The efficacy and tolerability of proteoglycan F in the treatment of knee osteoarthritis: A prospective, randomized, double-blind controlled trial.

Objective: To identify the efficacy and tolerability of Proteoglycan F in patients with primary knee OA.Design: A 24-week randomized, placebo-controlled, double-blind clinical trial with two arms: (1) Proteoglycan F (received 10 â€‹mg proteoglycan daily, for 24 weeks) and (2) control group (received placebo). Knee symptoms and joint cartilage status (evaluated by ultrasound and MRI of knee joints), quality of life, serum cytokine levels (IL-1ß and TNF-α), and safety evaluation were measured before, during, and after the treatment. Results: After 24-week treatment, pain reduction (in the KOOS pain score) of at least 20% and at least 50% (NRS scale) compared to baseline in the PGF group was significantly higher than those in the control group. The PGF group had greater reductions in the total scores of subchondral bone marrow edema, and bone cocoon under cartilage on knee MRI (classification according to WORMs), which were -2.27 (-4.0; -0.51) and -1.77 (-3.08; -0.46), respectively (p â€‹< â€‹0.05). The two groups had no statistically significant difference in knee ultrasound characteristics. After 4 weeks, 12, and 24 weeks compared to baseline, there was no statistically significant difference in levels of urea, creatinine, aspartate aminotransferase, and alanine aminotransferase within the group and between the two study groups. Conclusions: Salmon cartilage PG with 10 â€‹mg per day has potential to improve pain symptoms and subchondral bone marrow edema and bone cocoon under cartilage lesions in primary knee OA. However, the efficacy of PGF should be viewed with caution, and future studies are needed for more specific evaluation.

Pertussis seasonal variation in Northern Vietnam: the evidence from a tertiary hospital.

BACKGROUND: Pertussis is a highly contagious and dangerous respiratory disease that threatens children's health in many countries, including Vietnam, despite vaccine coverage. From 2015 to 2018, Vietnam experienced an increasing number of pertussis patients. Therefore, this study aimed to investigate the trend and examine the seasonal variations of pertussis in North Vietnam. METHODS: Data were collected from medical records of all under-5-year-old inpatients admitted to the National Children's Hospital in Hanoi, Vietnam (VNCH) 2015-2018. A descriptive analysis was performed to describe the distribution of incident cases by year and season. Linear multivariable regression was conducted to investigate the association between the incidence of cases and seasonality adjusted by age and vaccination status. RESULTS: We identified 1063 laboratory-confirmed patients during 2015-2018, including 247 (23.2%) severe patients. The number of pertussis patients admitted to VNCH per 1000 hospitalizations was 3.2 in 2015, compared to 1.9, 3.1, and 2.1 in 2016, 2017, and 2018, respectively. Outbreaks occurred biennially; however, there was no significant difference in the number of severe patients over this period. Most cases occurred in the hot season (509 patients, or nearly half of the study population). With the adjustment of the vaccination rate and average age, the risk of pertussis-associated hospitalization in the mild season and the hot season was 21% (95% CI [0.12; 0.3]) and 15% (95% CI [0.05; 0.25]) higher than that in the warm season, respectively. The rate of hospitalizations was high in the mild season (28.9%) and the warm season (30.8%), nearly twice as much as that in the hot season; nevertheless, the death rate was only striking high in the mild season, about 5-6 times as much as those in the other seasons. CONCLUSION: The pertussis incidence in Northern Vietnam varied between seasons, peaking in the hot season (April-July). However, severe patients and deaths increased in the mild season (December-March). Interventions, for example, communication activities on pertussis and vaccination, are of immense importance in lowering the prevalence of pertussis. In addition, early diagnoses and early warnings performed by health professionals should be encouraged.

Using the WHO Self-Reporting Questionnaire-20 (SRQ-20) to Detect Symptoms of Common Mental Disorders among Pregnant Women in Vietnam: a Validation Study.

Purpose: Detection of antenatal common mental disorders in low-resource settings like Vietnam is important and requires a reliable, valid and practical screening tool. Currently, there is no such tool validated for use among pregnant women in Vietnam. This study aims to assess the validity of the Vietnamese version of the 20-item Self Reporting Questionnaire (SRQ-20) by evaluating its reliability, factorial structure, and performance in detecting common mental disorder (CMD) symptoms, thereby identifying the optimum cut-off score for CMD screening among pregnant women in Vietnam. Participants and Methods: A total of 210 pregnant women from four rural communes participated in a face-to-face interview using the Vietnamese version of the SRQ-20, followed by a clinical diagnostic interview based on ICD-10 diagnostic criteria of CMDs. The reliability of the SRQ-20 was assessed by calculating the scale's Cronbach's alpha to measure internal consistency. Factor analyses were undertaken to examine the factor structure of the instrument. The Receiver Operating Characteristic (ROC) curve analysis was performed to assess the performance of the SRQ-20 against the clinical diagnosis and to identify the optimum cut-off score. Results: Internal consistency was good, with a Cronbach's alpha of 0.87. Factor analyses resulted in a 4-factor solution. The area under the ROC curve (AUC) for detection of CMDs was 0.90. The optimum cut-off score of the SRQ-20 for detection of CMD symptoms among Vietnamese pregnant women was 5/6. Conclusion: The Vietnamese version of the SRQ-20 has the capacity to detect CMDs among pregnant women effectively and is recommended for use as a screening tool for CMDs in antenatal care settings in Vietnam.

Trend of metabolic risk factors among the population aged 25-64 years for non-communicable diseases over time in Vietnam: A time series analysis using national STEPs survey data.

Introduction: The study aims to examine the trends of 4 metabolic NCDs risk factors including raised blood pressure, increased blood glucose, elevated blood lipids and overweight/obesity over the last 10 years in Vietnam as well as examine these trends among different sub-population by geographical area, gender, and age groups. Methods: The study combined the national representative data from three rounds of STEPs survey in Vietnam conducted in 2010, 2015, and 2020 on people aged 25-64 years. The overall prevalence of each metabolic factor together with 95% CI for each time point as well as the stratified prevalence by rural/urban, male/female, and 4 separated age groups were calculated and considered the sampling weight. Cochran-Armitage test for trend was used to test for the differences in the prevalence over time. Results: The prevalence of hypertension, overweight/obesity, hyperglycemia, and hyperlipidemia among the population aged 25-64 years old was 28.3, 20.57, 6.96, and 15.63%, respectively in the year 2020. All NCD metabolic risk factors examined in this analysis show significantly increasing trends over time. For most age groups, the increasing burden of NCD metabolic risk factors was more significant during the period 2015-2020 compared to the period 2010-2015. Male population and population aged 55-64 experienced the most dramatic changes in the burden of all NCD metabolic risk factors. Conclusion: To reverse the increasing trend of NCD metabolic factors in Vietnam, intervention, and policy need to apply a comprehensive life course approach.

The essential role of YAP in ERα36-mediated proliferation and the epithelial-mesenchymal transition in MCF-7 breast cancer cells.

Purpose: Most breast cancers are hormone-receptor-positive, and thus the first-line therapy for them is an anti-estrogen medication such as tamoxifen. If metastasis occurs or resistance to tamoxifen develops, the 5-year survival rates for breast cancer patients significantly decrease. Hence, a better understanding of the molecular mechanisms that contribute to breast cancer aggressiveness is of great importance. ERα36 is an estrogen receptor variant that is known to be upregulated in breast cancer patients receiving tamoxifen treatment or in triple-negative breast cancer cells. However, the specific molecular mechanism underlying ERα36-induced tamoxifen-resistance is not yet fully understood. Methods: ERα36-overexpressing MCF-7 cells were constructed by either plasmid transfection using ERα36 vector or retroviral infection using ERα36-V5-His vector. Target-gene expression was assessed by Western blot analysis and real-time PCR, and YAP activation was evaluated by luciferase assays and immunofluorescence. Cell proliferation and formation of three-dimensional spheroids were evaluated using the IncuCyte S3 Live Cell Analysis System. Results: We found that the expression patterns of Hippo signaling-related genes were significantly changed in ERα36-overexpressing MCF-7 cells compared to MCF-7 cells, which were also similarly observed in tamoxifen-resistant MCF-7 cells. Specifically, the protein expression level and activity of YAP, the core downstream protein of the Hippo pathway, were significantly increased in ERα36-overexpressing MCF-7 cells compared with MCF-7 cells. The aggressive phenotypes acquired by ERα36 overexpression in MCF-7 cells were destroyed by YAP knockout. On this basis, we propose that ERα36 regulates YAP activity by a new mechanism involving Src kinase. Conclusion: Our results suggest that YAP targeting may be a new therapeutic approach to the treatment of advanced breast cancers overexpressing ERα36.

Targeting Cdc20 for cancer therapy.

The Anaphase-Promoting Complex/Cyclosome (APC/C), an E3 ubiquitin ligase, and two co-activators, Cdc20 and Cdh1, enable the ubiquitin-dependent proteasomal degradation of various critical cell cycle regulators and govern cell division in a timely and precise manner. Dysregulated cell cycle events cause uncontrolled cell proliferation, leading to tumorigenesis. Studies have shown that Cdh1 has tumor suppressive activities while Cdc20 has an oncogenic property, suggesting that Cdc20 is an emerging therapeutic target for cancer treatment. Therefore, in this review, we discussed recent findings about the essential roles of APC/C-Cdc20 in cell cycle regulation. Furthermore, we briefly summarized that the regulation of Cdc20 expression levels is strictly controlled to order cell cycle events appropriately. Finally, given the function of Cdc20 as an oncogene, therapeutic interventions targeting Cdc20 activity may be beneficial in cancer treatment.

The adverse impact of excessive internet use during the COVID-19 pandemic on adolescents' coping skills: A case study in Hanoi, Vietnam 2021.

Introduction: The COVID-19 pandemic has created significant stressors in Vietnamese adolescents' lives. Coping skills play important roles in helping adolescents contend with stress. This study aimed to evaluate adolescents' coping skills during the COVID-19 pandemic and examine how those skills are impacted by excessive internet use during this pandemic. Methods: The study used respondent-driven sampling and Google online survey forms to collect data. The study sample included 5,315 high school students aged 11- 17 years in Hanoi's rural and urban areas. The Kid Coping Scale was applied to examine adolescents' coping, and the coping score was compared among adolescents with different levels of internet use. Results: The average coping score measured by Kid Coping Scale was 20.40 (std = 2.13). About half of adolescents often "avoid the problem or the area where it happened" when experiencing a hard time. One-third of adolescents often stopped thinking about the problem they faced. More than one-fourth of respondents stayed online for at least 8 h per day. The online time for learning/other activities showed a reverse dose-response relationship with the coping score; the longer the internet use duration, the lower the coping score. Conclusion: The mean score of coping of Hanoi adolescents was moderate. Internet use has an adverse impact on their coping skills.

Characteristics, in-hospital management, and complications of acute myocardial infarction in northern and Central Vietnam.

INTRODUCTION: Contemporary data on the epidemiology of acute myocardial infarction (AMI) in Vietnam are extremely limited. METHODS: We established population-based registries of residents from 2 provinces in a northern urban (Hai Phong), and a central rural (Thanh Hoa), province of Vietnam hospitalized with a validated first AMI in 2018. We described patient characteristics, in-hospital management and clinical complications, and estimated incidence rates of AMI in these two registries. RESULTS: A total of 785 patients (mean age = 71.2 years, 64.7% men) were admitted to the two hospitals with a validated first AMI. Approximately 64% of the AMI cases were ST-segment-elevation AMI. Patients from Thanh Hoa compared with Hai Phong were more likely to delay seeking acute hospital care. The incidence rates (per 100,000 population) of initial AMI in Thanh Hoa and Hai Phong were 16 and 30, respectively. Most patients were treated with aspirin (Thanh Hoa: 96%; Hai Phong: 90%) and statins (both provinces: 91%) during their hospitalization. A greater proportion of patients in Hai Phong (69%) underwent percutaneous revascularization than those in Thanh Hoa (58%). The most common in-hospital complications were heart failure (both provinces:12%), cardiogenic shock (Thanh Hoa: 10%; Hai phong: 7%); and cardiac arrest (both provinces: 9%). The in-hospital case-fatality rates for patients from Thanh Hoa and Hai Phong were 6.8% and 3.8%, respectively. CONCLUSIONS: The incidence and hospital case-fatality rates of AMI were low in two Vietnamese provinces. Extent of pre-hospital delay and in-hospital use of evidence-based therapies were suboptimal, being more prominent in the rural province.

S1P/S1PR3 signalling axis protects against obesity-induced metabolic dysfunction.

Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid that interacts via 5 G-protein coupled receptors, S1PR1-5, to regulate signalling pathways critical to biological processes including cell growth, immune cell trafficking, and inflammation.We demonstrate that in Type 2 diabetic (T2D) subjects, plasma S1P levels significantly increased in response to the anti-diabetic drug, rosiglitazone, and, S1P levels correlated positively with measures of improved glucose homeostasis. In HFD-induced obese C57BL/6 J mice S1PR3 gene expression was increased in adipose tissues (AT) and liver compared with low fat diet (LFD)-fed counterparts. On a HFD, weight gain was similar in both S1PR3-/- mice and WT littermates; however, HFD-fed S1PR3-/- mice exhibited a phenotype of partial lipodystrophy, exacerbated insulin resistance and glucose intolerance. This worsened metabolic phenotype of HFD-fed S1PR3-/- mice was mechanistically linked with increased adipose inflammation, adipose macrophage and T-cell accumulation, hepatic inflammation and hepatic steatosis. In 3T3-L1 preadipocytes S1P increased adipogenesis and S1P-S1PR3 signalling regulated the expression of PPARγ, suggesting a novel role for this signalling pathway in the adipogenic program. These results reveal an anti-diabetic role for S1P, and, that S1P-S1PR3 signalling in the adipose and liver defends against excessive inflammation and steatosis to maintain metabolic homeostasis at key regulatory pathways.

The plasminogen receptor Plg-RKT regulates adipose function and metabolic homeostasis.

BACKGROUND: Plg-RKT , a unique transmembrane plasminogen receptor, enhances the activation of plasminogen to plasmin, and localizes the proteolytic activity of plasmin on the cell surface. OBJECTIVES: We investigated the role of Plg-RKT in adipose function, metabolic homeostasis, and obesity. METHODS: We used adipose tissue (AT) sections from bariatric surgery patients and from high fat diet (HFD)-induced obese mice together with immunofluorescence and real-time polymerase chain reaction to study adipose expression of Plg-RKT . Mice genetically deficient in Plg-RKT and littermate controls fed a HFD or control low fat diet (LFD) were used to determine the role of Plg-RKT in insulin resistance, glucose tolerance, type 2 diabetes, and associated mechanisms including adipose inflammation, fibrosis, and ectopic lipid storage. The role of Plg-RKT in adipogenesis was determined using 3T3-L1 preadipocytes and primary cultures established from Plg-RKT -deficient and littermate control mice. RESULTS: Plg-RKT was highly expressed in both human and mouse AT, and its levels dramatically increased during adipogenesis. Plg-RKT -deficient mice, when fed a HFD, gained more weight, developed more hepatic steatosis, and were more insulin resistant/glucose intolerant than HFD-fed wild-type littermates. Mechanistically, these metabolic defects were linked with increased AT inflammation, AT macrophage and T-cell accumulation, adipose and hepatic fibrosis, and decreased insulin signaling in the AT and liver. Moreover, Plg-RKT regulated the expression of PPARγ and other adipogenic molecules, suggesting a novel role for Plg-RKT in the adipogenic program. CONCLUSIONS: Plg-RKT coordinately regulates multiple aspects of adipose function that are important to maintain efficient metabolic homeostasis.

The Ubiquitin System: An Emerging Therapeutic Target for Lung Cancer.

The ubiquitin system, present in all eukaryotes, contributes to regulating multiple types of cellular protein processes such as cell signaling, cell cycle, and receptor trafficking, and it affects the immune response. In most types of cancer, unusual events in ubiquitin-mediated signaling pathway modulation can lead to a variety of clinical outcomes, including tumor formation and metastasis. Similarly, ubiquitination acts as a core component, which contributes to the alteration of cell signaling activity, dictating biosignal turnover and protein fates. As lung cancer acquires the most commonly mutated proteins, changes in the ubiquitination of the proteins contribute to the development of lung cancer. Various inhibitors targeting the ubiquitin system have been developed for clinical applications in lung cancer treatment. In this review, we summarize the current research advances in therapeutics for lung cancer by targeting the ubiquitin system.

Ubiquitin-Conjugating Enzymes in Cancer.

The ubiquitin-mediated degradation system is responsible for controlling various tumor-promoting processes, including DNA repair, cell cycle arrest, cell proliferation, apoptosis, angiogenesis, migration and invasion, metastasis, and drug resistance. The conjugation of ubiquitin to a target protein is mediated sequentially by the E1 (activating)‒E2 (conjugating)‒E3 (ligating) enzyme cascade. Thus, E2 enzymes act as the central players in the ubiquitination system, modulating various pathophysiological processes in the tumor microenvironment. In this review, we summarize the types and functions of E2s in various types of cancer and discuss the possibility of E2s as targets of anticancer therapeutic strategies.

Moving to Social Health Insurance Financing and Payment for HIV/AIDS Treatment in Vietnam.

This study estimates the amount antiretroviral therapy (ART) clients paid out of pocket for preventive and treatment services and the percentage of ART clients incurring catastrophic payments during the period when ART services were transitioning from donor funding to domestic social health insurance (SHI) in Vietnam. Using a cross-sectional facility-based survey in 9 provinces, a sample of 582 clients across 18 ART facilities representatives of all facilities where SHI-financed ART was being implemented were interviewed in 2019. Results indicated 13.4% (95% CI: 5.7%, 28.2%) of clients incurred a payment for outpatient ART care. The average out of pocket expenditures for outpatient visits and HIV related outpatient visits was USD $71.2 and $8 per year, respectively. The average out of pocket expenditure for inpatient admission and HIV related inpatient admission was $7.1 and $1.6, respectively. Only 0.1% clients currently experienced HIV-related catastrophic payment at the 25% of total expenditures threshold. The study confirms the transition from donor-financed ART to SHI-financed ART is not causing financial hardship for ART clients. However, more commitment from the Government of Vietnam to strengthen HIV-related services under SHI may be needed in the future, and there is still need to ensure universal SHI coverage among people with HIV/AIDs in Vietnam.

Anxiety Among Inpatients With Cancer: Findings From a Hospital-Based Cross-Sectional Study in Vietnam.

Anxiety, a condition which is commonly found in patients with cancer, has negative impacts on their quality of life and treatment outcome. This study aimed to determine the level of anxiety in patients with cancer and explore sociodemographic, disease-related, and hospital-related factors associated with anxiety in those patients. A cross-sectional study was conducted on 510 inpatients with cancer at Thanh Hoa Oncology Hospital, Vietnam. Data were collected from self-administered questionnaire forms on hospital depression anxiety-A, interviews with patients, and patient medical records. The univariate and multivariate linear regression analyses were performed using STATA ver. 14.0. Our finding that the patients' mean anxiety score (standard deviation) was 7.22 (3.8); 27.6% of the patients had an anxiety score between 8 and 10 points, and 15.5% had an anxiety score of ≥11 points. In the multivariate model, in more advanced stages of cancer, and patients with metastasis were more likely to have higher levels of anxiety than those who presented no sign of metastasis. The longer the patients had cancer, the less anxious they became. Lower levels of anxiety were observed in patients who stated that hospital facilities were adequate or had trust in health workers. Patients with cancer need to be provided with psychological support in the early stage of cancer detection and when metastases form. A strong patient-health-care provider relationship after diagnosis may help reduce distress among patients with cancer with higher levels of medical mistrust.

The evolution of domestic violence prevention and control in Vietnam from 2003 to 2018: a case study of policy development and implementation within the health system.

BACKGROUND: Internationally, mental health and social care systems face significant challenges when implementing policy to prevent and respond to domestic violence (DV). This paper reviews the policy process pertaining to the national law on domestic violence prevention and control (DVPC) within the health system in Vietnam from 2003 to 2018, and critically examines the policy-making process and content, the involvement of key actors and the barriers to implementation within the health system. METHODS: 63 policy documents, 36 key informant interviews and 4 focus group discussions were conducted in Hanoi city, Bac Giang and Hai Duong provinces. The policy triangle framework was used to analyse the development and implementation process of the Law on DVPC. RESULTS: The Vietnamese government developed the law on DVPC in response to the Millennium Development Goals reporting requirements. The development was a top-down process directed by state bodies, but it was the first time that international agencies and civil society groups had been involved in the health policy development process. The major themes that emerged in the analysis include: policy content, policymaking and implementation processes, the nature of actors' involvement, contexts, and mechanisms for policy implementation. Policy implementation was slow and delayed due to implementation being optional, decentralization, socio-cultural factors related especially to sensitivity, insufficient budgets, and insufficient cooperation between various actors within the health system and other related DV support systems. CONCLUSION: The initial development process for DVPC Law in Vietnam was pressured by external and internal demands, but the subsequent implementation within the health system experienced protracted delays. It is recommended that the policy be revised to emphasise a rights-based approach. Implementation would be more effective if monitoring and evaluation mechanisms are improved, the quality of training for health workers is enhanced, and cooperation between the health sector and related actors in the community is required and becomes routine in daily work.

Trajectories of depression in adolescents and young adults in Vietnam during rapid urbanisation: evidence from a longitudinal study.

OBJECTIVES: This paper investigates the trajectories of depression symptoms in adolescents and young adults, and explores factors associated with their depression. METHOD: For each respondent, three waves of data were collected in 2006, 2009 and 2013 from adolescents and young adults aged 10 to 24 years. The modified Center for Epidemiological Studies Depression Scale was used to interview participants, while the generalised estimating equation (GEE) model was used to identify whether certain factors were associated with depression. RESULTS: The mean depression scores in 2006, 2009 and 2013 were 29.76, 30.80 and 30.51 respectively. Compared to boys, girls reported higher initial levels of depressive symptoms. The depression score was found to be highest among adolescents aged 15 to 17 years. Depression among young people was associated with age, gender, marital status, education levels, general health and living location. CONCLUSION: Using longitudinal design, this research demonstrated the different trajectories of depression scores between boys and girls over time and provided evidence for interventions improving adolescent mental health in a semi-urban area of Vietnam.

Home-Based Care and Perceived Quality of Life Among People Living with HIV in Ho Chi Minh City, Viet Nam.

We conducted a cross-sectional study to examine the perceptions of quality of life among people living with HIV who received home-based care services administered through outpatient clinics in Ho Chi Minh City, Viet Nam. Data were collected from a sample of 180 consecutively selected participants (86 cases, 94 controls) at four outpatient clinics, all of whom were on antiretroviral therapy. Quality of life was evaluated using the WHOQOL-BREF instrument. In adjusted analysis, those who received home-based care services had a quality of life score 4.08 points higher (on a scale of 100) than those who did not receive home-based care services (CI 95%, 2.32-5.85; p < 0.001). The findings suggest that home-based care is associated with higher self-perceptions of quality of life among people living with HIV.

Essential Role of Polo-like Kinase 1 (Plk1) Oncogene in Tumor Growth and Metastasis of Tamoxifen-Resistant Breast Cancer.

The most common therapy for estrogen receptor-positive breast cancer is antihormone therapy, such as tamoxifen. However, acquisition of resistance to tamoxifen in one third of patients presents a serious clinical problem. Polo-like kinase 1 (Plk1) is a key oncogenic regulator of completion of G2-M phase of the cell cycle. We assessed Plk1 expression in five chemoresistant cancer cell types and found that Plk1 and its downstream phosphatase Cdc25c were selectively overexpressed in tamoxifen-resistant MCF-7 (TAMR-MCF-7) breast cancer cells. Real-time monitoring of cell proliferation also showed that TAMR-MCF-7 cells were more sensitive to inhibition of cell proliferation by the ATP-competitive Plk1 inhibitor BI2536 than were the parent MCF-7 cells. Moreover, BI2536 suppressed expression of epithelial-mesenchymal transition marker proteins and 3D spheroid formation in TAMR-MCF-7 cells. Using TAMR-MCF-7 cell-implanted xenograft and spleen-liver metastasis models, we showed that BI2536 inhibited tumor growth and metastasis in vivo Our results suggest that Plk1 could be a novel target for the treatment of tamoxifen-resistant breast cancer. Mol Cancer Ther; 17(4); 825-37. ©2018 AACR.

Pharmacy Dashboard: An Innovative Process for Pharmacy Workload and Productivity.

Background: Innovative approaches, including LEAN systems and dashboards, to enhance pharmacy production continue to evolve in a cost and safety conscious health care environment. Furthermore, implementing and evaluating the effectiveness of these novel methods continues to be challenging for pharmacies. Objective: To describe a comprehensive, real-time pharmacy dashboard that incorporated LEAN methodologies and evaluate its utilization in an inpatient Central Intravenous Additives Services (CIVAS) pharmacy. Methods: Long Beach Memorial Hospital (462 adult beds) and Miller Children's and Women's Hospital of Long Beach (combined 324 beds) are tertiary not-for-profit, community-based hospitals that are served by one CIVAS pharmacy. Metrics to evaluate the effectiveness of CIVAS were developed and implemented on a dashboard in real-time from March 2013 to March 2014. Results: The metrics that were designed and implemented to evaluate the effectiveness of CIVAS were quality and value, financial resilience, and the department's people and culture. Using a dashboard that integrated these metrics, the accuracy of manufacturing defect-free products was ≥99.9%, indicating excellent quality and value of CIVAS. The metric for financial resilience demonstrated a cost savings of $78,000 annually within pharmacy by eliminating the outsourcing of products. People and value metrics on the dashboard focused on standard work, with an overall 94.6% compliance to the workflow. Conclusion: A unique dashboard that incorporated metrics to monitor 3 important areas was successfully implemented to improve the effectiveness of CIVAS pharmacy. These metrics helped pharmacy to monitor progress in real-time, allowing attainment of production goals and fostering continuous quality improvement through LEAN work.

Essential role of Notch4/STAT3 signaling in epithelial-mesenchymal transition of tamoxifen-resistant human breast cancer.

We previously demonstrated that tamoxifen (TAM)-resistant human breast cancer (TAMR-MCF-7) cells showed increased expression of mesenchymal marker proteins compared to the parent MCF-7 cells. Notch is functionally important in the promotion of epithelial-mesenchymal transition (EMT) during both development and tumor progression. Notch1 and Notch4 have been reported as prognostic markers in human breast cancer. Here, we indicated that Notch4, but not Notch1, plays a critical role in the regulation of EMT signaling in TAMR-MCF-7 cells. Notch4 suppression by either Notch inhibitors or Notch4 siRNA attenuated EMT signaling. Tyrosine-phosphorylated STAT3 protein is known as a crucial signaling molecule in the regulation of tumorigenesis and metastasis. We found that TAMR-MCF-7 cells exhibited constitutive STAT3 phosphorylation, and Notch inhibition reduced the level of activated STAT3 in TAMR-MCF-7 cells. An intrasplenic injection model of liver metastases was performed using TAMR-MCF-7 cells. Mice injected with N-[N-(3,5-Difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester (DAPT, 10 mg/kg) formed smaller splenic tumors and showed a reduced micrometastatic tumor burden in their livers compared with the control group treated with vehicle. To conclude, Notch4 could be a potential target to prevent metastasis in TAM-resistant breast cancer.