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The aim of this study was to compare the effects of 0.2% polyhexamethylene biguanide (PHMB) to 0.8% metronidazole on malignant wound (MW) odor, health-related quality of life (HRQOL), and pain upon application.A double-blinded, randomized, clinical trial.Twenty-four patients with malodorous MWs hospitalized in a referral cancer center in Sao Paulo, Brazil, participated in the trial.Participants were randomly allocated to treatment with 0.8% metronidazole solution (control group) or 0.2% PHMB (experimental group). Study outcomes were measured at baseline (day 0), 4 days, and 8 days. The primary end point was the odor that was measured in terms of its intensity, quality, and impact on participants during the study period. Health-related quality of life was measured with the Ferrans and Powers Quality of Life Index–Wounds Version (FPQLI-WV) on day 0 and on the day when odor was completely eliminated as per evaluation by the investigators. Pain intensity related to application of the control and experimental solutions was measured as a secondary outcome using a scale of 0 to 10.Twenty patients (83.3%) were classified as having “no wound odor” at 4 days, and 100% achieved no wound odor by day 8 (P < .001). Odor control in patients with MW significantly influenced their general HRQOL (P = .002). We found no difference in odor elimination, or HRQOL, when patients managed with PHMB were compared to those managed with metronidazole. There were no statistically significant differences over time in pain measurement between the 2 groups.Both PHMB and metronidazole significantly reduced odor in malodorous MWs within 4 days. Neither solution was found to be more effective than the other in the magnitude of odor reduction or its effect on condition-specific HRQOL.