妊娠期使用奥美拉唑对新生儿的安全性影响的Meta分析

摘要：目的 胃溃疡和胃食管反流是妊娠期妇女常见的临床症状,会严重影响患者的生活质量,甚至还能引起其他并发症。还有部分患者甚至会遭受更加严重的胃肠道疾病,比如幽门螺旋杆菌干扰、消化性溃疡以及埃氏综合征。因此,质子泵抑制剂（Proton pump inhibitors,PPIs）对于这类妊娠期妇女患者来说非常重要。妊娠期妇女患者若要使用此类药物,就必须先确定其对胎儿的安全性影响。因此,本研究旨在通过系统的文献回顾来分析PPIs中的奥美拉唑在早期妊娠期时使用对新生儿的安全性影响。方法：文献检索范围为英文文献,发表时间从1998年起至今。两位研究者分析文献并比较结果,讨论解决分歧。用Downs-Black评分法评价文献质量。Meta分析采用随机效果法。结果： 6篇文献符合分析标准。共有2161例暴露于奥美拉唑的病例组和125723例对照组被选入进行Meta分析。病例组和对照组新生儿不良率差异无统计学意义,OR=1.07,CI 95 %：0.82-1.40,P = 0.61。此外,我们还对奥美拉唑的安全性进行了二次评价,共有728例病例组和2676例对照组被选入进行Meta分析。结果显示,病例组和对照组新生儿不良率差异无统计学意义,OR=0.98,CI 95 %：0.61-1.59,P = 0.94。结论：在本文所检索到的数据背景下,奥美拉唑在治疗妊娠期严重的胃肠道类疾病对新生儿是比较安全的。     

EBT3胶片和辐射荧光屏测量质子重离子放疗设备照射野剂量分布的对比研究

目的 对比离线分析的EBT3胶片和在线实时分析的辐射荧光屏对医用质子重离子加速器照射野剂量分布的质控测量差异,选择更适合的设备质控测量的探测器系统。方法 针对主动式点扫描医用质子重离子加速器,在布喇格峰展宽为3 cm,射程分别为7、16、29 cm条件下,通过放疗计划系统规划100 mm×100 mm的质子和碳离子照射野,分别利用EBT3胶片和辐射荧光屏探测器测量各种条件下的照射野大小,EBT3胶片图像获取在照射24小时后通过平板扫描仪获取,辐射荧光屏图像在束流照射过程中由相机实时拍照获取,通过照射野剂量分布曲线的半高宽进行对比分析。结果 三种质子和碳离子射程条件下,通过对比分析,不论物理意义方面还是统计学方面,两种探测器测量质子重离子照射野剂量分布,结果一致性好,精度相当,辐射荧光屏探测器在结果处理时间上更有效率。结论 两种探测器都满足质子重离子照射野剂量学参数测量要求,在照射野剂量分布的指标测量方面,能够在线实时测量分析的辐射荧光屏探测器比EBT3胶片更符合放疗质控发展要求。     

Zero-order release and bioavailability enhancement of poorly water soluble Vinpocetine from self-nanoemulsifying osmotic pump tablet

Abstract

Solid self-nanoemulsifying (S-SNEDDS) asymmetrically coated osmotic tablets of the poorly water-soluble drug Vinpocetine (VNP) were designed. The aim was to control the release of VNP by the osmotic technology taking advantage of the solubility and bioavailability-enhancing capacity of S-SNEDDS. Liquid SNEDDS loaded with 2.5?mg VNP composed of Maisine? 35-1, Transcutol^® HP, and Cremophor^® EL was adsorbed on the solid carrier Aeroperl^®. S-SNEDDS was mixed with the osmotic tablet excipients (sodium chloride, Avicel^®, HPMC-K4M, PVP-K30, and Lubripharm^®), then directly compressed to form the core tablet. The tablets were dip coated and mechanically drilled. A 3²*2¹ full factorial design was adopted. The independent variables were: type of coating material (X₁), concentration of coating solution (X₂), and number of drills (X₃). The dependent variables included % release at 2?h (Y₁), at 4?h (Y₂), and at 8?h (Y₃). The in vivo performance of the optimum formula was assessed in rabbits. Zero-order VNP release was obtained by the single drilled 1.5% Opadry^® CA coated osmotic tablets and twofold increase in VNP bioavailability was achieved. The combination of SNEDDS and osmotic pump tablet system was successful in enhancing the solubility and absorption of VNP as well as controlling its release.     

Investigational hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHI) for the treatment of anemia associated with chronic kidney disease

Introduction: In the last decade, concerns have been raised around the use of erythropoiesis-stimulating agents (ESAs) and intravenous iron in chronic kidney disease (CKD) patients, especially when given at high doses. Moreover, treatment with ESA is expensive.

Areas covered: We searched PubMed for original articles, reviews, and editorials having as a topic anemia, CKD, hypoxia inducible factor, hepcidin, iron, and hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHI). HIF-PHI are a new class of small molecules activating HIF-alfa isoforms (the main mediators of the effects of hypoxia on the body). This causes the secretion of endogenous erythropoietin and increased iron availability. Differing from ESA, HIF-PHI are administered orally. Preliminary data from phase-II clinical studies have shown their efficacy and safety in the short term.

Expert Opinion: HIF-PHI are a new promising class of drugs. The results of large, phase-III clinical studies are awaited to prove their efficacy and safety on cardiovascular events and cancer development in the long term. Their capability of penetrating the ESA market in the future will be influenced also by their selling price. The oral administration of HIF-PHI will be weighed to the ‘intra-lines’ infusion of ESA in hemodialysis or to the infrequent subcutaneous injections of long-acting ESA.     

A comprehensive review on Brigatinib – A wonder drug for targeted cancer therapy in non-small cell lung cancer

The mortality rate in patients suffering from non-small cell lung cancer (NSCLC) is quite high. This type of cancer mainly occurs due to rearrangements in the anaplastic lymphoma kinase (ALK) gene which leads to form an oncogene of fused gene NPM-ALK. Brigatinib is recently approved by FDA in April 2017 as a potent tyrosine kinase inhibitor (TKI) for the NSCLC therapy. In the present scenario, it is no less than a wonder drug because it is indicated for the treatment of advanced stages of metastatic ALK positive NSCLC, a fatal disease to overcome the resistance of various other ALK inhibitors such as crizotinib, ceritinib and alectinib. In addition to ALK, it is also active against multiple types of kinases such as ROS1, Insulin like growth factor-1Receptor and EGFR. It can be synthesized by using N-[2-methoxy-4-[4-(dimethylamino) piperidin-1-yl] aniline] guanidine and 2,4,5-trichloropyrimidine respectively in two different ways. Its structure consists of mainly dimethylphosphine oxide group which is responsible for its pharmacological activity. It is active against various cell lines such as HCC78, H2228, H23, H358, H838, U937, HepG2 and Karpas- 299. Results of ALTA (ALK in Lung Cancer Trial of AP26113) phase ½ trial shows that 90?mg of brigatinib for 7?days and then 180?mg for next days is effective in the treatment of NSCLC. Brigatinib has been shown to have favorable risk benefit profile and is a safer drug than the available cytotoxic chemotherapeutic agents. In comparison to other FDA approved drugs for the same condition, it causes fewer minor adverse reactions which can be easily managed either by changing the dose or by providing good supportive care. This article is intended to provide readers with an overview of chemistry, pharmacokinetic, pharmacodynamic and safety profile of brigatinib, which addresses an unmet medical need.     

A qualitative study exploring patients’ experiences regarding insulin pump use

Background

Diabetes is a threat to peoples’ lives around the world, particularly in the Middle East. Medicine misuse and poor glycaemic control are prevalent among patients with type 2 diabetes, especially insulin-dependent patients (Alsairafi et al., 2016). With advances in medical technology, insulin pumps became a treatment option for patients with type 1 diabetes and those with insulin-dependent type 2 diabetes. However, use of these devices is still lacking in Kuwait, particularly in patients with type 2 diabetes. Information on how patients manage these devices and their efficacy and safety from the perspectives of patients is also lacking (Alsaleh et al., 2016).

Evaluation of WO2017098421: GSK’s benzothiazine compounds as CD73 inhibitor filings

Introduction: There are considerable interests in the development of novel small-molecule CD73 inhibitors for the treatment of cancers, autoimmune diseases, precancerous syndromes, and other diseases associated with CD73 activity.

Areas covered: The application claims novel substituted benzothiadiazine derivatives as CD73 inhibitors for the treatment of cancer, precancerous syndromes, AIDS, autoimmune diseases, infections, atherosclerosis, and ischemia-reperfusion injury. Many of the exemplified compounds have pIC50 values between 5 to 8.4 against CD73.

Expert Opinion: These benzothiadiazine derivatives provide good leads for the discovery of potent CD73 inhibitors for the treatment of cancer and other diseases mediated by adenosine and its action on adenosine receptors.     

Carbonic anhydrase enzymes for regulating mast cell hematopoiesis and type-2 inflammation: a patent evaluation (WO2017/058370)

Introduction: Activity modulators of carbonic anhydrases hold great potential for several therapeutic applications against ophthalmologic and neurological disease, cancer, and infectious diseases. The involvement of carbonic anhydrase in the regulation of mast cell response opens new ways for the treatment of mastocytosis, allergic inflammation, and parasite infection.

Areas covered: The application claims the use of carbonic anhydrase activity modulators (inhibitors or activators) for treating allergic disease, bacterial infection, fungal infection, viral infection, mastocytosis, or mast cell–mediated inflammation.

Expert opinion: Although there is a lack of essential biological data, this patent proposes a new type of applications for carbonic anhydrase inhibitors and deserves further studies. This may lead to new advances in the field of carbonic anhydrase with potential therapeutic implications in the management of type-2 inflammation.