2003年美国FDA批准的新药

2003年美国FDA批准了新分子实体(Newmolecular entities,NMEs)21个.按疗效分类,主要有抗感染药物6个(占28.57%),肿瘤治疗及辅助用药5个(占23.81%),其他类药物共10个(占47.62%).     

Influence of climatic conditions on antiperspirant efficacy determined at different test areas

Background: The efficacy of antiperspirants is a current topic among the developers of cosmetic products. According to the Food and Drug Administration (FDA) for the US market, efficacy testing performed in the axilla of human volunteers is mandatory. Another method is yet available, which enables comparison of more than one antiperspirant formula in a single study by performing the test on the backs of volunteers. However, how reproducible are these methods, comparing between the back and axilla? Do they differ as a result of seasonal variation? Is a correlation between the results of the two methods possible? Methods: To answer these questions, the antiperspirant efficacy of aluminium chlorohydrate (ACH) aqueous solutions was investigated in the axilla and on the backs of volunteers, in four separate clinical studies covering cold and warm seasons. Four days of product application were followed by thermal sweat induction on the fifth day, using a sauna. The amount of sweat recovered by weighing cotton pads before and after sweat induction was used to calculate sweat reduction. Testing in the axilla and on the back was performed on the same volunteers simultaneously to achieve the best comparable data. For this reason, the FDA guideline was slightly modified to thermal stimulation in a sauna instead of in a hot room. Results: Increasing concentrations of ACH in aqueous solutions on the backs of volunteers showed a saturation for 8% ACH with a sweat reduction of approximately 50%. The antiperspirant efficacy of solutions containing 4%, 8% or 12% ACH was repeatedly found at the same levels, when tested on the backs during summer, autumn and winter time. Axilla tests, with an 8% ACH aqueous solution, showed strongly varying results for summer and winter time, represented by sweat reduction values of ?2% to 25%. As an assumption, these high variations might result from reduced gel formation in cold seasons due to low humidity in the axillae during the application phase. On the back, this effect was avoided by applying occlusive foils after product application. To gain further insight, a study, during which summer conditions were artificially simulated by thermal stimulation during the application phase, again showed decreased antiperspirant efficacy in the axilla for winter conditions with sweat reduction values of 2%, compared with 25% under simulated summer conditions. Conclusion: These strongly varying values of sweat reduction in the axilla under summer and winter conditions make comparisons between antiperspirant products difficult and a statement about correlation between the two test sites back and axilla impossible. A standardization of the application phase, comparable to the simulated summer conditions described here, could be a solution to reduce the high variation of results in the axilla. Consequently, testing on the back is not only a more cost‐effective method to investigate the antiperspirant efficacy of more than one formulation, but a reproducible method more independent of climatic influences during test implementation than the axilla test method. It could, therefore, be regarded as the method of choice for discriminating antiperspirant efficacy between several products during development of new antiperspirant formulations.     

基于FDA不良事件报告系统的利奥西呱不良事件信号挖掘与分析

目的：挖掘和分析利奥西呱上市后的不良事件信号，为临床安全合理用药提供参考。方法：将FDA不良事件报告系统中2013年10月1日 ~ 2022年12月31日的原始数据导入SAS 9.4软件，采用报告比值比法以及英国药品和保健产品管理局综合标准法对利奥西呱不良事件信号进行挖掘，分层分析考察不同性别、年龄和体重的人群服用利奥西呱发生不良事件的差异。结果：以利奥西呱为主要可疑药物的不良事件报告共计10 528份，不良事件发生的中位时间为183 d。共挖掘出305个不良事件信号，涉及20个系统和器官分类，发生频次较高的不良事件信号与药品说明书基本一致。说明书未记载的不良事件包括肠道梗阻、食管炎、反应迟缓、听觉障碍等。女性患者出现头痛、心悸和颌骨疼痛的概率显著高于男性，而男性患者发生咯血的概率显著高于女性。18 ~ 64岁的患者发生头痛、心悸、颌骨疼痛和咯血概率显著高于64岁以上患者，而后者出现外周水肿（肿胀）、舒张压降低和贫血的概率显著增加。结论：临床使用利奥西呱时，应关注性别和年龄对不良事件的影响，以及说明书未载入的不良事件，加强药学监护。     

Comparing SGLT-2 inhibitors to DPP-4 inhibitors as an add-on therapy to metformin in patients with type 2 diabetes: A systematic review and meta-analysis

Aims

Our aim was to compare Sodium-glucose co-transporter 2 inhibitors (SGLT-2i) to Dipeptidyl peptidase-4 inhibitors (DPP-4i) as add-on therapy to metformin.

Effect of Exercise and Pharmacological Interventions on Visceral Adiposity: A Systematic Review and Meta-analysis of Long-term Randomized Controlled Trials

Objective

To assess the effectiveness of exercise and pharmacotherapy interventions in reducing visceral adipose tissue (VAT).

A cost-utility analysis of transcatheter versus surgical aortic valve replacement for the treatment of aortic stenosis in the population with intermediate surgical risk

Objective

Although transcatheter aortic valve implantation has been shown to be noninferior to surgical aortic valve replacement in patients with severe aortic stenosis at intermediate surgical risk, the cost-effectiveness of this strategy in this population is unknown. Our objective was to conduct a cost-utility analysis comparing transcatheter aortic valve implantation with surgical aortic valve replacement in the population with intermediate risk severe aortic stenosis.

Amyotrophic Lateral Sclerosis: An Update for 2018

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting motor neurons and other neuronal cells, leading to severe disability and eventually death from ventilatory failure. It has a prevalence of 5 in 100,000, with an incidence of 1.7 per 100,000, reflecting short average survival. The pathogenesis is incompletely understood, but defects of RNA processing and protein clearance may be fundamental. Repeat expansions in the chromosome 9 open reading frame 72 gene (C9orf72) are the most common known genetic cause of ALS and are seen in approximately 40% of patients with a family history and approximately 10% of those without. No environmental risk factors are proved to be causative, but many have been proposed, including military service. The diagnosis of ALS rests on a history of painless progressive weakness coupled with examination findings of upper and lower motor dysfunction. No diagnostic test is yet available, but electromyography and genetic tests can support the diagnosis. Care for patients is best provided by a multidisciplinary team, and most interventions are directed at managing symptoms. Two medications with modest benefits have Food and Drug Administration approval for the treatment of ALS: riluzole, a glutamate receptor antagonist, and, new in 2017, edaravone, a free radical scavenger. Many other encouraging treatment strategies are being explored in clinical trials for ALS; herein we review stem cell and antisense oligonucleotide gene therapies.     

Immunogenicity and safety of an AS03-adjuvanted H5N1 pandemic influenza vaccine in Korean adults: A phase IV,randomized, open-label,controlled study

BackgroundAS03-adjuvanted H5N1 pandemic influenza vaccines have been assessed in an extensive clinical development program conducted in North America, Europe, and Asia including children from 6 months of age, adults, and elderly adults. We evaluated AS03-H5N1 in Korean adults 18 through 60 years of age.MethodsThis Phase IV, randomized, study was conducted to assess the immunogenicity, reactogenicity, and safety of two doses (3.75 μg of hemagglutinin antigen) of A/Indonesia/5/2005 (H5N1) adjuvanted with AS03 given 21 days apart in Korean adults. Antibody responses were assessed using hemagglutination-inhibition (HI) assays against the vaccine strain and a vaccine-heterologous strain (A/Vietnam/1194/2004) 21 days after the second dose. A control group (safety) received a licensed seasonal inactivated trivalent influenza vaccine (TIV). Reactogenicity was assessed for 7 days after each vaccination, and unsolicited adverse events were assessed for 182 days following vaccination in both study groups (NCT01730378).ResultsAS03-H5N1 was immunogenic and elicited robust HI antibody responses with seroconversion rates of 100% for the vaccine strain and 69.1% for the heterologous strain (N = 81). HI antibody responses fulfilled the European licensure criteria for immunogenicity (primary endpoint). The incidence of local and systemic solicited adverse events (reactogenicity) was higher with AS03-H5N1 than TIV. There was no apparent difference in the rate of unsolicited adverse events in the AS03-H5N1 and TIV groups.ConclusionThe results indicate that AS03-H5N1 vaccine is immunogenic with reactogenicity and safety findings that are consistent with the established profile of AS03-H5N1 vaccine.     

Overview of digital breast tomosynthesis: Clinical cases,benefits and disadvantages

In France, the national breast cancer-screening program is based on mammography combined with clinical breast examination, and sometimes breast ultrasound for patients with high breast density. Digital breast tomosynthesis is a currently assessed 3D imaging technique in which angular projections of the stationary compressed breast are acquired automatically. When combined with mammography, clinicians can review both conventional (2D) as well as three-dimensional (3D) data. The purpose of this article is to review recent reports on this new breast imaging technique and complements this information with our personal experience. The main advantages of tomosynthesis are that it facilitates the detection and characterization of breast lesions, as well as the diagnosis of occult lesions in dense breasts. However, to do this, patients are exposed to higher levels of radiation than with 2D mammography. In France, the indications for tomosynthesis and its use in breast cancer-screening (individual and organized) are yet to be defined, as is its role in the diagnosis and staging of breast cancer (multiple lesions). Further studies assessing in particular the combined reconstruction of the 2D view using 3D tomosynthesis data acquired during a single breast compression event, and therefore reducing patient exposure to radiation, are expected to provide valuable insight.