Innovation in Chemistry,Manufacturing, and Controls—A Regulatory Perspective From Industry

This review describes the landscape of novel modalities such as cell and gene therapies, viruses, other novel biologics, oligomers, and emerging technologies, including modern analytics. We summarize the regulatory history and recent landmark developments in some major markets and examine specific chemistry, manufacturing, and controls (CMC) challenges, including suggestions for exploration of potential science-based approaches in support of regulatory strategy development from an industry perspective. In addition, we evaluate the economic factors contributing to patient access to innovation and discuss the impact of regulation. There is a desperate need for a consistent form of regulation where global approaches to regulatory strategies can be harmonized, and specific CMC challenges can be dealt with using the appropriate science and risk-based tools. Although these tools are well described in current guidance documents, the specifics of applicability to complex novel modalities can still result in differing regulatory advice and outcomes. The future goals for efficiently regulating innovative modalities and technologies could be aided by more regulatory harmonization, regulatory education, and industry cooperation through consortia, enabling industry to supply key information to regulators in a transparent yet well-defined manner, and utilizing mutually understood risk-benefit analyses to produce drugs with appropriate safety, efficacy, and quality characteristics.     

Influence of using knee sleeve and lateral wedge insole on knee loading among healthy individuals during stair negotiation

BackgroundFor individuals with knee osteoarthritis (OA), stair negotiation is a challenging task and the first task during which they report pain due to the high knee loading required. The use of lateral wedge insole (LWI) has been found to reduce loading in patients with OA but not to reduce pain, whereas the use of knee sleeve has been shown to result in good pain reduction. Understanding the effect of combining LWI and knee sleeve use on healthy individuals before testing on individuals with knee OA is an important step.Research questionThe current study aimed to evaluate the effect of combining the use of LWI and knee sleeve and compare the results with the application of each treatment separately and with the control condition.MethodsThis randomised cross-over study included 17 healthy participants who underwent 3D gait analysis. Participants performed ascending and descending stair activities with the following four treatment conditions: five-degree LWI, off-the-shelf knee sleeve, both LWI and knee sleeve and control condition. External knee adduction moment (EKAM) and knee frontal plane range of motion (ROM) were evaluated as primary outcomes. Repeated measure ANOVA or the Friedman test was selected based on meeting the assumption followed by multiple pairwise comparisons with Bonferroni correction.ResultsIn general, the use of LWI reduced the first peak EKAM significantly (p < 0.001) compared to the control condition in stir ascending (12% reduction) but not in stair descending (p > 0.05). Interestingly, knee sleeve use did not result in any reduction in the first peak EKAM compared to the control or any other condition. However, knee sleeve use led to a significant reduction in the knee frontal plane ROM during stair descending. The combined treatment was not superior to the LWI use when compared to control in the EKAM reduction.SignificanceCombined knee sleeve and LWI use was not superior to LWI use alone in reducing the knee loading, but it may be beneficial for individuals with knee OA since it helped in reduction of the knee frontal plane ROM during stair descending. Importantly, the effect of LWI use or any other treatment must be investigated for each different activity, and the results found in one activity must not be generalised across other activities.     

Predictors of Working Memory Maintenance and Decline in Older Adults

The aging process is associated with the gradual decline of several cognitive functions, and working memory is particularly affected. Although the majority of older adults experience a deterioration of their working memory, some individuals maintain their working memory in older age, and some suffer an extreme deterioration of their working memory. The purpose of the present study was to identify, among a total of 120 potential predictors, those that significantly contributed to these two extreme outcomes in working memory. A sample of 588 healthy adults was examined with the n-back task in the spatial and verbal domains using a 2-back level of difficulty. Individuals were classified as working memory maintainers or decliners if their discrimination level in the two domains was superior to the 80th percentile or inferior to the 20th percentile, respectively. Logistic regression identified eight and six significant predictors of working memory maintenance and decline, respectively. High vocabulary scores and smoking more were significant predictors of working memory maintenance; however, in the opposite direction, these same variables predicted working memory decline. Several consumption habits that influenced cerebrovascular function were found in both models. Psychological traits and everyday activities were present in both models. We identified specific predictors that contribute to extremely high or low working memory performance in older age.     

羟考酮注射液对腹腔镜袖状胃切除术患者血流动力学及镇痛效果的影响

目的探讨羟考酮注射液对腹腔镜袖状胃切除术(LSG)患者血流动力学及镇痛效果的影响。方法随机将2017年10月至2019年10月在我院进行LSG的180例患者分为观察组(n=90,羟考酮)与对照组(n=90,芬太尼)。比较两组血流动力学指标、血糖、Cor及E水平及镇痛效果。结果T0、T1、T2时,观察组的MAP、HR均低于对照组(P<0.05)。术后12 h,两组患者血糖、Cor及E水平均较术前升高,但观察组低于对照组(P<0.05)。术后6、12 h,观察组的VAS评分低于对照组(P<0.05)。结论羟考酮应用于LSG患者镇痛效果好,可减轻应激反应,促进患者血流动力学稳定。     

Metabolic Surgery: Weight Loss,Diabetes, and Beyond

The alarming rise in the worldwide prevalence of obesity is paralleled by an increasing burden of type 2 diabetes mellitus. Metabolic surgery is the most effective means of obtaining substantial and durable weight loss in individuals with obesity. Randomized trials have recently shown the superiority of surgery over medical treatment alone in achieving improved glycemic control, as well as a reduction in cardiovascular risk factors. The mechanisms seem to extend beyond the magnitude of weight loss alone and include improvements in incretin profiles, insulin secretion, and insulin sensitivity. Moreover, observational data suggest that the reduction in cardiovascular risk factors translates to better patient outcomes. This review describes commonly used metabolic surgical procedures and their current indications and summarizes the evidence related to weight loss and glycemic outcomes. It further examines their potential effects on cardiovascular outcomes and mortality and discusses future perspectives.     

The early use of Roux limb as surgical treatment for proximal postsleeve gastrectomy leaks

BackgroundLaparoscopic sleeve gastrectomy (LSG) is thought to be a simpler and safer operation compared with malabsorptive operations that include an enteric anastomosis. Leakage along the staple line at the gastroesophageal junction (GEJ) is difficult to treat and is a known complication of sleeve gastrectomy. Nonsurgical treatment methods often fail to heal the leaks and patients often require conversion to other procedures for definitive treatment. We report our experience with conversion to Roux-en-Y anastomosis over the leak site as a treatment option, comparing patients who had early treatment to late intervention. The purpose of the study is to stress the medical and social benefits of early surgical reintervention with conversion to Roux-en-Y anastomosis over the leak site.MethodsSix patients underwent Roux limb placement over the leak site. Four of the patients had delayed surgery (group A), and the other 2 had early intervention (group B).ResultsPatients in group A had a median increase of all medical cost by 500%, whereas the 2 patients who underwent early intervention (group B) had an increase by 200%. The mean time until complete recovery (removal of all drains, adequate oral intake, and return to normal daily activity) in group A was 131.25 days (range 99–165) versus 38 days (range 28–48) in group B.ConclusionsRoux-en-Y gastrojejunostomy over the leak site is an effective technique to treat refractory staple line leakage and can be adopted as early treatment in selected patients after stabilization, thereby reducing the cost and length of hospital stays.     

Analyzing psychological conditions of field-workers in the construction industry

The Korean construction industry has experienced poor labor productivity and high accident rates. Previous studies have reported that workers’ mental health can cause negative impacts on work performance; thus, enhancing workers’ psychological conditions would help achieve more productive and safer workplaces. This research aimed to understand the level of psychological conditions of construction field-workers using four categories: (1) stress (occupational stress and stress-coping style), (2) personal temperament, (3) emotional disturbance (depression and trait anxiety), and (4) drinking habits. This research used validated questionnaires commonly used in the field of clinical psychology, surveyed 430 respondents from road, bridge, tunnel, subway, and apartment construction sites in Korea, and analyzed the overall psychological tendency of construction workers with the collaboration of professional clinical psychologists using the Z-test, analysis of variance (ANOVA), and cross-tabulation. The research also investigated how the mental conditions differed according to different working conditions, such as demographic information, employment status, work types, work experience, and wage conditions. The results indicated that construction workers suffer from a high level of stress and showed high inclination for problem-focused coping: impulsive, cautious, and dependent on other people. Two out of five construction workers suffer from depression and experience trait anxiety. More seriously, three out of five workers show alcohol-use problems that require clinical attention. This study also revealed the particular psychological problems that occur under different working conditions. The findings can be used to promote the awareness of the importance of construction workers’ mental well-being and to help in setting targets for improvement.