Nanoparticle-enriched mass spectrometry proteomics in British South Asians identifies links between genetic variants, plasma protein levels and disease risk.

With time, approximately 10–30% of patients with Parkinson’s disease (PD) develop medication-related symptom fluctuations that are not sufficiently controlled with conventional treatments (, ), but can be improved with continuous, device-aided treatments (DATs), specifically deep brain stimulation (DBS) or dopaminergic infusion therapies including continuous subcutaneous apomorphine infusion (SCAI) and intestinal or subcutaneous infusion with levodopa or foslevodopa (, ). The timing of these DATs, in particular DBS, has been contested (), and earlier introduction has been proposed (, ). Currently it is, however, common that DAT is introduced only after some impairment of daily activities and health-related quality of life (HRQoL) has developed. Most patients have therefore ceased some activities because the fluctuations make it difficult to maintain them. Once a change in behaviour is established it is not self-evident that improving fluctuations will be enough to regain activities. One example is the degree of workforce participation, which does not seem to improve even after early DBS introduction despite improvement in many symptoms and in HRQoL (). Similarly, an observational study showed that workforce participation may be maintained, but rarely increased, after DAT introduction (). Research has shown that when people lose the ability to perform tasks that are important to them, their perception of themselves as capable and competent disappears, leading to a sense of being worthless and meaningless (). Reducing symptom fluctuations may, although beneficial overall, not be enough to regain capabilities when habits and self-perception have changed. Appropriate interventions may be needed to help the individual resume meaningful activities that can contribute to better health and well-being. Although all DATs have demonstrated clinically meaningful effects, health economic benefit is best established for deep brain stimulation (). DATs are costly, but infusion therapies incur higher costs over time, amounting to around €80 per day. It is therefore important to get the best possible efficacy from treatment. Early rehabilitation is one such strategy, but the evidence for this is limited to open uncontrolled studies and case reports after DBS (). Investigating the effect of early rehabilitation after DAT introduction is therefore an unmet need and the result of such studies could guide clinical practice to optimize the effectiveness of DAT in PD patients with uncontrolled symptom fluctuations. We hypothesized that active rehabilitation may improve the effect of symptom stabilization after DAT, and that this would increase activity, resulting in better ADL performance as well as autonomy and confidence. To investigate the possibility that dedicated rehabilitation improves the outcome of DAT in PD patients with symptom fluctuations, we randomized patients who were about to start treatment with DBS of the subthalamic nuclei (STN-DBS), SCAI, or intestinal continuous levodopa infusion with or without entacapone (ICLI), to either standard care plus a 3-month individualized rehabilitation programme, or standard care. The primary outcome was a standard assessment of motor skills, and secondary outcomes included standard assessment of process skills, patient-reported health-related quality of life, measures of participation and autonomy, fatigue and confidence in balance, as well as disease-specific symptom rating scales and cognition. This single-centre randomized controlled study enrolled PD patients initiating DAT for motor fluctuations between 2016 and 2021. DAT comprised subthalamic nucleus DBS, continuous intestinal levodopa/carbidopa or levodopa/entacapone/carbidopa infusion (ICLI), or subcutaneous apomorphine infusion (SCAI). Patients were randomized to standard care alone (SC) or to standard care plus a 3-month personalized rehabilitation programme (SC+R), with rehabilitation commencing 1 month post-DAT. DAT initiation was defined as first DBS activation, PEG placement for ICLI, or SCAI start. Outcomes were assessed at baseline (pre-DAT) and at 1, 3, 6, and 12 months post DAT initiation (). The study was conducted in collaboration between the Neurology clinic and the Rehabilitation Medicine clinic at Sahlgrenska University Hospital and primary care rehabilitation units in Västra Götaland/Halland, Sweden.