Assessing the Functional Accessibility, Actionability, and Quality of Patient Education Materials from Canadian Cancer Agencies.

Patient education materials (PEM)s were extracted from provincial cancer agencies to determine their organizational health literacy by evaluating the quality, actionability, and functional accessibility (e.g., readability and understandability) of their PEMs. PEMs from 10 provincial agencies were assessed for their grade reading level (GRL), using eight numerical and two graphical readability scales, and underwent a difficult word analysis. The agencies were assessed for PEM quality using two methods (JAMA benchmarks and DISCERN), while actionability and understandability were assessed using the Patient Education Materials Assessment Tool (PEMAT). Seven hundred and eighty-six PEMs were analyzed. The overall average GRL was 9.3 ± 2.1, which is above the recommended 7th GRL for health information. The difficult word analysis showed that 15.4% ± 5.1% of texts contained complex words, 35.8% ± 6.8% of texts contained long words, and 24.2% ± 6.6% of texts contained unfamiliar words. Additionally, there was high overlap between the most frequently identified difficult words in the PEMs and the most frequently misunderstood words by cancer patients identified in the literature. Regarding quality indicators, no agency displayed all four indicators according to the JAMA benchmarks and DISCERN scores ranged between 38 (poor) to 66 (excellent). PEMAT scores ranged between 68% to 88% for understandability and 57% to 88% for actionability. PEMs continue to be written at a level above the recommended GRL across all provinces, and there was overall high variability in the quality, understandability, and actionability of PEMs among provincial agencies. This represents an opportunity to optimize materials, thus ensuring understanding by a wider audience and improving health literacy among Canadian cancer patients.

Fractionated radiation suppresses Kruppel-like factor 2 pathway to a greater extent than by single exposure to the same total dose.

Kruppel-like factor 2 (KLF2) is a positive transcriptional regulator of several endothelial protective molecules, including thrombomodulin (TM), a surface receptor, and endothelial nitric oxide synthase (eNOS), an enzyme that generates nitric oxide (NO). Loss of TM and eNOS causes endothelial dysfunction, which results in suppressed generation of activated protein C (APC) by TM-thrombin complex and in upregulation of intercellular adhesion molecule 1 (ICAM-1). Mechanistic studies revealed that activation of extracellular signal-regulated kinase 5 (ERK5) via upregulation of myocyte enhancer factor 2 (MEF2) induces KLF2 expression. Radiation causes endothelial dysfunction, but no study has investigated radiation's effects on the KLF2 pathway. Because fractionated radiation is routinely used during cancer radiotherapy, we decided to delineate the effects of radiation dose fractionation on the KLF2 signaling cascade at early time points (up to 24 h). We exposed human primary endothelial cells to radiation as a series of fractionated or as a single exposure, with the same total dose delivered to each group. We measured the expression and activity of critical members of the KLF2 pathway at subsequent time points, and determined whether pharmacological upregulation of KLF2 can reverse the radiation effects. Compared to single exposure, fractionated radiation profoundly suppressed KLF2, TM, and eNOS levels, subdued APC generation, declined KLF2 binding ability to TM and eNOS promoters, enhanced ICAM-1 expression, and decreased expression of upstream regulators of KLF2 (ERK5 and MEF2). Pharmacological inhibitors of the mevalonate pathway prevented fractionated-radiation-induced suppression of KLF2, TM, and eNOS expression. Finally, fractionated irradiation to thoracic region more profoundly suppressed KLF2 and enhanced ICAM-1 expression than single exposure in the lung at 24 h. These data clearly indicate that radiation dose fractionation plays a critical role in modulating levels of KLF2, its upstream regulators, and its downstream target molecules in endothelial cells. Our findings will provide important insights for selecting fractionated regimens during radiotherapy and for developing strategies to alleviate radiotherapy-induced toxicity to healthy tissues.