The test-retest reliability of non-navigated transcranial magnetic stimulation (TMS) measures of corticospinal pathway excitability early after stroke.

PURPOSE: Motor evoked potential (MEP) characteristics are potential biomarkers of whether rehabilitation interventions drive motor recovery after stroke. The test-retest reliability of Transcranial Magnetic Stimulation (TMS) measurements in sub-acute stroke remains unclear. This study aims to determine the test-retest reliability of upper limb MEP measures elicited by non-neuronavigated transcranial magnetic stimulation in sub-acute-stroke. METHODS: In two identical data collection sessions, 1-3 days apart, TMS measures assessed: motor threshold (MT), amplitude, latency (MEP-L), silent period (SP), recruitment curve slope in the biceps brachii (BB), extensor carpi radialis (ECR), and abductor pollicis brevis (APB) muscles of paretic and non-paretic upper limbs. Test-retest reliability was calculated using the intra-class correlation coefficient (ICC) and 95% confidence intervals (CI). Acceptable reliability was set at a lower 95% CI of 0.70 or above. The limits of agreement (LOA) and smallest detectable change (SDC) were calculated. RESULTS: 30 participants with sub-acute stroke were included (av 36 days post stroke) reliability was variable between poor to good for the different MEP characteristics. The SDC values differed across muscles and MEP characteristics in both paretic and less paretic limbs. CONCLUSIONS: The present findings indicate there is limited evidence for acceptable test-retest reliability of non-navigated TMS outcomes when using the appropriate 95% CI for ICC, SDC and LOA values. CLINICAL TRIAL REGISTRATION: Current Controlled Trials: ISCRT 19090862, http://www.controlled-trials.com.

This study identified that Non-navigated Transcranial Magnetic Stimulation (TMS) demonstrates low reliability of TMS measures in upper limb with variation between muscles and measures in sub-acute strokeWhen using non-navigated TMS to explore corticospinal pathway excitability the individual target muscle and TMS measure should be taken into considerationNon-navigated TMS may be more useful in exploring group differences rather than individual differences in corticospinal pathway excitabilityNon-navigated TMS could provide a means of measuring recovery in clinical practice and could inform the development of more effective interventions but this needs further development before it can be used as a clinical recovery biomarker.

Hospital-based caregiver intervention for people following hip fracture surgery (HIP HELPER): multicentre randomised controlled feasibility trial with embedded qualitative study in England.

OBJECTIVES: To assess the feasibility of conducting a pragmatic, multicentre randomised controlled trial (RCT) to test the clinical and cost-effectiveness of an informal caregiver training programme to support the recovery of people following hip fracture surgery. DESIGN: Two-arm, multicentre, pragmatic, open, feasibility RCT with embedded qualitative study. SETTING: National Health Service (NHS) providers in five English hospitals. PARTICIPANTS: Community-dwelling adults, aged 60 years and over, who undergo hip fracture surgery and their informal caregivers. INTERVENTION: Usual care: usual NHS care. EXPERIMENTAL: usual NHS care plus a caregiver-patient dyad training programme (HIP HELPER). This programme comprised three, 1 hour, one-to-one training sessions for a patient and caregiver, delivered by a nurse, physiotherapist or occupational therapist in the hospital setting predischarge. After discharge, patients and caregivers were supported through three telephone coaching sessions. RANDOMISATION AND BLINDING: Central randomisation was computer generated (1:1), stratified by hospital and level of patient cognitive impairment. There was no blinding. MAIN OUTCOME MEASURES: Data collected at baseline and 4 months post randomisation included: screening logs, intervention logs, fidelity checklists, acceptability data and clinical outcomes. Interviews were conducted with a subset of participants and health professionals. RESULTS: 102 participants were enrolled (51 patients; 51 caregivers). Thirty-nine per cent (515/1311) of patients screened were eligible. Eleven per cent (56/515) of eligible patients consented to be randomised. Forty-eight per cent (12/25) of the intervention group reached compliance to their allocated intervention. There was no evidence of treatment contamination. Qualitative data demonstrated the trial and HIP HELPER programme was acceptable. CONCLUSIONS: The HIP HELPER programme was acceptable to patient-caregiver dyads and health professionals. The COVID-19 pandemic impacting on site's ability to deliver the research. Modifications are necessary to the design for a viable definitive RCT. TRIAL REGISTRATION NUMBER: ISRCTN13270387.

Validation of the Identification of Medication Adherence Barriers Questionnaire (IMAB-Q); a Behavioural Science-Underpinned Tool for Identifying Non-Adherence and Diagnosing an Individual's Barriers to Adherence.

Purpose: To validate the Identification of Medication Adherence Barriers Questionnaire (IMAB-Q) as a tool to guide practitioners to identify patients who require support to take their medicines as prescribed, their key barriers to adherence and select relevant behaviour change techniques. Patients and Methods: Adults prescribed medication for cardiovascular disease prevention were recruited from nine community pharmacies in England. Participants completed the IMAB-Q comprising 30 items representing potential barriers to adherence developed from our previous mixed methods study (scoping review and focus groups) underpinned by the Theoretical Domains Framework. Participants also self-reported their adherence on a visual analogue scale (VAS) ranging from perfect adherence (100) to non-adherence (1). A subgroup of 30 participants completed the IMAB-Q twice to investigate test-retest reliability using weighted Kappa. Mokken scaling was used to investigate IMAB-Q structure. Spearman correlation was used to investigate IMAB-Q criterion validity compared to the VAS score. Results: From 1407 invitations, 608 valid responses were received. Respondents had a mean (SD) age of 70.12 (9.9) years and were prescribed a median (IQ) 4 (3, 6) medicines. Worry about unwanted effects (n = 212, 34.5%) and negative emotions evoked by medicine taking (n = 99, 16.1%) were most frequently reported. Mokken scaling did not organise related IMAB-Q items according to the TDF domains (scalability coefficient H = 0.3 to 0.6). Lower VAS self-reported adherence correlated with greater IMAB-Q reported barriers (rho = -0.14, p = 0.001). Test-retest reliability of IMAB-Q items ranged from kappa co-efficient 0.9 to 0.3 (p < 0.05). Conclusion: The IMAB-Q is valid and reliable for identifying people not adhering and their barriers to adherence. Each IMAB-Q item is linked to a TDF domain which in turn is linked to relevant behaviour change techniques. The IMAB-Q can therefore guide patients and practitioners to select strategies tailored to a patient's identified barriers.

BabyBreathe trial: protocol for a randomised controlled trial of a complex intervention to prevent postpartum return to smoking.

INTRODUCTION: Many people quit smoking during pregnancy, but postpartum smoking relapse is common. Maintaining smoking abstinence achieved during pregnancy is key to improving maternal and child health. There are no evidence-based interventions for preventing postpartum smoking relapse. This trial aims to determine whether an intervention to prevent postpartum relapse is effective and cost-effective. METHODS AND ANALYSIS: A randomised controlled trial of a complex intervention to prevent postpartum smoking relapse (BabyBreathe), with internal pilot, economic and process evaluations. Participants are adults who are pregnant and who report having quit smoking in the 12 months before, or during pregnancy. Participants are eligible if they read and understand English, and provide informed consent. Following consent and biochemical validation of smoking abstinence, participants are randomised to intervention or usual care/control (no specific relapse prevention support). The BabyBreathe intervention consists of manualised advice from a trained member of the health visiting service, health information leaflets for participants and partners, access to the BabyBreathe website and app. At the time of birth, participants are posted the BabyBreathe box and support is provided by text message for up to 12 months postpartum. Target sample size is 880, recruiting across midwifery services at four hubs in England and Scotland and through remote advertising in England, Scotland, Wales and Northern Ireland. Outcomes are collected at 6 and 12 months. The primary outcome is self-reported sustained smoking abstinence at 12 months, carbon monoxide verified. Secondary outcomes include self-reported abstinence, time to relapse, partner smoking status and quality of life. ETHICS AND DISSEMINATION: The trial was approved by the North West Preston Research Ethics committee (21/NW/0017). Dissemination will include publication in peer-reviewed journals, presentation at academic and public conferences including patient and public involvement and to policymakers and practitioners. TRIAL REGISTRATION NUMBER: ISRCTN70307341.

CompreHensive geriAtRician-led MEdication Review (CHARMER): protocol for a feasibility study of a hospital deprescribing behaviour change intervention.

INTRODUCTION: Over 50% of older adults are prescribed a medicine where the risk of harm outweighs the chances of benefit. During a hospital admission, older adults and carers expect medicines to be reviewed for appropriateness and any inappropriate medicines proactively deprescribed. While the principle of proactive deprescribing is an expectation of good prescribing practice, it is yet to become routine. The CompreHensive geriAtRician-led MEdication Review (CHARMER) study aims to develop and test a five-component behaviour change intervention to equip geriatricians and pharmacists to proactively deprescribe inappropriate medicines with older adults in hospital. This study aims to test the feasibility and acceptability of study processes and CHARMER implementation. METHODS AND ANALYSIS: A two-arm purposive allocation feasibility study is being undertaken at four acute hospitals in England, UK (three intervention and one control). The target sample is 400 patients across all hospitals. Primary outcome measures are: (1) participant recruitment rate and (2) participant attrition rate. Secondary outcome measures are: (1) hospital readmission rate; (2) mortality rate and (3) quality of life. Quantitative data will be checked for completeness and quality, and practitioner and patient demographics descriptively analysed. We will undertake a rapid qualitative analysis on observations, interviews and study meeting minutes data. A subsequent thematic analysis will be undertaken with codes mapped to the Theoretical Domains Framework and Normalisation Process Theory. Triangulation of qualitative and quantitative data will be undertaken. ETHICS AND DISSEMINATION: Ethics approval was obtained from Wales Research Ethics Committee 1 (IRAS ID 312494) and study approval from the Health Research Authority (22/WA/0087). Informed consent will be sought from all hospital staff involved in data collection activities and for patients involved in enhanced data collection activities. The findings of this study will be disseminated in peer-reviewed journals and conference presentations. TRIAL REGISTRATION: ISRCTN11899506.

Comparison of the Journey II bicruciate stabilised (JII-BCS) and GENESIS II total knee arthroplasty for functional ability and motor impairment: the CAPAbility, blinded, randomised controlled trial.

OBJECTIVES: To determine if a newer design of total knee replacement (TKR) (Journey II BCS) produces superior patient-reported outcomes scores and biomechanical outcomes than the older, more established design (Genesis II). SETTING: Patients were recruited from an NHS University Hospital between July 2018 and October 2019 with surgery at two sites. Biomechanical and functional capacity measurements were at a University Movement and Exercise Laboratory. PARTICIPANTS: 80 participants undergoing single-stage TKR. INTERVENTIONS: Patients were randomised to receive either the Journey II BCS (JII-BCS) or Genesis II TKR. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome was the Oxford Knee Score (OKS), at 6 months. Secondary outcomes were: OKS Activity and Participation Questionnaire, EQ-5D-5L and UCLA Activity scores, Timed Up and Go Test, 6 min walk test, lower limb kinematics and lower limb muscle activity during walking and balance. RESULTS: This study found no difference in the OKS between groups. The OKS scores for the JII-BCS and Genesis II groups were mean (SD) 42.97 (5.21) and 43.13 (5.20) respectively, adjusted effect size 0.35 (-2.01,2.71) p=0.771In secondary outcome measures, the Genesis II group demonstrated a significantly greater walking range-of-movement (50.62 (7.33) vs 46.07 (7.71) degrees, adjusted effect size, 3.14 (0.61,5.68) p=0.02) and higher peak knee flexion angular velocity during walking (mean (SD) 307.69 (38.96) vs 330.38 (41.40) degrees/second, adjusted effect size was 21.75 (4.54,38.96), p=0.01) and better postural control (smaller resultant centre of path length) during quiet standing than the JII-BCS group (mean (SD) 158.14 (65.40) vs 235.48 (176.94) mm, adjusted effect size, 59.91 (-105.98, -13.85) p=0.01.). CONCLUSIONS: In this study population, the findings do not support the hypothesis that the Journey II BCS produces a better outcome than the Genesis II for the primary outcome of the OKS at 6 months after surgery. TRIAL REGISTRATION NUMBER: ISRCTN32315753.

Cessation of smoking trial in the emergency department (CoSTED): protocol for a multicentre randomised controlled trial.

INTRODUCTION: Attendees of emergency departments (EDs) have a higher than expected prevalence of smoking. ED attendance may be a good opportunity to prompt positive behaviour change, even for smokers not currently motivated to quit. This study aims to determine whether an opportunist smoking cessation intervention delivered in the ED can help daily smokers attending the ED quit smoking and is cost-effective. METHODS AND ANALYSIS: A two-arm pragmatic, multicentred, parallel-group, individually randomised, controlled superiority trial with an internal pilot, economic evaluation and mixed methods process evaluation. The trial will compare ED-based brief smoking cessation advice, including provision of an e-cigarette and referral to local stop smoking services (intervention) with the provision of contact details for local stop smoking services (control). Target sample size is 972, recruiting across 6 National Health Service EDs in England and Scotland. Outcomes will be collected at 1, 3 and 6 months. The primary outcome at 6 months is carbon monoxide verified continuous smoking abstinence. ETHICS AND DISSEMINATION: The trial was approved by the South Central-Oxford B Research Committee (21/SC/0288). Dissemination will include the publication of outcomes, and the process and economic evaluations in peer-reviewed journals. The findings will also be appropriately disseminated to relevant practice, policy and patient representative groups. TRIAL REGISTRATION NUMBER: NCT04854616; protocol V.4.2.

Informal caregiver training for people with chronic pain in musculoskeletal services (JOINT SUPPORT): protocol for a feasibility randomised controlled trial.

INTRODUCTION: Chronic musculoskeletal (bone, joint or muscle) pain is disabling. People with it frequently have difficulties in managing everyday activities. Individuals may rely on family members or friends to support them. These people are known as informal caregivers. No interventions have previously addressed the health needs of people with chronic musculoskeletal pain and their caregivers. In response, the JOINT SUPPORT programme was developed. In this study, we will assess the feasibility and acceptability of conducting a pragmatic, multicentre, randomised controlled trial (RCT) to test the clinical and cost-effectiveness of the JOINT SUPPORT programme to support these individuals. METHODS AND ANALYSIS: This will be a mixed-methods feasibility RCT. We will recruit 80 patients with chronic musculoskeletal pain with their informal caregivers. Patients will be randomised to usual National Health Service (NHS) care OR usual NHS care plus a caregiver-patient dyad training programme (JOINT SUPPORT). This programme comprises of five, 1-hour, group-based sessions for patients and caregivers, delivered by trained physiotherapists or occupational therapists. It includes developing skills in: understanding pain, pacing, graded activity, fear avoidance and goal-setting, understanding benefits of physical activity and skills in medication management. This will be re-enforced with a workbook. After the group-based sessions, patients and caregivers will be supported through three telephone sessions with a therapist. Data collected at baseline and 3 months will include: screening logs, intervention logs, fidelity checklists and clinical outcomes on quality of life, physical and emotional outcomes, adverse events and resource use. Qualitative research with 24 patient-caregiver dyads and 12 healthcare professionals will explore the acceptability of trial processes. Stop-go criteria will inform the progression to a full trial. ETHICS AND DISSEMINATION: Ethical approval was obtained on 22 February 2022 (National Research Ethics Committee Number: 22/NW/0015). Results will be reported at conferences, peer-review publications and across social media channels. TRIAL REGISTRATION NUMBER: ISRCTN78169443.

Comparison of the prognostic performance of the CURB-65 and a modified version of the pneumonia severity index designed to identify high-risk patients using the International Community-Acquired Pneumonia Collaboration Cohort.

BACKGROUND: Although the PSI and CURB-65 represent well-validated prediction rules for pneumonia prognosis, PSI was designed to identify patients at low risk and CURB- 65 patients at high risk of mortality. We compared the prognostic performance of a modified version of the PSI designed to identify high-risk patients (i.e., PSI-HR) to CURB-65 in predicting short-term mortality. METHODS: Using data from 6 pneumonia cohorts, we designed PSI-HR as a 6-class prediction rule using the original prognostic weights of all PSI variables and modifying the risk score thresholds to define risk classes. We calculated the proportion of low-risk and high-risk patients using CURB-65 and PSI-HR and 30-day mortality in these subgroups. We compared the rules' sensitivity, specificity, positive and negative predictive values for mortality at all risk class thresholds and assessed discriminatory power using areas under their receiver operating characteristic curves (AUROCs). RESULTS: Among 13,874 patients with pneumonia, 1,036 (7.5%) died. For PSI-HR versus CURB-65, aggregate mortality was lower in low-risk patients (1.6% vs. 2.2%, p = 0.005) and higher in high-risk patients (36.5% vs. 32.2%, p = 0.27). PSI-HR had higher sensitivities than CURB-65 at all thresholds; PSI-HR also had higher specificities at the 3 lowest thresholds and specificities within 0.5% points of CURB-65 at the 2 highest thresholds. The AUROC was larger for PSI-HR than CURB- 65 (0.82 vs. 0.77, p < 0.0001). CONCLUSIONS: PSI-HR demonstrated superior prognostic accuracy to CURB-65 at the lower end of the severity spectrum and identified high-risk patients with nonsignificant higher short-term mortality at the higher end.

Treating common mental disorder including psychotic experiences in the primary care improving access to psychological therapies programme (the TYPPEX study): protocol for a stepped wedge cluster randomised controlled trial with nested economic and process evaluation of a training package for therapists.

INTRODUCTION: At least one in four people treated by the primary care improving access to psychological therapies (IAPT) programme in England experiences distressing psychotic experiences (PE) in addition to common mental disorder (CMD). These individuals are less likely to achieve recovery. IAPT services do not routinely screen for nor offer specific treatments for CMD including PE. The Tailoring evidence-based psychological therapY for People with common mental disorder including Psychotic EXperiences study will evaluate the clinical and cost-effectiveness of an enhanced training for cognitive behavioural therapists that aims to address this clinical gap. METHODS AND ANALYSIS: This is a multisite, stepped-wedge cluster randomised controlled trial. The setting will be IAPT services within three mental health trusts. The participants will be (1) 56-80 qualified IAPT cognitive behavioural therapists and (2) 600 service users who are triaged as appropriate for cognitive behavioural therapy in an IAPT service and have PE according to the Community Assessment of Psychic Experiences-Positive 15-items Scale. IAPT therapists will be grouped into eight study clusters subsequently randomised to the control-intervention sequence. We will obtain pseudonymous clinical outcome data from IAPT clinical records for eligible service users. We will invite service users to complete health economic measures at baseline, 3, 6, 9 and 12-month follow-up. The primary outcome will be the proportion of patients with common mental disorder psychotic experiences who have recovered by the end of treatment as measured by the official IAPT measure for recovery. ETHICS AND DISSEMINATION: The study received the following approvals: South Central-Berkshire Research Ethics Committee on 28 April 2020 (REC reference 20/SC/0135) and Health Research Authority (HRA) on 23 June 2020. An amendment was approved by the Ethics Committee on 01 October 2020 and HRA on 27 October 2020. Results will be made available to patients and the public, the funders, stakeholders in the IAPT services and other researchers. TRIAL REGISTRATION NUMBER: ISRCTN93895792.

A multidomain decision support tool to prevent falls in older people: the FinCH cluster RCT.

BACKGROUND: Falls in care home residents are common, unpleasant, costly and difficult to prevent. OBJECTIVES: The objectives were to evaluate the clinical effectiveness and cost-effectiveness of the Guide to Action for falls prevention in Care Homes (GtACH) programme. DESIGN: A multicentre, cluster, parallel, 1 : 1 randomised controlled trial with embedded process evaluation and economic evaluation. Care homes were randomised on a 1 : 1 basis to the GtACH programme or usual care using a secure web-based randomisation service. Research assistants, participating residents and staff informants were blind to allocation at recruitment; research assistants were blind to allocation at follow-up. NHS Digital data were extracted blindly. SETTING: Older people's care homes from 10 UK sites. PARTICIPANTS: Older care home residents. INTERVENTION: The GtACH programme, which includes care home staff training, systematic use of a multidomain decision support tool and implementation of falls prevention actions, compared to usual falls prevention care. OUTCOMES: The primary trial outcome was the rate of falls per participating resident occurring during the 90-day period between 91 and 180 days post randomisation. The primary outcome for the cost-effectiveness analysis was the cost per fall averted, and the primary outcome for the cost-utility analysis was the incremental cost per quality adjusted life-year. Secondary outcomes included the rate of falls over days 0-90 and 181-360 post randomisation, activity levels, dependency and fractures. The number of falls per resident was compared between arms using a negative binomial regression model (generalised estimating equation). RESULTS: A total of 84 care homes were randomised: 39 to the GtACH arm and 45 to the control arm. A total of 1657 residents consented and provided baseline measures (mean age 85 years, 32% men). GtACH programme training was delivered to 1051 staff (71% of eligible staff) over 146 group sessions. Primary outcome data were available for 630 GtACH participants and 712 control participants. The primary outcome result showed an unadjusted incidence rate ratio of 0.57 (95% CI 0.45 to 0.71; p < 0.01) in favour of the GtACH programme. Falls rates were lower in the GtACH arm in the period 0-90 days. There were no other differences between arms in the secondary outcomes. Care home staff valued the training, systematic strategies and specialist peer support, but the incorporation of the GtACH programme documentation into routine care home practice was limited. No adverse events were recorded. The incremental cost was £20,889.42 per Dementia Specific Quality of Life-based quality-adjusted life-year and £4543.69 per quality-adjusted life-year based on the EuroQol-5 dimensions, five-level version. The mean number of falls was 1.889 (standard deviation 3.662) in the GtACH arm and 2.747 (standard deviation 7.414) in the control arm. Therefore, 0.858 falls were averted. The base-case incremental cost per fall averted was £190.62. CONCLUSION: The GtACH programme significantly reduced the falls rate in the study care homes without restricting residents' activity levels or increasing their dependency, and was cost-effective at current thresholds in the NHS. FUTURE WORK: Future work should include a broad implementation programme, focusing on scale and sustainability of the GtACH programme. LIMITATIONS: A key limitation was the fact that care home staff were not blinded, although risk was small because of the UK statutory requirement to record falls in care homes. TRIAL REGISTRATION: This trial is registered as ISRCTN34353836. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 9. See the NIHR Journals Library website for further project information.

Falls in care home residents are common, unpleasant, costly and hard to prevent. We tested whether or not the Guide to Action for falls prevention in Care Homes (GtACH) programme was effective in preventing falls. In this programme, care home staff were systematically trained and supported in the assessment of residents' risk of falling and the generation of a falls reduction care plan. We undertook a randomised controlled trial comparing the GtACH programme with usual care, which does not involve this systematic attention to falls prevention. We also undertook a process evaluation, observing organisational and care processes, and an economic study to evaluate value for money. A total of 39 care homes were randomly allocated to the GtACH programme and 45 care homes were randomly allocated to usual care, involving a total of 1657 residents. The main comparison between the two arms was the rate of falls during months 4­6 after randomisation, when we expected any effect to be at its peak. We also assessed the falls rates before and 6 months after this period. We measured activity and dependency levels, as it was important to be sure that any reduction in the rate of falls was not achieved through restrictive care practices. We saw a 43% reduction in the falls rates of the GtACH programme participants during months 4­6, without observing any reduction in residents' activity or dependency. Care home staff and relatives were positive about the GtACH programme. The GtACH programme was good value for money, as it was likely to be cost-effective. The effect of the programme waned over months 6­12, which may be because some staff did not embed the GtACH programme in their usual practice routines, and awareness levels may have dropped.

Predicting asthma-related crisis events using routine electronic healthcare data: a quantitative database analysis study.

BACKGROUND: There is no published algorithm predicting asthma crisis events (accident and emergency [A&E] attendance, hospitalisation, or death) using routinely available electronic health record (EHR) data. AIM: To develop an algorithm to identify individuals at high risk of an asthma crisis event. DESIGN AND SETTING: Database analysis from primary care EHRs of people with asthma across England and Scotland. METHOD: Multivariable logistic regression was applied to a dataset of 61 861 people with asthma from England and Scotland using the Clinical Practice Research Datalink. External validation was performed using the Secure Anonymised Information Linkage Databank of 174 240 patients from Wales. Outcomes were ≥1 hospitalisation (development dataset) and asthma-related hospitalisation, A&E attendance, or death (validation dataset) within a 12-month period. RESULTS: Risk factors for asthma-related crisis events included previous hospitalisation, older age, underweight, smoking, and blood eosinophilia. The prediction algorithm had acceptable predictive ability with a receiver operating characteristic of 0.71 (95% confidence interval [CI] = 0.70 to 0.72) in the validation dataset. Using a cut-point based on the 7% of the population at greatest risk results in a positive predictive value of 5.7% (95% CI = 5.3% to 6.1%) and a negative predictive value of 98.9% (95% CI = 98.9% to 99.0%), with sensitivity of 28.5% (95% CI = 26.7% to 30.3%) and specificity of 93.3% (95% CI = 93.2% to 93.4%); those individuals had an event risk of 6.0% compared with 1.1% for the remaining population. In total, 18 people would need to be followed to identify one admission. CONCLUSION: This externally validated algorithm has acceptable predictive ability for identifying patients at high risk of asthma-related crisis events and excluding those not at high risk.

Feasibility of investigating methylphenidate for the treatment of sarcoidosis-associated fatigue (the FaST-MP study): a double-blind, parallel-arm randomised feasibility trial.

INTRODUCTION: Sarcoidosis-associated fatigue (SAF) is a common clinical problem with limited treatment options. This study was undertaken to determine the feasibility of performing a definitive trial to determine the clinical efficacy methylphenidate in SAF. METHODS: This was a parallel-arm, double-blind, placebo-controlled randomised controlled feasibility trial enrolling sarcoidosis patients reporting significant fatigue. Patients with a Fatigue Assessment Scale score of more than 21 were randomised to receive up to either 10 mg two times per day methylphenidate or identical placebo capsules two times per day, in a dose escalation fashion, for up to 24 weeks. Outcomes included number of participants eligible and willing to participate, withdrawal rates, adherence rates and ability to maintain blinding. RESULTS: Of 385 patients screened, 56 (14.5%) were eligible and 23 (41% of eligible patients) were randomised. No withdrawals occurred. One participant in the methylphenidate arm discontinued study medications due to chest pain. The side effect profile was not different between the groups. Median medication adherence rates were 98% and 99% in the methylphenidate and placebo arms, respectively. A greater proportion of participants receiving methylphenidate predicted their allocated treatment while blinded compared with those receiving placebo (93.3% vs 57.1%). The investigator could not predict the treatment allocation. Both groups showed clinically meaningful improvements in fatigue from baseline, although no between-group difference was seen. CONCLUSIONS: The data support the feasibility of performing a double-blind parallel trial powered to determine the clinical efficacy of methylphenidate for SAF, however, a multicentre study will be required. TRIAL REGISTRATION NUMBER: NCT02643732.

Modified early warning score and risk of mortality after acute stroke.

OBJECTIVE: An accurate prediction tool may facilitate optimal management of patients with acute stroke from an early stage. We evaluated the association between admission modified early warning score (MEWS) and mortality in patients with acute stroke. METHOD: Data from the Anglia Stroke Clinical Network Evaluation Study (ASCNES) were analysed. We evaluated the association between admission MEWS and four outcomes; in-patient, 7-day, 30-day and 1-year mortality. Logistic regression models were used to calculate the odds of all mortality timeframes, whereas Cox proportional hazards models were used to calculate mortality at 1 year. Five univariate and multivariate models were constructed, adjusting for confounders. Patients with a moderate (2-3) or high (≥4) scores were compared to patients with a low score (0-1). RESULTS: The study population consisted of 2006 patients. A total of 1196 patients had low MEWS, 666 had moderate MEWS and 144 had a high MEWS. A high MEWS was associated with increased mortality as an in-patient (OR 4.93, 95 % CI: 2.88-8.42), at 7 days (OR 7.53, 95 % CI: 4.24-13.38), at 30 days (OR 5.74, 95 % CI: 3.38-9.76) and 1-year (HR 2.52, 95 % CI 1.88-3.39). At 1 year, model 5 had a 1.02 OR (95 % CI 0.83-1.24) with moderate MEWS and 2.52 (95 % CI 1.88-3.39) with high MEWS. CONCLUSION: Elevated MEWS on admission is a potential marker for acute-stroke mortality and may therefore be a useful risk prediction tool, able to guide clinicians attempting to prognosticate outcomes for patients with acute-stroke.

Revascularisation therapies improve the outcomes of ischemic stroke patients with atrial fibrillation and heart failure.

BACKGROUND: Atrial fibrillation (AF) and heart failure (HF) carry a poor prognosis in acute ischaemic stroke (AIS). The impact of revascularisation therapies on outcomes in these patients is not fully understood. METHOD: National Inpatient Sample (NIS) AIS admissions (January 2004-September 2015) were included (n = 4,597,428). Logistic regressions analysed the relationship between exposures (neither AF nor HF-reference, AF-only, HF-only, AF + HF) and outcomes (in-hospital mortality, length-of-stay >median and moderate-to-severe disability on discharge), stratifying by receipt of intravenous thrombolysis (IVT) or endovascular thrombectomy (ET). RESULTS: 69.2% patients had neither AF nor HF, 16.5% had AF-only, 7.5% had HF-only and 6.7% had AF + HF. 5.04% and 0.72% patients underwent IVT and/or ET, respectively. AF-only and HF-only were each associated with 75-85% increase in the odds of in-hospital mortality. AF + HF was associated with greater than two-fold increase in mortality. Patients with AF-only, HF-only or AF + HF undergoing IVT had better or at least similar in-hospital outcomes compared to their counterparts not undergoing IVT, except for prolonged hospitalisation. Patients undergoing ET with AF-only, HF-only or AF + HF had better (in-hospital mortality, discharge disability, all-cause bleeding) or at least similar (length-of-stay) outcomes to their counterparts not undergoing ET. Compared to AIS patients without AF, AF patients had approximately 50% and more than two-fold increases in the likelihood of receiving IVT or ET, respectively. CONCLUSIONS: We confirmed the combined and individual impact of co-existing AF or HF on important patient-related outcomes. Revascularisation therapies improve these outcomes significantly in patients with these comorbidities.

Association of chronic kidney disease with outcomes in acute stroke.

Previous studies have found an association between chronic kidney disease and poor outcomes in stroke patients. However, there is a paucity of literature evaluating this association by stroke type. We therefore aimed to explore the association between CKD and stroke outcomes according to type of stroke. The data consisting of 594,681 stroke patients were acquired from Universal Coverage Health Security Insurance Scheme Database in Thailand. Binary logistic regression was used to assess the relationship of CKD and outcomes, which were as follows; in-hospital mortality, long length of stay (>3 days), pneumonia, sepsis, respiratory failure and myocardial infarction. Results: after fully adjusting for covariates, CKD was associated with increased odds of in-hospital mortality in patients with ischemic (OR 1.32; 95% CI = 1.27-1.38), haemorrhagic (OR 1.31; 95% CI = 1.24-1.39), and other undetermined stroke type (OR 1.44; 95% CI = 1.21-1.73). CKD was found to be associated with increased odds of pneumonia, sepsis, respiratory failure and myocardial infarction in ischaemic stroke. While CKD was found to be associated with increase odds of sepsis, respiratory failure, and myocardial infarction, decrease odds of pneumonia was observed in patients with haemorrhagic stroke. In other undetermined stroke type, CKD was found to only be associated with increase odds of sepsis and respiratory failure, while there is no significant association of CKD and increase or decrease odds with pneumonia and myocardial infarction. CKD was associated with poor outcomes in all stroke types. CKD should be considered as part of stroke prognosis as well as identifying at risk patient population for in-hospital complications.

Cross-sectional associations of schoolchildren's fruit and vegetable consumption, and meal choices, with their mental well-being: a cross-sectional study.

BACKGROUND: Poor mental well-being is a major issue for young people and is likely to have long-term negative consequences. The contribution of nutrition is underexplored. We, therefore, investigated the association between dietary choices and mental well-being among schoolchildren. METHODS: Data from 7570 secondary school and 1253 primary school children in the Norfolk Children and Young People Health and Well-being Survey, open to all Norfolk schools during October 2017, were analysed. Multivariable linear regression was used to measure the association between nutritional factors and mental well-being assessed by the Warwick-Edinburgh Mental Well-being Scale for secondary school pupils, or the Stirling Children's Well-being Scale for primary school pupils. We adjusted all analyses for important covariates including demographic, health variables, living/home situation and adverse experience variables. RESULTS: In secondary school analyses, a strong association between nutritional variables and well-being scores was apparent. Higher combined fruit and vegetable consumption was significantly associated with higher well-being: well-being scores were 3.73 (95% CI 2.94 to 4.53) units higher in those consuming five or more fruits and vegetables (p<0.001; n=1905) compared with none (n=739). The type of breakfast or lunch consumed was also associated with significant differences in well-being score. Compared with children consuming a conventional type of breakfast (n=5288), those not eating any breakfast had mean well-being scores 2.73 (95% CI 2.11 to 3.35) units lower (p<0.001; n=1129) and those consuming only an energy drink had well-being scores 3.14 (95% CI 1.20 to 5.09) units lower (p=0.002; n=91). Likewise, children not eating any lunch had well-being scores 2.95 (95% CI 2.22 to 3.68) units lower (p<0.001; 860) than those consuming a packed lunch (n=3744). In primary school analyses, the type of breakfast or lunch was associated with significant differences in well-being scores in a similar way to those seen in secondary school data, although no significant association with fruit and vegetable intake was evident. CONCLUSION: These findings suggest that public health strategies to optimise the mental well-being of children should include promotion of good nutrition.

Effect of Co-trimoxazole (Trimethoprim-Sulfamethoxazole) vs Placebo on Death, Lung Transplant, or Hospital Admission in Patients With Moderate and Severe Idiopathic Pulmonary Fibrosis: The EME-TIPAC Randomized Clinical Trial.

Importance: Idiopathic pulmonary fibrosis (IPF) has a poor prognosis and limited treatment options. Patients with IPF have altered lung microbiota, with bacterial burden within the lungs associated with mortality; previous studies have suggested benefit with co-trimoxazole (trimethoprim-sulfamethoxazole). Objective: To determine the efficacy of co-trimoxazole in patients with moderate and severe IPF. Design, Setting, and Participants: Double-blind, placebo-controlled, parallel randomized trial of 342 patients with IPF, breathlessness (Medical Research Council dyspnea scale score >1), and impaired lung function (forced vital capacity ≤75% predicted) conducted in 39 UK specialist interstitial lung disease centers between April 2015 (first patient visit) and April 2019 (last patient follow-up). Interventions: Study participants were randomized to receive 960 mg of oral co-trimoxazole twice daily (n = 170) or matched placebo (n = 172) for between 12 and 42 months. All patients received 5 mg of folic acid orally once daily. Main Outcomes and Measures: The primary outcome was time to death (all causes), lung transplant, or first nonelective hospital admission. There were 15 secondary outcomes, including the individual components of the primary end point respiratory-related events, lung function (forced vital capacity and gas transfer), and patient-reported outcomes (Medical Research Council dyspnea scale, 5-level EuroQol 5-dimension questionnaire, cough severity, Leicester Cough Questionnaire, and King's Brief Interstitial Lung Disease questionnaire scores). Results: Among 342 individuals who were randomized (mean age, 71.3 years; 46 [13%] women), 283 (83%) completed the trial. The median (interquartile range) duration of follow-up was 1.02 (0.35-1.73) years. Events per person-year of follow-up among participants randomized to the co-trimoxazole and placebo groups were 0.45 (84/186) and 0.38 (80/209), respectively, with a hazard ratio of 1.2 ([95% CI, 0.9-1.6]; P = .32). There were no statistically significant differences in other event outcomes, lung function, or patient-reported outcomes. Patients in the co-trimoxazole group had 696 adverse events (nausea [n = 89], diarrhea [n = 52], vomiting [n = 28], and rash [n = 31]) and patients in the placebo group had 640 adverse events (nausea [n = 67], diarrhea [n = 84], vomiting [n = 20], and rash [n = 20]). Conclusions and Relevance: Among patients with moderate or severe IPF, treatment with oral co-trimoxazole did not reduce a composite outcome of time to death, transplant, or nonelective hospitalization compared with placebo. Trial Registration: ISRCTN Identifier: ISRCTN17464641.

Seasonality of stroke: Winter admissions and mortality excess: A Thailand National Stroke population database study.

OBJECTIVES: We examined the existence and potential burden of seasonality of stroke admissions and mortality within a tropical climate using cohort data collected between 1 st November 2003 and 31 st October 2012. PATIENTS AND METHODS: In a prospective cohort of hospitalised stroke patients from the catchment of ∼75 % of the Thai population (n = 569,307; mean SD age = 64(14.5)), incident stroke admissions, in-hospital mortality, prolonged hospitalisations, and stroke related complications by season were determined. Rates of incident stroke admissions by month and season were plotted. Winter excess indexes for study outcomes expressed as a percentage were calculated. Using logistic regression we examined the association between winter admission and in-hospital mortality (non-winter admission as reference) adjusting for age, sex, stroke type, year of admission, and presence of pre-existing comorbidities. RESULTS: We observed a winter excess in mortality during hospitalisation (+10.3 %) and prolonged length of stay (+7.3 %). Respective winter excess indexes for dyslipidaemias, arrhythmias, anaemia, and alcohol related disorders in patients that died during hospitalisation were +1.4 %, +6.2 %, +0.2 %, +1.5 %. In these patients, respective winter excess indexes for post-stroke complications of pneumonia and sepsis were +6.7 % and +3.2 %. In fully adjusted analyses, winter admission (compared to non-winter admission) was associated with increased odds of in-hospital mortality (OR (95 % CI) = 1.023 (1.006-1.040)). CONCLUSIONS: We provide robust evidence for the existence of an excess in winter stroke admissions and subsequent in-hospital deaths within a tropical region.

Infective endocarditis is associated with worse outcomes in stroke: A Thailand National Database Study.

BACKGROUND: There is lack of data on the association between infective endocarditis (IE) and outcomes of mortality and complications in stroke. We aimed to compare characteristics and outcomes of stroke patients with and without IE. METHODS: We retrospectively examined the above association using data obtained from an insurance database which covers ~75% of the Thai population. All hospitalised strokes between 8 January 2003 and 31 December 2013 were included in the current study. Characteristics and outcomes were compared between stroke patients with or without IE, and then between two main stroke types. Multiple logistic regression models including propensity score-matched analyses were constructed to assess study outcomes controlling for age, sex, stroke type and comorbidities. RESULTS: A total of 590 115 stroke patients (mean (SD) age = 64.2 ± 13.7 years; ischaemic = 51.7%; haemorrhagic = 32.6%; undetermined = 15.7%) were included, of whom 2129 (0.36%) had stroke associated with IE. After adjustment, we found that IE was significantly associated with the following complications: arrhythmias (adjusted odds ratio (95% CI) 6.94 (6.29-7.66)), sepsis (1.24 (1.01-1.52)), pneumonia (1.34 (1.17-1.53)), respiratory failure (1.43 (1.24-1.66)) and in-hospital mortality (1.29 (1.13-1.47)) (P for all <.001). Patients with haemorrhagic stroke with IE had poorer outcomes for in-hospital mortality and respiratory failure compared with their counterparts with ischaemic stroke. Propensity score-matched analysis showed similar results. CONCLUSIONS: Our results suggest that stroke patients with IE differ from that of the general stroke population and these patients have worse outcomes. Future studies are needed to determine the best treatment strategies for stroke patients with IE.