Catherine Ball

Optimal functional outcome measures for assessing treatment for Dupuytren's disease: a systematic review and recommendations for future practice.

BackgroundDupuytrens disease of the hand is a common condition affecting the palmar fascia, resulting in progressive flexion deformities of the digits and hence limitation of hand function. The optimal treatment remains unclear as outcomes studies have used a variety of measures for assessment.MethodsA literature search was performed for all publications describing surgical treatment, percutaneous needle aponeurotomy or collagenase injection for primary or recurrent Dupuytren’s disease where outcomes had been monitored using functional measures.ResultsNinety-one studies met the inclusion criteria. Twenty-two studies reported outcomes using patient reported outcome measures (PROMs) ranging from validated questionnaires to self-reported measures for return to work and self-rated disability. The Disability of Arm, Shoulder and Hand (DASH) score was the most utilised patient-reported function measure (n=11). Patient satisfaction was reported by eighteen studies but no single method was used consistently. Range of movement was the most frequent physical measure and was reported in all 91 studies. However, the methods of measurement and reporting varied, with seventeen different techniques being used. Other physical measures included grip and pinch strength and sensibility, again with variations in measurement protocols. The mean follow-up time ranged from 2 weeks to 17 years.ConclusionsThere is little consistency in the reporting of outcomes for interventions in patients with Dupuytren’s disease, making it impossible to compare the efficacy of different treatment modalities. Although there are limitations to the existing generic patient reported outcomes measures, a combination of these together with a disease-specific questionnaire, and physical measures of active and passive individual joint Range of movement (ROM), grip and sensibility using standardised protocols should be used for future outcomes studies. As Dupuytren’s disease tends to recur following treatment as well as extend to involve other areas of the hand, follow-up times should be standardised and designed to capture both short and long term outcomes.

Functional outcome following extensor synovectomy and excision of the distal ulna in patients with rheumatoid arthritis

We prospectively measured hand and wrist function in rheumatoid patients undergoing excision of the distal ulna. Range of motion, visual analogue pain scores and grip strength were measured in 22 wrists, and the Jebsen hand function test was administered to seven patients, preoperatively and at 3 and 12 months. At 1 year there were improvements in forearm pronation (P = 0.04), supination (P = 0.03) and wrist extension (P = 0.02), but a reduction in flexion (P = 0.009). Active radial deviation was reduced and ulnar deviation increased. There was a significant improvement in grip strength (P = 0.05) and reduction in wrist pain (P = < 0.0001). At 1 year the Jebsen hand function test showed improvements in simulated feeding, stacking checkers, and lifting large empty cans. Excision of the distal ulna in rheumatoid patients results in an improvement in some aspects of hand function.

Effects of extensor synovectomy and excision of the distal ulna in rheumatoid arthritis on long-term function.

PURPOSE Objective outcomes data after excision of the distal ulna in rheumatoid arthritis are lacking. The aim of this study was to evaluate the functional results of this surgery in the long term. METHODS We prospectively collected data on range of motion (22 wrists), visual analog pain scores (14 wrists), and grip strength measured using a Jamar dynamometer (20 hands) in a group of 23 patients (26 wrists) preoperatively and at 3 months, 12 months, and a minimum of 5 years postoperatively (range, 5.3-10.4 y). The Jebsen-Taylor hand function test was administered to 9 patients at the same time points. A subgroup of patients also underwent extensor carpi radialis longus to extensor carpi ulnaris tendon transfer (11 wrists). RESULTS At one year, there were improvements in wrist pronation and supination, which were maintained at final follow-up. Active radial deviation decreased significantly at 3 months (p = .01) and one year (p = .02); this remained reduced at final follow-up (not significant). Wrist extension and active ulnar deviation showed slight improvements by one year, but reduced to levels below that measured preoperatively by final follow-up. Wrist flexion was significantly reduced at all time points postoperatively. Grip strength showed improvement from 10.0 kg (standard deviation [SD] 4.1 kg) preoperatively to 12.5 kg (SD 4.6 kg) 1 year after surgery and returned to preoperative levels (9.5 kg, SD 5.6 kg) by final follow-up. Wrist pain was significantly reduced from a mean score of 5 (SD 4) preoperatively to 2 (SD 2) postoperatively (p = .01). The Jebsen-Taylor hand function test showed improvements in writing and card turning. CONCLUSIONS In the long term, excision of the distal ulna in rheumatoid patients results in an improvement in some aspects of hand function. There is a significant (p = .01) reduction in wrist pain but a reduction of wrist flexion. TYPE OF STUDY/LEVEL OF EVIDENCE Therapeutic IV.

What are we measuring? A critique of range of motion methods currently in use for Dupuytren’s disease and recommendations for practice

BackgroundRange of motion is the most frequently reported measure used in practice to evaluate outcomes. A goniometer is the most reliable tool to assess range of motion yet, the lack of consistency in reporting prevents comparison between studies. The aim of this study is to identify how range of motion is currently assessed and reported in Dupuytren’s disease literature. Following analysis recommendations for practice will be made to enable consistency in future studies for comparability. This paper highlights the variation in range of motion reporting in Dupuytren’s disease.MethodsA Participants, Intervention, Comparison, Outcomes and Study design format was used for the search strategy and search terms. Surgery, needle fasciotomy or collagenase injection for primary or recurrent Dupuytren’s disease in adults were included if outcomes were monitored using range of motion to record change. A literature search was performed in May 2013 using subject heading and free-text terms to also capture electronic publications ahead of print. In total 638 publications were identified and following screening 90 articles met the inclusion criteria. Data was extracted and entered onto a spreadsheet for analysis. A thematic analysis was carried out to establish any duplication, resulting in the final range of motion measures identified.ResultsRange of motion measurement lacked clarity, with goniometry reportedly used in only 43 of the 90 studies, 16 stated the use of a range of motion protocol. A total of 24 different descriptors were identified describing range of motion in the 90 studies. While some studies reported active range of motion, others reported passive or were unclear. Eight of the 24 categories were identified through thematic analysis as possibly describing the same measure, ‘lack of joint extension’ and accounted for the most frequently used.ConclusionsPublished studies lacked clarity in reporting range of motion, preventing data comparison and meta-analysis. Percentage change lacks context and without access to raw data, does not allow direct comparison of baseline characteristics. A clear description of what is being measured within each study was required. It is recommended that range of motion measuring and reporting for Dupuytren’s disease requires consistency to address issues that fall into 3 main categories:-Definition of termsProtocol statementOutcome reporting

Study protocol: A multi-centre, double blind, randomised, placebo-controlled, parallel group, phase II trial (RIDD) to determine the efficacy of intra-nodular injection of anti-TNF to control disease progression in early Dupuytren's disease, with an embedded dose response study.

Dupuytrens disease is a common fibrotic condition of the hand affecting 4% of the population and causes the fingers to curl irreversibly into the palm. It has a strong familial tendency, there is no approved treatment for early stage disease, and patients with established digital contractures are most commonly treated by surgery. This is associated with prolonged recovery, and less invasive techniques have high recurrence rates.The myofibroblasts, the cells responsible for the excessive matrix deposition and contraction, are aggregated in nodules. Using excised diseased and control human tissue, we found that immune cells interspersed amongst the myofibroblasts secrete cytokines. Of these, only tumour necrosis factor (TNF) promoted the development of myofibroblasts. The clinically approved anti-TNF agents led to inhibition of the myofibroblast phenotype in vitro. This clinical trial is designed to assess the efficacy of the anti-TNF agent adalimumab on participants with early disease. The first part is a dose-ranging study where nodules of participants already scheduled for surgery will be injected with either placebo (saline) or varying doses of adalimumab. The excised tissue will then be analysed for markers of myofibroblast activity.The second part of the study will recruit participants with early stage disease. They will be randomised 1: 1 to receive either adalimumab or placebo at 3 month intervals over 1 year and will then be followed for a further 6 months. Outcome measures will include nodule hardness, size and disease progression. The trial will also determine the cost-effectiveness of adalimumb treatment for this group of participants.

Tonometry as an Outcome Measure for the Treatment of Early Dupuytren Disease

There is at present no approved treatment for early Dupuytren disease. Various treatments have been proposed, including intralesional steroid injections, physical therapy and radiotherapy. However existing literature relies on clinical assessment of nodule consistency and progression of flexion deformities of the digits. We performed a clinical trial to determine whether tonometry can be used to distinguish between the hardness of palmar nodules in patients with early Dupuytren disease and palmar skin of healthy volunteers at an equivalent site. The mean of three readings by two independent assessors of 25 patients with early Dupuytren disease and 12 matched healthy volunteers were compared. We found significant difference between groups p˂0.0001 with high intra- and inter-observer reliability r =0.9240 p˂0.0001 for assessing tissue hardness in patients with early Dupuytren disease when using tonometry.

Anti-Tumour Necrosis Factor Therapy for Dupuytren's Disease: A Randomised Dose Response Proof of Concept Phase 2a Clinical Trial.

Background Dupuytrens disease is a common fibrotic condition of the hand that causes irreversible flexion contractures of the fingers, with no approved therapy for early stage disease. Our previous analysis of surgically-excised tissue defined tumour necrosis factor (TNF) as a potential therapeutic target. Here we assessed the efficacy of injecting nodules of Dupuytrens disease with a TNF inhibitor. Methods Patients were randomised to receive adalimumab on one occasion in dose cohorts of 15 mg in 0.3 ml, 35 mg in 0.7 ml, or 40 mg in 0.4 ml, or an equivalent volume of placebo in a 3:1 ratio. Two weeks later the injected tissue was surgically excised and analysed. The primary outcome measure was levels of mRNA expression for α-smooth muscle actin (ACTA2). Secondary outcomes included levels of α-SMA and collagen proteins. The trial was registered with ClinicalTrial.gov (NCT03180957) and the EudraCT (2015-001780-40). Findings We recruited 28 patients, 8 assigned to the 15 mg, 12 to the 35 mg and 8 to the 40 mg adalimumab cohorts. There was no change in mRNA levels for ACTA2, COL1A1, COL3A1 and CDH11. Levels of α-SMA protein expression in patients treated with 40 mg adalimumab (1.09 ± 0.09 ng per μg of total protein) were significantly lower (p = 0.006) compared to placebo treated patients (1.51 ± 0.09 ng/μg). The levels of procollagen type I protein expression were also significantly lower (p < 0.019) in the sub group treated with 40 mg adalimumab (474 ± 84 pg/μg total protein) compared with placebo (817 ± 78 pg/μg). There were two serious adverse events, both considered unrelated to the study drug. Interpretation In this dose-ranging study, injection of 40 mg of adalimumab in 0.4 ml resulted in down regulation of the myofibroblast phenotype as evidenced by reduction in expression of α-SMA and type I procollagen proteins at 2 weeks. These data form the basis of an ongoing phase 2b clinical trial assessing the efficacy of intranodular injection of 40 mg adalimumab in 0.4 ml compared to an equivalent volume of placebo in patients with early stage Dupuytrens disease. Funding Health Innovation Challenge Fund (Wellcome Trust and Department of Health) and 180 Therapeutics LP.

What do we know about managing Dupuytren’s disease cost-effectively?

BackgroundDupuytren’s disease (DD) is a common and progressive, fibroproliferative disorder of the palmar and digital fascia of the hand. Various treatments have been recommended for advanced disease or to retard progression of early disease and to prevent deterioration of the finger contracture and quality of life. Recent studies have tried to evaluate the clinical and cost-effectiveness of therapies for DD, but there is currently no systematic assessment and appraisal of the economic evaluations.MethodsA systematic literature review was conducted, following PRISMA guidelines, to identify studies reporting economic evaluations of interventions for managing DD. Databases searched included the Ovid MEDLINE/Embase (without time restriction), National Health Service (NHS) Economic Evaluation Database (all years) and the National Institute for Health Research (NIHR) Journals Library) Health Technology Assessment (HTA). Cost-effectiveness analyses of treating DD were identified and their quality was assessed using the CHEERS assessment tool for quality of reporting and Phillips checklist for model evaluation.ResultsA total of 103 studies were screened, of which 4 met the study inclusion criteria. Two studies were from the US, one from the UK and one from Canada. They all assessed the same interventions for advanced DD, namely collagenase Clostridium histolyticum injection, percutaneous needle fasciotomy and partial fasciectomy. All studies conducting a cost-utility analysis, two implemented a decision analytic model and two a Markov model approach. None of them were based on a single randomised controlled trial, but rather synthesised evidence from various sources. Studies varied in their time horizon, sources of utility estimates and perspective of analysis. The overall quality of study reporting was good based on the CHEERS checklist. The quality of the model reporting in terms of model structure, data synthesis and model consistency varied across the included studies.ConclusionCost-effectiveness analyses for patients with advanced DD are limited and have applied different approaches with respect to modelling. Future studies should improve the way they are conducted and report their findings according to established guidance for conducting economic modelling of health care technologies.Trial registrationThe protocol was registered (CRD42016032989; date 08/01/2016) with the PROSPERO international prospective register of systematic reviews.

Variation in Range of Movement Reporting in Dupuytren Disease

Range of movement is the most commonly reported outcome used to evaluate interventions in Dupuytren disease; however, there is considerable variation in how this measure is reported. This lack of consistency prevents comparison between studies.