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Nam Nguyen Van,1 Pham Ngoc Hung,2,3 Le Tien Dung,4 Le Viet Anh,1 Dinh Cong Pho,5 Bui Dang The Anh,2 Vu Anh Hai1 1Department of Thoracic Surgery, Military Hospital 103, Vietnam Military Medical University, Hanoi, Vietnam; 2Department of Epidemiology, Vietnam Military Medical University, Hanoi, Vietnam; 3Department of Training, Vietnam Military Medical University, Hanoi, Vietnam; 4Department of Thoracic Surgery, Phạm Ngọc Thạch Hospital, Ho Chi Minh City, Vietnam; 5Department of Infection Control, Military Hospital 103, Vietnam Military Medical University, Hanoi, VietnamCorrespondence: Vu Anh HaiDepartment of Thoracic Surgery, Military Hospital 103, Vietnam Military Medical University, Ha Dong District, Hanoi, VietnamTel +84986112345Email vuanhhai.ncs@gmail.comBackground: Mid-term outcomes of video-assisted thoracoscopic surgery (VATS) lobectomy for early stage non-small cell lung cancer (NSCLC) in Vietnam should be evaluated and discussed.Methods: This prospective descriptive study was conducted on 94 patients with NSCLC under stages I–IIA who were treated with VATS from November 2011 to July 2014.Results: The median patient age was 55.5 ± 10.8 years. The rate of successful VATS for NSCLC treatment was 98.9%, and the conversion rate (from VATS to thoracotomy) was 1.1%. The operative time was 143.8 ± 38.9 minutes, the amount of blood loss was 194.8 ± 150.5 mL, and the postoperative complication rate was 10.6%. The ICU length stay was 2.8 ± 1.0 days, and the postoperative hospital length stay was 7.7 ± 2.1 days. Among the 89 patients with successful follow-up, one (1.1%) had a recurrent tumor, and ten (11.8%) had metastasis. The 1- and 2-year relative survival rates were 95.9% (3 deaths) and 80.8% (9 deaths), respectively.Conclusion: VATS treatment for early stage NSCLC is an effective method with safe outcomes. The mid-term outcomes were acceptable with 1- and 2-year relative survival rates of 95.9% and 80.8%, respectively.Keywords: video-assisted thoracoscopic surgery, VATS, non-small cell lung cancer, NSCLC, early-stage, short-term outcomes, mid-term outcomes

Context: Realist evaluation is increasingly employed in health professions education research (HPER) because it can unpack the extent to which complex educational interventions work (or not), for whom under what circumstances and how. While realist evaluation is not wedded to particular methods, realist interviews are commonly the primary, if not only, data collection method in realist evaluations. While qualitative interviewing from an interpretivist standpoint has been well‐articulated in the HPER literature, realist interviewing differs substantially. The former elicits participants' views and experiences of a topic of inquiry, whereas realist interviewing focuses on building, testing and/or refining programme theory. Therefore, this article aims to help readers better understand, conduct, report and critique realist interviews as part of realist evaluations. Methods: In this paper, we describe what realist approaches are, what realist interviewing is and why realist interviewing matters. We outline five stages to realist interviewing (developing initial programme theory, realist sampling/samples, the interview itself, realist analysis and reporting realist interviews), drawing on two illustrative cases from our own realist evaluations employing interviewing to bring theory to life. We provide a critical analysis of 12 realist evaluations employing interviewing in the HPER literature. Alongside reporting standards, and our own realist interviewing experiences, this critical analysis of published articles serves to foreground our recommendations for realist interviewing. Conclusions: We encourage HPE researchers to consider realist interviews as part of realist evaluations of complex interventions. Our critical analysis reveals that realist interviews can provide unique insights into HPE, but authors now need to report their sampling approach, type of interviewing and interview questions more explicitly. Studies should also more explicitly draw on existing realist interviewing literature and follow reporting guidelines for realist evaluations. We hope this paper provides a useful roadmap to conducting, reporting and critically appraising realist interviews in HPER. Realist interviews are increasing in #MedEd #HPE but how can we better understand, conduct, report & critique them? This work teaches us that @charlreessidhu @KarenMattick @VanNBNguyen @crndvs [ABSTRACT FROM AUTHOR]

The worldwide prevalence of chronic hepatitis C virus (HCV) infection is estimated to be approaching 200 million people (1). Current therapy relies upon a combination of pegylated interferon-a and ribavirin, a poorly tolerated regimen typically associated with less than 50% sustained virological response rate in those infected with genotype 1 virus (2,3). The development of direct-acting antiviral agents to treat HCV has focused predominantly on inhibitors of the viral enzymes NS3 protease and the RNA-dependent RNA polymerase NS5B (4). Here we describe the profile of BMS-790052, a small molecule inhibitor of the HCV NS5A protein that exhibits picomolar half-maximum effective concentrations ([EC.sub.50]) towards replicons expressing a broad range of HCV genotypes and the JFH-1 genotype 2a infectious virus in cell culture. In a phase I clinical trial in patients chronically infected with HCV, administration of a single 100-mg dose of BMS-790052 was associated with a 3.3 [log.sub.10] reduction in mean viral load measured 24 h post-dose that was sustained for an additional 120 h in two patients infected with genotype 1b virus. Genotypic analysis of samples taken at baseline, 24 and 144 h post-dose revealed that the major HCV variants observed had substitutions at amino-acid positions identified using the in vitro replicon system. These results provide the first clinical validation of an inhibitor of HCV NS5A, a protein with no known enzymatic function, as an approach to the suppression of virus replication that offers potential as part of a therapeutic regimen based on combinations of HCV inhibitors., We designed a mechanistically unbiased approach based on chemical genetics to identify chemical starting points for interfering with HCV replication. Our differentiating strategy centred on the identification of compounds functionally [...]

Introduction: Cost studies are increasingly popular given resource constraints. While scholars stress the context‐dependent nature of cost, and the importance of theory, cost studies remain context‐blind and atheoretical. However, realist economic evaluation (REE) privileges context and the testing/refinement of economic programme theory. This preliminary REE serves to test and refine economic programme theory for supervision training programmes of different durations to better inform future programme design/implementation. Methods: Our preliminary REE unpacked how short (half‐day) and extended (12 week) supervision training programmes in Victoria, Australia, produced costs and outcomes. We employed mixed methods: qualitative realist and quantitative cost methods. Economically optimised programme models were developed guided by identified cost‐sensitive mechanisms and contexts. Results: As part of identified context‐mechanism‐outcome configurations (CMOCs) for both training programmes, we found a wider diversity of positive outcomes but greater costs for the extended programme (11 outcomes; AU$3069/learner) compared with the short programme (7 outcomes; $385/learner). We identified four shared cost‐sensitive mechanisms for both programmes (training duration, learner protected time, learner engagement, and facilitator competence) and one shared cost‐sensitive context (learners' supervisory experience). We developed two economically optimised programme models: (1) short programme for experienced supervisors facilitated by senior educators ($406/learner); and (2) extended programme for inexperienced supervisors facilitated by junior educators ($2104/learner). Discussion Our initial economic programme theory was somewhat supported, refuted and refined. Results were partly consistent with previous research, but also extended it through unpacking cost‐sensitive mechanisms and contexts. Although our preliminary REE fills a pressing gap in the methodology literature, conducting REE was challenging given our desire to integrate economic and realist analyses fully, and remain faithful to realist principles. Attention to training duration and experience levels of the facilitator–learner dyad may help to balance the cost and outcomes of training programmes. The authors test and refine economic program theory for supervision training programs of different durations to better inform program design and implementation. [ABSTRACT FROM AUTHOR]

Background Realist Analysis Methods Conclusions Qualitative realist analysis is gaining in popularity in health professions education research (HPER) as part of theory‐driven program evaluation. Although realist approaches such as syntheses and evaluations typically advocate mixed methods, qualitative data dominate currently. Various forms of qualitative analysis have been articulated in HPER, yet realist analysis has not. Although realist analysis is interpretive, it moves beyond description to explain generative causation employing retroductive theorising. Ultimately, it attempts to build and/or ‘test’ (confirm, refute or refine) theory about how, why, for whom, when and to what extent programs work using the context‐mechanism‐outcome configuration (CMOC) heuristic. This paper aims to help readers better critique, conduct and report qualitative realist analysis.We describe four fundamentals of qualitative realist analysis: (1) simultaneous data collection/analysis; (2) retroductive theorising; (3) configurational analysis (involving iterative phases of identifying CMOCs, synthesising CMOCs into demi‐regularities and translating demi‐regularities into program theory); and (4) realist analysis quality (relevance, rigour, richness). Next, we provide a critical analysis of realist analyses employed in 15 HPER outputs—three evaluations and 12 syntheses. Finally, drawing on our understandings of realist literature and our experiences of conducting qualitative realist analysis (both evaluations and syntheses), we articulate three common analysis challenges (coding, consolidation and mapping) and strategies to mitigate these challenges (teamwork, reflexivity and consultation, use of data analysis software and graphical representations of program theory).Based on our critical analysis of the literature and realist analysis experiences, we encourage researchers, peer reviewers and readers to better understand qualitative realist analysis fundamentals. Realist analysts should draw on relevant realist reporting standards and literature on realist analysis to improve the quality and reporting of realist analysis. Through better understanding the common challenges and mitigation strategies for realist analysis, we can collectively improve the quality of realist analysis in HPER. [ABSTRACT FROM AUTHOR]

Abstract: Aims: To describe how clinical nurse educators (CliNEs) in Vietnam are prepared for their role; to identify which preparation strategies assist development of confidence in clinical teaching; and to measure the effect of educational qualifications and professional background on perceived confidence levels. Background: The quality of clinical teaching can directly affect the quality of the student learning experience. The role of the clinical educator is complex and dynamic and requires a period of adjustment for successful role transition to occur. Planned orientation and specific preparation programmes assist transition and reduce anxiety for new CliNEs. There is, however, a lack of clear evidence to identify the form this preparation should take or which strategies are likely to facilitate the development of role confidence. Design: Descriptive survey study. Methods: Cross‐sectional surveys were used to collect data from 334 CliNEs during January–March 2015. Results: Eight preparation methods commonly used in Vietnam were identified. There was a small yet significant association between preparation and CliNEs’ perceived confidence. Formal preparation methods, and postgraduate qualifications and years of clinical teaching experience were linked to increased confidence in clinical teaching. Conversely, informal mentorship was found to hinder confidence development. Conclusions: This study identifies several preparation strategies that significantly enhance clinical educator confidence and readiness for their complex role. These preparation strategies drawn from the Vietnamese context, provide important examples for the wider nursing community to consider. [ABSTRACT FROM AUTHOR]

A medicinal chemistry campaign thatwas conducted to address apotential genotoxic liability associated with an aniline-derived scaffoldin a series of HCV NS5A inhibitors with dual GT-1a/-1b inhibitoryactivity is described. Anilides 3band 3cwere used as vehicles to explore structural modifications that retainedantiviral potency while removing the potential for metabolism-basedunmasking of the embedded aniline. This effort resulted in the discoveryof a highly potent biarylimidazole chemotype that established a potencybenchmark in replicon assays, particularly toward HCV GT-1a, a strainwith significant clinical importance. Securing potent GT-1a activityin a chemotype class lacking overt structural liabilities was a criticalmilestone in the effort to realize the full clinical potential oftargeting the HCV NS5A protein. [ABSTRACT FROM AUTHOR]

The biphenyl derivatives 2and 3areprototypes of a novel class of NS5A replication complex inhibitorsthat demonstrate high inhibitory potency toward a panel of clinicallyrelevant HCV strains encompassing genotypes 1–6. However, thesecompounds exhibit poor systemic exposure in rat pharmacokinetic studiesafter oral dosing. The structure–activity relationship investigationsthat improved the exposure properties of the parent bis-phenylimidazole chemotype, culminating in the identification ofthe highly potent NS5A replication complex inhibitor daclatasvir (33) are described. An element critical to success was therealization that the arylglycine cap of 2could be replacedwith an alkylglycine derivative and still maintain the high inhibitorypotency of the series if accompanied with a stereoinversion, a findingthat enabled a rapid optimization of exposure properties. Compound 33had EC50values of 50 and 9 pM toward genotype-1aand -1b replicons, respectively, and oral bioavailabilities of 38–108%in preclinical species. Compound 33provided clinicalproof-of-concept for the NS5A replication complex inhibitor class,and regulatory approval to market it with the NS3/4A protease inhibitorasunaprevir for the treatment of HCV genotype-1b infection has recentlybeen sought in Japan. [ABSTRACT FROM AUTHOR]

Abstract: In a recent disclosure,1 we described the discovery of dimeric, prolinamide-based NS5A replication complex inhibitors exhibiting excellent potency towards an HCV genotype 1b replicon. That disclosure dealt with the SAR exploration of the peripheral region of our lead chemotype, and herein is described the SAR uncovered from a complementary effort that focused on the central core region. From this effort, the contribution of the core region to the overall topology of the pharmacophore, primarily vector orientation and planarity, was determined, with a set of analogs exhibiting <10nM EC50 in a genotype 1b replicon assay. [Copyright &y& Elsevier]

The worldwide prevalence of chronic hepatitis C virus (HCV) infection is estimated to be approaching 200 million people. Current therapy relies upon a combination of pegylated interferon-α and ribavirin, a poorly tolerated regimen typically associated with less than 50% sustained virological response rate in those infected with genotype 1 virus. The development of direct-acting antiviral agents to treat HCV has focused predominantly on inhibitors of the viral enzymes NS3 protease and the RNA-dependent RNA polymerase NS5B. Here we describe the profile of BMS-790052, a small molecule inhibitor of the HCV NS5A protein that exhibits picomolar half-maximum effective concentrations (EC50) towards replicons expressing a broad range of HCV genotypes and the JFH-1 genotype 2a infectious virus in cell culture. In a phase I clinical trial in patients chronically infected with HCV, administration of a single 100-mg dose of BMS-790052 was associated with a 3.3 log10 reduction in mean viral load measured 24 h post-dose that was sustained for an additional 120 h in two patients infected with genotype 1b virus. Genotypic analysis of samples taken at baseline, 24 and 144 h post-dose revealed that the major HCV variants observed had substitutions at amino-acid positions identified using the in vitro replicon system. These results provide the first clinical validation of an inhibitor of HCV NS5A, a protein with no known enzymatic function, as an approach to the suppression of virus replication that offers potential as part of a therapeutic regimen based on combinations of HCV inhibitors. [ABSTRACT FROM AUTHOR]