Efficacy and safety of collagenase clostridium histolyticum for Dupuytren disease nodules: a randomized controlled trial.

BACKGROUND: To determine the safety and efficacy of collagenase clostridium histolyticum (CCH) injection for the treatment of palmar Dupuytren disease nodules. METHODS: In this 8-week, double-blind trial, palpable palmar nodules on one hand of adults with Dupuytren disease were selected for treatment. Patients were randomly assigned using an interactive web response system to receive a dose of 0.25 mg, 0.40 mg, or 0.60 mg (1:1:1 ratio) and then allocated to active treatment (CCH) or placebo (4:1 ratio). All patients and investigators were blinded to treatment. One injection was made in the selected nodule on Day 1. Caliper measurements of nodule length and width were performed at screening and at Weeks 4 and 8. Investigator-reported nodular consistency and hardness were evaluated at baseline and Weeks 1, 4, and 8. Investigator-rated patient improvement (1 [very much improved] to 7 [very much worse]) and patient satisfaction were assessed at study end. RESULTS: In the efficacy population (n = 74), percentage changes in area were significantly greater with CCH 0.40 mg (-80.1%, P = 0.0002) and CCH 0.60 mg (-78.2%, P = 0.0003), but not CCH 0.25 mg (-58.3%, P = 0.079), versus placebo (-42.2%) at post-treatment Week 8. Mean change in nodular consistency and hardness were significantly improved with CCH versus placebo at Weeks 4 and 8 (P ≤ 0.0139 for all). At Week 8, investigator global assessment of improvement was significantly greater with CCH 0.40 mg and 0.60 mg (P ≤ 0.0014) but not statistically significant with CCH 0.25 mg versus placebo (P = 0.13). Most patients were "very satisfied" or "quite satisfied" with CCH 0.40 mg and 0.60 mg. Contusion/bruising (50.0% to 59.1%) was the most common adverse event with CCH treatment. CONCLUSION: In patients with Dupuytren disease, a single CCH injection significantly improved palmar nodule size and hardness. The safety of CCH was similar to that observed previously in patients with Dupuytren contracture. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02193828 . Date of trial registration: July 2, 2014 to December 5, 2014.

Monitoring cryptic amphibians and reptiles in a Florida state park.

We monitored cryptic herpetofauna at Savannas Preserve State Park, Florida, by combining artificial cover counts with a quantitative paradigm for constructing and calculating population indices. Weekly indices were calculated from two consecutive days of data collection each week for 7 months from mid-winter to mid-summer in three habitats. Seventeen species were observed at least once, and time trends using index values were followed for six species. Among these, abundance and seasonal pattern information were obtained for an exotic species (greenhouse frog) and a species identified by the Florida Committee on Rare and Endangered Plants and Animals as threatened (Florida scrub lizard). We identified winter as the optimal time in this area to monitor populations for conducting annual assessments. This combined observation and indexing approach could provide managers or researchers with an economical means to quantitatively index population trends for multiple cryptic herpetofauna species simultaneously. Using artificial cover to sample within a population indexing design can be generalized beyond monitoring herpetofauna. Other forms of artificial cover that can be used as observation stations include aquatic artificial substrates, artificial tree cavities, artificial reefs, and other artificial aquatic structures and artificial sea grass units, among many others, and a wide range of taxa are suitable for population monitoring using artificial cover as observation stations in the approach we present, including insects, soil invertebrates, micro and macro aquatic invertebrates, fish, crustaceans, and small mammals.

Multiple concurrent collagenase clostridium histolyticum injections to Dupuytren's cords: an exploratory study.

BACKGROUND: Dupuytren's contracture (DC) is a progressive fibroproliferative disorder characterized by development of nodules and collagen cords within the palmar fascia of the hand. Collagenase clostridium histolyticum (CCH) is currently approved in adults with DC for the nonsurgical treatment of a single palpable cord during a 30-day treatment cycle. This open-label pilot study was designed to examine the safety, efficacy, and multiple-dose pharmacokinetics of injecting two cords (affected joints) with multiple doses of CCH concurrently into the same hand in subjects with DC and multiple contractures. METHODS: Twelve subjects with DC were enrolled, each with ≥3 contractures caused by palpable cords. Efficacy assessments were taken 30 days after treatment and adverse events (AEs) were recorded throughout. In the first treatment period, all subjects were injected with a single dose of CCH (0.58 mg) into a single cord. The same subjects entered a second treatment period 30 days later, where two different cords (affected joints) were injected concurrently on the same hand. A finger extension procedure was performed 24 hours after each administration of CCH to disrupt the enzymatically weakened cord. RESULTS: For metacarpophalangeal (MP) joints, mean contracture reduction per joint treated was 29.0 ± 20.7 degrees following single injection vs 30.3 ± 10.9 degrees per treated joint following multiple injections. For proximal interphalangeal (PIP) joints, mean reduction in contracture was 30.7 ± 21.1 and 22.1 ± 4.9 degrees per treated joint, respectively, for the two periods. All patients (100%) were either "quite satisfied" or "very satisfied" following either treatment cycle. The most common treatment-related AEs were edema peripheral, contusion, and pain in the treated extremity; the differences in severity for local effects of the injections were minimal between treatment periods. No serious treatment-related AEs or systemic complications were reported. CONCLUSION: These results provide preliminary evidence that two cords (affected joints) can be treated concurrently with CCH with similar efficacy and safety as cords treated individually in a sequential fashion. Multiple concurrent injections would eliminate the 30-day wait between single treatments and allow for rapid and effective treatment of patients with multiple affected joints, a significant advantage for both patient and physician. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry #ACTRN12610001045000.

Phase 2b study of the clinical efficacy and safety of collagenase Clostridium histolyticum in patients with Peyronie disease.

PURPOSE: Collagenase Clostridium histolyticum is an investigational nonsurgical treatment for Peyronie disease. In this phase 2b, double-blind, randomized, placebo controlled study we determined the safety and efficacy of collagenase C. histolyticum and assessed a patient reported outcome questionnaire. MATERIALS AND METHODS: A total of 147 subjects were randomized into 4 groups to receive collagenase C. histolyticum or placebo (3:1) with or without penile plaque modeling (1:1). Per treatment cycle 2 injections of collagenase C. histolyticum (0.58 mg) were given 24 to 72 hours apart. Subjects received up to 3 cycles at 6-week intervals. When designated, investigator modeling was done 24 to 72 hours after the second injection of each cycle. We evaluated penile curvature by goniometer measurement, patient reported outcomes and adverse event profiles. RESULTS: After collagenase C. histolyticum treatment significant improvements in penile curvature (29.7% vs 11.0%, p=0.001) and patient reported outcome symptom bother scores (p=0.05) were observed compared to placebo. In modeled subjects 32.4% improvement in penile curvature was observed in those on collagenase C. histolyticum compared to 2.5% worsening of curvature in those on placebo (p<0.001). Those treated with collagenase C. histolyticum who underwent modeling also showed improved Peyronie disease symptom bother scores (p=0.004). In subjects without modeling there were minimal differences between the active and placebo cohorts. Most adverse events in the collagenase C. histolyticum group occurred at the injection site and were mild or moderate in severity. No treatment related serious adverse events were reported. CONCLUSIONS: Collagenase C. histolyticum treatment was well tolerated. We noted significant improvement in penile curvature and patient reported outcome symptom bother scores, suggesting that this may be a safe, nonsurgical alternative for Peyronie disease.

Orbital cellulitis following cataract surgery.

Orbital cellulitis is an extremely uncommon complication following cataract surgery. Herein, a patient who developed orbital cellulitis less than 24 h after undergoing cataract surgery is described. She responded well to systemic antibiotic treatment and ultimately achieved good visual acuity in the affected eye. The most likely mode of pathogen entry in such cases is considered to be the anaesthetic block given before the cataract surgery. It has been suggested that a careful skin antiseptic preparation before the block is given could prevent this occurrence, but such a preparation did not do so in our case.