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

帕金森病（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，其患病率正在快速增长。问题是左旋多巴（L-dopa），用于治疗PD的标准药物，在约90分钟后效果消失。此外，药物的治疗效果有限，因为只有1-5%的L-dopa到达大脑。因此，药物水平波动很大，患者需要在24小时内多次服用左旋多巴。当药物起作用时，患者的PD症状显著改善，包括僵硬，缓慢和震颤。然而，在低药物水平下，患者经历“关闭期”，并且高药物水平导致使人衰弱的不受控制的运动。随着PD的进展，“关闭期”变得更加频繁（通常为2- 5小时/天），患者失去关键功能，如语言和移动性。在这个阶段，患者完全依赖护理人员或医疗保健人员，导致抑郁症的发病率很高，并且需要支付大量的自付护理费用。市场上有一些可穿戴设备可以提醒PD患者何时服药，但其功能有限。在本提案中，我们将开发一套数字化工具，用于PD的远程监测和改善临床管理。这将包括可以监测PD患者的移动性和运动症状的可穿戴设备，以及可以通过测量组织间液（皮肤下方的液体）来实时监测左旋多巴水平的设备。将开发算法和软件，以适应性的个性化药物水平取代目前僵化的“一刀切”药物治疗方案。未来，我们将整合这些数字化工具，使其成为一个可穿戴设备，可以为PD患者确定最佳的药物方案。这个平台是独一无二的，因为它可以从患者舒适的家中实时测量药物水平和症状。它将通过改善PD患者的药物依从性，更好地了解临床决策，并通过减少“停药期”的长度和频率来提高他们的独立性，从而为PD患者带来显着的益处。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，以确保预期的可穿戴设备适合该目的。在未来，预计该平台可以扩展到其他治疗方法的监测，并将提高管理多种（慢性）疾病的患者的药物依从性。

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.