Accelerated healing of chronic sickle-cell leg ulcers treated with RGD peptide matrix. RGD Study Group. A randomized controlled trial of 0.5% ferric hyaluronate gel (Intergel) in the prevention of adhesions following abdominal surgery. A group randomized trial to improve safe use of nonsteroidal anti-inflammatory drugs. Synergistic action of protease-modulating matrix and autologous growth factors in healing of diabetic foot ulcers. A prospective randomized trial. [Evaluation of a neuropathic ulcers prevention program for patients with diabetes]. [Experiences with adjuvant prostaglandin therapy in vascular surgery interventions]. Enamel matrix proteins and guided tissue regeneration with titanium-reinforced expanded polytetrafluoroethylene membranes in the treatment of infrabony defects: a comparative controlled clinical trial. Enamel matrix proteins in the regenerative therapy of deep intrabony defects. An evaluation of Hyalofill-F plus compression bandaging in the treatment of chronic venous ulcers.
Leg ulcers are a chronic manifestation of sickle-cell disease (SCD) and are often painful, disabling, and difficult to treat. RGD peptide matrix treatment is a novel therapy designed to provide a topical synthetic extracellular matrix that can act as a temporary substitute for the damaged natural matrix at the ulcer site. In this randomized, placebo-controlled, double-blind, prospective, multicenter investigation, SCD patients with full-thickness leg ulcers were treated with standard therapy plus RGD peptide matrix or saline placebo once weekly for up to 10 weeks. Healing in patients with chronic ulcers (2 months or greater in duration) was significantly accelerated (P = .0085) in RGD peptide matrix recipients compared with the placebo group. In these chronic ulcer cases, the average percent ulcer closure (decrease in ulcer surface area) in the RGD peptide matrix group (54.4% +/- 8.9%) exceeded that in the placebo group (19.0% +/- 24.3%) nearly threefold by study endpoint. Furthermore, RGD peptide matrix was equally effective in promoting healing of long persistent ulcers and ulcers of shorter duration. In contrast, standard therapy plus placebo was significantly less effective (P = .001) in promoting healing for ulcers of progressively greater duration. The results of this study provide preliminary evidence that RGD peptide matrix treatment may significantly accelerate healing of chronic sickle-cell leg ulcers. Intestinal adhesion following abdominal surgery is a significant sequela to abdominal surgery. Intergel is a hyaluronate-based gel that reduces the incidence of postoperative adhesions when added to the peritoneal cavity before closure in gynecologic surgery. This is a randomized controlled trial evaluating the efficacy and safety of Intergel in colorectal resections. Although the study aimed to recruit 200 patients based on power analysis, recruitment was suspended because of the high morbidity in the treatment group.
                A total of 32 patients were randomized to either Intergel treatment (treatment group) or no treatment (control group) following open abdominal surgery. Primary endpoints included the incidence of adhesive obstruction, the need for subsequent adhesiolysis, and the incidence of wound and anastomotic complications. A secondary endpoint involved quality-of-life assessment.
                Seventeen patients were randomized to the treatment group and 15 to the control group. All patients, except 1 in the treatment group, underwent resection and anastomosis of the colon or rectum for benign or malignant disease. A significant difference was observed in the number of patients with postoperative morbidities between the 2 groups (65% treatment group versus 27% control group, P = 0.031). There was a high rate of anastomotic dehiscence (5 treatment group versus 1 control group, P = 0.178) and prolonged postoperative ileus (10 treatment group versus 2 control group, P = 0.011) observed in treatment group. One case of peritonitis occurred in the treatment group in the presence of an intact anastomosis. Wound complications were more common in treatment group but failed to reach statistical significance.
                The use of Intergel in abdominal surgery where the gastrointestinal tract is opened leads to unacceptably high rates of postoperative complications. To determine whether audit/feedback and educational materials improve adherence to recommendations for laboratory monitoring and cytoprotective agents to detect and prevent adverse events caused by nonsteroidal anti-inflammatory agents (NSAIDs).
                Controlled, cluster-randomized trial.
                Physicians commonly prescribing NSAIDs were identified within a large managed care organization and randomized to a control or an intervention group (audit/feedback with peer-derived benchmarks and continuing medical education). Medical records were examined 10 months before and after the intervention for clinical data and receipt of complete blood count (CBC), creatinine testing, and cytoprotective agents (process measures). Primary analysis compared intervention versus control physicians among those who initially performed below a peer-derived benchmark. General estimating equations accounted for patient clustering.
                Of 101 physicians initially randomized, 85 remained eligible (38 internists, 36 family physicians, 11 rheumatologists) postintervention. Mean percent change in performance between intervention and control physicians for CBC monitoring was 16% versus 10%; for creatinine monitoring, 0% versus 17%; and use of cytoprotective agents, -3% versus -1%. None of these changes were significant. Rheumatology specialty, number of NSAID prescriptions and physician visits, and patient risk factors for NSAID-related toxicity were more strongly associated with improved safety practices than the intervention.
                Audit/feedback and educational materials had no observed effect on improving NSAID-related safety practices. Potentially contributing factors include high baseline performance (ceiling effect), dilution of the intervention effect by case mix and provider factors, nonreceipt of intervention materials, and diverse indications for lab tests. This study tests the hypothesis that addition of a protease-modulating matrix enhances the efficacy of autologous growth factors in diabetic ulcers. Fifty-one patients with chronic diabetic foot ulcers were managed as outpatients at the Democritus University Hospital of Alexandroupolis and followed up for 8 weeks. All target ulcers were > or = 2.5 cm in any one dimension and had been previously treated only with moist gauze. Patients were randomly allocated in three groups of 17 patients each: Group A was treated only with the oxidized regenerated cellulose/collagen biomaterial (Promogran, Johnson & Johnson, New Brunswick, NJ), Group B was treated only with autologous growth factors delivered by Gravitational Platelet Separation System (GPS, Biomet), and Group C was managed by a combination of both. All ulcers were digitally photographed at initiation of the study and then at change of dressings once weekly. Computerized planimetry (Texas Health Science Center ImageTool, Version 3.0) was used to assess ulcer dimensions that were analyzed for homogeneity and significance using the Statistical Package for Social Sciences, Version 13.0. Post hoc analysis revealed that there was significantly greater reduction of all three dimensions of the ulcers in Group C compared to Groups A and B (all P<.001). Although reduction of ulcer dimensions was greater in Group A than in Group B, these differences did not reach statistical significance. It is concluded that protease-modulating dressings act synergistically with autologous growth factors and enhance their efficacy in diabetic foot ulcers. Neuropathic foot ulcers are among the major health problems faced by patients with diabetes mellitus.
                To evaluate the preventive efficacy of a therapeutic education and protective footwear program in the incidence and recurrence of neuropathic ulcers due to diabetes.
                Fifty-three patients with diabetes and neuropathy from a public healthcare unit in Porto Alegre, Rio Grande do Sul, took part in a clinical trial for two years. The participants were randomly allocated to an intervention group (n=30) or a control group (n=23). Therapeutic education was provided in group sessions, and protective footwear was supplied in accordance with individual prescriptions. The nonparametric Mann-Whitney test was used to determine differences in incidence and recurrence of ulceration between the groups. Life-table analysis and the Kaplan-Meier method were used to measure the duration of ulcer-free survival.
                In the intervention group, the ulcer incidence rate was 38.1% compared to 51.1% in the control group. Among the participants who presented ulcers, 83% were in the control group and 16.7% in the intervention group. After one year, the participants in the intervention group had a 75% chance of being ulcer-free, compared with 61% in the control group, and these percentages reduced to 60% and 52% respectively after two years. There was a tendency toward shorter survival among the control group participants.
                Although the proposed program lowered recurrence rates and increased the duration of ulcer-free survival, it was unable to prevent occurrence and recurrence of neuropathic ulcers due to diabetes. Two prospective randomized trials were referred. In the first study 50 patients with femorotibial greater saphenous vein in situ bypasses were treated intraarterially with 0.2 ng PGE 1/kg body weight/min and 15,000 i.U. of heparine continuously. The control group of 50 patients also got 15,000 i.U. of heparine and 3 x 0.5 g of Aspirin. We observed 2 (4%) immediate occlusions in the PGE 1 group and 7 (14%) immediate occlusions in the control group. This difference proved to be statistically significant. In the second study 83 patients with three level occlusions (ilio-femoro-tibial) in stage III and IV were treated with a profundaplasty. 42 patients received 60 micrograms PGE 1 in 250 ml saline twice daily. The control group of 41 patients only got twice 250 ml saline over a period of three weeks. In the PGE 1 group 26 patients (61%) showed disappearance of rest pain and healing of necrotic lesions, whereas in the control group this could only be achieved in 15 patients (35%). The difference proved to be statistically significant. Several studies have documented the clinical efficacy of guided tissue regeneration (GTR) with non-resorbable expanded polytetrafluoroethylene (ePTFE) membranes and enamel matrix proteins (EMP) in the treatment of infrabony defects. The objective of this controlled clinical study was to compare the clinical outcomes of 3 surgical modalities in the treatment of deep interproximal infrabony defects.
                Ninety (90) defects in 90 healthy subjects affected by chronic periodontitis were assigned to 1 of 3 treatment groups by blocking to prognostic variables. The test group was treated with the application of EMP and the simplified papilla preservation (SPP) technique; the second group was treated with titanium-reinforced ePFTE membranes and the SPP technique; and the third group was treated with the SPP technique used as access flap control procedure. No differences were observed in terms of baseline oral hygiene and defect characteristics among the 3 groups, indicating that the blocking approach was effective. A stringent infection control program was adopted for 1 year.
                The 1-year results indicated that: 1) all treatment modalities resulted in clinically significant improvements in clinical attachment levels (CAL) and reduction in probing depth (PD); 2) a statistically significant treatment effect was demonstrated comparing the EMP test, the membrane control, and the flap control groups in terms of CAL gains; 3) both the EMP test and the membrane control groups showed significant CAL gains compared to the flap control group; 4) a statistically significantly greater amount of CAL gain was demonstrated in GTR-treated compared to EMP-treated patients; 5) deeper residual probing depths but smaller increases in gingival recession were demonstrated following EMP therapy; and 6) smoking habits reduced the clinical outcomes of both regenerative procedures.
                The use of a regenerative procedure is indicated in the treatment of deep vertical bony defects since both the regenerative techniques (GTR and EMD) in the present study resulted in clinically and statistically significant improvements in clinical parameters compared to the access flap procedure. The use of EMP can be helpful in esthetically-sensitive sites and in reducing patient morbidity. This prospective multicentre randomized controlled clinical trial was designed to compare the clinical outcomes of papilla preservation flap surgery with or without the application of enamel matrix proteins (EMD).
                172 patients with advanced chronic periodontitis were recruited in 12 centers in 7 countries. All patients had at least one intrabony defect of > or =3mm. Heavy smokers (> or =20 cigarettes/day) were excluded. The surgical procedures included access for root instrumentation using either the simplified or the modified papilla preservation flap in order to obtain optimal tissue adaptation and primary closure. After debridement, roots were conditioned for 2 min with a gel containing 24% EDTA. EMD was applied in the test subjects, and omitted in the controls. Postsurgically, a strict plaque control protocol was followed. At baseline and 1 year following the interventions, clinical attachment levels (CAL), pocket probing depths (PPD), recession (REC), full-mouth plaque scores and full-mouth bleeding scores were assessed. A total of 166 patients were available for the 1-year follow-up.
                At baseline, 86 test and 86 control patients presented with similar subject and defect characteristics. On average, the test defects gained 3.1+/-1.5 mm of CAL, while the control defects yielded a significantly lower CAL gain of 2.5+/-1.5 mm. Pocket reduction was also significantly higher in the test group (3.9+/-1.7 mm) when compared to the controls (3.3+/-1.7 mm). A multivariate analysis indicated that the treatment, the clinical centers, cigarette smoking, baseline PPD, and defect corticalisation significantly influenced CAL gains. A frequency distribution analysis of the studied outcomes indicated that EMD increased the predictability of clinically significant results (CAL gains > or =4 mm) and decreased the probability of obtaining negligible or no gains in CAL (CAL gains <2 mm).
                The results of this trial indicated that regenerative periodontal surgery with EMD offers an additional benefit in terms of CAL gains, PPD reductions and predictability of outcomes with respect to papilla preservation flaps alone. Hyaluronan, a component of the extracellular matrix, plays a significant role in several aspects of tissue repair and the wound healing process.
                In this Italian study Hyalofill-F, a partial benzyl ester derivative of hyaluronan, used in combination with compression bandaging, was compared with the well-established therapy in Italy of non-adherent gauze plus compression therapy in the treatment of chronic venous leg ulcers.
                Hyalofill-F plus compression bandaging performed significantly better than non-adherent gauze plus compression bandage in all of the clinically relevant efficacy parameters. Mean reduction in ulcer area in the hyaluronan-derivative group was 8.1 cm2 after eight weeks of treatment, compared with 0.4 cm2 in the comparator group. The resulting difference of 7.7 cm2 between the two groups was statistically significant (p = 0.0019). Furthermore, statistically significant results in favour of the hyaluronan-derivative group were obtained in the following: speed of epithelialisation; leveling of the margins; degree of maceration; pain intensity and frequency.
                Hyalofill-F plus compression bandaging resulted in an earlier and greater decrease in ulcer area compared with non-adherent gauze plus compression bandaging, therapy supporting its use in the treatment of chronic venous ulcers.
There is evidence that a topical intervention (RGD peptide matrix) reduced ulcer size in treated participants compared to controls. This evidence of efficacy is limited by the generally high risk of bias associated with these reports.
We planned to analyse results according to general groups: pharmaceutical interventions (systemic and topical); and non-pharmaceutical interventions (surgical and non-surgical). However, we were unable to pool findings due to the heterogeneity in outcome definitions, and inconsistency between the unit of randomisation and the unit of analysis. This heterogeneity, along with a paucity of identified trials, prevented us performing any meta-analyses.
This Cochrane review provides some evidence for the effectiveness of one topical intervention - RGD peptide matrix. However, this intervention was assessed as having a high risk of bias due to inadequacies in the single trial report. Other included studies were also assessed as having a high risk of bias. We recommend that readers interpret the trial results with caution. The safety profile of the all interventions was inconclusive.