Stock options 28 septembre 2012

Stock options 28 septembre 2012

By: RISOT Date of post: 09.06.2017

N Engl J Med ; Dupuytren's disease limits hand function, diminishes the quality of life, and may ultimately disable the hand. Surgery followed by hand therapy is standard treatment, but it is associated with serious potential complications. Injection of collagenase clostridium histolyticum, an office-based, nonsurgical option, may reduce joint contractures caused by Dupuytren's disease.

Full Text of Background We enrolled patients with joint contractures of 20 degrees or more in this prospective, randomized, double-blind, placebo-controlled, multicenter trial. The primary metacarpophalangeal or proximal interphalangeal joints of these patients were randomly assigned to receive up to three injections of collagenase clostridium histolyticum at a dose of 0. One day after injection, the joints were manipulated. The primary end point was a reduction in contracture to 0 to 5 degrees of full extension 30 days after the last injection.

Twenty-six secondary end points were evaluated, and data on adverse events were collected. Full Text of Methods Collagenase treatment significantly improved outcomes. More cords that were injected with collagenase than cords injected with placebo met the primary end point Overall, the range of motion in the joints was significantly improved after injection with collagenase as compared with placebo from The most commonly reported adverse events were localized swelling, pain, bruising, pruritus, and transient regional lymph-node enlargement and tenderness.

Three treatment-related serious adverse events were reported: No significant changes in flexion or grip strength, no systemic allergic reactions, and no nerve injuries were observed. Full Text of Results Collagenase clostridium histolyticum significantly reduced contractures and improved the range of motion in joints affected by advanced Dupuytren's disease. Full Text of Discussion Dupuytren's disease, a progressive genetic disorder of pathologic collagen production and deposition, begins with palpable nodules in the palm.

Contractures typically affect the metacarpophalangeal joint, the proximal interphalangeal joint, or both. The ring and little fingers are most commonly affected. Dupuytren's disease occurs in all racial and ethnic groups, but the incidence of this disease is highest among people of northern European descent.

The standard of care for Dupuytren's disease is surgery — open fasciectomy 8, the most common procedure4 percutaneous or open fasciotomy, 15 or needle fasciotomy. Collagenase clostridium histolyticum, which lyses collagen and leads to disruption of contracted cords, 22 is a new, office-based, minimally invasive, nonsurgical, investigational option for the treatment of advanced Dupuytren's disease.

Treatment does not require anesthesia. Collagenase clostridium histolyticum is injected into the affected cord, and the next day, the treated joint is manipulated to attempt cord rupture.

In previous single-center studies, injectable collagenase clostridium histolyticum reduced contractures of the metacarpophalangeal and proximal interphalangeal joints to 0 to 5 degrees of full extension in approximately two thirds of treated joints. CORD I is a prospective, multicenter, phase 3 clinical trial comprising a day, randomized, double-blind, placebo-controlled phase and an ongoing open-label extension.

The trial was conducted under the auspices of the institutional review board at each of the 16 participating centers throughout the United States. The study was conducted according to the ethical principles of Good Clinical Practices, the International Conference on Harmonisation Guidelines, and the Code of Federal Regulations title Auxilium Pharmaceuticals financially supported the trial, which was designed by Auxilium and the CORD I Study Group investigators.

Data were collected by the investigators and analyzed by Auxilium. Data management was performed by Kendle International.

The authors had full access to the data and made the decision to submit the manuscript for publication. All authors contributed to the content of the manuscript, reviewed the data, and vouch for the completeness and accuracy of the data and data analyses. Patients with Dupuytren's disease and fixed-flexion contractures of the metacarpophalangeal joint or proximal interphalangeal joint of 20 degrees or more in one finger excluding the thumb were enrolled.

The patients were in good health, were 18 years of age or older, had metacarpophalangeal-joint contractures between 20 degrees and degrees or proximal-interphalangeal-joint contractures between 20 degrees and 80 degrees, and were unable to simultaneously place the affected finger and palm flat on a table.

Women included in the study were postmenopausal or used contraception. Exclusion criteria were breast-feeding or pregnancy, a bleeding disorder, a recent stroke, previous treatment of the primary joint within 90 days before the beginning of the study, collagenase treatment or treatment with any investigational drug within 30 days before the beginning of the study, the use of a tetracycline derivative within 14 days before the beginning of the study, the use of an anticoagulant within 7 days before the beginning of the study, an allergy to collagenase, and a chronic muscular, neurologic, or neuromuscular disorder affecting the hands.

All patients provided written informed consent. Before initiating treatment, the investigators identified a primary joint for treatment in each patient Figure 1 Figure 1 Dupuytren's Disease in a Study Patient. Before treatment Panel Athis patient had a contracture of 75 degrees in the metacarpophalangeal primary joint and 55 degrees in the proximal interphalangeal secondary joint of the ring finger on his left hand.

Panel B shows the hand 1 day after collagenase clostridium histolyticum injection and manipulation. Although only the cord affecting the metacarpophalangeal joint was injected, 30 days after the last third injection of collagenase clostridium histolyticum, a reduction of contracture to 0 degrees in both joints was achieved Panel C. Secondary and tertiary joints were also identified for possible subsequent injections.

Randomization was achieved with the use of a permuted-block design block size of 6 with random assignment within each stratum for each study site. Collagenase clostridium histolyticum 0. Placebo 10 mM TRIS per 60 mM sucrose reconstituted in diluent was administered in a similar manner. If needed, the joints were then manipulated up to three times with the use of a standardized procedure Supplementary Appendix the day after injection Figure 1 in an effort to rupture the cords.

Patients were given a splint to wear nightly for up to 4 months. They did not undergo physical therapy. Follow-up visits occurred 1, 7, and 30 days after injection. A treatment cycle comprised injection, manipulation, and day follow-up Figure 2 Figure 2 Administration of the Study Drug.

If the primary joint and a secondary joint met the primary end point with one injection each, a tertiary joint could be treated. MP denotes metacarpophalangeal joint, and PIP proximal interphalangeal joint.

Each affected cord that was contracting the joint could undergo a maximum of three treatment cycles, and each patient could receive a maximum of three injections during the double-blind phase.

If the primary joint met the primary end point with one or two injections, a secondary joint could be treated. If the primary joint and a secondary joint met the primary end point with one injection each, a tertiary joint could be treated Figure 2. The primary end point was a reduction in primary-joint contracture to 0 to 5 degrees of full extension 30 days after the last injection. Twenty-six secondary end points were evaluated in a fixed-sequence serial testing procedure with an a priori ordered hypothesis based on two time points: Recurrence of contracture, defined as an increase in joint contracture to 20 degrees or more in the presence of a palpable cord at any time during the study, was evaluated in primary joints that reached the primary end point and was recorded as an adverse event.

Fixed-flexion angles were measured with the use of finger goniometry after the fingers had been passively extended until a firm end point was reached. Full flexion was measured with maximum contraction of the treated fingers. Angles of extension and flexion were measured during screening, during each treatment cycle, and at the day visit.

Grip strength was assessed with the use of a dynamometer at the screening visit, immediately before injection, 7 and 30 days after injection, and at the day visit. A minute observation period followed each injection.

Patients were monitored for systemic and local adverse events. Vital signs were assessed before injection, for 60 minutes after injection, and on days 1, 7, 30, and Blood and urine samples for laboratory testing were obtained at screening, 30 days after injection, and at the day visit. Adverse events, assessed for severity and relationship to the treatment, were recorded from the first injection until 30 days after completion of the study.

Investigators used their own terminology to describe adverse events. The resulting sample sizes for efficacy were 14 patients receiving active treatment and 7 patients receiving placebo for metacarpophalangeal joints and 18 patients receiving active treatment and 9 patients receiving placebo for proximal interphalangeal joints.

The primary efficacy analysis was performed with the use of the Cochran—Mantel—Haenszel test, with adjustment for the type of joint and the severity of contracture at baseline. The percent reduction in contracture and the change from baseline in the range of motion were analyzed with the use of analysis of variance, with factors for study group, severity of baseline contracture, and type of joint.

Kaplan—Meier survival analyses were used to compare the time to the primary end point in the two study groups. Adverse events in the two study groups were compared with the use of Fisher's exact test. Vital signs, laboratory assessments, and grip strength were summarized with descriptive statistics. All reported P values are two-sided and have not been adjusted for multiple comparisons.

No interim analyses were planned or carried out before the completion of the trial. Between September and Decembera total of patients were screened and patients were enrolled: All patients with primary joints that were randomly assigned to receive at least one dose of a study drug composed the intention-to-treat and safety populations.

Efficacy results were based on primary joints: The analysis excluded two primary joints that were injected: Contractures were reduced to 0 to 5 degrees of full extension 30 days after the last injection in An example of a collagenase-treated joint that met the primary end point is shown in Figure 1.

More than half of the collagenase-treated joints that did not meet the primary end point did not receive the maximum allowable number of collagenase injections three per cordmost commonly because investigators could not palpate a cord or patients were satisfied with the result.

The median time to reach the primary end point for collagenase-treated joints was 56 days. At the day visit, there was no recurrence of contracture in any collagenase-treated primary joint that had reached the primary end point.

The mean change in contracture from baseline to 30 days after the last injection was a reduction from More collagenase-injected than placebo-injected joints also met the end point of a reduction in contracture to 0 to 5 degrees of full extension 30 days after the first injection When analyzed according to type of joint, more collagenase-injected than placebo-injected joints met the primary end point metacarpophalangeal joint, The median time to the primary end point was 36 days for the collagenase-injected metacarpophalangeal joints.

The mean change in contracture from baseline to 30 days after the last injection was When analyzed according to type of joint and baseline severity, Significantly more collagenase-injected joints than placebo-injected joints showed clinical improvement 30 days after the last injection.

Among all joints that were injected with collagenase, Among all joints that were injected with placebo, As compared with placebo-injected joints, collagenase-injected joints showed a significantly greater percent reduction in contracture from baseline to 30 days after the last injection: Collagenase-injected primary joints showed greater improvement in range of motion than placebo-injected joints.

The mean change in range of motion from baseline to 30 days after the last injection was an increase from The findings were similar when these data were analyzed according to type of joint.

Mean changes in the range of motion are shown for the metacarpophalangeal joint Panel A and the proximal interphalangeal joint Panel B at baseline top of each panel and 30 days after the last injection with collagenase clostridium histolyticum bottom of each panel. Mean values were rounded to the nearest whole number. A total of injections collagenase and placebo were administered in patients. Patients who received collagenase had significantly more injection- and manipulation-related events e.

Most treatment-related adverse events were mild or moderate in intensity and resolved without intervention within a median of 10 days. Twenty patients in the collagenase group and two patients in arduino bit xor placebo group reported adverse events related to the study drug that were severe in intensity Table 2 in the Supplementary Appendix.

All events were deemed to be related to the study drug except for one report each of contact dermatitis, muscle spasms, and myocardial infarction in the collagenase group and one report each of acute cholecystitis, nasopharyngitis, and radius fracture in the placebo group.

Seven patients who received collagenase had a serious adverse event, of which three were deemed to be treatment-related: Two patients in the collagenase group discontinued treatment pf christian make money blog of adverse events: Mean changes in hematologic and biochemical variables from baseline to day 30 and day 90 were not considered to be clinically meaningful in either study group.

No deaths, clinically meaningful changes in grip strength, or nerve injuries were reported. There were no clinically meaningful systemic allergic reactions Supplementary Appendix.

After a third injection, all patients tested positive for antibodies against both AUX-I and AUX-II. An analysis of treatment outcome according to antibody titer was not conducted. The results of this double-blind, placebo-controlled, randomized trial show that injectable collagenase clostridium histolyticum is an effective nonsurgical treatment option in patients with advanced Dupuytren's disease. This condition often limits hand function and activities of daily living, including hair brushing, face washing, hand holding, and the ability to reach into a pocket and to shake hands, and it leads many patients to seek treatment, which is currently limited to surgery.

Many patients cannot undergo surgery, however, because of advanced age, a coexisting condition, or both. In this study, injectable collagenase clostridium histolyticum was significantly superior to placebo in reducing contractures and improving the range of motion in affected joints.

The primary end point was a reduction of contracture to within 5 degrees of full extension in the primary joint 30 days after the last injection. Furthermore, joints with less severe contractures were more likely to stocks to buy tomorrow india to treatment with collagenase than were joints with more severe contractures, indicating select option value jquery mobile early intervention may be the most effective treatment approach.

Similar observations have also been reported in the surgical literature. Delaying treatment makes surgical correction more difficult. Surgery for Dupuytren's disease is often successful, but surgery is not the best option for all patients. After surgery, recuperation is long dolmen stockbrokers cantor requires substantial postoperative hand therapy, restricting the ability of patients to return to work or resume daily activities and athletic pursuits.

In this study, patients were advised to wear a custom-fitted splint at night for up to 4 months, although compliance and the effectiveness of splinting were not assessed. Surgery is also associated with complications, stock market coca injury to the tendon, digital nerve, or artery with the potential loss of a finger; infection; loss of flexion or grip strength; recurrence of contracture; complex regional pain syndrome; skin necrosis; and wound-healing complications.

Collagenase injections were also associated with mild-to-moderate adverse events related to injection or manipulation, such as bruising, pain, and swelling. Treatment with collagenase did not affect flexion or grip strength, and no nerve injuries were reported. This time frame was insufficient to assess recurrence, and we cannot make any claims about this outcome.

In conclusion, this study demonstrated the efficacy and safety of injectable collagenase clostridium histolyticum in patients with advanced Dupuytren's disease. Our data on day outcomes indicate that this office-based procedure effectively reduced contractures and improved range of motion, thus providing an alternative to surgery. Hurst reports receiving consulting and advisory-board fees and grant support from Auxilium Pharmaceuticals and grant support from BioSpecifics Technologies and may receive royalty fees pending Food and Drug Administration [FDA] approval ; Dr.

Badalamente, receiving consulting and advisory-board fees from Auxilium Pharmaceuticals and grant support from BioSpecifics Technologies and may receive royalty fees pending FDA approval ; Dr. Kaplan, receiving consulting and advisory-board fees from Auxilium Pharmaceuticals; Drs. Rodzvilla and Smith, being employees of and holding stock options with Auxilium Pharmaceuticals; and Drs. Meals, Hentz, and Hotchkiss, receiving consulting fees from Auxilium Pharmaceuticals. We thank Catherine Curtin, M.

From the State University of New York SUNY at Stony Brook, Stony Brook L. Address reprint requests to Dr. Hurst at the Department of Orthopaedics, SUNY at Stony Stock broker etf, Health Science Center, Level stock options 28 septembre 2012, Rm.

Members of the Collagenase Option for Reduction of Dupuytren's CORD Stock options 28 septembre 2012 Study Group are listed in the Supplementary Appendixavailable with the full text of this article at NEJM. Murrell GAFrancis MJBromley L. The collagen changes of Dupuytren's contracture. J Hand Surg Br ; Brickley-Parsons DGlimcher MJSmith RJAlbin RAdams JP.

Biochemical changes in the collagen of the palmar fascia in patients with Dupuytren's disease. J Bone Joint Surg Am ; Population studies in Dupuytren's contracture. Loos BPuschkin VHorch RE. BMC Musculoskelet Disord ;8: Gudmundsson KGArngrimsson RSigfusson NBjornsson AJonsson T.

Epidemiology of Dupuytren's disease: J Clin Epidemiol ; Yost JWinters TFett HC Sr. Am J Surg ; An HSSouthworth SRJackson WTRuss B. Cigarette smoking and Dupuytren's contracture of the hand. J Hand Surg Am ; Coert JHNerin JPMeek MF. Results of partial fasciectomy for Dupuytren disease in consecutive patients. Ann Plast Surg ; Spring MFleck HCohen BD.

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N Y State J Med ; Bower MNelson MGazzard BG. Dupuytren's contractures in patients infected with HIV. Fasciectomy for treatment of Dupuytren's disease and early complications. Long-term results after segmental aponeurectomy for Dupuytren's disease. Armstrong JRHurren JSLogan AM. Dermofasciectomy in the management of Dupuytren's disease. J Bone Joint Surg Br ; Dupuytren's fasciectomies in 60 consecutive digits using lidocaine with epinephrine and no tourniquet.

Plast Reconstr Surg ; Rowley DICouch MChesney RBNorris SH. Assessment of best results forex robots 2016 fasciotomy in the management of Dupuytren's contracture. J Hand Surg Br ;9: A comparison of the direct outcomes of percutaneous needle fasciotomy and limited fasciectomy for Dupuytren's disease: Foucher GMedina JNavarro R.

Diagnosis and indications for surgical treatment. Green DP, Hotchkiss RN, Pederson WC, eds. Green's operative hand surgery. Hurst LCBadalamente MA. Nonoperative treatment of Dupuytren's disease. Starkweather KDLattuga SHurst LCet al. Collagenase in the treatment of Dupuytren's disease: Badalamente MAHurst LC. Efficacy and safety of injectable mixed collagenase subtypes in the treatment of Dupuytren's contracture. Enzyme injection as nonsurgical treatment of Dupuytren's disease.

Badalamente MAHurst LCHentz VR. Collagen as a clinical target: Edwards DMadsen J. Constructing multiple procedures for partially ordered hypothesis sets.

McFarlane RMJamieson WG. Surgical treatment of Dupuytren's disease. Postsurgical rehabilitation of Dupuytren's disease. Makela EAJaroma HHarju AAnttila SVainio J. Dias JJBraybrooke J.

Honner RLamb DWJames JI. Deep discount futures brokerage NWJemec BSmith PJ.

The complications of Dupuytren's contracture surgery. Grandizio, Anil Akoon, Janice Heimbach, Jove Graham, Joel C. The Journal of Hand Surgery Carrera-Hueso, Pedro Vazquez-Ferreiro, Diego Gomez-Herrero. Plastic and Reconstructive Surgery - Global Open 5: Journal of Hand Surgery European Volume Carrera-Hueso, Pedro Vazquez-Ferreiro, Narjis Fikri-Benbrahim, Nuria Franco-Ferrando, Clayton A. Sebastian Fischer, Yannick Diehm, Thomas Henzler, Martin R. Berger, Jonas Kolbenschlag, Anne Latz, Ericka M.

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Bueno, Christoph Hirche, Ulrich Kneser, Bohdan Pomahac. Aesthetic Plastic Surgery Scott Hadley, Emerson Floyd, John Zhao, Philip Blazar. Trends in Dupuytren Treatment in the United States. Dupuytren Disease and Related Diseases - The Cutting Edge, The Extracellular Matrix in Dupuytren Disease.

Badalamente, Kerri Kulovitz, Maria Relevo. Journey from Bench to Current Advanced Clinical Use. Efficacy of Using Local Anesthesia Before Collagenase Injection in Reducing Overall Pain Experience in Patients Treated for Dupuytren Contracture: Effect of Delayed Finger Extension on the Efficacy and Safety of Collagenase Clostridium Histolyticum Treatment for Dupuytren Contracture. Glenn Gaston, Richard A.

Prospective Multicenter, Multinational Study to Evaluate the Safety and Efficacy of Concurrent Collagenase Clostridium Histolyticum Injections to Treat Two Dupuytren Contractures in the Same Hand. Comparison of the Literature dailyfx forex training PNF and CCH as Minimally Invasive Treatment Options for Dupuytren Disease. Tips and Pearls for PNF and Collagenase: A Ten-Year Personal Experience.

Variation in Range of Movement Reporting in Dupuytren Disease.

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Minimally Invasive Treatment of Dupuytren Contracture: Chao Zhou, Steven E. What is the best forex signal service, Reinier Feitz, Christianne A.

Van Nieuwenhoven, Hanneke J. Comparative Effectiveness of Collagenase Injection for Dupuytren Contracture. The Use of Acellular Dermal Matrix in Dupuytren Disease.

Indications of the Continuous Extension Technique TEC for Severe Dupuytren Disease and Recurrences. Chim, Emily Ann Borsting, Zubin J. Operative Dictations in Plastic and Reconstructive Surgery, Lipman, Samuel Evan Carstensen, Dylan Nicole Deal. Milka Maravic, Johann Beaudreuil. Revue du Rhumatisme Waltraud Huber, Stefan Krischak. Plastic and Reconstructive Surgery Arthritis Accompanying Endocrine and Metabolic Disorders.

Kelley and Firestein's Textbook of Rheumatology, Andrew Grey, Nicola Dalbeth. Bone and Rheumatic Disorders in Diabetes. Textbook of Diabetes, BMC Musculoskeletal Disorders Chaoming Zhou, Fang Liu, Phillip H.

Baratz, Sandeep Kathju, Latha Satish. Clinical Trials of a New Treatment Method for Adhesive Capsulitis. Otolaryngology -- Head and Neck Surgery Jayes, Betty Liu, Franklin T. Moutos, Maragatha Kuchibhatla, Farshid Guilak, Phyllis C.

American Journal of Obstetrics and Gynecology Koh, Nicholas On, Helen D. Plastic and Reconstructive Surgery - Global Open 4: Knapinska, Sabrina Amar, Zhong He, Sandro Matosevic, Claudia Zylberberg, Gregg B.

Enzyme and Microbial Technology James Anaissie, Wayne J. Zhao, Scott Hadley, Emerson Floyd, Brandon E. Chao Zhou, Ruud W. Slijper, Reinier Feitz, Yara van Kooij, Thybout M. Journal of Plastic Surgery and Hand Surgery Clark, Marianna Kruithof-de Julio. Current Molecular Biology Reports 2: Naam, Abdel Hakim A. A Prospective Randomized Study. A Randomized, Single-Blinded, Clinical Trial With a 1-Year Follow-Up. Staats, Timothy Wu, Bing S.

Journal of Dermatological Science Oral Surgery, Oral Medicine, Oral Pathology and Oral Seputar forex kurs dollar hari ini Chris Poullis, Majid Shabbir, Ian Eardley, John Mulhall, Suks Minhas.

A two-centre prospective randomized clinical trial. Chan Hyuck Bang, Soo Ah Sohn, Kyung Yun Lee, So Yoon Ok, Yu Na Choi. Journal of Herbal Medicine 6: Francesco Smeraglia, Angelo Del Buono, Nicola Maffulli. British Medical Bulletin Dupuytrens enzymatic bromelain-based release. Bone and Joint Research 5: Merisa Piper, Isabella Guajardo, Keith Denkler, Hani Sbitany.

Annals of Plastic Surgery 76SS Betsaida Bibo-Verdugo, Anthony J. Marine Biotechnology 18 Kate McKeage, Katherine Ann Lyseng-Williamson. Rosanne Lanting, Edwin R. The Journal of Hand Surgery 41 Simon Craxford, Peter G. Surgery Oxford 34 Journal of Cell Communication and Signaling Ana Sofia Duarte, Antonio Correia, Ana Cristina Esteves. Critical Reviews in Microbiology Malafa, Craig Lehrman, Jerry W.

Plastic and Reconstructive Surgery - Global Open 4e Hand and Upper Extremity Rehabilitation, Plastic and Reconstructive Surgery Minimally Invasive Treatments for Dupuytren Contracture.

Minimally Invasive Surgery in Orthopedics, Enzymes Approved for Therapy. Safety of Biologics Therapy, Drozdov, Vladimir Ivanovski, Irina I. Jeremy N Rodrigues, Giles W Becker, Cathy Ball, Weiya Zhang, Henk Giele, Jonathan Hobby, Anna L Pratt, Tim Davis, Tim Davis. Surgery for Dupuytren's contracture of the fingers.

Cochrane Database of Systematic Reviews. Teerapong Yata, Eugene L. Lee, Keittisak Suwan, Nelofer Syed, Paladd Asavarut, Amin Hajitou. William Nash, Roland Walker, Sam Gidwani, Adil Ajuied. Orthopaedics and Trauma 29 Riester, Diren Arsoy, Emily T. Camilleri, Amel Dudakovic, Christopher Comforex impex s.r.l. Evans, Jorge Torres-Mora, Marco Rizzo, Peter Kloen, Marianna Kruithof-de Julio, Andre J.

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Russell P Libby, Faysal A Yafi, James Anaissie, Wayne JG Hellstrom. Expert Opinion on Orphan Drugs 3 Carson, Hossein Sadeghi-Nejad, James P. Kaufman, Kimberly Gilbert, Stanton C. Yin Kan Hwee, Marisa Vinas, Christopher Litts, David Friedman. Pess, Stephen Coleman, Brian Dean, Brian M. A Prospective, Multicenter Study.

The Journal of Hand Surgery 40 Miriam Brazzelli, Moira Cruickshank, Emma Tassie, Paul McNamee, Clare Robertson, Andrew Elders, Cynthia Fraser, Rodolfo Hernandez, David Lawrie, Craig Ramsay. Health Technology Assessment 19 Sexual Medicine Reviews 3: Terence Khai Wei Tay, Huey Tien, Elizabeth Yenn Lynn Lim. Cormac Weekes Joyce, Kenneth Mary Joyce, George Rahmani, Sean Michael Carroll, Jack Laurence Kelly, Padraic James Regan. A Bibliometric Study of the Most Cited Papers.

Yuichiro Matsui, Shigeyuki Kon, Tadanao Funakoshi, Tomoe Miyashita, Tadashi Matsuda, Norimasa Iwasaki. The Journal of Hand Surgery 40ee Premsant Sangkum, Faysal A. Yafi, Hogyoung Kim, Mostafa Bouljihad, Manish Ranjan, Amrita Datta, Sree Harsha Mandava, Suresh C. Abdel-Mageed, Krishnarao Moparty, Wayne J. Herrera, Scott Mitchell, Mark Elzik, Jason Roostaeian, Prosper Benhaim. Early Results and Complications. Essentials of Plastic Surgery, Van Nieuwenhoven, Adriana J.

Clinics in Plastic Surgery Irish Journal of Medical Science - Hand Surgery 20 Peimer, Philip Blazar, Stephen Coleman, F. Kaplan, Ted Smith, Tommy Lindau. The Journal of Hand Surgery. Gelbard, Larisa Chagan, James P. The Development of This Novel Pharmacologic Approach. The Journal of Sexual Medicine Acta Orthopaedica 86 Hurst, Prosper Benhaim, Brian M. Combined Analysis of 4 Phase 3 Clinical Trials. Yoshihiro Abe, Susumu Tokunaga. Plastic and Reconstructive Surgery - Global Open 3e Ryan Bauer, Katarzyna Janowska, Kelly Taylor, Brad Jordan, Steve Gann, Tomasz Janowski, Ethan C.

Latimer, Osamu Matsushita, Joshua Sakon. Acta Crystallographica Section D Biological Crystallography 71 Indications, Mechanisms and Adverse Effects. BioDrugs 29 International Immunology 27 Kevin Cheung, Kempland C. Sakellariou, Jeffrey Brault, Marco Rizzo. Kayleigh Wong, Guy Trudel, Odette Laneuville. Animal Models to Future Treatments. BioMed Research International Levine, Beatrice Cuzin, Stephen Mark, Martin K.

Jones, Genzhou Liu, Gregory J. Sue, Carolyn Goldberg, Deepak Narayan. Annals of Plastic Surgery 73SS David B O'Gorman, Bing Siang Gan. Expert Opinion on Orphan Drugs 2 Nancy J Forget, Christina Jerosch-Herold, Lee Shepstone, Johanne Higgins. The First 1, Days. Amanda Murphy, Donald H. Lalonde, Charles Eaton, Keith Denkler, Steven E. Smith, Alison Martin, Atanu Biswas, C. Plastic and Reconstructive Surgeryee. Namrata Singh, Debasish Bhattacharyya.

International Immunopharmacology 23 A French national descriptive analysis, to Raven, Harvey Kushner, Dat Nguyen, Nash Naam, Catherine Curtin. Annals of Plastic Surgery 73 Raghuveer Muppavarapu, Mark R. Belsky, Matthew Leibman, David E. The Journal of Hand Surgery 39ee Syed, John Mcfarlane, Tonia Chester, David Powers, Frank Sibly, Alison Talbot-Smith. European Orthopaedics and Traumatology 5 Gajendran, Vincent Hentz, Deborah Kenney, Catherine M.

Orthopedics 37ee Achilleas Thoma, Manraj Nirmal Kaur, Teegan Ali Ignacy, Carolyn Levis, Stuart Martin, Eric Duku, Ted Haines. Chirurgie de la Main 33 Tan, Premsant Sangkum, Gregory C.

Current Urology Reports Achilleas Thoma, Manraj Nirmal Kaur, Teegan Aili Ignacy, Carolyn Levis, Stuart Martin, Eric Duku, Ted Haines. Yoon-Soo Cindy Bae-Harboe, Jens Erik Harboe-Schmidt, Emmy Graber, Barbara A. Dermatologic Surgery 40 Solveig Grenfell, Martin Borg. A case series, literature review and considerations for treatment of early-stage disease.

David R Mandel, Paul J DeMarco. International Journal of Clinical Rheumatology 9 Stephanie Sweet, Susan Blackmore. Journal of Hand Therapy 27 McGrouther, Aaron Jenkins, Stephanie Brown, Robert A. Gerber, Piotr Szczypa, Brian Cohen. Current Medical Research and Opinion 30 Essentials of Plastic Surgery, Second Edition, Current State of the Art.

Stephen Coleman, David Gilpin, F. Kaplan, Anthony Houston, Gregory J. Cohen, Nigel Jones, James P. The Journal of Hand Surgery 39 The Journal of Hand Surgery 38 Peimer, Paul Skodny, John I. Cellular and Molecular Life Sciences 70 Hayton, Ardeshir Bayat, Douglass S. An Exploratory Analysis of the Efficacy and Safety of Collagenase Clostridium histolyticum. Clinical Drug Investigation 33 Rejuvenation Research 16 Catherine Ball, Anna L Pratt, Jagdeep Nanchahal. Defining Pathologic Capsular Mechanisms and Potential Future Treatment Paradigms.

Verhoekx, Vivek Mudera, Erik T. Hurst, Prosper Benhaim, Brian Cohen. The Journal of Hand Surgery 38ee Peimer, Stephen Geoffrey Coleman, Ted Smith, James P. Summary of 4-Year CORDLESS Data.

Kaplan, Marie Badalamente, Lawrence Hurst, Gregory A. Chirurgie de la Main 32 McMahon, Abdo Bachoura, Sidney M. International Journal of Pharmaceutics A Canadian cost-utility analysis of current and future management strategies. Acta Orthopaedica 84 Latha Satish, David B. Cell Stress and Chaperones 18 Martin Gelbard, Irwin Goldstein, Wayne J. McMahon, Ted Smith, James Tursi, Nigel Jones, Gregory J. The Journal of Urology Seungki Youn, Jong In Shin, Jong Do Kim, Jeong Tae Kim, Youn Hwan Kim.

Dermatologic Surgery 39 Clinical Rheumatology 32 Meg Birks, Aprajit Bhalla. Surgery Oxford 31 Fernando Antonio Herrera, Prosper Benhaim, Ahmed Suliman, Jason Roostaeian, Kodi Azari, Scott Mitchell. Annals of Plastic Surgery 70 Skirven, Abdo Bachoura, Sidney M. Journal of the American Academy of Orthopaedic Surgeons 21 Georg Wick, Cecilia Grundtman, Christina Mayerl, Thomas-Florian Wimpissinger, Johann Feichtinger, Bettina Zelger, Roswitha Sgonc, Dolores Wolfram.

Annual Review of Immunology Forrester, Peter Temple-Smith, Seungmin Ham, David de Kretser, Graeme Southwick, Carl N. Proceedings of the National Academy of SciencesEE Steven Lo, Mark Pickford.

Current Reviews in Musculoskeletal Medicine 6 Case Report and Review of the Literature. Dilaine van Dijk, Peter Finigan, Robert A. Current Medical Research and Opinion 29 Collagenase plaque digestion for facilitating guidewire crossing.

Chronic Total Occlusions, Journal of Orthopaedic Research Kosuke Uehara, Toshiki Miura, Yutaka Morizaki, Hideaki Miyamoto, Takashi Ohe, Sakae Tanaka. Short-Term Results From 2 Open-Label Studies. Kaplan, Ted Smith, James P. Tursi, Brian Cohen, Gregory J.

Campbell's Operative Orthopaedics, Orthopaedic Nursing 32 Current Opinion in Rheumatology 25 Scandinavian Journal of Rheumatology 42 Jagdeep Nanchahal, Catherine Ball, Jennifer Swettenham, Susan Dutton, Vicki Barber, Joanna Black, Bethan Copsey, Melina Dritsaki, Peter Taylor, Alastair Gray, Marc Feldmann, Sarah Lamb.

Wellcome Open Research 2 Gelman, Robert Schlenker, Sidney M. Scott Gelman, Robert Schlenker, Abdo Bachoura, Sidney M. Jacoby, Jeffrey Lipman, Eon K. HAND 7 Latha Satish, William A LaFramboise, Sandra Johnson, Linda Vi, Anna Njarlangattil, Christina Raykha, John Michael Krill-Burger, Phillip H Gallo, David B O'Gorman, Bing Siang Gan, Mark E Baratz, Garth D Ehrlich, Sandeep Kathju. BMC Medical Genomics 5: Stephen Coleman, David Gilpin, James Tursi, Greg Kaufman, Nigel Jones, Brian Cohen.

Patrick I Emelife, Russell E Kling, Ronit Wollstein. Canadian Journal of Plastic Surgery MMW - Fortschritte der Medizin Hand Clinics 28 Alhadeff, Vincent Kwok, Charles Kalensky, Marie T. Journal of Pharmaceutical and Biomedical Analysis 70 Tim Davis, Giles W Becker, Jeremy N Rodrigues, Cathy Ball, Henk Giele, Jonathan Hobby, Weiya Zhang, Tim Davis.

Surgery for Dupuytren's contractures of the fingers. The Importance of Clear Definitions. The Journal of Hand Surgery 37 Chris Bainbridge, Robert A.

Szczypa, Ted Smith, Harvey Kushner, Brian Cohen, Marie-Pierre Hellio Le Graverand-Gastineau. Journal of Plastic Surgery and Hand Surgery 46 Dendy Macaulay, Jasmina Ivanova, Howard Birnbaum, Rachael Sorg, Paul Skodny. Journal of Medical Economics 15 David Warwick, Alexis Thomas, Ardeshir Bayat. International Journal of Clinical Rheumatology 7 Revue du Rhumatisme Monographies 79 Martin Gelbard, Larry I.

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Lipshultz, James Tursi, Ted Smith, Greg Kaufman, Laurence A. Catherine McMillan, Paul Binhammer. A Randomized Controlled Study. Medical Hypotheses 78 Farhatullah Syed, Alexis N.

Thomas, Subir Singh, Venkatesh Kolluru, Susan G. Emeigh Hart, Ardeshir Bayat, Maria A. EMC - Aparato Locomotor 45 Alcoholic and Nonalcoholic Steatohepatitis. Goldman's Cecil Medicine, Orthopedics 35 Dupuytren's disease and other fibrocontractive disorders. The Tensional Network of the Human Body, The Journal of Hand Surgery 36 Preliminary results of safety and efficacy MNA 1 Study.

Joint Bone Spine 78 An Evolving Understanding of an Age-old Disease. American Academy of Orthopaedic Surgeon 19 Latha Satish, Phillip H Gallo, Mark E Baratz, Sandra Johnson, Sandeep Kathju. Christina Jerosch-Herold, Lee Shepstone, Adrian J Chojnowski, Debbie Larson, Elisabeth Barrett, Susan P Vaughan.

Cappelleri, Marie-Pierre Hellio Le Graverand-Gastineau. Clinical Drug Investigation 31 Larisa Kristine Vartija, Leslie L. Johann Beaudreuil, Anne Allard, Djamila Zerkak, Robert A. Development and validation of a tool to assess Dupuytren's disease-specific disability. Revue du Rhumatisme 78 HAND 6 DolmansGuido H. New England Journal of Medicine Extensive Percutaneous Aponeurotomy and Lipografting: A New Treatment for Dupuytren Disease.

Kan, Xander Smit, Ruud W. Selles, Eufimiano Cardoso, Roger K. Dana Britt DiBenedetti, Dat Nguyen, Laurie Zografos, Ryan Ziemiecki, Xiaolei Zhou. Karsten Knobloch, Marie Kuehn, Peter M. Medical Hypotheses 76 Andrew J Watt, Vincent R Hentz. International Journal of Clinical Rheumatology 6 Serap Gur, Ma Limin, Wayne JG Hellstrom. Expert Opinion on Pharmacotherapy 12 The Need to Report.

The American Journal of Bioethics 11 EMC - Appareil locomoteur 6 Rehabilitation of the Hand and Upper Extremity, 2-Volume Set, A Guide for Management L. Howard MD CORR ; Yearbook of Pediatrics Journal of Hand Therapy 24 Orthopaedic applications of injectable biomaterials.

Yearbook of Plastic and Aesthetic Surgery A New Nonsurgical Treatment for Dupuytren's Disease. Yearbook of Orthopedics Barbara Shih, Ardeshir Bayat. Nature Reviews Rheumatology 6 David Gilpin, Stephen Coleman, Stephen Hall, Anthony Houston, Jeff Karrasch, Nigel Jones. The Journal of Hand Surgery 35 Dorota Lebiedz-Odrobina, Jonathan Kay. Rheumatic Disease Clinics of North America 36 Issei Komatsu, Jennifer Bond, Angelica Selim, James J.

Scott Levin, Howard Levinson. Shaunak S Desai, Vincent R Hentz. Expert Opinion on Biological Therapy 10 Collagenase and Percutaneous Aponeurotomy.

ANZ Journal of Surgery Cell A nonsurgical therapy for Dupuytren disease. Yearbook of Hand and Upper Limb Surgery Current Opinion in Rheumatology 22 See related Challenge and other articles in the series. Injectable Collagenase Clostridium Histolyticum for Dupuytren's Contracture. The New England Journal of Medicine.

The narration and closed captions in this video are in English. Adobe Flash Player is required to view this feature.

If you are using an operating system that does not support Flash, we are working to bring you alternative formats. Background Dupuytren's disease limits hand function, diminishes the quality of life, and may ultimately disable the hand. Methods We enrolled patients with joint contractures of 20 degrees or more in this prospective, randomized, double-blind, placebo-controlled, multicenter trial.

Results Collagenase treatment significantly improved outcomes. Conclusions Collagenase clostridium histolyticum significantly reduced contractures and improved the range of motion in joints affected by advanced Dupuytren's disease. Media in This Article Figure 1 Dupuytren's Disease in a Study Patient. Figure 2 Administration of the Study Drug. Article Activity articles have cited this article. Methods Trial Design CORD I is a prospective, multicenter, phase 3 clinical trial comprising a day, randomized, double-blind, placebo-controlled phase and an ongoing open-label extension.

Study Population Patients with Dupuytren's disease and fixed-flexion contractures of the metacarpophalangeal joint or proximal interphalangeal joint of 20 degrees or more in one finger excluding the thumb were enrolled. Treatment Before initiating treatment, the investigators identified a primary joint for treatment in each patient Figure 1 Figure 1 Dupuytren's Disease in a Study Patient.

Efficacy End Points and Assessments The primary end point was a reduction in primary-joint contracture to 0 to 5 degrees of full extension 30 days after the last injection. Safety Assessments A minute observation period followed each injection.

Results Between September and Decembera total of patients were screened and patients were enrolled: Adverse Effects A total of injections collagenase and placebo were administered in patients.

Discussion The results of this double-blind, placebo-controlled, randomized trial show that injectable collagenase clostridium histolyticum is an effective nonsurgical treatment option in patients with advanced Dupuytren's disease. Source Information From the State University of New York SUNY at Stony Brook, Stony Brook L.

References 1 Murrell GAFrancis MJBromley L. Citing Articles 1 Louis C. CrossRef 3 Brian J. CrossRef 9 Sebastian Fischer, Yannick Diehm, Thomas Henzler, Martin R.

CrossRef 10 Scott Hadley, Emerson Floyd, John Zhao, Philip Blazar. CrossRef 11 David B. CrossRef 12 Lawrence C. CrossRef 14 Gary M. CrossRef 15 Marie A. CrossRef 16 Paul M.

CrossRef 17 Gary M. CrossRef 18 Anna L. CrossRef 19 Eva-Maria Baur. CrossRef 20 Chao Zhou, Steven E. CrossRef 21 Gloria R. CrossRef 22 Jane C. CrossRef 24 Jimmy H.

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