Research Inefficiency in Degenerative Cervical Myelopathy: Findings of a Systematic Review on Research Activity Over the Past 20 Years.

STUDY DESIGN: Scoping review. OBJECTIVE: To describe activity, themes and trends in degenerative cervical myelopathy (DCM) research over the past 20 years with a view to considering DCM research inefficiency. METHODS: A systematic review of MEDLINE and Embase for "Cervical" AND "Myelopathy" was conducted following PRISMA guidelines. Full-text papers in English, exclusively studying DCM, published between January 1, 1995 and December 31, 2015 were considered eligible. Country of origin, number of papers published, number of patients studied, research theme, and year of publication were assessed. Comparison was made between developed and developing countries. RESULTS: A total of 1485 papers and 4 117 051 patients were included. Japan published more papers (450) than any other country while the United States studied the greatest number of patients (3 674 737). Over 99.4% of papers and 78.6% of patients were from developed countries. The number of papers (r = 0.96, P < .001) and patients (r = 0.83 P < .001) studied each year increased significantly overall and for both developed (r = 0.93, P < .001; r = 0.81, P < .001) and developing countries (r = 0.90, P < .001; r = 0.87, P < .001). Surgery was the most prevalent theme (58.3% papers; 55.7% patients) for developed and developing countries. Research from developing countries showed greater thematic variability. CONCLUSIONS: DCM research activity is increasing internationally, with surgery remaining the focus. Research output has predominantly been from developed countries; however, the rate of growth for developed and developing countries is comparable

Development of a core measurement set for research in degenerative cervical myelopathy: a study protocol (AO Spine RECODE-DCM CMS)

INTRODUCTION Progress in degenerative cervical myelopathy (DCM) is hindered by inconsistent measurement and reporting. This impedes data aggregation and outcome comparison across studies. This limitation can be reversed by developing a core measurement set (CMS) for DCM research. Previously, the AO Spine Research Objectives and Common Data Elements for DCM (AO Spine RECODE-DCM) defined 'what' should be measured in DCM: the next step of this initiative is to determine 'how' to measure these features. This protocol outlines the steps necessary for the development of a CMS for DCM research and audit. METHODS AND ANALYSIS The CMS will be developed in accordance with the guidance developed by the Core Outcome Measures in Effectiveness Trials and the Consensus-based Standards for the selection of health Measurement Instruments. The process involves five phases. In phase 1, the steering committee agreed on the constructs to be measured by sourcing consensus definitions from patients, professionals and the literature. In phases 2 and 3, systematic reviews were conducted to identify tools for each construct and aggregate their evidence. Constructs with and without tools were identified, and scoping reviews were conducted for constructs without tools. Evidence on measurement properties, as well as on timing of assessments, are currently being aggregated. These will be presented in phase 4: a consensus meeting where a multi-disciplinary panel of experts will select the instruments that will form the CMS. Following selection, guidance on the implementation of the CMS will be developed and disseminated (phase 5). A preliminary CMS review scheduled at 4 years from release. ETHICS AND DISSEMINATION Ethical approval was obtained from the University of Cambridge (HBREC2019.14). Dissemination strategies will include peer-reviewed scientific publications; conference presentations; podcasts; the identification of AO Spine RECODE-DCM ambassadors; and engagement with relevant journals, funders and the DCM community

Genetics of Degenerative Cervical Myelopathy: A Systematic Review and Meta-Analysis of Candidate Gene Studies

Degenerative cervical myelopathy (DCM) is estimated to be the most common cause of adult spinal cord impairment. Evidence that is suggestive of a genetic basis to DCM has been increasing over the last decade. A systematic search was conducted in MEDLINE, EMBASE, Cochrane, and HuGENet databases from their origin up to 14th December 2019 to evaluate the role of single genes in DCM in its onset, clinical phenotype, and response to surgical intervention. The initial search yielded 914 articles, with 39 articles being identified as eligible after screening. We distinguish between those contributing to spinal column deterioration and those contributing to spinal cord deterioration in assessing the evidence of genetic contributions to DCM. Evidence regarding a total of 28 candidate genes was identified. Of these, 22 were found to have an effect on the radiological onset of spinal column disease, while 12 genes had an effect on clinical onset of spinal cord disease. Polymorphisms of eight genes were found to have an effect on the radiological severity of DCM, while three genes had an effect on clinical severity. Polymorphisms of six genes were found to have an effect on clinical response to surgery in spinal cord disease. There are clear genetic effects on the development of spinal pathology, the central nervous system (CNS) response to bony pathology, the severity of both bony and cord pathology, and the subsequent response to surgical intervention. Work to disentangle the mechanisms by which the genes that are reviewed here exert their effects, as well as improved quality of evidence across diverse populations is required for further investigating the genetic contribution to DCM

The Role of Nutrition in Degenerative Cervical Myelopathy: A Systematic Review.

INTRODUCTION: Degenerative cervical myelopathy (DCM) is the commonest cause of adult spinal cord impairment worldwide, encompassing chronic compression of the spinal cord, neurological disability and diminished quality of life. Evidence on the contribution of environmental factors is sparse; in particular, the role of nutrition in DCM is unknown. The objective of this review was to assess the effect of nutrition on DCM susceptibility, severity and surgical outcome. METHODS: A systematic review in MEDLINE and Embase was conducted following PRISMA guidelines. Full-text papers in English papers, focussing on cervical myelopathy and nutrition, published before January 2020 were considered eligible. Quality assessments were performed using the GRADE assessment tool. Patient demographics, nutritional factor and DCM outcomes measures were recorded. Relationships between nutritional factors, interventions and disease prognosis were assessed. RESULTS: In total, 5835 papers were identified of which 44 were included in the final analysis. DCM patients with pathological weight pre-operatively were more likely to see poorer improvements post-surgically. These patients experienced poorer physical and mental health improvements from surgery compared to normal weight patients and were more likely to suffer from post-operative complications such as infection, DVT, PE and hospital readmissions. Two trials reporting benefits of nutritional supplements were identified, with 1 suggesting Cerebrolysin to be significant in functional improvement. An unbalanced diet, history of alcohol abuse and malnourishment were associated with poorer post-operative outcome. CONCLUSION: Although the overall strength of recommendation is low, current evidence suggests nutrition may have a significant role in optimising surgical outcome in DCM patients. Although it may have a role in onset and severity of DCM, this is a preliminary suggestion. Further work needs to be done on how nutrition is defined and measured, however, the beneficial results from studies with nutritional interventions suggest nutrition could be a treatment target in DCM.Funding: Dr Benjamin M. Davies is supported by an NIHR Clinical Doctoral Research Fellowship. This report is independent research arising from a Clinician Scientist Award, CS-2015-15-023, supported by the National Institute for Health Research

RE-CODE DCM (search Objectives and ommon ata lements for egenerative ervical yelopathy): A Consensus Process to Improve Research Efficiency in DCM, Through Establishment of a Standardized Dataset for Clinical Research and the Definition of the Research Priorities

Study Design ixed-method consensus process. Objectives egenerative cervical myelopathy (DCM) is a common and disabling condition that arises when mechanical stress damages the spinal cord as a result of degenerative changes in the surrounding spinal structures. RECODE-DCM (search Objectives and ommon ata lements for egenerative ervical yelopathy) aims to improve efficient use of health care resources within the field of DCM by using a multi-stakeholder partnership to define the DCM research priorities, to develop a minimum dataset for DCM clinical studies, and confirm a definition of DCM. Methods his requires a multi-stakeholder partnership and multiple parallel consensus development processes. It will be conducted via 4 phases, adhering to the guidance set out by the COMET (Core Outcomes in Effectiveness Trials) and JLA (James Lind Alliance) initiatives. Phase 1 will consist of preliminary work to inform online Delphi processes (Phase 2) and a consensus meeting (Phase 3). Following the findings of the consensus meeting, a synthesis of relevant measurement instruments will be compiled and assessed as per the COSMIN (Consensus-based Standards for the Selection of Health Measurement Instruments) criteria, to allow recommendations to be made on how to measure agreed data points. Phase 4 will monitor and promote the use of eventual recommendations. Conclusions ECODE-DCM sets out to establish for the first time an index term, minimum dataset, and research priorities together. Our aim is to reduce waste of health care resources in the future by using patient priorities to inform the scope of future DCM research activities. The consistent use of a standard dataset in DCM clinical studies, audit, and clinical surveillance will facilitate pooled analysis of future data and, ultimately, a deeper understanding of DCM

Development of a validated search filter for Ovid Embase for degenerative cervical myelopathy.

Funder: Royal College of Surgeons of England; Id: http://dx.doi.org/10.13039/501100000297BACKGROUND: Degenerative cervical myelopathy (DCM) is a recently proposed umbrella term for symptomatic cervical spinal cord compression secondary to degeneration of the spine. Currently literature searching for DCM is challenged by the inconsistent uptake of the term 'DCM' with many overlapping keywords and numerous synonyms. OBJECTIVES: Here, we adapt our previous Ovid medline search filter for the Ovid embase database, to support comprehensive literature searching. Both embase and medline are recommended as a minimum for systematic reviews. METHODS: References contained within embase identified in our prior study formed a 'development gold standard' reference database (N = 220). The search filter was adapted for embase and checked against the reference database. The filter was then validated against the 'validation gold standard'. RESULTS: A direct translation was not possible, as medline indexing for DCM and the keywords search field were not available in embase. We also used the 'focus' function to improve precision. The resulting search filter has 100% sensitivity in testing. DISCUSSION AND CONCLUSION: We have developed a validated search filter capable of retrieving DCM references in embase with high sensitivity. In the absence of consistent terminology and indexing, this will support more efficient and robust evidence synthesis in the field

Targeting patient recovery priorities in degenerative cervical myelopathy:design and rationale for the RECEDE-Myelopathy trial-study protocol

Introduction: Degenerative cervical myelopathy (DCM) is a common and disabling condition of symptomatic cervical spinal cord compression secondary to degenerative changes in spinal structures leading to a mechanical stress injury of the spinal cord. RECEDE-Myelopathy aims to test the disease-modulating activity of the phosphodiesterase 3/phosphodiesterase 4 inhibitor Ibudilast as an adjuvant to surgical decompression in DCM. Methods and analysis: RECEDE-Myelopathy is a multicentre, double-blind, randomised, placebo-controlled trial. Participants will be randomised to receive either 60-100 mg Ibudilast or placebo starting within 10 weeks prior to surgery and continuing for 24 weeks after surgery for a maximum of 34 weeks. Adults with DCM, who have a modified Japanese Orthopaedic Association (mJOA) score 8-14 inclusive and are scheduled for their first decompressive surgery are eligible for inclusion. The coprimary endpoints are pain measured on a visual analogue scale and physical function measured by the mJOA score at 6 months after surgery. Clinical assessments will be undertaken preoperatively, postoperatively and 3, 6 and 12 months after surgery. We hypothesise that adjuvant therapy with Ibudilast leads to a meaningful and additional improvement in either pain or function, as compared with standard routine care. Study design: Clinical trial protocol V.2.2 October 2020. Ethics and dissemination: Ethical approval has been obtained from HRA - Wales. The results will be presented at an international and national scientific conferences and in a peer-reviewed journals.Trial registration number: ISRCTN Number: ISRCTN16682024.</p

Systematic review of the impact of cannabinoids on neurobehavioral outcomes in preclinical models of traumatic and nontraumatic spinal cord injury.

STUDY DESIGN: Systematic review. OBJECTIVES: To evaluate the impact of cannabinoids on neurobehavioral outcomes in preclinical models of nontraumatic and traumatic spinal cord injury (SCI), with the aim of determining suitability for clinical trials involving SCI patients. METHODS: A systematic search was performed in MEDLINE and Embase databases, following registration with PROPSERO (CRD42019149671). Studies evaluating the impact of cannabinoids (agonists or antagonists) on neurobehavioral outcomes in preclinical models of nontraumatic and traumatic SCI were included. Data extracted from relevant studies, included sample characteristics, injury model, neurobehavioural outcomes assessed and study results. PRISMA guidelines were followed and the SYRCLE checklist was used to assess risk of bias. RESULTS: The search returned 8714 studies, 19 of which met our inclusion criteria. Sample sizes ranged from 23 to 390 animals. WIN 55,212-2 (n = 6) and AM 630 (n = 8) were the most used cannabinoid receptor agonist and antagonist respectively. Acute SCI models included traumatic injury (n = 16), ischaemia/reperfusion injury (n = 2), spinal cord cryoinjury (n = 1) and spinal cord ischaemia (n = 1). Assessment tools used assessed locomotor function, pain and anxiety. Cannabinoid receptor agonists resulted in statistically significant improvement in locomotor function in 9 out of 10 studies and pain outcomes in 6 out of 6 studies. CONCLUSION: Modulation of the endo-cannabinoid system has demonstrated significant improvement in both pain and locomotor function in pre-clinical SCI models; however, the risk of bias is unclear in all studies. These results may help to contextualise future translational clinical trials investigating whether cannabinoids can improve pain and locomotor function in SCI patients.NIHR Clinical Doctoral Research Fellowship

Secondary Analysis of a James Lind Alliance Priority Setting Partnership to Facilitate Knowledge Translation in Degenerative Cervical Myelopathy (DCM): Insights from AO Spine RECODE-DCM

OBJECTIVES: To explore whether a James Lind Alliance Priority Setting Partnership could provide insights on knowledge translation within the field of degenerative cervical myelopathy (DCM). DESIGN: Secondary analysis of a James Lind Alliance Priority Setting Partnership process for DCM. PARTICIPANTS AND SETTING: DCM stake holders, including spinal surgeons, people with myelopathy and other healthcare professionals, were surveyed internationally. Research suggestions submitted by stakeholders but considered answered were identified. Sampling characteristics of respondents were compared with the overall cohort to identify subgroups underserved by current knowledge translation. RESULTS: The survey was completed by 423 individuals from 68 different countries. A total of 22% of participants submitted research suggestions that were considered \u27answered\u27. There was a significant difference between responses from different stakeholder groups (p CONCLUSIONS: Knowledge translation challenges exist within DCM. This practical approach to measuring knowledge translation may offer a more responsive assessment to guide interventions, complementing existing metrics