The effectiveness and safety of proton beam radiation therapy in children and young adults with Central Nervous System (CNS) tumours: a systematic review.

BACKGROUND: Central nervous system (CNS) tumours account for around 25% of childhood neoplasms. With multi-modal therapy, 5-year survival is at around 75% in the UK. Conventional photon radiotherapy has made significant contributions to survival, but can be associated with long-term side effects. Proton beam radiotherapy (PBT) reduces the volume of irradiated tissue outside the tumour target volume which may potentially reduce toxicity. Our aim was to assess the effectiveness and safety of PBT and make recommendations for future research for this evolving treatment. METHODS: A systematic review assessing the effects of PBT for treating CNS tumours in children/young adults was undertaken using methods recommended by Cochrane and reported using PRISMA guidelines. Any study design was included where clinical and toxicity outcomes were reported. Searches were to May 2021, with a narrative synthesis employed. RESULTS: Thirty-one case series studies involving 1731 patients from 10 PBT centres were included. Eleven studies involved children with medulloblastoma / primitive neuroectodermal tumours (n = 712), five ependymoma (n = 398), four atypical teratoid/rhabdoid tumour (n = 72), six craniopharyngioma (n = 272), three low-grade gliomas (n = 233), one germ cell tumours (n = 22) and one pineoblastoma (n = 22). Clinical outcomes were the most frequently reported with overall survival values ranging from 100 to 28% depending on the tumour type. Endocrine outcomes were the most frequently reported toxicity outcomes with quality of life the least reported. CONCLUSIONS: This review highlights areas of uncertainty in this research area. A well-defined, well-funded research agenda is needed to best maximise the potential of PBT. SYSTEMATIC REVIEW REGISTRATION: PROSPERO-CRD42016036802.

Self-management of health care behaviors for COPD: a systematic review and meta-analysis.

PURPOSE: This systematic review aimed to identify the most effective components of interventions to facilitate self-management of health care behaviors for patients with COPD. PROSPERO registration number CRD42011001588. METHODS: We used standard review methods with a systematic search to May 2012 for randomized controlled trials of self-management interventions reporting hospital admissions or health-related quality of life (HRQoL). Mean differences (MD), hazard ratios, and 95% confidence intervals (CIs) were calculated and pooled using random-effects meta-analyses. Effects among different subgroups of interventions were explored including single/multiple components and multicomponent interventions with/without exercise. RESULTS: One hundred and seventy-three randomized controlled trials were identified. Self-management interventions had a minimal effect on hospital admission rates. Multicomponent interventions improved HRQoL (studies with follow-up >6 months St George's Respiratory Questionnaire (MD 2.40, 95% CI 0.75-4.04, I (2) 57.9). Exercise was an effective individual component (St George's Respiratory Questionnaire at 3 months MD 4.87, 95% CI 3.96-5.79, I (2) 0%). CONCLUSION: While many self-management interventions increased HRQoL, little effect was seen on hospital admissions. More trials should report admissions and follow-up participants beyond the end of the intervention.

Supported self-management for patients with COPD who have recently been discharged from hospital: a systematic review and meta-analysis.

PURPOSE: Although many hospitals promote self-management to chronic obstructive pulmonary disease (COPD) patients post discharge from hospital, the clinical effectiveness of this is unknown. We undertook a systematic review of the evidence as part of a Health Technology Assessment review. METHODS: A comprehensive search strategy with no language restrictions was conducted across relevant databases from inception to May 2012. Randomized controlled trials of patients with COPD, recently discharged from hospital after an acute exacerbation and comparing a self-management intervention with control, usual care or other intervention were included. Study selection, data extraction, and risk of bias assessment were undertaken by two reviewers independently. RESULTS: Of 13,559 citations, 836 full texts were reviewed with nine randomized controlled trials finally included in quantitative syntheses. Interventions were heterogeneous. Five trials assessed highly supported multi-component interventions and four trials were less supported with fewer contacts with health care professionals and mainly home-based interventions. Total sample size was 1,466 (range 33-464 per trial) with length of follow-up 2-12 months. Trials varied in quality; poor patient follow-up and poor reporting was common. No evidence of effect in favor of self-management support was observed for all-cause mortality (pooled hazard ratio =1.07; 95% confidence interval [0.74 to 1.55]; I (2)=0.0%, [n=5 trials]). No clear evidence of effect on all-cause hospital admissions was observed (hazard ratio 0.88 [0.61, 1.27] I (2)=66.0%). Improvements in St George's Respiratory Questionnaire score were seen in favor of self-management interventions (mean difference =3.84 [1.29 to 6.40]; I (2)=14.6%), although patient follow-up rates were low. CONCLUSION: There is insufficient evidence to support self-management interventions post-discharge. There is a need for good quality primary research to identify effective approaches.

Supported self-management for patients with moderate to severe chronic obstructive pulmonary disease (COPD): an evidence synthesis and economic analysis.

BACKGROUND: Self-management (SM) support for patients with chronic obstructive pulmonary disease (COPD) is variable in its coverage, content, method and timing of delivery. There is insufficient evidence for which SM interventions are the most effective and cost-effective. OBJECTIVES: To undertake (1) a systematic review of the evidence for the effectiveness of SM interventions commencing within 6 weeks of hospital discharge for an exacerbation for COPD (review 1); (2) a systematic review of the qualitative evidence about patient satisfaction, acceptance and barriers to SM interventions (review 2); (3) a systematic review of the cost-effectiveness of SM support interventions within 6 weeks of hospital discharge for an exacerbation of COPD (review 3); (4) a cost-effectiveness analysis and economic model of post-exacerbation SM support compared with usual care (UC) (economic model); and (5) a wider systematic review of the evidence of the effectiveness of SM support, including interventions (such as pulmonary rehabilitation) in which there are significant components of SM, to identify which components are the most important in reducing exacerbations, hospital admissions/readmissions and improving quality of life (review 4). METHODS: The following electronic databases were searched from inception to May 2012: MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and Science Citation Index [Institute of Scientific Information (ISI)]. Subject-specific databases were also searched: PEDro physiotherapy evidence database, PsycINFO and the Cochrane Airways Group Register of Trials. Ongoing studies were sourced through the metaRegister of Current Controlled Trials, International Standard Randomised Controlled Trial Number database, World Health Organization International Clinical Trials Registry Platform Portal and ClinicalTrials.gov. Specialist abstract and conference proceedings were sourced through ISI's Conference Proceedings Citation Index and British Library's Electronic Table of Contents (Zetoc). Hand-searching through European Respiratory Society, the American Thoracic Society and British Thoracic Society conference proceedings from 2010 to 2012 was also undertaken, and selected websites were also examined. Title, abstracts and full texts of potentially relevant studies were scanned by two independent reviewers. Primary studies were included if ≈90% of the population had COPD, the majority were of at least moderate severity and reported on any intervention that included a SM component or package. Accepted study designs and outcomes differed between the reviews. Risk of bias for randomised controlled trials (RCTs) was assessed using the Cochrane tool. Random-effects meta-analysis was used to combine studies where appropriate. A Markov model, taking a 30-year time horizon, compared a SM intervention immediately following a hospital admission for an acute exacerbation with UC. Incremental costs and quality-adjusted life-years were calculated, with sensitivity analyses. RESULTS: From 13,355 abstracts, 10 RCTs were included for review 1, one study each for reviews 2 and 3, and 174 RCTs for review 4. Available studies were heterogeneous and many were of poor quality. Meta-analysis identified no evidence of benefit of post-discharge SM support on admissions [hazard ratio (HR) 0.78, 95% confidence interval (CI) 0.52 to 1.17], mortality (HR 1.07, 95% CI 0.74 to 1.54) and most other health outcomes. A modest improvement in health-related quality of life (HRQoL) was identified but this was possibly biased due to high loss to follow-up. The economic model was speculative due to uncertainty in impact on readmissions. Compared with UC, post-discharge SM support (delivered within 6 weeks of discharge) was more costly and resulted in better outcomes (£683 cost difference and 0.0831 QALY gain). Studies assessing the effect of individual components were few but only exercise significantly improved HRQoL (3-month St George's Respiratory Questionnaire 4.87, 95% CI 3.96 to 5.79). Multicomponent interventions produced an improved HRQoL compared with UC (mean difference 6.50, 95% CI 3.62 to 9.39, at 3 months). Results were consistent with a potential reduction in admissions. Interventions with more enhanced care from health-care professionals improved HRQoL and reduced admissions at 1-year follow-up. Interventions that included supervised or unsupervised structured exercise resulted in significant and clinically important improvements in HRQoL up to 6 months. LIMITATIONS: This review was based on a comprehensive search strategy that should have identified most of the relevant studies. The main limitations result from the heterogeneity of studies available and widespread problems with their design and reporting. CONCLUSIONS: There was little evidence of benefit of providing SM support to patients shortly after discharge from hospital, although effects observed were consistent with possible improvement in HRQoL and reduction in hospital admissions. It was not easy to tease out the most effective components of SM support packages, although interventions containing exercise seemed the most effective. Future work should include qualitative studies to explore barriers and facilitators to SM post exacerbation and novel approaches to affect behaviour change, tailored to the individual and their circumstances. Any new trials should be properly designed and conducted, with special attention to reducing loss to follow-up. Individual participant data meta-analysis may help to identify the most effective components of SM interventions. STUDY REGISTRATION: This study is registered as PROSPERO CRD42011001588. FUNDING: The National Institute for Health Research Health Technology Assessment programme.