usually when i'm playing a fullscreen game, pressing esc or ctrl alt del to go to desktop just disables stroeksplus. its not that often though, maybe about half the time.
Does the S+ tray icon have the red disabled symbol on it when it seems to be disabled?
If so, I'd check the Configure Hotkeys tab for possible conflicts or key assignments that have the acDisable() or acDisableNext() lua commands in them.
If not, I'd check for deactivated apps in the Configure Actions tab or the Ignored List tab.