The landscape of knowledge translation interventions in cancer control: What do we know and where to next? A review of systematic reviews

<p>Abstract</p> <p>Background</p> <p>Effective implementation strategies are needed to optimize advancements in the fields of cancer diagnosis, treatment, survivorship, and end-of-life care. We conducted a review of systematic reviews to better understand the evidentiary base of implementation strategies in cancer control.</p> <p>Methods</p> <p>Using three databases, we conducted a search and identified English-language systematic reviews published between 2005 and 2010 that targeted consumer, professional, organizational, regulatory, or financial interventions, tested exclusively or partially in a cancer context (primary focus); generic or non-cancer-specific reviews were also considered. Data were extracted, appraised, and analyzed by members of the research team, and research ideas to advance the field were proposed.</p> <p>Results</p> <p>Thirty-four systematic reviews providing 41 summaries of evidence on 19 unique interventions comprised the evidence base. AMSTAR quality ratings ranged between 2 and 10. Team members rated most of the interventions as promising and in need of further research, and 64 research ideas were identified.</p> <p>Conclusions</p> <p>While many interventions show promise of effectiveness in the cancer-control context, few reviews were able to conclude definitively in favor of or against a specific intervention. We discuss the complexity of implementation research and offer suggestions to advance the science in this area.</p

Evidence for prereg posters as a platform for preregistration

Prereg posters are conference posters that present planned scientific projects. We provide preliminary evidence for their value in receiving constructive feedback, promoting open science and supporting early-career researchers

Evidence for prereg posters as a platform for preregistration.

Prereg posters are conference posters that present planned scientific projects. We provide preliminary evidence for their value in receiving constructive feedback, promoting open science, and supporting early career researchers

Role of X11 and ubiquilin as In Vivo Regulators of the Amyloid Precursor Protein in Drosophila

The Amyloid Precursor Protein (APP) undergoes sequential proteolytic cleavages through the action of β- and γ-secretase, which result in the generation of toxic β-amyloid (Aβ) peptides and a C-terminal fragment consisting of the intracellular domain of APP (AICD). Mutations leading to increased APP levels or alterations in APP cleavage cause familial Alzheimer's disease (AD). Thus, identification of factors that regulate APP steady state levels and/or APP cleavage by γ-secretase is likely to provide insight into AD pathogenesis. Here, using transgenic flies that act as reporters for endogenous γ-secretase activity and/or APP levels (GAMAREP), and for the APP intracellular domain (AICDREP), we identified mutations in X11L and ubiquilin (ubqn) as genetic modifiers of APP. Human homologs of both X11L (X11/Mint) and Ubqn (UBQLN1) have been implicated in AD pathogenesis. In contrast to previous reports, we show that overexpression of X11L or human X11 does not alter γ-secretase cleavage of APP or Notch, another γ-secretase substrate. Instead, expression of either X11L or human X11 regulates APP at the level of the AICD, and this activity requires the phosphotyrosine binding (PTB) domain of X11. In contrast, Ubqn regulates the levels of APP: loss of ubqn function leads to a decrease in the steady state levels of APP, while increased ubqn expression results in an increase in APP levels. Ubqn physically binds to APP, an interaction that depends on its ubiquitin-associated (UBA) domain, suggesting that direct physical interactions may underlie Ubqn-dependent regulation of APP. Together, our studies identify X11L and Ubqn as in vivo regulators of APP. Since increased expression of X11 attenuates Aβ production and/or secretion in APP transgenic mice, but does not act on γ-secretase directly, X11 may represent an attractive therapeutic target for AD

Turn of Events: Academic events as a platform for preregistration

Prereg posters are conference posters that present planned scientific projects (Tibon, CBU Open Science Committee, &amp; Henson, 2018) and were recently adopted by the BNA2019 Festival of Neuroscience (https://meetings.bna.org.uk/bna2019/). The organisers of the event collected survey data about prereg posters, to provide empirical evidence for their value. Nearly a fifth of all presented posters at the BNA2019 Festival conformed to the new prereg format, covering a diverse range of neuroscience topics and disciplines, and the overall impression was that they were enthusiastically welcomed. The survey data were collected at two time points (before and after the event), via two different surveys. We analyse data from the questionnaire items that address three main themes: prereg posters as means to (1) receive valuable feedback, (2) promote Open Science, and (3) support Early Career Researchers (ECRs)

A mixed methods approach to understand variation in lung cancer practice and the role of guidelines

Abstract Introduction Practice pattern data demonstrate regional variation and lower than expected rates of adherence to practice guideline (PG) recommendations for the treatment of stage II/IIIA resected and stage IIIA/IIIB unresected non-small cell lung cancer (NSCLC) patients in Ontario, Canada. This study sought to understand how clinical decisions are made for the treatment of these patients and the role of PGs. Methods Surveys and key informant interviews were undertaken with clinicians and administrators. Results Participants reported favorable ratings for PGs and the evidentiary bases underpinning them. The majority of participants agreed more patients should have received treatment and that regional variation is problematic. Participants estimated that up to 30% of patients are not good candidates for treatment and up to 20% of patients refuse treatment. The most common barrier to implementing PGs was the lack of organizational support by clinical administrative leadership. There was concern that the trial results underpinning the PG recommendations were not generalizable to the typical patients seen in clinic. The qualitative analysis yielded five themes related to physicians’ decision making: the unique patient, the unique physician, the family, the clinical team, and the clinical evidence. A dynamic interplay between these factors exists. Conclusion Our study demonstrates the challenges inherent in (i) the complexity of clinical decision making; (ii) how quality of care problems are perceived and operationalized; and (iii) the clinical appropriateness and utility of PG recommendations. We argue that systematic and rigorous methodologies to help decision makers mitigate or negotiate these challenges are warranted

Computed tomography angiography spot sign does not predict case fatality in aneurysmal subarachnoid hemorrhage with intraparenchymal extension

BACKGROUND AND PURPOSE: Many patients with aneurysmal subarachnoid hemorrhage (SAH) with intraparenchymal extension develop early hematoma expansion, which is not explained by aneurysmal rerupture in half of cases. In patients with primary intracerebral hemorrhage, the computed tomography angiography (CTA) spot sign predicts hematoma expansion and poor outcome. We conducted a 2-center prospective cohort study to evaluate whether CTA spot sign predicts case fatality in aneurysmal subarachnoid hemorrhage with intraparenchymal extension. METHODS: We studied consecutive patients with aneurysmal subarachnoid hemorrhage with intraparenchymal extension. Two experienced readers, blinded to clinical data, analyzed CTAs for spot sign presence. We assessed the proportion of patients with the CTA spot sign and tested its association with in-hospital and 90-day case fatality, using univariable and multivariable logistic regression. RESULTS: In 32 of 236 patients (14%), we found at least 1 spot sign. Acute surgical hematoma evacuation with aneurysm occlusion occurred in 120 patients (51%). The overall in-hospital case fatality rate was 37%. The CTA spot sign was not associated with in-hospital (multivariable odds ratio, 0.51 [95% confidence interval, 0.06-3.26]) or 90-day (multivariable odds ratio, 0.59 [0.21-1.65]) case fatality. CONCLUSIONS: The found frequency of CTA spot signs is lower after aneurysmal than primary intracerebral hemorrhage and is not associated with in-hospital or 90-day case fatality in patients with aneurysmal subarachnoid hemorrhage with intraparenchymal extension. KEYWORDS: CTA spot sign, in-hospital death, intracerebral hemorrhage, subarachnoid hemorrhage