Guideline for the management of Clostridioides difficile infection in pediatric patients with cancer and hematopoietic cell transplantation recipients: 2024 update.

Our objective was to update a clinical practice guideline for the prevention and treatment of Clostridioides difficile infection (CDI) in pediatric patients with cancer and hematopoietic cell transplantation recipients. We reconvened an international multi-disciplinary panel. A systematic review of randomized controlled trials (RCTs) for the prevention or treatment of CDI in any population was updated and identified 31 new RCTs. Strong recommendations were made to use either oral metronidazole or oral vancomycin for non-severe CDI treatment, and to use either oral vancomycin or oral fidaxomicin for severe CDI. A strong recommendation that fecal microbiota transplantation should not be routinely used to treat CDI was also made. The panel made two new good practice statements to follow infection control practices including isolation in patients experiencing CDI, and to minimize systemic antibacterial administration where feasible, especially in patients who have experienced CDI.

A systematic review of combined surgery and brachytherapy approaches for children and young people with relapsed and refractory rhabdomyosarcoma (Local-REFoRMS).

Approximately one third of children with rhabdomyosarcoma relapse or have refractory disease. Treatment approaches include a combination of systemic therapies and local therapies, directed at tumour site(s). This review was conducted to evaluate the effectiveness and safety of the combination of surgery and brachytherapy as local therapy for treating children and young people with relapsed/refractory rhabdomyosarcoma. This review identified studies based on a previous systematic review looking at the treatments for children and young people under 18 years old with relapsed/refractory rhabdomyosarcoma. Studies conducted after 2000 were included. Survival outcomes, relapse rates, adverse events and functional outcomes were extracted. From 16,965 records identified in the baseline systematic review, 205 included the words 'AMORE' or 'brachytherapy', and were screened for eligibility in this substudy. Thirteen studies met the inclusion criteria for Local-REFoRMS, including over 55 relapsed and refractory rhabdomyosarcoma patients. Most studies were retrospective cohort studies conducted within Europe. Most patients had embryonal disease within the head and neck or bladder/prostate regions, and received local therapy for first relapse. Approximately one quarter of patients relapsed following surgery and brachytherapy, with local relapses occurring more than metastatic relapse. Adverse events and functional outcomes were infrequently reported, but related to the site of surgery and brachytherapy. Study quality was limited by inconsistent reporting and potential selection bias. Outcomes following surgery and brachytherapy for a selected group of relapsed and refractory rhabdomyosarcoma show reasonable benefits, but reporting was often unclear and based on small sample sizes.

A systematic review of early phase studies for children and young people with relapsed and refractory rhabdomyosarcoma: The REFoRMS-SR project.

Rhabdomyosarcoma is the commonest soft tissue sarcoma in children. Around one-third of children with rhabdomyosarcoma experience relapse or have refractory disease, which is associated with a poor prognosis. This systematic review of early phase studies in pediatric relapsed/refractory rhabdomyosarcoma was conducted to inform future research and provide accurate information to families and clinicians making difficult treatment choices. Nine databases and five trial registries were searched in June 2021. Early phase studies of interventions for disease control in patients under 18 years old with relapsed/refractory rhabdomyosarcoma were eligible. No language/geographic restrictions were applied. Studies conducted after 2000 were included. Survival outcomes, response rates, quality of life and adverse event data were extracted. Screening, data extraction and quality assessment (Downs and Black Checklist) were conducted by two researchers. Owing to heterogeneity in the included studies, narrative synthesis was conducted. Of 16,965 records screened, 129 published studies including over 1100 relapsed/refractory rhabdomyosarcoma patients were eligible. Most studies evaluated systemic therapies. Where reported, 70% of studies reported a median progression-free survival ≤6 months. Objective response rate was 21.6%. Adverse events were mostly hematological. One-hundred and seven trial registry records of 99 studies were also eligible, 63 of which report they are currently recruiting. Study quality was limited by poor and inconsistent reporting. Outcomes for children with relapsed/refractory rhabdomyosarcoma who enroll on early phase studies are poor. Improving reporting quality and consistency would facilitate the synthesis of early phase studies in relapsed/refractory rhabdomyosarcoma (PROSPERO registration: CRD42021266254).

What matters to you? Engaging with children in the James Lind Alliance Children's Cancer Priority Setting Partnership.

BACKGROUND: Previous priority setting exercises have sought to involve children, but in the final reporting, it is evident that few children had been engaged through the process. A primary aim in the Children's Cancer Priority Setting Partnership was to find out from children what they want research to focus on. We report on our experience to inform methods of engagement with children in future James Lind Alliance Priority Setting Partnerships and similar exercises. METHODS: We followed the James Lind Alliance process, collecting and shortlisting questions via online surveys with adult survivors of childhood cancer, carers, and professionals, and holding a final workshop. Alongside this, a parallel process to collect and prioritise questions from children was undertaken. We created animations for parents/carers to explain the project and surveys to children, gathered questions via online surveys and held a workshop with children to identify their priorities. RESULTS: Sixty-one children and young people with cancer and 10 siblings, aged 3-21 years, submitted 252 potential questions/topics via the surveys. Submissions were refined into 24 summary questions. These questions were discussed at a workshop with eight children; they also added more questions on topics of importance to them. Workshop participants prioritised the Top 5 questions; top priority was, 'How can we make being in hospital a better experience for children and young people? (like having better food, internet, toys, and open visiting so other family members can be more involved in the child's care)'. The Top 5 also included cancer prevention, treatments closer to home, early diagnosis, and emotional support. These questions were taken to the final workshop at which the Top 10 priorities were decided, all five children's priorities were reflected in the final Top 10. CONCLUSIONS: We have demonstrated that it is possible to successfully involve children directly in setting priorities for future research. Future priority setting exercises on topics relevant to children, should seek to include their views. The Children's Cancer Top 10 priorities reflect the voices of children and should inform the funding of future research.

Priority Setting Partnerships find out what areas of research are important to patients, families, and the professionals who care for them. Few Priority Setting Partnerships have involved children, so what matters to them may not have been well-represented. The Children's Cancer Priority Setting Partnership aimed to find out directly from children what research we should do. We collected questions/topics for research from children using online surveys. We made animations to explain the project and surveys to children. Two-hundred and fifty-two questions were sent in by 61 children and young people with cancer and 10 siblings. We grouped similar questions together into 24 summary questions. Summary questions were discussed at a workshop with eight children. Workshop participants added more questions on topics that mattered to them, and decided their Top 5 questions. The top question was, 'How can we make being in hospital a better experience for children and young people? (like having better food, internet, toys, and open visiting so other family members can be more involved in the child's care)'. The Top 5 questions included: preventing cancer, having treatments nearer home, early diagnosis, and emotional support. These questions were taken to the final project workshop, this was with adults, including childhood cancer survivors, where the Top 10 priorities were decided. All five children's priorities were included in the Top 10. We have shown it is possible to successfully involve children in setting research priorities. Future priority setting exercises on topics that affect children should actively seek and include their views.

Guideline for the management of fatigue in children and adolescents with cancer or pediatric hematopoietic cell transplant recipients: 2023 update.

Objective was to update a clinical practice guideline (CPG) for the management of fatigue in children and adolescents with cancer or pediatric hematopoietic cell transplant recipients. We reconvened a multi-disciplinary and multi-national panel. While the previous 2018 CPG evaluated adult and pediatric randomized controlled trials (RCTs) to manage fatigue, this 2023 update revised previous recommendations based only on pediatric RCTs. Twenty RCTs were included in the updated systematic review. Physical activity significantly reduced fatigue (standardized mean difference -0.44, 95% confidence interval -0.64 to -0.24; n = 8 RCTs). Using the 2018 recommendations as a basis, the panel continued to make strong recommendations to use physical activity, and to offer relaxation, mindfulness or both, to manage fatigue in pediatric patients. Cognitive or cognitive behavioral therapies may be offered. Pharmacological approaches should not be routinely used. The panel made a new good practice statement to routinely assess for fatigue, ideally using a validated scale.

Serum Amyloid Beta Precursor Protein, Neurofilament Light, and Visinin-like Protein-1 in Rugby Players: An Exploratory Study.

Concussion diagnosis is difficult and may be improved with the addition of a blood-based biomarker that indicates concussion. The purpose of this research was to investigate the capability of serum amyloid beta precursor protein (APP), neurofilament light (NfL), and visinin-like protein-1 (VILIP-1) to distinguish athletes who were diagnosed with a concussion pitch-side. An observational cross-sectional study design was used to replicate sideline concussion diagnosis. Subjects included mutually exclusive pre-match (n = 9), post-match (n = 15), and SRC (n = 7) groups. Six paired pre-and post-match subjects were analyzed for APP. APP increased significantly from pre-match (mean = 57.98 pg·mL−1, SD = 63.21 pg·mL−1) to post-match (mean = 111.37 pg·mL−1, SD = 106.89 pg·mL−1, p = 0.048) in the paired subjects. NfL was lower in the SRC group (median = 8.71 pg·mL−1, IQR = 6.09 pg·mL−1) compared to the post-match group (median = 29.60 pg·mL−1, IQR = 57.45 pg·mL−1, p < 0.001). VILIP-1 was higher in the post-match group (median = 212.18 pg·mL−1, IQR = 345.00 pg·mL−1) compared to both the pre-match (median = 32.63 pg·mL−1, IQR = 52.24 pg·mL−1), p = 0.001) and SRC (median = 30.21 pg·mL−1, IQR = 47.20 pg·mL−1), p = 0.003) groups. APP, NfL, and VILIP-1 were all able to distinguish between pre-match and post-match groups (AUROC > 0.700) but not from the SRC group (AUROC < 0.660). Our results show that APP, NfL, and VILIP-1 were not helpful in differentiating concussed from non-concussed athletes pitch-side in this study.

Complete Genome Sequences of Mycobacterium smegmatis Phages MelsMeow, Yorick, Virgeve, and Mikro.

Mycobacterium phages Mikro, Yorick, Virgeve, and MelsMeow were isolated from soil in Rock Hill, South Carolina. Mikro is a myovirus with a comparatively large genome of 157,166 bp. The remainder are siphoviruses with genome lengths ranging from 59,227 bp to 68,563 bp. All phages were isolated on Mycobacterium smegmatis.

Ubiquitin carboxyl-terminal esterase L1 is not elevated in the serum of concussed rugby players: an observational cross-sectional study.

Concussion diagnosis is complicated by a lack of objective measures. Ubiquitin carboxyl-terminal esterase L1 (UCHL1) is a biomarker that has been shown to increase following traumatic brain injury but has not been investigated in concussed athletes on the sideline of athletic events. Therefore, this study was conducted to determine if UCHL1 can be used to aid in sideline concussion diagnosis. Blood was taken via standard venipuncture from a recreationally active control group, a group of rugby players prior to match play (pre-match), rugby players following match-play (match-control), and rugby players after suffering a sport-related concussion (SRC). UCHL1 was not significantly different among groups (p > 0.05) and was unable to distinguish between SRC and controls (AUROC < 0.400, p > 0.05). However, when sex-matched data were used, it was found that the female match-control group had a significantly higher serum UCHL1 concentration than the pre-match group (p = 0.041). Differences were also found in serum UCHL1 concentrations between male and female athletes in the match-control group (p = 0.007). This study does not provide evidence supporting the use of UCHL1 in sideline concussion diagnosis when blood is collected soon after concussion but does show differences in serum UCHL1 accumulation between males and females.

Using Evidence-Based Medicine to Support Clinical Decision-Making in RMS.

The foundations of evidence-based practice are the triad of patient values and preferences, healthcare professional experience, and best available evidence, used together to inform clinical decision-making. Within the field of rhabdomyosarcoma, collaborative groups such as the European Paediatric Soft Tissue Sarcoma Group (EpSSG) have worked to develop evidence to support this process. We have explored many of the key research developments within this review, including patient and public involvement, decision-making research, research into areas other than drug development, core outcome sets, reporting and dissemination of research, evidence synthesis, guideline development and clinical decision rules, research of research methodologies, and supporting research in RMS.

Optimising Antimicrobial Selection and Duration in the Treatment of Febrile Neutropenia in Children.

Febrile neutropenia (FN) is a frequent complication of cancer treatment in children. Owing to the potential for overwhelming bacterial sepsis, the recognition and management of FN requires rapid implementation of evidenced-based management protocols. Treatment paradigms have progressed from hospitalisation with broad spectrum antibiotics for all patients, through to risk adapted approaches to management. Such risk adapted approaches aim to provide safe care through incorporating antimicrobial stewardship (AMS) principles such as implementation of comprehensive clinical pathways incorporating de-escalation strategies with the imperative to reduce hospital stay and antibiotic exposure where possible in order to improve patient experience, reduce costs and diminish the risk of nosocomial infection. This review summarises the principles of risk stratification in FN, the current key considerations for optimising empiric antimicrobial selection including knowledge of antimicrobial resistance patterns and emerging technologies for rapid diagnosis of specific infections and summarises existing evidence on time to treatment, investigations required and duration of treatment. To aid treating physicians we suggest the key features based on current evidence that should be part of any FN management guideline and highlight areas for future research. The focus is on treatment of bacterial infections although fungal and viral infections are also important in this patient group.

Protein S100B and Brain Lipid-Binding Protein Concentrations in the Serum of Recently Concussed Rugby Players.

The purpose of this study was to test the ability of serum protein S100B (S100B) and brain lipid-binding protein (BLBP) to identify athletes who sustained a sports-related concussion (SRC). Subjects included a non-athlete group, whereas the rugby players were separated into two match-control and two SRC groups. The match-control <1-h group included players undergoing venipuncture within 60-min post-match, and the match-control >1-h/<8-h group included players undergoing venipuncture between 1 and 8 h post-match; the SRC <1-h group included players undergoing venipuncture within 60-min post-SRC, and the SRC >1-h/<8-h group included players undergoing venipuncture between 1 and 8 h post-SRC. Serum S100B concentrations were not significantly different (p = 0.112) among protocols. Serum BLBP was greater in the match-control <1-h group (p < 0.001) and the SRC >1-h/<8-h group (p = 0.003) compared to the non-athlete group. The ability of serum BLBP to distinguish between SRC groups and the non-athlete group was shown to be good to excellent (AUROC, >0.8; p < 0.05), and between match-control groups and the non-athlete group were shown to be excellent (AUROC, >0.9; p < 0.05). Our results show that serum S100B is not useful in distinguishing concussed or post-match athletes from non-athletes. However, serum BLBP was shown to distinguish non-athletes from post-match or concussed athletes. Serum BLBP could not distinguish between athletes experiencing an SRC within 1 h of blood draw and those participating in a contact sport.

COVID-19 and children with cancer: Parents' experiences, anxieties and support needs.

BACKGROUND: Children with cancer were designated as clinically extremely vulnerable if they were to contract SARS-CoV-2 due to immune suppression in the early phase of the COVID-19 pandemic. Our aim was to explore experiences, information and support needs, and decision making of parents with a child with cancer in response to this phase in the United Kingdom. METHODS: Parents of a child with cancer completed a survey at a time when the UK moved into a period of 'lockdown'. An online survey was developed by the research team to capture parents' experiences, information and support needs, and decision making, using closed statements and open text boxes. Descriptive quantitative analyses and qualitative thematic content analysis were undertaken. FINDINGS: One hundred seventy-one parents/caregivers completed the survey. Eighty-five percent were worried about the virus and they were vigilant about the virus (92%) or cancer symptoms (93.4%). For two-thirds (69.6%), hospital was no longer considered a safe place. Eight overarching themes were identified related to the virus: (a) risk of infection; (b) information, guidance and advice; (c) health care provision; (d) fears and anxieties; or related to lockdown/isolation: (e) psychological and social impact; (f) keeping safe under lockdown; (g) provisions and dependence; and (h) employment and income. CONCLUSIONS: This is the first study, to the best of our knowledge, to report experiences of parents of a child with cancer during the SARS-CoV-2/COVID-19 pandemic. The majority of parents were worried about SARS-CoV-2 and transmitting the virus to their child. Hospital was no longer perceived to be a safe place, and parents were worried about suboptimal cancer care. Parents described fear and anxiety and the psychological, social and economic impact of isolation.

How to be successful in an academic interview in pediatric oncology: A survey of Children's Oncology Group (COG) and International Society of Paediatric Oncology (SIOP) mentors.

BACKGROUND: A successful academic interview has been reported as the most important factor contributing to ranking of candidates for residency. However, little published guidance exists to help a prospective oncologist or researcher give such an interview. The International Society of Paediatric Oncology (SIOP) Young Investigator (YI) Network and Children's Oncology Group (COG) YI group thus cosponsored a survey of senior investigators seeking their advice. METHODS: An electronic survey covering aspects of the academic interview of both trainees and faculty were sent to all current/past mentors serving in the COG YI mentorship program and those registered as mentors in the SIOP YI mentorship program. The responses were quantitatively and qualitatively analyzed. RESULTS: The response rate was 43.7% (118/270) from 25 countries. Majority of United States (US) interviewers (86.8%) conducted interviews individually, while 74% of non-US interviewers conducted panel interviews or both types equally (P < .001). Majority of interviewers (83.4%) at least occasionally contacted colleagues for off the record opinions on candidates, and 40.9% conducted an internet or social media search. Enthusiasm for the job (97.2%) and being a team player (95.3%) were the qualities most rated as at least moderately important, while a priority for work-life balance (45.4%) and having interests/hobbies outside of medicine (29.2%) were considered less important. Interviewers provided interview questions, tips for candidates, and key pitfalls to avoid. DISCUSSION: Candidates should prepare for their academic interviews in advance, be enthusiastic and honest when giving responses. Detailed guidance for those applying at different career stages and in different countries are provided.

Sharing Roles and Control in Pediatric Low Risk Febrile Neutropenia: A Multicenter Focus Group Discussion Study Involving Patients, Parents, and Health Care Professionals.

INTRODUCTION: Reducing treatment intensity for pediatric low risk febrile neutropenia may improve quality of life, and reduce hospital-acquired infections and costs. Key stakeholders' attitudes toward early discharge regimens are unknown. This study explored perceptions of reduced therapy regimens in the United Kingdom. MATERIALS AND METHODS: Three study sites were purposively selected for their approaches to risk stratification, treatment protocols, shared care networks, and geographical spread of patients. Patients aged 13 to 18 years, parents of children of all ages and health care professionals participated in focus group discussions. A constant comparison analysis was used. RESULTS: Thirty-two participants spoke of their different roles in managing febrile neutropenia and how these would change if reduced therapy regimens were implemented, how mutual trust would need to be strengthened and responsibility redistributed. Having identified a need for discretion and a desire for individualized care, negotiation within a spectrum of control allows achievement of the potential for realized discretion. Nonattendance exemplifies when control is different and families use their assessments of risk and sense of mutual trust, along with previous experiences, to make decisions. CONCLUSIONS: The significance of shared decision making in improving patient experience through sharing risks, developing mutual trust, and negotiating control to achieve individualized treatment cannot be underestimated.

A systematic review of evidence for and against routine surveillance imaging after completing treatment for childhood extracranial solid tumors.

BACKGROUND: Regular off-treatment imaging is often used to assess for recurrence of disease after childhood cancer treatment. It is unclear if this increases survival, or what burden surveillance places on patients, families, or health-care services. This systematic review examines the impact of routine surveillance imaging after treatment of pediatric extracranial solid tumors. METHODS: Collaborative patient and public involvement informed the design and interpretation of this work. Thirteen electronic databases, conference proceedings, and trial registries were searched alongside reference list checking and forward citation searching from 1990 onwards. Studies were screened and data were extracted by two researchers. Risk of bias was assessed using a modified ROBINS-I tool. Relevant outcomes were overall survival, psychological distress indicators, number of imaging tests, cost-effectiveness, and qualitative data regarding experiences of surveillance programs. PROSPERO (CRD42018103764). RESULTS: Of 17 727 records identified, 55 studies of 10 207 patients were included. All studies used observational methods. Risk of bias for all except one study was moderate, serious, or critical. Data were too few to conduct meta-analysis; however, narrative synthesis was performed. Surveillance strategies varied, and poorly reported, involving many scans and substantial radiation exposure (eg, neuroblastoma, median 133.5 mSv). For most diseases, surveillance imaging was not associated with increased overall survival, with the probable exception of Wilms tumor. No qualitative or psychological distress data were identified. CONCLUSIONS: At present, there is insufficient evidence to evaluate the effects of routine surveillance imaging on survival in most pediatric extracranial solid tumors. More high-quality data are required, preferably through randomized controlled trials with well-conducted qualitative elements.

From the sticky floor to the glass ceiling and everything in between: protocol for a systematic review of barriers and facilitators to clinical academic careers and interventions to address these, with a focus on gender inequality.

BACKGROUND: Gender inequality within academic medicine and dentistry is a well-recognised issue, but one which is not completely understood in terms of its causes, or interventions to facilitate equality. This systematic review aims to identify, critically appraise, and synthesise the literature on facilitators and barriers to progression through a clinical academic career across medicine and dentistry. It will also explore interventions developed to increase recruitment and retention to clinical academic careers, with a particular focus on gender inequality. METHODS: The search will cover five databases (MEDLINE (including MEDLINE Epub Ahead of Print, MEDLINE In-Process & Other Non-Indexed Citations, and MEDLINE Daily), Cochrane Controlled Register of Trials (CENTRAL), PsycINFO, and Education Resource Information Center (ERIC)), reference lists, and forward citation searching. We will include studies of doctors, dentists, and/or those with a supervisory role over their careers, with or without an academic career. Outcomes will be study defined, but relate to success rates of joining or continuing within a clinical academic career, including but not limited to success in gaining funding support, proportion of time spent in academic work, and numbers of awards/higher education qualifications, as well as experiences of professionals within the clinical academic pathway. Study quality will be assessed using the Cochrane risk of bias tool for randomised controlled trials, the Newcastle-Ottawa tool for non-randomised studies, and the QARI tool for qualitative studies. Detailed plans for screening, data extraction, and analysis are provided within this protocol. DISCUSSION: This systematic review is situated within a larger project evaluating gender inequalities in clinical academic careers. This review will identify and synthetize barriers, facilitators, and interventions addressing gender inequalities in clinical academia. Our findings will increase awareness of inequalities in clinical academic careers through informing clinical academics, regulators and funders of the issues involved, and potential interventions to counteract these. Results will be published in a peer-reviewed journal. SYSTEMATIC REVIEW REGISTRATION: Open Science Framework: https://osf.io/mfy7a.

Association of time to antibiotics and clinical outcomes in patients with fever and neutropenia during chemotherapy for cancer: a systematic review.

PURPOSE: Prompt antibiotic therapy is standard of care for patients with fever and neutropenia (FN) during chemotherapy for cancer. We systematically reviewed the association between time to antibiotics (TTA) and clinical outcomes. METHODS: The search covered seven databases; confounding biases and study quality were assessed with the ROBINS-I tool. Safety (death, intensive care unit (ICU) admission, sepsis) and treatment adequacy (relapse of infection, persistence or recurrence of fever) were assessed as primary outcomes. RESULTS: Of 6296 articles identified, 13 observational studies were included. Findings regarding safety were inconsistent. Three studies controlling for triage bias showed a possible association between longer TTA and impaired safety. Meta-analysis for TTA ≤ 60 min versus > 60 min was feasible on four studies, with three studies each reporting on death (OR 0.78, 95%CI 0.16-3.69) and on ICU admission (OR 1.43, 95%CI 0.57-3.60). No study reported data on treatment adequacy. Triage bias, i.e. faster treatment of patients with worse clinical condition, was identified as a relevant confounding factor. CONCLUSION: There seems to be an association between longer TTA and impaired safety. More knowledge about TTA effects on safety are important to optimise treatment guidelines for FN. Controlling for triage and other biases is necessary to gain further evidence. TRIAL REGISTRATION: Registration: PROSPERO [http://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42018092948].

Interventions aiming to reduce time to antibiotics (TTA) in patients with fever and neutropenia during chemotherapy for cancer (FN), a systematic review.

PURPOSE: Multiple interventions have been developed aiming to reduce time to antibiotics (TTA) in patients with fever and neutropenia (FN) following chemotherapy for cancer. We evaluated their effect to reduce TTA and their impact on important clinical outcomes in a systematic review. METHODS: The search covered seven databases. Biases and quality of studies were assessed with the Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) tool. Interventions could be implemented in any setting and performed by any person included in the FN management. Absolute change of TTA was the primary outcome. Registration: PROSPERO (CRD42018092948). RESULTS: Six thousand two hundred ninety-six titles and abstracts were screened, 177 studies were retrieved and 30 studies were included. Risk of bias was moderate to serious in 28 studies and low in two studies. All but one study reported a reduction of TTA after the intervention. Various types of interventions were implemented; they most commonly aimed at professionals. Most of the studies made more than one single intervention. CONCLUSION: This review may help centers to identify their specific sources of delay and barriers to change and to define what intervention may be the best to apply. This review supports the assertion that TTA can be considered a measure of quality of care, emphasizes the importance of education and training, and describes the very different interventions which have effectively reduced TTA.

Does routine surveillance imaging after completing treatment for childhood solid tumours cause more harm than good? A systematic review and meta-analysis protocol.

BACKGROUND: This systemic review aims to synthesise the current literature surrounding off-therapy surveillance imaging in children and young people with extra-cranial solid tumours, with a view to establishing if routine imaging studies after treatment for childhood cancer increase overall survival, increase the psychological distress caused to patients and families, result in other harms to patients and are cost-effective strategies. Within this manuscript, we also describe how patient and public involvement has impacted upon the protocol. METHODS: The search will cover thirteen different databases, key conference proceedings and trial registers, as well as reference lists and forward citations of included papers. Prominent authors/clinicians in the field will be contacted. A full search strategy is provided. The study designs to be included in the review will be added in an iterative way (RCTs, quasi-randomised trials, prospective cohorts and retrospective cohorts). Qualitative studies will also be eligible for inclusion. We will include studies which examine a programme of surveillance imaging that aims to detect relapse in children or young people up to age 25 years who have completed treatment for a malignant extracranial solid tumour and have no evidence of active and ongoing disease at end of treatment. The primary outcome is overall survival, with secondary outcomes including psychological distress indicators, number of imaging tests performed, other harms of imaging and cost-effectiveness measures. Studies will be screened and data extracted by two researchers. Studies will be critically appraised using a stratified version of the ROBINS-I tool. Where appropriate, data will be synthesised using a random effects meta-analysis. A detailed analysis plan, including assessment of heterogeneity and publication bias, is provided. DISCUSSION: The aim of routine surveillance imaging is to detect recurrence of disease before clinical symptoms and signs develop. Some studies have suggested that most relapses of childhood cancer are detected due to clinical symptoms or signs, particularly in those with extra-cranial solid tumours, and when these relapses are detected by imaging, there is no increase in survival. This review aims to establish whether routine surveillance imaging is beneficial, as well as evaluating the potential negative impacts of surveillance programmes. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018103764.