Good clinical research practice (GCRP) in pharmacodynamic studies of neuromuscular blocking agents III: The 2023 Geneva revision

The set of guidelines for good clinical research practice in pharmacodynamic studies of neuromuscular blocking agents was developed following an international consensus conference in Copenhagen in 1996 (Viby-Mogensen et al., Acta Anaesthesiol Scand 1996, 40 , 59–74); the guidelines were later revised and updated following the second consensus conference in Stockholm in 2005 (Fuchs-Buder et al., Acta Anaesthesiol Scand 2007, 51 , 789–808). In view of new devices and further development of monitoring technologies that emerged since then, (e.g., electromyography, three-dimensional acceleromyography, kinemyography) as well as novel compounds (e.g., sugammadex) a review and update of these recommendations became necessary. The intent of these revised guidelines is to continue to help clinical researchers to conduct high-quality work and advance the field by enhancing the standards, consistency, and comparability of clinical studies. There is growing awareness of the importance of consensus-based reporting standards in clinical trials and observational studies. Such global initiatives are necessary in order to minimize heterogeneous and inadequate data reporting and to improve clarity and comparability between different studies and study cohorts. Variations in definitions of endpoints or outcome variables can introduce confusion and difficulties in interpretation of data, but more importantly, it may preclude building of an adequate body of evidence to achieve reliable conclusions and recommendations. Clinical research in neuromuscular pharmacology and physiology is no exception.     

Methodological advances in the design of peptide-based vaccines

The tremendous advances in genomics, recombinant DNA technology, bioengineering and nanotechnology, in conjunction with the development of high-end computations, have been instrumental in the process of rational design of peptide-based vaccines. The use of peptide vaccines was limited owing to their inherent instability when systemically administered; however, advanced formulation techniques have been developed for their systemic delivery, thereby overcoming their degradation, clearance, cellular uptake and off-target effects. With the rise of sophisticated immunological predictors and experimental techniques, several methodological advances have occurred in this field. This review examines contemporary methods to identify and optimize epitopes, engineer their immunogenic properties and develop their safe and efficient delivery into the host.     

Overview of Recognition and Prevention of Child Sex Trafficking in the Primary Care Setting: A Primer for Nurse Practitioners

Child sex trafficking (CST) has become a global public health crisis and is a $150 billion criminal enterprise. Nurse practitioners are key in the recognition and prevention of CST in health care settings. Evidence demonstrates that up to 80% of CST victims have had a recent health care encounter. It is the role of the NP in practice to understand risk factors, screen for CST, and educate parents and caregivers on signs of victimization and prevention.     

Safety and immunogenicity of NVX-CoV2373 (TAK-019) vaccine in healthy Japanese adults: Interim report of a phase I/II randomized controlled trial

BackgroundWe evaluated the safety and immunogenicity of NVX-CoV2373, a recombinant SARS-CoV-2 nanoparticle vaccine, in healthy Japanese participants.MethodsThis phase 1/2, randomized, observer-blind, placebo-controlled trial conducted in Japan (two sites), enrolled healthy Japanese adults aged ≥ 20 years with no history/risk of SARS-CoV-2 infection and no prior exposure to other approved/investigational SARS-CoV-2 vaccines or treatments. Participants were stratified by age (< 65 or ≥ 65 years) and randomized to receive two doses of either NVX-CoV2373 (5 μg SARS-CoV-2 rS; 50 μg Matrix-M1) or placebo, 21 days apart. Primary outcomes were safety and immunogenicity assessed by serum IgG antibody levels against SARS-CoV-2 rS protein on day 36. Herein, we report the primary data analysis at 4 weeks after the second dose, ahead of 12-month follow-up completion (data cut-off: 8 May 2021).ResultsBetween 12 February 2021 and 17 March 2021, 326 subjects were screened, and 200 participants enrolled and randomized: NVX-CoV2373, n = 150; placebo, n = 50. Solicited adverse events (AEs) through 7 days after each injection occurred in 121/150 (80.7%) and 11/50 (22.0%) participants in the NVX-CoV2373 and placebo arms, respectively. In the NVX-CoV2373 arm, tenderness and injection site pain were the most frequently reported solicited AEs after each vaccination, irrespective of age. Robust immune responses occurred with NVX-CoV2373 (n = 150) by day 36: IgG geometric mean fold rise (95% confidence interval) 259 (219, 306); seroconversion rate 100% (97.6, 100). No such response occurred with placebo (n = 49).ConclusionTwo doses of NVX-CoV2373 given with a 21-day interval demonstrated acceptable safety and induced robust anti-SARS-CoV-2 immune responses in healthy Japanese adults. Funding: Takeda Pharmaceutical Company Limited and Japan Agency for Medical Research and Development (AMED). ClinicalTrials.gov identifier: NCT04712110.     

一测多评法在中药质量控制中的应用及研究进展＊

一测多评法（quantitative analysis of multi-components by single marker，QAMS）已成熟应用于中药材、中药提取物及中成药领域等中药复杂体系的质量评价研究中，有效解决了因对照品缺乏而导致的多指标质控技术推广难问题。本文查阅近五年的国内外研究文献，重点总结了高效液相色谱、气相色谱和质谱等技术在QAMS法中药质量控制中的应用。高效液相色谱联用紫外检测器（UV）技术应用最为广泛，最适合于中药QAMS法定量，结果稳定、准确；而高效液相色谱联用蒸发光检测器在中药QAMS法应用中，其测定准确性和适用性仍然需进一步探索和验证。液质联用技术虽然具有灵敏度高、线性范围宽等优点，但易受仪器参数、基质效应等的影响。进一步发展HPLC-UV技术在中成药制剂质量评价中的应用，是QAMS法多成分定量值得关注的方向；探索LC-MS和GC技术在中药QAMS质量评价中的稳定性和普适性是未来将面临的挑战。     

玻璃体腔内注射抗血管内皮生长因子治疗早产儿视网膜病复发的危险因素分析

目的 探讨玻璃体腔内注射抗血管内皮生长因子（vascular endothelial growth factor，VEGF）治疗早产儿视网膜病（retinopathy of prematurity，ROP）的效果及复发的危险因素。 方法 回顾性收集2016年1月—2021年12月在郑州大学第一附属医院出生行抗VEGF治疗的ROP患儿159例的临床资料，根据首次抗VEGF治疗后随访周期内ROP复发与否分为复发组（24例）和非复发组（135例），比较分析2组临床资料，采用多因素logistic回归分析探讨抗VEGF治疗ROP复发的危险因素。 结果 经单次抗VEGF治疗后，所有159例患儿均显示附加病变消退。24例（15.1%）抗VEGF治疗后复发，复发平均时间为治疗后（8.4±2.6）周。多因素logistic回归分析显示，术前眼底出血、总用氧时间较长是ROP复发的危险因素（P<0.05），而妊娠高血压是保护因素（P<0.05）。 结论 玻璃体腔内注射抗VEGF治疗ROP是有效的。术前眼底出血和氧疗时间较长可增加ROP复发的风险，而对于妊娠高血压对ROP复发的影响，还需进一步研究证实。     

Quantitative assessment of bony orbital volume symmetry: CT analysis in the uninjured caucasian population

There is a surprising lack of evidence documenting the volumetric symmetry of the bony orbit. This paper establishes reference values for orbital volume (OV) and symmetry in the 25 - 40 year old caucasian population. Secondarily, this paper sets a landmark for the tolerances in OV that can be expected when reconstructing the bony defects which may occur from trauma. A standardised method of quantitative OV measurement was developed using CT sinus examinations acquired for indications unrelated to orbital trauma. Sex, ethnicity, age, right and left OV were recorded. Data for 100 patients was obtained (50 male, 50 female). Mean left OV was 23.1cm³ and mean right OV was 23.3cm³. Left and right OV were strongly positively correlated (correlation coefficient: 0.96). Mean female OV was 21.6cm³ and mean male OV was 24.8cm³. On average, male OV is 3.2cm³ larger than female OV. The mean difference between left and right OV was 0.5cm³ in females and 0.6cm³ in males. The intra-class coefficient score between the two assessors was 0.973 (excellent). There is strong positive correlation between left and right OV in this study population. Previous work suggests that orbital volume loss less than 1cm³ would not lead to significant clinical symptoms of orbital fracture. When orbital reconstruction is undertaken, this study suggests that a volume symmetry difference of <0.5cm³ in females and <0.6cm³ in males would be consistent with the variation seen in the study population of uninjured caucasian 25-40 year olds and is therefore a reasonable goal of surgical management.     

Desarrollo y validación de la versión abreviada del Transsexual Voice Questionnaire for Male-to-Female Transsexuals en español

ObjectiveThe aim of this study was to create and validate an abbreviated version of the Spanish Transsexual Voice Questionnaire for Male-to-Female Transsexuals (SvTVQ^MtF).SettingThe study was conducted by two referral hospitals for voice feminization surgery and by a university department of psychology and speech therapy, all in Spain.Subjects and methodsWe prospectively studied 51 male-to-female transsexuals who underwent voice feminization surgery between January 2017 and December 2018. The SvTVQ^MtF was completed before and after surgery, and the 10 items with the greatest variation were selected by clinical consensus of an expert panel to develop the short version of the SvTVQ^MtF (SvTVQ^MtF-10). The correlation between the total score and the score for each item on the SvTVQ^MtF and the SvTVQMtF-10 was studied. The internal consistency of the SvTVQ^MtF-10 was analysed.ResultsGood correlation (Pearson coefficient above .90) was found between the two questionnaires. A significant correlation was found between the total SvTVQ^MtF-10 score and the score for each item. A significant negative correlation was found between the SvTVQ^MtF and fundamental frequency after voice feminization surgery. Cronbach's α was .79.ConclusionThe SvTVQ^MtF-10 is a valid short version of the SvTVQ^MtF and can be used to quantify voice-related quality of life in MtF transsexuals.