Award Title: Clinical and Patient Reported Long-Term Outcomes in Children with Chronic Intestinal Pseudo Obstruction: A UK Multi-Centre Study.
Funder: Health Education England

Abstract: Background Chronic Intestinal Pseudo-Obstruction (CIPO) affects the nerves, muscles, or both, of the intestine, resembling a physical obstruction in the absence of a true mechanical obstruction. This syndrome represents one of the main cause of intestinal failure in children and is characterised by pain, distended abdomen, incontinence, severe feeding difficulties, high morbidity and mortality. It is reported that 70% of children with severe CIPO require life-long Intravenous (IV) nutrition. Failure of IV Nutrition therapy indicates the need for bowel transplantation, with CIPO accounting for 50% of children/young people (CYP) awaiting bowel transplantation in the UK today. As well as significantly impairing quality of life (QoL) of affected CYP, CIPO results in considerable psychological and emotional burden for both patients and their families. CYP are reported to have significant pain, depression and anxiety, whilst their parents have poor emotional functioning. Current Practice Since 2012, diagnosticservices for CYP with suspected CIPO in the UK have been centralised. NHS England commissioned a National CIPO Diagnostic Service, with the aim of providing timely and accurate diagnosis, enabling early appropriate management strategies in order to change the natural history of the disease. Since April 2012 the service has investigated over 120 children. In a recent small study families stated they are living with fears around 'uncertainty' and 'death' of their child. Consultation with families identified that even when the CYP's health improves, these fears remain. Progress for CYP with CIPO has been made in recent years in the areas of IV Nutrition and transplant. With more CYP being diagnosed, and surviving, it is imperative that QoL is also explored. Long-term outcomes relating to early life interventions are needed now. Clinicians need to be providing the right treatment choices from the start. There is a hypothesis of early surgical intervention (forming a stoma), providing better patient outcomes, which is evidenced with some patients - but there are no long-term larger cohort studies. Research Questions 1. What are the long-term clinical, nutritional, educational and QoL outcomes of children and young people with Chronic Intestinal Pseudo-Obstruction in the UK? 2. Is there a difference in QoL between those with and without a stoma? Research Plan Design: A multi-centre mixed methods cohort study conducted over 4 phases with each phase informing the next. PHASE 1: Qualitative interviews, conducted in clinic or at home, with 15-20 CYP and their parents to understand the factors that impact on their QoL and what outcomes matter to them. Creative methods will be used with younger children. PHASE 2: Themes identified from the interviews will be used to select questionnaires measuring factors of importance which will be used in Phase 3 with the larger cohort. PHASE 3: Follow-up of all 85 CYP diagnosed with CIPO since April 2012, the majority of whom are seen in the collaborating 9 UK paediatric centres. Data will be collected under 4 main domains: Clinical, Nutrition, Education and QoL. Parents/CYP will complete questionnaires assessing areas identified in the interviews and clinical and nutritional data will be collected from the clinical notes. PHASE 4: A dissemination workshop to develop recommendations for practice. Results from this study will provide clinicians with the evidence to support their decisions about treatment pathways. This will result in improvements in mortality and morbidity, and fewer transplant referrals for CYP with CIPO in the UK today. A UK cohort study is needed to provide families with information about treatment and survival. Newly diagnosed families will be able to plan around an up-to-date prognosis. The NHS goals of improving care, reducing variability in patient pathways and increasing efficiency will be addressed for this unique patient group.

Lay Abstract: Background Chronic Intestinal Pseudo-Obstruction (CIPO) is a rare bowel disease of childhood. It is a condition in which the nerves, muscles, or both, throughout the bowel do not function. Symptoms are pain, bloated abdomen, vomiting, incontinence, and feeding difficulty. Over half the children who have this condition are affected so badly they are unable to process enough food for them to grow or survive, and they present with gut failure; around 50% of children waiting for a bowel transplant in the UK have CIPO. Children with gut failure survive in a similar way to children with renal failure - with a dependency on machines. They are regularly attached to pumps to have Intravenous (IV) Nutrition filtered into their blood. Unfortunately treatment itself is life-threatening. Interviews in 2012 identified that parents feel 'overwhelming sadness' during the diagnostic period. They fear their child will die, and worry about feeding and schooling. In a follow-up study 4 years later the families still expressed fears of death, even if a child's condition had improved. The children themselves worried about schooling, social exclusion and dignity.Current practice The NHS is supporting doctors in the UK to recognise CIPO in children. A centrally based National CIPO Diagnostic Service was commissioned by the NHS in 2012. Paediatricians now have established pathways to follow if they suspect a child/young person has this condition. Paediatric specialists make treatment recommendations, the aims of which are to reduce pain, maximise normal feeding, and prevent further damage to the affected bowel, thus improving survival. The primary and frequently controversial decision is whether to have a bowel operation or not, and when. There is emerging evidence that some children/young people who have an operation for a stoma (artificial opening from the bowel onto the stomach wall) have reduced dependency on IV nutrition, manage oral feeding, get to school, and are surviving. What we need to know is whether this bowel operation has been effective with others, and if there is an optimal time to operate on the next newly diagnosed child. There is reluctance amongst doctors to perform this operation without evidence from a larger group, and families are seeking reassurance that this body-changing surgery will help. Once diagnosed at the national centre, children/young people return to their local hospital for ongoing management. There is no standardised care. Following-up these families could reveal who does better. Doctors across the UK would then have evidence to help future children/young people with CIPO avoid IV nutrition or transplant.Research questions What are the long-term clinical, nutritional and quality of life outcomes of children/young people with CIPO in the UK? Is there a difference in quality of life between those with and without a stoma?Research Plan The study will be conducted over four phases, each phase informing the next. Phase 1: 15-20 children/young people and their parents will be invited to take part in interviews to understand the factors that impact on their quality of life and what matters to them. Interviews will be conducted in clinic or at home. Creative methods (e.g. drawing) will be used with younger children. Phase 2: Themes from the interviews will be identified and will inform the selection of questionnaires to be used in Phase 3 with the larger group of children/young people. Phase 3: We aim to recruit all 85 children/young people with CIPO, diagnosed through the UK service, between 3-9 years ago, with and without stomas. Their progress will be explored in 4 domains, chosen as a result of what parents/CYP have told us is important to them: 1) Medical - hospitalisations, surgery, complications/transplants. 2) Nutrition -h; improvement/deterioration in feeding. 3) Education -h; school attendance and teachers' assessment. 4) Quality of Life -h; measuring what matters to parents and children, as described by them. Visits will be made to families when they attend their regular local hospital outpatient appointment. Phase 4: A workshop will be held with families and staff to tell them the results of the study and develop draft recommendations for changing practice. Currently, we do not know if surgical stomas are helping avoid IV nutrition, or transplant in the long term. Results of this study will help doctors make evidenced-based decisions, improving survival and quality of life for children/young people with CIPO in the UK today. A UK cohort study is needed to provide families with information about treatment and survival. They may be given hope, to replace fear of death, and so can then accurately plan their child's education and future.

Research Activity Codes: 6.4 SURGERY
Health Categories: ORAL AND GASTROINTESTINAL