Ethnicity and deprivation negatively impact the access to disease-modifying therapy for relapsing-remitting multiple sclerosis: a retrospective, single-centre study.

BACKGROUND: A growing body of evidence suggests inequitable access to disease-modifying therapies (DMTs) for multiple sclerosis (MS) in publicly funded healthcare systems. This retrospective study examined the impact of ethnicity and deprivation on the access to DMTs. METHODS: All adults diagnosed with relapsing-remitting MS between 2010 and 2020 were included. The impact of ethnicity and deprivation on being offered and starting any DMTs and high-efficacy DMTs were measured using binary, multinomial logistic and Cox regression models. These analyses were adjusted for sex, age at diagnosis and year of diagnosis. RESULTS: 164/1648 people with MS (PwMS) were from non-white ethnicities. 461/1648 who were living in the most deprived areas, were less likely to be offered DMTs, with an OR of 0.66 (95% CI 0.47 to 0.93), less likely to start high-efficacy DMTs with an OR of 0.67 (95% CI 0.48 to 0.93) and more likely to experience a delay in starting high-efficacy DMTs with an HR of 0.76 (95% CI 0.63 to 0.92), when also adjusted for ethnicity. Although the offer of DMTs did not depend on ethnicity, PwMS from non-white ethnicities were more likely to decline DMTs, less likely to start any DMTs and high-efficacy DMTs with ORs of 0.60 (95% CI 0.39 to 0.93) and 0.61 (95% CI 0.38 to 0.98), respectively, and more likely to experience a delay in starting DMTs with an HR of 0.79 (95% CI 0.66 to 0.95), when also adjusted for deprivation. CONCLUSIONS: In a publicly funded healthcare system, the access to DMTs varied depending on ethnicities and levels of deprivation.

Metacognitive therapy home-based self-help for anxiety and depression in cardiovascular disease patients in the UK: A single-blind randomised controlled trial.

BACKGROUND: Anxiety and depression in cardiac rehabilitation (CR) are associated with greater morbidity, mortality, and increased healthcare costs. Current psychological interventions within CR have small effects based on low-quality studies of clinic-based interventions with limited access to home-based psychological support. We tested the effectiveness of adding self-help metacognitive therapy (Home-MCT) to CR in reducing anxiety and depression in a randomised controlled trial (RCT). METHODS AND FINDINGS: We ran a single-blind, multi-centre, two-arm RCT. A total of 240 CR patients were recruited from 5 NHS-Trusts across North West England between April 20, 2017 and April 6, 2020. Patients were randomly allocated to Home-MCT+CR (n = 118, 49.2%) or usual CR alone (n = 122, 50.8%). Randomisation was 1:1 via randomised blocks within hospital site, balancing arms on sex and baseline Hospital Anxiety and Depression Scale (HADS) scores. The primary outcome was the HADS total score at posttreatment (4-month follow-up). Follow-up data collection occurred between August 7, 2017 and July 20, 2020. Analysis was by intention to treat. The 4-month outcome favoured the MCT intervention group demonstrating significantly lower end of treatment scores (HADS total: adjusted mean difference = -2.64 [-4.49 to -0.78], p = 0.005, standardised mean difference (SMD) = 0.38). Sensitivity analysis using multiple imputation (MI) of missing values supported these findings. Most secondary outcomes also favoured Home-MCT+CR, especially in reduction of post-traumatic stress symptoms (SMD = 0.51). There were 23 participants (19%) lost to follow-up in Home-MCT+CR and 4 participants (3%) lost to follow-up in CR alone. No serious adverse events were reported. The main limitation is the absence of longer term (e.g., 12-month) follow-up data. CONCLUSION: Self-help home-based MCT was effective in reducing total anxiety/depression in patients undergoing CR. Improvement occurred across most psychological measures. Home-MCT was a promising addition to cardiac rehabilitation and may offer improved access to effective psychological treatment in cardiovascular disease (CVD) patients. TRIAL REGISTRATION: NCT03999359.

The epidemiology of primary FSGS including cluster analysis over a 20-year period.

INTRODUCTION: Focal segmental glomerulosclerosis (FSGS) is one of the leading causes of nephrotic syndrome in adults. This epidemiological study describes a renal centre's 20-year experience of primary FSGS. METHODS: Patients were identified with a diagnosis of primary FSGS after exclusion of known secondary causes. In this retrospective observational study, data was collected for baseline demographics, immunosuppression and outcomes. A two-step cluster analysis was used to identify natural groupings within the dataset. RESULTS: The total cohort was made up of 87 patients. Those who received immunosuppression had lower median serum albumin than those who did not- 23g/L vs 40g/L (p<0.001) and higher median urine protein creatinine ratios (uPCR)- 795mg/mmol vs 318mg/mmol (p <0.001). They were more likely to achieve complete remission (62% vs 40%, p=0.041), but relapsed more 48.6% vs 22% (p=0.027). Overall 5 year mortality was 10.3% and 5 year progression to RRT was seen in 17.2%. Complete remission was observed in 49.4%. The 2-step cluster analysis separated the cohort into 3 clusters: cluster 1 (n=26) with 'nephrotic-range proteinuria'; cluster 2 (n=43) with 'non-nephrotic-range proteinuria'; and cluster 3 (n=18) with nephrotic syndrome. Immunosuppression use was comparable in clusters 1 and 3, but lower in cluster 2 (77.8% and 69.2% vs 11.6%, p<0.001). Rates of complete remission were greatest in clusters 1 and 3 vs cluster 2: 57.7% and 66.7% vs 37.2%. CONCLUSION: People who received immunosuppression had lower serum albumin and achieved remission more frequently, but were also prone to relapse. Our cluster analysis highlighted 3 FSGS phenotypes: a nephrotic cluster that clearly require immunosuppression; a cohort with preserved serum albumin and non-nephrotic range proteinuria who will benefit from supportive care; and lastly a cluster with heavy proteinuria but serum albumin > 30g/L. This group may still have immune mediated disease and thus could potentially benefit from immunosuppression. TRIAL REGISTRATION: This study protocol was reviewed and approved by the 'Research and Innovation committee of the Northern Care Alliance NHS Group', study approval number (Ref: ID 22HIP54).

Improving access to psychological therapies: Analysis of effects associated with remote provision during COVID-19.

BACKGROUND: COVID-19 had an immediate impact on the way Improving Access to Psychological Therapy (IAPT) services in the United Kingdom were delivered, requiring services to move to remote therapy. While remote therapy has been shown to be effective, little is known about the effects associated with moving to remote therapy delivered during COVID-19 within IAPT services. OBJECTIVE: The objective of the study was to assess the characteristics of those undergoing remote therapy and test the effects associated with the effect of remote delivery on anxiety and depression symptoms compared with in-person therapy before lockdown. METHODS: We conducted a retrospective, cross-sectional benchmark comparison of remote therapy across four IAPT services in Greater Manchester. Routinely collected measures of anxiety (GAD-7) and depression (PHQ-9) were used to compare effects across the two time periods. A mixed-effects model was conducted to assess within and between group changes in anxiety and depression, while controlling for pre-specified confounders. FINDINGS: Remote therapy did not appear to impact on service provision, with the number of sessions offered and attended being similar to those prior to COVID-19. Both face-to-face (pre-COVID-19) and remote therapy (during COVID-19) were associated with variable improvements in anxiety and depression with no significant difference between them. However, remote therapy was associated with a more rapid decrease in symptoms in comparison with face-to-face treatment. Mean improvement in symptoms was small and increased as number of sessions/time increased and analysis of rates of improvement indicated that both face-to-face and remote therapy might need more time to reach target cut-off points on measures. CONCLUSIONS: Both face-to-face and remote therapies delivered under IAPT were associated with improvements in symptoms with no apparent difference apart from the finding that remote therapy was associated with more rapid change. CLINICAL IMPLICATIONS: Remote therapy delivery in IAPT does not appear to confer a disadvantage over face-to-face contact, but at a group mean level the magnitude of improvement associated with both treatments was small. Remote therapy provision may widen patient access to and engagement with psychological services.

Time to change the reference ranges of children's physiological observations in emergency care? A prospective study.

AIM: High heart and respiratory rates are key indicators in many published guidelines to identify and treat serious bacterial infection and sepsis in children, but the credibility of evidence underpinning what is considered abnormal is questionable. This study established the distribution of heart and respiratory rates of children using a large data set to inform debate on what the 'normal' range of these should look like. The primary aim was to compare the distribution of heart and respiratory rates measured in children recruited from non-tertiary emergency care settings with those published by Advanced Paediatric Life Support (APLS). The secondary aim was to compare the distribution of this study's data set to other national guidance on what constitutes a severe (high-risk) measurement and previously published data sets. METHOD: Prospective study using anonymised patient data, extracted from electronic patient records of children and young people 0-16 years, recruited from three Emergency Departments and one Urgent Care Centre in Northwest England, UK. RESULTS: Heart and respiratory rates, including the reporting of values at certain centiles and comparisons of averages. Distribution of heart and respiratory rate were consistently higher than those used by the APLS guidance, resulting in a large proportion exceeding the 'severe' cut-offs proposed. This varied greatly by age. CONCLUSIONS: This study's data set suggests normal heart rate ranges proposed by the APLS and others is too low and therefore 'abnormal' measurements encompass too large a proportion. The respiratory rate of this data set was more consistent with the guidelines and other published data sets.

Do the indices of deprivation or smoking affect post-operative 1-year mortality in patients undergoing a craniotomy for a brain tumour in a public healthcare system?

OBJECTIVE: We sought to determine the 1-year survival following craniotomy for tumour resection in a public healthcare system and analyse the effect of indices of multiple deprivation (IMD) as well as smoking, alcohol, BMI, ASA grade and medical co-morbidities on post-operative morbidity and mortality. METHODS: This is a retrospective, single-centre study in a high volume neurosurgical centre, over a 2-year period. All patients undergoing a craniotomy for a brain tumour were included. Data was collected from the neuro-oncology database and electronic patient records. Individual patient IMD data was obtained using their postcode from a national government database. Each English postcode being ranked from 1 to 32,844, with 1 being the most deprived and 32,844 the most affluent. Descriptive results are described along with further data analysis using multiple linear and logistic regression analyses. RESULTS: 630 patients underwent an elective or urgent craniotomy for tumour. 10% of all patients underwent urgent surgery. 68% (95% CI: 64 to 71%) survived at least 1-year post-surgery. Our study found that social deprivation (IMD postcode rank) was not associated with mortality at 1 year after adjusting for potential confounding factors. Those from decile 1 had the lowest risk of death at 12 months for all tumour types (p = 0.0070). Previous smokers carried an increased risk of death at 12 months when compared with people who had never smoked RR 1.40 CI 1.10-1.78 (p = 0.006) but this risk was not evident in current smokers RR 0.92 CI 0.65-1.31 (p = 0.64). Increasing age and male gender were also found to be associated with higher mortality at 1 year (p = < 0.001). CONCLUSIONS: In the UK despite the discrepancy in the health of the general population between the north and south, social deprivation does not appear to be detrimental to neurooncological outcomes although smoking status, advancing age and male sex are.

Early mobilisation is associated with lower subacute blood pressure and variability in ICH: A retrospective cohort study✰.

BACKGROUND: Very early rehabilitation after stroke appears to worsen outcome, particularly in intracerebral haemorrhage (ICH). Plausible mechanisms include increased mean blood pressure (BP) and BP variability. AIMS: To test associations between early mobilisation, subacute BP and survival, in observational data of ICH patients during routine clinical care. METHODS: We collected demographic, clinical and imaging data from 1372 consecutive spontaneous ICH patients admitted between 2 June 2013 and 28 September 2018. Time to first mobilisation (defined as walking, standing, or sitting out-of-bed) was extracted from electronic records. We evaluated associations between early mobilisation (within 24 h of onset) and both subacute BP and death by 30 days using multifactorial linear and logistic regression analyses respectively. RESULTS: Mobilisation at 24 h was not associated with increased odds of death by 30 days when adjusting for key prognostic factors (OR 0.4, 95% CI 0.2 to 1.1, p = 0.07). Mobilisation at 24 h was independently associated with both lower mean systolic BP (-4.5 mmHg, 95% CI -7.5 to -1.5 mmHg, p = 0.003) and lower diastolic BP variability (-1.3 mmHg, 95% CI -2.4 to -0.2 mg, p = 0.02) during the first 72 h after admission. CONCLUSIONS: Adjusted analysis in this observational dataset did not find an association between early mobilisation and death by 30 days. We found early mobilisation at 24 h to be independently associated with lower mean systolic BP and lower diastolic BP variability over 72 h. Further work is needed to establish mechanisms for the possible detrimental effect of early mobilisation in ICH.

Improving the Effectiveness of Psychological Interventions for Depression and Anxiety in Cardiac Rehabilitation: PATHWAY-A Single-Blind, Parallel, Randomized, Controlled Trial of Group Metacognitive Therapy.

BACKGROUND: Depression and anxiety in cardiovascular disease are significant, contributing to poor prognosis. Unfortunately, current psychological treatments offer mixed, usually small improvements in these symptoms. The present trial tested for the first time the effects of group metacognitive therapy (MCT; 6 sessions) on anxiety and depressive symptoms when delivered alongside cardiac rehabilitation (CR). METHODS: A total of 332 CR patients recruited from 5 National Health Service Trusts across the North-West of England were randomly allocated to MCT+CR (n=163, 49.1%) or usual CR alone (n=169, 50.9%). Randomization was 1:1 via minimization balancing arms on sex and Hospital Anxiety and Depression Scale scores within hospital site. The primary outcome was Hospital Anxiety and Depression Scale total after treatment (4-month follow-up). Secondary outcomes were individual Hospital Anxiety and Depression Scales, traumatic stress symptoms, and psychological mechanisms including metacognitive beliefs and repetitive negative thinking. Analysis was intention to treat. RESULTS: The adjusted group difference on the primary outcome, Hospital Anxiety and Depression Scale total score at 4 months, significantly favored the MCT+CR arm (-3.24 [95% CI, -4.67 to -1.81], P<0.001; standardized effect size, 0.52 [95% CI, 0.291 to 0.750]). The significant difference was maintained at 12 months (-2.19 [95% CI, -3.72 to -0.66], P=0.005; standardized effect size, 0.33 [95% CI, 0.101 to 0.568]). The intervention improved outcomes significantly for both depression and anxiety symptoms when assessed separately compared with usual care. Sensitivity analysis using multiple imputation of missing values supported these findings. Most secondary outcomes favored MCT+CR, with medium to high effect sizes for psychological mechanisms of metacognitive beliefs and repetitive negative thinking. No adverse treatment-related events were reported. CONCLUSIONS: Group MCT+CR significantly improved depression and anxiety compared with usual care and led to greater reductions in unhelpful metacognitions and repetitive negative thinking. Most gains remained significant at 12 months. Study strengths include a large sample, a theory-based intervention, use of longer-term follow-up, broad inclusion criteria, and involvement of a trials unit. Limitations include no control for additional contact as part of MCT to estimate nonspecific effects, and the trial was not intended to assess cardiac outcomes. Nonetheless, results demonstrated that addition of the MCT intervention had broad and significant beneficial effects on mental health symptoms. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: ISRCTN74643496.

Digital pitting scars are associated with a severe disease course and death in systemic sclerosis: a study from the EUSTAR cohort.

OBJECTIVE: Digital pitting scars (DPS) are frequent, but little studied in SSc to date. METHODS: An analysis of SSc patients enrolled in the EUSTAR database. Primary objectives were to (i) examine DPS prevalence; (ii) examine whether DPS are associated with digital ulcers (DUs) and active digital ischaemia (DUs or gangrene); and (iii) describe other associations with DPS including internal organ complications. Secondary objectives were whether DPS are associated with (i) functional impairment; (ii) structural microvascular disease; and (iii) mortality. Descriptive statistics and parametric/non-parametric tests were used. Binary logistic regression was used to examine the association between DPS and DUs, active digital ischaemia and mortality. RESULTS: A total of 9671 patients were included with reported DPS at any time point (n = 4924) or 'never' DPS (n = 4747). The majority (86.9%) were female and mean age was 55.7 years. DPS were associated with longer disease and Raynaud's duration (both P ≤ 0.001). DPS were associated with interstitial lung disease, pulmonary hypertension, conduction blocks, telangiectases, calcinosis (all P ≤ 0.001) and joint synovitis (P = 0.021). Patients were more likely to have more severe capillaroscopic abnormality and greater hand functional impairment. Multivariable logistic regression analyses showed that DPS were associated (odds ratio) with DUs: 22.03 (19.51-24.87), active digital ischaemia: 6.30 (5.34-7.42) and death: 1.86 (1.48-2.36). CONCLUSION: DPS are associated with a severe disease course including death. The impact of DPS on hand function and ischaemia is significant. The presence of DPS should alert the clinician to a poor prognosis and need to optimize the therapeutic strategy.

Mid to late-life scores of depression in the cognitively healthy are associated with cognitive status and Alzheimer's disease pathology at death.

OBJECTIVES: Early diagnosis of Alzheimer's disease (AD) is essential for early interventions. Symptoms of depression could represent a prodromal stage of AD. Very early mood alterations may help to stratify those at highest risk of late-life AD. We aim to investigate associations between baseline/longitudinal scores for depression, presence of cognitive impairment and/or AD pathology at death. METHODS/DESIGN: Between 1991 and 2015, participants from The University of Manchester Longitudinal Study of Cognition in Normal Healthy Old Age underwent 10 waves of assessment using the Geriatric Depression Scale (GDS). AD pathology at death was evaluated in 106 eligible cases. Analyses aimed to examine associations between GDS scores, cognitive status and AD pathology (as measured by Braak stage, Thal phase and CERAD). RESULTS: Baseline GDS scores were significantly higher for those cognitively impaired at death than those cognitively normal. Significantly higher baseline GDS scores were found for those with greater Consortium to Establish a Registry for Alzheimer's Disease (CERAD) scores than those with lower CERAD scores. Similarly, significantly higher baseline GDS scores were found for those with a greater Braak stage than those with lower tau burden. These correlations remained after controlling for age at death, education and APOE ε4, but were less robust. Mean longitudinal GDS scores associated with cognition but not pathology. CONCLUSIONS: GDS scores collected approximately 20 years before death were associated with cognitive status and AD pathology at death. We postulate that early AD-related pathological change produces raised GDS scores due to an overlapping neural basis with depression, and that this may be considered as an early diagnostic marker for AD.

Non-pharmacological interventions for spatial neglect or inattention following stroke and other non-progressive brain injury.

BACKGROUND: People with spatial neglect after stroke or other brain injury have difficulty attending to one side of space. Various rehabilitation interventions have been used, but evidence of their benefit is unclear. OBJECTIVES: The main objective was to determine the effects of non-pharmacological interventions for people with spatial neglect after stroke and other adult-acquired non-progressive brain injury. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register (last searched October 2020), the Cochrane Central Register of Controlled Trials (CENTRAL; last searched October 2020), MEDLINE (1966 to October 2020), Embase (1980 to October 2020), the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1983 to October 2020), and PsycINFO (1974 to October 2020). We also searched ongoing trials registers and screened reference lists. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of any non-pharmacological intervention specifically aimed at spatial neglect. We excluded studies of general rehabilitation and studies with mixed participant groups, unless separate neglect data were available. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Review authors categorised the interventions into eight broad types deemed to be applicable to clinical practice through iterative discussion: visual interventions, prism adaptation, body awareness interventions, mental function interventions, movement interventions, non-invasive brain stimulation, electrical stimulation, and acupuncture. We assessed the quality of evidence for each outcome using the GRADE approach. MAIN RESULTS: We included 65 RCTs with 1951 participants, all of which included people with spatial neglect following stroke. Most studies measured outcomes using standardised neglect assessments. Fifty-one studies measured effects on ADL immediately after completion of the intervention period; only 16 reported persisting effects on ADL (our primary outcome). One study (30 participants) reported discharge destination, and one (24 participants) reported depression. No studies reported falls, balance, or quality of life. Only two studies were judged to be entirely at low risk of bias, and all were small, with fewer than 50 participants per group. We found no definitive (phase 3) clinical trials. None of the studies reported any patient or public involvement. Visual interventions versus any control: evidence is very uncertain about the effects of visual interventions for spatial neglect based on measures of persisting functional ability in ADL (2 studies, 55 participants) (standardised mean difference (SMD) -0.04, 95% confidence interval (CI) -0.57 to 0.49); measures of immediate functional ability in ADL; persisting standardised neglect assessments; and immediate neglect assessments. Prism adaptation versus any control: evidence is very uncertain about the effects of prism adaptation for spatial neglect based on measures of persisting functional ability in ADL (2 studies, 39 participants) (SMD -0.29, 95% CI -0.93 to 0.35); measures of immediate functional ability in ADL; persisting standardised neglect assessments; and immediate neglect assessments. Body awareness interventions versus any control: evidence is very uncertain about the effects of body awareness interventions for spatial neglect based on measures of persisting functional ability in ADL (5 studies, 125 participants) (SMD 0.61, 95% CI 0.24 to 0.97); measures of immediate functional ability in ADL; persisting standardised neglect assessments; immediate neglect assessments; and adverse events. Mental function interventions versus any control: we found no trials of mental function interventions for spatial neglect reporting on measures of persisting functional ability in ADL. Evidence is very uncertain about the effects of mental function interventions on spatial neglect based on measures of immediate functional ability in ADL and immediate neglect assessments. Movement interventions versus any control: we found no trials of movement interventions for spatial neglect reporting on measures of persisting functional ability in ADL. Evidence is very uncertain about the effects of body awareness interventions on spatial neglect based on measures of immediate functional ability in ADL and immediate neglect assessments. Non-invasive brain stimulation (NIBS) versus any control: evidence is very uncertain about the effects of NIBS on spatial neglect based on measures of persisting functional ability in ADL (3 studies, 92 participants) (SMD 0.35, 95% CI -0.08 to 0.77); measures of immediate functional ability in ADL; persisting standardised neglect assessments; immediate neglect assessments; and adverse events. Electrical stimulation versus any control: we found no trials of electrical stimulation for spatial neglect reporting on measures of persisting functional ability in ADL. Evidence is very uncertain about the effects of electrical stimulation on spatial neglect based on immediate neglect assessments. Acupuncture versus any control: we found no trials of acupuncture for spatial neglect reporting on measures of persisting functional ability in ADL. Evidence is very uncertain about the effects of acupuncture on spatial neglect based on measures of immediate functional ability in ADL and immediate neglect assessments. AUTHORS' CONCLUSIONS: The effectiveness of non-pharmacological interventions for spatial neglect in improving functional ability in ADL and increasing independence remains unproven. Many strategies have been proposed to aid rehabilitation of spatial neglect, but none has yet been sufficiently researched through high-quality fully powered randomised trials to establish potential or adverse effects. As a consequence, no rehabilitation approach can be supported or refuted based on current evidence from RCTs. As recommended by a number of national clinical guidelines, clinicians should continue to provide rehabilitation for neglect that enables people to meet their rehabilitation goals. Clinicians and stroke survivors should have the opportunity, and are strongly encouraged, to participate in research. Future studies need to have appropriate high-quality methodological design, delivery, and reporting to enable appraisal and interpretation of results. Future studies also must evaluate outcomes of importance to patients, such as persisting functional ability in ADL. One way to improve the quality of research is to involve people with experience with the condition in designing and running trials.

Clinical and cost effectiveness of arthritis gloves in rheumatoid arthritis (A-GLOVES): randomised controlled trial with economic analysis.

BACKGROUND: Arthritis (or compression) gloves are widely prescribed to people with rheumatoid arthritis and other forms of hand arthritis. They are prescribed for daytime wear to reduce hand pain and improve hand function, and/or night-time wear to reduce pain, improve sleep and reduce morning stiffness. However, evidence for their effectiveness is limited. The aims of this study were to investigate the clinical and cost effectiveness of arthritis gloves compared to placebo gloves on hand pain, stiffness and function in people with rheumatoid arthritis and persistent hand pain. METHODS: A parallel randomised controlled trial, in adults (≥ 18 years) with rheumatoid or undifferentiated inflammatory arthritis at 16 National Health Service sites in the UK. Patients with persistent hand pain affecting function and/or sleep were eligible. Randomisation (1:1) was stratified by recent change (or not) in medication, using permuted blocks of random sizes. Three-quarter-finger length arthritis gloves (Isotoner®: applying 23-32 mmHg pressure) (intervention) were compared to loose-fitting placebo gloves (Jobskin® classic: providing no/minimal pressure) (control). Both gloves (considered to have similar thermal qualities) were provided by occupational therapists. Patients and outcome assessors were blinded; clinicians were not. The primary outcome was dominant hand pain on activity (0-10) at 12 weeks, analysed using linear regression and intention to treat principles. RESULTS: Two hundred six participants were randomly assigned (103 per arm) and 163 (84 intervention: 79 control) completed 12-week follow-up. Hand pain improved by 1.0 (intervention) and 1.2 (control), an adjusted mean difference of 0.10 (95% CI: - 0.47 to 0.67; p = 0.72). Adverse events were reported by 51% of intervention and 36% of control group participants; with 6 and 7% respectively, discontinuing glove wear. Provision of arthritis gloves cost £129, with no additional benefit. CONCLUSION: The trial provides evidence of no clinically important effect of arthritis gloves on any of the trial outcomes (hand pain, function and stiffness) and arthritis gloves are not cost-effective. The clinical and cost-effectiveness results support ceasing provision of arthritis gloves in routine clinical practice. FUNDING: National Institute for Health Research. TRIAL REGISTRATION: ISRCTN, ISRCTN25892131 ; Registered 05/09/2016: retrospectively registered.

SCIL-STROKE (Subcutaneous Interleukin-1 Receptor Antagonist in Ischemic Stroke): A Randomized Controlled Phase 2 Trial.

BACKGROUND AND PURPOSE: The proinflammatory cytokine IL-1 (interleukin-1) has a deleterious role in cerebral ischemia, which is attenuated by IL-1 receptor antagonist (IL-1Ra). IL-1 induces peripheral inflammatory mediators, such as interleukin-6, which are associated with worse prognosis after ischemic stroke. We investigated whether subcutaneous IL-1Ra reduces the peripheral inflammatory response in acute ischemic stroke. METHODS: SCIL-STROKE (Subcutaneous Interleukin-1 Receptor Antagonist in Ischemic Stroke) was a single-center, double-blind, randomized, placebo-controlled phase 2 trial of subcutaneous IL-1Ra (100 mg administered twice daily for 3 days) in patients presenting within 5 hours of ischemic stroke onset. Randomization was stratified for baseline National Institutes of Health Stroke Scale score and thrombolysis. Measurement of plasma interleukin-6 and other peripheral inflammatory markers was undertaken at 5 time points. The primary outcome was difference in concentration of log(interleukin-6) as area under the curve to day 3. Secondary outcomes included exploratory effect of IL-1Ra on 3-month outcome with the modified Rankin Scale. RESULTS: We recruited 80 patients (mean age, 72 years; median National Institutes of Health Stroke Scale, 12) of whom 73% received intravenous thrombolysis with alteplase. IL-1Ra significantly reduced plasma interleukin-6 (P<0.001) and plasma C-reactive protein (P<0.001). IL-1Ra was well tolerated with no safety concerns. Allocation to IL-1Ra was not associated with a favorable outcome on modified Rankin Scale: odds ratio (95% confidence interval)=0.67 (0.29-1.52), P=0.34. Exploratory mediation analysis suggested that IL-1Ra improved clinical outcome by reducing inflammation, but there was a statistically significant, alternative mechanism countering this benefit. CONCLUSIONS: IL-1Ra reduced plasma inflammatory markers which are known to be associated with worse clinical outcome in ischemic stroke. Subcutaneous IL-1Ra is safe and well tolerated. Further experimental studies are required to investigate efficacy and possible interactions of IL-1Ra with thrombolysis. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: ISRCTN74236229.

Refining and testing the diagnostic accuracy of an assessment tool (PAT-POPS) to predict admission and discharge of children and young people who attend an emergency department: protocol for an observational study.

BACKGROUND: Increasing attendances by children (aged 0-16 years) to United Kingdom Emergency Departments (EDs) challenges patient safety within the National Health Service (NHS) with health professionals required to make complex judgements on whether children attending urgent and emergency care services can be sent home safely or require admission. Health regulation bodies have recommended that an early identification systems should be developed to recognise children developing critical illnesses. The Pennine Acute Hospitals NHS Trust Paediatric Observation Priority Score (PAT-POPS) was developed as an ED-specific tool for this purpose. This study aims to revise and improve the existing tool and determine its utility in determining safe admission and discharge decision making. METHODS/DESIGN: An observational study to improve diagnostic accuracy using data from children and young people attending the ED and Urgent Care Centre (UCC) at three hospitals over a 12 month period. The data being collected is part of routine practice; therefore opt-out methods of consent will be used. The reference standard is admission or discharge. A revised PAT-POPs scoring tool will be developed using clinically guided logistic regression models to explore which components best predict hospital admission and safe discharge. Suitable cut-points for safe admission and discharge will be established using sensitivity and specificity as judged by an expert consensus meeting. The diagnostic accuracy of the revised tool will be assessed, and it will be compared to the former version of PAT-POPS using ROC analysis. DISCUSSION: This new predictive tool will aid discharge and admission decision-making in relation to children and young people in hospital urgent and emergency care facilities. TRIAL REGISTRATION: NIHR RfPB Grant: PB-PG-0815-20034. ClinicalTrials.gov: 213469. Retrospectively registered on 11 April 2018.

ROC-king onwards: intraepithelial lymphocyte counts, distribution & role in coeliac disease mucosal interpretation.

OBJECTIVES: Counting intraepithelial lymphocytes (IEL) is central to the histological diagnosis of coeliac disease (CD), but no definitive 'normal' IEL range has ever been published. In this multicentre study, receiver operating characteristic (ROC) curve analysis was used to determine the optimal cut-off between normal and CD (Marsh III lesion) duodenal mucosa, based on IEL counts on >400 mucosal biopsy specimens. DESIGN: The study was designed at the International Meeting on Digestive Pathology, Bucharest 2015. Investigators from 19 centres, eight countries of three continents, recruited 198 patients with Marsh III histology and 203 controls and used one agreed protocol to count IEL/100 enterocytes in well-oriented duodenal biopsies. Demographic and serological data were also collected. RESULTS: The mean ages of CD and control groups were 45.5 (neonate to 82) and 38.3 (2-88) years. Mean IEL count was 54±18/100 enterocytes in CD and 13±8 in normal controls (p=0.0001). ROC analysis indicated an optimal cut-off point of 25 IEL/100 enterocytes, with 99% sensitivity, 92% specificity and 99.5% area under the curve. Other cut-offs between 20 and 40 IEL were less discriminatory. Additionally, there was a sufficiently high number of biopsies to explore IEL counts across the subclassification of the Marsh III lesion. CONCLUSION: Our ROC curve analyses demonstrate that for Marsh III lesions, a cut-off of 25 IEL/100 enterocytes optimises discrimination between normal control and CD biopsies. No differences in IEL counts were found between Marsh III a, b and c lesions. There was an indication of a continuously graded dose-response by IEL to environmental (gluten) antigenic influence.

The prevalence of growth hormone deficiency in survivors of subarachnoid haemorrhage: results from a large single centre study.

OBJECTIVE: The variation in reported prevalence of growth hormone deficiency (GHD) post subarachnoid haemorrhage (SAH) is mainly due to methodological heterogeneity. We report on the prevalence of GHD in a large cohort of patients following SAH, when dynamic and confirmatory pituitary hormone testing methods are systematically employed. DESIGN: In this cross-sectional study, pituitary function was assessed in 100 patients following SAH. Baseline pituitary hormonal profile measurement and glucagon stimulation testing (GST) was carried out in all patients. Isolated GHD was confirmed with an Arginine stimulation test and ACTH deficiency was confirmed with a short synacthen test. RESULTS: The prevalence of hypopituitarism in our cohort was 19% and the prevalence of GHD was 14%. There was no association between GHD and the clinical or radiological severity of SAH at presentation, treatment modality, age, or occurrence of vasospasm. There were statistically significant differences in terms of Glasgow Outcome Scale (GOS; p = 0.03) between patients diagnosed with GHD and those without. Significant inverse correlations between GH peak on GST with body mass index (BMI) and waist hip ratio (WHR) was also noted (p < 0.0001 and p < 0.0001 respectively). CONCLUSION: Using the current testing protocol, the prevalence of GHD detected in our cohort was 14%. It is unclear if the BMI and WHR difference observed is truly due to GHD or confounded by the endocrine tests used in this protocol. There is possibly an association between the development of GHD and worse GOS score. Routine endocrine screening of all SAH survivors with dynamic tests is time consuming and may subject many patients to unnecessary side-effects. Furthermore the degree of clinical benefit derived from growth hormone replacement in this patient group, remains unclear. Increased understanding of the most appropriate testing methodology in this patient group and more importantly which SAH survivors would derive most benefit from GHD screening is required.

A Comparison of Hearing Thresholds, and the Resulting Prescribed Gain and Hearing Aid Outputs, Using Gold Standard Audiometry and the TympaHealth Hearing Assessment Tool.

OBJECTIVE: Phone- and tablet-based hearing testing systems are now widely available. Here, we evaluated one such system from TympaHealth by comparing air conduction thresholds and resultant hearing aid targets and output, measured with the TympaHealth system with those measured using standard audiometry. DESIGN: The hearing thresholds of 35 adults were measured using standard audiometry and the TympaHealth system. Each set of thresholds was used to generate NAL-NL2 targets and program a hearing aid. The data from each system were compared. RESULTS: Bland-Altman analyses showed overall mean differences between thresholds measured with each system to be small, with 85% of TympaHealth thresholds being within ±5 dB of the standard audiometric thresholds, although TympaHealth thresholds were higher (poorer) than the standard audiometric thresholds. The hearing aid targets and gains generated from the standard audiometric thresholds were lower (less amplification) than those generated from the TympaHealth thresholds but again, mean differences at each frequency were small and likely imperceptible. CONCLUSION: These findings support the possibility that valid hearing testing can take place outside of a clinical booth using portable systems like that from TympaHealth, opening up the possibility of testing hearing and fitting hearing aids through pharmacies, opticians, and in care homes.

Mobile phone thermography of the toes in patients with systemic sclerosis-a pilot study.

Objectives: To investigate the hypotheses that in patients with SSc, the temperature gradient between the dorsum of the foot and toes (distal-dorsal difference [DDD]) is 'more negative' (toes cooler) than in healthy controls, is greatest along the first (great) toe and that the severities of thermographic abnormalities in the feet and hands are correlated. Methods: Thermographic images of the dorsum of each hand and foot were captured using a thermal camera attached to an iPhone in 40 patients with SSc and 20 healthy controls. DDDs along the fingers (index, middle, ring and little) and toes (great toe and 'others') were measured. Results: There was a non-significant trend for the great toes to be colder in patients with SSc than in controls. The mean great toe DDD was more negative in patients (right: -2.89°C, left: -2.91°C, mean: -2.90°C) than in controls (right: -2.36°C, left: -2.42°C, mean: -2.39°C) (P = 0.37 for mean values). Patients' great toes were colder than 'other' (lesser) toes (right: -2.58°C, left: -2.63°C), although not significantly. In patients with SSc, finger and great toe temperature gradients were correlated (r = 0.406, ρ = 0.01). Conclusion: Our findings suggest that the great toe is the coldest in patients with SSc and that patients with the coldest fingers tend to have the coldest toes. Severe RP symptoms in the hands should prompt podiatry assessment and foot care education. Mobile phone thermography is a convenient tool for assessing the digital vasculature but first requires validation in larger studies with a longitudinal component.

Reported Hearing Outcome Measures Following Stereotactic Radiosurgery for Vestibular Schwannoma: A Scoping Review.

Background Evidence on hearing outcome measures when assessing hearing preservation following stereotactic radiosurgery (SRS) for adults with vestibular schwannoma (VS) has not previously been collated in a structured review. Objective The objective of the present study was to perform a scoping review of the evidence regarding the choice of hearing outcomes and other methodological characteristics following SRS for adults with VS. Methods The protocol was registered in the International Platform of Registered Systematic Review and Meta-Analysis Protocols (INPLASY) and reported according to the Preferred Reporting Items for Systematic Review and Meta-Analyses extension guidelines for scoping reviews. A systematic search of five online databases revealed 1,591 studies, 247 of which met the inclusion criteria. Results The majority of studies ( n = 213, 86%) were retrospective cohort or case series with the remainder ( n = 34, 14%) prospective cohort. Pure-tone audiometry and speech intelligibility were included in 222 (90%) and 158 (64%) studies, respectively, often summarized within a classification scheme and lacking procedural details. Fifty-nine (24%) studies included self-report measures. The median duration of follow-up, when reported, was 43 months (interquartile range: 29, 4-150). Conclusion Evidence on hearing disability after SRS for VS is based on low-quality studies which are inherently susceptible to bias. This review has highlighted an urgent need for a randomized controlled trial assessing hearing outcomes in patients with VS managed with radiosurgery or radiological observation. Similarly, consensus and coproduction of a core outcome set to determine relevant hearing and communication outcome domains is required. This will ensure that patient priorities, including communication abilities in the presence of background noise and reduced participation restrictions, are addressed.