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Background Physical activity (PA) is associated with improved health-related quality of life (HRQoL) among women with breast cancer; however, uncertainty remains regarding PA types and dose (frequency, duration, intensity) and various HRQoL measures. A systematic review and meta-analysis of randomized controlled trials was conducted to clarify whether specific types and doses of physical activity was related to global and specific domains of HRQoL, as part of the Global Cancer Update Programme, formerly known as the World Cancer Research Fund–American Institute for Cancer Research Continuous Update Project. Methods PubMed and CENTRAL databases were searched up to August 31, 2019. Weighted mean differences (WMDs) in HRQoL scores were estimated using random effects models. An independent expert panel graded the evidence. Results A total of 79 randomized controlled trials (14 554 breast cancer patients) were included. PA interventions resulted in higher global HRQoL as measured by the Functional Assessment of Cancer Therapy–Breast (WMD = 5.94, 95% confidence intervals [CI] = 2.64 to 9.24; I2 = 59%, n = 12), Functional Assessment of Cancer Therapy–General (WMD = 4.53, 95% CI = 1.94 to 7.13; I2 = 72%, n = 18), and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire–C30 (WMD = 6.78, 95% CI = 2.61 to 10.95; I2 = 76.3%, n = 17). The likelihood of causality was considered probable that PA improves HRQoL in breast cancer survivors. Effects were weaker for physical function and mental and emotional health. Evidence regarding dose and type of PA remains insufficient for firm conclusions. Conclusion PA results in improved global HRQoL in breast cancer survivors with weaker effects observed for physical function and mental and emotional health. Additional research is needed to define the impact of types and doses of activity on various domains of HRQoL.

ObjectivesTo estimate the prevalence of 25-hydroxyvitamin D (25(OH)D) deficiency and investigate its association with mortality in children with acute or critical conditions.DesignSystematic review and meta-analysis of observational studies.Data sourcesPubMed, OVID, Google Scholar and the Cochrane Library searched until 21 December 2018.Eligibility criteriaStudies of children hospitalised with acute or critical conditions who had blood 25(OH)D levels measured.Data extraction and synthesisWe obtained pooled prevalence estimates of 25(OH)D deficiency and ORs for mortality. We calculated 95% CI and prediction intervals and investigated heterogeneity and evidence of small-study effects.ResultsFifty-two studies were included. Of 7434 children, 3473 (47.0%) were 25(OH)D deficient (2=95.3%, p2=89.3%, p2=94.3%, p2=25.7%, p=0.153). Four (22.0%) of the 18 studies statistically adjusted for confounders. There were insufficient studies to meta-analyse sepsis and RTI-related mortality.ConclusionsOur results suggest that 25(OH)D deficiency in acute and critically ill children is high and associated with increased mortality. Small-study effects, reverse causation and other biases may have confounded results. Larger, carefully designed studies in homogeneous populations with confounder adjustment are needed to clarify the association between 25(OH)D levels with mortality and other outcomes.Prospero registration numberCRD42016050638.

Background To summarise the evidence on the associations between body mass index (BMI) and BMI in early adulthood, height, waist circumference (WC) and waist-to-hip ratio (WHR), and risk of lympho-haematopoietic cancers. Method We conducted a meta-analysis of prospective studies and identified relevant studies published up to December 2017 by searching PubMed. A random-effects model was used to calculate dose–response summary relative risks (RRs). Results Our findings showed BMI, and BMI in early adulthood (aged 18–21years) is associated with the risk of Hodgkin's and non-Hodgkin's lymphoma (HL and NHL), diffuse large beta-cell lymphoma (DLBCL), Leukaemia including acute and chronic myeloid lymphoma (AML and CML), and chronic lymphocytic leukaemia (CLL) and multiple myeloma (MM). The summary RR per 5kg/m2 increase in BMI were 1.12 [95% confidence interval (CI): 1.05–1.20] for HL, 1.05 (95% CI: 1.03–1.08) for NHL, 1.11 (95% CI: 1.05–1.16) for DLBCL, 1.06 (95% CI: 1.03–1.09) for ML, 1.09 (95% CI: 1.03–1.15) for leukaemia, 1.13 (95% CI: 1.04–1.24) for AML, 1.13 (95% CI: 1.05–1.22) for CML and 1.04 (95% CI: 1.00–1.09) for CLL, and were1.12 (95% CI: 1.05–1.19) for NHL, 1.22 (95% CI: 1.09–1.37) for DLBCL, and 1.19 (95% CI: 1.03–1.38) for FL for BMI in early adulthood analysis. Results on mortality showed a 15%, 16% and 17% increased risk of NHL, MM and leukaemia, respectively. Greater height increased the risk of NHL by 7%, DLBCL by 10%, FL by 9%, MM by 5% and Leukaemia by 7%. WHR was associated with increased risk of DLBCL by 12%. No association was found between higher WC and risk of MM. Conclusion Our results revealed that general adiposity in adulthood and early adulthood, and greater height may increase the risk of almost all types of lympho-haematopoietic cancers and this adds to a growing body of evidence linking body fatness to several types of cancers.

OBJECTIVETo evaluate the strength and validity of evidence on the association between the neutrophil to lymphocyte ratio (NLR) or tumour-associated neutrophils (TAN) and cancer prognosis.DESIGNUmbrella review of systematic reviews and meta-analyses of observational studies.DATA SOURCESMedline, EMBASE, and Cochrane Database of Systematic Reviews.ELIGIBILITY CRITERIASystematic reviews or meta-analyses of observational studies evaluating the association between NLR or TAN and specific cancer outcomes related to disease progression or survival.DATA SYNTHESISThe available evidence was graded as strong, highly suggestive, suggestive, or weak through the application of pre-set grading criteria. For each included meta-analysis, the grading criteria considered the significance of the random effects estimate, the significance of the largest included study, the number of studies and individuals included, the heterogeneity between included studies, the 95% prediction intervals, presence of small study effects, excess significance and credibility ceilings.RESULTS239 meta-analyses investigating the association between NLR or TAN and cancer outcomes were identified from 57 published studies meeting the eligibility criteria, with 81 meta-analyses from 36 studies meeting the criteria for inclusion. No meta-analyses found a hazard ratio (HR) in the opposite direction of effect (HRCONCLUSIONDespite many publications exploring the association between NLR and cancer prognosis, the evidence is limited by significant heterogeneity and small study effects. There is a lack of evidence on the association between TAN and cancer prognosis, with all nine associations identified arising from the same study. Further research is required to provide strong evidence for associations between both TAN and NLR and poor cancer prognosis.REGISTRATIONThis umbrella review is registered on PROSPERO (CRD42017069131)FUNDINGMedical Research CouncilCOPYRIGHTOpen access article under terms of CC BYSHORT TITLENeutrophils and cancer prognosis: an umbrella reviewKEY RESULTWhen assessed for significance and bias related to heterogeneity and small study effects, only three (4%) associations between NLR and overall survival and progression-free survival in gastrointestinal and nasopharyngeal cancers were supported by strong evidence.WHAT THIS PAPER ADDSWHAT IS ALREADY KNOWN ON THE TOPICNeutrophil counts have been linked to the progression of cancer due to their tumourigenic role in the cancer microenvironment.Numerous meta-analyses and individual studies have explored the association between neutrophil counts and cancer outcomes for a variety of cancer sites, leading to a large body of evidence with variable strength and validity.Uncertainty exists around the association between neutrophils and cancer outcomes, depending on the site, outcome and treatments considered.WHAT THIS STUDY ADDSAll meta-analyses included in this review indicated an association between high neutrophil counts and poor cancer prognosis.There is strong evidence supporting the association between the neutrophil to lymphocyte ratio and poor cancer prognosis in some respiratory and gastrointestinal cancers.Further research is required to strengthen the existing body of evidence, particularly for the association between tumour-associated neutrophils and cancer outcomes.

Background: Critical care and sepsis remain high priority concerns in children. Observational studies report high prevalence of vitamin D deficiency and present mixed results regarding the correlation between vitamin D status and adverse outcomes. Associations between deficiency and mortality, particularly in children with sepsis, remain unclear. We performed a systematic review and meta-analysis to address this uncertainty. Methods: PubMed, OVID and Google Scholar were searched for observational studies in critically ill children. We obtained pooled prevalence estimates for vitamin D deficiency and odds ratios for the association of mortality in critically ill children treated in intensive care units, with subgroup analysis for those with sepsis and those with respiratory tract infections. Meta-regression and sensitivity analyses were used to investigate heterogeneity. Findings: Forty-eight studies were included. Total sample size was 7,199 with 1,679 (23%) children acting as controls in case-control studies. Of 5,520 critically ill children, 2,664 (48%) were vitamin D deficient (< 50 nmol/L). Results of the random effects model demonstrated a pooled prevalence of vitamin D deficiency of 54·9% (95% CI 48·0-61·6, I²=95·0%, 95% CI 94·0-95·8, p < 0·0001). In subgroup analysis of children with sepsis (16 studies, 788 total individuals) we observed higher prevalence of deficiency (63·8%, 95% CI 49·9-75·7, I²=90·5%, 95% CI 86·2-93·5%, p < 0·0001). In patients admitted for respiratory tract infections (24 studies, 1,683 total individuals), prevalence was 49·9% (95% CI 37·6- 62·2; I² = 93·9%, 95% CI 92·1-95·3, p < 0·0001). Only one identified study assessed vitamin D levels in sepsis and mortality. A metaregression model with all available variables (year of publication, total study sample size, quality score, study design, country group and clinical setting) explained 37·52% of I² (F = 5·1119, p = 0·0005) with clinical setting and country groups being significant predictors for prevalence. Meta-analysis of mortality (18 studies, 2,463 total individuals) showed an increased risk of death in vitamin D deficient critically ill children both with random (OR 1·81, 95% CI 1·24-2·64, p-value = 0·002) and fixed effects (OR 1·72, 95% CI 1·27-2·33, p= 0·0005) models with low heterogeneity (I² = 25·7%, 95% CI 0·0-58·0, p = 0·153) and low evidence of publication bias (p = 0·084, Egger's test). There were insufficient studies to perform meta-analyses for sepsis and respiratory tract infection related mortality. Interpretation: Circulating vitamin D deficiency is common amongst critically ill children, particularly in those with sepsis. Our results suggest that vitamin D deficiency in critically ill children is associated with increased mortality. Clinical trials, studies with larger sample sizes and standardized approaches are needed to further assess associations between circulating levels of vitamin D and mortality and other outcomes in the paediatric population. Funding Statement: The study received funding from the UK Medical Research Council. AJBT was supported by the Medical Research Council (UK MED-BIO Programme Fellowship, MR/L01632X/1). The funders had no role in data collection, analysis, interpretation or writing of the report. Declaration of Interests: The authors declare no conflicts of interest. Ethics Approval Statement: The study protocol is registered in PROSPERO (CRD42016050638). The authors declare ethics approval "not applicable."