Publications by authors named "Jessica E Morgan"

19 Publications

  • Page 1 of 1

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

Infect Drug Resist 2021 30;14:1283-1293. Epub 2021 Mar 30.

Royal Marsden Hospital and Institute of Cancer Research, Sutton, SM2 5PT, UK.

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.
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http://dx.doi.org/10.2147/IDR.S238567DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019605PMC
March 2021

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

J Neurotrauma 2021 Mar 27. Epub 2021 Mar 27.

Rutgers University Newark, 67206, Department of Veteran Affairs and Department of Pharmacology, Physiology, and Neuroscience, Newark, New Jersey, United States;

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, while the rugby players were separated into two match-control and two SRC groups. The match-control < 1-hr. group included players undergoing venipuncture within 60-minutes post-match and the match-control > 1-hr. < 8-hrs. group included players undergoing venipuncture between one and eight-hours post-match; the SRC < 1-hr. group included players undergoing venipuncture within 60-minutes post-SRC, and the SRC > 1-hr. < 8-hrs. group included players undergoing venipuncture between one and eight-hours post-SRC. Serum S100B concentrations were not significantly different (p = 0.112) among protocols. Serum BLBP was greater in the match-control < 1-hr. group (p < 0.001) and the SRC > 1-hr. < 8-hrs. 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 were 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 distinguish non-athletes from post-match or concussed athletes. Serum BLBP could not distinguish between athletes experiencing an SRC within one-hour of blood draw and those participating in a contact sport.
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http://dx.doi.org/10.1089/neu.2021.0004DOI Listing
March 2021

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.

Pediatr Blood Cancer 2021 Mar 23;68(3):e28855. Epub 2020 Dec 23.

Monroe Carell Jr. Children's Hospital, Vanderbilt Division of Pediatric Hematology-Oncology and Vanderbilt-Ingram Cancer Center, Nashville, Tennessee.

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.
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http://dx.doi.org/10.1002/pbc.28855DOI Listing
March 2021

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

Pediatr Blood Cancer 2021 02 21;68(2):e28790. Epub 2020 Nov 21.

Centre for Reviews and Dissemination, University of York, York, UK.

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.
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http://dx.doi.org/10.1002/pbc.28790DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744834PMC
February 2021

Meta-analytic validation of new 'AUS' febrile neutropenia risk score.

Pediatr Blood Cancer 2021 01 25;68(1):e28580. Epub 2020 Jul 25.

Centre for Reviews and Dissemination, University of York, York, UK.

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http://dx.doi.org/10.1002/pbc.28580DOI Listing
January 2021

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

Cancer Med 2020 07 19;9(14):4949-4961. Epub 2020 May 19.

Centre for Reviews and Dissemination, University of York, York, UK.

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.
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http://dx.doi.org/10.1002/cam4.3110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7367646PMC
July 2020

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

J Pediatr Hematol Oncol 2020 07;42(5):337-344

Department of Health Sciences, University of York, York.

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.
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http://dx.doi.org/10.1097/MPH.0000000000001827DOI Listing
July 2020

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.

Syst Rev 2020 02 10;9(1):26. Epub 2020 Feb 10.

Centre for Reviews and Dissemination, University of York, York, UK.

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.
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http://dx.doi.org/10.1186/s13643-020-1286-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7011470PMC
February 2020

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

Support Care Cancer 2020 May 5;28(5):2369-2380. Epub 2019 Sep 5.

Centre for Reviews and Dissemination, University of York, York, UK.

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.
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http://dx.doi.org/10.1007/s00520-019-05056-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7083808PMC
May 2020

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

Syst Rev 2019 07 12;8(1):168. Epub 2019 Jul 12.

Centre for Reviews and Dissemination, University of York, Heslington, York, YO10 5DD, UK.

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.
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http://dx.doi.org/10.1186/s13643-019-1096-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6624999PMC
July 2019

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

Support Care Cancer 2020 Mar 1;28(3):1369-1383. Epub 2019 Jul 1.

Centre for Reviews and Dissemination, University of York, York, UK.

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].
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http://dx.doi.org/10.1007/s00520-019-04961-4DOI Listing
March 2020

Fifteen minute consultation: Fever in children being treated for cancer.

Authors:
Jessica E Morgan

Arch Dis Child Educ Pract Ed 2019 06 13;104(3):124-128. Epub 2018 Aug 13.

Fever is a common symptom in children receiving treatment for cancer. Clinicians and families are most concerned about febrile neutropenia, though non-neutropenic fever often causes more challenging treatment dilemmas. This article provides a structured approach to the initial assessment, examination, investigation and risk assessment of children with fever during treatment for childhood cancer. Non-neutropenic fever in children with cancer is not well researched. There are no systematic reviews of its management and no National Institute for Health and Care Excellence (NICE) (or other international) guidance about what to do. Features to consider when managing non-neutropenic fever are discussed. Febrile neutropenia, meanwhile, is an oncological emergency and requires management using standard sepsis principles including administration of broad-spectrum antibiotics. Relevant NICE guidance provides a clear structure for treatment. Ongoing management depends on the response to initial treatment.
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http://dx.doi.org/10.1136/archdischild-2017-314718DOI Listing
June 2019

Quest for certainty regarding early discharge in paediatric low-risk febrile neutropenia: a multicentre qualitative focus group discussion study involving patients, parents and healthcare professionals in the UK.

BMJ Open 2018 05 14;8(5):e020324. Epub 2018 May 14.

Department of Health Sciences, University of York, York, UK.

Objectives: A systematic review of paediatric low-risk febrile neutropenia found that outpatient care is safe, with low rates of treatment failure. However, this review, and a subsequent meta-ethnography, suggested that early discharge of these patients may not be acceptable to key stakeholders. This study aimed to explore experiences and perceptions of patients, parents and healthcare professionals involved in paediatric febrile neutropenia care in the UK.

Setting: Three different centres within the UK, purposively selected from a national survey on the basis of differences in their service structure and febrile neutropenia management.

Participants: Thirty-two participants were included in eight focus group discussions.

Primary Outcomes: Experiences and perceptions of paediatric febrile neutropenia care, including possible future reductions in therapy.

Results: Participants described a quest for certainty, in which they attempted to balance the uncertainty involved in understanding, expressing and negotiating risk with the illusion of certainty provided by strict protocols. Participants assessed risk using both formal and informal stratification tools, overlaid with emotional reactions to risk and experiences of risk within other situations. The benefits of certainty provided by protocols were counterbalanced by frustration at their strict constraints. The perceived benefits and harms of previous inpatient care informed participants' appraisals of future treatment strategies.

Conclusions: This study highlighted the previously underestimated harms of admission for febrile neutropenia and the paternalistic nature of decision making, along with the frustrations and challenges for all parties involved in febrile neutropenia care. It demonstrates how the same statistics, generated by systematic reviews, can be used by key stakeholders to interpret risk differently, and how families in particular can view the harms of therapeutic options as different from the outcomes used within the literature. It justifies a reassessment of current treatment strategies for these children and further exploration of the potential to introduce shared decision making.
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http://dx.doi.org/10.1136/bmjopen-2017-020324DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5961608PMC
May 2018

Paired learning - improving collaboration between clinicians and managers.

J Health Organ Manag 2018 Mar 9;32(1):101-112. Epub 2018 Jan 9.

Centre for Reviews and Dissemination, University of York , York, UK.

Purpose Close collaboration between NHS clinicians and managers is essential in providing effective healthcare, but relationships between the two groups are often poor. Paired learning is a peer-peer buddying tool that can break down barriers, increase knowledge and change attitudes. Paired learning has been used with doctors and managers but not for multi-professional clinicians. The purpose of this paper is to assess whether a paired learning programme (PLP) can improve knowledge and attitudes between multi-professional NHS clinicians and managers. Design/methodology/approach A PLP pairing clinicians and managers over a four-month period to participate in four buddy meetings and three group meetings was delivered. A mixed methods study was completed which collected quantitative and qualitative data in the form of pre- and post-course questionnaires and focus group discussions. Findings Participants reported increased understanding, changed attitudes and better communication between clinicians and managers following the PLP. Self-rated knowledge increased across all domains but was only statistically significant for ability to engage, ability to establish shared goals and knowledge of decision-making processes. Research limitations/implications This paper highlights the value of paired learning in encouraging collaboration between clinicians and managers but is of a small size. The PLP did not provide enough data to examine relationships and interaction between clinicians and managers, this should be considered in any future work. Originality/value To the authors' knowledge, this is the only published paper showing data from a PLP involving multi-disciplinary health professionals.
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http://dx.doi.org/10.1108/JHOM-10-2017-0263DOI Listing
March 2018

Meta-ethnography of experiences of early discharge, with a focus on paediatric febrile neutropenia.

Support Care Cancer 2018 Apr 29;26(4):1039-1050. Epub 2017 Dec 29.

Department of Health Sciences, University of York, York, UK.

Purpose (stating The Main Purposes And Research Question): Many children have no significant sequelae of febrile neutropenia. A systematic review of clinical studies demonstrated patients at low risk of septic complications can be safely treated as outpatients using oral antibiotics with low rates of treatment failure. Introducing earlier discharge may improve quality of life, reduce hospital acquired infection and reduce healthcare service pressures. However, the review raised concerns that this might not be acceptable to patients, families and healthcare professionals.

Methods: This qualitative synthesis explored experiences of early discharge in paediatric febrile neutropenia, including reports from studies of adult febrile neutropenia and from other paediatric conditions. Systematic literature searching preceded meta-ethnographic analysis, including reading the studies and determining relationships between studies, translation of studies and synthesis of these translations.

Results: Nine papers were included. The overarching experience of early discharge is that decision-making is complex and difficult and influenced by fear, timing and resources. From this background, we identified two distinct themes. First, participants struggled with practical consequences of treatment regimens, namely childcare, finances and follow-up. A second theme identified social and emotional issues, including isolation, relational and environmental challenges. Linking these, participants considered continuity of care and the need for information important.

Conclusions: Trust and confidence appeared interdependent with resources available to families-both are required to manage early discharge. Socially informed resilience is relevant to facilitating successful discharge strategies. Interventions which foster resilience may mediate the ability and inclination of families to accept early discharge. Services have an important role in recognising and enhancing resilience.
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http://dx.doi.org/10.1007/s00520-017-3983-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5847030PMC
April 2018

Aminoaciduria in the prediction of ifosfamide-induced tubulopathy after childhood cancer: a feasibility study.

Pilot Feasibility Stud 2016 22;2. Epub 2016 Jan 22.

Department of Paediatric Oncology, Leeds Teaching Hospitals NHS Trust, Leeds, UK ; Centre for Reviews and Dissemination, University of York, Leeds, UK.

Background: Ifosfamide, an alkylating agent used widely in the treatment of childhood malignancy, can cause many side effects including a proximal tubulopathy. Studies suggest that aminoaciduria is seen most commonly of all the biochemical abnormalities of ifosfamide-induced tubulopathy. A recent systematic review has found a paucity of data regarding the value of early markers indicating clinically significant tubulopathy. We undertook a pilot study to determine the feasibility of examining whether patients can be risk-stratified on the basis of aminoaciduria for the development of future significant ifosfamide-induced tubulopathy, to allow the evolution of appropriate follow-up strategies. We also aimed to define accrual rates, costs and clinical demands for a future larger study.

Methods: This observational study recruited 21 patients from the Leeds Paediatric Oncology service. The medical notes of each patient were reviewed for demographic and clinical data. Simultaneous samples of blood and urine were obtained.

Results: The investigations in the feasibility study were acceptable to patients and were minimally demanding on both clinical and laboratory staff. Financially, the cost per patient was minimal. This study was not powered to detect significant associations with TmP/GFR (ratio of renal tubular maximum reabsorption rate of phosphate to glomerular filtration rate), growth and electrolyte supplementation. However, all patients with minimal aminoaciduria (≤2 elevated urinary amino acids) had normal TmP/GFR and no need for electrolyte supplementation.

Conclusions: This pilot study has shown that a larger study is feasible and may provide clinically useful data to change current practice. This should aim to establish whether the number of abnormal amino acids or the degree of abnormality is most significant in predicting clinically significant proximal tubulopathy.
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http://dx.doi.org/10.1186/s40814-015-0040-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5154030PMC
January 2016

Critical review of current clinical practice guidelines for antifungal therapy in paediatric haematology and oncology.

Support Care Cancer 2017 01 11;25(1):221-228. Epub 2016 Sep 11.

Centre for Reviews and Dissemination, University of York, York, YO10 5DD, UK.

Purpose: The incidence of invasive fungal disease (IFD) is rising, but its treatment in paediatric haematology and oncology patients is not yet standardised. This review aimed to critically appraise and analyse the clinical practice guidelines (CPGs) that are available for paediatric IFD.

Methods: Electronic searches of MEDLINE, MEDLINE in-Process & Other non-Indexed Citations, the Guidelines International Network (GIN), guideline.gov and Google were performed and combined fungal disease (Fung* OR antifung*OR Candida* OR Aspergill*) with prophylaxis or treatment (prophyl* OR therap* OR treatment). All guidelines were assessed using the AGREE II tool and recommendations relating to prophylaxis, empirical treatment and specific therapy were extracted.

Results: Nineteen guidelines met the inclusion criteria. The AGREE II scores for the rigour of development domain ranged from 11 to 92 % with a median of 53 % (interquartile range 32-69 %). Fluconazole was recommended as antifungal prophylaxis in all nine of the included guidelines which recommended a specific drug. Liposomal amphotericin B was recommended in all five guidelines giving empirical therapy recommendations. Specific therapy recommendations were given for oral or genital candidiasis, invasive candida infection, invasive aspergillosis and other mould infections.

Conclusions: In many areas, recommendations were clear about appropriate practice but further clarity was required, particularly relating to the decision to discontinue empirical antifungal treatment, the relative benefits of empiric and pre-emptive strategies and risk stratification. Future CPGs could consider working to published guideline production methodologies and sharing summaries of evidence appraisal to reduce duplication of effort, improving the quality and efficiency of CPGs in this area.
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http://dx.doi.org/10.1007/s00520-016-3412-yDOI Listing
January 2017

Systematic review of reduced therapy regimens for children with low risk febrile neutropenia.

Support Care Cancer 2016 06 13;24(6):2651-60. Epub 2016 Jan 13.

Centre for Reviews and Dissemination, University of York, Heslington, York, YO10 5DD, UK.

Purpose: Reduced intensity therapy for children with low-risk febrile neutropenia may provide benefits to both patients and the health service. We have explored the safety of these regimens and the effect of timing of discharge.

Methods: Multiple electronic databases, conference abstracts and reference lists were searched. Randomised controlled trials (RCT) and prospective observational cohorts examining the location of therapy and/or the route of administration of antibiotics in people younger than 18 years who developed low-risk febrile neutropenia following treatment for cancer were included. Meta-analysis using a random effects model was conducted. I (2) assessed statistical heterogeneity not due to chance.

Registration: PROSPERO (CRD42014005817).

Results: Thirty-seven studies involving 3205 episodes of febrile neutropenia were included; 13 RCTs and 24 prospective observational cohorts. Four safety events (two deaths, two intensive care admissions) occurred. In the RCTs, the odds ratio for treatment failure (persistence, worsening or recurrence of fever/infecting organisms, antibiotic modification, new infections, re-admission, admission to critical care or death) with outpatient treatment was 0.98 (95% confidence interval (95%CI) 0.44-2.19, I (2) = 0 %) and with oral treatment was 1.05 (95%CI 0.74-1.48, I (2) = 0 %). The estimated risk of failure using outpatient therapy from all prospective data pooled was 11.2 % (95%CI 9.7-12.8 %, I (2) = 77.2 %) and using oral antibiotics was 10.5 % (95%CI 8.9-12.3 %, I (2) = 78.3 %). The risk of failure was higher when reduced intensity therapies were used immediately after assessment, with lower rates when these were introduced after 48 hours.

Conclusions: Reduced intensity therapy for specified groups is safe with low rates of treatment failure. Services should consider how these can be acceptably implemented.
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http://dx.doi.org/10.1007/s00520-016-3074-9DOI Listing
June 2016

Protocol for a systematic review of reductions in therapy for children with low-risk febrile neutropenia.

Syst Rev 2014 Oct 21;3:119. Epub 2014 Oct 21.

Centre for Reviews and Dissemination, University of York, York, UK.

Background: Febrile neutropenia is a common complication of therapy in children with cancer. Some patients are at low risk of complications, and research has considered reduction in therapy for these patients. A previous systematic review broadly considered whether outpatient treatment and oral antibiotics were safe in this context and concluded that this was likely to be the case. Since that review, there has been further research in this area. Therefore, we aim to provide a more robust answer to these questions and to additionally explore whether the exact timing of discharge, including entirely outpatient treatment, has an impact on outcomes.

Methods/design: The search will cover MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, CDSR, CENTRAL, LILACS, HTA and DARE. A full search strategy is provided. Key conference proceedings and reference lists of included papers will be hand searched. Prominent authors/clinicians in the field will be contacted. We will include randomised and quasi-randomised controlled trials along with prospective single-arm studies that examine the location of therapy and/or the route of administration of antibiotics in children or young adults (aged less than 18 years) who attend paediatric services with fever and neutropenia due to treatment for cancer and are assessed to be at low risk of medical complications. Studies will be screened and data extracted by one researcher and independently checked by a second. All studies will be critically appraised using tools appropriate to the study design. Data from randomised controlled trials (RCTs) will be combined to provide comparative estimates of treatment failure, safety and adequacy. Information from quasi-randomised trials and single-arm studies will provide further data on the safety and adequacy of regimes. Random effects meta-analysis will be used to combine studies. A detailed analysis plan, including assessment of heterogeneity and publication bias, is provided.

Discussion: This study will aim to specifically define the features of a low-risk strategy that will maintain levels of safety and adequacy equivalent to those of traditional treatments. This will both inform the development of services and provide patients and families with data to help them make an informed decision about care.

Systematic Review Registration: PROSPERO CRD42014005817.
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http://dx.doi.org/10.1186/2046-4053-3-119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4234526PMC
October 2014