What is the effect of a low literacy talking book on patient knowledge, anxiety and communication before radiation therapy starts? A pilot study

Introduction: Radiation therapy is a common cancer treatment, requiring timely information to help patients prepare for treatment. We pilot tested a low literacy, psycho-educational talking book (written booklet, with accompanying audio recording) to examine (i) the effect of the tool on knowledge, anxiety and communication; (ii) acceptability, and (iii) how it was used in appointments. Methods: A pre-post design was employed. Patients scheduled to receive radiation therapy for any cancer were recruited from two hospitals in Sydney, Australia. Participants were sent the talking book before treatment planning and completed baseline and follow-up surveys, before and after the intervention. Results: Forty participants were recruited, and 39 completed all study assessments. Overall, knowledge increased after receiving the talking book by 3.8 points from 13.9 to 17.7/20 (95% confidence interval (CI) 2.7, 4.8, P < 0.001). Anxiety and concerns were significantly lower after receiving the talking book (P = 0.015 and P = 0.004, respectively). Nearly half of participants (s = 17, 48%) reported using the book during appointments. Most reported finding it easier to communicate (n = 31, 89%) and to ask more questions (n = 21, 62%). Conclusion: The talking book shows promise in improving knowledge, reducing anxiety and enhancing communication. Strategies to support the implementation of the talking book are required. Further studies to translate the book into different languages are also planned

Distinct lung cell signatures define the temporal evolution of diffuse alveolar damage in fatal COVID-19

\ua9 2023 The Author(s)Background: Lung damage in severe COVID-19 is highly heterogeneous however studies with dedicated spatial distinction of discrete temporal phases of diffuse alveolar damage (DAD) and alternate lung injury patterns are lacking. Existing studies have also not accounted for progressive airspace obliteration in cellularity estimates. We used an imaging mass cytometry (IMC) analysis with an airspace correction step to more accurately identify the cellular immune response that underpins the heterogeneity of severe COVID-19 lung disease. Methods: Lung tissue was obtained at post-mortem from severe COVID-19 deaths. Pathologist-selected regions of interest (ROIs) were chosen by light microscopy representing the patho-evolutionary spectrum of DAD and alternate disease phenotypes were selected for comparison. Architecturally normal SARS-CoV-2-positive lung tissue and tissue from SARS-CoV-2-negative donors served as controls. ROIs were stained for 40 cellular protein markers and ablated using IMC before segmented cells were classified. Cell populations corrected by ROI airspace and their spatial relationships were compared across lung injury patterns. Findings: Forty patients (32M:8F, age: 22–98), 345 ROIs and &gt;900k single cells were analysed. DAD progression was marked by airspace obliteration and significant increases in mononuclear phagocytes (MnPs), T and B lymphocytes and significant decreases in alveolar epithelial and endothelial cells. Neutrophil populations proved stable overall although several interferon-responding subsets demonstrated expansion. Spatial analysis revealed immune cell interactions occur prior to microscopically appreciable tissue injury. Interpretation: The immunopathogenesis of severe DAD in COVID-19 lung disease is characterised by sustained increases in MnPs and lymphocytes with key interactions occurring even prior to lung injury is established. Funding: UK Research and Innovation/ Medical Research Council through the UK Coronavirus Immunology Consortium, Barbour Foundation, General Sir John Monash Foundation, Newcastle University, JGW Patterson Foundation, Wellcome Trust

Specific β-Tubulin Isotypes Can Functionally Enhance or Diminish Epothilone B Sensitivity in Non-Small Cell Lung Cancer Cells

Epothilones are a new class of microtubule stabilizing agents with promising preclinical and clinical activity. Their cellular target is β-tubulin and factors influencing intrinsic sensitivity to epothilones are not well understood. In this study, the functional significance of specific β-tubulin isotypes in intrinsic sensitivity to epothilone B was investigated using siRNA gene knockdown against βII-, βIII- or βIVb-tubulins in two independent non-small cell lung cancer (NSCLC) cell lines, NCI-H460 and Calu-6. Drug-treated clonogenic assays showed that sensitivity to epothilone B was not altered following knockdown of βII-tubulin in both NSCLC cell lines. In contrast, knockdown of βIII-tubulin significantly increased sensitivity to epothilone B. Interestingly, βIVb-tubulin knockdowns were significantly less sensitive to epothilone B, compared to mock- and control siRNA cells. Cell cycle analysis of βIII-tubulin knockdown cells showed a higher percentage of cell death with epothilone B concentrations as low as 0.5 nM. In contrast, βIVb-tubulin knockdown cells displayed a decrease in epothilone B-induced G2-M cell cycle accumulation compared to control siRNA cells. Importantly, βIII-tubulin knockdowns displayed a significant dose-dependent increase in the percentage of apoptotic cells upon treatment with epothilone B, as detected using caspase 3/7 activity and Annexin-V staining. Higher concentrations of epothilone B were required to induce apoptosis in the βIVb-tubulin knockdowns compared to control siRNA, highlighting a potential mechanism underlying decreased sensitivity to this agent. This study demonstrates that specific β-tubulin isotypes can influence sensitivity to epothilone B and may influence differential sensitivity to this promising new agent

Supporting patients with low health literacy: what role do radiation therapists play?

Purpose: Health literacy plays a key role in a patient’s ability to use health information and services, and can affect health outcomes. This study aimed to explore radiation therapists’ perspectives on how they support people with lower health literacy who are undergoing radiotherapy. Methods: Semi-structured interviews were conducted with 25 radiation therapists working in radiation oncology departments in New South Wales, Australia. Results: The four key themes were (1) the process of identifying a patient with low health literacy, (2) the perceived consequences of low health literacy, (3) managing and responding to the needs of different health literacy groups and (4) recommendations to address low health literacy in radiotherapy. Radiation therapists appeared to make an informal, intuitive judgment about a patient’s health literacy, using a variety of verbal and non-verbal cues as well as impromptu conversations with the multi-disciplinary team. Patients perceived to have lower health literacy were described as having greater difficulties assimilating knowledge and engaging in self-care. Although participants reported communicating to patients at a basic level initially, they subsequently tailored their communication to match a patient’s health literacy. Strategies reported to communicate to low health literacy groups ranged from using lay language with minimal medical terminology, using visual aids (photos), using analogies, reiterating information and asking family members with higher literacy to attend consultations. Conclusion: A more structured approach to supporting patients with low health literacy and integrating health literacy training in radiation oncology departments may help to minimise the adverse outcomes typically experienced by this population

Role of the progesterone receptor for paclitaxel resistance in primary breast cancer

Paclitaxel plays an important role in the treatment of primary breast cancer. However, a substantial proportion of patients treated with paclitaxel does not appear to derive any benefit from this therapy. We performed a prospective study using tumour cells isolated from 50 primary breast carcinomas. Sensitivity of primary tumour cells to paclitaxel was determined in a clinically relevant range of concentrations (0.85–27.2 μg ml−1 paclitaxel) using an ATP assay. Chemosensitivity data were used to study a possible association with immunohistochemically determined oestrogen and progesterone receptor (ER and PR) status, as well as histopathological parameters. Progesterone receptor (PR) mRNA expression was also determined by quantitative RT–PCR. We observed a clear association of the PR status with chemosensitivity to paclitaxel. Higher levels of immunohistochemically detected PR expression correlated with decreased chemosensitivity (P=0.008). Similarly, high levels of PR mRNA expression were associated with decreased paclitaxel chemosensitivity (P=0.007). Cells from carcinomas with T-stages 3 and 4 were less sensitive compared to stages 1 and 2 (P=0.013). Multiple regression analysis identified PR receptor status and T-stage as independent predictors of paclitaxel chemosensitivity, whereas the ER, N-stage, grading and age were not influential. In conclusion, in vitro sensitivity to paclitaxel was higher for PR-negative compared with PR-positive breast carcinoma cells. Thus, PR status should be considered as a possible factor of influence when designing new trials and chemotherapy protocols