Some adjustments (eg. supercharger or mixture) are required for flight at altitude. If you want to get fancy and you are trailing fuel you could try adjusting prop pitch in order to increase fuel efficiency. Generally speaking, use the radiator and throttle to try and prevent the engine from staying overheated for more than a few minutes. This will avoid you blowing out your engine.
I recall a couple of interviews with Russian vets saying things like that they went to full throttle and closed the radiator until encountering the enemy and never changed these settings afterward, that older aircraft lost about 20kph due to wear and that they would have all been dead if they followed the manuals and flew "by the book"... So, I wouldn't worry about it.
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