Beverly Marchant

Tgf-β3 in the Treatment of Pressure Ulcers: A Preliminary Report

OBJECTIVE To determine the safety, tolerability, and efficacy of TGF-beta3 in the treatment of chronic, nonhealing pressure ulcers. DESIGN A subset analysis of data from a randomized, blind, parallel, placebo-controlled trial involving 270 patients. SETTING University of Michigan Wound Care Center. PATIENTS A total of 14 patients (6 women and 8 men aged > or = 18 years) with pressure ulcers were randomly assigned to 1 of 3 groups to receive once daily topical application of recombinant TGF-beta3 or placebo gel for a period of no more than 16 weeks. Group 1 (n=4) received 1.0 microg/cm2 of TGF-beta3, Group 2 (n=5) received 2.5 microg/cm2 of TGF-beta3, and Group 3 (n=5) received placebo gel. All subjects received standardized wound care as well. Weekly evaluations were performed for efficacy, determined by relative wound surface areas and volumes, and were compared with initial baseline values and safety parameters. MAIN OUTCOME MEASURE Reduction in pressure ulcer area and volume. MAIN RESULTS Group 2 had a significantly increased rate of wound healing at the fourth visit (P<.05). No significant difference was observed in the healing rate among the groups at the termination of the study. Treatment with TGF-beta3 was well tolerated and there were no significant adverse reactions. CONCLUSION The findings of this study indicate that the topical application of TGF-beta3 is safe and useful in the treatment of pressure ulcers and is most effective at the earliest stages of therapy.

Role of platelet-derived growth factor as an adjunct to surgery in the management of pressure ulcers

&NA; Management options for pressure ulcers include local wound care, surgical repair, and, more recently, topical application of platelet‐derived growth factor (PDGF). PDGF is a glycoprotein that is mitogenic for mesenchymal cells and has been studied extensively for applicability in promoting the healing of chronic human wounds. Using data obtained from a multicenter clinical trial for the treatment of full‐thickness pressure ulcers, a subset analysis was performed to investigate the outcome of salvage surgery for pressure ulcers, after incomplete closure occurred with the topical use of either recombinant human PDGF‐BB (rhPDGF‐BB) or placebo gel. At the University of Michigan Wound Care Center, subset data from a randomized, double‐blind, placebo‐controlled, parallel group clinical trial were reviewed to compare the effects of three concentrations of rhPDGF‐BB on full‐thickness pressure ulcers of the trunk with those of the placebo. Twenty‐eight patients were enrolled and 27 completed the trial. An intent‐to‐treat analysis was used to evaluate data. If the ulcer did not heal by the end of the 16‐week trial period, the surgeon, still blinded to the treatment group, offered salvage surgical repair of the pressure ulcer. Eleven patients underwent salvage surgical repair using myocutaneous flaps, primary closure, or skin grafts. Of three patients who received placebo followed by surgery, none progressed to full healing within 1 year. Of 12 patients in the treatment group who received rhPDGF‐BB and salvage surgery, 11 (92 percent) ultimately healed the ulcers within 1 year after the start of the clinical trial. These findings suggest that treatment with rhPDGF‐BB before surgery enhances the ability to achieve a closed wound over surgery alone. It must yet be determined to what degree rhPDGF‐BB contributed to the excellent results seen in the rhPDGF‐BB/surgery group. It is possible that rhPDGF‐BB “primes” the local wound milieu to make it more responsive to complete closure following surgical treatment. (Plast. Reconstr. Surg. 106: 1243, 2000.)

Outcomes following vaginal prolapse repair and mid urethral sling (OPUS) trial - Design and methods

Background The primary aims of this trial are to determine whether the use of a concomitant prophylactic anti-incontinence procedure may prevent stress urinary incontinence symptom development in women undergoing vaginal prolapse surgery and to evaluate the cost-effectiveness of this prophylactic approach. Purpose To present the rationale and design of a randomized controlled surgical trial (RCT), the Outcomes following vaginal Prolapse repair and mid Urethral Sling (OPUS) Trial highlighting the challenges in the design and implementation. Methods The challenges of implementing this surgical trial combined with a cost-effectiveness study and patient preference group are discussed including the study design, ethical issues regarding use of sham incision, maintaining the masking of study staff, and pragmatic difficulties encountered in the collection of cost data. The trial is conducted by the NICHD-funded Pelvic Floor Disorders Network. Results The ongoing OPUS trial started enrollment in May 2007 with a planned accrual of 350. The use of sham incision was generally well accepted but the collection of cost data using conventional billing forms was found to potentially unmask key study personnel. This necessitated changes in the study forms and planned timing for collection of cost data. To date, the enrollment to the patient preference group has been lower than the limit established by the protocol suggesting a willingness on the part of women to participate in the randomization. Limitations Given the invasive nature of surgical intervention trials, potential participants may be reluctant to accept random assignment, potentially impacting generalizability. Conclusion Findings from the OPUS trial will provide important information that will help surgeons to better counsel women on the benefits and risks of concomitant prophylactic anti-incontinence procedure at the time of vaginal surgery for prolapse. The implementation of the OPUS trial has necessitated that investigators consider ethical issues up front, remain flexible with regards to data collection and be constantly aware of unanticipated opportunities for unmasking. Future surgical trials should be aware of potential challenges in maintaining masking and collection of cost-related information. Clinical Trials 2009; 6: 162—171. http://ctj.sagepub.com

Non-surgical management of stress urinary incontinence: ambulatory treatments for leakage associated with stress (ATLAS) trial.

Background Non-surgical treatment for stress urinary incontinence (SUI) is recommended as first-line therapy, yet few prospective studies and no randomized trials compare the most common non-surgical treatments for SUI. Purpose To present the design and methodology of the ambulatory treatments for leakage associated with stress (ATLAS) trial, a randomized clinical trial comparing three interventions for predominant SUI in women: intravaginal continence pessary; behavioral therapy (including pelvic floor muscle training and exercise and bladder control strategies); and a combination of the two treatments. Methods Treatment outcome measures, collected at 12 weeks and six and 12 months post randomization, include the Patient Global Impression of Improvement (PGI-I), the Stress Incontinence Scale of the Pelvic Floor Distress Inventory (PFDI), seven-day bladder diaries, Pelvic Floor Impact Questionnaire (PFIQ), Pelvic Organ Prolapse-Urinary Incontinence Sexual Function Questionnaire (PISQ-12), Patient Satisfaction Questionnaire (PSQ) and the Medical Outcomes Study Short Form Health Survey (SF-36). Limitations The study design reduces most common biases, but some degree of selection bias may remain. Conclusion This trial will provide useful information to help counsel women with stress and mixed incontinence about the relative efficacy and satisfaction with pessary, behavioral therapy and both treatments combined.