PROFILE ANALYSIS FOR ASSESSING IN VITRO BIOEQUIVALENCE

For locally acting drug products such as nasal aerosols and nasal sprays, therapeutic equivalence between two drug products may be established by in vitro bioequivalence studies based on measurements intended to reflect the rate and extent to which the active ingredient becomes available at the site of action. For cascade impaction or multistage liquid impinger for particle size distribution, profile analysis is required. However, we find that the analysis procedure described in the 1999 FDA guidance lacks statistical justification. In this article, we explain why FDA's approach is incorrect and propose a correct statistical method for profile analysis using the basic ideas in the FDA guidance.     

水化疗法预防造影剂肾病的效果研究

目的研究水化疗法预防造影剂肾病的效果。方法随机选取2016年6月～2018年6月我院收治的造影剂肾病高危患者60例,依据预防方法分为两组,即氯化钠水化疗法组和复方氯化钠水化疗法组,每组30例,统计分析两组患者的Cr、pH、GFR、HCO3~-、K~+水平、造影剂肾病、二级终点事件发生情况。结果复方氯化钠水化疗法组患者的Cr水平显著低于氯化钠水化疗法组(P0.05),pH、GFR水平均显著高于氯化钠水化疗法组(P0.05),造影剂肾病、二级终点事件发生率为3.3%(1/30)、0,均显著低于氯化钠水化疗法组的13.3%(4/30)、10.0%(3/30)(P0.05)。结论复方氯化钠水化疗法预防造影剂肾病的效果较氯化钠水化疗法好,值得在临床推广。     

Adjunct Effect of Immunostimulating Hexapeptide Analogous to Human Beta‐Casein Fragment (54–59) to Sodium Stibogluconate Against Experimental Visceral Leishmaniasis

Visceral leishmaniasis (VL) is a major public health problem in many tropical countries of the world. The available chemotherapeutics require parenteral administration and have other limitations like cost, toxicity, variable efficacy or restricted supplies. There is no effective treatment for immunosuppressed patients with leishmaniasis‐ HIV co‐infection. Hence, new therapies, that are effective when treatment with the currently available drugs fails, must be developed. One of the major strategies for effective and safe treatment of leishmaniasis and other infectious diseases, in the last decade, involves the use of immunomodulators as adjunct to chemotherapy. In this context, we studied the immunomodulatory activity of a hexapeptide Val‐Glu‐Pro‐Ile‐Gly‐Tyr (CDRI compound 89‐215) corresponding to (54–59) fragment of human β‐casein in mice and its efficacy in adjunct chemotherapy with SSG using L. donovani/hamster model. The hexapeptide was found to enhance both humoral and CMI responses. In animal model the hexapeptide per se showed no antileishmanial activity. However, when given alongwith suiboptimal dose of SSG, it enhanced the efficacy of SSG from 24% to 80%. The activity was very close to the efficacy (85%) recorded for curative dose of SSG. Adjunct chemotherapy with immunomodulator in visceral leishmaniasis appears to be a fruitful preposition.     

五加减正气散化裁对溃疡性结肠炎大鼠干扰素-γ的影响

目的:讨论五加减正气散化裁对溃疡结肠炎(UC)大鼠血中的干扰素-γ(INF-γ)的影响。方法:实验动物分成4组,分别为空白组、模型组、西药组和中药组,采用乙酸诱导法造模,观察大鼠结肠黏膜病理变化,用ELISA法检测大鼠血中INF-γ的水平。结果:空白组大鼠血中INF-γ和结肠黏膜无变化,模型组的大鼠血中INF-γ和结肠黏膜变化明显,西药组与中药组大鼠血中INF-γ和结肠黏膜无明显变化。西药组、中药组与空白组间差异无统计学意义;模型组与空白组比较,大鼠血清中INF-γ显著升高,结肠黏膜充血、水肿、糜烂并有溃疡形成,两者之间差异有统计学意义(P<0.05);模型组与西药组、中药组间大鼠血清中INF-γ显著升高,结肠黏膜充血、水肿、糜烂并有溃疡形成,差异有统计学意义(P<0.05)。结论:五加减正气散化裁能干预实验性UC大鼠血中的INF-γ的活性,对UC大鼠结肠溃疡面有修复和保护作用。     

Afatinib for the Treatment of NSCLC Harboring Uncommon EGFR Mutations: A Database of 693 Cases

IntroductionLimited clinical data are available regarding the efficacy of EGFR tyrosine kinase inhibitors (EGFR TKIs) in patients with NSCLC harboring uncommon EGFR mutations. This pooled analysis assessed the activity of afatinib in 693 patients with tumors harboring uncommon EGFR mutations treated in randomized clinical trials, compassionate-use and expanded-access programs, phase IIIb trials, noninterventional trials, and case series or studies.MethodsPatients had uncommon EGFR mutations, which were categorized as follows: (1) T790M; (2) exon 20 insertions; (3) “major” uncommon mutations (G719X, L861Q, and S768I, with or without any other mutation except T790M or an exon 20 insertion); (4) compound mutations; and (5) other uncommon mutations. Key end points were overall response rate (ORR), duration of response, and time to treatment failure (TTF).ResultsIn EGFR TKI–naive patients (n = 315), afatinib demonstrated activity against major uncommon mutations (median TTF = 10.8 mo; 95% confidence interval [CI]: 8.1–16.6; ORR = 60.0%), compound mutations (median TTF = 14.7 mo; 95% CI: 6.8–18.5; ORR = 77.1%), other uncommon mutations (median TTF = 4.5 mo; 95% CI: 2.9–9.7; ORR = 65.2%), and some exon 20 insertions (median TTF = 4.2 mo; 95% CI: 2.8–5.3; ORR = 24.3%). The median duration of response for major uncommon mutations, compound mutations, other uncommon mutations, and some exon 20 insertions was 17.1, 16.6, 9.0, and 11.9 months, respectively. Activity of afatinib was also observed in EGFR TKI–pretreated patients (n = 378). A searchable database of these outcomes by individual genotype was generated.ConclusionsAfatinib has clinical activity in NSCLC against major uncommon and compound EGFR mutations. It also has broad activity against other uncommon EGFR mutations and some exon 20 insertions. The data support the use of afatinib in these settings.     

复方妥布霉素滴眼液与普南扑灵滴眼液在儿童斜视术后的疗效观察

目的比较复方妥布霉素滴眼液及普南扑灵滴眼液在儿童斜视术后的抗炎效果及安全性。方法征得患儿父母同意,87例（174眼）3～11岁儿童经全身麻醉或局部麻醉下行双眼斜视术矫正后,随机一眼用普南扑灵滴眼液,另一眼用复方妥布霉素滴眼液,自术后第1天开始,每天4次,持续4周,比较两种滴眼液在术后的抗炎作用及对眼内压的影响。结果两种滴眼液对术后炎症反应均有显著的抑制作用,其抗炎效果比较差异无统计学意义（P〉0.05）,复方妥布霉素滴眼液组有明显的升高眼内压作用,普南扑灵组无明显的升高眼内压作用,两者比较差异有统计学意义（P〈0.01）。结论两种滴眼液均对儿童斜视术后有较好的抗炎作用,但普南扑灵无明显的升高眼内压作用。     

Endoscopic haemostasis: An overview of procedures and clinical scenarios

Acute gastrointestinal bleeding is among the most urgent situations in daily gastroenterological practise. Endoscopy plays a key role in the diagnosis and treatment of such cases. Endoscopic haemostasis is probably the most important technical challenge that must be mastered by gastroenterologists. It is essential for both the management of acute gastrointestinal haemorrhage and the prevention of bleeding during high-risk endoscopic procedures. During the last decade, endoscopic haemostasis techniques and tools have grown in parallel with the number of devices available for endotherapy. Haemostatic powders, over-the-scope clips, haemostatic forceps, and other emerging technologies have changed daily practise and complement the standard available armamentarium (injectable, thermal, and mechanical therapy). Although there is a lack of strong evidence-based information on these procedures because of the difficulty in designing statistically powerful trials on this topic, physicians must be aware of all available devices to be able to choose the best haemostatic tool for the most effective procedure. We herein present an overview of procedures and clinical scenarios to optimise the management of gastrointestinal bleeding in daily practise.     

Reversible electrophysiological abnormalities in hypokalemic paralysis: Case report of two cases

Compound muscle action potential (CMAP) amplitude declines during a paralytic attack in patients with hypokalemic periodic paralysis (HPP). However, serial motor nerve conduction studies in hypokalemic paralysis have not been commonly reported. We report two cases with hypokalemic paralysis, who had severely reduced CMAPs in all motor nerves at presentation during the episode of quadriparesis. However, the amplitude of CMAPs increased and reached normal levels, as the serum potassium concentration and motor power returned to normal state.     

复方芪术汤对四氯化碳致大鼠肝纤维化的影响研究

目的探讨复方芪术汤对四氯化碳(CCl4)致大鼠肝纤维化药效的干预作用。方法Wistar雄性大鼠30只,随机分为正常组10只和四氯化碳处理组(20只),四氯化碳1 ml/kg,每周2次腹腔注射,正常组注射等量的生理盐水。造模的第8周,四氯化碳处理组大鼠随机分为复方芪术汤组和模型组,每组10只。在继续造模的同时,复方芪术汤组给予70千克成人的10倍量灌胃,模型组给予等量的生理盐水灌胃,给药4周。12周末处死全部大鼠,留取肝组织样本和血清,测定谷丙转氨酶(ALT)、谷草转氨酶(AST)、白蛋白(ALB)、总胆红素(TBiL)。结果四氯化碳造模12周,模型组血清ALT、AST活性显著升高;ALB含量显著下降。血清TBiL含量显著升高。与模型组相比,复方芪术汤组大鼠血清ALB含量显著升高,血清ALT和AST活性显著降低(P<0.01)。但复方芪术汤对血清TBiL降低不明显。病理组织学显示,模型组假小叶形成,肝脏纤维化程度分级均为2、3级;复方芪术汤干预组肝小叶结构不同程度被破坏,肝脏纤维化程度分级大部分在1、2级。结论复方芪术汤可以显著改善大鼠肝功能,对CCl4引起的慢性肝纤维化大鼠有很好的降低肝纤维化程度的作用。     

头孢哌酮钠及其复方制剂的配伍禁忌

目的了解头孢哌酮钠及其复方制剂的配伍禁忌，供临床用药参考，避免其不良反应的发生。方法通过检索2009—2011年期间公开发表的头孢哌酮钠及其复方制剂配伍禁忌文献，进行总结归纳。鳍果头孢哌酮钠及其复方制剂与很多药物配伍试验均存在不同程度的配伍反应。结论头孢哌酮钠及其复方制剂的配伍禁忌较多，联合应用时应该谨慎，促进用药合理有效。