An Update on the Clinical Development of Proprotein Convertase Subtilisin Kexin 9 Inhibitors,Novel Therapeutic Agents for Lowering Low‐Density Lipoprotein Cholesterol

Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays an essential role in the degradation of low‐density lipoprotein C (LDL‐C) receptors, and PCSK9 inhibitors have recently emerged as a potential treatment option to reduce LDL‐C. Our paper reviewed the current available Phase II clinical trials of PCSK9 inhibitors for the treatment of dyslipidemia. A second objective of this review was to evaluate the potential clinical role of PCSK9 inhibitors in the management of dyslipidemia. Studies evaluating the efficacy and safety of any PCSK9 inhibitors in patients with dyslipidemia were included. The monoclonal antibodies REGN727/SAR236553 and AMG145 have the most published clinical data. Seven phase II trials were retrieved that evaluated the efficacy and safety of REGN727/SAR236553 or AMG145 in patients with either hypercholesterolemia or heterozygous familial hypercholesterolemia (HeFH). These two agents significantly decreased LDL‐C levels either as monotherapy or in combination with other lipid‐lowering agents. REGN727/SAR236553 and AMG145 have been well tolerated. The ongoing phase III trials of these two agents are summarized. REGN727/SAR236553 and AMG145 have demonstrated the potential to further decrease LDL‐C levels when added to conventional lipid‐lowering therapy. Morbidity and mortality data are required to define their roles in clinical practice.     

Effects of four treatment strategies for temporomandibular joint closed lock

A previous randomized controlled trial (RCT) by Schiffman et al. (2007)¹⁵ compared four treatments strategies for temporomandibular joint (TMJ) disc displacement without reduction with limited mouth opening (closed lock). In this parallel group RCT, 106 patients with magnetic resonance imaging (MRI)-confirmed TMJ closed lock were randomized between medical management, non-surgical rehabilitation, arthroscopic surgery, and arthroplasty. Surgical groups also received rehabilitation post-surgically. The current paper reassesses the effectiveness of these four treatment strategies using outcome measures recommended by the International Association of Oral and Maxillofacial Surgeons (IAOMS). Clinical assessments at baseline and at follow-up (3, 6, 12, 18, 24, and 60 months) included intensity and frequency of TMJ pain, mandibular range of motion, TMJ sounds, and impairment of chewing. TMJ MRIs were performed at baseline and 24 months, and TMJ tomograms at baseline, 24 and 60 months. Most IAOMS recommended outcome measures improved significantly over time (P ≤ 0.0003). There was no difference between treatment strategies relative to any treatment outcome at any follow-up (P ≥ 0.16). Patient self-assessment of treatment success correlated with their ability to eat, with pain-free opening ≥35 mm, and with reduced pain intensity. Given no difference between treatment strategies, non-surgical treatment should be employed for TMJ closed lock before considering surgery.     

Implementing change in the neonatal unit: Part 2 – The change process

Pain management in premature and sick babies has long been recognised as a vital component of neonatal care; however practices pertaining to pain assessment and administration of analgesia remain variable in Neonatal Units (NNU). Sucrose has been identified as an effective agent in reducing pain during minor painful procedures in premature babies but the uptake has been modest.This article (part 2) follows on from an earlier article on evidence to support the implementation of sucrose administration as a measure for pain relief for minor procedures (part 1) and will centre on practice-based change in the NNU and reflect on the strategies used as well as the effectiveness of the proposed change. A theoretical change model will be used as a framework to help unpack the influences inherent within the change process.     

胆管镜联合腹腔镜治疗肝胆管结石的临床效果分析

目的探讨胆管镜联合腹腔镜治疗肝胆管结石的临床效果。方法选择本院外科利用胆管镜联合腹腔镜治疗肝胆管结石的47例患者为腹腔镜组,采用传统开腹手术切开肝胆管取石的47例患者为开腹组,比较两组疗效。结果腹腔镜组手术时间较长,但术中出血量、平均住院时间及术后并发症发生率明显低于开腹组,差异有统计学意义（P〈0.05）。结论胆管镜联合腹腔镜治疗肝胆管结石出血量少,并发症少,能有效减轻患者的痛苦,值得临床推广。     

DP、EP化疗方案治疗非小细胞肺癌的临床疗效及其对血清血管内皮生长因子的影响

目的对比DP、EP化疗方案治疗非小细胞肺癌（NSCLC）的临床疗效及其对血清血管内皮生长因子（VEGF）的影响。方法102例晚期NSCLC患者随机分为DP组（n=58）和EP组（n=44）。DP组静脉注射多西紫杉醇75mg／m2，dl；静脉滴注顺铂75mg／m2，d1～4；EP组静脉滴注依托泊苷0．1g／d，d1～5；顺铂用法同上。两组28d为1个周期，治疗3个周期，化疗前后常规给予止呕类药物及对症治疗。检测两组临床疗效和血清VEGF水平。结果DP组、EP组，总有效率分别为74．14％和29．55％，DP组总有效率明显高于EP组。与治疗前比较，两组治疗后血清VEGF水平均明显降低。DP组治疗后血清VEGF水平明显低于EP组治疗后。结论DP治疗中晚期NSCLC临床疗效确切，有效率、生存率均较高。     

Does prophylactic antidepressant treatment boost interferon-alpha treatment completion in HCV?

Depression is often a side effect of interferon-alpha treatment for hepatitis C, and is recognized as a cause for treatment discontinuation. When detected, antidepressant treatment begins promptly. In contrast to this rescue approach, prophylactic antidepressant treatment has been considered as a superior approach. While studies indicate that depression is lower with prophylaxis, no study has prospectively evaluated the degree that treatment completion might be boosted by the prophylactic strategy. A structured literature search was conducted to discover all trials of antidepressant prophylaxis for patients undergoing antiviral treatment for chronic hepatitis C. Selection criteria included: antidepressant prophylaxis study; report of depression treatment outcome; report of numbers discontinuing and reason for discontinuation (including any of the following: discontinuation data for medical side effects (i.e., thrombocytopenia); discontinuation due to lack of antiviral response; discontinuation due to lack of antidepressant effect; discontinuation due to antidepressant side effects; discontinuation due to patient preference; discontinuation due to loss to follow-up; or unspecified discontinuation). Across the studies, total enrollees were determined for the prophylaxis arms and the rescue arms, and then, again across studies, those discontinuing for reasons other than lack of antiviral response or medical side effect were summed for each of these two arms. Twelve studies were discovered. One was a retrospective chart review, one was an uncontrolled trial, and ten were controlled trials. Discontinuation of antiviral therapy was not less common in the prophylaxis arms: of the 396 patients treated by the prophylaxis strategy, 47 (11.9%) discontinued; of the 380 patients in the rescue strategy, 45 (11.8%) discontinued. While the prophylaxis strategy seems to manage depression symptoms, it does not seem to boost treatment completion. Rescue was a very successful strategy when indicated. While antidepressant prophylaxis has benefit in antiviral treatment, it should not generally be valued for boosting the likelihood of treatment completion.     

开展药学监护的案例分析

临床药师参与我院主要科室查房,在药物的选择、治疗方案的实施中为医务人员和患者提供服务,发挥药物的最佳临床治疗作用,提高患者的治疗效果,减少了药物不良反应,促进了临床合理用药,同时对临床药师自身的培养起到了积极的作用。