Duncan Appelbe

Predicting Risk of Serious Bacterial Infections in Febrile Children in the Emergency Department

Multinomial regression is used to model the risk of SBIs in febrile children in the ED. BACKGROUND: Improving the diagnosis of serious bacterial infections (SBIs) in the children’s emergency department is a clinical priority. Early recognition reduces morbidity and mortality, and supporting clinicians in ruling out SBIs may limit unnecessary admissions and antibiotic use. METHODS: A prospective, diagnostic accuracy study of clinical and biomarker variables in the diagnosis of SBIs (pneumonia or other SBI) in febrile children <16 years old. A diagnostic model was derived by using multinomial logistic regression and internally validated. External validation of a published model was undertaken, followed by model updating and extension by the inclusion of procalcitonin and resistin. RESULTS: There were 1101 children studied, of whom 264 had an SBI. A diagnostic model discriminated well between pneumonia and no SBI (concordance statistic 0.84, 95% confidence interval 0.78–0.90) and between other SBIs and no SBI (0.77, 95% confidence interval 0.71–0.83) on internal validation. A published model discriminated well on external validation. Model updating yielded good calibration with good performance at both high-risk (positive likelihood ratios: 6.46 and 5.13 for pneumonia and other SBI, respectively) and low-risk (negative likelihood ratios: 0.16 and 0.13, respectively) thresholds. Extending the model with procalcitonin and resistin yielded improvements in discrimination. CONCLUSIONS: Diagnostic models discriminated well between pneumonia, other SBIs, and no SBI in febrile children in the emergency department. Improvements in the classification of nonevents have the potential to reduce unnecessary hospital admissions and improve antibiotic prescribing. The benefits of this improved risk prediction should be further evaluated in robust impact studies.

Development of an internationally agreed minimal dataset for juvenile dermatomyositis (JDM) for clinical and research use

BackgroundJuvenile dermatomyositis (JDM) is a rare autoimmune inflammatory disorder associated with significant morbidity and mortality. International collaboration is necessary to better understand the pathogenesis of the disease, response to treatment and long-term outcome. To aid international collaboration, it is essential to have a core set of data that all researchers and clinicians collect in a standardised way for clinical purposes and for research. This should include demographic details, diagnostic data and measures of disease activity, investigations and treatment. Variables in existing clinical registries have been compared to produce a provisional data set for JDM. We now aim to develop this into a consensus-approved minimum core dataset, tested in a wider setting, with the objective of achieving international agreement.Methods/DesignA two-stage bespoke Delphi-process will engage the opinion of a large number of key stakeholders through Email distribution via established international paediatric rheumatology and myositis organisations. This, together with a formalised patient/parent participation process will help inform a consensus meeting of international experts that will utilise a nominal group technique (NGT). The resulting proposed minimal dataset will be tested for feasibility within existing database infrastructures. The developed minimal dataset will be sent to all internationally representative collaborators for final comment. The participants of the expert consensus group will be asked to draw together these comments, ratify and ‘sign off’ the final minimal dataset.DiscussionAn internationally agreed minimal dataset has the potential to significantly enhance collaboration, allow effective communication between groups, provide a minimal standard of care and enable analysis of the largest possible number of JDM patients to provide a greater understanding of this disease. The final approved minimum core dataset could be rapidly incorporated into national and international collaborative efforts, including existing prospective databases, and be available for use in randomised controlled trials and for treatment/protocol comparisons in cohort studies.

Protocol for an online randomised controlled trial to evaluate the clinical and cost-effectiveness of a peer-supported self-management intervention for relatives of people with psychosis or bipolar disorder: Relatives Education And Coping Toolkit (REACT)

Introduction Despite clinical guidelines recommendations, many relatives of people with psychosis or bipolar disorder do not currently receive the support they need. Online information and support may offer a solution. Methods and analysis This single-blind, parallel, online randomised controlled trial will determine clinical and cost-effectiveness of the Relatives Education And Coping Toolkit (REACT) (including an online resource directory (RD)), compared with RD only, for relatives of people with psychosis or bipolar disorder. Both groups continue to receive treatment as usual. Independent, web-based variable, block, individual randomisation will be used across 666 relatives. Primary outcome is distress at 24 weeks (measured by General Health Questionnaire; GHQ-28) compared between groups using analysis of covariance, adjusting for baseline score. Secondary clinical outcomes are carer well-being and support. Cost-effectiveness analysis will determine cost of a significant unit change (three-point reduction) in the GHQ-28. Costs include offering and supporting the intervention in the REACT arm, relevant healthcare care costs including health professional contacts, medications prescribed and time off (or ability to) work for the relative. Cost utility analysis will be calculated as the marginal cost of changes in quality-adjusted life years, based on EuroQol. We will explore relatives’ beliefs, perceived coping and amount of REACT toolkit use as possible outcome mediators. We have embedded two methodological substudies in the protocol to determine the relative effectiveness of a low-value (£10) versus higher value (£20) incentive, and an unconditional versus conditional incentive, on improving follow-up rates. Ethics and dissemination The trial has ethical approval from Lancaster National Research Ethics Service (NRES)Committee (15/NW/0732) and is overseen by an independent Data Monitoring and Ethics Committee and Trial Steering Committee. Protocol version 1.5 was approved on 9 January 2017. All updates to protocols are uploaded to the National Institute for Health Research (NIHR) Journals Library. A full statistical analysis plan is available at https://figshare.com/account/home#/projects/19975. Publications will be in peer-reviewed journals (open access wherever possible). Requests for access to the data at the end of the study will be reviewed and granted where appropriate by the Trial Management Group. Trial registration number ISRCTN72019945, pre-results.

Introducing personalised risk based intervals in screening for diabetic retinopathy: development, implementation and assessment of safety, cost-effectiveness and patient experience (ISDR): a case study in the use of automated systems in trials

ISDR is a 5 year NIHR funded programme of applied research aiming to introduce a step-change in screening for sight threatening diabetic retinopathy utilising personalised risk based intervals. The research programme includes a Randomised Controlled Trial (RCT) to assess the validity of these intervals. The RCT aims to recruit 4400 participants from a pool of 18,000 subjects in Liverpool. Due to the size of the cohort and that much of the data required for the study is collected routinely in multiple NHS organisations, the RCT relies heavily on the integration of multiple databases/data sources and automated systems across multiple networks to reduce the workload on the study team and medical practitioners and to maintain data quality. Data for the RCT is obtained from the following systems: EMIS Web (GP Data), OptoMize (screening software provided by Digital Healthcare), OpenClinica (study database), randomisation system (bespoke system), risk engine (a bespoke application to calculate personalised screening intervals) and a record of those subjects who have consented for their data to be used by the ISDR programme. This paper will present the processes and solutions undertaken to automate, test and validate the import/export of data, create bespoke systems to clean these data and integrate the different data sources. Thereby ensuring the timely transfer and format of data minimise the disruption to patient care while ensuring integrity of the trials data. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health.

OTU-028 Benchmarking of activity, process and outcome of emergency admission for ulcerative colitis across english hospitals

Introduction The UK IBD Registry aims to make information work better for patients, clinical teams and the NHS. As part of the benchmarking reports provided to participating Trusts, we have developed organisational level metrics from routinely collected hospital episode statistics (HES) data – working with front-line teams to iteratively develop reports with feedback on content and local face-validity. We report national-level findings and institutional variation in activity, process and outcome of emergency care for UC. Methods Admitted patient care data for English hospitals were analysed, identifying all-cause admissions for patients with UC and constructing algorithms to identify emergency activity, track process and outcome for UC-specific emergency admissions (UC-Em-Ad), including in-hospital death (I-H-D) and emergency surgery (Em-Surg), all-cause 30 day readmission (30D-RA) and twelve month outcome. Reports containing 5 year national and local trends and cumulative 5 year performance were distributed to sites in Dec 2017. This analysis summarises selected data for 133 Trusts present in all fiscal years (11/12 to 15/16). Results Nationally, there were 31,371 UC-Em-Ad (2 65 799 bed days; median LoS 6 days; 22 809 patients; mean age 40 years; male 50%; additional coded co-morbidities in 23%) with 1451 Em-Surg (4.62%=crude surgery rate; mean age 44 years; male 56.1%), 324 I-H-D (1.03%=crude mortality rate; mean age 76 years; 67% had additional coded co-morbidities; only 16% of deaths were post-surgery), 4916 30D-RA (15.7%=crude readmission rate). At Trust level, mean (95% limits) for indirectly standardised rates were: I-H-D 1.03% (0.90%–1.15%), Em-Surg 4.79% (4.31%–5.27%), 30D-RA 15.55% (15.0%–16.1%). Few outliers were identified and none consistently over time, with no significant trends identified for volume-outcome relationships. Funnel plots and regression analyses will be presented. Conclusions These data provide real-world insights into processes and outcomes of emergency care for UC across England in the last five years, with a series of metrics to support both national and local quality improvement efforts. Linkages between HES and local Registry data offers potential to validate, refine and extend these benchmarking metrics. Funding Crohn’s and Colitis UK.

A software program to assist coding of prelinguistic vocalizations in real time

ABSTRACT Numerous studies have confirmed that prelinguistic utterances are precursors to speech, and there is ample evidence that, for example, frequency of canonical syllables and syllable inventory size correlate with speech and language measures at older ages. Traditionally, prelinguistic utterances have been assessed by phonetic transcription which is difficult and time-consuming in infants. Recently, a more time-efficient methodology to assess prelinguistic utterances in real time, called naturalistic listening, was developed (Ramsdell et al., 2012). In a large international NIDCR-funded randomized controlled trial, Timing of Primary Surgery for with Cleft Palate (TOPS), including many coders, a software program (TimeStamper) was developed to assist in coding of prelinguistic vocalizations in real time, to ensure consistency of the coding procedures. Coders upload a video (or audio) file and watch and listen to the recording in real time without any possibility of pausing or taking notes. In real time, the coder registers each speech-like syllable as canonical or non-canonical. TimeStamper automatically calculates the percentage of canonical syllables of all syllables registered (canonical babbling ratio). At the end of a recording, TimeStamper assists in assessing presence/absence of canonical babbling and syllable inventory size. The software is presented and instructions for free access are provided.

Development of a consensus core dataset in juvenile dermatomyositis for clinical use to inform research

Objectives This study aimed to develop consensus on an internationally agreed dataset for juvenile dermatomyositis (JDM), designed for clinical use, to enhance collaborative research and allow integration of data between centres. Methods A prototype dataset was developed through a formal process that included analysing items within existing databases of patients with idiopathic inflammatory myopathies. This template was used to aid a structured multistage consensus process. Exploiting Delphi methodology, two web-based questionnaires were distributed to healthcare professionals caring for patients with JDM identified through email distribution lists of international paediatric rheumatology and myositis research groups. A separate questionnaire was sent to parents of children with JDM and patients with JDM, identified through established research networks and patient support groups. The results of these parallel processes informed a face-to-face nominal group consensus meeting of international myositis experts, tasked with defining the content of the dataset. This developed dataset was tested in routine clinical practice before review and finalisation. Results A dataset containing 123 items was formulated with an accompanying glossary. Demographic and diagnostic data are contained within form A collected at baseline visit only, disease activity measures are included within form B collected at every visit and disease damage items within form C collected at baseline and annual visits thereafter. Conclusions Through a robust international process, a consensus dataset for JDM has been formulated that can capture disease activity and damage over time. This dataset can be incorporated into national and international collaborative efforts, including existing clinical research databases.

Development and evaluation of an electronic diary for recording patient reported outcomes in the overt study

The OVERT study is a pilot randomised controlled trial to compare the effectiveness of intravesical onabotulin toxin A with extended release tolterodine in the management of children aged 7-16 with Idiopathic Overactive Bladder. The primary and secondary outcomes for this study are recorded in a bladder diary, as recommended by the International Childrens Continence Society. In order to collect these data a web based diary (C#/MVC .Net/MySql Database) has been developed to make it easier for study participants to record the data required by the study. Feasibility data suggested that the vast majority of potentially eligible children and families have access to the internet. Participants included in the study are required to complete two diaries prior to randomisation into the trial, along with four symptom assessment questionnaires post randomisation. Each diary/questionnaire is completed at four time points during the day (morning, afternoon, evening and after going to bed) for seven days, with the questions presented to the participant varying based on the type of day (volume measuring or non-volume measuring) and the questionnaire type. The eDiary is configured with different roles so as to facilitate data entry by the participant, entry of diaries completed on paper by a research nurse and a review of data by clinical staff, thereby ensuring that all data can be entered into the application. This paper will discuss the development process undertaken to create the eDiary, present results from the evaluation of the system and future plans to enhance this application.