• A meta-analysis of remote ischaemic conditioning in experimental stroke.

      England, Tim (2020-06)
      Remote ischaemic conditioning (RIC) is achieved by repeated transient ischaemia of a distant organ/limb and is neuroprotective in experimental ischaemic stroke. However, the optimal time and methods of administration are unclear. Systematic review identified relevant preclinical studies; two authors independently extracted data on infarct volume, neurological deficit, RIC method (administration time, site, cycle number, length of limb occlusion (dose)), species and quality. Data were analysed using random effects models; results expressed as standardised mean difference (SMD). In 57 publications incorporating 99 experiments (1406 rats, 101 mice, 14 monkeys), RIC reduced lesion volume in transient (SMD -2.0; 95% CI -2.38, -1.61; p < 0.00001) and permanent (SMD -1.54; 95% CI -2.38, -1.61; p < 0.00001) focal models of ischaemia and improved neurological deficit (SMD -1.63; 95% CI -1.97, -1.29, p < 0.00001). In meta-regression, cycle length and number, dose and limb number did not interact with infarct volume, although country and physiological monitoring during anaesthesia did. In all studies, RIC was ineffective if the dose was <10 or ≥50 min. Median study quality was 7 (range 4-9/10); Egger's test suggested publication bias (p < 0.001). RIC is most effective in experimental stroke using a dose between 10 and 45 min. Further studies using repeated dosing in animals with co-morbidities are warranted.
    • MiR-126 and miR-126* regulate shear-resistant firm leukocyte adhesion to human brain endothelium.

      Edwards, Laura (2017-03)
      Leukocyte adhesion to brain endothelial cells, the blood-brain barrier main component, is a critical step in the pathogenesis of neuroinflammatory diseases such as multiple sclerosis (MS). Leukocyte adhesion is mediated mainly by selectins, cell adhesion molecules and chemokines induced by pro-inflammatory cytokines such as TNFα and IFNγ, but the regulation of this process is not fully clear. This study investigated the regulation of firm leukocyte adhesion to human brain endothelium by two different brain endothelial microRNAs (miRs), miR-126 and miR-126*, that are downregulated by TNFα and IFNγ in a human brain endothelial cell line, hCMEC/D3. Using a leukocyte adhesion in vitro assay under shear forces mimicking blood flow, we observed that reduction of endothelial miR-126 and miR-126* enhanced firm monocyte and T cell adhesion to hCMEC/D3 cells, whereas their increased expression partially prevented THP1, Jurkat and primary MS patient-derived PBMC firm adhesion. Furthermore, we observed that miR-126* and miR-126 downregulation increased E-selectin and VCAM1, respectively, while miR-126 overexpression reduced VCAM1 and CCL2 expression by hCMEC/D3 cells, suggesting that these miRs regulate leukocyte adhesion by modulating the expression of adhesion-associated endothelial mRNA targets. Hence, human brain endothelial miR-126 and miR-126* could be used as a therapeutic tool to reduce leukocyte adhesion and thus reduce neuroinflammation.
    • Mortality and Institutionalization After Percutaneous Endoscopic Gastrostomy in Parkinson's Disease and Related Conditions.

      Skelly, Robert; Brown, Lisa (2020-06)
      Background: Percutaneous endoscopic gastrostomy (PEG) can facilitate feeding and medication administration in dysphagic patients with Parkinson's disease and related disorders. Information on survival, institutionalization, and complications post PEG might inform feeding decisions. Method: A total of 93 patients with Parkinson's disease and related disorders were identified by review of PEG registers and by searching the administrative databases in 2 large UK university hospitals (2005-2017); 83 case notes were available for retrospective review. Care processes and outcomes were assessed. Results: The following were the diagnoses: 58 (70%) had Parkinson's disease, 10 (12%) had progressive supranuclear palsy, 5 (6%) had multiple system atrophy, 3 (4%) had dementia with Lewy bodies, and 7 (8%) had vascular parkinsonism. The median age was 78 years (interquartile range 72-82); 29 (35%) were women. Care processes included a future care plan in place prior to admission for 18 patients (22%), and PEG was placed during emergency admission in 68 patients (82%). The outcomes included median survival at 422 days; 30-day mortality rate was 6% (5 patients); and of 56 patients admitted from home, 18 (32%) were discharged to institutions (nursing or care homes). The most common complication was aspiration pneumonia for 18 (22%) of patients. Age, sex, diagnosis, admission type, comorbidities, and place of residence did not predict survival. Discharge to own home and follow-up by the home enteral feeding team were associated with longer survival. Conclusion: We recommend markers of advanced disease should prompt advanced care planning. Discussions about PEG feeding should include information about post-PEG survival, complications, and risk of institutionalization. Further research is needed on quality-of-life post PEG and ways to reduce aspiration pneumonia. All PEG patients should have nutrition team follow-up.
    • A multidisciplinary approach to Parkinson's disease.

      Lindop, Fiona (2012-04)
      Overview of the Parkinson's Disease Service model developed by the multidisciplinary team (MDT) at Derby Hospitals NHS Foundation Trust. The importance of understanding basal ganglia function and subsequent dysfunction in Parkinson disease, cues and strategies in MDT management of basal ganglia dysfunction and the roles of different members of the Derby MDT are discussed
    • Neurocysticercosis presenting as a 'Stroke Mimic'.

      England, Tim; Ghasemi, R; Rowe, Aimee; Venkatesan, P (2016)
      A 62 year old Nepalese gentleman presented with left sided weakness and sensory loss. Initial brain CT scanning was suggestive of acute infarction but a subsequent MRI scan showed cysts with oedema. Cysticercosis serology was positive and a diagnosis of neurocysticercosis was made. The patient made almost a complete recovery after treatment with albendazole, praziquantel and steroids. Neurocysticercosis should be considered in the diffierential diagnosis when patients originating from endemic areas present with focal neurological deficit.
    • Neuromuscular conditions for physicians - what you need to know.

      Edwards, Laura; Phillips, Margaret (2016-06)
      The Royal College of Physicians (RCP) and the British Society of Rehabilitation Medicine co-hosted a meeting entitled 'Neuromuscular conditions for physicians - what you need to know' at the RCP on 30 November 2015. There was a series of talks, ranging from in-depth genetic and molecular descriptions of pathology to multidisciplinary management of chronic neuromuscular conditions, which stimulated lively debate and discussion. Some overarching themes emerged from the day, most notably: i) the changing expectations and survival rates in Duchenne muscular dystrophy (DMD), which are transforming this disorder into an adult as much as a paediatric condition; ii) the need for integrated management and good communication -between services - whether primary, secondary and tertiary care, medical teams and intensivists, or the multiple teams involved in providing treatment to neuromuscular patients; and iii) in line with the above, the essential need for streamlining care such that patients can avoid spending most of their time attending outpatient appointments, and instead concentrate on living full lives and exploring educational, occupational, leisure and social opportunities.
    • Online patient information resources on gout provide inadequate information and minimal emphasis on potentially curative urate lowering treatment.

      Edwards, Laura (2016-07)
      Objectives To assess the content and readability of online patient information resources against the current understanding of gout. Methods An online survey was undertaken using Google UK, USA, Australia and Canada. Information was assessed for content and accuracy on nineteen key points regarded core content for gout patient information resource. Readability was assessed using Flesch-Kincaid Reading Ease score. Fifteen randomly selected websites were reviewed by a blinded second observer. Results Eighty-five websites were selected. More than 50% of websites provided no information or had inaccuracies regarding the pathogenesis of gout. Most websites contained infomraiton on dietary and lifestyle modifications for treating gout and did not emphasise urate lowering therapy (ULT) and its potential for "cure". Over 75% websites had no/inaccurate information on the role of ULT or prophylaxis for preventing gout attacks on starting ULT. The majority of websites were difficult to read, with information in 68% websites rated at least fairly difficult. Conclusion Only few web-based patient information resources provide accurate and easy to read information on gout. This study will help physicians direct patients to currently reliable resources, but there is a need to improve many web-based patient information resources which at present act as barriers to care.
    • Optimal healthcare delivery to care homes in the UK: a realist evaluation of what supports effective working to improve healthcare outcomes.

      Gordon, Adam (2018-01)
      Introduction: care home residents have high healthcare needs not fully met by prevailing healthcare models. This study explored how healthcare configuration influences resource use. Methods: a realist evaluation using qualitative and quantitative data from case studies of three UK health and social care economies selected for differing patterns of healthcare delivery to care homes. Four homes per area (12 in total) were recruited. A total of 239 residents were followed for 12 months to record resource-use. Overall, 181 participants completed 116 interviews and 13 focus groups including residents, relatives, care home staff, community nurses, allied health professionals and General Practitioners. Results: context-mechanism-outcome configurations were identified explaining what supported effective working between healthcare services and care home staff: (i) investment in care home-specific work that legitimises and values work with care homes; (ii) relational working which over time builds trust between practitioners; (iii) care which 'wraps around' care homes; and (iv) access to specialist care for older people with dementia. Resource use was similar between sites despite differing approaches to healthcare. There was greater utilisation of GP resource where this was specifically commissioned but no difference in costs between sites. Conclusion: activities generating opportunities and an interest in healthcare and care home staff working together are integral to optimal healthcare provision in care homes. Outcomes are likely to be better where: focus and activities legitimise ongoing contact between healthcare staff and care homes at an institutional level; link with a wider system of healthcare; and provide access to dementia-specific expertise.
    • Orthotic management of instability of the knee related to neuromuscular and central nervous system disorders: systematic review, qualitative study, survey and costing analysis

      Phillips, Margaret (2016-07)
      BACKGROUND: Patients who have knee instability that is associated with neuromuscular disease (NMD) and central nervous system (CNS) conditions can be treated using orthoses, such as knee-ankle-foot orthoses (KAFOs). OBJECTIVES: To assess existing evidence on the effectiveness of orthoses; patient perspectives; types of orthotic devices prescribed in the UK NHS; and associated costs. METHODS: Qualitative study of views of orthoses users - a qualitative in-depth interview study was undertaken. Data were analysed for thematic content. A coding scheme was developed and an inductive approach was used to identify themes. Systematic review - 18 databases were searched up to November 2014: MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, Cumulative Index to Nursing and Allied Health, EMBASE, PASCAL, Scopus, Science Citation Index, BIOSIS Previews, Physiotherapy Evidence Database, Recal Legacy, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Health Technology Assessment database, Cochrane Central Register of Controlled Trials, Conference Proceedings Citation Index: Science, Health Management Consortium, ClinicalTrials.gov, International Clinical Trials Registry Platform and National Technical Information Service. Studies of adults using an orthosis for instability of the knee related to NMD or a CNS disorder were included. Data were extracted and quality was assessed by two researchers. Narrative synthesis was undertaken. Survey and costing analysis - a web survey of orthotists, physiotherapists and rehabilitation medicine physicians was undertaken. Telephone interviews with orthotists informed a costing analysis. RESULTS: Qualitative study - a total of 24 people participated. Potential for engagement in daily activities was of vital importance to patients; the extent to which their device enabled this was the yardstick by which it was measured. Patients' prime desired outcome was a reduction in pain, falls or trips, with improved balance and stability. Effectiveness, reliability, comfort and durability were the most valued features of orthoses. Many expressed frustration with perceived deficiencies in service provision relating to appointment and administrative systems and referral pathways. Systematic review - a total of 21 studies (478 participants) were included of people who had post-polio syndrome, inclusion body myositis, were post stroke or had spinal cord injury. The studies evaluated KAFOs (mainly carbon fibre), stance control KAFO and hip KAFOs. All of the studies were at risk of bias and, in general, were poorly reported. Survey and costing analysis - in total, 238 health-care professionals responded. A range of orthoses is prescribed for knee instability that is related to NMD or CNS conditions, approximately half being custom-made. At least 50% of respondents thought that comfort and confidence in mobility were extremely important treatment outcomes. The cost of individual KAFOs was highly variable, ranging from £73 to £3553. CONCLUSIONS: Various types of orthoses are used in the NHS to manage patients with NMD/CNS conditions and knee instability, both custom-made and prefabricated, of variable cost. Evidence on the effectiveness of the orthoses is limited, especially in relation to the outcomes that are important to orthoses users. LIMITATIONS: The population included was broad, limiting any in-depth consideration of specific conditions. The response rate to the survey was low, and the costing analysis was based on some assumptions that may not reflect the true costs of providing KAFOs. FUTURE WORK: Future work should include high-quality research on the effectiveness and cost-effectiveness of orthoses; development of a core set of outcome measures; further exploration of the views and experiences of patients; and the best models of service delivery. STUDY REGISTRATION: This study is registered as PROSPERO CRD42014010180. The qualitative study is registered as Current Controlled Trials ISRCTN65240228. FUNDING: The National Institute for Health Research Health Technology Assessment programme.
    • Patients' attitudes towards cost feedback to doctors to prevent unnecessary testing: a qualitative focus group study

      Skelly, Robert; Thurley, Peter; Sturrock, Nigel; Norwood, Mark (2020-07)
      OBJECTIVES: There is a need to improve efficiency in healthcare delivery without compromising quality of care. One approach is the development and evaluation of behavioural strategies to reduce unnecessary use of common tests. However, there is an absence of evidence on patient attitudes to the use of such approaches in the delivery of care. Our objective was to explore patient acceptability of a nudge-type intervention that aimed to modify blood test requests by hospital doctors. STUDY DESIGN: Single-centre qualitative study. METHODS: The financial costs of common blood tests were presented to hospital doctors on results reports for 1 year at a hospital. Focus group discussions were conducted with recent inpatients at the hospital using a semi-structured question schedule. Discussions were transcribed and analysed using qualitative content analysis to identify and prioritise common themes explaining attitudes to the intervention approach. RESULTS: Three focus groups involving 17 participants were conducted. Patients were generally apprehensive about the provision of blood test cost feedback to doctors. Attitudes were organised around themes representing beliefs about blood tests, the impact on doctors and their autonomy, and beliefs about unnecessary testing. Patients thought that blood tests were important, powerful and inexpensive, and cost information could place doctors under additional pressure. CONCLUSION: The findings identify predominantly positive beliefs about testing and negative attitudes to the use of financial costs in the decision-making of hospital doctors. Public discussion and education about the possible overuse of common tests may allow more resources to be allocated to evidence-based healthcare, by reducing the perception that such strategies to improve healthcare efficiency negatively impact on quality of care.
    • Pet Ownership and Multiple Sclerosis during COVID-19

      Edwards, Laura (2021)
      Background: Multiple sclerosis (MS) is associated with lower quality of life, reduced social participation, and decreased self-efficacy. The COVID-19 pandemic has had documented effects on the health and wellbeing of people with and without MS. Previous research has demonstrated the positive impact pets can have for people living with long-term conditions. Objectives: To explore the rates of pet ownership and pet attachment in people living with MS and pet ownership associations with quality of life, satisfaction with social roles, and self-efficacy scores; and to explore the effects of the COVID-19 outbreak on people's perceived relationships with their pets. Materials and Methods: A postal questionnaire was distributed to members of a local MS Register and a control group of people without MS. The questionnaire assessed quality of life, satisfaction with social roles, self-efficacy, the perceived roles of pets, and pet-related concerns experienced during the COVID-19 pandemic. Results: No apparent difference in attachment to pets was found between the patient and control groups. Pet ownership and level of attachment were not associated with differences in quality of life or self-efficacy scores in people living with MS. Using multiple regression analysis, pet ownership was associated with a decrease in satisfaction with participation in social roles, but with the estimated effect being small compared to having a diagnosis of MS or being unemployed. Most participants reported that pets had positive roles during the pandemic, and the most reported pet-related concern was access to veterinary treatment. Conclusion: Pet owners both with and without MS reported subjective benefits to their wellbeing from pet ownership during COVID-19, although analysis suggested that pet ownership was associated with a reduction in satisfaction with social roles. The study had several limitations and suggestions are made for future work.
    • Physiotherapist-led suprascapular nerve blocks for persistent shoulder pain: Evaluation of a new service in the UK.

      Salt, Emma; Mainwaring, Frederick; Ashwood, Neil (2018-03)
      INTRODUCTION: This service evaluation explored and reported findings from a new physiotherapist-led service offering suprascapular nerve blocks (SSNBs) to patients with persistent shoulder pain. METHODS: We collected data before the SSNB injection and at the 6-weeks and 6-month follow-up from consecutive patients with persistent shoulder pain being treated by physiotherapists or an anaesthetist. Outcomes were patient-reported pain (numerical rating scale [NRS 0 to 10]), patient-specific functional score (PSFS) and health-related quality of life [the EuroQol five dimensions questionnaire (EQ5D-5 L)]. Exploratory analyses compared baseline and follow-up scores within each clinician delivery group (physiotherapists, anaesthetist). RESULTS: Forty patients (mean age 57 years [standard deviation {SD} 12]; 63% female) received an SSNB from a physiotherapist, eight patients (mean age 59 years [SD 11]; female 88%) received an SSNB from an anaesthetist. At the 6-week follow-up, the physiotherapy group showed a mean reduction in pain (on the NRS): 2.2 (95% confidence interval [CI] 1.3 to 3.0) and an improvement in function (on the PSFS): -1.3 (95% CI -1.9 to -0.4). Similar changes were found in those treated by the anaesthetist (pain: 1.3 [95% CI -1.18 to 3.80]; function: -1.4 (95% CI -3.18 to 0.35]). Very small changes, that were not statistically significant, were found in EQ5D-5 L scores. At the 6-month follow-up, the mean reduction in pain (NRS) was maintained at 2.0 (95% CI 0.99 to 2.95) for the physiotherapy group. CONCLUSION: The results provide early, exploratory evidence that patients with persistent shoulder pain treated by physiotherapists using palpation-guided SSNBs achieve clinically important changes in pain and function in the short and medium term.
    • Physiotherapy treatment for atraumatic recurrent shoulder instability: early results of a specific exercise protocol using pathology-specific outcome measures

      Bateman, Marcus; Smith, Benjamin; Osborne, Sally (2015-10)
      BACKGROUND: Recurrent shoulder instability is usually caused by a traumatic event resulting in structural pathology, although a small subgroup of patients experience symptomatic recurrent shoulder instability without trauma. These patients are usually treated non-operatively but limited evidence exists regarding effective conservative management. In particular, there is a lack of reproducible exercise regimes and none that have been tested with condition-specific outcome measures. METHODS: A service evaluation was conducted over a 15-month period to assess our current treatment protocol used in the management of patients with atraumatic recurrent shoulder instability. The regime is reproducible with target-led progression milestones. Oxford Instability Shoulder Scores (OISS) and Western Ontario Shoulder Index (WOSI) scores were compared between baseline and final follow-up. RESULTS: Eighteen consecutive patients were included with mean follow-up of 4.5 months (range 1.35 months to 11.77 months). A statistically significant improvement was seen in both outcome measures. Mean OISS improved by 16.67 points (confidence interval: 12.34 to 20.99; p < 0.001). Mean WOSI improved by 36.76% (confidence interval: 28.46 to 45.06; p < 0.001). CONCLUSIONS: For this small group of patients with recurrent atraumatic shoulder instability, the Derby Shoulder Instability Programme produced significant improvements over the short term, with a high level of patient compliance. This is the first study to include pathology-specific patient-reported outcome measures to assess outcomes from a specific and reproducible exercise regime in this group of patients. The findings support further research to evaluate the exercise protocol in a larger group of patients over the longer term.
    • A pilot study of a crossover trial with randomized use of ankle-foot orthoses for people with Charcot–Marie–Tooth disease

      Phillips, Margaret (2012-06)
      Objectives: This was a pilot and feasibility study of a crossover trial with randomized use of ankle-foot orthoses by people with Charcot–Marie–Tooth (CMT) disease, investigating the effects of these on gait parameters, practical aspects of use and achievement of goals. Design: A randomized crossover trial. Setting: The community and ambulatory care. Participants: Eight adults with CMT disease type 1 or 2. Interventions: Ligaflex™, custom-made polypropylene and silicone ankle-foot orthoses worn in randomized order for three weeks each, with a washout week in-between; the orthoses of each participant’s choice were then worn until 28 weeks. Main outcome measures: The primary outcome measure was gait velocity; other outcome measures included Goal Attainment Scaling; Likert scores, concerning aspects of orthosis use and gait analysis parameters. Results: Gait velocity was greatest wearing polypropylene orthoses, median 0.96 (interquartile range (IQR) 0.75–1.18) ms −1, compared with silicone orthoses, median 0.88 (0.71–1.12) ms −1, and no orthosis, median 0.79 (0.56–0.84) ms −1, P = 0.006. The silicone orthoses met goals more successfully and scored more favourably for comfort, 5.0 (5.0–6.0), P = 0.003 and pain, 5.5 (4.0–7.0), P = 0.015. Future modifications to study methodology were identified, such as a longer period of wear and measurement of walking in different situations. Conclusions: This study confirmed the feasibility of a larger trial. It indicated differences in walking velocity and parameters concerning wear of the orthoses that could be explored further. A further crossover trial would require 27 participants in order to show a clinically meaningful difference in velocity of 0.13 ms −1 with 90% power and alpha of 5%.
    • Predicting fracture risk in osteoporosis: the use of fracture prediction tools in an osteoporosis clinic population.

      Chua, Wei Mei (2016-07)
      BACKGROUND: In the UK, the National Institute for Health and Care Excellence recommends either fracture risk assessment tool (FRAX) or QFracture to estimate the 10 year fracture risk of individuals. However, it is not known how these tools compare in determining risk and subsequent treatment using set intervention thresholds or guidelines. METHODS: The 10 year major osteoporotic (MO) and hip (HI) fracture risks were calculated for 100 women attending osteoporosis clinic in 2010 using FRAX and QFracture, and subsequent agreement to treatment between the tools was looked at using National Osteoporosis Foundation and National Bone Health Alliance thresholds (FRAX-20/3 and QFracture 20/3). We also looked at using these thresholds for QFracture and comparing them with the National Osteoporosis Guideline Group (NOGG) guidelines for FRAX (FRAX-NOGG). RESULTS: The 10 year risk for MO fracture for FRAX was 17.0% (IQR 10.8-24.0) and that of QFracture was 15.8% (IQR 9.5-27.7) (p=0.732). The 10 year risk for HI fracture for FRAX was 5.0% (IQR 2.1-8.9) and that of QFracture was 8.1% (IQR 2.5-21.6) (p<0.001). The agreement between FRAX-20/3 and QFracture-20/3 was greater than the agreement between FRAX-20/3 and FRAX-NOGG or QFracture-20/3 and FRAX-NOGG. CONCLUSIONS: The calculated 10 year risk for MO fracture between FRAX and QFracture was similar, whereas that of HI fracture was significantly different. The agreement to treatment between QFracture-20/3 and FRAX-NOGG was only 45%. Treatment decisions can differ depending on the fracture calculation tool used when coupled with certain intervention thresholds or guidelines.
    • Prehospital Transdermal Glyceryl Trinitrate for Ultra-Acute Intracerebral Hemorrhage: Data From the RIGHT-2 Trial.

      England, Tim (2019-11)
      Background and Purpose- Pilot trials suggest that glyceryl trinitrate (GTN; nitroglycerin) may improve outcome when administered early after stroke onset. Methods- We undertook a multicentre, paramedic-delivered, ambulance-based, prospective randomized, sham-controlled, blinded-end point trial in adults with presumed stroke within 4 hours of ictus. Participants received transdermal GTN (5 mg) or a sham dressing (1:1) in the ambulance and then daily for three days in hospital. The primary outcome was the 7-level modified Rankin Scale at 90 days assessed by central telephone treatment-blinded follow-up. This prespecified subgroup analysis focuses on participants with an intracerebral hemorrhage as their index event. Analyses are intention-to-treat. Results- Of 1149 participants with presumed stroke, 145 (13%; GTN, 74; sham, 71) had an intracerebral hemorrhage: time from onset to randomization median, 74 minutes (interquartile range, 45-110). By admission to hospital, blood pressure tended to be lower with GTN as compared with sham: mean, 4.4/3.5 mm Hg. The modified Rankin Scale score at 90 days was nonsignificantly higher in the GTN group: adjusted common odds ratio for poor outcome, 1.87 (95% CI, 0.98-3.57). A prespecified global analysis of 5 clinical outcomes (dependency, disability, cognition, quality of life, and mood) was worse with GTN; Mann-Whitney difference, 0.18 (95% CI, 0.01-0.35; Wei-Lachin test). GTN was associated with larger hematoma and growth, and more mass effect and midline shift on neuroimaging, and altered use of hospital resources. Death in hospital but not at day 90 was increased with GTN. There were no significant between-group differences in serious adverse events. Conclusions- Prehospital treatment with GTN worsened outcomes in patients with intracerebral hemorrhage. Since these results could relate to the play of chance, confounding, or a true effect of GTN, further randomized evidence on the use of vasodilators in ultra-acute intracerebral hemorrhage is needed. Clinical Trial Registration- URL: http://www.controlled-trials.com. Unique identifier: ISRCTN26986053.
    • Protocol of a single group prospective observational study on the diagnostic value of 3T susceptibility weighted MRI of nigrosome-1 in patients with parkinsonian symptoms: the N3iPD study (nigrosomal iron imaging in Parkinson's disease).

      Birchall, James; Skelly, Robert (2017-12)
      INTRODUCTION: Parkinson's disease (PD) is the most common movement disorder in the elderly and is characterised clinically by bradykinesia, tremor and rigidity. Diagnosing Parkinson's can be difficult especially in the early stages. High-resolution nigrosome MRI offers promising diagnostic accuracy of patients with established clinical symptoms; however, it is unclear whether this may help to establish the diagnosis in the early stages of PD, when there is diagnostic uncertainty. In this scenario, a single photon emission CT scan using a radioactive dopamine transporter ligand can help to establish the diagnosis, or clinical follow-up may eventually clarify the diagnosis. A non-invasive, cost-effective diagnostic test that could replace this would be desirable. We therefore aim to prospectively test whether nigrosome MRI is as useful as DaTSCAN to establish the correct diagnosis in people with minor or unclear symptoms suspicious for PD. METHODS AND ANALYSIS: In a prospective study we will recruit 145 patients with unclear symptoms possibly caused by Parkinson's from three movement disorder centres in the UK to take part in the study. We will record the Movement Disorder Society - Unified Parkinson's Disease Rating Scale, and participants will undergo DaTSCAN and high-resolution susceptibility weighted MRI at a field strength of 3T. DaTSCANs will be assessed visually and semiquantitatively; MRI scans will be visually assessed for signal loss in nigrosome-1 by blinded investigators. We will compare how the diagnosis suggested by MRI compares with the diagnosis based on DaTSCAN and will also validate the diagnosis based on the two tests with a clinical examination performed at least 1 year after the initial presentation as a surrogate gold standard diagnostic test. ETHICS AND DISSEMINATION: The local ethics commission (Health Research Authority East Midlands - Derby Research Ethics Committee) has approved this study (REC ref.: 16/EM/0229). The study is being carried out under the principles of the Declaration of Helsinki (64th, 2013) and Good Clinical Practice standards. We have included a number of 15 research-funded DaTSCAN in the research protocol. This is to compensate for study site-specific National Health Service funding for this investigation in affected patients. We therefore have also obtained approval from the Administration of Radioactive Substances Administration Committee (ARSAC Ref 253/3629/35864). All findings will be presented at relevant scientific meetings and published in peer-reviewed journals, on the study website, and disseminated in lay and social media where appropriate.
    • Randomised Controlled Trial for the Efficacy of Cervical Lateral Glide Mobilisation in the Management of Cervicobrachial Pain.

      Salt, Emma (2016-08)
      Objectives: To investigate the long-term efficacy of lateral glide mobilisation for patients with chronic Cervicobrachial Pain (CP). Methods: A randomised controlled trial which involved ninetynine participants with chronic CP. Participants were randomised to receive either the lateral glide with self-management (n = 49) or self-management alone (n = 50). Four assessments were made (at baseline and 6, 26 and 52 weeks post intervention). The primary outcome measure was the Visual Analogue Scale (VAS) for pain. Patient perceived recovery used the Global Rating of Change score (GROC). Functional outcomes included the Neck and Upper Limb Index score (NULI) and the Short-From 36 (SF36). Costs and reported number of harmful effects in response to intervention were evaluated. An intention to treat approach was followed for data analysis. Results: No statistically significant between-group differences were found for pain (using VAS) in the short-term at six weeks (p = 0.52; 95% CI −14.72 to 7.44) or long-term at one year (p = 0.37; 95% CI −17.76 to 6.61) post-intervention. The VAS outcomes correlated well with GROC scores (p < 0.001). There was a statistically significant difference in NULI scores favouring self-management alone (p = 0.03), but no between-group differences for SF36 (p = 0.07). The cost of providing lateral glide and self-management was twice that of providing self-management alone. Minor harm was reported in both groups, with 11% more harm being associated with the lateral glide. Conclusion: In patients with chronic CP, the addition of a lateral-glide mobilization to a self-management program did not produce improved outcomes and resulted in higher health-care costs.