-
[show abstract]
[hide abstract]
ABSTRACT: 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.
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.
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.
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.
Australian New Zealand Clinical Trials Registry #ACTRN12610001045000.
BMC Musculoskeletal Disorders 04/2012; 13:61. · 1.58 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The Collagenase Option for the Reduction of Dupuytren's (CORD) II study investigated the efficacy and safety of injectable Xiaflex (collagenase clostridium histolyticum), in patients with Dupuytren's contracture.
This was a prospective, randomized, placebo-controlled trial with 90-day double-blind and 9-month open-label phases. We randomized patients with contractures affecting metacarpophalangeal (MCP) or proximal interphalangeal (PIP) joints 2 to 1 to collagenase (0.58 mg) or placebo. Cords received a maximum of 3 injections. Cord disruption was attempted the day after injection using a standardized finger extension procedure. Primary end point was reduction in contracture to 0° to 5° of normal 30 days after the last injection.
We enrolled 66 patients; 45 cords (20 MCP to 25 PIP joints) received collagenase and 21 cords (11 MCP to 10 PIP joints) received placebo in the double-blind phase. Statistically significantly more cords injected with collagenase than placebo met the primary end point (44.4% vs 4.8%; p <. 001). The mean percentage decrease in degree of joint contracture from baseline to 30 days after last injection was 70.5% ± 29.2% in the collagenase group and 13.6% ± 26.1% in the placebo group (p < .001). The mean increase in range of motion was significantly greater in the collagenase (35.4° ± 17.8°) than in the placebo (7.6° ± 14.9°; p < .001) group. Efficacy after open-label treatment was similar to that after the double-blind phase: 50.7% of all joints achieved 0° to 5° of normal. More patients were satisfied with collagenase (p < .001). No joint had recurrence of contracture. One patient had a flexion pulley rupture and one patient underwent routine fasciectomy to address cord proliferation and sensory abnormality. No tendon ruptures or systemic allergic reactions were reported. Most adverse events were related to the injection or finger extension procedure.
Collagenase clostridium histolyticum is the first Food and Drug Administration-approved, nonsurgical treatment option for adult Dupuytren's contracture patients with a palpable cord that is highly effective and well tolerated.
Therapeutic I.
The Journal of hand surgery 12/2010; 35(12):2027-38.e1. · 1.33 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: With the proclamation of the Directive on Environmental Noise (200249), the process of noise mapping and action planning has begun around Europe. Large scale wide area noise modelling requires an extensive range of data inputs. The requirements for these inputs are driven by several factors, including the noise calculation methodologies, noise mapping software system, GIS and the deliverables set out within the Directive and recommended Reporting Mechanism. Utilising a staged approach to project design led to the development of detailed noise mapping data schema specifications prior to the collation of input datasets for the calculation process. The data schema may be used throughout the mapping project as a framework to manage dataset concatenation, data capture or the use of defaults and GPGv2 Toolkits to infill data gaps. They also enable data pre-processing guidelines to be passed to non-acoustic GIS specialists, and help to guide and catalogue data processing steps. This paper presents experience gained whilst developing a number of noise mapping data schema specifications and their implementation within successful projects during the first round of mapping. Railway noise mapping is used as an example of how a data schema may be used to develop solutions to technical problems as well as coordinate data capture.
The Journal of the Acoustical Society of America 06/2008; 123(5):3263. · 1.55 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: With the proclamation of the Directive on Environmental Noise (200249), the process of noise mapping and action planning has begun around Europe. As the development of strategic noise maps is arguably a new experience for many end-users, the first round of noise mapping could potentially lead to uncertainties within many aspects of the process. Noise maps represent a baseline for the implementation of noise management systems and any systematic errors within the noise maps could reduce the effective implementation of the whole management system. The extensive range of data inputs required in strategic noise mapping are usually obtained from different data sources or base datasets and as such, cataloguing with the use of metadata is key. The implementation of a quality assurance system is imperative to maintain consistency between technicians and within multi-disciplinary teams. It is also essential to ensure the control of processes and the ability to review inputs, intermediaries and deliverables. A similar approach may also be applied to calculation and post processing of noise levels. This paper presents collective experience of the implementation of quality assurance procedures used in several EU countries during the successful completion of projects within the first round of mapping.
The Journal of the Acoustical Society of America 06/2008; 123(5):3135. · 1.55 Impact Factor
