Visual hindsight bias for abnormal mammograms in radiologists.

Purpose: Hindsight bias-where people falsely believe they can accurately predict something once they know about it-is a pervasive decision-making phenomenon, including in the interpretation of radiological images. Evidence suggests it is not only a decision-making phenomenon but also a visual perception one, where prior information about an image enhances our visual perception of the contents of that image. The current experiment investigates to what extent expert radiologists perceive mammograms with visual abnormalities differently when they know what the abnormality is (a visual hindsight bias), above and beyond being biased at a decision level. Approach: N=40 experienced mammography readers were presented with a series of unilateral abnormal mammograms. After each case, they were asked to rate their confidence on a 6-point scale that ranged from confident mass to confident calcification. We used the random image structure evolution method, where the images repeated in an unpredictable order and with varied noise, to ensure any biases were visual, not cognitive. Results: Radiologists who first saw an original image with no noise were more accurate in the max noise level condition [area under the curve (AUC)=0.60] than those who first saw the degraded images (AUC=0.55; difference: p=0.005), suggesting that radiologists' visual perception of medical images is enhanced by prior visual experience with the abnormality. Conclusions: Overall, these results provide evidence that expert radiologists experience not only decision level but also visual hindsight bias, and have potential implications for negligence lawsuits.

Outcome domains measured in randomized controlled trials of physical activity for older adults: a rapid review.

BACKGROUND: Toward development of a core outcome set for randomized controlled trials (RCTs) of physical activity (PA) interventions for older adults, the purpose of this study was to identify outcome domains and subdomains ('what' was measured) in previously published RCTs of PA for older adults. METHODS: We conducted a rapid review and searched Ovid MEDLINE for recently- published (2015-2021), English-language, RCTs of PA interventions for older adults (mean age 60+ yrs). We limited to articles published in Web of Science top-10 journals in general and internal medicine, geriatrics and gerontology, rehabilitation, and sports science. Two reviewers independently completed eligibility screening; two other reviewers abstracted trial descriptors and study outcomes. We classified study outcomes according to the standard outcome classification taxonomy endorsed by the Core Outcome Measures in Effectiveness Trials Initiative. RESULTS: Our search yielded 548 articles; 67 articles were eligible to be included. Of these, 82% were efficacy/effectiveness trials, 85% included both male and female participants, and 84% recruited community-dwelling older adults. Forty percent of articles reported on interventions that involved a combination of group and individual PAs, and 60% involved a combination of PA modes (e.g., aerobic, resistance). Trial sample size ranged from 14 to 2157 participants, with median (IQR) of 94 (57-517); 28,649 participants were included across all trials. We identified 21 unique outcome domains, spanning 4/5 possible core areas (physiological/clinical; life impact; resource use; adverse events). The five most commonly reported outcome domains were physical functioning (included in n=51 articles), musculoskeletal and connective tissue (n=30), general (n=26), cognitive functioning (n=16), and emotional functioning/wellbeing (n=14). Under these five outcome domains, we further identified 10 unique outcome subdomains (e.g., fall-related; body composition; quality of life). No outcome domains or subdomains were reported consistently in all RCTs. CONCLUSIONS: We found extensive variability in outcome domains and subdomains used in RCTs of PA for older adults, reflecting the broad range of potential health benefits derived from PA and also investigator interest to monitor a range of safety parameters related to adverse events. This study will inform development of a core outcome set to improve outcome reporting consistency and evidence quality.

Implementation and scale-up of physical activity and behavioural nutrition interventions: an evaluation roadmap.

BACKGROUND: Interventions that work must be effectively delivered at scale to achieve population level benefits. Researchers must choose among a vast array of implementation frameworks (> 60) that guide design and evaluation of implementation and scale-up processes. Therefore, we sought to recommend conceptual frameworks that can be used to design, inform, and evaluate implementation of physical activity (PA) and nutrition interventions at different stages of the program life cycle. We also sought to recommend a minimum data set of implementation outcome and determinant variables (indicators) as well as measures and tools deemed most relevant for PA and nutrition researchers. METHODS: We adopted a five-round modified Delphi methodology. For rounds 1, 2, and 3 we administered online surveys to PA and nutrition implementation scientists to generate a rank order list of most commonly used; i) implementation and scale-up frameworks, ii) implementation indicators, and iii) implementation and scale-up measures and tools. Measures and tools were excluded after round 2 as input from participants was very limited. For rounds 4 and 5, we conducted two in-person meetings with an expert group to create a shortlist of implementation and scale-up frameworks, identify a minimum data set of indicators and to discuss application and relevance of frameworks and indicators to the field of PA and nutrition. RESULTS: The two most commonly referenced implementation frameworks were the Framework for Effective Implementation and the Consolidated Framework for Implementation Research. We provide the 25 most highly ranked implementation indicators reported by those who participated in rounds 1-3 of the survey. From these, the expert group created a recommended minimum data set of implementation determinants (n = 10) and implementation outcomes (n = 5) and reconciled differences in commonly used terms and definitions. CONCLUSIONS: Researchers are confronted with myriad options when conducting implementation and scale-up evaluations. Thus, we identified and prioritized a list of frameworks and a minimum data set of indicators that have potential to improve the quality and consistency of evaluating implementation and scale-up of PA and nutrition interventions. Advancing our science is predicated upon increased efforts to develop a common 'language' and adaptable measures and tools.

Selumetinib in patients receiving standard pemetrexed and platinum-based chemotherapy for advanced or metastatic KRAS wildtype or unknown non-squamous non-small cell lung cancer: A randomized, multicenter, phase II study. Canadian Cancer Trials Group (CCTG) IND.219.

INTRODUCTION: Activation of the RAS/RAF/MEK/ERK pathway may confer resistance to chemotherapy in non-small cell lung cancer (NSCLC). Selumetinib (AZD6244, ARRY142886), a MEK1/2 inhibitor combined with chemotherapy in patients with NSCLC was evaluated in two schedules to evaluate efficacy and toxicity. METHODS: IND.219 was a three-arm study of first line pemetrexed/platinum chemotherapy with two schedules of selumetinib (Arm A: intermittent given on days 2-19; Arm B: continuous given on days 1-21) versus chemotherapy alone (Arm C). The primary endpoint was objective response rate (ORR); secondary objectives were tolerability, progression-free survival (PFS), overall survival (OS). The trial was stopped at the planned interim analysis. RESULTS: Arms A/B/C enrolled 20/21/21 patients, ORR was 35% (95% CI 15-59% median duration 3.8 months), 62% (95% CI 38-82%; median duration 6.3 months), 24% (95% CI 8-47%; median duration 11.6 months) respectively. The PFS (months Arm A, B, C) was 7.5, 6.7, 4.0 respectively (hazard ratio (HR) PFS Arm A over Arm C: 0.76 [95% CI, 0.38-1.51, 2-sided p = 0.42]; Arm B over Arm C 0.75 [95% CI 0.37-1.54, p = 0.43]. Skin and gastrointestinal adverse events were more common with the addition of selumetinib. A high incidence of venous thromboembolism was seen in all arms. CONCLUSIONS: Selumetinib combined with chemotherapy was associated with a higher response rate. Continuous selumetinib appeared to be superior to an intermittent schedule. PFS was prolonged with the addition of selumetinib, however this was not statistically significant.

The effect of nanoparticle size on in vivo pharmacokinetics and cellular interaction.

Nanoparticle-based technologies offer exciting new approaches to disease diagnostics and therapeutics. To take advantage of unique properties of nanoscale materials and structures, the size, shape and/or surface chemistry of nanoparticles need to be optimized, allowing their functionalities to be tailored for different biomedical applications. Here we review the effects of nanoparticle size on cellular interaction and in vivo pharmacokinetics, including cellular uptake, biodistribution and circulation half-life of nanoparticles. Important features of nanoparticle probes for molecular imaging and modeling of nanoparticle size effects are also discussed.

Survivin and COX-2 expression in male breast carcinoma.

Male breast carcinoma (Male BC) is a distinct biological subtype of breast cancer. We previously reported an association between 5-year overall survival and strong intratumoral aromatase (ITA) expression in Male BC. In this study, we investigate survivin and COX-2 expression and their relationship to ITA. Clinical data were abstracted for all Male BC patients diagnosed between 1985 and 2005 in Nova Scotia, Canada. Archival tissues were retrieved for tissue microarray (TMA) and immunohistochemistry (IHC). Of 54 Male BCs identified, 39 cases had tissue available for IHC. Survivin expression was noted in 27 cases (69%); 12 nuclear and 26 cytoplasmic while strong COX-2 expression was observed in 14 cases (36%). Cytoplasmic survivin and COX-2 expressions were positively associated with ITA expression. However, survivin and COX-2 expression were not predictive of survival. Additional studies are needed to further elucidate the correlation between cytoplasmic survivin, COX-2 and ITA expression in Male BC considering their potential therapeutic implications.

Clinical and pathological correlations in male breast cancer: intratumoral aromatase expression via tissue microarray.

BACKGROUND: Male breast cancer (MBC) commonly expresses hormone receptors and there is anecdotal evidence of disease responsivity to aromatase inhibitors in the metastatic setting. Our objectives were to: (i) assess clinical-pathologic characteristics in a consecutive cohort of MBC (ii) evaluate intratumoral aromatase (ITA) expression via tissue microarray (TMA) and (iii) assess the prognostic impact of ITA METHODS: A retrospective review was conducted to identify all cases of MBC seen at the Nova Scotia Cancer Center between 1985 and 2005. Specimens were reviewed for standard pathologic characteristics and tumor blocks were incorporated into three TMA's (four 1 mm cores per tumor). Immunohistochemistry (IHC) for ER, PR, Her2-neu and ITA was performed blinded to clinical outcomes. ITA staining intensity was compared to control, benign hepatic tissue and if greater than or equal to liver was scored positive and if less than liver was scored negative. The log-rank test was used for survival comparisons and Kaplan-Meyer curves were used to estimate 3- and 5-year progression-free and overall survival probabilities. RESULTS: Fifty-four cases were identified with a median age of 64 (31-85 years). Median tumor size was 2.6 cm (0.3-8.0 cm) and 22(41%) had nodal metastases. Forty-five cases had tissue available for IHC. Of these, 40 (89%) were ER and 33 (73%) were PR positive. Her2-neu was overexpressed in four cases (10%) and 12 (27%) were positive for ITA expression. ITA positive tumors were less likely to be grade 3, have lymphovascular invasion or nodal metastases and were more likely to be of favorable histology compared to ITA negative tumors. In univariate analysis strong (versus weak) ITA expression was associated with improved 5 year overall (92% vs. 49%, P = 0.038) but not progression-free (82% vs. 76% P = 0.44) survival rates. CONCLUSIONS: Tumors with strong ITA expression may have a less aggressive phenotype compared to those with negative/weak ITA expression. Further investigation of ITA as a relevant prognostic factor as well as a potential therapeutic target in MBC is warranted.