Table.
GRADE Evaluation of interventions for Venous leg ulcers.
| Important outcomes | Adverse effects, Healing rates, Recurrence rates | ||||||||
| Studies (Participants) | Outcome | Comparison | Type of evidence | Quality | Consistency | Directness | Effect size | GRADE | Comment |
| What are the effects of standard treatments for venous leg ulcers? | |||||||||
| 7 (467) | Healing rates | Compression bandages and stockings versus no compression | 4 | 0 | 0 | 0 | 0 | High | |
| 1 (140) | Recurrence rates | Compression bandages and stockings versus no compression | 4 | –1 | –1 | 0 | 0 | Low | Quality point deducted for sparse data. Consistency point deducted for conflicting results |
| 11 (869) | Healing rates | Compression stockings or tubular garments versus compression bandages | 4 | –2 | 0 | –2 | 0 | Very low | Quality points deducted for incomplete reporting of data and methodological flaws. Directness points deducted for inclusion of people with different severities of ulcers and for differences in treatment regimens in both groups, affecting generalisability of results |
| 1 (138) | Recurrence rates | Compression stockings or tubular garments versus compression bandages | 4 | 0 | 0 | 0 | 0 | High | |
| 9 (679) | Healing rates | Multilayer elastomeric high-compression regimens versus other layered regimens | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for incomplete reporting of results. Directness point deducted for inclusion of multiple interventions in comparison |
| 4 (280) | Healing rates | Multilayer high-compression bandages versus single-layer bandage | 4 | 0 | 0 | 0 | 0 | High | |
| 6 (850) | Healing rates | Multilayer elastomeric high-compression bandages versus short-stretch bandages or Unna's boot | 4 | 0 | –1 | 0 | 0 | Moderate | Consistency point deducted for conflicting results |
| 1 (24) | Healing rates | Single-layer non-elastic system versus multilayer elastic system | 4 | –2 | 0 | –1 | 0 | Very low | Quality points deducted for sparse data and incomplete reporting of results. Directness point deducted for uncertainty about generalisability of results in people with different conditions |
| 1 (38) | Healing rates | Single-layer non-elastic system versus multilayer non-elastic system | 4 | –2 | 0 | 0 | 0 | Low | Quality points deduced for sparse data and incomplete reporting of results |
| 1 (60) | Healing rates | Peri-ulcer injection of granulocyte-macrophage colony-stimulating factor | 4 | –1 | 0 | 0 | +1 | High | Quality points deduced for sparse data. Effect-size point added for RR <5 |
| 6 (459) | Healing rates | Semi-occlusive dressings (foam, film, hyaluronic acid-derived dressings, collagen, cellulose, or alginate) versus simple low-adherent dressings, in the presence of compression | 4 | –1 | –1 | 0 | 0 | Low | Quality point deducted for spare data. Consistency point deducted for conflicting results |
| 1 (113) | Healing rates | Alginate dressings versus zinc oxide dressings | 4 | –1 | –1 | 0 | 0 | Low | Quality point deducted for sparse data. Consistency point deducted for conflicting results |
| 4 (168) | Healing rates | Intermittent pneumatic compression plus compression stockings versus compression stockings or bandages alone | 4 | –1 | –1 | 0 | 0 | Low | Quality point deduced for sparse data. Consistency point deducted for conflicting results |
| 27 studies at most (1401 at most) | Healing rates | Topical antimicrobial agents versus placebo or usual care | 4 | –1 | 0 | –2 | 0 | Very low | Quality point deducted for incomplete reporting of results. Directness points deducted for assessing different outcome in 1 study and the inclusion of a mixed population in 1 review |
| 1 (213) | Recurrence rates | Topical antimicrobial agents versus placebo or usual care | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of data |
| 1 (66) | Healing rates | Topical calcitonin gene-related peptide plus vasoactive intestinal polypeptide versus placebo | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for sparse data |
| 1 (40) | Healing rates | Topical mesoglycan versus a plant-based extract | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and incomplete reporting of results |
| 1 (60) | Healing rates | Topical negative pressure versus usual care | 4 | –1 | 0 | –2 | 0 | Very low | Quality point deducted for sparse data. Directness points deducted for inclusion of people with non-venous ulcers and for uncertainty about generalisability of results outside a hospital setting |
| 1 (60) | Recurrence rates | Topical negative pressure versus usual care | 4 | –1 | 0 | –2 | 0 | Very low | Quality point deducted for sparse data. Directness points deducted for inclusion of people with non-venous ulcers and for uncertainty about generalisability of results outside a hospital setting |
| 1 (94) | Healing rates | Topical recombinant human keratinocyte growth factor 2 plus compression versus placebo plus compression | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for sparse data |
| 2 (135) | Healing rates | Platelet-derived growth factor versus placebo | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and incomplete reporting of results |
| at least 22 (at least 792) | Healing rates | Hydrocolloid (occlusive) dressings versus simple dressings in the presence of compression | 4 | 0 | 0 | 0 | 0 | High | |
| 4 (311) | Healing rates | Hydrocolloids versus other occlusive or semi-occlusive dressings | 4 | 0 | 0 | 0 | 0 | High | |
| 3 (388) | Healing rates | Different occlusive or semi-occlusive dressings (excluding hydrocolloids) versus each other | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 1 (86) | Healing rates | Topically applied autologous platelet lysate versus placebo | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for sparse data |
| 1 (200) | Healing rates | Topically applied freeze-dried keratinocyte lysate versus vehicle or usual care | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| What are the effects of adjuvant treatments for venous leg ulcers? | |||||||||
| 7 (659) | Healing rates | Oral pentoxifylline versus placebo | 4 | 0 | 0 | 0 | 0 | High | |
| 2 (345) | Healing rates | Cultured allogenic bilayer skin replacement versus non-adherent dressing | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 5 (723) | Healing rates | Flavonoids plus compression versus compression alone | 4 | –1 | –1 | 0 | +1 | Moderate | Quality point deducted for incomplete reporting of results. Consistency point deducted for conflicting results. Effect-size point added for RR/OR >2 but <5 |
| 4 (488) | Healing rates | Oral sulodexide plus compression versus compression alone | 4 | 0 | 0 | 0 | 0 | High | |
| 1 (183) | Healing rates | Systemic mesoglycan plus compression versus placebo plus compression | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for sparse data |
| 2 (71) | Healing rates | Cultured allogenic single-layer dermal replacement versus usual care | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and incomplete reporting of results |
| 1 (87) | Healing rates | Intravenous prostaglandin E1 versus placebo | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and methodological flaws |
| 1 (267) | Healing rates | Larval therapy versus usual care | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 7 (301) | Healing rates | Low-level laser treatment versus sham treatment | 4 | –2 | 0 | –2 | 0 | Very low | Quality points deducted for incomplete reporting of results and for differences in length of follow-up. Directness points deducted for treatment inconsistencies between groups and for assessing different measures of healing |
| 1 (reported as "small") | Healing rates | Oral aspirin versus placebo | 4 | –3 | 0 | 0 | 0 | Very low | Quality points deducted for sparse data and for methodological weaknesses |
| 1 (reported as "small") | Healing rates | Oral rutosides versus placebo | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and incomplete reporting of results |
| 1 (165) | Healing rates | Oral thromboxane alpha2 antagonists versus placebo | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and incomplete reporting of results |
| 1 (120) | Healing rates | Skin grafts versus usual care or versus each other | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for poor studies and insufficient evidence. Directness point deducted for generalisability of results |
| 1 (47) | Healing rates | Perforator ligation versus no surgery or versus surgery plus skin grafting in the presence of compression | 4 | –3 | 0 | 0 | 0 | Very low | Quality points deducted for sparse data, incomplete reporting of results, and no intention-to-treat analysis |
| 2 (215) | Healing rates | Minimally invasive surgery versus compression bandages or usual care | 4 | –1 | –1 | 0 | 0 | Low | Quality point deducted for incomplete reporting of results. Consistency point deducted for conflicting results |
| 5 (at least 341 people) | Healing rates | Venous surgery (based on duplex scan) plus compression versus compression alone | 4 | 0 | 0 | 0 | 0 | High | |
| 3 (745 legs) | Recurrence rates | Venous surgery (based on duplex scan) plus compression versus compression alone | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 1 (39) | Healing rates | Open perforator surgery versus subfascial endoscopic perforator surgery | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and incomplete reporting of results |
| 1 (39) | Adverse effects | Open perforator surgery versus subfascial endoscopic perforator surgery | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for sparse data |
| 1 (337) | Healing rates | Therapeutic ultrasound versus no or sham ultrasound | 4 | 0 | 0 | 0 | 0 | High | |
| 1 (337) | Recurrence rates | Therapeutic ultrasound versus no or sham ultrasound | 4 | 0 | 0 | 0 | 0 | High | |
| What are the effects of organisational interventions for venous leg ulcers? | |||||||||
| 4 (at least 279 people) | Healing rates | Leg ulcer clinics versus usual care | 4 | –1 | 0 | –2 | 0 | Very low | Quality point deducted for incomplete reporting of results. Directness points deducted for differences in treatments received by both groups and uncertainty about generalisability of results |
| 2 (246) | Recurrence rates | Leg ulcer clinics versus usual care | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of data. |
| What are the effects of interventions to prevent recurrence of venous leg ulcers? | |||||||||
| 1 (153) | Recurrence rates | Compression stockings versus no compression | 4 | –1 | 0 | 0 | +1 | High | Quality point deducted for sparse data. Effect-size point added for RR <0.5 |
| 2 (466) | Recurrence rates | Compression stockings versus other forms of compression | 4 | 0 | 0 | –1 | 0 | Moderate | Directness point deducted for change-over |
| 4 (673) | Recurrence rates | Surgery plus compression versus compression alone | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for methodological flaws |
| 1 (39) | Recurrence rates | Open versus endoscopic surgery | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and incomplete reporting |
| 1 (139) | Recurrence rates | Oral rutoside versus placebo | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and incomplete reporting |
| 1 (48) | Recurrence rates | Oral stanozolol versus placebo | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and weak methods (unit of randomisation and unit of assessment differed) |
We initially allocate 4 points to evidence from RCTs, and 2 points to evidence from observational studies. To attain the final GRADE score for a given comparison, points are deducted or added from this initial score based on preset criteria relating to the categories of quality, directness, consistency, and effect size. Quality: based on issues affecting methodological rigour (e.g., incomplete reporting of results, quasi-randomisation, sparse data [<200 people in the analysis]). Consistency: based on similarity of results across studies. Directness: based on generalisability of population or outcomes. Effect size: based on magnitude of effect as measured by statistics such as relative risk, odds ratio, or hazard ratio.