New and emerging immune-targeted drugs for the treatment of multiple sclerosis

Multiple sclerosis (MS) is a neurodegenerative disease with a major inflammatory component that constitutes the most common progressive and disabling neurological condition in young adults. Injectable immunomodulatory medicines such as interferon drugs and glatiramer acetate have dominated the MS market for over the past two decades but this situation is set to change. This is because of: (i) patent expirations, (ii) the introduction of natalizumab, which targets the interaction between leukocytes and the blood–CNS barrier, (iii) the launch of three oral immunomodulatory drugs (fingolimod, dimethyl fumarate and teriflunomide), with another (laquinimod) under regulatory review and (iv) a number of immunomodulatory monoclonal antibodies (alemtuzumab, daclizumab and ocrelizumab) about to enter the market. Current and emerging medicines are reviewed and their impact on people with MS considered.     

Effectiveness of newspaper advertising for patient recruitment into a clinical trial

Aims

To measure the impact of newspaper advertising across Scotland on patient interest, and subsequent recruitment into the Standard Care vs. Celecoxib Outcome Trial (SCOT), a clinical trial investigating the cardiovascular safety of non-steroidal anti-inflammatory drugs in patients with osteoarthritis or rheumatoid arthritis.

Methods

Newspaper advertisements about the SCOT trial were placed sequentially in regional and national Scottish newspapers. The number of phone calls as a result of exposure to the advertisements and ongoing study recruitment rates were recorded before, during and after the advertising campaign. To enroll in SCOT individuals had to be registered with a participating GP practice.

Results

The total cost for the advertising campaign was £46 250 and 320 phone calls were received as a result of individuals responding to the newspaper advertisements. One hundred and seventy-two individuals were identified as possibly suitable to be included in the study. However only 36 were registered at participating GP practices, 17 completed a screening visit and 15 finally were randomized into the study. The average cost per respondent individual was £144 and the average cost per randomized patient was £3083. Analysis of recruitment rate trends showed that there was no impact of the newspaper advertising campaign on increasing recruitment into SCOT.

Conclusions

Advertisements placed in local and national newspapers were not an effective recruitment strategy for the SCOT trial. The advertisements attracted relatively small numbers of respondents, many of whom did not meet study inclusion criteria or were not registered at a participating GP practice.     

控制性超促排卵中溢乳症的临床处理分析

目的探讨不同临床处理对体外授精-胚胎移植(in vitro fertilization and embryo transfer,IVF-ET)中伴溢乳症的不孕症患者妊娠结局的影响。方法选择在邢台不孕不育专科医院生殖中心接受IVF-ET的不孕症患者358例,其中伴溢乳症296例,无溢乳症及基础血清催乳素(prolactin,PRL)正常的62例。按有无溢乳症、高PRL血症及其处理方法分为5组,A组为溢乳症不伴有高PRL血症,应用甲磺酸溴隐亭治疗;B组为溢乳症伴有高PRL血症,应用甲磺酸溴隐亭治疗;C组为溢乳症不伴有高PRL血症,应用中药治疗;D组为溢乳症不伴有高PRL血症,未给予药物治疗;E组为无溢乳症及基础血清PRL正常。比较5组不孕症患者外源性促性腺激素(gonadotropin,Gn)启动日PRL水平、注射绒毛膜促性腺激素(chorionic gonadotrophin,HCG)日PRL水平、获卵数、可用胚胎数、临床妊娠率。结果 5组不孕症患者比较,A组临床妊娠率最低(P0.05);在Gn启动日和注射HCG日,A组PRL水平低于其他4组(P0.05)。结论不孕症患者无高PRL血症的溢乳症状无需进行治疗,为改善症状,中药治疗可作为很好的尝试。     

Randomized controlled trial of MICBT for co-existing alcohol misuse and depression: Outcomes to 36-months

Integrated psychological treatment addressing co-existing alcohol misuse and depression has not been compared with single-focused treatment. This trial evaluates changes over 36 months following randomization of 284 outpatients to one of four motivational interviewing and cognitive–behavior therapy (MICBT) based interventions: (1) brief integrated intervention (BI); or BI plus 9 further sessions with (2) an integrated-, (3) alcohol-, or (4) depression-focus. Outcome measures included changes in alcohol consumption, depression (BDI-II: Beck Depression Inventory) and functioning (GAF: Global Assessment of Functioning), with average improvements from baseline of 21.8 drinks per week, 12.6 BDI-II units and 8.2 GAF units. Longer interventions tended to be more effective in reducing depression and improving functioning in the long-term, and in improving alcohol consumption in the short-term. Integrated treatment was at least as good as single-focused MICBT. Alcohol-focused treatment was as effective as depression-focused treatment at reducing depression and more effective in reducing alcohol misuse. The best approach seems to be an initial focus on both conditions followed by additional integrated- or alcohol-focused sessions.     

Evolution of interventional vancomycin trials in light of new antibiotic development in the USA, 1999–2012

Use of vancomycin has increased following the emergence of resistant Gram-positive bacterial infections. Investigation into recent vancomycin clinical studies provides insight into the optimal use of vancomycin and the development of novel antibiotics for the treatment of resistant infections. Interventional vancomycin trials registered in ClinicalTrials.gov from January 1999 to December 2012 were identified. Trial trends and characteristics were evaluated in the context of vancomycin use and new antibiotic development. Overall, 122 interventional vancomycin trials were identified, with a significant increase in the number of registered trials per year (P < 0.001). The top three indications studied were skin and soft-tissue infections (28.7%), Clostridium difficile infections (13.1%) and surgical prophylaxis (12.3%). Trials testing vancomycin as an experimental agent differed from trials using vancomycin as an active comparator. Experimental agent trials commonly investigated new formulations, dosing regimen optimisation and combination therapy, which were less likely to be in phase 2 or 3 (25% vs. 70%; P < 0.001), adopt a randomisation procedure (70% vs. 98%; P < 0.001), report results (15% vs. 35%; P = 0.02) or be funded by industry (8% vs. 76%; P < 0.001). Active comparator trials mainly focused on monotherapy, which led to six FDA-approved drug products and ten investigational new drugs in late-phase development. This study demonstrated a significant increase in interventional vancomycin trials and its recent success, which resulted in several novel agents against resistant Gram-positive bacteria. Further studies are warranted to determine how these agents can best be incorporated within clinical practice.     

他汀类药物引起肝功能异常的系统评价

目的:系统评价他汀类药物引起肝功能异常的风险。方法:计算机检索中国生物医学文献数据库、中国期刊全文数据库、万方数据库、PubMed、EMBase、Medline、Cochrane Library、康健数据库中有关他汀类药物引起肝功能异常的随机对照试验(RCT),评价纳入研究的文献质量,提取有效数据后,采用Rev Man 5.0统计软件对数据进行Mate分析。结果:共纳入9项研究,合计9 084例患者。研究包含药物有辛伐他汀、阿托伐他汀、氟伐他汀、瑞舒伐他汀、洛伐他汀。Meta分析结果显示,使用他汀类药物治疗的患者肝功能异常发生率显著高于使用安慰剂治疗的患者,差异有统计学意义[OR=2.00,95%CI(1.23,3.25),P=0.005];并且他汀类药物高剂量组患者肝功能异常发生率显著高于低剂量组,差异亦有统计学意义[OR=1.84,95%CI(1.04,3.27),P=0.04]。结论:使用他汀类药物有引起患者肝功能异常的风险,且高剂量较易发生肝功能异常,临床应谨慎用药。由于纳入研究数量较少,该结论尚需大样本、高质量的RCT进一步证实。     

右美托咪啶联合丙泊酚对全麻手术患者血流动力学的影响

目的:观察右美托咪啶联合丙泊酚对全麻手术患者血流动力学的影响。方法:将60例择期行全麻手术患者按随机数字表法均分为氯化钠注射液组(C组)、右美托咪啶组(D1^D4组)。所有患者均给予丙泊酚进行麻醉诱导,C组患者给予氯化钠注射液,D1D4组)。所有患者均给予丙泊酚进行麻醉诱导,C组患者给予氯化钠注射液,D1^D4组患者均给予右美托咪啶。监测5组患者诱导前(T0)、给药后5 min(T1)、10 min(T2)、睫毛反射消失时(T3)、意识消失时(T4)、气管插管前即刻(T5)、气管插管后1 min(T6)、3 min(T7)时的心率(HR)、平均动脉压(MAP)变化;记录睫毛反射消失时、意识消失时丙泊酚效应室浓度(ECC)及剂量;记录患者气管插管阳性反应及不良反应发生情况。结果:C组、D1组患者T5及T6时HR、MAP均显著高于T0时,差异有统计学意义(P<0.05);D2组、D3组患者T1D4组患者均给予右美托咪啶。监测5组患者诱导前(T0)、给药后5 min(T1)、10 min(T2)、睫毛反射消失时(T3)、意识消失时(T4)、气管插管前即刻(T5)、气管插管后1 min(T6)、3 min(T7)时的心率(HR)、平均动脉压(MAP)变化;记录睫毛反射消失时、意识消失时丙泊酚效应室浓度(ECC)及剂量;记录患者气管插管阳性反应及不良反应发生情况。结果:C组、D1组患者T5及T6时HR、MAP均显著高于T0时,差异有统计学意义(P<0.05);D2组、D3组患者T1^T4时HR、MAP均显著低于T0时,差异有统计学意义(P<0.05);D4组患者各时点HR均显著低于T0时,T1、T2时点MAP均显著高于T0时,差异均有统计学意义(P<0.05);D2组、D3组、D4组患者HR较C组、D1组在T2T4时HR、MAP均显著低于T0时,差异有统计学意义(P<0.05);D4组患者各时点HR均显著低于T0时,T1、T2时点MAP均显著高于T0时,差异均有统计学意义(P<0.05);D2组、D3组、D4组患者HR较C组、D1组在T2^T6时点均显著降低,D2组、D3组患者MAP较C组、D1组在T3T6时点均显著降低,D2组、D3组患者MAP较C组、D1组在T3^T6时点均显著降低,差异均有统计学意义(P<0.05);睫毛反射消失时和意识消失时D2组、D3组、D4组患者ECC及剂量较D1组、C组均显著降低,且D3、D4组显著低于D2组,差异均有统计学意义(P<0.05),D2组、D3组患者不良反应发生率显著低于C、D1、D4组患者,且D2组显著低于D3组,差异均有统计学意义(P<0.05)。结论:右美托咪啶联合丙泊酚应用于全麻手术患者,不仅可以维持患者全麻诱导期间血流动力学稳定,还可有效控制患者的应激反应。但是,右美托咪啶用于老年患者麻醉诱导期间的确切疗效和安全性尚须进一步临床研究。