Justifying Clinical Deception: Some Amendments to Brummett and Salter

In Abram Brummett and Erica K. Salter's excellent paper, “Mapping the Moral Terrain of Clinical Deception,” they rightly note that it is sometimes ethically appropriate for health care professionals to deceive patients and families. However, they also note that because doing so violates a prima facie duty of honesty, the ethical burden of proof falls upon the deceiver. Hence, they also provide a sophisticated framework for determining whether any given case is warranted. I applaud their overall approach but also critique some of their claims, in particular, their conclusion that lies of commission require greater justification than those of omission and their conflation of the principles of beneficence and nonmaleficence. I also urge them to give greater attention to how power asymmetries should be accounted for and to the impact such deceptive choices might have on the clinician's character.     

Phase 1/2 clinical trial of COVID-19 vaccine in Japanese participants: A report of interim findings

We initiated a randomized, placebo-controlled, phase 1/2 trial to evaluate the safety and immunogenicity of the S-268019-b recombinant protein vaccine, scheduled as 2 intramuscular injections given 21 days apart, in 60 randomized healthy Japanese adults. We evaluated 2 regimens of the S-910823 antigen (5 μg [n = 24] and 10 μg [n = 24]) with an oil-in-water emulsion formulation and compared against placebo (n = 12). Reactogenicity was mild in most participants. No serious adverse events were noted. For both regimens, vaccination resulted in robust IgG and neutralizing antibody production at days 36 and 50 and predominant T-helper 1-mediated immune reaction, as evident through antigen-specific polyfunctional CD4+ T-cell responses with IFN-γ, IL-2, and IL-4 production on spike protein peptides stimulation. Based on the interim analysis, the S-268019-b vaccine is safe, produces neutralizing antibodies titer comparable with that in convalescent serum from COVID-19-recovered patients. However, further evaluation of the vaccine in a large clinical trial is warranted.     

Contemporary Management of Ischemic Mitral Regurgitation at Coronary Artery Bypass Grafting

BackgroundRecent guidelines for the treatment of moderate or severe ischemic mitral regurgitation (IMR) in patients undergoing coronary artery bypass grafting (CABG) have changed. This study assessed the real-world impact of changing guidelines on the management of IMR during CABG over time. We hypothesized that the utilization of mitral valve repair for IMR would decrease over time, whereas mitral valve replacement for severe IMR would increase.MethodsPatients undergoing CABG in a statewide collaborative database (2011-2020) were stratified by severity of IMR. Trends in mitral valve repair or replacement were evaluated. To account for differences of the patients, propensity score–matched analyses were used to compare patients with and without mitral intervention.ResultsA total of 11,676 patients met inclusion criteria, including 1355 (11.6%) with moderate IMR and 390 (3.3%) with severe IMR. The proportion of patients undergoing mitral intervention for moderate IMR decreased over time (2011, 17.7%; 2020, 7.5%; P_trend = .001), whereas mitral replacement for severe IMR remained stable (2011, 11.1%; 2020, 13.3%; P_trend = .14). Major morbidity was higher for patients with moderate IMR who underwent mitral intervention (29.1% vs 19.9%; P = .005). In a propensity analysis of 249 well-matched pairs, there was no difference in major morbidity (29.3% with mitral intervention vs 23.7% without; P = .16) or operative mortality (1.2% vs 2.4%; P = .5).ConclusionsConsistent with recent guideline updates, patients with moderate IMR were less likely to undergo mitral repair. However, the rate of replacement for severe IMR did not change. Mitral intervention during CABG did not increase operative mortality or morbidity.     

Trends of self-reported non-adherence among type 2 diabetes medication users in the United States across three years using the self-reported Medication Adherence Reasons Scale

Background & aimsTo determine the trends of self-reported non-adherence rates among adults taking Type 2 medicines (T2D) medicines between 2017 and 2019 and to identify the patterns for the frequently reported reasons for non-adherence in the United States.Methods & resultsData from the National Health and Wellness Survey, a self-administered, internet-based cross-sectional survey of US adults from 2017 to 2019 was used. Non-adherence was measured using the self-reported Medication Adherence Reasons Scale (MAR-Scale). Frequencies were used to identify the reasons for non-adherence for insulin and non-insulin therapies for T2D.Data were obtained from 2983 respondents in 2017, 5416 in 2018, and 5268 in 2019. Based on the MAR-Scale, the self-reported medication non-adherence rate was 25% in 2017, 21% in 2018, and 27% in 2019. The most common reason for non-adherence across all the three years was simple forgetfulness, yet patients reported the lowest mean number of days missing medication for that reason. Though less frequently reported, non-adherence lasted longer when patient did not know how to take their medicines, cost was a reason, or had concerns about the long term effects of the medicines.ConclusionsWith no significant improvement in adherence with T2D medicines over time, regardless of better awareness and extensive diabetes education, focus should be on individualized non-adherence reasons-based interventions.     

FDA“治疗等效性评价供企业用指导原则”（草案）介绍

美国食品药品管理局（FDA）于2022年7月发布了"治疗等效性评价供企业用指导原则"（草案）。该指导原则阐明了FDA治疗等效性的标准以及治疗等效性编码系统，目的是准确评价仿制药与参比制剂的治疗等效性并通过治疗等效性代码，在"橙皮书"中迅速检索到治疗等效的仿制药。而中国目前尚无类似的指导原则，详细介绍FDA该指导原则主要内容，期望对中国加强仿制药的治疗等效性评价和加速完善和实施符合国情的治疗等效性编码系统有所帮助。     

异牡荆素对非小细胞性肺癌细胞自我更新和凋亡的影响

目的研究异牡荆素(ISO)对非小细胞性肺癌(NSCLC)细胞的影响和潜在的机制。方法将A549和H1650细胞分别分为空白组、低剂量实验组(4μmol·L^-1 ISO)和高剂量实验组(16μmol·L^-1 ISO)。用噻唑蓝法检测NSCLC细胞活性,用肿瘤球形成实验检测NSCLC细胞的细胞球形成率,用Western blot法检测NSCLC细胞凋亡、自我更新、无翅型MMTV整合位点家族/β-连环蛋白(Wnt/β-catenin)信号通路相关蛋白的表达水平。结果与空白组比较,低、高剂量实验组中A549和H1650细胞在24,48和72 h的细胞活性均显著降低。低、高剂量实验组和空白组中A549细胞的细胞球形成率分别为(4.18±0.45)%,(2.01±0.67)%和(6.02±0.57)%,切割的半胱氨酸蛋白酶-3相对表达量分别为0.24±0.08,1.25±0.13和0.06±0.07,SRY相关高迁移率族盒蛋白-2相对表达量分别为0.49±0.04,0.25±0.03和1.00±0.09,Kruppel样因子4相对表达量分别为0.68±0.04,0.44±0.03和1.01±0.06,Wnt1相对表达量分别为0.63±0.06,0.28±0.04和1.00±0.06,β-catenin相对表达量分别为0.41±0.05,0.22±0.03和1.01±0.09;与空白组比较,低、高剂量实验组中A549细胞的上述指标的差异均有统计学意义(P<0.05,P<0.01)。上述3组中H1650细胞的上述指标也呈现一致的现象。结论ISO可能通过抑制Wnt/β-catenin信号通路来抑制NSCLC细胞活性和自我更新,并促进其凋亡。     

Process evaluation of implementation strategies to reduce potentially inappropriate medication prescribing in older population: A scoping review

ObjectivesSeveral implementation strategies can reduce potentially inappropriate medication (PIM) prescribing. Although use of PIMs has declined in recent years, it remains prevalent. Various strategies exist to improve the appropriateness of medication use. However, little is known about the processes of these different implementation strategies. This scoping review aims to investigate how the process evaluation of implementation strategies for reducing PIM prescribing in the older population has been studied.MethodsWe searched for process evaluations of implementation strategies for reducing PIM prescribing in PUBMED, SCOPUS and Web of Science published between January 2000 and November 2019 in English. We applied the following inclusion criteria: patients aged ≥65 years, validated PIM criteria, and implementation process evaluated. The review focuses on decision support for health care professionals. We described the findings of the process evaluations, and compared the authors’ concepts of process evaluation of the included publications to those of Proctor et al.( 2010).ResultOf 9131 publications screened, 29 met our inclusion criteria. Different process evaluation conceptualizations were identified. Most process evaluations took place in the initial stages of the process (acceptability, adoption, appropriateness, and feasibility) and sustainability and implementation costs were seldom evaluated. None of the included publications evaluated fidelity.Multifaceted interventions were the most studied implementation strategies. Medication review was more common in acceptability evaluations, multidisciplinary interventions in adoption evaluations, and computerized systems and educational interventions in feasibility evaluations. Process evaluations were studied from the health care professionals’ viewpoint in most of the included publications, but the management viewpoint was missing.DiscussionThe conceptualization of process evaluation in the field of PIM prescribing is indeterminate. There is also a current gap in the knowledge of sustainability and implementation costs. Clarifying the conceptualization of implementation process evaluation is essential in order to effectively translate research knowledge into practice.     

Pure laparoscopic living donor liver transplantation: Dreams come true

Minimally invasive approaches are increasingly being applied in surgeries and have recently been used in living donor hepatectomy. We have developed a safe and reproducible method for minimally invasive living donor liver transplantation, which consists of pure laparoscopic explant hepatectomy and pure laparoscopic implantation of the graft, which was inserted through a suprapubic incision. Pure laparoscopic explant hepatectomy without liver fragmentation was performed in a 60-year-old man with alcoholic liver cirrhosis and hepatocellular carcinoma. The explanted liver was retrieved through a suprapubic incision. A modified right liver graft, procured from his 24-year-old son using the pure laparoscopic method, was inserted through a suprapubic incision, and implantation was performed intracorporeally throughout the procedure. The time required to remove the liver was 369 min, and the total operative time was 960 min. No complications occurred during or after the surgery. The patient recovered well, and his hospital stay was of 11 days. Pure laparoscopic living donor liver transplantation from explant hepatectomy to implantation was performed successfully. It is a feasible procedure when performed by a highly experienced surgeon and transplantation team. Further studies with larger sample sizes are needed to confirm its safety and feasibility.