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

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.

A systematic review of time to diagnosis in children and young adults with cancer.

PURPOSE: It is often assumed that prolonged time to diagnosis (TTD) for cancer negatively influences overall survival and survivorship through advanced stage disease at diagnosis. This systematic review assesses existing early diagnosis research in childhood and young adult cancer and aims to identify whether a consensus exists within the literature in relation to the terminology and methodologies used to investigate TTD in this population. METHODS: Medline, Embase, the Centre for Reviews and Dissemination database and Cochrane library were searched for papers on children and young adults (0-30 years) published from 1948 to the present. RESULTS: Of the 1665 potentially eligible citations identified, 32 papers met the inclusion criteria. The majority of work was in European (n=15) or North American (n=8) populations. Most work focused on brain tumours (n=10), retinoblastomas (n=5) and bone and soft tissue sarcomas (n=4). The majority of studies were in hospital-based settings (n=25), with only seven papers adopting a population-based setting. Summary statistics presented were mostly median TTD, the skewed distribution of the data meant comparisons between studies based on medians were difficult and combining studies within a meta-analysis was not appropriate. CONCLUSIONS: Within the childhood and young adult population, TTD for cancer varies between diagnostic groups and with age at diagnosis in the majority of studies. In order that clear conclusions can be drawn from early diagnosis research in children and young adults, specific criteria identifying circumstances in which delay has occurred should accompany a defined time line to diagnosis or treatment in every study.

Bisphosphonate therapy for reduced bone mineral density during treatment of acute lymphoblastic leukemia in childhood and adolescence: a report of preliminary experience.

BACKGROUND: Osteopenia is a common consequence of the treatment of acute lymphoblastic leukemia (ALL) in children and adolescents, due predominantly to glucocorticosteroid therapy. The pathogenesis relates to an imbalance of resorption over formation of bone. METHODS: Alendronate (Fosamax), an inhibitor of osteoclastic bone resorption, was administered for at least 6 months to 15 children with ALL during maintenance chemotherapy, after the diagnosis of osteopenia/osteoporosis by dual energy x-ray absorptiometry. The height velocity was also measured during the administration of alendronate and again 2 years later. RESULTS: Areal bone mineral density Z scores of the lumbar spine had a median value of -1.32 before administration of alendronate and a median gain of +0.64, with 14/15 children showing improvement. There was no adverse effect of alendronate on height velocity, and the drug was well tolerated with no short-term toxicity. CONCLUSIONS: This preliminary experience suggests a potential value in the use of alendronate for the treatment of osteopenia/osteoporosis in children with ALL and points to the need for a randomized controlled trial of this intervention.