Parkinson’s disease (PD) is a common neurodegenerative disease, which has extensive pathology that critically includes the loss of midbrain dopaminergic neurons. This loss leads to debilitating motor features such as bradykinesia and rigidity, as well as some non-motor symptoms. Intracerebral dopamine cell transplants have been explored for many years as a new approach to treating PD and initially used human fetal ventral mesencephalic tissue with inconsistent results, related in part to major logistical challenges in sourcing enough tissue of the right quality and the limited possibilities for quality control and standardisation. Dopaminergic neurons can now be derived reliably from human stem cell sources, which may overcome some of the challenges associated with fetal tissue transplantations.

STEM-PD is a multi-centre, single-arm, dose-escalation, first-in-human advanced therapy investigational medicinal product (ATIMP) trial in Europe using a cell product that consists of dopaminergic neural progenitors derived from the RC17 human embryonic stem cell line. The aim of the study is to assess the safety, tolerability and feasibility of intraputamenal transplantation of this cell product in patients with moderately advanced PD. Eight participants will be recruited from two sites, Skånes University Hospital (Lund, Sweden) and Cambridge University Hospital (Cambridge, UK). The primary outcome of the trial is safety and tolerability, assessed by the number and nature of adverse events and serious adverse events, and the absence of space-occupying lesions on cranial MRI, in the first 12 months following transplantation. Secondary and exploratory outcomes, including clinical measures, changes in anti-Parkinson’s medication and measures of graft survival using positron emission tomography imaging, will be assessed at both 12 and 36 months post-grafting.

Ethical approval was obtained from the Swedish Ethical Review Authority (EPM dnr 2021-06945-01) and South Central - Oxford A Research Ethics Committee (reference 23/SC/0243). Clinical Trial Authorisation was given by the Swedish Medical Products Agency (Dnr: 5.1-2022-57953) and the Medicines and Healthcare products Regulatory Agency for clinical trials authorisation (reference CTA 40773/0001/001-0001). Authorisation for transfer to Clinical Trial Regulation (EU) 536/2014 was given by the Swedish Medical Products Agency (Dnr: 5.1.1-2024-100773). Potential participants will receive verbal and written information about the trial and written informed consent will be obtained prior to enrolment. A lay summary of the results of the trial will be uploaded to the trial website which is publicly accessible. Trial results will be published in peer-reviewed journals.

NCT05635409.

We evaluated the performance of risk models that incorporate ambulatory ECG data and clinical information for prediction of healthcare expenditures related to heart failure (HF) and stroke events in treated and untreated patients.

A retrospective cohort study of Medicare patients who underwent Zio XT ambulatory monitoring in the USA was conducted between 2014 and 2020.

14-day ambulatory ECG data and claims data were evaluated in the study sample which included 89 923 patients in the HF hospitalisation group, 75 870 in the new-onset HF group and 90 159 in the stroke hospitalisation group. Predictive models for new-onset HF, HF hospitalisation and stroke hospitalisation were generated using LASSO Cox regression with ambulatory ECG variables and components of the CHA₂DS₂-VASc. For each outcome, we scored patients using standardised linear predictors from three composite risk models, and we evaluated the association between risk score and total Medicare cost.

The following hazard ratios per one SD increase in the new risk score were observed for the model that included all CHA₂DS₂-VASc components and ECG variables: HF hospitalisation in treated 2.94, 95% CI 2.75 to 3.15; new-onset HF in treated 1.84, 95% CI 1.75 to 1.93; HF hospitalisation in untreated 3.51, 95% CI 3.23 to 3.82; and new-onset HF in untreated 1.92, 95% CI 1.85 to 2.00. Risk scores generated by the model were also predictive of Medicare cost in both treated and untreated patients, with patients in the high-risk category for all outcomes having the greatest Medicare costs during 1 year of follow-up.

Integrating arrhythmia data from ambulatory ECG monitoring into clinical risk models allows for better prediction of healthcare utilisation and cost in both treated and untreated patients at high risk for HF and stroke events.