A software package for efficient patient trajectory analysis applied to analyzing bladder cancer development.

We present the Patient Trajectory Analysis Library (PTRA), a software package for explorative analysis of patient development. PTRA provides the tools for extracting statistically relevant trajectories from the medical event histories of a patient population. These trajectories can additionally be clustered for visual inspection and identifying key events in patient progression. The algorithms of PTRA are based on a statistical method developed previously by Jensen et al, but we contribute several modifications and extensions to enable the implementation of a practical tool. This includes a new clustering strategy, filter mechanisms for controlling analysis to specific cohorts and for controlling trajectory output, a parallel implementation that executes on a single server rather than a high-performance computing (HPC) cluster, etc. PTRA is furthermore open source and the code is organized as a framework so researchers can reuse it to analyze new data sets. We illustrate our tool by discussing trajectories extracted from the TriNetX Dataworks database for analyzing bladder cancer development. We show this experiment uncovers medically sound trajectories for bladder cancer.

Augmenting THerapeutic Effectiveness Through Novel Analytics (ATHENA) - A Public and Private Partnership Project Funded by the Flemish Government (VLAIO).

The complexity and heterogeneity of cancers leads to variable responses of patients to treatments and interventions. Developing models that accurately predict patient's care pathways using prognostic and predictive biomarkers is increasingly important in both clinical practice and scientific research. The main objective of the ATHENA project is to: (1) accelerate data driven precision medicine for two use cases - bladder cancer and multiple myeloma, (2) apply distributed and privacy-preserving analytical methods/ algorithms to stratify patients (decision support), (3) help healthcare professionals deliver earlier and better targeted treatments, and (4) explore care pathway automations and improve outcomes for each patient. Challenges associated with data sharing and integration will be addressed and an appropriate federated data ecosystem will be created, enabling an interoperable foundation for data exchange, analysis and interpretation. By combining multidisciplinary expertise and tackling knowledge gaps in ATHENA, we propose a novel federated privacy preserving platform for oncology research.

SDI-118, a novel procognitive SV2A modulator: First-in-human randomized controlled trial including PET/fMRI assessment of target engagement.

Background: Current treatments for progressive neurodegenerative disorders characterized by cognitive impairment either have limited efficacy or are lacking altogether. SDI-118 is a small molecule which modulates the activity of synaptic vesicle glycoprotein 2A (SV2A) in the brain and shows cognitive enhancing effects in a range of animal models of cognitive deficit. Methods: This first-in-human study evaluated safety, tolerability, and pharmacokinetics/pharmacodynamics of SDI-118 in single ascending oral doses up to 80 mg administered to 32 healthy male subjects. Brain target occupancy was measured in eight subjects using positron emission tomography with PET-ligand [11C]-UCB-J. Food effect was assessed in seven subjects. Mood state was regularly evaluated using standardized questionnaires, and resting state fMRI data were analyzed as exploratory objectives. Key Results: At all doses tested, SDI-118 was well tolerated and appeared safe. Adverse events were mainly dizziness, hypersomnia, and somnolence. All were mild in intensity and increased in frequency with increasing administered dose. No dose-limiting adverse reactions were observed at any dose. SDI-118 displayed a linear pharmacokinetic profile with no significant food effect. Brain penetration and target engagement were demonstrated by a dose-proportional SV2A occupancy. Conclusion: Single oral doses of SDI-118 up to 80 mg were very well tolerated in healthy male subjects. Dose-proportional SV2A occupancy in the brain was demonstrated with brain imaging. Adverse effects in humans mainly occurred in higher dose ranges, with high occupancy levels, and were all mild and self-limiting. These data support further clinical exploration of the compound in patients with cognitive disorders. Clinical Trial Registration: https://clinicaltrials.gov/, identifier NCT05486195.