Fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin with gemtuzumab ozogamicin improves event-free survival in younger patients with newly diagnosed aml and overall survival in patients with npm1 and flt3 mutations

Purpose To determine the optimal induction chemotherapy regimen for younger adults with newly diagnosed AML without known adverse risk cytogenetics. Patients and Methods One thousand thirty-three patients were randomly assigned to intensified (fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin [FLAG-Ida]) or standard (daunorubicin and Ara-C [DA]) induction chemotherapy, with one or two doses of gemtuzumab ozogamicin (GO). The primary end point was overall survival (OS). Results There was no difference in remission rate after two courses between FLAG-Ida + GO and DA + GO (complete remission [CR] + CR with incomplete hematologic recovery 93% v 91%) or in day 60 mortality (4.3% v 4.6%). There was no difference in OS (66% v 63%; P = .41); however, the risk of relapse was lower with FLAG-Ida + GO (24% v 41%; P < .001) and 3-year event-free survival was higher (57% v 45%; P < .001). In patients with an NPM1 mutation (30%), 3-year OS was significantly higher with FLAG-Ida + GO (82% v 64%; P = .005). NPM1 measurable residual disease (MRD) clearance was also greater, with 88% versus 77% becoming MRD-negative in peripheral blood after cycle 2 (P = .02). Three-year OS was also higher in patients with a FLT3 mutation (64% v 54%; P = .047). Fewer transplants were performed in patients receiving FLAG-Ida + GO (238 v 278; P = .02). There was no difference in outcome according to the number of GO doses, although NPM1 MRD clearance was higher with two doses in the DA arm. Patients with core binding factor AML treated with DA and one dose of GO had a 3-year OS of 96% with no survival benefit from FLAG-Ida + GO. Conclusion Overall, FLAG-Ida + GO significantly reduced relapse without improving OS. However, exploratory analyses show that patients with NPM1 and FLT3 mutations had substantial improvements in OS. By contrast, in patients with core binding factor AML, outcomes were excellent with DA + GO with no FLAG-Ida benefit

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

A systematic review of the quality of conduct and reporting of systematic reviews and meta-analyses in paediatric surgery.

Our objective was to evaluate quality of conduct and reporting of published systematic reviews and meta-analyses in paediatric surgery. We also aimed to identify characteristics predictive of review quality.Systematic reviews summarise evidence by combining sources, but are potentially prone to bias. To counter this, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was published to aid in reporting. Similarly, the Assessing the Methodological Quality of Systematic Reviews (AMSTAR) measurement tool was designed to appraise methodology. The paediatric surgical literature has seen an increasing number of reviews over the past decade, but quality has not been evaluated.Adhering to PRISMA guidelines, we performed a systematic review with a priori design to identify systematic reviews and meta-analyses of interventions in paediatric surgery. From 01/2010 to 06/2016, we searched: MEDLINE, EMBASE, Cochrane, Centre for Reviews and Dissemination, Web of Science, Google Scholar, reference lists and journals. Two reviewers independently selected studies and extracted data. We assessed conduct and reporting using AMSTAR and PRISMA. Scores were calculated as the sum of reported items. We also extracted author, journal and article characteristics, and used them in exploratory analysis to determine which variables predict quality.112 articles fulfilled eligibility criteria (53 systematic reviews; 59 meta-analyses). Overall, 68% AMSTAR and 56.8% PRISMA items were reported adequately. Poorest scores were identified with regards a priori design, inclusion of structured summaries, including the grey literature, citing excluded articles and evaluating bias. 13 reviews were pre-registered and 6 in PRISMA-endorsing journals. The following predicted quality in univariate analysis:, word count, Cochrane review, journal h-index, impact factor, journal endorses PRISMA, PRISMA adherence suggested in author guidance, article mentions PRISMA, review includes comparison of interventions and review registration. The latter three variables were significant in multivariate regression.There are gaps in the conduct and reporting of systematic reviews in paediatric surgery. More endorsement by journals of the PRISMA guideline may improve review quality, and the dissemination of reliable evidence to paediatric clinicians

star chart illustrating PRISMA scores achieved for systematic reviews, meta-analyses and their cumulative total, as percentage of adequately reported items.

<p>star chart illustrating PRISMA scores achieved for systematic reviews, meta-analyses and their cumulative total, as percentage of adequately reported items.</p

showing only those variables that were identified as significant (p < 0.05) in univariate regression for AMSTAR scores and the results of subsequent input to multiple regression, again showing only significant results.

<p>The overall model fit for final multiple regression equation was R² = 0.51. Change in AMSTAR score refers to the expected change in AMSTAR score with a unit increase in the variable assessed with all other variables being constant. N.B. systematic review (SR); meta-analysis (MA); confidence interval (CI).</p

PRISMA flow diagram.

<p>PRISMA flow diagram.</p

Excluded studies and reasoning.

<p>Excluded studies and reasoning.</p

Eligibility criteria employed.

<p>Eligibility criteria employed.</p