ObjectiveTo assess (1) how well validated existing paediatric track and trigger tools (PTTT) are for predicting adverse outcomes in hospitalised children, and (2) how effective broader paediatric early warning systems are at reducing adverse outcomes in hospitalised children.DesignSystematic review.Data sourcesBritish Nursing Index, Cumulative Index of Nursing and Allied Health Literature, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effectiveness, EMBASE, Health Management Information Centre, Medline, Medline in Process, Scopus and Web of Knowledge searched through May 2018.Eligibility criteriaWe included (1) papers reporting on the development or validation of a PTTT or (2) the implementation of a broader early warning system in paediatric units (age 0–18 years), where adverse outcome metrics were reported. Several study designs were considered.Data extraction and synthesisData extraction was conducted by two independent reviewers using template forms. Studies were quality assessed using a modified Downs and Black rating scale.Results36 validation studies and 30 effectiveness studies were included, with 27 unique PTTT identified. Validation studies were largely retrospective case-control studies or chart reviews, while effectiveness studies were predominantly uncontrolled before-after studies. Metrics of adverse outcomes varied considerably. Some PTTT demonstrated good diagnostic accuracy in retrospective case-control studies (primarily for predicting paediatric intensive care unit transfers), but positive predictive value was consistently low, suggesting potential for alarm fatigue. A small number of effectiveness studies reported significant decreases in mortality, arrests or code calls, but were limited by methodological concerns. Overall, there was limited evidence of paediatric early warning system interventions leading to reductions in deterioration.ConclusionThere are several fundamental methodological limitations in the PTTT literature, and the predominance of single-site studies carried out in specialist centres greatly limits generalisability. With limited evidence of effectiveness, calls to make PTTT mandatory across all paediatric units are not supported by the evidence base.PROSPERO registration numberCRD42015015326

PURPOSE Eczema may flare because of bacterial infection, but evidence supporting antibiotic treatment is of low quality. We aimed to determine the effect of oral and topical antibiotics in addition to topical emollient and corticosteroids in children with clinically infected eczema.

BackgroundChronic breathlessness has devastating consequences. The minimal clinically important difference (MCID) for current intensity has been estimated as 9 mm on a 100 mm visual analogue scale (VAS). We aimed to determine MCIDs for commonly used dimensions and recall periods: the current unpleasantness and current, average, best and worst intensity of the last 24 h for chronic breathlessness.MethodsThis was a secondary analysis of a randomised controlled trial of morphine versus placebo during seven days in people with chronic breathlessness from severe disease. The breathlessness scores were self-reported using a diary each evening on 100 mm VAS. The MCID for improvement in each score was estimated using anchor based and distribution based methods.Results283 participants (mean age 74.2 years; 63% males; 58% COPD; 87.0% mMRC 3–4) were included. Anchor-based MCIDs for breathlessness scores ranged from −13.9 mm to −9.5 mm. The MCIDs were similar when using different anchors and across all participants, and participants with more severe BREATHLESSNESS (mMRC 3–4), respectively. Distribution based effect sizes were: small (−4.7 to −6.3 mm), moderate (−9.4 to −12.5 mm) and large effect (−15.0 to −20.0 mm). Sample sizes for trials using the different scores were proposed. MCIDs of absolute change were more stable than using relative change from baseline.ConclusionAn improvement of about 10 mm on a 100 mm VAS is likely to be clinically meaningful across commonly used measures of chronic breathlessness (current intensity, unpleasantness, and average, best and worst intensity over the last 24 h) – to evaluate clinical benefit and effects in therapeutic trials.

The present study was designed to determine the significance of DNA topoisomerase IIa (TopoIIα) and Ki67 in hepatocellular carcinoma cells (HCCs). The present study included 353 patients with HCC. The association of clinicopathological data with the expression of TopoIIα and Ki67 by immunohistochemistry was analyzed by χ2 test. Cox multivariate proportional hazards regression analysis and Kaplan-Meier analysis were performed with all the variables to derive risk estimates associated with overall survival (OS)/recurrence-free survival (RFS) and to control for confounders. TopoIIα and Ki67 were detected in the nuclei of the tumor cells. With TopoIIα, 35.7% of cells exhibited high expression, which was associated with tumor-node-metastasis stage, tumor size and α-fetoprotein level. With Ki67, 37.1% of cells exhibited high expression, which was associated with tumor-node-metastasis stage, tumor size and α-fetoprotein level. Correlation was identified between the expression level of TopoIIα and Ki67 in HCCs (r=0.444). Multivariate analysis revealed that high TopoIIα expression is a prognostic indicator for RFS [hazard ratio (HR), 2.002; 95% confidence interval (CI), 1.429–2.806] and OS (HR, 2.749; 95% CI, 1.919–3.939), and high Ki67 expression is a prognostic indicator for OS (HR, 1.816; 95% CI, 1.273–2.589). The TopoIIα-low group had a significantly increased RFS rate (55.6 vs. 31.7%) and OS rate (66.5 vs. 23.8%) compared with the TopoIIα-high group. The OS rate was increased in the Ki67-low group compared with the Ki67-high group (67.0 vs. 26.5%). Expression of TopoIIα and Ki67 are independent prognostic factors for survival in HCCs. TopoIIα was positively associated with Ki67 expression.

No abstract

No abstract

No abstract

Background: The GINS complex has been implicated in the prognosis of various cancers. It comprises four subunits, encoded by GINS1, GINS2, GINS3, and GINS4 genes. Based on the current understanding, no report exists on the role of the GINS complex in pancreatic cancer. Methods: We employed various bioinformatics databases including GEPIA, UALCAN, GEPIA2, and Kaplan Meier Plotter to identify the expression profile of the four genes (GINS1, GINS2, GINS3, and GINS4), their correlation with pancreatic cancer grade as well as their prognostic value of in pancreatic cancer. Western blotting and qRT-PCR analyses were conducted to verify the expression profiles of the four genes in pancreatic cancer. CCK8 and EdU cell experiments were conducted to reveal the role played by the four genes in pancreatic cancer cell proliferation. Results: Based on GEPIA, Western blotting, and qRT-PCR analyses, all the four genes in the GINS complex were overexpressed in pancreatic cancer. Notably, the expression of each member was significantly associated with pancreatic cancer grade. The prognostic analysis revealed that not only the whole GINS complex but also each individual were prognostic biomarkers for pancreatic cancer. CCK8 and EdU experiments demonstrated that inhibition of the expression of each GINS member lowered pancreatic cancer cell proliferation. Conclusion: This work implicated GINS1, GINS2, GINS3, and GINS4 genes as critical prognostic markers for pancreatic cancer.