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

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          Abstract

          Background

          Dupuytren’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.

          Methods

          A 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.

          Results

          A 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.

          Conclusion

          Cost-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 registration

          The protocol was registered ( CRD42016032989; date 08/01/2016) with the PROSPERO international prospective register of systematic reviews.

          Electronic supplementary material

          The online version of this article (10.1186/s12891-018-1949-2) contains supplementary material, which is available to authorized users.

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          Most cited references15

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          Good practice guidelines for decision-analytic modelling in health technology assessment: a review and consolidation of quality assessment.

          The use of decision-analytic modelling for the purpose of health technology assessment (HTA) has increased dramatically in recent years. Several guidelines for best practice have emerged in the literature; however, there is no agreed standard for what constitutes a 'good model' or how models should be formally assessed. The objective of this paper is to identify, review and consolidate existing guidelines on the use of decision-analytic modelling for the purpose of HTA and to develop a consistent framework against which the quality of models may be assessed. The review and resultant framework are summarised under the three key themes of Structure, Data and Consistency. 'Structural' aspects relate to the scope and mathematical structure of the model including the strategies under evaluation. Issues covered under the general heading of 'Data' include data identification methods and how uncertainty should be addressed. 'Consistency' relates to the overall quality of the model. The review of existing guidelines showed that although authors may provide a consistent message regarding some aspects of modelling, such as the need for transparency, they are contradictory in other areas. Particular areas of disagreement are how data should be incorporated into models and how uncertainty should be assessed. For the purpose of evaluation, the resultant framework is applied to a decision-analytic model developed as part of an appraisal for the National Institute for Health and Clinical Excellence (NICE) in the UK. As a further assessment, the review based on the framework is compared with an assessment provided by an independent experienced modeller not using the framework. It is hoped that the framework developed here may form part of the appraisals process for assessment bodies such as NICE and decision models submitted to peer review journals. However, given the speed with which decision-modelling methodology advances, there is a need for its continual update.
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            Epidemiological evaluation of Dupuytren's disease incidence and prevalence rates in relation to etiology.

            Dupuytren's Disease (DD) is a common, fibroproliferative disorder affecting the palmar surface of the hands which is often irreversible and progressive. Understanding the epidemiology of DD is important in order to provide clues to its etiopathogenesis. This review aims to evaluate the epidemiological studies carried out in DD since 1951. Studies evaluating the epidemiology of DD were searched using Medline, Pubmed, and Scopus which dated back from 1951 to current date. Inclusion criteria were any studies investigating the prevalence or incidence of DD in any population group. A total of 620 articles were cited. Forty-nine studies were subsequently identified as relevant to evaluating the epidemiology of DD. The prevalence of DD in all studies increased with age with a male to female ratio of approximately 5.9:1. Prevalence rates ranged from 0.2% to 56% in varying age, population groups, and methods of data collection. The highest prevalence rate was reported in a study group of epileptic patients. Although, only one study calculated the incidence (as opposed to prevalence) of DD to be equal to 34.3 per 100,000 men (0.03%). In conclusion, the prevalence of DD in different geographical locations is extremely variable, and it is not clear whether this is genetic, environmental, or a combination of both. The majority of the prevalence studies have been conducted in Scandinavia or the UK, and the vast changes in population structure, the changes in prevalence of associated diseases, and the change in diagnostic criteria of DD makes understanding the epidemiology of this condition difficult.
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              Unraveling the signaling pathways promoting fibrosis in Dupuytren's disease reveals TNF as a therapeutic target.

              Dupuytren's disease is a very common progressive fibrosis of the palm leading to flexion deformities of the digits that impair hand function. The cell responsible for development of the disease is the myofibroblast. There is currently no treatment for early disease or for preventing recurrence following surgical excision of affected tissue in advanced disease. Therefore, we sought to unravel the signaling pathways leading to the development of myofibroblasts in Dupuytren's disease. We characterized the cells present in Dupuytren's tissue and found significant numbers of immune cells, including classically activated macrophages. High levels of proinflammatory cytokines were also detected in tissue from Dupuytren's patients. We compared the effects of these cytokines on contraction and profibrotic signaling pathways in fibroblasts from the palmar and nonpalmar dermis of Dupuytren's patients and palmar fibroblasts from non-Dupuytren's patients. Exogenous addition of TNF, but not other cytokines, including IL-6 and IL-1β, promoted differentiation into specifically of palmar dermal fibroblasts from Dupuytren's patients in to myofibroblasts. We also demonstrated that TNF acts via the Wnt signaling pathway to drive contraction and profibrotic signaling in these cells. Finally, we examined the effects of targeted cytokine inhibition. Neutralizing antibodies to TNF inhibited the contractile activity of myofibroblasts derived from Dupuytren's patients, reduced their expression of α-smooth muscle actin, and mediated disassembly of the contractile apparatus. Therefore, we showed that localized inflammation in Dupuytren's disease contributes to the development and progression of this fibroproliferative disorder and identified TNF as a therapeutic target to down-regulate myofibroblast differentiation and activity.
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                Author and article information

                Contributors
                melina.dritsaki@ndorms.ox.ac.uk
                oliver.rivero@npeu.ox.ac.uk
                alastair.gray@dph.ox.ac.uk
                cathy.ball@kennedy.ox.ac.uk
                jagdeep.nanchahal@kennedy.ox.ac.uk
                Journal
                BMC Musculoskelet Disord
                BMC Musculoskelet Disord
                BMC Musculoskeletal Disorders
                BioMed Central (London )
                1471-2474
                25 January 2018
                25 January 2018
                2018
                : 19
                : 34
                Affiliations
                [1 ]ISNI 0000 0004 1936 8948, GRID grid.4991.5, Oxford Clinical Trials Research Unit, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, , University of Oxford, ; Oxford, OX3 7LD UK
                [2 ]ISNI 0000 0004 1936 8948, GRID grid.4991.5, National Perinatal Epidemiology Unit (NPEU), Nuffield Department of Population Health, University of Oxford, ; Oxford, OX3 7LF UK
                [3 ]ISNI 0000 0004 1936 8948, GRID grid.4991.5, Health Economics Research Centre, Nuffield Department of Population Health, , University of Oxford, ; Oxford, OX3 7LF UK
                [4 ]ISNI 0000 0004 1936 8948, GRID grid.4991.5, Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, , University of Oxford, ; Oxford, OX3 7FY UK
                Article
                1949
                10.1186/s12891-018-1949-2
                5785840
                29370792
                4bfac74f-d45a-49f2-bc66-c698e9d6e71d
                © The Author(s). 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 18 December 2017
                : 17 January 2018
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100004440, Wellcome Trust;
                Funded by: Health Innovation Challenge Fund (HICF)
                Funded by: Oxford Biomedical Research Centre
                Funded by: FundRef http://dx.doi.org/10.13039/501100000272, National Institute for Health Research;
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2018

                Orthopedics
                dupuytren’s disease,systematic review,economic evaluation,economic modelling
                Orthopedics
                dupuytren’s disease, systematic review, economic evaluation, economic modelling

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