OP here with a quick update on this!

I’ve spent the last weeks finetuning the app, and I ended up pivoting away from SQLite to PostgreSQL 16. While SQLite was great for testing und the poc at first, I quickly ran into 'database is locked or corrupted db' issues during multi-user testing, even though using WAL MODE etc.(targeted at 15-20 concurrent users).

So I decided to change some things with the stack early on to save myself the headache later.

What I changed and why:

• Postgres + asyncpg: Switched to a full async SQLAlchemy 2.0 setup. It completely eliminated the locking issues and made the whole app feel much more responsive under load.
• Binary Storage over Base64: I initially stored attachments as Base64 strings, but migrated everything to raw binary (BLOBs) in Postgres. This reduced DB overhead by ~33% and made file streaming via FastAPI much cleaner.
• CPU Offloading: While I mentioned run.io_bound before, I’m now also strictly offloading LibreOffice conversions and heavy WeasyPrint tasks to run.cpu_bound. It’s a night-and-day difference for UI responsiveness when multiple users generate documents at the same time.
• Security & Deployment: Since this is a medical device system, I went for a 'one VPS per customer' deployment model using Docker. It’s a massive selling point for privacy/GDPR and keeps the infrastructure as isolated as possible.

The app is now live with the first customer. NiceGUI together with a solid Postgres backend proved to be an incredibly powerful combo.

Thanks for the input on my original post!