Background There are increasing opportunities for healthcare professionals outside medicine to be involved in and lead clinical research. However, there are few roles within these professions that include time for research. In order to develop such roles, and evaluate effective use of this time, the range of impacts of this clinical academic activity need to be valued and understood by healthcare leaders and managers. To date, these impacts have not been comprehensively explored, but are suggested to extend beyond traditional quantitative impact metrics, such as publications, citations and funding awards. Methods Ten databases, four grey literature repositories and a naïve web search engine were systematically searched for articles reporting impacts of clinical academic activity by healthcare professionals outside medicine. Specifically, this did not include the direct impacts of the research findings, rather the impacts of the research activity. All stages of the review were performed by a minimum of two reviewers and reported impacts were categorised qualitatively according to a modified VICTOR (making Visible the ImpaCT Of Research) framework. Results Of the initial 2704 identified articles, 20 were eligible for inclusion. Identified impacts were mapped to seven themes: impacts for patients; impacts for the service provision and workforce; impacts to research profile, culture and capacity; economic impacts; impacts on staff recruitment and retention; impacts to knowledge exchange; and impacts to the clinical academic. Conclusions Several overlapping sub-themes were identified across the main themes. These included the challenges and benefits of balancing clinical and academic roles, the creation and implementation of new evidence, and the development of collaborations and networks. These may be key areas for organisations to explore when looking to support and increase academic activity among healthcare professionals outside medicine. The modified VICTOR tool is a useful starting point for individuals and organisations to record the impact of their research activity. Further work is needed to explore standardised methods of capturing research impact that address the full range of impacts identified in this systematic review and are specific to the context of clinical academics outside medicine.

Background: HTLV-1 is a neglected sexually transmitted infection despite being the cause of disabling neurological disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). There is no treatment for this infection and public health policies are essential to reduce its transmission. However, there are no data to support adequate cost-effective analysis in this field. The aim of this study was to obtain health state utility values for individuals with HAM/TSP and HTLV-1 asymptomatic carriers (AC). The impact of both states on quality of life (QoL) is described and compared to other diseases. Methods: A cross-sectional observational study of 141 individuals infected with HTLV-1 (79 with HAM/TSP and 62 AC) from three Brazilian states (Rio de Janeiro, São Paulo and Alagoas) and from the United Kingdom. Participants completed a validated general health questionnaire (EQ-5D, Euroqol) from which country specific health state utility values are generated. Clinical and epidemiological data were collated. Principal findings: Health state utility value for HAM/TSP was 0.2991. QoL for 130 reported clinical conditions ranges from 0.35 to 0.847. 12% reported their quality of life as worse as death. Low QoL was associated with severity rather than duration of disease with a moderate inverse correlation between QoL and Osame’s Motor Disability Score (-0.4933) Patients who are wheelchair dependent had lowest QoL whilst those still walking unaided had the highest. AC also reported impaired QoL (0.7121) compared to general population. Conclusion: HTLV-1 and its associated neurological disease has a marked impact on QoL. This study provides robust data to support the development of cost-utility analysis of interventions for HTLV-1.

Introduction Patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) become progressively impaired, with chronic pain, immobility and bladder, bowel and sexual dysfunction. Tested antiretroviral therapies have not been effective and most patients are offered a short course of corticosteroids or interferon-α, physiotherapy and symptomatic management. Pathogenesis studies implicate activated T-lymphocytes and cytokines in tissue damage. We therefore tested the hypothesis that inhibition of T-cell activation with ciclosporin A would be safe and clinically beneficial in patients with early and/or clinically progressing HAM/TSP. Materials and Methods Open label, proof of concept, pilot study of 48 weeks therapy with the calcineurin antagonist, ciclosporin A (CsA), in seven patients with ‘early’ (50% deterioration in timed walk during the preceding three months) HAM/TSP. Primary outcomes were incidence of clinical failure at 48 weeks and time to clinical failure. Results All patients completed 72 weeks study participation and five showed objective evidence of clinical improvement after 3 months treatment with CsA. Two patients exhibited clinical failure over 6.4 person-years of follow-up to week 48. One patient had a >2 point deterioration in IPEC (Insituto de Pesquisa Clinica Evandro Chagas) disability score at weeks 8 and 12, and then stopped treatment. The other stopped treatment at week 4 because of headache and tremor and deterioration in timed walk, which occurred at week 45. Overall pain, mobility, spasticity and bladder function improved by 48 weeks. Two patients recommenced CsA during follow-up due to relapse. Conclusions These data provide initial evidence that treatment with CsA is safe and may partially reverse the clinical deterioration seen in patients with early/progressive HAM/TSP. This trial supports further investigation of this agent's safety and effectiveness in larger, randomised controlled studies in carefully selected patients with disease progression.

Background Over the past 20 years Functional Electrical Stimulation (FES) has grown in clinical use to support walking in people with lower limb weakness or paralysis due to upper motor neuron lesions. Despite growing consensus regarding its benefits, provision across the UK and internationally is variable. This study aimed to explore stakeholder views relating to the value of a clinical guideline focusing on service provision of FES to support walking, how people might use it and what should be included. Methods A mixed methods exploration sought the views of key stakeholders. A pragmatic online survey (n = 223) focusing on the study aim was developed and distributed to the email distribution list of the UK Association for Chartered Physiotherapists Interested in Neurology (ACPIN). In parallel, a qualitative service evaluation and patient public involvement consultation was conducted. Two group, and seven individual interviews were conducted with: FES-users (n = 6), their family and carers (n = 3), physiotherapists (n = 4), service providers/developers (n = 2), researchers (n = 1) and distributors of FES (n = 1). Descriptive analysis of quantitative data and framework analysis of qualitative data were conducted. Results Support for clinical guideline development was clear in the qualitative interviews and the survey results. Survey respondents most strongly endorsed possible uses of the clinical guideline as ensuring best practice and supporting people seeking access to a FES service. Data analysis and synthesis provided clear areas for inclusion in the clinical guidelines, including current research evidence and consensus relating to who is most likely to benefit and optimal service provision as well as pathways to access this. Specific areas for further investigation were summarised for inclusion in the first stage of a Delphi consensus study. Conclusions Key stakeholders believe in the value of a clinical guideline that focuses on the different stages of service provision for FES to support walking. A Delphi consensus study is being planned based on the findings.

BackgroundFive to ten million persons, are infected by HTLV-1 of which 3% will develop HTLV-1-associated myelopathy (HAM) a chronic, disabling inflammation of the spinal cord. Walking, a fundamental, complex, multi-functional task is demanding of multiple body systems. Restricted walking ability compromises activity and participation levels in people with HAM (pwHAM). Therapy aims to improve mobility but validated measures are required to assess change.Study DesignProspective observational study.ObjectivesTo explore walking capacity in pwHAM, walking endurance using the 6 minute walk (6MW), and gait speed, using the timed 10m walk (10mTW).SettingOut-patient setting in an inner London Teaching hospital.MethodsProspective documentation of 10mTW and 6MW distance; walking aid usage and pain scores measured twice, a median of 18 months apart.ResultsData analysis was completed for twenty-six pwHAM, (8♂; 18♀; median age: 57.8 years; median disease duration: 8 years). Median time at baseline to: complete 10m was 17.5 seconds, versus 21.4 seconds at follow up; 23% completed the 6MW compared to 42% at follow up and a median distance of 55m was covered compared to 71m at follow up. Using the 10mTW velocity to predict the 6MW distance, overestimated the distance walked in 6 minutes (p<0.01). Functional decline over time was captured using the functional ambulation categories.ConclusionsThe 10mTW velocity underestimated the degree of disability. Gait speed usefully predicts functional domains, shows direction of functional change and comparison with published healthy age matched controls show that these patients have significantly slower gait speeds. The measured differences over 18 months were sufficient to reliably detect change and therefore these assessments can be useful to detect improvement or deterioration within broader disability grades. Walking capacity in pwHAM should be measured using the 10mTW for gait speed and the 6MW for endurance.

Functional Electrical Stimulation (FES) has been used to support mobility for people with upper motor neuron conditions such as stroke and multiple sclerosis for over 25 years. Recent development and publication of clinical practice guidelines (CPGs) provide evidence to guide clinical decision making for application of FES to improve mobility. Understanding key barriers to the implementation of these CPGs is a critical initial step necessary to create tailored knowledge translation strategies. A public involvement and engagement consultation was conducted with international stakeholders including researchers, clinicians and engineers working with FES to inform implementation strategies for CPG use internationally. Reflexive thematic analysis of the consultation transcripts revealed themes including inconsistent use of CPGs, barriers to implementation such as limited access to FES and low clinician confidence, and the need for a tiered education approach with ongoing support. Insights derived from this consultation will inform the development of knowledge translation strategies to support the next steps to implementing FES use for mobility.

HTLV-1-associated myelopathy (HAM; HTLV-1 is human T-lymphotropic virus type 1) is a chronic debilitating neuroinflammatory disease with a predilection for the thoracic cord. Tissue damage is attributed to the cellular immune response to HTLV-1-infected lymphocytes. The brains of HTLV-1-infected patients, with and without HAM but no clinical evidence of brain involvement, were examined using a specific 18-kDa translocator protein ligand, 11 C-PBR28, and T1-weighted and diffusion-weighted MRI. Methods: Five subjects with HAM and 2 HTLV-1 asymptomatic carriers were studied. All underwent clinical neurologic assessment including cognitive function and objective measures of gait, quantification of HTLV-1 proviral load in peripheral blood mononuclear cells, and human leukocyte antigenantigen D related expression on circulating CD81 lymphocytes. 11 C-PBR28 PET and MRI were performed on the same day. 11 C-PBR28 PET total volume of distribution and distribution volume ratio (DVR) were estimated using 2-tissue-compartment modeling. MRI data were processed using tools from the FMRIB Software Library to estimate mean diffusivity (MD) and gray matter (GM) fraction changes. The results were compared with data from age-matched healthy volunteers. Results: Across the whole brain, the total volume of distribution for the subjects with HAM (5.44 ± 0.84) was significantly greater than that of asymptomatic carriers (3.44 ± 0.80). The DVR of the thalamus in patients with severe and moderate HAM was higher than that in the healthy volunteers, suggesting increased translocator protein binding (z . 4.72). Subjects with more severe myelopathy and with high DR expression on CD81 lymphocytes had increased DVR and MD (near-significant correlation found for the right thalamus MD: P 5 0.06). On the T1-weighted MRI scans, the GM fraction of the brain stem was reduced in all HTLV-1-infected patients compared with controls (P , 0.001), whereas the thalamus GM fraction was decreased in patients with HAM and correlated with the disease severity. There was no correlation between neurocognitive function and these markers of central nervous system inflammation. Conclusion: This pilot study suggests that some patients with HAM have asymptomatic inflammation in the brain, which can be detected and monitored by 11 C-PBR28 PET together with structural and diffusion-weighted MRI.

BackgroundTo advance the treatment of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), randomised controlled therapeutic studies with appropriate and sensitive outcomes are reuired. One candidate outcome is the 10-metre walk test (10MWT), a patient-centred, simple and functional measure. To calculate sample size based on 10MWT as the primary outcome, variability within and between subjects must be known.MethodsData on 10MWT from 76 patients with HAM/TSP were prospectively collected from four specialist centres in Brazil, Japan, USA and UK. Data, collected at two time points, 6 months apart, were log transformed and subjected to analysis of covariance.ResultsBaseline mean (standard deviation = SD), median 10MWT were 23.5 (18.9), 16.3 s/10 m and at 6 months 24.9 (23.9), 16.4 s/10 m. The mean (SD) % increase in walk time was 5.74 % (28.2 %). After logarithmic transformation, the linear correlation between baseline and 24 weeks 10MWT was r = 0.938. Using these data, it was determined that a randomised controlled trial with 30 participants per group would have 90 % power to detect a 19 % decrease or a 23 % increase in 10MWT.ConclusionsThe intra-patient variability of 10MWT is relatively small in HAM/TSP over 6 months. 10MWT is a feasible outcome measure for a clinical trial in HAM/TSP. To our knowledge, this is the first ever recommendation for the sample size required for trials in HAM/TSP patients.