Quality assurance of radiotherapy in the ongoing EORTC 22042–26042 trial for atypical and malignant meningioma: Results from the dummy runs and prospective individual case Reviews

BACKGROUND: The ongoing EORTC 22042–26042 trial evaluates the efficacy of high-dose radiotherapy (RT) in atypical/malignant meningioma. The results of the Dummy Run (DR) and prospective Individual Case Review (ICR) were analyzed in this Quality Assurance (QA) study. MATERIAL/METHODS: Institutions were requested to submit a protocol compliant treatment plan for the DR and ICR, respectively. DR-plans (n=12) and ICR-plans (n=50) were uploaded to the Image-Guided Therapy QA Center of Advanced Technology Consortium server (http://atc.wustl.edu/) and were assessed prospectively. RESULTS: Major deviations were observed in 25% (n=3) of DR-plans while no minor deviations were observed. Major and minor deviations were observed in 22% (n=11) and 10% (n=5) of the ICR-plans, respectively. Eighteen% of ICRs could not be analyzed prospectively, as a result of corrupted or late data submission. CTV to PTV margins were respected in all cases. Deviations were negatively associated with the number of submitted cases per institution (p=0.0013), with a cutoff of 5 patients per institutions. No association (p=0.12) was observed between DR and ICR results, suggesting that DR’s results did not predict for an improved QA process in accrued brain tumor patients. CONCLUSIONS: A substantial number of protocol deviations were observed in this prospective QA study. The number of cases accrued per institution was a significant determinant for protocol deviation. These data suggest that successful DR is not a guarantee for protocol compliance for accrued patients. Prospective ICRs should be performed to prevent protocol deviations

Imaging biomarker roadmap for cancer studies.

Imaging biomarkers (IBs) are integral to the routine management of patients with cancer. IBs used daily in oncology include clinical TNM stage, objective response and left ventricular ejection fraction. Other CT, MRI, PET and ultrasonography biomarkers are used extensively in cancer research and drug development. New IBs need to be established either as useful tools for testing research hypotheses in clinical trials and research studies, or as clinical decision-making tools for use in healthcare, by crossing 'translational gaps' through validation and qualification. Important differences exist between IBs and biospecimen-derived biomarkers and, therefore, the development of IBs requires a tailored 'roadmap'. Recognizing this need, Cancer Research UK (CRUK) and the European Organisation for Research and Treatment of Cancer (EORTC) assembled experts to review, debate and summarize the challenges of IB validation and qualification. This consensus group has produced 14 key recommendations for accelerating the clinical translation of IBs, which highlight the role of parallel (rather than sequential) tracks of technical (assay) validation, biological/clinical validation and assessment of cost-effectiveness; the need for IB standardization and accreditation systems; the need to continually revisit IB precision; an alternative framework for biological/clinical validation of IBs; and the essential requirements for multicentre studies to qualify IBs for clinical use.Development of this roadmap received support from Cancer Research UK and the Engineering and Physical Sciences Research Council (grant references A/15267, A/16463, A/16464, A/16465, A/16466 and A/18097), the EORTC Cancer Research Fund, and the Innovative Medicines Initiative Joint Undertaking (grant agreement number 115151), resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007-2013) and European Federation of Pharmaceutical Industries and Associations (EFPIA) companies' in kind contribution

Antimicrobial stewardship: Staff nurse knowledge and attitudes

Background: Registered nurses are uniquely qualified to augment antimicrobial stewardship (AS) processes. However, the role of nursing in AS needs further development. More information is needed regarding gaps in registered nurse knowledge, attitudes toward AS, and how infection preventionists can help. Methods: An online descriptive survey was deployed to a convenience sample of approximately 2,000 nurses at the bedside. The survey included 15 questions addressing: (1) overall knowledge of AS; (2) antimicrobial delivery; (3) knowledge and attitudes regarding antimicrobial use; (4) antimicrobial resistance; and (5) antimicrobial resources and education. Results: Three hundred sixteen staff nurses from 3 hospitals (15.8%) responded to the survey. Fifty-two percent of nurses were not familiar with the term “antimicrobial stewardship,” although 39.6% of nurses indicated that an AS program was moderately or extremely important in their health care setting. Almost all nurses (95%) believed that they should be involved in AS interventions. Discussion: These findings suggest gaps in nursing knowledge rearding AS. However, nurses believed AS programs were important and were eager to be involved. Conclusions: This study showed that many nurses are not aware of AS, or do not understand their role in contributing to AS endeavors. Infection preventionist education should focus on increasing staff nurse awareness and demonstrating how nurses can make specific AS interventions

Jacoby-Whitehouse illusion from taxonomic and thematic associations

peer reviewe

Jacoby-Whitehouse illusion from taxonomic and thematic associations.

peer reviewe

Jacoby-Whitehouse illusion from taxonomic and thematic associations in Alzheimer disease

peer reviewedAlzheimer's disease patients (AD) show an impairment of recognition memory, mainly characterized by deficient recollection. The other process supporting recognition, familiarity, is relatively preserved. Familiarity is built on fluency cues (i.e., ease of processing due to repetition) and provides a sense of the strength of a memory trace. In a word recognition task, Jacoby & Whitehouse (1989) showed that false recognitions of unlearned words can be elicited by the prior masked presentation of the same word. Such false recognitions have been replicated using semantically related primes. The specific impairment of structural links in semantic memory in Alzheimer's disease follows a hierarchical order, taxonomic links (concepts within the same category, e.g. dog-cat) being more rapidly impaired than thematic links (concepts often encountered together, e.g. hair-brush). In this word recognition task, we preceded the test word by a 33-ms prime and manipulated the type of link, either perceptual (repetition) or semantic (taxonomic, thematic), and the prime-test word relationship (related or unrelated). The experimental group, composed of 17 early-stage AD patients was contrasted with an age-matched control group. Taxonomic impairment in AD starts with the alteration of the distinctive attributes between concepts, creating a taxonomic priming effect that should be close to repetition priming. AD group was affected by early taxonomic impairment, with more false alarms in the thematic and repetition conditions than in the taxonomic. But contrary to our expectations, the taxonomic impairment did not result in hyperpriming for that condition. Keywords: Alzheimer, recognition memory, priming, perceptive, thematic, taxonomical Reference Jacoby, L. L., & Whitehouse, K. (1989). An illusion of memory: False recognition influenced by unconscious perception. Journal of Experimental Psychology: General, 118(2), 126

Continuous glucose monitoring in pregnant women with type 1 diabetes (CONCEPTT): a multicentre international randomised controlled trial

Background: Pregnant women with type 1 diabetes are a high-risk population who are recommended to strive for optimal glucose control, but neonatal outcomes attributed to maternal hyperglycaemia remain suboptimal. Our aim was to examine the effectiveness of continuous glucose monitoring (CGM) on maternal glucose control and obstetric and neonatal health outcomes. Methods: In this multicentre, open-label, randomised controlled trial, we recruited women aged 18–40 years with type 1 diabetes for a minimum of 12 months who were receiving intensive insulin therapy. Participants were pregnant (≤13 weeks and 6 days' gestation) or planning pregnancy from 31 hospitals in Canada, England, Scotland, Spain, Italy, Ireland, and the USA. We ran two trials in parallel for pregnant participants and for participants planning pregnancy. In both trials, participants were randomly assigned to either CGM in addition to capillary glucose monitoring or capillary glucose monitoring alone. Randomisation was stratified by insulin delivery (pump or injections) and baseline glycated haemoglobin (HbA1c). The primary outcome was change in HbA1c from randomisation to 34 weeks' gestation in pregnant women and to 24 weeks or conception in women planning pregnancy, and was assessed in all randomised participants with baseline assessments. Secondary outcomes included obstetric and neonatal health outcomes, assessed with all available data without imputation. This trial is registered with ClinicalTrials.gov, number NCT01788527. Findings: Between March 25, 2013, and March 22, 2016, we randomly assigned 325 women (215 pregnant, 110 planning pregnancy) to capillary glucose monitoring with CGM (108 pregnant and 53 planning pregnancy) or without (107 pregnant and 57 planning pregnancy). We found a small difference in HbA1c in pregnant women using CGM (mean difference −0·19%; 95% CI −0·34 to −0·03; p=0·0207). Pregnant CGM users spent more time in target (68% vs 61%; p=0·0034) and less time hyperglycaemic (27% vs 32%; p=0·0279) than did pregnant control participants, with comparable severe hypoglycaemia episodes (18 CGM and 21 control) and time spent hypoglycaemic (3% vs 4%; p=0·10). Neonatal health outcomes were significantly improved, with lower incidence of large for gestational age (odds ratio 0·51, 95% CI 0·28 to 0·90; p=0·0210), fewer neonatal intensive care admissions lasting more than 24 h (0·48; 0·26 to 0·86; p=0·0157), fewer incidences of neonatal hypoglycaemia (0·45; 0·22 to 0·89; p=0·0250), and 1-day shorter length of hospital stay (p=0·0091). We found no apparent benefit of CGM in women planning pregnancy. Adverse events occurred in 51 (48%) of CGM participants and 43 (40%) of control participants in the pregnancy trial, and in 12 (27%) of CGM participants and 21 (37%) of control participants in the planning pregnancy trial. Serious adverse events occurred in 13 (6%) participants in the pregnancy trial (eight [7%] CGM, five [5%] control) and in three (3%) participants in the planning pregnancy trial (two [4%] CGM and one [2%] control). The most common adverse events were skin reactions occurring in 49 (48%) of 103 CGM participants and eight (8%) of 104 control participants during pregnancy and in 23 (44%) of 52 CGM participants and five (9%) of 57 control participants in the planning pregnancy trial. The most common serious adverse events were gastrointestinal (nausea and vomiting in four participants during pregnancy and three participants planning pregnancy). Interpretation: Use of CGM during pregnancy in patients with type 1 diabetes is associated with improved neonatal outcomes, which are likely to be attributed to reduced exposure to maternal hyperglycaemia. CGM should be offered to all pregnant women with type 1 diabetes using intensive insulin therapy. This study is the first to indicate potential for improvements in non-glycaemic health outcomes from CGM use