Right, so rebooted the computer and did a run with the usual stuff set up.
Result, click registration issue increased significantly by shard 3 and resulted in my death in SR30 due lack of adcth, made boss room hard. Ended up unplugging and replugging in the mouse and SR31 went much smoother with minimal issues.
So - need to unplug and replug in mouse on game start up, as it seems to help significantly.
A bit weird too that in the BIOS it showed 4 keyboards and 2 mice, I assume due to how the keyboard and mouse actually work these days. No ability to mess with IRQ stuff though, which is bloody typical for modern UEFI BIOS’s and their move to being “user friendly” by not exposing more technical stuff to the user.
Edit - okay, unpicked some of the behaviour of this bug.
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Gets worse with the more level transitions that occur, easily triggered in SR, much slower in Campaign.
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Get’s worse the more SR is run. Usually. Cleared on restarting the computer though to previously noted pattern of run 1 being fine and run 3 being borderline unplayable.
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Keyboard button presses seem to be linked to triggering it and briefly resolving it before triggering it again. Found this out running the Campaign world, harder to notice in SR due to frenetic pace.
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Changing USB ports has to be done in SR, does not work outside of it. Confirmed tonight after changing ports before starting the game, only to run right into issues.
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More importantly Event Viewer’s logs are absent any conflicts with IRQ, so it’s not a USB conflict. Probably.
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Before I forget, deleted the keybindings.txt, ran GD with admin rights, no banana, issue persisted.
Conclusion - it may actually be the bloody keyboard, will test this with a new one tomorrow, assuming PBtech gets it ready tomorrow morning. Which tracks, because this issue became more prevalent after I brought the SteelSeries Apex 7.
I will also note this issue became a lot more noticeable when I started moving around the places the keyboard etc where plugged in. Something screwy is going on here, but without logging tools I can’t untangle things. All I can do is swap out hardware and see what happens.
I also still expect that there maybe some issues with the mouse itself, but at the driver level. Because before I got the keyboard EoR was acting weird sometimes, while FoI and auto-attacks were fine. Put it down to grip issues, but now…
Right, bed, finally, can’t troubleshoot if I’m running on now sleep 
Learnt that the hard way in my mid 20’s with hardware compatibility fuckery and one of ASUS’s stupider decisions to “boost” Nvidia AGP GPU performance by juicing the AGP slot’s power level. Result, ATi GPU’s didn’t work and the motherboard was more prone to dying via electrical faults.