Title: Imaging in Paediatric Osteomyelitis (the PICBONE study): a multi-centre cohort study to understand the role of MRI and ultrasound in the diagnosis of acute haematogenous osteomyelitis in children
Funder: Department of Health and Social Care

Abstract: Aims:_x000D_ 1. To understand how helpful ultrasound and MRI (Magnetic Resonance Imaging) scans are in diagnosing bone and joint infections in children._x000D_ 2. To create a pathway that doctors and nurses can use in the emergency department to more sucessfully diagnose bone and joint infections._x000D_ _x000D_ Background_x000D_ When a child is brought to the emergency department with a painful limb they could either have:_x000D_ · A serious infection of their bones or joints OR_x000D_ · A temporary swelling within their joints._x000D_ Serious infections in bones are rare, but can be limb and life threatening. They require urgent treatment (antibiotics) and sometimes surgery. On the other hand, temporary joint swelling is common and resolves without any intervention within a few days. The challenge is to quickly identify which child has an infection and which has joint swelling. Telling these apart is often not easy, and involves x-rays and blood tests. Often, special tests are also used, which are ultrasound and/or MRI scans. Doctors around the world are unsure about the best choice of test, particularly the ‘special tests’, and what order tests should be performed when a bone infection is suspected. _x000D_ A clear pathway to know which tests to perform and when is needed, to ensure that bone infections are not missed. This will also reduce unnecessary tests on children who do not have an infection._x000D_ _x000D_ Methods_x000D_ 1. Learn from children who have had bone infection (retrospective study)_x000D_ We will look at past records of children who had suspected bone infections in 30 hospitals in the UK. These will tell us which tests were performed and when. We will work-out how useful the ‘special tests’ were at detecting bone infections, and identify patterns in how and when tests should be performed._x000D_ 2. Apply what we’ve learnt to diagnose future infections (prospective study)_x000D_ We will use the information from our first study to develop a clear pathway to investigate suspected bone infections. We shall then test how well this pathway works on a new group of children with suspected infections._x000D_ 3. An interview study will be carried out to see if this pathway is acceptable to children, parents and doctors and to assess how best to address children’s and parents’ needs and concerns._x000D_ _x000D_ Public Patient Involvement_x000D_ Amy is a parent co-investigator, who has worked with us to develop this application. We have also keenly involved members of GenerationR (young people) and a Parents Advisory Group (PAG) in our study design. GenerationR came up with an acronym and logo for our study. The PAG highlighted that patients wanted to know what was wrong as quickly as possible._x000D_ GenerationR and PAG said that children might be scared about needles (blood tests) and parents did not like the idea of their children being put to sleep for a test (MRI scan). Both groups thought it would be helpful to have information booklets about the tests: we will develop those during the study. We will also ensure that patient needs and concerns are explored throughout the study using questionnaires and feedback forms._x000D_ _x000D_ Dissemination_x000D_ Results of this study will be widely spread. We shall present reports at conferences and publish in medical journals. We will also make the study accessible to the general public: engaging with social media, producing explainer videos and infographics. We hope that the pathway we produce will be adopted widely by doctors and help develop national guidelines for the investigation of bone infections.

Lay abstract: Research question_x000D_ What is the role of MRI and ultrasound in the diagnosis of paediatric osteomyelitis?_x000D_ _x000D_ Background_x000D_ Osteomyelitis (OM) is a bacterial infection of bone. In children, it is typically introduced through the blood (haematogenous). Acute osteomyelitis presents with symptoms of less than two weeks, including pain, loss of limb function, raised temperature and malaise. The burden is significant, with approximately 1800 children admitted yearly to hospitals in England. Untreated OM rapidly progresses to irreversible joint damage and bone destruction, leading to a limb threatening situation, while systemic sepsis can be life threatening. Early differentiation of OM from less urgent conditions mimicking the symptoms is critical._x000D_ Patients typically present to the Emergency Department. After initial work-up (history, clinical examination, routine blood tests and radiographs), diagnosis is often uncertain and advanced imaging is considered: ultrasound scan (USS) and magnetic resonance imaging (MRI). USS is more accessible but the overall diagnostic value is unknown. MRI has high diagnostic value in adult OM but often requires anaesthesia in children. Understanding the sensitivity and specificity of diagnostic imaging, along with a clear decision tool that includes all diagnostic parameters, would be of great value. Relevant studies show this is a priority from both the clinicians’ and patients/families’ perspectives._x000D_ _x000D_ Aims and objectives_x000D_ • Primary objective: to determine the diagnostic accuracy of MRI and USS in the investigation of OM in children._x000D_ • Secondary objectives: to derive and validate a clinical algorithm for the timely diagnosis of OM in children, to determine the added value of MRI and USS imaging for use in the emergency, secondary and tertiary settings and explore acceptability to children, parents and health practitioners._x000D_ _x000D_ Methods_x000D_ The study will consist of two phases: _x000D_ (i) A multicentre retrospective cohort study based on hospital records to establish the diagnostic accuracy of MRI and USS and to develop a clinical algorithm for diagnosis._x000D_ (ii) A multicentre prospective cohort study to externally validate the clinical algorithm. _x000D_ (iii) In parallel, a qualitative study will aim to inform the management of patients being investigated for OM, including how best to address their information needs and how to support them during the process._x000D_ _x000D_ The anticipated outcomes include:_x000D_ 1. Diagnostic accuracy study (retrospective cohort)_x000D_ Primary: Sensitivity and specificity of MRI and USS._x000D_ Secondary: Positive Predictive Value (PPV), Negative Predictive Value (NPV), likelihood ratio and diagnostic odds ratio for MRI and USS. _x000D_ 2. Clinical algorithm development (retrospective cohort)_x000D_ Primary: A model to predict the probability of OM._x000D_ Secondary: Added value of USS and MRI compared to current standard investigations. _x000D_ 3. Clinical algorithm external validation (prospective cohort)_x000D_ Primary: External validation of the model’s predictive performance (in terms of calibration and discrimination)._x000D_ _x000D_ We have established the feasibility of reliable retrospective data collection through a pilot study. _x000D_ _x000D_ Anticipated impact and dissemination_x000D_ The findings will inform NHS clinical practice for the management of children with suspected OM. We will disseminate the results across the wider health professionals’ community, NICE and policy makers, and to the public via parent groups/charities.

Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: INFECTION