Amphotericin B for treatment of visceral leishmaniasis: systematic review and meta-analysis of prospective comparative clinical studies including dose-ranging studies

ObjectivesTo evaluate the evidence for use of different formulations of amphotericin B (AmB), minimum effective dose for each formulation and its comparative efficacy against other drugs in achieving definitive cure of visceral leishmaniasis.MethodsThis systematic review and meta-analysis included following data sources: PubMed, Embase, Scopus, Web of Science and CINAHL. Controlled prospective clinical trials (randomized or nonrandomized, including dose-ranging studies) conducted between 1996 and 2017 with at least one treatment group receiving AmB were included (published data only). The primary outcome was definitive cure at 6 months. Adverse events and mortality were assessed as secondary outcomes. The PROSPERO registration number for this review is CRD42017067488.ResultsThirty-one studies (26 from India) that enrolled 6903 patients into 84 study groups met the selection criteria. In India, liposomal AmB was not inferior to AmB deoxycholate (relative risk 1.00, 95% confidence interval (CI) 0.96–1.03, two randomized controlled trials (RCTs), 514 participants, high-quality evidence), and a single dose of the earlier formulation as low as 3.75 mg/kg achieved a cure rate of over 89% (95% CI 70.6–97.2). AmB deoxycholate was as effective as miltefosine (relative risk 0.99, 95% CI 0.95–1.03, two trials, 523 participants, high-quality evidence) and may be better than paromomycin (relative risk 1.04, 95% CI 1.02–1.07, one trial, 667 participants, low-quality evidence) in achieving definitive cure.ConclusionsAmB is an efficacious drug in the Indian subcontinent. Further evidence is needed from prospective clinical trials in other endemic geographical regions.     

Involving children and young people in clinical research through the forum of a European Young Persons’ Advisory Group: needs and challenges

Children and young people are seen as fundamental to the design and delivery of clinical research as active and reflective participants. In Europe, involvement of children and young people in clinical research is promoted extensively in order to engage young people in research as partners and to give them a voice to raise their own issues or opinions and for their involvement in planning and decision making in addition to learning research skills. Children and young people can be trained in clinical research through participation in young person advisory groups (YPAGs). Members of YPAGs assist other children and young people to learn about clinical research and share their experience and point of view with researchers, thereby possibly influencing all phases of research including the development and prioritization of research questions, design and methods, recruitment plans, and strategies for results dissemination. In the long term, the expansion of YPAGs in Europe will serve as a driving force for refining pediatric clinical research. It will help in a better definition of research projects according to the patients’ needs. Furthermore, direct engagement of children and young people in research will be favorable to both researchers and young people.     

纳达合剂治疗胃阴不足型慢性浅表性胃炎临床疗效观察

目的 :旨在研究纳达合剂治疗胃阴不足型慢性浅表性胃炎(CSG)的有效性及安全性。方法:共收集胃阴不足型CSG病例110例,随机分为中药组、西药组。中药组予纳达合剂,西药组予胃达喜片,疗程均为8周。最终完成病例106例,治疗组与对照组各53例。分析治疗前后中医证候积分、胃黏膜积分,并观察治疗前后三大常规、肝肾功能的变化。结果:治疗组中医证候总体疗效优于对照组(P0.05),在改善胃脘痞胀、大便干结、嘈杂、口干方面治疗组优于对照组(P0.05);治疗组胃黏膜疗效优于对照组(P0.05),在改善胃黏膜红斑、糜烂、胆汁反流及活动性炎症方面治疗组优于对照组(P0.05);治疗前后两组患者的安全性指标差异无统计学意义。结论:纳达合剂可显著改善该型CSG患者相关中医证候,在改善胃脘痞胀、大便干结、嘈杂、口干方面疗效优于胃达喜;纳达合剂可显著改善该型患者胃黏膜病变,在改善胃黏膜红斑、糜烂、胆汁反流及活动性炎症方面优于胃达喜;纳达合剂临床使用安全,未发现毒性反应。     

不同中药制剂治疗骨折临床观察

目的:探讨复方三七片及复方接骨片在骨折治疗中的作用。方法:选取180例门诊治疗的桡骨远端骨折患者,随机分为复方三七片组、复方接骨片组和对照组。观察3组患者消肿止痛效果、血碱性磷酸酶水平及原始骨痂出现时间。结果:止痛效果显示,复方三七片组及复方接骨片组的止痛效果优于对照组。消肿效果显示,复方三七片及复方接骨片组有效率分别达90%、80%,优于对照组的61.67%。血碱性磷酸酶水平显示,复方三七片及复方接骨片组有效率分别达86.67%、95%,优于对照组的75%。复方三七片及复方接骨片组在第2周即有原始骨痂开始出现,4周内分别有93.33%、96.67%的患者出现原始骨痂,而对照组在第3周才可见原始骨痂出现,4周内有66.67%的患者出现原始骨痂。结论:复方三七片及复方接骨片均能够减轻患部疼痛,促进患部肿胀消退,提高血碱性磷酸酶水平,促进原始骨痂形成。骨折早期(2周内)口服复方三七片有利于消肿止痛,骨折2周后口服复方接骨片有利于骨痂生长、骨折愈合。     

Statistical inference for response adaptive randomization procedures with adjusted optimal allocation proportions

Seamless phase II/III clinical trials have attracted increasing attention recently. They mainly use Bayesian response adaptive randomization (RAR) designs. There has been little research into seamless clinical trials using frequentist RAR designs because of the difficulty in performing valid statistical inference following this procedure. The well-designed frequentist RAR designs can target theoretically optimal allocation proportions, and they have explicit asymptotic results. In this paper, we study the asymptotic properties of frequentist RAR designs with adjusted target allocation proportions, and investigate statistical inference for this procedure. The properties of the proposed design provide an important theoretical foundation for advanced seamless clinical trials. Our numerical studies demonstrate that the design is ethical and efficient.     

高频振荡通气与常频机械通气治疗新生儿气胸的临床对照研究

【摘要】 目的 研究高频振荡通气（High frequency oscillatorg ventilation，HFOV）与常频机械通气(Conventional menchanical ventilation，CMV)治疗新生儿气胸的临床疗效，寻找更适合与优越性的通气方法。方法 选取新生儿病房在2013年10月~2016年2月收治的80例需要机械通气治疗的气胸新生儿。按治疗方法分为两组，观察组40例采用高频振荡通气（HFOV）治疗；对照组40例则采用常频机械通气（CMV）治疗。观察两组患儿在不同时期的血气分析指标及肺功能恢复时间，两组患儿治疗疗效与有无并发症。结果 两组患儿一般资料及原发病构成比较，差异无统计学意义（P＞005）。两组患儿在治疗前氧分压（PaO2）、二氧化碳分压（PaCO2）、氧合指数（OI）、动脉/肺泡氧分压（a/APO2）的比较，差异无统计学意义（P＞005）。两组患儿治疗4、8、12、24、48h后，观察组和对照组各时段PaO2值均较治疗前上升（P＜005）；PaCO2值较治疗前下降（P＜005）；OI值较治疗前明显下降（P＜005）；a/APO2值较治疗前升高（P＜005）。但观察组治疗4、8、12、24、48h时后PaO2、PaCO2、OI、a/APO2值改善情况明显优于对照组，（P＜005）。观察组呼吸机平均使用时间为（37±13）/d明显短于对照组的（71±18）/d（P＜005）。观察组X线胸片恢复时间为（41±19）/d明显短于对照组的（95±23）/d（P＜005）。治疗过程中两组患者无明显并发症情况发生（P＞005）。结论 HFOV和CMV两种通气治疗新生儿气胸均有明显效果，但HFOV的临床治疗疗效更好，检测血气分析指标及肺功能改善更明显，且安全性更高，无明显并发症，更适合治疗新生儿气胸。     

Genetic diversity and complexity of Plasmodium falciparum infections in Lagos,Nigeria

ObjectiveTo analyse the genetic diversity of Plasmodium falciparum (P. falciparum) using msp-1 and msp-2 as antigenic markers.MethodsParasite DNA was extracted from 100 blood samples collected from P. falciparum-positive patients confirmed by microscopy, and followed by PCR-genotyping targeting the msp-1 (block2) and msp-2 (block 3) allelic families.ResultsAll the families of msp-1 (K1, MAD20 and R033) and msp-2 (FC27 and 3D7) locus were observed. Results revealed that K1 (60/100) was the most predominant genotype of msp-1 allelic family followed by the genotypes of MAD20 (50/100) and R033 (45/100). In the msp-2 locus, FC27 genotype (62/100) showed higher frequency than 3D7 genotype (55/100). The allelic families were detected either alone or in combination with other families. However, no R033/MAD20 combination was observed. Multiplicity of infection (MOI) with msp-1 was higher in the locality of Ikorodu (1.50) than in Lekki (1.39). However, MOI with msp-2 was lower in the locality of Ikorodu (1.14) than in Lekki (1.76). There was no significant difference in the mean MOI between the two study areas (P=0.427).ConclusionsThe observation of limited diversity of malaria parasites may imply that the use of antigenic markers as genotyping tools for distinguishing recrudescence and re-infections with P. falciparum during drug trials is subjective.