Effect of deuteration on the single dose pharmacokinetic properties and postoperative analgesic activity of methadone

Although methadone is effective in the management of acute pain, the complexity of its absorption-distribution-metabolism-excretion profile limits its use as an opioid of choice for perioperative analgesia. Because deuteration is known to improve the pharmacokinetic, pharmacodynamic and toxicological properties of some drugs, here we characterized the single dose pharmacokinetic properties and post-operative analgesic efficacy of d₉-methadone.The pharmacokinetic profiles of d₉-methadone and methadone administered intravenously to CD-1 male mice revealed that deuteration leads to a 5.7- and 4.4-fold increase in the area under the time-concentration curve and maximum concentration in plasma, respectively, as well as reduction in clearance (0.9 ± 0.3 L/h/kg vs 4.7 ± 0.8 L/h/kg). The lower brain-to-plasma ratio of d₉-methadone compared to that of methadone (0.35 ± 0.12 vs 2.05 ± 0.62) suggested that deuteration decreases the transfer of the drug across the blood-brain barrier. The estimated LD₅₀ value for a single intravenous dose of d₉-methadone was 2.1-fold higher than that for methadone. Moreover, d₉-methadone outperformed methadone in the efficacy against postoperative pain by primarily activating peripheral opioid receptors. Collectively, these data suggest that the replacement of three hydrogen atoms in three methyl groups of methadone altered its pharmacokinetic properties, improved safety, and enhanced its analgesic efficacy.     

Research hotspots and effectiveness of repetitive transcranial magnetic stimulation in stroke rehabilitation

Repetitive transcranial magnetic stimulation, as a relatively new type of rehabilitation treatment, is a painless and non-invasive method for altering brain excitability. Repetitive transcranial magnetic stimulation has been widely used in the neurorehabilitation of stroke patients. Here, we used CiteSpace software to visually analyze 315 studies concerning repetitive transcranial magnetic stimulation for stroke rehabilitation from 1999 to 2019, indexed by Web of Science, to clarify the research hotspots in different periods and characterize the gradual process of discovery in this field. We found that four main points were generally accepted:(1) repetitive transcranial magnetic stimulation has a positive effect on motor function recovery in patients with subcortical stroke;(2) it may be more advantageous for stroke patients to receive low-frequency repetitive transcranial magnetic stimulation in the unaffected hemispheres than to receive high-frequency repetitive transcranial magnetic stimulation in affected hemisphere;(3) low-frequency repetitive transcranial magnetic stimulation has become a potential therapeutic tool for patients with non-fluent aphasia after chronic stroke for neurological rehabilitation and language recovery; and(4) there are some limitations to these classic clinical studies, such as small sample size and low test efficiency. Our assessment indicates that prospective, multi-center, large-sample, randomized controlled clinical trials are still needed to further verify the effectiveness of various repetitive transcranial magnetic stimulation programs for the rehabilitation of stroke patients.     

单孔加一孔联合ERAS在高位直肠及乙状结肠癌中的应用

目的 探讨单孔加一孔腹腔镜手术联合 ERAS 治疗高位直肠及乙状结肠癌的近期疗效。方法 回顾性分析 2017 年 11 月至2018 年 10 月在福建省肿瘤医院胃肠肿瘤外科进行加速康复外科干预的 92 例高位直肠及乙状结肠癌患者资料，根 据手术方式的不同，分为单孔加一孔手术联合快速康复外科组39 例及常规腹腔镜手术联合ERAS 组 53 例，对比两组围术 期情况。结果 两组患者基线资料无明显统计学差异（P ＞ 0.05），且在手术时间、出血量、上下切缘、清扫淋巴结数量及 并发症方面无明显统计学差异（P ＞ 0.05）。但单孔加一孔手术联合ERAS 组较常规手术联合ERAS 组，总切口长度更短 [（6.7±1.1）cm 比（8.5±1.3）cm，P=0.000]，术后首次下床时间更早 [（22.2±5.2）h 比（27.1±7.9）h，P=0.001]，首次排便 时间更早[（70.2±19.8）h比（83.1±20.4）h，P=0.005]，术后第一天C反应蛋白值更低[（43.5±28.6）mg/L比（57.2±33.2） mg/L，P=0.038]，术后住院时间更短 [（7.0±1.7）d 比（8.1±2.1）d，P=0.010]，且术后 2~4 天疼痛评分更低（P ＜ 0.05）。 结论 经验丰富的腔镜医师采用单孔加一孔手术治疗高位直肠及乙状结肠癌并联合 ERAS 干预是安全可行的，且单孔加一孔 手术可减低操作难度，具有疼痛轻、术后恢复快等优势，值得临床推广。     

Effectiveness of cognitive rehabilitation for people with multiple sclerosis: a meta-synthesis of patient perspectives

While previous randomised controlled trials and meta-analyses offer only limited evidence for the effectiveness of cognitive rehabilitation, qualitative studies examining patient perspectives report more positive outcomes. This meta-synthesis of qualitative studies examined patient perspectives of cognitive rehabilitation for memory, attention, and executive function problems in people with multiple sclerosis. Using set eligibility criteria, we screened electronic databases, reference lists, and academic networks for relevant papers. Seven papers (195 participants) were selected. Two independent researchers conducted quality appraisals of papers. Data analysis, guided by the thematic synthesis approach, yielded six main themes. These suggested that patients benefitted from the group environment in rehabilitation. Cognitive rehabilitation facilitated the participants’ reflection and awareness of their cognitive deficits, and was associated with increased knowledge and understanding of their illness. Increased strategy use was reported and associated with improvements in cognitive functioning and greater confidence and perseverance. Participants reported emotional and social improvements, and felt more optimistic. Overall, these changes had a positive impact on participants’ quality of life. This synthesis of qualitative studies indicates that people with multiple sclerosis who experience cognitive deficits benefit from cognitive rehabilitation programmes. This finding must, however, be viewed in light of the limitations of this meta-synthesis. The meta-synthesis was registered in the PROSPERO database under CRD42017040148.     

Pre- or postoperative radiotherapy for soft tissue sarcomas

Sarcomas are rare tumours arising from mesenchymal tissue. A multimodal management in an expert centre combining surgery and radiotherapy is the current standard of care for localized soft-tissue sarcomas of the extremities, to enable limb-sparing strategies. The delivery of pre- radiotherapy or postoperative radiotherapy offers similar local control and survival rates but the toxicity profile is quite different: preoperative radiotherapy increases the risk of wound complications and postoperative radiotherapy affects long-term functional outcomes. While postoperative radiotherapy has long been the rule, especially in Europe, technical improvements with image-guided- and intensity-modulated radiotherapy associated with a better management of postoperative wounds has tended to change practices with more frequent preoperative radiotherapy. More recently the possibilities of a hypofractionated regimen or potentiation by nanoparticles to increase the therapeutic index plead in favour of a preoperative delivery of radiotherapy. The aim of this paper is to report pros and cons of pre- and post-operative radiotherapy for soft-tissue sarcomas.     

坐骨重叠征与发育性髋关节脱位手术后再脱位的相关性分析

目的提出坐骨重叠征(ischium overlap sign,IOS)的概念,并分析其与发育性髋关节脱位(developmental dysplasia of the hip,DDH)手术后再脱位的关系。方法回顾性分析2013年9月至2017年5月山东大学附属省立医院治疗的88例(105髋)DDH患儿病例资料,其中男童16例、女童72例;平均年龄12(5~24)个月,平均随访时间34(15~59)个月;双侧17例,左侧63髋,右侧42髋;1髋为髋臼发育不良,11髋半脱位,93髋全脱位。术中行髋关节造影检查,按照Bowen标准选择闭合或切开复位石膏固定术。IOS是指在人类位髋关节造影平片上股骨头软骨内缘与坐骨外缘的重叠关系,二者重叠为Ⅰ度,相接为Ⅱ度,分离为Ⅲ度。将93髋全脱位按照IOS分度进行分组,比较组间再脱位发生率。结果 1髋髋臼发育不良和11髋半脱位者IOS均为Ⅰ度。93髋全脱位中IOSⅠ度14髋,Ⅱ度39髋,此两组均行闭合复位石膏固定,无再脱位病例;Ⅲ度40髋中,闭合复位石膏固定17髋,6髋再脱位;切开复位石膏固定23髋,1髋再脱位。本研究发现Ⅲ度组的再脱位发生率(7/40,17.5%)高于其他两组(P=0.006)。IOS为Ⅲ度的40髋中,闭合复位的再脱位发生率(6/17,35.3%)高于切开复位(1/23,4.4%),差异有统计学意义(X^2=4.518,P=0.034)。结论 IOS与DDH术后再脱位有一定的关系,IOS为Ⅲ度的髋关节如行闭合复位,再脱位的风险较高。     

胸痹心痛病患者的中医心脏康复护理意义研究

目的探讨胸痹心痛病患者的中医心脏康复护理意义。方法选取2018年1月-2019年1月在大连中医医院内一病房就诊的80例胸痹心痛病患者,经辨证分型为气虚血瘀型胸痹,随机分为试验组和对照组,对照组40例采取常规护理,试验组40例在对照组的基础上使用中医心脏康复护理,主要包括:证候施护、饮食护理、中医特色技术、情志护理、健康指导等。通过中医证候评分对治疗的有效率进行观察。结果试验组有效率为92.5%,对照组有效率为77.5%,试验组优于对照组,差异有统计学意义(P<0.05)。结论对胸痹心痛病患者的中医心脏康复护理,可以有效提高临床有效率,改善临床症状,提高患者生活质量,值得在临床推广。     

康复护理教学中应用Seminar教学法的分析

目的 探讨康复护理教学中应用Seminar教学法的效果.方法 选择医院2018年6月—2019年6月在肿瘤科实习的80名护理学生作为本次研究入组对象,根据随机数字表随机分为研究组和对照组,每组40名学生.对照组采用传统护理教学方法 ,研究组采用Seminar教学法,分析对比两组护理学生的教学效果.结果 研究组护理学生理论考试、技能考试、综合成绩高于对照组护理学生成绩(P<0.05).研究组护理学生自主学习情况由于对照组护理学生(P<0.05).结论 康复护理教学中应用Seminar教学法的效果好,有利于激发学生学习兴趣,巩固学生护理基本知识技能,提高护理思维能力,从而提高护理教学质量.