A t the time that I write this, the world is in the grip of the COVID-19 disease pandemic. As you likely have heard more times than you care to count by now, the viral agent causing this disease is related to the virus that causes severe acute respiratory syndrome (SARS), and for that reason the virus is officially called SARS-CoV-2. The CoV indicates that the virus is a member of the Coronaviridae family, whose name is derived from the spikeor crown-like appearance of the surface proteins that are visible under an electron microscope. As you have probably also heard many times, a vaccine for this virus is likely to be at least a year in development. Given that this vaccine represents a determined worldwide endeavor with billions of dollars being poured into the effort, like me, you may have been curious about the reason for this extended time frame for the vaccine development process. In tracking down the answer to this question, I was struck by the similarities between the history and process of vaccine development and that of the development of neurologic physical therapy interventions. Vaccines have advanced tremendously since the first-generation approaches that represent the types of vaccines we received as children. In these earliest, whole-pathogen vaccines, injection of small amounts of attenuated or inactivated virus activates the immune system, triggering the development of antibodies that protect us against infection. Second-generation, subunit vaccines, rather than being based on whole viruses, involve only the antigens that activate the immune system. Finally, third-generation, nucleic acid vaccines involve injection of plasmid with the encoding gene of the desired antigen to induce the immune system to express antibodies.1,2 Each of the 3 forms of vaccines is of value, and their utility depends on the viral target. There are striking parallels between the evolution of vaccine development and the evolution of neurologic physical therapist practice, with our conventional, contemporary, and emergent approaches. One might consider conventional interventions that target compensation to be our first-generation approaches. The more contemporary, task-specific training interventions intended to promote restoration through use-dependent plasticity would be our second-generation approaches. Lastly, emergent interventions that combine neuromodulation with training interventions designed to promote use-dependent plasticity could be thought of as our third-generation approaches. Despite the similarities in the evolution of vaccine development and the advancement of neurologic physical therapy interventions, there are conspicuous differences in the processes of investigating the value of these respective classes of interventions. Vaccines undergo the stepwise process used with almost all other pharmacologic and biologic interventions. In the vast majority of cases, prior to being made available on a broad scale, they progress from basic mechanistic studies through small phase 1 safety studies to moderately sized phase 2 dose-response studies to large phase 3 randomized clinical trials. For various reasons, the advancement of neurologic physical therapy interventions has mostly followed a different path. Our conventional, first-generation physical therapy treatments primarily arose from a trial-and-error approach in the clinical setting and were passed along as part of our academic and clinical training. Second-generation physical

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COVID-19 关于干预措施逐步发展的经验教训

在我写这篇文章的时候，世界正处于 COVID-19 疾病大流行的控制之中。到目前为止，您可能听到的次数比您想数的要多，导致这种疾病的病毒病原体与导致严重急性呼吸系统综合症 (SARS) 的病毒有关，因此该病毒被正式称为 SARS-CoV-2 . 冠状病毒表明该病毒是冠状病毒科的成员，其名称来源于在电子显微镜下可见的表面蛋白的穗状冠状外观。正如您可能也多次听到的那样，针对这种病毒的疫苗可能至少要开发一年。鉴于这种疫苗代表了一项坚定的全球努力，像我一样投入了数十亿美元，您可能对疫苗开发过程时间延长的原因感到好奇。在追查这个问题的答案时，我对疫苗开发的历史和过程与神经物理治疗干预的开发之间的相似性感到震惊。自代表我们小时候接种的疫苗类型的第一代方法以来，疫苗取得了巨大的进步。在这些最早的全病原体疫苗中，注射少量减毒或灭活病毒会激活免疫系统，从而引发保护我们免受感染的抗体的发展。第二代亚单位疫苗不是基于整个病毒，而是仅涉及激活免疫系统的抗原。最后，第三代，核酸疫苗涉及注射含有所需抗原编码基因的质粒，以诱导免疫系统表达抗体。1,2 3 种形式的疫苗中的每一种都是有价值的，它们的效用取决于病毒靶标。疫苗开发的演变与神经物理治疗师实践的演变以及我们的传统、现代和新兴方法之间存在惊人的相似之处。人们可能会认为以补偿为目标的传统干预措施是我们的第一代方法。旨在通过依赖使用的可塑性促进恢复的更现代的、针对特定任务的培训干预措施将是我们的第二代方法。最后，将神经调节与旨在促进使用依赖性可塑性的训练干预相结合的紧急干预可以被认为是我们的第三代方法。尽管疫苗开发的演变和神经物理治疗干预措施的进步有相似之处，但在调查这些各自类别的干预措施的价值的过程中存在显着差异。疫苗经历了与几乎所有其他药理学和生物干预措施一起使用的逐步过程。在绝大多数情况下，在大规模提供之前，它们从基本的机制研究进展到小型 1 期安全性研究，再到中等规模的 2 期剂量反应研究，再到大型 3 期随机临床试验。由于种种原因，神经物理治疗干预的进展大多遵循不同的路径。我们传统的第一代物理疗法主要源于临床环境中的反复试验方法，并作为我们学术和临床培训的一部分进行传递。第二代物理