Transforming Parkinson's disease clinical management with integrated digital health technologies

帕金森氏病(PD)是一种无法治愈的进行性神经系统疾病，由于人口老龄化，其患病率正在迅速增长。问题是，用于治疗帕金森病的标准药物左旋多巴(L-多巴)的效果在大约90分钟后就会消失。此外，该药物的治疗效果有限，因为只有1%-5%的L-多巴到达大脑。因此，药物水平波动很大，患者需要在24小时内多次服用L-多巴。当药物起作用时，患者的帕金森病症状显著改善，包括僵硬、迟缓和震颤。然而，在低用药水平下，患者会经历“休止期”，而高用药水平会导致虚弱的不受控制的运动。随着帕金森病的进展，“休息期”变得越来越频繁(通常是每天2-5小时)，患者失去了关键功能，如语言和行动能力。在这个阶段，患者完全依赖护理人员或医护人员，导致抑郁症的高发生率和大量自掏腰包的护理支出。市场上有一些可穿戴设备可以提醒PD患者何时服药，但它们的功能有限。在这项提案中，我们将开发一套数字工具，用于远程监测和改善PD的临床管理。这将包括可以监测帕金森氏症患者活动和运动症状的可穿戴设备，以及通过测量间质液体(皮肤下的液体)实时监测L-多巴水平的设备。将开发算法和软件，用自适应的、个性化的用药水平取代目前僵化的“一刀切”用药制度。未来，我们将整合这些数字工具，拥有一个单一的可穿戴设备，可以确定PD患者的最佳用药方案。这个平台是独一无二的，因为它可以在患者舒适的家中实时测量用药水平和症状。它将通过提高PD患者的服药依从性，更好地进行知情的临床决策，并通过减少“休息期”的长度和频率来提高他们的独立性，从而为他们带来显著的好处。我们将与患者、护理人员、临床医生和当地政策制定者密切合作，确保预期的可穿戴设备适合这一目的。在未来，预计这个平台可以扩展到对其他疗法的监测，并将改善管理多种(慢性)疾病的患者的用药依从性。

Parkinson's disease (PD) is an incurable and progressive neurological disorder, which is growing fast in prevalence due to an ageing population. The problem is that the effect of Levodopa (L-dopa), the standard drug used to treat PD, wears off after ~90 min. In addition, the drug's therapeutic effect is limited since only 1-5% of L-dopa reaches the brain. Therefore, medication levels fluctuate significantly and patients require multiple L-dopa doses over a 24-h period. When medication is working, patients experience significant improvement of their PD symptoms which include stiffness, slowness, and tremors. However, at low medication levels patients experience "off periods" and high medication levels result in debilitating uncontrolled movements. As PD progresses, "off periods" become more frequent (typically 2-5h/day) and patients lose critical function such as speech and mobility. At this stage patients are fully reliant on carers or healthcare personnel, leading to high incidence of depression and substantial out-of-pocket expenditure for care. There are some wearable devices on the market to remind PD patients when to take medication but their functionality is limited. In this proposal, we will develop a package of digital tools for the remote monitoring and improved clinical management of PD. This will comprise wearables that can monitor the mobility and motor symptoms of PD patients and a device that can monitor in real-time levels of L-dopa by measuring interstitial fluid, the fluid just below the skin. Algorithms and software will be developed to replace the current rigid "one-size-fits-all" medication regime with adaptive, personalized medication levels. In the future, we will integrate these digital tools to have a single wearable device that can determine the optimized drug regime for PD patients. This platform is unique because it can measure both medication levels and symptoms in real-time from the comfort of the patient's home. It will bring significant benefits to PD patients by improving their medication adherence, better informed clinical-decision making, and improving their independence by reducing length and frequency of "off periods". We will work closely with patients, carers, clinicians, and local policy makers to ensure the intended wearable is fit for the purpose. In the future, it is envisaged that this platform can be extended to monitoring of other therapeutics and will improve medication adherence for patients managing multiple (chronic) conditions.