Acute effects of brain-responsive neurostimulation in drug-resistant partial onset epilepsy

ObjectiveUnderstanding the acute effects of responsive stimulation (AERS) based on intracranial EEG (iEEG) recordings in ambulatory patients with drug-resistant partial epilepsy, and correlating these with changes in clinical seizure frequency, may help clinicians more efficiently optimize responsive stimulation settings.MethodsIn patients implanted with the NeuroPace® RNS® System, acute changes in iEEG spectral power following active and sham stimulation periods were quantified and compared within individual iEEG channels. Additionally, acute stimulation-induced acute iEEG changes were compared within iEEG channels before and after patients experienced substantial reductions in clinical seizure frequency.ResultsResponsive stimulation resulted in a 20.7% relative decrease in spectral power in the 2–4 second window following active stimulation, compared to sham stimulation. On several detection channels, the AERS features changed when clinical outcomes improved but were relatively stable otherwise. AERS change direction associated with clinical improvement was generally consistent within detection channels.ConclusionsIn this retrospective analysis, patients with drug-resistant partial epilepsy treated with direct brain-responsive neurostimulation showed an acute stimulation related reduction in iEEG spectral power that was associated with reductions in clinical seizure frequency.SignificanceIdentifying favorable stimulation related changes in iEEG activity could help physicians to more rapidly optimize stimulation settings for each patient.     

基于数据挖掘和“味性化味”理论的藏医治疗疫病用药规律及肺疫方剂药性研究＊

目的 研究藏医治疗疫病的用药规律及肺疫方剂药性。方法 收集和整理藏医古籍文献中治疗疫病的方剂，运用IBM SPSS软件进行藏药频数、聚类和因子分析，运用SPSS Modeler和TBtools软件分别进行关联规则分析和肺疫病方剂的药性聚类分析。结果 共纳入160首方剂，涉及219味藏药材，统计频次≥16的高频藏药材34种，多以清热、解毒祛瘟和消疫药材为主。关联规则分析得到28项药物组，体现出藏医消疫祛邪、调隆祛寒的用药特点。聚类分析得到8个药物组合，反应了泻疫解毒和除瘟镇痛的藏医治法特点。因子分析提出6个公因子，反应了驱虫止疠的藏医治法，并表明藏药五味麝香丸在治疗疫病方剂配伍中占有举足轻重的地位。治疗肺疫经典方剂的藏药材主要以草本类药材为主。方剂药性聚类结果显示凉、钝、稀等治疗赤巴的药性值最高，符合藏医消疫、清热和调“隆”的治疗原则。结论 藏医治疗肺疫病主要采取消疫清热为主、调“隆”补益为辅的治疗原则。     

Multi stakeholders of health and industries perspectives on medicine price transparency initiative in private health care settings in Malaysia

IntroductionMedicine price transparency initiatives provide public or government on information about the product's prices and the components that may influence the prices, such as volume and product quality. In Malaysia, medicine price transparency has become part of the government's strategies in ensuring adequate, continuous and equitable access to quality, safe, effective and affordable medicines. Since the effect of medicine price transparency depend critically on how prices are presented, this study aims to evaluate the stakeholders' perspective of medicine price transparency practice in the private healthcare system in Malaysia.MethodsThis study was conducted as face-to-face, semi-structured interview. Respondents from private pharmaceutical industries, community pharmacists, general practitioners, private hospital pharmacists, governments, academicians and senior pharmacist were recruited using purposive sampling. Using phenomenological study approach, interviews were conducted, and audio recorded with their consent. Data were transcribed verbatim and analysed using thematic analysis with Atlas.ti 8 software and categorised as strengths, weaknesses, opportunities and threats (SWOT).ResultsA total of 28 respondents were interviewed. There was a mixed perception regarding the price transparency implementation in Malaysia's private healthcare settings. The potential strengths include it will provide price standardization, reduce price manipulation and competition, hence allowing the industry players to focus more on patient-care services. Moreover, the private stakeholders were concerned that the practice may affect stakeholders' business and marketing strategy, reduce profit margin, increase general practitioner's consultation fees and causing impact on geographical discrepancies. The practice was viewed as an opportunity to disseminate the truth price information to consumer and strengthen collaboration between healthcare industries and Ministry of Health although this may become a threat that affect the business survival.ConclusionPrice transparency initiatives would benefit the pharmaceutical industries, consumer and countries, but it needs to be implemented appropriately to prevent price manipulation, market monopoly, and business closure. Future study may want to evaluate the impact of the initiatives on the business in the industry.     

异黏蛋白调控鼻咽癌细胞增殖及紫杉醇耐药的研究

 目的 探讨异黏蛋白（Metadherin, MTDH）对鼻咽癌细胞增殖及紫杉醇耐药的影响。方法 采用慢病毒介导的MTDH cDNA和MTDH-shRNA转染鼻咽癌细胞，分别上调和抑制MTDH的表达。CCK-8法、流式细胞实验分别检测细胞增殖能力、细胞周期及凋亡改变。CCK-8法确定紫杉醇对鼻咽癌细胞的IC₃₀、IC₅₀、IIC₇₀，并检测IC₃₀、IC₅₀、IC₇₀浓度下MTDH过表达组与沉默组细胞生存率改变。结果 MTDH上调后5-8F、HNE-1细胞的增殖能力均增强，而沉默MTDH后细胞的增殖能力均降低。MTDH沉默组的G1期细胞比例明显增加。MTDH过表达组细胞凋亡率降低，MTDH沉默组细胞凋亡率增加。MTDH表达上调之后，鼻咽癌细胞对紫杉醇的敏感度降低，在IC₇₀、IC₅₀浓度下，MTDH过表达组细胞的生存率高于对照组细胞。沉默MTDH之后，鼻咽癌细胞对紫杉醇的敏感度升高，在IC₅₀、IC₃₀浓度下，MTDH沉默组细胞的生存率低于对照组细胞。结论 MTDH在促进鼻咽癌细胞增殖中起重要作用，其高表达可促进鼻咽癌细胞紫杉醇耐药性的产生。     

口腔感染的病原菌分布及药敏情况调查分析

目的分析口腔感染患者病原菌分布及药敏情况,为临床合理用药提供参考。方法选取口腔感染患者86例作为研究对象,收集口腔分泌物进行病原菌培养,并行药敏实验。结果本组86例患者中,≤15岁、≥56岁口腔感染患者比例较高,分别占30.2%、40.7%。共检出病原菌351株,其中厌氧菌236株,占67.2%,其在厌氧菌中黑色素普氏菌比例最高(50.4%),其次为口腔链球菌(16.5%);需氧菌115株,占32.8%。对苯唑西林、头孢唑肟、庆大霉素、环丙沙星的耐药较高,分别为49.2%、46.6%、42.0%、40.2%;对万古霉素、四环素、头孢曲松的敏感性较高,分别为98.3%、95.8%、93.6%。结论厌氧菌是口腔感染较为常见的菌种,可选用万古霉素、四环素、头孢曲松等敏感性高的药物治疗。     

不同药物方案治疗儿童双相情感障碍疗效比较及代谢指标观察

目的 探讨儿童双相情感障碍经不同药物方案治疗后代谢指标的变化及治疗疗效。方法 回顾性分析2017年1月至2020年1月于该院就诊的220例儿童双相情感障碍患儿的临床资料。根据治疗方法分组，单纯采用非典型抗精神病药物治疗的112例患儿纳入对照组，采用非典型抗精神病药物联合心境稳定剂治疗的108例患儿纳入研究组。比较两组基线资料水平，治疗前后代谢指标空腹胰岛素（FIN）、糖化血红蛋白（HbAlc）、总胆固醇（TC）、三酰甘油（TG）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）水平变化，以及代谢综合征发生情况及临床疗效。结果 两组患儿年龄、性别、病程等基线资料比较差异均无统计学意义（P > 0.05）。研究组总有效率为92.6%，高于对照组（82.1%，P < 0.05）。治疗前，两组FIN、HbAlc水平比较差异无统计学意义（P > 0.05）；治疗后，对照组FIN水平高于治疗前，且高于研究组（P < 0.05）；但研究组治疗前后FIN水平比较差异无统计学意义（P > 0.05）；两组治疗前后HbAlc水平比较差异无统计学意义（P > 0.05）。治疗前，两组TC、TG、HDL-C、LDL-C水平比较，差异无统计学意义（P > 0.05）；治疗后，对照组TC、TG水平均高于治疗前，且高于研究组（P < 0.05）；但研究组治疗前后TC、TG水平比较差异无统计学意义（P > 0.05）；两组治疗前后HDL-C、LDL-C水平比较差异无统计学意义（P > 0.05）。研究组代谢综合征发生率（2.8%）低于对照组（9.8%）（P < 0.05）。结论 儿童双相情感障碍采用非经典抗精神病药物联合心境稳定剂治疗对代谢指标水平影响较小，且疗效显著。     

Enhanced normograms and pregnancy outcome analysis in nonhuman primate developmental toxicity studies

The incidence of spontaneous pregnancy/infant losses is highly variable in long-tailed macaques (cynomolgus monkey), making it potentially difficult to ascertain test item-related effects in developmental toxicity studies. Therefore, pregnancy normograms had been developed by Jarvis et al. [1] to aid in the distinction of normal (e.g. test facility background) versus non-normal pregnancy outcomes. These normograms were mostly derived from embryo-fetal development studies and from PPND studies with a postnatal phase limited to seven days. However, the enhanced pre- and postnatal developmental (ePPND) study paradigm has essentially replaced these former study types. This work aims at providing enhanced normograms (e-normograms) in the context of regulatory ePPND studies. Survival functions for the prenatal phase (286 control pregnancies) and the postnatal phase (222 live infants) were estimated using the Kaplan-Meier estimator. Normograms were generated from survival curves and pseudo-study simulations. Data were available from two test facilities with comparable EU-compliant animal husbandry. Pregnancy duration/outcome as well as survival functions did not differ significantly between test facilities indicating that this husbandry system yields comparable developmental observations across different test facilities, at least in this NHP species. These novel e-normograms were developed for pregnant long-tailed macaques and provide an extended postnatal period up to three months, a new concept of separate normograms for the prenatal and the postnatal period, specific information on the perinatal phase events, a prediction of expected number of live infants for group size management, and the option to evaluate effects on pregnancy duration through distinction of live births and infant losses.