FDA“通过1项充分和良好对照的临床研究和确证性证据证明有效性的实质性证据的供企业用的指导原则”介绍

“如果FDA根据相关科学确定,1项充分且良好对照的临床研究的数据和确证性证据足以确定有效性,FDA可认为这项数据和证据构成实质性证据。”尽管自1998年以来,FDA这一有效性证据标准没有改变,但药物开发和科学不断发展,使药物开发方案的性质发生变化,需要提供更多指导原则阐明该标准的灵活性。为满足这种需求,美国食品药品管理局(FDA)于2023年9月发布了“通过1项充分且良好对照的临床研究和确证性证据证明有效性的实质性证据的供企业用的指导原则草案”,对FDA的2019年有效性指导原则草案和1998年有效性指导原则做了补充。该指导原则描述了在评估1项充分且良好对照的临床研究和确证性证据是否足以证明有效性的实质性证据时,需要考虑的因素,还提供了确证性证据的数据类型的示例。我国目前还没有类似的指导原则,详细介绍该指导原则,期望对我国这方面的研究和监管有益。     

FDA “肽类药物产品临床药理学的考虑的供企业用的指导原则草案” 及其启示

美国食品药品管理局（FDA）于2023年9月发布了“肽类药物产品临床药理学的考虑的供企业用的指导原则草案”。该指导原则描述了FDA对肽类药物产品开发方案的临床药理学的建议,包括肝损害、药物-药物相互作用评估、心电图按心率校正的QT间期（QTc）延长风险评估以及免疫原性风险及其对药动学、安全性和有效性评估的影响。详细介绍FDA该指导原则的主要内容,期望对我国肽类药物产品临床药理学研究和监管有所启示。     

FDA对眼用制剂的质量研究要求及启示

美国食品药品管理局(FDA)于2023年12月28日发布了题为"局部外用眼科药品的质量考虑"的指导原则草案,对2023年10月发布的同名指导原则草案进行了修订。该指导原则草案讨论了用于眼内和眼周局部给药的眼用产品,包括凝胶、软膏、乳膏和液体制剂等剂型的眼用制剂的一些质量考虑,涵盖质量研究中微生物学、可见颗粒物、可提取物和可浸出物、杂质和降解产物、稳定性研究5个方面,并对容器密封系统(CCS)设计等提出了相关建议。详细介绍FDA该指导原则草案主要内容,期望对该类药物的研发和质量评价有所启示。     

Cybersecurity for Cardiac Implantable Electronic Devices: What Should You Know?

Medical devices have been targets of hacking for over a decade, and this cybersecurity issue has affected many types of medical devices. Lately, the potential for hacking of cardiac devices (pacemakers and defibrillators) claimed the attention of the media, patients, and health care providers. This is a burgeoning problem that our newly electronically connected world faces. In this paper from the Electrophysiology Section Council, we briefly discuss various aspects of this relatively new threat in light of recent incidents involving the potential for hacking of cardiac devices. We explore the possible risks for the patients and the effect of device reconfiguration in an attempt to thwart cybersecurity threats. We provide an outline of what can be done to improve cybersecurity from the standpoint of the manufacturer, government, professional societies, physician, and patient.     

An age-adjusted instruction video enhances the correct use of nasal corticosteroid sprays in children

Introduction and objectivesAllergic rhinitis is a common disorder. Intranasal corticosteroid sprays are used to control symptoms. However, incorrect use of these sprays can decrease efficacy and lead to side effects such as nose bleeding. We studied if watching an age-adjusted instruction video is effective to improve administration technique.Materials and methodsWe invited children who used intranasal corticosteroid sprays. We examined their administration technique before, directly after, and one month after showing them an age-adjusted instruction video. We compared their administration technique with the instructions in the patient information leaflet. We assessed whether the children performed the seventeen maneuvers mentioned in the patient information leaflet and the eight we considered essential.ResultsOf the 99 eligible children, 23 (15 boys, median age nine years) participated. Before watching the instruction video none of them administered according to all maneuvers in the patient information leaflet or showed all essential maneuvers. One month after seeing the instruction video, three children demonstrated correct inhalation as per the patient information leaflet. Three performed the essential maneuvers. When a 75% threshold level for carrying out all 17 maneuvers was used, still none showed 75% of all or of the essential maneuvers before watching the video. Yet, after one month 12 children showed sufficient administration technique (52%, 95% confidence interval (CI) 31%–73%, p = 0.004). Nine showed all essential manoeuvres (47%, 95%CI 24%–71%, p = 0.004).ConclusionsAn age-adjusted instruction video is a useful and easy method to teach children to administer nasal intranasal corticosteroid sprays correctly.     

Fecal Microbiota Transplantation for Recurrent C difficile Infection During the COVID-19 Pandemic: Experience and Recommendations

ObjectiveTo report experience with fecal microbiota transplantation (FMT) for recurrent Clostridioides difficile infection (rCDI) and provide recommendations for management of rCDI and donor testing during the COVID-19 pandemic.MethodsA retrospective study of patients with rCDI who underwent FMT from May 26, 2020, to September 30, 2020, with stool from well-screened donors with health and infectious screening and a newly implemented strategy for COVID-19 screening with every 2-week bookend testing with stool quarantine. Patients were followed up for development of rCDI and COVID-19.ResultsOf the 57 patients who underwent FMT for rCDI, 29 were tested for COVID-19 via nasopharyngeal polymerase chain reaction (PCR) and 22 via serology. All results were negative, except for 1 positive serology. Donor testing every 2 weeks for COVID-19 via serology and nasopharyngeal swab PCR was negative, except for 2 donors at 1 center who were excluded. Three patients had rCDI after FMT, and 1 underwent repeat FMT. One patient developed respiratory symptoms suggestive of COVID-19 and tested negative via nasopharyngeal PCR. Eleven patients who underwent COVID-19 testing for elective procedures or hospitalizations tested negative. No SARS-CoV-2 transmission was noted.ConclusionsWith appropriate donor screening, FMT can be performed safely for rCDI during the COVID-19 pandemic. Development of a validated stool assay for SARS-CoV-2 will simplify this process further.     

Diagnosis of von Willebrand's disease. A comparative study of diagnostic tests on nine families with von Willebrand's disease and its differential diagnosis from hemophilia and thrombocytopathy.

Nine probands with von Willebrand's disease, and their family members, totalling 43 people, were examined. Twenty-seven had a history of bleeding; 29 had an increased factor VIII activity:factor VIII related antigen ratio; 24 had a decreased factor VIII related antigen; 23 had a prolonged bleeding time; 19 had a reduced platelet adhesiveness; 16 had a decreased factor VIII activity; and 14 had an abnormal ristocetin-induced platelet aggregation. Eight members with both normal beleeding time and normal factor VIII activity were found to have other abnormal tests: elevated ratio of factor VIII activity to factor VIII related antigen in seven; decreased factor VIII related antigen in four; and reduced platelet adhesiveness in one. Therefore, ratio of factor VIII activity to factor VIII related antigen and factor VIII related antigen are more sensitive and may be used for the detection of heterozygous carriers of von Willebrand's disease. Although patients with thrombocytopathy may have a prolonged bleeding time, decreased platelet adhesiveness and reduced platelet aggregation by ristocetin, their factor VIII activity, factor VIII related antigen and ratio of factor VIII activity to factor VIII related antigen are normal and their abnormal ristocetin test cannot be corrected by the addition of factor VIII concentrate. Hemophilic subjects and hemophilic carriers, who are deficient in factor VIII activity, usually have a normal bleeding time, normal platelet adhesiveness, and normal ristocetin test. In contrast to patients with von Willebrand's disease, their factor VIII related antigen is normal or slightly increased and their ratio of factor VIII activity to factor VIII related antigen is significantly reduced. We conclude that ratio of factor VIII activity to factor VIII related antigen and factor VIII related antigen are not only more sensitive but also more specific for the diagnosis of von Willebrand's disease.     

基于数据挖掘探讨葛琳仪治疗慢性泄泻用药规律

目的:研究国医大师葛琳仪治疗慢性泄泻的用药规律,总结其相关学术思想。方法:利用Excel收集整理葛琳仪治疗慢性泄泻的处方数据,采用SPSS Clementine12.0进行关联分析,Apriori算法建立数据挖掘模型,用SPSS20.0对数据进行描述性分析及聚类分析。结果:共筛选出329个处方,包含216味中药,用药频次总计5 299次,使用频率较高的药物是陈皮、广木香、枳壳、生白芍、厚朴等,主要为理气药、补虚药、清热药、化湿药、消食药等,挖掘出药对或药物组合8组。结论:葛琳仪治疗慢性泄泻有立足脾胃,调畅气机;培补正气,标本同治;用药轻灵,思辨加减的特点,值得医者学习并传承。