Adjuvant chemotherapy in locally advanced rectal cancer after neo-adjuvant concurrent chemoradiotherapy and surgery: A retrospective study in Vietnamese patients.

Background: Advances in preoperative chemoradiotherapy and surgical techniques offered improvements in rates of locoregional recurrence but did not address distant metastasis. Traditionally, adjuvant chemotherapy has been administered with the goal of limiting systemic recurrences. Objective: Evaluation of the efficacy and safety of adjuvant chemotherapy in patients with locally advanced rectal cancer after preoperative chemoradiotherapy and surgery. Methods: From January 2017 to December 2018, 103 patients diagnosed with clinical stage II or III rectal cancer received adjuvant chemotherapy with capecitabine or XELOX regimens after neoadjuvant concurrent chemoradiotherapy and total mesorectal excision. Overall survival, disease-free survival, and toxicity were analyzed. Results: The median follow-up time was 52.5 months (6.5-66.8 months). The mean 3-year disease-free survival and 3-year overall survival were 86.2% (95% CI: 82.8-89.6) and 92.2% (95% CI: 86.9-97.5), respectively. The rate of hematologic and nonhematologic toxicity was low, mostly grades 1 and 2 including anemia, leucopenia, thrombocytopenia, and liver enzymes elevations were 85.4, 50.5, 42.8, and 45.6%, respectively. Conclusion: The capecitabine and XELOX regimen in adjuvant settings for rectal cancer patients receiving neoadjuvant chemoradiotherapy and surgery was a safe and effective modality. Further randomized trials need to be conducted to evaluate the role of postoperative therapy for these individuals.

The impact of progressive overload on the proportion and frequency of positive cardio-respiratory fitness responders.

The proportion of individuals whose cardio-respiratory fitness change after endurance training does not exceed the test's measurement error can be 40 %. We determined if progressively increasing treadmill run intensity compared to maintaining the same run intensity, improved the responder proportion to a 6-week 20-minute treadmill training regimen. The intervention response standard deviation method estimated the proportion of responders attributable to progressively increasing run intensity. The mixed-effects model demonstrated V̇O2 peak improved significantly more in the progressive versus constant run intensity group. The proportion of V̇O2 peak responses above the smallest worthwhile change attributable to progressively increasing run intensity was 63.6 %.

Efficacy of a Digital Mental Health Biopsychosocial Transdiagnostic Intervention With or Without Therapist Assistance for Adults With Anxiety and Depression: Adaptive Randomized Controlled Trial.

BACKGROUND: Digital mental health (DMH) interventions incorporating elements that adapt to the evolving needs of consumers have the potential to further our understanding of the optimal intensity of therapist assistance and inform stepped-care models. OBJECTIVE: The primary objective was to compare the efficacy of a transdiagnostic biopsychosocial DMH program, with or without therapist assistance for adults with subthreshold symptoms or a diagnosis of anxiety or depression. METHODS: In a randomized adaptive clinical trial design, all participants had access to the DMH program, with eligibility to have their program augmented with therapist assistance determined by program engagement or symptom severity. Participants who met stepped-care criteria were randomized to have their treatment program augmented with either low-intensity (10 min/week of video chat support for 7 weeks) or high-intensity (50 min/week of video chat support for 7 weeks) therapist assistance. A total of 103 participants (mean age 34.17, SD 10.50 years) were assessed before (week 0), during (weeks 3 and 6), and after the intervention (week 9) and at the 3-month follow-up (week 21). The effects of 3 treatment conditions (DMH program only, DMH program+low-intensity therapist assistance, and DMH program+high-intensity therapist assistance) on changes in the 2 primary outcomes of anxiety (7-item Generalized Anxiety Disorder Scale [GAD-7]) and depression (9-item Patient Health Questionnaire [PHQ-9]) were assessed using the Cohen d, reliable change index, and mixed-effects linear regression analyses. RESULTS: There were no substantial differences in the outcome measures among intervention conditions. However, there were significant time effect changes in most outcomes over time. All 3 intervention conditions demonstrated strong and significant treatment effect changes in GAD-7 and PHQ-9 scores, with absolute Cohen d values ranging from 0.82 to 1.79 (all P<.05). The mixed-effects models revealed that, in the Life Flex program-only condition at week 3, mean GAD-7 and PHQ-9 scores significantly decreased from baseline by 3.54 and 4.38 (all P<.001), respectively. At weeks 6, 9, and 21, GAD-7 and PHQ-9 scores significantly decreased from baseline by at least 6 and 7 points (all P<.001), respectively. Nonresponders at week 3 who were stepped up to therapist assistance increased program engagement and treatment response. At the postintervention time point and 3-month follow-up, 67% (44/65) and 69% (34/49) of the participants, respectively, no longer met diagnostic criteria for anxiety or depression. CONCLUSIONS: The findings highlight that early detection of low engagement and non-treatment response presents an opportunity to effectively intervene by incorporating an adaptive design. Although the study findings indicate that therapist assistance was no more effective than the DMH intervention program alone for reducing symptoms of anxiety or depression, the data highlight the potential influence of participant selection bias and participant preferences within stepped-care treatment models. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12620000422921; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=378317&isReview=true. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/45040.

The relationship between team dynamics with healthcare coordination and clinical work satisfaction among Commune Health Workers: A Bayesian model averaging study.

OBJECTIVE: To determine the relationship between team dynamics with healthcare coordination and clinical job satisfaction of the community health workers (CHWs). METHODS: A cross-sectional study was conducted among 133 health workers (including doctors, nurses, or midwives) at 21 Commune Health Cent in Quoc Oai District, Vietnam, from July 2015 to May 2017. A self-administered questionnaire consisting of 5-Likert items regarding team dynamics and healthcare coordination clinical work satisfaction was utilised. Descriptive statistics and correlation matrix were applied for seven factors of team dynamic, clinical work satisfaction, and patient care coordination queried by primary care providers. Bayesian model averaging (BMA) was used to identify the predictors of the level of team dynamics and healthcare coordination. RESULTS: The mean score of overall team dynamics among the study participants was 4.08. Clinical work satisfaction and patient care coordination scores among resident physicians were higher than those of attending clinicians; however, the differences were not statistically significant. The results of BMA analysis indicated that team dynamics significantly associated with clinical work satisfaction, and it explains 9% of the total variance in clinical work satisfaction. Team dynamics level was also positively associated with patient care coordination. Patient care coordination was not a significant mediator between team dynamics and clinical work satisfaction. CONCLUSION: Team dynamics is a potential contributor to improving patient care coordination and clinical job satisfaction of CHWs. As no significant correlation between patient care coordination and clinical job satisfaction was observed, to improve team performance, providing conditions that facilitate team building and teamwork should be conducted for CHWs in CHCs.

Translation, validation and psychometric properties of Effort-Reward Imbalance questionnaire among nurses in Vietnam.

We translated the Effort-Reward imbalance questionnaire, an instrument for measuring work stress, into the Vietnamese language and investigated its psychometric properties among nurses in Vietnam. In a hospital-based cross-sectional study design, we sampled and interviewed 207 nurses working full-time (response rate 83%). We evaluated the internal consistency using standardized Cronbach's alpha coefficients and structural validity using confirmatory factor analysis. Discriminative validity was assessed by comparing the measured scores between age groups, gender, education levels, income groups, and job positions. In addition, we confirmed the criterion validity by investigating its association with self-reported health using simple and multiple logistic regression models. Most of the participants were female (73.3%), young (average 28.5 years old), and had education levels of college or higher (53.5%). We observed sufficient internal consistency in effort, reward, and over-commitment scales (Cronbach's alpha 0.80, 0.76, and 0.68, respectively). Confirmatory factor analysis of the three-factor hierarchical model showed an acceptable fit and fair construct validity with most moderate or stronger (>0.3) factor loading coefficients. Poor self-rated health was more likely in respondents in both Effort-Reward ratio's middle tertile (adjusted Odd-Ratio = 2.80, p-value = 0.031) and highest tertile (adjusted Odd-Ratio = 2.64, p-value = 0.05), adjusting for age, gender, and education levels. The Effort-reward imbalance scale has adequate reliability and validity for assessing work stress among nurses in Vietnam. Its significant association with poor self-rated health warrants further investigation. The validated instrument can help measure the effort-reward imbalance to manage better work-related emotional strains and mental health issues among nurses and ensure human resources' stability in healthcare in Vietnam.

The COVID-19 pandemic in Australia: Public health responses, opportunities and challenges.

In responding to the COVID-19 pandemic, each country is presented with both opportunities and challenges, some unique and some shared with the global community. It is important to not only recognize, but to embrace them as drivers of the public to the current pandemic success. In this commentary, we discuss the opportunities and challenges that may affect ongoing public health programming in Australia within the current context of epidemiology. COVID-19 within Australia has to date been effectively suppressed through the implementation of nationally coordinated, in which the state delivered public policy, guidelines and practice, and successful establishment of a comprehensive testing, contact tracing, patient isolation and contact quarantine regime combined with national and state social distancing, hygiene etiquette and movement restrictions. However, despite its success to date great challenges lay ahead for future public health policy with the threat of a second wave, or more likely, multiple smaller outbreaks across various population centres. Therefore, policies that aim to balance the twin socioeconomic and health impacts are crucial. The experience of Australia in managing its COVID-19 response can provide a case study for other countries to reshape or adapt their policies and actions in the context of emerging global health crises.

Targeting of antithrombin in hemophilia A or B with investigational siRNA therapeutic fitusiran-Results of the phase 1 inhibitor cohort.

BACKGROUND: Fitusiran, an investigational small interfering RNA therapy, reduces antithrombin production to rebalance hemostasis in people with hemophilia A or B, with or without inhibitors. OBJECTIVES: To evaluate the safety and efficacy of fitusiran treatment for people with moderate/severe hemophilia A or B with inhibitors. PATIENTS/METHODS: In this open-label phase 1, part D study, 17 males with hemophilia A or B with inhibitors received three once-monthly subcutaneous injections of fitusiran 50 mg (n = 6) or 80 mg (n = 11); followed for up to 112 days. Endpoints included safety (primary), pharmacokinetics/pharmacodynamics (secondary), annualized bleeding rate, and patient-reported outcomes (exploratory). RESULTS: The most common adverse event was injection site erythema (n = 8). No thrombotic events were reported. At nadir, mean (standard error of the mean [SEM]) antithrombin activity decreased from baseline by 82.0% (2.2) and 87.4% (0.7) in the 50 mg and 80 mg groups, respectively. Antithrombin reduction was associated with increased thrombin generation. 11/17 (64.7%) participants had no bleeds during the observation period (mean [standard deviation] 69.4 [16.3] days). Mean (SEM) changes from baseline in Haemophilia Quality of Life Questionnaire for Adults total (-9.2 [2.9]) and physical health (-12.3 [3.9]) domain scores suggested clinically meaningful improvement. CONCLUSIONS: Monthly fitusiran was generally well tolerated, lowered antithrombin levels from baseline, and resulted in improved thrombin generation. These preliminary results suggest that monthly fitusiran treatment may reduce bleeding episodes and improve quality of life in participants with hemophilia A or B with inhibitors.

Changes in, and predictors of, quality of life among patients with unstable angina after percutaneous coronary intervention.

RATIONALE, AIMS AND OBJECTIVES: Changes in, and predictors of, quality of life (QoL) among unstable angina patients are informative for both clinical and public health practice. However, there is little research on this topic, especially in health care settings with limited resources. This study aims to detect changes in QoL and its associated factors among patients with unstable angina after percutaneous coronary intervention. METHODS: A longitudinal design was conducted with two repeated rounds of measurements, 1 and 3 months after intervention, using the generic SF-36 questionnaire, in 120 patients from Vietnam National Heart Institute. A linear mixed-effects model was used to assess changes in patient QoL over time while adjusting for other covariates. RESULTS: Only two out of eight QoL subscales (social functioning and emotional well-being) declined after 1 month, but these tended to rise again after 3 months, while scores of all other QoL subscales increased. Adjusting for covariates, QoL increased slightly after 1 month of intervention (ß = 0.65, 95%CI = -0.86 to 2.16) but improved by almost six QoL points after 3 months (ß = 5.99, 95%CI = 4.48 to 7.50). Four confounders significantly associated with a decline in QoL were older age, being retired, living in rural areas, and having abnormal troponin level. CONCLUSION: QoL of the patients with unstable angina improves significantly 3 months after intervention, rather than after 1 month. More attention should be given to patients, who are old, retired, live in rural areas and have abnormal troponin level.

Traphanoside GO1, a new triterpenoid saponin from the aerial parts of Glinus oppositifolius with the inhibitory effect on PGE2 production in LPS-induced HepG2 cells.

A new saponin, 3-O-[α-ʟ-rhamnosyl-(1→3)-ß-D-glucopyranosyl]-28-O-ß-D-glucopyranosyl serjanic acid (Traphanoside GO1, 11) along with eleven compounds (1-10 and 12) were isolated from the aerial parts of Glinus oppositifolius. The structures of all isolates were elucidated by analyzing extensive 1 D- and 2 D-NMR and HR-ESI-MS, comparing with reported literature data. Compounds 7-8, 10-11, and 90% ethanol extract (GOE90) were evaluated for the inhibitory effect on PGE2 production from activated HepG2 cells. Among these, new compound 11 showed the most potent inhibitory activity by suppressing LPS-induced PGE2 production on the HepG2 cells.

An adaptive model of health system organization and responses helped Vietnam to successfully halt the Covid-19 pandemic: What lessons can be learned from a resource-constrained country.

Coping with the COVID-19 pandemic has been painful and no single model for such a purpose is perfect. However, sharing experiences is the best way for countries to learn real-time lessons and adapt to this rapidly changing pandemic. This commentary shares with the international community how an adaptive model of health system organization and responses helped Vietnam to break transmission of coronavirus. We find that an effective model is adaptive to time and context, and mobilizes and engages the wider society. We identify merging of different health system units into Center for Diseases Controls as a health system organization that saved massive resources. The early establishment of a formal committee responding to the pandemic helped unify every public health strategy. The mobilization of different stakeholders and communities added resources and facilitated a synchronous implementation of response strategies, even where those strategies involved significant personal or financial sacrifice. National training on Covid-19 treatment for healthcare professionals across the entire hospital system was useful to expand the health service availability. Quickly published response guidelines helped to activate every level of the health system and involve every sector of society. A strategy of keeping high alert and preemptive action is also essential for coping with the pandemic.

Thrombin generation in plasma of patients with haemophilia A and B with inhibitors: Effects of bypassing agents and antithrombin reduction.

Antithrombin (AT) reduction has been shown to improve thrombin generation (TG) in haemophilia with or without inhibitors. As treatment with bypassing agents (BPAs) may be required in patients with breakthrough bleeding while receiving AT-lowering therapy, we assessed TG in platelet-poor plasma samples from haemophilia patients in the presence of BPA (recombinant activated factor VII [rFVIIa; 1.25 or 2.5 µg mL-1] or activated prothrombin complex concentrate [aPCC; 0.5 or 1 U mL-1]) and AT reduction (anti-AT antibody). Mean ± SEM baseline peak thrombin height was 19.9 ± 4.3 nM in plasma from haemophilia patients (n = 12) and 230.5 ± 9.8 nM in healthy males (n = 24). Reduced AT improved mean peak thrombin height in haemophilia patient plasma to 75.4 ± 17.4 nM. Spiking of 90% AT-reduced haemophilia patient plasma with 2.5 µg mL-1 rFVIIa or 1 U mL-1 aPCC increased the mean peak thrombin height to 82.5 ± 12 nM and 134.8 ± 18.7 nM, respectively. Peak thrombin levels did not exceed the range for healthy volunteers when plasma samples from haemophilia patients with in vitro AT reduction were treated with BPAs, suggesting the potential use of BPAs in conjunction with AT reduction. Further clinical investigations are needed to confirm the safety of this approach.

Balancing Bulkiness in Gold(I) Phosphino-triazole Catalysis.

The syntheses of a series of 1-phenyl-5-phosphino 1,2,3-triazoles are disclosed, within which, the phosphorus atom (at the 5-position of a triazole) is appended by one, two or three triazole motifs, and the valency of the phosphorus(III) atom is completed by two, one or zero ancillary (phenyl or cyclohexyl) groups respectively. This series of phosphines was compared with tricyclohexylphosphine and triphenylphosphine to study the effect of increasing the number of triazoles appended to the central phosphorus atom from zero to three triazoles. Gold(I) chloride complexes of the synthesised ligands were prepared and analysed by techniques including single-crystal X-ray diffraction structure determination. Gold(I) complexes were also prepared from 1-(2,6-dimethoxy)-phenyl-5-dicyclohexyl-phosphino 1,2,3-triazole and 1-(2,6-dimethoxy)-phenyl-5-diphenyl-phosphino 1,2,3-triazole ligands. The crystal structures thus obtained were examined using the SambVca (2.0) web tool and percentage buried volumes determined. The effectiveness of these gold(I) chloride complexes to serve as precatalysts for alkyne hydration were assessed. Furthermore, the regioselectivity of hydration of but-1-yne-1,4-diyldibenzene was probed.

Knowledge and Determinants of Health Consequences of Cigarette Smoking Among Vietnamese Adults, 2015.

Background. Vietnam was one of 16 countries that implemented the second round of the GATS (Global Adult Tobacco Survey) in 2015. Aims. To assess knowledge and determinants of health consequences of different types of cigarette smoking among Vietnamese adults. Methods. A cross-sectional study among adults aged 15 years combined with using 15% of the master sample from the national sampling frame of the population and housing census was conducted. Multilevel analysis using Poisson regression was undertaken. Results. Knowledge on the health consequences of cigarette smoking has not significantly improved in the GATS-2015. Adults believe that active smoking had more of an impact on health than secondhand smoking and 24.5% and 43% of them answered that smoking light and e-cigarettes, respectively, causes less harm than regular cigarettes, and 17.3% and 18.1% of adults are not aware of the difference between them, respectively. Conclusion. Household and community's role had little impact in the adult knowledge of smoking health consequences. It is necessary to disseminate information on the "other tobacco product" and to improve public knowledge on specific health consequences, to enhance household and community's role in conveying health education messages to individuals.

A cell cycle-coordinated Polymerase II transcription compartment encompasses gene expression before global genome activation.

Most metazoan embryos commence development with rapid, transcriptionally silent cell divisions, with genome activation delayed until the mid-blastula transition (MBT). However, a set of genes escapes global repression and gets activated before MBT. Here we describe the formation and the spatio-temporal dynamics of a pair of distinct transcription compartments, which encompasses the earliest gene expression in zebrafish. 4D imaging of pri-miR430 and zinc-finger-gene activities by a novel, native transcription imaging approach reveals transcriptional sharing of nuclear compartments, which are regulated by homologous chromosome organisation. These compartments carry the majority of nascent-RNAs and active Polymerase II, are chromatin-depleted and represent the main sites of detectable transcription before MBT. Transcription occurs during the S-phase of increasingly permissive cleavage cycles. It is proposed, that the transcription compartment is part of the regulatory architecture of embryonic nuclei and offers a transcriptionally competent environment to facilitate early escape from repression before global genome activation.

Phosphino-Triazole Ligands for Palladium-Catalyzed Cross-Coupling.

Twelve 1,5-disubtituted and fourteen 5-substituted 1,2,3-triazole derivatives bearing diaryl or dialkyl phosphines at the 5-position were synthesized and used as ligands for palladium-catalyzed Suzuki-Miyaura cross-coupling reactions. Bulky substrates were tested, and lead-like product formation was demonstrated. The online tool SambVca2.0 was used to assess steric parameters of ligands and preliminary buried volume determination using XRD-obtained data in a small number of cases proved to be informative. Two modeling approaches were compared for the determination of the buried volume of ligands where XRD data was not available. An approach with imposed steric restrictions was found to be superior in leading to buried volume determinations that closely correlate with observed reaction conversions. The online tool LLAMA was used to determine lead-likeness of potential Suzuki-Miyaura cross-coupling products, from which 10 of the most lead-like were successfully synthesized. Thus, confirming these readily accessible triazole-containing phosphines as highly suitable ligands for reaction screening and optimization in drug discovery campaigns.

Risks for HIV infection among male street laborers in urban Vietnam.

Risks for HIV infection remain unknown in male street laborers. This research investigates patterns of self-reported risk behaviors among these men in urban Vietnam. In a cross-sectional survey using a social mapping technique, 450 men, mostly low-skilled and unregistered migrant laborers across 13 districts in Hanoi were approached for interviews. The study revealed that male street laborers were at high risk of acquiring and transmitting HIV. One in every 12 men reported homosexual or bisexual behavior. These men on average had three sexual partners within the preceding year, and condom use was inconsistent. Close to 95 % of the men had reported sexual encounters with regular partners. One-third with commercial sex workers (CSW) and 24.2 % with casual partners, but just under one-third had ever used condoms with regular partners and CSWs and very few (17.6 %) with casual partners at their last sexual encounter. 17.11 % used illicit drugs sometimes, with 66.7 % of them frequently sharing injecting equipment with peers. These men had limited HIV knowledge; 51.4 % incorrectly believed that, once you trust your partner, you no longer need to use condoms and 42.4 % believed that you can tell by looking at someone if they have HIV. Access to HIV prevention was also limited; only 19.8 % of men had been tested for HIV during the previous 12 months, almost 10 % of whom neither returned for the result nor knew their HIV status. The study provides interesting directions for future research and suggests ways to effectively design prevention strategies for these men.