Pippa Hemingway

Intensity-modulated radiotherapy for the treatment of prostate cancer: a systematic review and economic evaluation

BACKGROUND Prostate cancer (PC) is the most common cancer in men in the UK. Radiotherapy (RT) is a recognised treatment for PC and high-dose conformal radiotherapy (CRT) is the recommended standard of care for localised or locally advanced tumours. Intensity-modulated radiotherapy (IMRT) allows better dose distributions in RT. OBJECTIVE This report evaluates the clinical effectiveness and cost-effectiveness of IMRT for the radical treatment of PC. DATA SOURCES The following databases were searched: MEDLINE (1950-present), EMBASE (1980-present), Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982-present), BIOSIS (1985-present), the Cochrane Database of Systematic Reviews (1991-present), the Cochrane Controlled Trials Register (1991-present), the Science Citation Index (1900-present) and the NHS Centre for Reviews and Dissemination databases (Database of Abstracts of Reviews of Effects, NHS Economic Evaluation Database, Health Technology Assessment) (1991-present). MEDLINE In-Process & Other Non-Indexed Citations was searched to identify any studies not yet indexed on MEDLINE. Current research was identified through searching the UK Clinical Research Network, National Research Register archive, the Current Controlled Trials register and the Medical Research Council Clinical Trials Register. In addition, abstracts of the American Society of Clinical Oncology, the American Society for Therapeutic Radiology and Oncology, and European Society for Therapeutic Radiology and Oncology conferences were browsed. REVIEW METHODS A systematic literature review of the clinical effectiveness and cost-effectiveness of IMRT in PC was conducted. Comparators were three-dimensional conformal radiotherapy (3DCRT) or radical prostatectomy. Outcomes sought were overall survival, biochemical [prostate-specific antigen (PSA)] relapse-free survival, toxicity and health-related quality of life (HRQoL). Fifteen electronic bibliographic databases were searched in January 2009 and updated in May 2009, and the reference lists of relevant articles were checked. Studies only published in languages other than English were excluded. An economic model was developed to examine the cost-effectiveness of IMRT in comparison to 3DCRT. Four scenarios were modelled based on the studies which reported both PSA survival and late gastrointestinal (GI) toxicity. In two scenarios equal PSA survival was assumed for IMRT and 3DCRT, the other two having greater PSA survival for the IMRT cohort. As there was very limited data on clinical outcomes, the model estimates progression to clinical failure and PC death from the surrogate outcome of PSA failure. RESULTS No randomised controlled trials (RCTs) of IMRT versus 3DCRT in PC were available, but 13 non-randomised studies comparing IMRT with 3DCRT were found, of which five were available only as abstracts. One abstract reported overall survival. Biochemical relapse-free survival was not affected by treatment group, except where there was a dose difference between groups, in which case higher dose IMRT was favoured over lower dose 3DCRT. Most studies reported an advantage for IMRT in GI toxicity, attributed to increased conformality of treatment compared with 3DCRT, particularly with regard to volume of rectum treated. There was some indication that genitourinary toxicity was worse for patients treated with dose escalated IMRT, although most studies did not find a significant treatment effect. HRQoL improved for both treatment groups following radiotherapy, with any group difference resolved by 6 months after treatment. No comparative studies of IMRT versus prostatectomy were identified. No comparative studies of IMRT in PC patients with bone metastasis were identified. LIMITATIONS The strength of the conclusions of this review are limited by the lack of RCTs, and any comparative studies for some patient groups. CONCLUSIONS The comparative data of IMRT versus 3DCRT seem to support the theory that higher doses, up to 81 Gy, can improve biochemical survival for patients with localised PC, concurring with data on CRT. The data also suggest that toxicity can be reduced by increasing conformality of treatment, particularly with regard to GI toxicity, which can be more easily achieved with IMRT than 3DCRT. Whether differences in GI toxicity between IMRT and 3DCRT are sufficient for IMRT to be cost-effective is uncertain, depending on the difference in incidence of GI toxicity, its duration and the cost difference between IMRT and 3DCRT.

An evidence and consensus based guideline for the management of a child after a seizure

Structured in the format recommended by Hayward et al1 for guideline reports. Objective: An evidence and consensus based guideline for the management of the child who presents to hospital having had a seizure. It does not deal with the child who is still seizing. The guideline is intended for use by junior doctors, and was developed for this common problem (5% of all paediatric medical attenders) where variation in practice occurs. Options: Assessment, investigations (biochemistry, lumbar puncture, serum anticonvulsant levels, EEG in particular), and/or admission are examined. Outcomes: The guideline aims to direct junior doctors in recognising those children who are at higher risk of serious intracranial pathology including infection, and conversely to recognise those children at low risk who are safe to go home. Evidence: A systematic review of the literature was performed. Articles were identified using the electronic data bases Medline (from 1966 to June 1998), Embase (from 1980 to June 1998) and Cochrane (to June 1998), and selected if they investigated the specified clinical question. Personal reviews were excluded. Selected articles were appraised, graded, and synthesised qualitatively. Statements of recommendation were made. Consensus: An anonymous, postal Delphi consensus development was used. A national panel of 30 medical and nursing staff regularly caring for these children were asked to grade their agreement with the statements generated. They were sent the relevant original publications, the appraisals, and literature review. On the second and third rounds they were asked whether they wished to re-grade their agreement in the light of other panellists’ responses. Consensus was defined as 83% of panellists agreeing with the statement. Recommendations in brief: For afebrile seizures all children should have their blood pressure recorded, but no other investigations are routine although a seizing or somnolent child should have blood glucose measured; all children under 1 year should be admitted. For seizures with fever, clinical signs indicating the need to treat as meningitis are given. Children should be admitted if they are under 18 months old, have had a complex seizure, or after pretreatment with antibiotics. Validation: The guideline has undergone implementation and evaluation in a paediatric accident and emergency department, the results of which will be published separately. Only one alteration was made to the guideline as a result of this validation process, which is included here.

The impact of presenting problem based guidelines for children with medical problems in an accident and emergency department

Aims: To evaluate the impact of presenting problem based guidelines in managing children with either diarrhoea (with or without vomiting) or seizure (with or without fever). Methods: This prospective observational study with an intervention was based on a paediatric accident and emergency (A&E) department in Nottingham. All patients (either GP or self referred) were acute attenders aged 0–15 years, with a medical presenting problem during 4 months in the spring of 1997 and 1999. Five hundred and thirty-one diarrhoea attendances (292 before guideline implementation and 239 after) and 411 seizure attendances (212 before guideline implementation and 199 after) were recorded. Evidence based and consensus ratified guidelines developed for the study were implemented using care pathway documentation. Process (documentation, time in the department, investigations, treatment) and outcome (admission to hospital, returns to A&E) data were collected from case notes. Results: The percentage of children investigated with blood tests fell significantly (haematology requests in diarrhoea presentations from 11% to 4%, biochemistry in seizure presentations from 29% to 17%). Intravenous infusions in diarrhoea presenters fell (9% to 1%), and more appropriate oral fluids were used. Management time in A&E was reduced (diarrhoea presenters: median of 55–40 minutes, seizure presenters: 80–55 minutes, but remained static for other presenting problems). Marked improvements in documentation were seen. Admission rates for diarrhoea attenders increased (27% to 34%) but remained the same for seizure (69% v 73%) Conclusions: The implementation of a presenting problem based guideline as a care pathway was associated with improvements in the quality of care by: improved documentation; reduced invasive investigations; more appropriate treatment, and reduced time spent in A&E.

Children and young people's participation in healthcare consultations in the emergency department.

Approximately 4 million children attend emergency departments (ED) in England, United Kingdom, per annum. It is important for children and young people to have an active say in their assessment and treatment during each emergency care episode. However the reality of hearing the child or young persons voice within active participation in health care consultations remains low at approximately 6% of voices recorded. In the context of policy drivers and patient benefits, there is a need to increase the level of participation by children and young people within the emergency care environment. However, noise, child and parental anxiety and distress, professional time pressure, and severity of child illness or injury add to the inherent complexity of triadic communication (parent, child, healthcare professional) in the ED. Research examining child participation in decision-making in ED is sparse and guidance for all parties is limited. Therefore methods drawn from the wider literature on child participation are discussed which may be implemented, validated and evaluated with an ED context.

An evidence-based guideline for children presenting with acute breathing difficulty

Objective: The aim of this study was to develop an evidence-based guideline for use primarily by junior clinicians to assist with the management of children presenting to the hospital with an acute breathing difficulty. Methods: An overview of the literature provided a framework of clinical questions for the management of a child with an acute breathing difficulty on which to base a systematic literature review. Relevant articles were appraised by the research fellow and graded according to their quality. A national panel of 50 clinicians was provided, by post, with the clinical questions, research papers, appraisals and the grades of recommendations generated. They were asked to check the grades allocated to the recommendations and the accuracy of the language used. They were also provided with all the clinical questions for which there was insufficient evidence to reach a conclusion but for which a consensus recommendation was required. A Delphi method was used to formalise the consensus process. For all recommendations, panel members were asked to rate their level of agreement on a 1–9-point Likert scale. The results of the first round were fed back, and appropriate alterations to the recommendations made or additional recommendations included. The process of rating was repeated, and the final guideline was developed based on the consensus reached. Results: Following two iterative rounds, the guideline was completed as a full technical document, with a series of key recommendations and an algorithm. It was based on 10 grade A (evidence from systematic review or meta-analyses), 5 grade B, 17 grade C and 31 grade D (consensus or expert opinion) recommendations. Conclusion: We have developed an evidence-based guideline that has subsequently been successfully implemented in the paediatric emergency departments and disseminated nationally. Results showing the effect of the guideline upon practice will be published separately.

Protocol for a longitudinal qualitative study: survivors of childhood critical illness exploring long-term psychosocial well-being and needs—The SCETCH Project

Introduction Life-threatening critical illness affects over a quarter of a million children and adolescents (0–18 years old) annually in the USA and the UK. Death from critical illness is rare; however, survivors and their families can be exposed to a complex array of negative physical, psychological and social problems. Currently, within the literature, there is a distinct paucity of child and adolescent survivor self-reports, thus limiting our understanding of how survivors perceive this adversity and subsequently cope and grow in the long-term following their critical illness. This study aims to explore and understand psychosocial well-being and needs of critical illness survivors, 6–20 months post paediatric intensive care admission. Methods and analysis A longitudinal, qualitative approach will provide a platform for a holistic and contextualised exploration of outcomes and mechanisms at an individual level. Up to 80 participants, including 20 childhood critical illness survivors and 60 associated family members or health professionals/teachers, will be recruited. Three interviews, 7–9 weeks apart, will be conducted with critical illness survivors, allowing for the exploration of psychosocial well-being over time. A single interview will be conducted with the other participants enabling the exploration of contextual information and how psychosocial well-being may inter-relate between critical illness survivors and themselves. A ‘tool box’ of qualitative methods (semi-structured interviews, draw and tell, photo-elicitation, graphic-elicitation) will be used to collect data. Narrative analysis and pattern matching will be used to identify emergent themes across participants. Ethics and dissemination This study will provide an insight and understanding of participants’ experiences and perspectives of surviving critical illness in the long term with specific relation to their psychosocial well-being. Multiple methods will be used to ensure that the findings are effectively disseminated to service users, clinicians, policy and academic audiences. The study has full ethical approval from the East Midlands Research Ethics Committee and has received National Health Service (NHS) governance clearance.

Stories of survival: Children’s narratives of psychosocial well-being following paediatric critical illness or injury

Survival from critical illness can expose children to an array of negative physical and psychological problems. While the perspective of parents and professionals have been well documented, there is limited understanding of how childhood critical care survivors make sense of their experiences in relation to psychosocial well-being. We aimed to explore long-term psychosocial well-being of childhood survivors of critical illness through their stories. A qualitative, exploratory study using serial in-depth interviews was employed. Nine children (aged 6–15 years) were recruited to the study, 6–14 months post-discharge from a paediatric intensive care unit. Qualitative art-based methods were used with a responsive interviewing technique and data were analysed using narrative psychological analysis. Four themes emerged: disrupted lives and stories; survivors revealed uncertainties in their stories as they recalled their critical care event, exposure to death and dying; talking about extreme physical vulnerability provoked anxieties, mediating between different social worlds and identities; revealed the dynamic nature of survival and getting on with life; the prospective outlook survivors had on their existence despite newly manifesting adversities. Childhood survivors’ stories identify challenges and adversities that are faced when attempting to readjust to life following critical illness that both enhance and impair psychosocial well-being.

Children’s, parents’ and other stakeholders’ perspectives on early dietary self-management to delay disease progression of chronic disease in children: a protocol for a mixed studies systematic review with a narrative synthesis

BackgroundChronic disease of childhood may be delayed by early dietary intervention. The purpose of this systematic review is to provide decision-makers with a perspective on the role of early dietary intervention, as a form of self-management, to delay disease progression in children with early chronic disease, as described by children, parents and other stakeholders.MethodsThe study will systematically review empirical research (qualitative, quantitative and mixed method designs), including grey literature, using a narrative synthesis. A four-stage search process will be conducted involving a scoping search, the Scottish Intercollegiate Guidelines Network (SIGN) Patient Issues search filter on MEDLINE, the search of seven databases using a chronic disease and chronic kidney disease (CKD) search strategy, and hand searching the reference lists of identified papers for additional studies. All studies retrieved during the search process will undergo a screening and selection process against the inclusion/exclusion criteria. Methodological quality of relevant studies will be assessed using a validated Mixed Studies Review scoring system, before inclusion in the review. Relevant grey literature will be assessed for methodological quality and relative importance using McGrath et al.’s framework and the Academy Health advisory committee categories, respectively. Data extraction will be guided by the Centre for Review and Dissemination guidance and Popay et al.’s work. The narrative synthesis of the findings will use elements of Popay et al.’s methodology of narrative synthesis, applying recognised tools for each of the four elements: (1) developing a theory of how the intervention works, why and for whom; (2) developing a preliminary synthesis of findings of included studies; (3) exploring relationships in the data; and (4) assessing the robustness of the synthesis.DiscussionThis mixed studies systematic review with a narrative synthesis seeks to elucidate the gaps in current knowledge and generate a fresh explanation of research findings on early dietary self-management in chronic disease, with particular application to CKD, from the stakeholders’ perspective. The review will provide an important platform to inform future research, identifying the facilitators and barriers to implementing early dietary interventions. Ultimately, the review will contribute vital information to inform future improvements in chronic disease. The lead author has a particular interest in CKD paediatric service delivery.Systematic review registrationThe review has been registered with PROSPERO (CRD42017078130).

Survived so what? Identifying priorities for research with children and families post-paediatric intensive care unit: Survived so what? Identifying priorities for research with children and families post-PICU

The involvement of patients and the public in the development, implementation and evaluation of health care services and research is recognized to have tangible benefits in relation to effectiveness and credibility. However, despite >96% of children and young people surviving critical illness or injury, there is a paucity of published reports demonstrating their contribution to informing the priorities for aftercare services and outcomes research. We aimed to identify the service and research priorities for Paediatric Intensive Care Unit survivors with children and young people, their families and other stakeholders. We conducted a face-to-face, multiple-stakeholder consultation event, held in the Midlands (UK), to provide opportunities for experiences, views and priorities to be elicited. Data were gathered using write/draw and tell and focus group approaches. An inductive content analytical approach was used to categorize and conceptualize feedback. A total of 26 individuals attended the consultation exercise, including children and young people who were critical care survivors; their siblings; parents and carers; health professionals; academics; commissioners; and service managers. Consultation findings indicated that future services, interventions and research must be holistic and family-centred. Children and young people advisors reported priorities that focused on longer-term outcomes, whereas adult advisors identified priorities that mapped against the pathways of care. Specific priorities included developing and testing interventions that address unmet communication and information needs. Furthermore, initiatives to optimize the lives and longer-term functional and psycho-social outcomes of Paediatric Intensive Care Unit survivors were identified. This consultation exercise provides further evidence of the value of meaningful patient and public involvement in identifying the priorities for research and services for Paediatric Intensive Care Unit survivors and illuminates differences in proposed priorities between children, young people and adult advisors.

What are the predictors, barriers and facilitators to effective management of acute pain in children by ambulance services? A mixed-methods systematic review protocol

Introduction The management of pain is complex, especially in children, as age, developmental level, cognitive and communication skills and associated beliefs must be considered. Without effective pain treatment, children may suffer long-term changes in stress hormone responses and pain perception and are at risk of developing posttraumatic stress disorder. Pre-hospital analgesic treatment of injured children is suboptimal, with very few children in pain receiving analgesia. The aim of this review is to identify predictors, barriers and facilitators to effective management of acute pain in children by ambulance services. Methods A mixed-methods approach has been adopted due to the research question lending itself to qualitative and quantitative inquiry. The segregated methodology will be used where quantitative and qualitative papers are synthesised separately, followed by mixed-methods synthesis (meta-integration). We will search from inception: MEDLINE, CINAHL and PsycINFO via EBSCOHost, EMBASE via Ovid SP, Web of Science and Scopus. The Cochrane Library, the Joanna Briggs Institute, PROSPERO, ISRCTN and ClinicalTrials.gov will be searched. We will include empirical qualitative and quantitative studies. We will exclude animal studies, reviews, audits, service evaluations, simulated studies, letters, Best Evidence Topics, case studies, self-efficacy studies, comments and abstracts. Two authors will perform full screening and selection, data extraction and quality assessment. GRADE and CERQual will determine the confidence in cumulative evidence. Discussion If confidence in the cumulative evidence is deemed Moderate, Low or Very Low, then this review will inform the development of a novel mixed-methods sequential explanatory study which aims to comprehensively identify predictors, barriers and facilitators to effective pain management of acute pain in children within ambulance services. Future research will be discussed among authors if confidence is deemed High.Systematic Review Registration: PROSPERO: CRD42017058960.