Table A6:
GRADE Evidence Profile for Comparison of HBOT and Standard Care for the Treatment of Diabetic Foot Ulcers
| Number of Studies (Design) | Risk of Bias | Inconsistency | Indirectness | Imprecision | Publication Bias | Upgrade Considerations | Quality |
|---|---|---|---|---|---|---|---|
| Major Amputations | |||||||
| 3 (RCTs) | No serious limitations | Serious limitations (−1)a | No serious limitations | Serious limitations (−1)b | Undetected | No other considerations | ⊕⊕ Low |
| 1 (NRCT) | No serious limitations | No serious limitationsa | No serious limitations | Serious limitations (−1)b | Undetected | No other considerations | ⊕ Very Low |
| Ulcers Healed | |||||||
| 4 (RCTs) | Serious limitations (−1)c | No serious limitationsd | Serious limitations (−1)e,f | No serious limitationsg | Undetected | No other considerations | ⊕⊕ Low |
| 1 (NRCT) | No serious limitations | No serious limitations | No serious limitations | No serious limitations | Undetected | No other considerations | ⊕⊕ Low |
| Adverse Events | |||||||
| 6 (RCTs) | Serious limitations (−1)c | No serious limitations | No serious limitations | No serious limitations | Undetected | No other considerations | ⊕⊕⊕ Moderate |
| Mortality | |||||||
| 1 (RCT) | No serious limitations | No serious limitations | No serious limitations | Serious limitations (−1)h | Undetected | No other considerations | ⊕⊕⊕ Moderate |
| 1 (NRCT) | No serious limitations | No serious limitations | No serious limitations | Serious limitations (−1)h | Undetected | No other considerations | ⊕ Very Low |
| Minor Amputations | |||||||
| 4 (RCTs) | Serious limitations (−1)c | Serious limitations (−1)i | Serious limitations (−1)e,f | No serious limitations | Undetected | No other considerations | ⊕ Very Low |
| Ulcer Size Reduction | |||||||
| 3 (RCTs) | No serious limitations | No serious limitations | Serious limitations (−1)e,f | Serious limitations (−1)j | Undetected | No other considerations | ⊕⊕ Low |
| Time to Heal | |||||||
| 1 (RCT) | No serious limitations | No serious limitations | No serious limitations | Very serious limitations (−2)k | Undetected | No other considerations | ⊕⊕ Low |
| 1 (NRCT) | No serious limitations | No serious limitations | No serious limitations | Very serious limitations (−2)k | Undetected | No other considerations | ⊕ Very Low |
| 2 (RCTs) | No serious limitations | No serious limitations | No serious limitations | No serious limitationsl | Undetected | No other considerations | ⊕⊕⊕ Moderate |
Abbreviations: GRADE, Grading of Recommendations Assessment, Development, and Evaluation; HBOT, hyperbaric oxygen therapy; NRCT, nonrandomized controlled trial; RCT, randomized controlled trial.
I2 was about 80%, but no clear explanation for this result was provided. (Kalani et al34 did not provide baseline characteristics for multiple factors [e.g., prior amputations, previous vascular issues]; however, the three other RCTs provided information on comorbidities, and there were no significant differences in baseline characteristics between arms in these three studies. Abidia et al28 included three patients (one in HBOT, two in sham) with chronic obstructive pulmonary disease; these patients should not have been included in the study as chronic obstructive pulmonary disease is a contraindication for HBOT). Also, Londahl et al32 had more strict exclusion criteria than the other studies.
Lack of power to determine a difference in amputation rates between the HBOT and standard care groups.
Unclear allocation concealment, unclear blinding, and a lack of intention-to-treat analyses.
Including Duzgun et al makes the I2 value jump from 0% to 80%.
The interventions varied across studies in terms of how many sessions were given (20–60), how many sessions occurred daily (1 vs. 2), and whether treatment was given in a monoplace or multiplace hyperbaric chamber.
Standard care was not delivered to the control groups in the same way across studies, and several standard care treatment protocols did not meet standard wound care guidelines.
The overall result may be inflated as one study (Duzgun et al29) reported no ulcers healed in the standard care group, which may not be accurate.
Wider confidence intervals, which, if aligned with true estimate, may either increase or decrease risk of mortality.
No trend in estimates; some studies reported more minor amputations in the HBOT group, whereas others reported more minor amputations in the standard care group.
Abidia et al28 had only eight patients in each study arm. Ulcer size reduction was reported as a percentage, with a range from −206% to 100%. A negative number indicates that an ulcer had grown in size. The wide range is likely a result of the small sample size.
The range of time to heal was quite wide. Median time would have been a more appropriate measure for time to heal.
Quality of life was determined based on two small sample sizes.