin at Histone H2A-K15. We used fusions of the Ubiquitin binding domain (UBD) of Rad18 or RNF169 with BRCA1 to promote HDR initiation and UBD fusions with DNA binding domains to attract donor templates and facilitate HDR processing. Using a traffic light reporter system in human HEK293 cells we found that the coexpression of both types of UBD fusion proteins promotes HDR, reduces NHEJ and shifts the HDR/NHEJ balance up to 6-fold. The HDR enhancing effect of UBD fusion proteins was confirmed at multiple endogenous loci. CONCLUSIONS: Our findings provide a novel efficient approach to promote precise gene editing in human cells.

Current status of clinical pharmacy workforce, services and clinical pharmacist recruitment in Ho Chi Minh City, Vietnam.

OBJECTIVES: Clinical pharmacy practices in Vietnam have not been well studied. We aimed to describe clinical pharmacy practices in terms of workforce, activities and the recruitment demand for clinical pharmacists (CPs) in hospitals. METHODS: A cross-sectional survey was conducted, and 123 questionnaires were distributed to Heads/Deputy heads of Pharmacy department and Boards of directors in all of hospitals in Ho Chi Minh City, Vietnam between August 2018 and June 2019. RESULTS: There were 187 CPs in 79 participating hospitals, whereas the ratio of CPs per 100 patient beds was 0.67. The median number of CPs was 2 (1-4), with a significantly low median full time equivalent [0.4 (1, 2)]. The income of CPs was significantly low. Antibiotics were the most common medications that CPs discussed with physicians (93.06%). Interventions commonly performed by CPs were "Checking drug interactions" (77.78%), "Counseling physicians about the route of administration" (61.11%), "Checking drug allergies" (51.39%). The median number of CPs needed to recruit according to Heads/Deputy heads of Pharmacy Department and Boards of directors was 2 (1-3) and 2 (1-3.5), respectively. CONCLUSION: The shortage of CPs, which was likely attributable to low income, might lead to numerous obstacles for delivering comprehensive healthcare services. Thus, the hospital recruitment strategies should focus on salary and benefits to attract more CPs, especially those with postgraduate degree.

Macrophage Cytokines Enhance Cell Proliferation of Normal Prostate Epithelial Cells through Activation of ERK and Akt.

Macrophage infiltrations (inflammation) are associated with prostate disorders such as prostatitis, prostatic hyperplasia and prostate cancer. All prostate disorders have elevated cell proliferation, and are initiated from normal prostate epithelial cells. To date, the mechanism of how macrophages regulate normal prostate epithelial cell proliferation remains largely unknown. Using a 3D co-culture system, we here show that Raw 264.7 macrophages increased cell proliferation of normal prostate epithelial PZ-HPV-7 cells. In addition, these Raw 264.7 macrophages expressed higher levels of Ym1 and CD206. We further identify macrophage-secreted cytokines including CCL3, IL-1ra, osteopontin, M-CSF1 and GDNF as mediators for potentiating PZ-HPV-7 cell proliferation in 3D. All these cytokines differentially activated ERK and Akt. Blockade of both kinases through their inhibitors hindered macrophage-induced cell proliferation of PZ-HPV-7 cells. Hence, our data provide mechanistic insight of how inflammation may contribute to development of prostatic diseases at a very early stage through augment of cell proliferation of normal prostate epithelial cells.

Imatinib in myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRB in chronic or blast phase.

We evaluated clinical characteristics and outcome on imatinib of 22 patients with myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRB. Median age was 49 years (range 20-80), 91% were male. Fifteen different PDGFRB fusion genes were identified. Eosinophilia was absent in 4/19 (21%) cases and only 11/19 (58%) cases had eosinophils ≥1.5×109/L. On imatinib, 17/17 (100%) patients in chronic phase achieved complete hematologic remission after median 2 months (range 0-13)​. Complete cytogenetic remission and/or complete molecular remission by RT-PCR were achieved in 12/13 (92%) and 12/14 patients (86%) after median 10 (range 3-34) and 19 months (range 7-110), respectively. In patients with blast phase (myeloid, n = 2; lymphoid, n = 3), treatment included combinations of imatinib (n = 5), intensive chemotherapy (n = 3), and/or allogeneic stem cell transplantation (n = 3). All 3 transplanted patients (complex karyotype, n = 2) experienced early relapse. Initially, patients were treated with imatinib 400 mg/day (n = 15) or 100 mg/day (n = 7), the dose was reduced from 400 mg/day to 100 mg/day during follow-up in 9 patients. After a median treatment of 71 months (range 1-135), the 5-year survival rate was 83%; 4/22 (18%) patients died (chronic phase; n = 2; blast phase, n = 2) due to progression (n = 3) or comorbidity while in remission (n = 1). Of note, 3/4 patients had a complex karyotype. In summary, the most important characteristics of myeloid/lymphoid neoplasms with rearrangement of PDGFRB include (a) male predominance, (b) frequent lack of hypereosinophilia,

Fusion of PDGFRB to MPRIP, CPSF6, and GOLGB1 in three patients with eosinophilia-associated myeloproliferative neoplasms.

In eosinophilia-associated myeloproliferative neoplasms (MPN-eo), constitutive activation of protein tyrosine kinases (TK) as consequence of translocations, inversions, or insertions and creation of TK fusion genes is recurrently observed. The most commonly involved TK and their potential TK inhibitors include PDGFRA at 4q12 or PDGFRB at 5q33 (imatinib), FGFR1 at 8p11 (ponatinib), and JAK2 at 9p24 (ruxolitinib). We here report the identification of three new PDGFRB fusion genes in three male MPN-eo patients: MPRIP-PDGFRB in a case with t(5;17)(q33;p11), CPSF6-PDGFRB in a case with t(5;12)(q33;q15), and GOLGB1-PDGFRB in a case with t(3;5)(q13;q33). The fusion proteins identified by 5'-rapid amplification of cDNA ends polymerase chain reaction (PCR) or DNA-based long distance inverse PCR are predicted to contain the TK domain of PDGFRB. The partner genes contain domains like coiled-coil structures, which are likely to cause dimerization and activation of the TK. In all patients, imatinib induced rapid and durable complete remissions.