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BackgroundMendelian stroke causes nearly 7% of ischaemic strokes and is also an important aetiology of cryptogenic stroke. Identifying the genetic abnormalities in Mendelian strokes is important as it would facilitate therapeutic management and genetic counselling. Next-generation sequencing makes large-scale sequencing and genetic testing possible.MethodsA systematic literature search was conducted to identify causal genes of Mendelian strokes, which were used to construct a hybridization-based gene capture panel. Genetic variants for target genes were detected using Illumina HiSeq X10 and the Novaseq platform. The sensitivity and specificity were evaluated by comparing the results with Sanger sequencing.Results53 suspected patients of Mendelian strokes were analysed using the panel of 181 causal genes. According to the American College of Medical Genetics and Genomics standard, 16 likely pathogenic/variants of uncertain significance genetic variants were identified. Diagnostic testing was conducted by comparing the consistency between the results of panel and Sanger sequencing. Both the sensitivity and specificity were 100% for the panel.ConclusionThis panel provides an economical, time-saving and labour-saving method to detect causal mutations of Mendelian strokes.

IntroductionAustralia has the highest incidence of melanoma in the world with variable care provided by a diverse range of clinicians. Clinical quality registries aim to identify these variations in care and provide anonymised, benchmarked feedback to clinicians and institutions to improve patient outcomes. The Australian Melanoma Clinical Outcomes Registry (MelCOR) aims to collect population-wide, clinical-level data for the early management of cutaneous melanoma and provide anonymised feedback to healthcare providers.Methods and analysisA modified Delphi process will be undertaken to identify key clinical quality indicators for inclusion in the MelCOR pilot. MelCOR will prospectively collect data relevant to these quality indicators, initially for all people over the age of 18 years living in Victoria and Queensland with a melanoma diagnosis confirmed by histopathology, via a two-stage recruitment and consent process. In stage 1, existing State-based cancer registries contact the treating clinician and provide an opportunity for them to opt themselves or their patients out of direct contact with MelCOR. After stage 1, re-identifiable clinical data are provided to the MelCOR under a waiver of consent. In stage 2, the State-based cancer registry will approach the patient directly and invite them to opt in to MelCOR and share identifiable data. If a patient elects to opt in, MelCOR will be able to contact patients directly to collect patient-reported outcome measures. Aggregated data will be used to provide benchmarked, comparative feedback to participating institutions/clinicians.Ethics and disseminationFollowing the successful collection of pilot data, the feasibility of an Australia-wide roll out will be evaluated. Key quality indicator data will be the core of the MelCOR dataset, with additional data points added later. Annual reports will be issued, first to the relevant stakeholders followed by the public. MelCOR is approved by the Alfred Ethics Committee (58280/127/20).

Track cycling is a fast, exciting sport and requires a specific sports-related concussion (SRC) assessment protocol. This paper proposes the first SRC assessment protocol for use in track cycling and proposes that this should occur in three stages. Stage 1 will occur at the trackside, whilst stage 2 occurs in the changing room immediately after the event and stage 3 the day following the suspected SRC. This SRC protocol is in its first iteration and we hope it stimulates debate to allow further refinement.

Background and purposeStroke is the leading cause of mortality and disability in China. Precise aetiological classification, imaging and biological markers may predict the prognosis of stroke. The Third China National Stroke Registry (CNSR-III), a nationwide registry of ischaemic stroke or transient ischaemic attack (TIA) in China based on aetiology, imaging and biology markers, will be considered to clarify the pathogenesis and prognostic factors of ischaemic stroke.MethodsBetween August 2015 and March 2018, the CNSR-III recruited consecutive patients with ischaemic stroke or TIA from 201 hospitals that cover 22 provinces and four municipalities in China. Clinical data were collected prospectively using an electronic data capture system by face-to-face interviews. Patients were followed for clinical outcomes at 3 months, 6 months and 1–5 year annually. Brain imaging, including brain MRI and CT, were completed at baseline. Blood samples were collected and biomarkers were tested at baseline.ResultsA total of 15 166 stroke patients were enrolled, among which 31.7% patients were women with the average age of 62.2±11.3 years. Ischaemic stroke was predominant (93.3%, n=14 146) and 1020 (6.7%) TIAs were enrolled.ConclusionsCNSR-III is a large scale nationwide registry in China. Data from this prospective registry may provide opportunity to evaluate imaging and biomarker prognostic determinants of stroke.

IntroductionIncreasing numbers of children and young people (CYP) are receiving prescriptions for antidepressants. This is the protocol of a study aiming to describe the trends and variation in antidepressant prescriptions in CYP in England, and to examine the indications for the prescriptions recorded and whether there was contact with secondary care specialists on or around the time of the first antidepressant prescription.Methods and analysisAll eligible CYP aged between 5 and 17 years in 1998–2017 from the QResearch primary care database will be included. Incidence and prevalence rates of any antidepressant prescription in each year will be calculated. We will examine four different antidepressant classes: selective serotonin reuptake inhibitors, tricyclic and related antidepressants, serotonin and norepinephrine reuptake inhibitors and other antidepressants, as well as for individual drugs. Linked primary and secondary care data (hospital episode statistics) in the year before and up to 6 months after the first antidepressant prescription will be examined for CYP whose first antidepressant prescription was in 2006–2017. Whether there were records of indications and being seen by psychiatric or paediatric specialists will be identified. Trends over time and differences by region, deprivation and ethnicity will be examined using Poisson regression.DiscussionThis large, population-based study will give an up-to-date picture of antidepressant prescribing in CYP and identify any variation. Understanding what indications are recorded when CYP are being prescribed antidepressants, and whether this was done in partnership with secondary care specialists, will provide evidence of whether appropriate guidelines are being followed.

IntroductionConcussion is a clinical diagnosis, based on self-reported patient symptoms supported by clinical assessments across many domains including postural control, ocular/vestibular dysfunction, and neurocognition. Concussion incidence may be rising in motorsport which, combined with unresolved challenges to accurate diagnosis and lack of guidance on the optimal return-to-race timeframe, creates a difficult environment for healthcare practitioners.Methods and analysisResearch Evaluating Sports ConcUssion Events—Rapid Assessment of Concussion and Evidence for Return (RESCUE-RACER) evaluates motorsports competitors at baseline (Competitor Assessment at Baseline; Ocular, Neuroscientific (CArBON) study) and post-injury (Concussion Assessment and Return to motorSport (CARS) study), including longitudinal data. CArBON collects pre-injury neuroscientific data; CARS repeats the CArBON battery sequentially during recovery for competitors involved in a potentially concussive event. As its primary outcome, RESCUE-RACER will develop the evidence base for an accurate trackside diagnostic tool. Baseline objective clinical scoring (Sport Concussion Assessment Tool—5th edition (SCAT5)) and neurocognitive data (Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT)) will be assessed for specificity to motorsport and relationship to existing examinations. Changes to SCAT5 and ocular, vestibular, and reaction time function (Dx 100) will be estimated by the reliability change index as a practical tool for trackside diagnosis. Neuropsychological (Cambridge Neuropsychological Test Automated Battery (CANTAB)) assessments, brain MRI (7 Tesla) and salivary biomarkers will be compared with the new tool to establish utility in diagnosing and monitoring concussive injuries.Ethics and disseminationEthical approval was received from East of England-Cambridge Central Research Ethics Committee (18/EE/0141). Participants will be notified of study outcomes via publications (to administrators) and summary reports (funder communications). Ideally, all publications will be open access.Trial registration numberFebruary 2019 nationally (Central Portfolio Management System 38259) and internationally (ClinicalTrials.gov NCT03844282).

Funder: National Institute for Health Research (NIHR), INTRODUCTION: There has been an increase in the birth prevalence of congenital hypothyroidism (CH) since the introduction of newborn screening, both globally and in the UK. This increase can be accounted for by an increase in CH with gland in situ (CH-GIS). It is not known why CH-GIS is becoming more common, nor how it affects the health, development and learning of children over the long term. Our study will use linked administrative health, education and clinical data to determine risk factors for CH-GIS and describe long-term health and education outcomes for affected children. METHODS AND ANALYSIS: We will construct a birth cohort study based on linked, administrative data to determine what factors have contributed to the increase in the birth prevalence of CH-GIS in the UK. We will also set up a follow-up study of cases and controls to determine the health and education outcomes of children with and without CH-GIS. We will use logistic/multinomial regression models to establish risk factors for CH-GIS. Changes in the prevalence of risk factors over time will help to explain the increase in birth prevalence of CH-GIS. Multivariable generalised linear models or Cox proportional hazards regression models will be used to assess the association between type of CH and school performance or health outcomes. ETHICS AND DISSEMINATION: This study has been approved by the London Queen Square Research Ethics Committee and the Health Research Authority's Confidentiality Advisory Group CAG. Approvals are also being sought from each data provider. Obtaining approvals from CAG, data providers and information governance bodies have caused considerable delays to the project. Our methods and findings will be published in peer-reviewed journals and presented at academic conferences.

ObjectivesTo investigate the safety, feasibility and acceptability of the Neurofenix platform for home-based rehabilitation of the upper limb (UL).DesignA non-randomised intervention design with a parallel process evaluation.SettingParticipants’ homes, South-East England.ParticipantsThirty adults (≥18 years), minimum 12-week poststroke, not receiving UL rehabilitation, scoring 9–25 on the Motricity Index (elbow and shoulder), with sufficient cognitive and communicative abilities to participate.InterventionsParticipants were trained to use the platform, followed by 1 week of graded game-play exposure and 6-week training, aiming for a minimum 45 min, 5 days/week.OutcomesSafety was determined by assessing pain and poststroke fatigue at 8 and 12 weeks, and adverse events (AEs). Impairment, activity and participation outcomes were measured. Intervention feasibility was determined by the amount of specialist training and support required to complete the intervention, time and days spent training, and number of UL movements performed. Acceptability was assessed by a satisfaction questionnaire and semistructured interviews.ResultsParticipants (14 women; mean (SD) age 60.0 (11.3) years) were a median of 4.9 years poststroke (minimum-maximum: 1–28 years). Twenty-seven participants completed the intervention. The odds of having shoulder pain were lower at 8 weeks (OR 0.45, 95% CI 0.24 to 0.83, p=0.010) and 12 weeks (OR 0.46, 95% CI 0.25 to 0.86, p=0.014) compared with baseline. Fugl-Meyer upper extremity, Motor Activity Log and passive range of movement improved. No other gains were recorded. Poststroke fatigue did not change. Thirty mild and short-term AEs and one serious (unrelated) AE were reported by 19 participants. Participants trained with the platform for a median of 17.4 hours over 7 weeks (minimum-maximum: 0.3–46.9 hours), equating to a median of 149 min per week. The median satisfaction score was 36 out of 40.ConclusionThe Neurofenix platform is a safe, feasible and well accepted way to support UL training for people at least three months poststroke.Trial registration numberISRCTN60291412.

Physical activity (PA) has evidence-based benefits for physical, social and mental health, but investigation of how PA interventions for patients with chronic disease affects their PA practice up to 1 year after programmes are rare. Moreover, few studies document how the context and intervention mechanisms of PA programmes affect sustainable PA practice and its determinants. The present protocol describes a mixed methods study comparing the effectiveness and conditions for the effectiveness of two PA resumption programmes (a hospital-led and a community-based programme). Using a comparative longitudinal study, 60 patients (3-month duration) will be followed for 1 year though four data collections: before (T0) and at the end (T1) of the intervention, 6 months (T2) and 1 year (T3) after the start of the programme. The primary outcome will be PA practice in min/week and categorised as light, moderate or vigorous (using International Physical Activity Questionnaire (IPAQ)), and secondary outcomes will include sedentary time in min/week (IPAQ), quality of life evaluated though the physical and mental composite scores (‘Medical Outcome Study Short Form 12’), and enjoyment using four statements rated from 1 to 5, a high score being synonymous of enjoyment (Intrinsic Motivation Inventory). Qualitative data on further determinants of PA practice and intervention mechanisms will be collected. The expected results will offer the opportunity to understand how the intervention context contributes to a more effective, sustainable PA practice. Trial registration number: NCT04954209.

ObjectiveSymptoms and clinical course during inflammatory bowel disease (IBD) vary among individuals. Personalised care is therefore essential to effective management, delivered by a strong patient-centred multidisciplinary team, working within a well-designed service. This study aimed to fully rewrite the UK Standards for the healthcare of adults and children with IBD, and to develop an IBD Service Benchmarking Tool to support current and future personalised care models.DesignLed by IBD UK, a national multidisciplinary alliance of patients and nominated representatives from all major stakeholders in IBD care, Standards requirements were defined by survey data collated from 689 patients and 151 healthcare professionals. Standards were drafted and refined over three rounds of modified electronic-Delphi.ResultsConsensus was achieved for 59 Standards covering seven clinical domains; (1) design and delivery of the multidisciplinary IBD service; (2) prediagnostic referral pathways, protocols and timeframes; (3) holistic care of the newly diagnosed patient; (4) flare management to support patient empowerment, self-management and access to specialists where required; (5) surgery including appropriate expertise, preoperative information, psychological support and postoperative care; (6) inpatient medical care delivery (7) and ongoing long-term care in the outpatient department and primary care setting including shared care. Using these patient-centred Standards and informed by the IBD Quality Improvement Project (IBDQIP), this paper presents a national benchmarking framework.ConclusionsThe Standards and Benchmarking Tool provide a framework for healthcare providers and patients to rate the quality of their service. This will recognise excellent care, and promote quality improvement, audit and service development in IBD.

IntroductionStatins reduce the incidence of cardiovascular disease (CVD) and cause few adverse effects. Half of patients prescribed statins discontinue treatment due to perceived intolerance. Placebo-controlled (blinded) n-of-1 trials have shown people with perceived intolerance that the statin does not cause adverse events and most resume treatment. However, blinded n-of-1 trials are impractical to deliver in routine practice. Tackling Statin Intolerance using n-of-1 trials (TaSINI) will test the feasibility of a general practitioner (GP)-delivered behavioural intervention endorsing an unblinded n-of-1 trial to increase adherence to statins relative to usual care.Methods and analysisTaSINI is a feasibility randomised controlled trial with a nested qualitative substudy. Ninety primary care patients who have discontinued statins due to intolerance or refused treatment will be randomised to an unblinded n-of-1 trial, a blinded n-of-1 trial (positive control) or usual care (negative control). Participants randomised to usual care will be advised to take statin therapy to prevent CVD. In both n-of-1 trial arms, GPs will deliver a behaviourally informed intervention that accessibly explains the benefits of statins, the prevalence of adverse effects and endorse the benefit of experimenting with medication. Participants will alternate between 4 weeks of medication and no medication (unblinded arm) or randomly sorted active and placebo (blinded arm) and will record adherence, symptoms and symptom attributions throughout. After 6 months, GPs will feedback symptom data during active/inactive treatment periods. All participants will be asked if they would like to initiate statin treatment. Measures of feasibility will be met if 4% of invited patients enrol, 50% of participants randomised to n-of-1 trials engage with the experiment and 25% more participants initiate statin in the unblinded n-of-1 arm than in usual care.Ethics and disseminationThis study has been granted ethical approval by North of Scotland Research Ethics Service. The results will be written up for publication and show whether to progress to an effectiveness trial where the primary outcome would be differences in low-density lipoprotein concentration.

IntroductionThe National Early Warning Score is used as standard clinical practice in the UK as a track and trigger system to monitor hospitalised patients. Currently, nurses are tasked to take routine vital signs measurements and manually record these on a clinical chart. Wearable devices could provide an easier, reliable, more convenient and cost-effective method of monitoring. Our aim is to evaluate the clinical validity of Polso (ChroniSense Medical, Yokneam Illit, Israel), a wrist-based device, to provide National Early Warning Scores.Methods and analysisWe will compare Polso National Early Warning Score measurements to the currently used manual measurements in a UK Teaching District General Hospital. Patients aged 18 years or above who require recordings of observations of vital signs at least every 6 hours will be enrolled after consenting. The sample size for the study was calculated to be 300 participants based on the assumption that the final dataset will include four pairs of measurements per-patient and per-vital sign, resulting in a total of 1200 pairs of data points per vital sign. The primary outcome is the agreement on the individual parameter scores and values of the National Early Warning Score: (1) respiratory rate, (2) oxygen saturation, (3) body temperature, (4) systolic blood pressure and (5) heart rate. Secondary outcomes are the agreement on the aggregate National Early Warning Score. The incidence of adverse events will be recorded. The measurements by the device will not be used for the clinical decision-making in this study.Ethics and disseminationWe obtained ethical approval, reference number 18/LO/0123 from London—Hampstead Research Ethics Committee, through the Integrated Research Application System, (reference number: 235 034. The study received no objection from the Medicine and Health Regulatory Authority, reference number: CI/20018/005 and has National Institute for Health Research portfolio adoption status CPMS number: 32 532.Trial registration numberNCT03448861; Pre-results.

IntroductionThere is a renewed global interest in improving community health worker (CHW) programmes. For CHW programmes to be effective, key intervention design factors which contribute to the performance of CHWs need to be identified. The recent WHO guidelines recommends the combination of financial and non-financial incentives to improve CHW performance. However, evidence gaps remain as to what package of incentives will improve their performance in different country contexts. This study aims to evaluate CHW incentive preferences to improve performance and retention which will strengthen CHW programmes and help governments leverage limited resources appropriately.Methods and analysisA discrete choice experiment (DCE) will be conducted with CHWs in Bangladesh, Haiti, Kenya and Uganda with different levels of maturity of CHWs programmes. This will be carried out in two phases. Phase 1 will involve preliminary qualitative research including focus group discussions (FGDs) and key informant interviews to develop the DCE design which will include attributes relevant to the CHW country settings. Phase 2 will involve a DCE survey with CHWs, presenting them with a series of job choices with varying attribute levels. An orthogonal design will be used to generate the choice sets for the surveys. The surveys will be administered in locally-appropriate languages to at least 150 CHWs from each of the cadres in each country. Conditional and mixed multinomial logit (MMNL) models will be used for the estimation of stated preferences.Ethics and disseminationThis study has been reviewed and approved by the Population Council’s Institutional Review Board in New York, and appropriate ethics review boards in Kenya, Uganda, Bangladesh and Haiti. The results of the study will be disseminated through in-country dissemination workshops, meetings with country-level stakeholders and policy working groups, print media, online blogs and peer-reviewed journals.

BackgroundIn June 2015, the Chinese Stroke Association (CSA) initiated the Chinese Stroke Center Alliance (CSCA) to establish the national hospital-based stroke care quality assessment and improvement platform. This article outlines its objectives, operational structure, patient population, quality improvement (QI) intervention tools, data elements, data collection methodology and current patient and hospital data.MethodsThe CSCA is a national, hospital-based, multicentre, voluntary, multifaceted intervention and continuous QI initiative. This multifaceted intervention includes stroke centre development, written care protocols, workshops and a monitoring/feedback system of evidence-based performance measures. The data coordinating centre of the CSCA resides at the China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital.ResultsAs of July 2017, 1576 hospitals in China have contributed detailed clinical information to serve as a benchmark for the stroke care quality of 433 264 patients with acute stroke/transient ischaemic attacks (TIA), including 352 572 (81.38%) acute ischaemic stroke, 30 362 (7.01%) TIA, 42 080 (9.71%) spontaneous intracranial haemorrhage, 5505 (1.27%) subarachnoid haemorrhage and 2745 (0.63%) not specified stroke.ConclusionThe CSCA programme is designed to establish a continuous national stroke registry and help healthcare providers develop stroke centres and treat patients in a consistent manner in accordance with accepted national guidelines and, ultimately, improve patient outcomes. It supports the CSA mission to reduce stroke burden in China.

IntroductionThe South African Department of Health has developed and implemented the Integrated Chronic Disease Management (ICDM) model to respond to the increased utilisation of primary healthcare services due to a surge of non-communicable diseases coexisting with a high prevalence of communicable diseases. However, some of the expected outcomes on implementing the ICDM model have not been achieved. The aims of this study are to assess if the observed suboptimal outcomes of the ICDM model implementation are due to lack of fidelity to the ICDM model, to examine the contextual factors associated with the implementation fidelity and to calculate implementation costs.Methods and analysisA process evaluation, mixed methods study in 16 pilot clinics from two health districts to assess the degree of fidelity to four major components of the ICDM model. Activity scores will be summed per component and overall fidelity score will be calculated by summing the various component scores and compared between components, facilities and districts. The association between contextual factors and the degree of fidelity will be asseseed by multivariate analysis, individual and team characteristics, facility features and organisational culture indicators will be included in the regression. Health system financial and economic costs of implementing the four components of the ICDM model will be calculated using an ingredient approach. The unit of implementation costs will be by activity of each of the major components of the ICDM model. Sensitivity analysis will be carried out using clinic size, degree of fidelity and different inflation situations.Ethics and disseminationThe protocol has been approved by the University of Cape Town and University of the Witwatersrand Human Research ethics committees. The results of the study will be shared with the Department of Health, participating health facilities and through scientific publications and conference presentations.

IntroductionPrimary school-based physical activity interventions, such as The Daily Mile initiative, have the potential to increase children’s physical activity levels over time, which is associated with a variety of health benefits. Comparing interventions or combining results of several studies of a single intervention is challenging because previous studies have examined different outcomes or used different measures that are not feasible or relevant for researchers in school settings. The development and implementation of a core outcome set (COS) for primary school-based physical activity interventions would ensure outcomes important to those involved in implementing and evaluating interventions are standardised.Methods and analysisOur aim is to develop a COS for studies of school-based physical activity interventions. We will achieve this by undertaking a four-stage process:(1) identify a list of outcomes assessed in studies through a systematic review of international literature; (2) establish domains from these outcomes to produce questionnaire items; (3) prioritise outcomes through a two-stage Delphi survey with four key stakeholder groups (researchers, public health professionals, educators and parents), where stakeholders rate the importance of each outcome on a 9-point Likert scale (consensus that the outcomes should be included in the COS will be determined as 70% or more of all stakeholders scoring the outcome 7%–9% and 15% or less scoring 1 to 3); (4) achieve consensus on a final COS in face-to-face meetings with a sample of stakeholders and primary school children.Ethics and disseminationWe have received ethical approval from Imperial College London (ref: 19IC5428). The results of this study will be disseminated via conference presentations/public health meetings, peer-reviewed publications and through appropriate media channels.Trial registration numberCore Outcome Measures in Effectiveness Trials Initiative (COMET) number: 1322.

IntroductionPaediatric acquired brain injury is a leading cause of mortality in children in the UK. Improved treatment during the acute phase has led to increased survival rates, although with life-long morbidity in terms of social and emotional functioning. This is the protocol for a feasibility randomised controlled trial with an embedded qualitative study and feasibility economic evaluation. If feasible, a later definitive trial will test the effectiveness and cost-effectiveness of an online intervention to enhance problem solving ability versus treatment as usual.Methods and analysisTwenty-five adolescents and their families identified by primary or secondary care clinicians at participating UK National Health Service Trusts will be recruited and individually randomised in a 1:1 ratio to receive the online intervention or treatment as usual. Participants will be followed up by online questionnaires 17 weeks after randomisation to capture acceptability of the study and intervention and resource use data. Qualitative interviews will capture participants’ and clinicians’ experiences of the study.Ethics and disseminationThis study has been granted ethical approval by the South West-Exeter Research Ethics Committee (ref 17/SW/0083). Results will be disseminated via peer-reviewed publications and will inform the design of a larger trial.Trial registration numberISRCTN10906069

IntroductionTechnology has been placed at the centre of global health policy and has been cited as having the potential to increase efficiency and remove geographical boundaries for patients to access care. Communication technology may support patients with orthopaedic problems, which is one of the leading causes of disability worldwide. There are several examples of technology being used in clinical research, although uptake in practice remains low. An understanding of patient preferences will support the design of a communication technology supported treatment pathway for patients undergoing orthopaedic rehabilitation.Methods and analysisThis mixed methods project will be conducted in four phases. In phase I, a systematic review of qualitative studies reporting communication technology use for orthopaedic rehabilitation will be conducted to devise a taxonomy of tasks patients’ face when using these technologies to access their care. In phase II, qualitative interviews will investigate how the work of being a patient changes during face-to-face and communication technology consultations and how these changes influence preference. In phase III, a discrete choice experiment will investigate the factors that influence preferences for the use of communication technology for orthopaedic rehabilitation consultations. Phase IV will be a practical application of these results. We will design a ‘minimally disruptive’ communication technology supported pathway for patients undergoing orthopaedic rehabilitation.Ethics and disseminationThe design of a pathway and underpinning patient preference will assist in understanding factors that might influence technology implementation for clinical care. This study requires ethical approval for phases II, III and IV. Approvals have been received for phase II (approval received on 4 December 2016 from the South Central-Oxford C Research Ethics Committee (IRAS ID: 255172, REC Reference 18/SC/0663)) and phase III (approval received on 18 October 2019 from the London-Hampstead Research Ethics Committee (IRAS ID: 248064, REC Reference 19/LO/1586)) and will be sought for phase IV. All participants will provide informed written consent prior to being enrolled onto the study.PROSPERO registration numberCRD42018100896.

IntroductionPharmacological interventions to address behavioural and psychological symptoms of dementia (BPSD) can have undesirable side effects, therefore non-pharmacological approaches to managing symptoms may be preferable. Past studies show that music therapy can reduce BPSD, and other studies have explored how formal caregivers use music in their caring roles. However, no randomised study has examined the effects on BPSD of music interventions delivered by informal caregivers (CGs) in the home setting. Our project aims to address the need for improved informal care by training cohabiting family CGs to implement music interventions that target BPSD, and the quality of life (QoL) and well-being of people with dementia (PwD) and CGs.Methods and analysisA large international three-arm parallel-group randomised controlled trial will recruit a sample of 495 dyads from Australia, Germany, UK, Poland and Norway. Dyads will be randomised equally to standard care (SC), a home-based music programme plus SC, or a home-based reading programme plus SC for 12 weeks. The primary outcome is BPSD of PwD (measured using the Neuropsychiatric Inventory-Questionnaire). Secondary outcomes will examine relationship quality between CG and PwD, depression, resilience, competence, QoL for CG and QoL for PwD. Outcomes will be collected at baseline, at the end of the 12-week intervention and at 6 months post randomisation. Resource Utilisation in Dementia will be used to collect economic data across the life of the intervention and at 6-month follow-up. We hypothesise that the music programme plus SC will generate better results than SC alone (primary comparison) and the reading programme plus SC (secondary comparison).Ethics and disseminationEthical approval has been obtained for all countries. Results will be presented at national and international conferences and published in scientific journals and disseminated to consumer and caregiver representatives and the community.Trial registration numbersACTRN12618001799246p; NCT03907748

IntroductionEmergency department (ED) visits for epilepsy are common, costly, often clinically unnecessary and typically lead to little benefit for epilepsy management. An ‘Alternative Care Pathway’ (ACP) for epilepsy, which diverts people with epilepsy (PWE) away from ED when ‘999’ is called and leads to care elsewhere, might generate savings and facilitate improved ambulatory care. It is unknown though what features it should incorporate to make it acceptable to persons from this particularly vulnerable target population. It also needs to be National Health Service (NHS) feasible. This project seeks to identify the optimal ACP configuration.Methods and analysisMixed-methods project comprising three-linked stages. In Stage 1, NHS bodies will be surveyed on ACPs they are considering and semi-structured interviews with PWE and their carers will explore attributes of care important to them and their concerns and expectations regarding ACPs. In Stage 2, Discrete Choice Experiments (DCE) will be completed with PWE and carers to identify the relative importance placed on different care attributes under common seizure scenarios and the trade-offs people are willing to make. The uptake of different ACP configurations will be estimated. In Stage 3, two Knowledge Exchange workshops using a nominal group technique will be run. NHS managers, health professionals, commissioners and patient and carer representatives will discuss DCE results and form a consensus on which ACP configuration best meets users’ needs and is NHS feasible.Ethics and disseminationEthical approval: NRES Committee (19/WM/0012) and King’s College London ethics Committee (LRS-18/19-10353). Primary output will be identification of optimal ACP configuration which should be prioritised for implementation and evaluation. A pro-active dissemination strategy will make those considering developing or supporting an epilepsy ACP aware of the project and opportunities to take part in it. It will also ensure they are informed of its findings.Project registration numberResearchregistry4723.

IntroductionIn addition to their high mortality rates, road traffic collisions (RTC) are considered a burden within those who do survive. In Africa, injuries related to RTC have been identified as the 10th most common cause of disability-adjusted life years lost for all ages and categories. Moreover, non-fatal RTC are the biggest cause associated with the burden of musculoskeletal disorders (MSD) in Africa. Despite this, the epidemiology of MSD related to non-fatal RTC within this region is still unknown.The objective of this review is to identify and summarise available data regarding the prevalence, incidence and patterns of MSD resulting from non-fatal RTC in Africa.Methods and analysisA systematic review of observational epidemiological studies will be conducted. On October 2019, MEDLINE, Embase, CINAHL Plus, PsycINFO, Web of Science, Global Health and African Journals OnLine will be searched for literature that is in English and published between 1990 and 2018. Two reviewers (MY ad TG) will independently screen results and extract the data, with a third reviewer (FF) resolving any discrepancies through discussion. Additionally, two reviewers (MY and TG) will independently assess the quality of the eligible studies using the US National Institutes of Health National Heart, Lung, and Blood Institute Quality Assessment Tool.Within the eligible studies, data on citation, methods and results will be extracted. Extracted data will be analysed using a narrative synthesis. Findings will be presented in tables, with the main outcomes being prevalence, incidence and disease pattern of MSD and determinants of non-fatal RTC. The final systematic review will be conducted as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline.Ethics and disseminationAs individual patients will not be involved in this study, no ethical approval will be sought. Findings from this review will be disseminated through peer-reviewed journals and relevant conferences.Trial registration numberCRD42019139538

IntroductionThe scale-up of integrated Human Immunodeficiency Virus (HIV) and tuberculosis (TB) treatment has been an important intervention to curb the burden of HIV and TB co-infection worldwide. Uptake of and adherence to antiretroviral therapy (ART) are key determinants of the quality and therapeutic endpoints of this intervention. This study aims to conduct an up-to-date collection and synthesis of evidence on barriers to and facilitators of uptake of and adherence to ART in HIV/TB integrated treatment programs in sub-Saharan Africa (SSA).MethodA systematic review of peer-reviewed literature on the uptake of and adherence to ART in the context of integrated therapy for HIV and TB in SSA will be performed. We will review qualitative and quantitative studies reporting on the uptake of and adherence to ART during integrated treatment for TB and HIV among adults. These will include studies that involve HIV-infected TB patients initiating ART and studies involving PLWHA already on ART who are newly diagnosed with TB. Qualitative studies, quantitative studies, randomised trials and observational studies will be included. Six databases including Medline and Embase will be searched for relevant studies published from March 2004 to July 2019. Two authors will independently screen the search output and retrieve full texts of eligible studies. Disagreements between the two authors will be resolved by arbitration by a third author. Data will be abstracted from the eligible studies and synthesis will be done through descriptive synthesis for qualitative data and meta-analysis for quantitative data.Ethics and disseminationThis study will be a review of the literature and will not involve primary collection of individuals’ data. Amendments to the protocol will be documented in the final review. The final study will be published in a peer-reviewed journal and presented at conferences. The review is expected to contribute to improving strategies to enhance uptake of and adherence to ART in integrated care.PROSPERO registration numberCRD42019131933.

ObjectiveLack of standardised outcomes hampers effective analysis and comparison of data when comparing treatments in fistulising perianal Crohn’s disease (pCD). Development of a standardised set of outcomes would resolve these issues. This study provides the definitive core outcome set (COS) for fistulising pCD.DesignCandidate outcomes were generated through a systematic review and patient interviews. Consensus was established via a three-round Delphi process using a 9-point Likert scale based on how important they felt it was in determining treatment success culminating in a final consensus meeting. Stakeholders were recruited nationally and grouped into three panels (surgeons and radiologists, gastroenterologists and IBD specialist nurses, and patients). Participants received feedback from their panel (in the second round) and all participants (in the third round) to allow refinement of their scores.ResultsA total of 295 outcomes were identified from systematic reviews and interviews that were categorised into 92 domains. 187 stakeholders (response rate 78.5%) prioritised 49 outcomes through a three-round Delphi study. The final consensus meeting of 41 experts and patients generated agreement on an eight domain COS. The COS comprised three patient-reported outcome domains (quality of life, incontinence and a combined score of patient priorities) and five clinician-reported outcome domains (perianal disease activity, development of new perianal abscess/sepsis, new/recurrent fistula, unplanned surgery and faecal diversion).ConclusionA fistulising pCD COS has been produced by all key stakeholders. Application of the COS will reduce heterogeneity in outcome reporting, thereby facilitating more meaningful comparisons between treatments, data synthesis and ultimately benefit patient care.

IntroductionThe I-KID study aims to determine the clinical efficacy, outcomes and safety of a novel non-CE-marked infant haemodialysis machine, the Newcastle Infant Dialysis Ultrafiltration System (NIDUS), compared with currently available therapy in the UK. NIDUS is specifically designed for renal replacement therapy in small babies between 0.8 and 8 kg.Methods and analysisThe clinical investigation is taking place in six UK centres. This is a randomised clinical investigation using a cluster stepped-wedge design. The study aims to recruit 95 babies requiring renal replacement therapy in paediatric intensive care units over 20 months.Ethics and disseminationThe study has high parent and public involvement at all stages in its design and parents will be involved in dissemination of results to parents and professionals via publications, conference proceedings and newsletters. The study has has ethics permissions from Tyne and Wear South Research Ethics Committee.Trial registration numbersIRAS ID number: 170 481MHRA Reference: CI/2017/0066ISRCT Number: 13 787 486CPMS ID number: 36 558NHS REC reference: 16/NE/0008Eudamed number: CIV-GB-18-02-023105Link to full protocol v6.0: https://fundingawards.nihr.ac.uk/award/14/23/26

BackgroundPremature birth is a global epidemic of significant public health concern. Counselling and education of pregnant women at risk of preterm birth or mothers with premature infants are essential to improve mother and infant health. Mobile applications are an increasingly popular tool among parents to receive health information and education. This study aims to evaluate the usages and the effects of a mobile application designed for premature births in order to improve health outcomes.MethodsThis review will include all studies of different designs which evaluated the use and impact of interventions provided via mobile applications on pregnant women at risk of preterm birth or mothers with premature infants in order to address all health outcomes. A combination of keywords and MeSH(Medical Subject Headings) terms is used in the search strategy. Literature databases including Scopus, PubMed, ISI Web of Science, ProQuest, CINAHL and Cochrane Library will be searched to May 2021. Furthermore, eligible studies will be chosen from the reference list of retrieved papers. Two researchers will independently review the retrieved citations to decide whether they meet the inclusion criteria. Mixed Methods Appraisal Tool (MMAT) V.2018 will be used to assess the quality of studies. Relevant data are collected in a data extraction form and analysed. Results are reported under the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.DiscussionThis systematic review will recognize and combine evidence about the usages and impact of mobile application interventions on the health improvement of pregnant women at risk of preterm birth or mothers with premature infants.

IntroductionHealth Data Research UK designated seven UK-based Hubs to facilitate health data use for research. PIONEER is the Hub in Acute Care. PIONEER delivered workshops where patients/public citizens agreed key principles to guide access to unconsented, anonymised, routinely collected health data. These were used to inform the protocol.MethodsThis paper describes the PIONEER infrastructure and data access processes. PIONEER is a research database and analytical environment that links routinely collected health data across community, ambulance and hospital healthcare providers. PIONEER aims ultimately to improve patient health and care, by making health data discoverable and accessible for research by National Health Service, academic and commercial organisations. The PIONEER protocol incorporates principles identified in the public/patient workshops. This includes all data access requests being reviewed by the Data Trust Committee, a group of public citizens who advise on whether requests should be supported prior to licensed access.Ethics and disseminationEast Midlands–Derby REC (20/EM/0158): Confidentiality Advisory Group (20/CAG/0084). www.PIONEERdatahub.co.uk

Background Sports-related concussion (SRC) is a recognised risk in road cycling and can have serious health consequences. Recent high-profile cases of professional road cyclists continuing to participate in races despite suffering obvious SRC have highlighted the difficulties in assessing SRC within road cycling.Purpose To undertake a systematic review of the literature on SRC assessment in road cycling.Study design Systematic review.Methods Literature describing SRC assessment in road cycling was identified by searching MEDLINE, EMBASE, PsycINFO and Web of Science. Two reviewers independently screened titles and abstracts for eligibility and a qualitative analysis was undertaken of included studies.Results From 94 studies identified, two were included for review. Gordon et al describe the presentation of a single case of paediatric concussion following a cycling crash. They highlight the utility of SRC evaluation using the Sport Concussion Assessment Tool (SCAT) as well as the importance of a stepwise return-to-play protocol. Greve and Modabber discuss a number of traumatic brain injuries that occurred during the 2011 road cycling season and, as a minimum, call for riders to be withdrawn from competition following loss of consciousness or amnesia. Both studies are at high risk of bias and of low quality.Conclusion Road cycling poses unique challenges for the assessment of SRC. This review illustrates the lack of published evidence to advise effective means of SRC assessment within road cycling. The Union Cycliste Internationale (UCI) regulations advise the use of SCAT-5 for concussion assessment but this tool is impractical, requiring modification for use in road cycling. We would like to call on the UCI to hold a consensus meeting to establish an evidence-based SRC assessment protocol and return-to-riding protocol for road cycling.

Introduction Matching treatment to specific patients is too often a matter of trial and error, while treatment efficacy should be optimised by limiting risks and costs and by incorporating patients’ preferences. Factors influencing an individual’s drug response in major depressive disorder may include a number of clinical variables (such as previous treatments, severity of illness, concomitant anxiety etc) as well demographics (for instance, age, weight, social support and family history). Our project, funded by the National Institute of Health Research, is aimed at developing and subsequently testing a precision medicine approach to the pharmacological treatment of major depressive disorder in adults, which can be used in everyday clinical settings. Methods and analysis We will jointly synthesise data from patients with major depressive disorder, obtained from diverse datasets, including randomised trials as well as observational, real-world studies. We will summarise the highest quality and most up-to-date scientific evidence about comparative effectiveness and tolerability (adverse effects) of antidepressants for major depressive disorder, develop and externally validate prediction models to produce stratified treatment recommendations. Results from this analysis will subsequently inform a web-based platform and build a decision support tool combining the stratified recommendations with clinicians and patients’ preferences, to adapt the tool, increase its’ reliability and tailor treatment indications to the individual-patient level. We will then test whether use of the tool relative to treatment as usual in real-world clinical settings leads to enhanced treatment adherence and response, is acceptable to clinicians and patients, and is economically viable in the UK National Health Service. Discussion This is a clinically oriented study, coordinated by an international team of experts, with important implications for patients treated in real-world setting. This project will form a test-case that, if effective, will be extended to non-pharmacological treatments (either face-to-face or internet-delivered), to other populations and disorders in psychiatry (for instance, children and adolescents, or schizophrenia and treatment-resistant depression) and to other fields of medicine.

IntroductionHepatitis C virus (HCV) is the second largest contributor to liver disease in the UK, with injecting drug use as the main risk factor among the estimated 200 000 people currently infected. Despite effective prevention interventions, chronic HCV prevalence remains around 40% among people who inject drugs (PWID). New direct-acting antiviral (DAA) HCV therapies combine high cure rates (>90%) and short treatment duration (8 to 12 weeks). Theoretical mathematical modelling evidence suggests HCV treatment scale-up can prevent transmission and substantially reduce HCV prevalence/incidence among PWID. Our primary aim is to generate empirical evidence on the effectiveness of HCV ‘Treatment as Prevention’ (TasP) in PWID.Methods and analysisWe plan to establish a natural experiment with Tayside, Scotland, as a single intervention site where HCV care pathways are being expanded (including specialist drug treatment clinics, needle and syringe programmes (NSPs), pharmacies and prison) and HCV treatment for PWID is being rapidly scaled-up. Other sites in Scotland and England will act as potential controls. Over 2 years from 2017/2018, at least 500 PWID will be treated in Tayside, which simulation studies project will reduce chronic HCV prevalence among PWID by 62% (from 26% to 10%) and HCV incidence will fall by approximately 2/3 (from 4.2 per 100 person-years (p100py) to 1.4 p100py). Treatment response and re-infection rates will be monitored. We will conduct focus groups and interviews with service providers and patients that accept and decline treatment to identify barriers and facilitators in implementing TasP. We will conduct longitudinal interviews with up to 40 PWID to assess whether successful HCV treatment alters their perspectives on and engagement with drug treatment and recovery. Trained peer researchers will be involved in data collection and dissemination. The primary outcome – chronic HCV prevalence in PWID – is measured using information from the Needle Exchange Surveillance Initiative survey in Scotland and the Unlinked Anonymous Monitoring Programme in England, conducted at least four times before and three times during and after the intervention. We will adapt Bayesian synthetic control methods (specifically the Causal Impact Method) to generate the cumulative impact of the intervention on chronic HCV prevalence and incidence. We will use a dynamic HCV transmission and economic model to evaluate the cost-effectiveness of the HCV TasP intervention, and to estimate the contribution of the scale-up in HCV treatment to observe changes in HCV prevalence. Through the qualitative data we will systematically explore key mechanisms of TasP real world implementation from provider and patient perspectives to develop a manual for scaling up HCV treatment in other settings. We will compare qualitative accounts of drug treatment and recovery with a ‘virtual cohort’ of PWID linking information on HCV treatment with Scottish Drug treatment databases to test whether DAA treatment improves drug treatment outcomes.Ethics and disseminationExtending HCV community care pathways is covered by ethics (ERADICATE C,ISRCTN27564683, Super DOT C Trial clinicaltrials.gov:NCT02706223). Ethical approval for extra data collection from patients including health utilities and qualitative interviews has been granted (REC ref: 18/ES/0128) and ISCRCTN registration has been completed (ISRCTN72038467). Our findings will have direct National Health Service and patient relevance; informing prioritisation given to early HCV treatment for PWID. We will present findings to practitioners and policymakers, and support design of an evaluation of HCV TasP in England.

IntroductionIndividualising therapy is an important challenge for intensive care of patients with severe traumatic brain injury (TBI). Targeting a cerebral perfusion pressure (CPP) tailored to optimise cerebrovascular autoregulation has been suggested as an attractive strategy on the basis of a large body of retrospective observational data. The objective of this study is to prospectively assess the feasibility and safety of such a strategy compared with fixed thresholds which is the current standard of care from international consensus guidelines.Methods and analysisCPPOpt Guided Therapy: Assessment of Target Effectiveness (COGiTATE) is a prospective, multicentre, non-blinded randomised, controlled trial coordinated from Maastricht University Medical Center, Maastricht (The Netherlands). The other original participating centres are Cambridge University NHS Foundation Trust, Cambridge (UK), and University Hospitals Leuven, Leuven (Belgium). Adult severe TBI patients requiring intracranial pressure monitoring are randomised within the first 24 hours of admission in neurocritical care unit. For the control arm, the CPP target is the Brain Trauma Foundation guidelines target (60–70 mm Hg); for the intervention group an automated CPP target is provided as the CPP at which the patient’s cerebrovascular reactivity is best preserved (CPPopt). For a maximum of 5 days, attending clinicians review the CPP target 4-hourly. The main hypothesis of COGiTATE are: (1) in the intervention group the percentage of the monitored time with measured CPP within a range of 5 mm Hg above or below CPPopt will reach 36%; (2) the difference in between groups in daily therapy intensity level score will be lower or equal to 3.Ethics and disseminationEthical approval has been obtained for each participating centre. The results will be presented at international scientific conferences and in peer-reviewed journals.Trial registration numberNCT02982122

IntroductionChildren and young people (CYP) in many high-income settings have poor healthcare outcomes, especially those with long-term conditions (LTCs). Emergency and outpatient hospital service use is increasing unsustainably. To address these problems, the Children and Young People’s Health Partnership (CYPHP) has developed and is evaluating an integrated model of care as part of a health systems strengthening programme across two boroughs of London, UK that are characterised by mixed ethnic populations and varying levels of deprivation. The CYPHP Evelina London model of care comprises proactive case-finding and triage, specialist clinics and transformative education and training for professionals working with CYP. Services are delivered by multidisciplinary health teams with an emphasis on increased coordination across primary, community and hospital settings and integration of physical and mental healthcare that accounts for the CYP’s social context.Methods and analysisThe phased roll out of the CYPHP Evelina London model allows an opportunistic population-based evaluation using a cluster randomised controlled trial design. Seventy general practices across two London boroughs, grouped into 23 clusters, were randomised to provide either the CYPHP model of care (n=11) or enhanced usual care (n=12).The evaluation will measure the impact of the CYPHP Evelina London model of care on child and parent health and well-being, healthcare quality and health service use up to 2 years postimplementation. A population-level evaluation will use routinely collected pseudonymised healthcare data to conduct a service-use analysis for all CYP registered with a participating general practice (n=~90 000) with the rate of non-elective admissions as the primary outcome. We will seek consent from a subset of this population, with specific conditions (target n=2138) to assess the impact on patient-reported outcomes using the Paediatric Quality of Life Inventory (PedsQL) and Warwick-Edinburgh Mental Well-Being Scale (WEBWMS) as, respectively, the child- and parent-related primary outcomes.Ethics and disseminationEthics approval obtained from South West-Cornwall & Plymouth Research Ethics Committee. Results will be submitted for publication in peer-reviewed journals. Findings will be generalisable to community-based models of care, especially in urban settings. Our process evaluation will identify barriers and enablers of implementation and delivery of care salient to the context and condition.Trial registration numberNCT03461848; Pre-results.

Introduction Childhood obesity is a public health challenge. There is evidence for associations between parentsâ feeding behaviours and childhood obesity risk. Primary care provides a unique opportunity for delivery of infant feeding interventions for childhood obesity prevention. Implementation strategies are needed to support infant feeding intervention delivery. The Choosing Healthy Eating for Infant Health (CHErIsH) intervention is a complex infant feeding intervention delivered at infant vaccination visits, alongside a healthcare professional (HCP)-level implementation strategy to support delivery.Methods and analysis This protocol provides a description of a non-randomised feasibility study of an infant feeding intervention and implementation strategy, with an embedded process evaluation and economic evaluation. Intervention participants will be parents of infants aged â ¤6 weeks at recruitment, attending a participating HCP in a primary care practice. The intervention will be delivered at the infantâ s 2, 4, 6, 12 and 13â month vaccination visits and involves brief verbal infant feeding messages and additional resources, including a leaflet, magnet, infant bib and sign-posting to an information website. The implementation strategy encompasses a local opinion leader, HCP training delivered prior to intervention delivery, electronic delivery prompts and additional resources, including a training manual, poster and support from the research team. An embedded mixed-methods process evaluation will examine the acceptability and feasibility of the intervention, the implementation strategy and study processes including data collection. Qualitative interviews will explore parent and HCP experiences and perspectives of delivery and receipt of the intervention and implementation strategy. Self-report surveys will examine fidelity of delivery and receipt, and acceptability, suitability and comprehensiveness of the intervention, implementation strategy and study processes. Data from electronic delivery prompts will also be collected to examine implementation of the intervention. A costâ outcome description will be conducted to measure costs of the intervention and the implementation strategy.Ethics and dissemination This study received approval from the Clinical Research Ethics Committee of the Cork Teaching Hospitals. Study findings will be disseminated via peer-reviewed publications and conference presentations. The authors would like to thank Charlotte Griffin, Lisa Delaney and Jennifer Cooney who worked as research assistants on this project. We would like to thank the staff at the Mallow Primary Healthcare Centre, in particular Ms Ruth Haugh, Mr Carl Beame and Mr Conor Healy. We would like to thank Dr Phil Jennings and Ms Anne Pardy from the HSE National Healthy Childhood Programme, and Ms Joanne O Halloran from the HSE for their assistance in development and refinement of the infant feeding messages. We would like to thank Holly McGrath for her graphic design work on the intervention materials. We would also like to thank all the attendees of the 2018 CHErIsH Steering Committee meeting for their feedback and input on the project. peer-reviewed

IntroductionSurvival after stroke is improving, leading to increased demand on primary care and community services to meet the long-term care needs of people living with stroke. No formal primary care-based holistic model of care with clinical trial evidence exists to support stroke survivors living in the community, and stroke survivors report that many of their needs are not being met. We have developed a multifactorial primary care model to address these longer term needs. We aim to evaluate the clinical and cost-effectiveness of this new model of primary care for stroke survivors compared with standard care.Methods and analysisImproving Primary Care After Stroke (IPCAS) is a two-arm cluster-randomised controlled trial with general practice as the unit of randomisation. People on the stroke registers of general practices will be invited to participate. One arm will receive the IPCAS model of care including a structured review using a checklist; a self-management programme; enhanced communication pathways between primary care and specialist services; and direct point of contact for patients. The other arm will receive usual care. We aim to recruit 920 people with stroke registered with 46 general practices. The primary endpoint is two subscales (emotion and handicap) of the Stroke Impact Scale (SIS) as coprimary outcomes at 12 months (adjusted for baseline). Secondary outcomes include: SIS Short Form, EuroQol EQ-5D-5L, ICEpop CAPability measure for Adults, Southampton Stroke Self-management Questionnaire, Health Literacy Questionnaire and medication use. Cost-effectiveness of the new model will be determined in a within-trial economic evaluation.Ethics and disseminationFavourable ethical opinion was gained from Yorkshire and the Humber-Bradford Leeds NHS Research Ethics Committee. Approval to start was given by the Health Research Authority prior to recruitment of participants at any NHS site. Data will be presented at national and international conferences and published in peer-reviewed journals. Patient and public involvement helped develop the dissemination plan.Trial registration numberNCT03353519

IntroductionPatient and staff experiences are strongly influenced by attitudes and behaviours, and provide important insights into care quality. Patient and staff feedback could be used more effectively to enhance behaviours and improve care through systematic integration with techniques for reflective learning. We aim to develop a reflective learning framework and toolkit for healthcare staff to improve patient, family and staff experience.Methods & analysisLocal project teams including staff and patients from the acute medical units (AMUs) and intensive care units (ICUs) of three National Health Service trusts will implement two experience surveys derived from existing instruments: a continuous patient and relative survey and an annual staff survey. Survey data will be supplemented by ethnographic interviews and observations in the workplace to evaluate barriers to and facilitators of reflective learning. Using facilitated iterative co-design, local project teams will supplement survey data with their experiences of healthcare to identify events, actions, activities and interventions which promote personal insight and empathy through reflective learning. Outputs will be collated by the central project team to develop a reflective learning framework and toolkit which will be fed back to the local groups for review, refinement and piloting. The development process will be mapped to a conceptual theory of reflective learning which combines psychological and pedagogical theories of learning, alongside theories of behaviour change based on capability, opportunity and motivation influencing behaviour. The output will be a locally-adaptable workplace-based toolkit providing guidance on using reflective learning to incorporate patient and staff experience in routine clinical activities.Ethics & disseminationThe PEARL project has received ethics approval from the London Brent Research Ethics Committee (REC Ref 16/LO/224). We propose a national cluster randomised step-wedge trial of the toolkit developed for large-scale evaluation of impact on patient outcomes.

IntroductionUnderstanding the impact of cancer and its treatment on people’s everyday lives will help prepare people for what to expect, enable health professionals to predict likely recovery trajectories and shape care management according to needs. HORIZONS will recruit people awaiting treatment and follow them up at regular intervals to assess recovery of health and well-being.Research questionsWhat impact does cancer diagnosis and treatment have on people’s lives in the short, medium and long term? What are people’s health and well-being outcomes, experiences and self-management activities over time across different cancer types and what influences these? How do people connect with and relate to others in mobilising resources that enable them to self-manage the consequences of cancer and treatment?Methods and analysisHORIZONS is a multicentre, prospective cohort study exploring recovery of health and well-being in 3000 people diagnosed with breast cancer (Ethics and disseminationEthics and Health Research Authority approvals granted (IRAS Project ID: 202342, REC reference number 16/NW/0425). Adopted onto the National Institute for Health Research Clinical Research Network portfolio. We will engage with our Scientific Advisory Board, Tumour Specific Expert Panels, User Reference Group, Macmillan and the University of Southampton to ensure maximum publicity and benefit.

IntroductionArteriovenous fistulas (AVFs) are considered the best and safest modality for providing haemodialysis in patients with end-stage renal disease. Only 20% of UK centres achieve the recommended 80% target for achieving dialysis of the prevalent dialysis population via permanent access (as opposed to a central venous catheter). This is partly due to the relatively poor maturation rate of newly created fistulas, with as many as 50% of fistulas failing to mature.The Surveillance Of arterioveNous fistulAe using ultRasound study will examine whether a protocolised programme of Doppler ultrasound (US) surveillance can identify, early after creation, potentially correctable problems in those AVFs that subsequently fail to mature.Methods and analysisThis is a multicentre observational study that will assess newly created AVFs by Doppler US performed at 2, 4, 6 and 10 weeks after creation. The primary outcome measure will be primary fistula patency at week 10. Secondary outcome measures include: successful use of the fistula; clinical suitability for dialysis; creation of new fistula or radiological salvage; fistula thrombosis; secondary fistula patency rate and patient acceptability.Ethics and disseminationThe study has been approved by the Cambridgeshire and Hertfordshire Research Ethics Committee and by the Health Research Authority (REC 18/EE/0234). The results generated from this work will be published as open access, within 3 years of trial commencement. We will also present our findings at key national/international renal meetings, as well as support volunteers at renal patient groups to disseminate the trial outcome.Trial registration numberISRCTN36033877

IntroductionCurrently, all people with diabetes (PWD) aged 12 years and over in the UK are invited for screening for diabetic retinopathy (DR) annually. Resources are not increasing despite a 5% increase in the numbers of PWD nationwide each year. We describe the rationale, design and methodology for a randomised controlled trial (RCT) evaluating the safety, acceptability and cost-effectiveness of personalised variable-interval risk-based screening for DR. This is the first randomised trial of personalised screening for DR and the largest ophthalmic RCT in the UK.Methods and analysisPWD attending seven screening clinics in the Liverpool Diabetic Eye Screening Programme were recruited into a single site RCT with a 1:1 allocation to individualised risk-based variable-interval or annual screening intervals. A risk calculation engine developed for the trial estimates the probability that an individual will develop referable disease (screen positive DR) within the next 6, 12 or 24 months using demographic, retinopathy and systemic risk factor data from primary care and screening programme records. Dynamic, secure, real-time data connections have been developed. The primary outcome is attendance for follow-up screening. We will test for equivalence in attendance rates between the two arms. Secondary outcomes are rates and severity of DR, visual outcomes, cost-effectiveness and health-related quality of life. The required sample size was 4460 PWD. Recruitment is complete, and the trial is in follow-up.Ethics and disseminationEthical approval was obtained from National Research Ethics Service Committee North West – Preston, reference 14/NW/0034. Results will be presented at international meetings and published in peer-reviewed journals. This pragmatic RCT will inform screening policy in the UK and elsewhere.Trial registration numberISRCTN87561257; Pre-results.

IntroductionChou-Ling-Dan (CLD) (Laggerapterodonta) granules are an ethnic herbal medicine from Yunnan province of China. CLD granules have been used for the treatment of inflammatory conditions and feverish diseases in China, including seasonal influenza, but few evidence-based medicine (EBM) clinical studies have been conducted to assess its efficacy and safety in the treatment of influenza. Here, we performed an EBM clinical trial combining Western Chinese medicine and traditional Chinese medicine (TCM) evaluation systems to evaluate the efficacy and safety of CLD granules in the treatment of seasonal influenza.Methods and analysisThe study is designed as a multicentre, randomised, double-blinded, double-simulation, oseltamivir-controlled and placebo-controlled, parallel-design clinical trial. Eligible subjects (n=318) will be allocated after satisfying the criteria (Western medicine). Subjects will be randomised to receive CLD granules, oseltamivir, or a placebo for 5 days of treatment and with follow-up after treatment to record symptoms and signs and to collect pharyngeal/throat swabs and serum samples for detecting the virus and antibodies. At the same time, the syndrome differentiation criteria of TCM, such as tongue body, furred tongue and type of pulse, will be recorded as determined by doctors of both Western and Chinese medicine. Participants will be instructed to comply with the protocol and to keep a daily record of symptoms. The primary and secondary outcomes and safety indicators will be used to evaluate the efficacy and safety of CLD granules in the treatment of seasonal influenza based on both Western Chinese medicine and TCM evaluation systems.Ethics and disseminationThe CLD granules clinical trial will be conducted in accordance with the Declaration of Helsinki and Good Clinical Practice and has been approved by the Ethics Committee of the First Affiliated Hospital of Guangzhou Medical University. All participants must provide written informed consent. The results obtained will be disseminated at international medical conferences and in peer-reviewed publications.Trial registration numberNCT02662426; Pre-results.

IntroductionImmune reconstitution after haematopoietic stem cell transplantation (HSCT) is a complex and dynamic process, varying from a state of nearly complete immunosuppression to an expected full immune recovery. Specific vaccination guidelines recommend reimmunisation after HSCT but data regarding vaccine efficacy in this unique population are scarce. New immune functional assays could enable prediction of vaccine response in the setting of HSCT.Methods and analysisA prospective, longitudinal single-centre cohort study of autologous and allogeneic HSCT recipients was designed in order to determine the vaccine response to five vaccine targets (pneumococcus, hepatitis B virus,Haemophilus Influenzaetype b, tetanus and diphtheria) and to correlate it to immune function parameters. A workflow was set up to study serological response to vaccines and to describe the functional immune status of 100 HSCT recipients (50 autologous and 50 allogeneic) before and 3, 12 and 24 months after primary immunisation. At each time point, ‘basic’ immune status recording (serology, immunophenotyping of lymphocyte subsets by flow cytometry) will be assessed. The immune response will furthermore be evaluated before and 3 months after primary vaccination by two ex vivo immune functional assays assessing: (1) tumour necrosis factor alpha, interferon gamma production and host messenger RNA expression on whole-blood stimulation by lipopolysaccharide orStaphylococcus aureusenterotoxin B and (2) T-lymphocyte proliferation in response to a standard mitogen (phytohaemagglutinin) or to selected recall antigens. Reference intervals will be determined from a cohort of 30 healthy volunteers. This translational study will provide data describing vaccine response, immune functionality of HSCT recipients over time and will allow mapping HSCT recipients with regard to their immune function.Ethics and disseminationEthical approval has been obtained from the institutional review board (no 69HCL17_0769). Results will be communicated at scientific meetings and submitted for publication in peer-reviewed journals.Trial registration numberNCT03659773; Pre-results.

IntroductionChronic obstructive pulmonary disease (COPD) is a progressive lung disease associated with breathlessness, inability to exercise, frequent infections, hospitalisation and reduced quality of life. Pulmonary rehabilitation (PR), providing supervised exercise and education, is an effective and cost-effective treatment for COPD but is significantly underused. Interventions to improve referral and uptake have been tested and some positive results reported. However, interventions are diverse and no clear recommendations for practice can be made. This study aims to understand the challenges to referral and uptake in primary care, where most referrals originate, and to develop a flexible toolkit of resources to support referral and uptake to PR in primary care in the UK.Methods and analysisThis is a mixed methods study informed by normalisation process theory and burden of treatment theory. In the first phase, general practitioners, practice nurses and PR providers will be invited to complete an online survey to inform a broad exploration of the topic areas. In phase 2 interviews and focus groups will be conducted with patients, healthcare professionals (HCP) in primary care, PR providers and commissioners to gain an in-depth understanding of the issues and needs. Toolkit development in phase 3 will draw together the learning from phases 1 and 2 and employ an iterative development process to build the toolkit jointly with patients and HCPs. It will be tested in primary care for usability and acceptability.Ethics and disseminationThe study has ethical and Health Research Authority approval (Research Ethics Committee reference number 17/EE/0136). It is registered with the International Standard Registered Clinical/Social Study Number (ISRCTN) registry (trial ID:ISRCTN20669629, assignment date 20 March 2018, trial start date 1 April 2016). Dissemination will be aimed at patients, carers/families, service providers, commissioners and national interest groups. Methods will include conferences, presentations, academic publications and plain English reports and will be supported by the British Lung Foundation.Trial registration numberISRCTN20669629; Pre-results.

BMJ Open, 9 (1), ISSN:2044-6055

Introduction: Although a great majority of patients with cervical radiculopathy syndrome can successfully be treated non-operatively, a considerable proportion experience persistent symptoms, severe enough to require neurosurgical intervention. During the past decade, cervical spine procedures have increasingly been performed on an outpatient basis and retrospective database analyses have shown this to be feasible and safe. However, there are no randomised controlled studies comparing outpatient care with inpatient care, particularly with emphasis on the patients’ perception of symptom relief and their ability to return to normal daily activities and work. Methods and analysis: This is a prospective, randomised, controlled, parallel group non-inferiority trial comparing the traditional hospital surveillance (inpatient, patients staying in the hospital for 1–3 nights after surgery) with outpatient care (discharge on the day of the surgery, usually within 6–8 hours after procedure) in patients who have undergone anterior cervical decompression and fusion procedure. To determine whether early discharge (outpatient care) is non-inferior to inpatient care, we will randomise 104 patients to these two groups and follow them for 6 months using the Neck Disability Index (NDI) as the primary outcome. We expect that early discharge is not significantly worse than the current care in terms of change in NDI. Non-inferiority will be declared if the mean improvement for outpatient care is no worse than the mean improvement for inpatient care, by a margin of 17.3%. We hypothesise that a shorter hospital stay results in more rapid return to normal daily activities, shorter duration of sick leave and decreased secondary costs to healthcare system. Secondary outcomes in our study are arm pain and neck pain using the Numeric Rating Scale, operative success (Odom’s criteria), patient’s satisfaction to treatment, general quality of life (EQ-5D-5L), Work Ability Score, sickness absence days, return to previous leisure activities and complications. Ethics and dissemination: The study was approved by the institutional review board of the Helsinki and Uusimaa Hospital District on 6 June 2019 (1540/2019) and duly registered at ClinicalTrials.gov. We will disseminate the findings of this study through peer-reviewed publications and conference presentations.

IntroductionIn previous studies, it is estimated that sexual minorities (eg, lesbian, gay, bisexual, transgender and questioning (LGBTQ) individuals) are overrepresented in the child welfare system. However, the numbers are unclear, and there are limited studies in this field. No systematic review of LGBTQ issues across a broader context (ie, youth, foster parents and service providers) of child welfare services exists. The overall objective of this scoping review is to systematically scope the existing research on LGBTQ issues in the context of child welfare services, including policy, practice, service providers and users’ perspectives.Methods and analysisThe scoping review framework outlined by the Joanna Briggs Institute (JBI) based on previous work by Arksey and O’Malley and Levac and colleagues will guide this review. In addition, the PRISMA Extension for Scoping Reviews (PRISMA-ScR): Checklist and Explanation will be used throughout the process. We will search electronic databases (PubMed, EMBASE, PsycINFO, Web of Science and Idunn) and grey literature sources to identify studies that are appropriate for inclusion in this review. Using inclusion and exclusion criteria based on the ‘Population–Concept–Context’ framework, two researchers will independently screen titles, abstracts and full-text articles considered for inclusion. Any qualitative, quantitative and mixed-method study of LGBTQ issues in the child welfare context will be described and synthesised using a thematic synthesis approach.Ethics and disseminationA scoping review is a secondary analysis of published literature and does not require ethics approval. This scoping review is meant to provide an overview of the existing literature, aiming to expand policy-makers’ and practitioners’ knowledge of LGBTQ issues in a child welfare context and identify research gaps that can be used as a basis for further research. The results will be disseminated through a peer-reviewed publication, a conference presentation and a presentation to the key stakeholders.

AimsThere has been a paradigm shift proposing that comorbidities are a major contributor towards the heart failure with preserved ejection fraction (HFpEF) syndrome. Furthermore, HFpEF patients have abnormal macrovascular and microvascular function, which may significantly contribute towards altered ventricular-vascular coupling in these patients. The IDENTIFY-HF study will investigate whether gradually increased arterial stiffness (in addition to ageing) as a result of increasing common comorbidities, such as hypertension and diabetes, is associated with HFpEF.Methods and analysisIn our observational study, arterial compliance and microvascular function will be assessed in five groups (Groups A to E) of age, sex and body mass index matched subjects (age ≥70 years in all groups):Group A; normal healthy volunteers without major comorbidities such as hypertension and diabetes mellitus (control). Group B; patients with hypertension without diabetes mellitus or heart failure (HF). Group C; patients with hypertension and diabetes mellitus without HF. Group D; patients with HFpEF. Group E; patients with heart failure and reduced ejection fraction (parallel group). Vascular function and arterial compliance will be assessed using pulse wave velocity, as the primary outcome measure. Further outcome measures include cutaneous laser Doppler flowmetry as a measure of endothelial function, transthoracic echocardiography and exercise tolerance measures. Biomarkers include NT-proBNP, high-sensitivity troponin T, as well as serum galectin-3 as a marker of fibrosis.Ethics and disseminationThe study was approved by the regional research ethics committee (REC), West Midland and Black Country 17/WM/0039, UK, and permission to conduct the study in the hospital was also obtained from the RDI, UHCW NHS Trust. The results will be published in peer-reviewed journals and presented in local, national and international medical society meetings.Trial registration numberNCT03186833

IntroductionWe describe the protocol for a project that will use linkage of routinely collected NHS data to answer a question about the nature and effectiveness of liaison psychiatry services in acute hospitals in England.Methods and analysisThe project will use three data sources: (1) Hospital Episode Statistics (HES), a database controlled by NHS Digital that contains patient data relating to emergency department (ED), inpatient and outpatient episodes at hospitals in England; (2) ResearchOne, a research database controlled by The Phoenix Partnership (TPP) that contains patient data relating to primary care provided by organisations using the SystmOne clinical information system and (3) clinical databases controlled by mental health trusts that contain patient data relating to care provided by liaison psychiatry services. We will link patient data from these sources to construct care pathways for patients who have been admitted to a particular hospital and determine those patients who have been seen by a liaison psychiatry service during their admission.Patient care pathways will form the basis of a matched cohort design to test the effectiveness of liaison intervention. We will combine healthcare utilisation within care pathways using cost figures from national databases. We will compare the cost of each care pathway and the impact of a broad set of health-related outcomes to obtain preliminary estimates of cost-effectiveness for liaison psychiatry services. We will carry out an exploratory incremental cost-effectiveness analysis from a whole system perspective.Ethics and disseminationIndividual patient consent will not be feasible for this study. Favourable ethical opinion has been obtained from the NHS Research Ethics Committee (North of Scotland) (REF: 16/NS/0025) for Work Stream 2 (phase 1) of the Liaison psychiatry—measurement and evaluation of service types, referral patterns and outcomes study. The Confidentiality Advisory Group at the Health Research Authority determined that Section 251 approval under Regulation 5 of the Health Service (Control of Patient Information) Regulations 2002 was not required for the study ‘on the basis that there is no disclosure of patient identifiable data without consent’ (REF: 16/CAG/0037).Results of the study will be published in academic journals in health services research and mental health. Details of the study methodology will also be published in an academic journal. Discussion papers will be authored for health service commissioners.

Introduction: Behavioural and mental disorders have become a public health crisis and by 2020 may surpass physical illness as a major cause of disability. Early prevention is key. Two Incredible Years (IY) parent programmes that aim to enhance child well-being and development, IY Infant and IY Toddler, will be delivered and evaluated in a proportionate universal intervention model called Enhancing Social-Emotional Health and Wellbeing in the Early Years (E-SEE) Steps. The main research question is: Does E-SEE Steps enhance child social emotional well-being at 20 months when compared with services as usual? Methods and analysis: E-SEE Steps will be delivered in community settings by Early Years Children’s Services and/ or Public Health staff across local authorities. Parents of children aged 8 weeks or less, identified by health visitors, children’s centre staff or self-referral, are eligible for participation in the trial. The randomisation allocation ratio is 5:1 (intervention to control). All intervention parents will receive an Incredible Years Infant book (universal level), and may be offered the Infant and/or Toddler group-based programme/s—based on parent depression scores on the Patient Health Questionnaire or child social emotional well-being scores on the Ages and Stages Questionnaire: Social Emotional, Second Edition (ASQ:SE-2). Control group parents will receive services as usual. A process and economic evaluation are included. The primary outcome for the study is social emotional well-being, assessed at 20 months, using the ASQ:SE-2. Intention-to-treat and per protocol analyses will be conducted. Clustering and hierarchical effects will be accounted for using linear mixed models. Ethics and dissemination: Ethical approvals have been obtained from the University of York Education Ethics Committee (ref: FC15/03, 10 August 2015) and UK NHS REC 5 (ref: 15/WA/0178, 22 May 2015. The current protocol is Version 9, 26 February 2018. The sponsor of the trial is the University of York. Dissemination of findings will be via peer-reviewed journals, conference presentations and public events. Trial registration number ISRCTN11079129; Pre-results.

BACKGROUND: The course of Crohn's disease (CD) varies substantially between individuals, but reliable prognostic markers do not exist. This hinders disease management because patients with aggressive disease are undertreated by conventional 'step-up' therapy (in which treatment is gradually escalated in response to refractory or relapsing disease) while those with more indolent disease would be exposed to unnecessary treatment-related toxicity if a more aggressive 'top-down' approach was indiscriminately used. The Predicting outcomes for Crohn's disease using a molecular biomarker trial will assess whether a prognostic transcriptional biomarker, that we have developed and validated, can improve clinical outcomes by facilitating personalised therapy in CD. This represents the first the biomarker-stratified trial in inflammatory bowel disease. METHODS AND ANALYSIS: This biomarker-stratified trial will compare the relative efficacy of 'top-down' and 'accelerated step-up' therapy between biomarker-defined subgroups of patients with newly diagnosed CD. 400 participants from ~50 UK centres will be recruited. Subjects within each biomarker subgroup (IBDhi or IBDlo) will be randomised (1:1) to receive one of the treatment strategies until trial completion (48 weeks). The primary outcome is the incidence of sustained surgery and steroid-free remission from the completion of induction treatment through to week 48. Secondary outcomes include mucosal healing, quality-of-life assessments and surrogate measures of disease burden including number of flares, cumulative steroid exposure, number of hospital admissions and number of Crohn's-related surgeries (assessed hierarchically). Analyses will compare the relative benefit of the treatment strategies in each biomarker-defined subgroup, powered as an interaction analysis, to determine whether the biomarker can accurately match patients to the most appropriate therapy. ETHICS AND DISSEMINATION: Ethical approval has been obtained and recruitment is under way at sites around the UK. Following trial completion and data analysis, the results of the trial will be submitted for publication in peer-reviewed journals and presented at international conferences. TRIAL REGISTRATION NUMBER: ISRCTN11808228; Pre-results.

IntroductionAs rapid urbanisation transforms the sociodemographic structures within cities, standard survey methods, which have remained unchanged for many years, under-represent the urban poorest. This leads to an overly positive picture of urban health, distorting appropriate allocation of resources between rural and urban and within urban areas. Here, we present a protocol for our study which (i) tests novel methods to improve representation of urban populations in household surveys and measure mental health and injuries, (ii) explores urban poverty and compares measures of poverty and ‘slumness’ and (iii) works with city authorities to understand, and potentially improve, utilisation of data on urban health for planning more equitable services.Methods and analysisWe will conduct household surveys in Kathmandu, Hanoi and Dhaka to test novel methods: (i) gridded population sampling; (ii) enumeration using open-access online maps and (iii) one-stage versus two-stage cluster sampling. We will test reliability of an observational tool to categorise neighbourhoods as slum areas. Within the survey, we will assess the appropriateness of a short set of questions to measure depression and injuries. Questionnaire data will also be used to compare asset-based, consumption-based and income-based measures of poverty. Participatory methods will identify perceptions of wealth in two communities in each city. The analysis will combine quantitative and qualitative findings to recommend appropriate measures of poverty in urban areas. We will conduct qualitative interviews and establish communities of practice with government staff in each city on use of data for planning. Framework approach will be used to analyse qualitative data allowing comparison across city settings.Ethics and disseminationEthical approvals have been granted by ethics committees from the UK, Nepal, Bangladesh and Vietnam. Findings will be disseminated through conference papers, peer-reviewed open access articles and workshops with policy-makers and survey experts in Kathmandu, Hanoi and Dhaka.