Deleu 2000.

Methods	Single‐centre RCT
Participants	Setting: a hospital in Sultanate of Oman Inclusion criteria: patients aged 55 years or above undergoing ophthalmic surgery Exclusion criteria: patients had suffering from any major organ failure; patients had clinical signs or symptoms of cobalamin or folate deficiency; patients had macrocytosis (mean corpuscular volume lower than 96 fl) or anaemia (haematocrit higher than 0.30); or patients had cobalamin and/or folate substitution therapy during the preceding months Participant numbers: 69 randomly assigned; 51 analysed
Interventions	Intervention: patients were premedicated with midazolam 5 to 7.5 mg by mouth 1 h before being transferred to the operating theatre. Anaesthesia was induced and maintained nitrous oxide‐based with propofol. Control: patients were premedicated with midazolam 5 to 7.5 mg by mouth 1 h before being transferred to the operating theatre. Anaesthesia was induced and maintained nitrous oxide‐free with propofol.
Outcomes	Secondary outcomes: Stroke: new neurological signs (paralysis, weakness or speech difficulties) that persisted for 24 hours
Notes	18 patients were either lost to follow‐up (n = 6), had one or more laboratory values missing (n = 9) or had taken folic acid or cobalamin‐containing vitamins during the interval between surgery and re‐evaluation (n = 3).
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Described as randomized but no further details.
Allocation concealment (selection bias)	Unclear risk	No details given.
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Described as double‐blind but no further details.
Blinding of outcome assessment (detection bias) Inhospital case fatality rate/length of stay	Unclear risk	—
Blinding of outcome assessment (detection bias) Complications	Unclear risk	Described as double‐blind but no further details.
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Insufficient information.
Selective reporting (reporting bias)	Low risk	All outcomes described in methods section reported.
Other bias	High risk	Fewer than 50 participants per arm.