Summary of findings 4. Summary of findings: Folic acid versus placebo.

Folic acid versus placebo for treatment of Buerger's disease
Patient or population: patients with Buerger's disease Settings: community Intervention: folic acid Comparison: placebo
Outcomes	Illustrative comparative risks* (95% CI)		Relative effect (95% CI)	No of Participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Placebo	Folic acid
Ulcer healing	see comment		‐			Ulcer healing was not appraised by the study in this comparison
Pain (0 month) VAS. Scale from: 0 to 10; higher score = more pain	The mean pain in the placebo group was 5.09 points	The mean pain in the intervention group was 1.17 higher (0.66 lower to 3.00 higher)		30 (1 RCT)	⊕⊝⊝⊝1 very low
Pain (2 months) VAS. Scale from: 0 to 10; higher score = more pain Follow‐up: 2 months	The mean pain in the placebo group was 5.75 points	The mean pain in the intervention group was 0.3 lower (2.04 lower to 1.44 higher)		30 (1 RCT)	⊕⊝⊝⊝1 very low
Pain (6 months) VAS. Scale from: 0 to 10; higher score = more pain Follow‐up: 6 months	The mean pain in the placebo group was 4.82 points	The mean pain in the intervention group was 1.36 lower (3.17 lower to 0.45 higher)		30 (1 RCT)	⊕⊝⊝⊝1 very low
Change in rate of amputation (2 months) (Difference in number of amputations at start of treatment) Follow‐up: 2 months	see comment			30 (1 RCT)	⊕⊝⊝⊝1 very low	No new cases of amputations two months after start of treatment
Change in rate of amputation (6 months) (Difference in number of amputations at start of treatment) Follow‐up: 6 months	see comment			30 (1 RCT)	⊕⊝⊝⊝1 very low	No new cases of amputations six months after start of treatment
*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; RR: Risk ratio; MD: Mean difference; VAS: Visual analogue scale
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.

¹ participants without critical ischaemia, resulting in absence of amputations and no differences in pain score in both groups, one single small study ‐ downgraded by three levels