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Abstract Background Research in treatment of non-small cell lung cancer (NSCLC) has shown promising results with stereotactic ablative radiotherapy (SABR) of oligometastatic disease, wherein distant disease may be limited to one or a few distant organs by host factors. Traditionally, PET/CT has been used in detecting metastatic disease and avoiding futile surgical intervention, however, sensitivity and specificity is limited to only 81 and 79%, respectively. Mediastinal staging still identifies occult nodal disease in up to 20% of NSCLC patients initially thought to be operative candidates. Endobronchial ultrasound and transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive tool for the staging and diagnosis of thoracic malignancy. When EBUS is combined with endoscopic ultrasound using the same bronchoscope (EUS-B), the diagnostic sensitivity and negative predictive value increase to 84 and 97%, respectively. Endoscopic staging in patients with advanced disease has never been studied, but may inform treatment if a curative SABR approach is being taken. Methods This is a multi-centre, prospective, cohort study with two-stage design. In the first stage, 10 patients with oligometastatic NSCLC (lung tumour ± hilar/mediastinal lymphadenopathy) with up to 5 synchronous metastases will be enrolled An additional 19 patients will be enrolled in the second stage if rate of treatment change is greater than 10% in the first stage. Patients will be subject to EBUS or combined modality EBUS/EUS-B to assess bilateral lymph node stations using a N3 to N2 to N1 progression. Primary endpoint is defined as the rate of change to treatment plan including change from SABR to conventional dose radiation, change in mediastinal radiation field, and change from curative to palliative intent treatment. Discussion If a curative approach with SABR for oligometastatic disease is being explored, invasive mediastinal staging may guide treatment and prognosis. This study will provide insight into the use of endoscopic mediastinal staging in determining changes in treatment plan of NSCLC. Results will inform the design of future phase II trials. Trial registration Clinicaltrials.gov identifier NCT04852588. Date of registration: April 19, 2021. Protocol version: 1.1 on December 9, 2021.

Bioethicists have long advocated for patients’ rights by deliberating on what physicians should or should not do for the well-being of patients. Part of this advocacy has involved challenging a paternalistic medical model where physicians are seen as authoritative figures above reproach. Through ombudsperson offices, patients can submit complaints that may lead to medical examiners conducting detailed examinations of physicians’ conduct and decision-making. Prior research indicates that complaints can have serious and broad effects on physicians. We conducted a scoping review to explore and evaluate the extent of the quantitative and qualitative literature examining the effects of complaints on physicians in European and Commonwealth countries. We systematically searched electronic databases (CINAHL, MEDLINE and PsycInfo) and grey literature for primary research that collected information directly from physicians on at least one potential effect of formal complaints. After screening the titles/abstracts of 14,913 records and reviewing 137 full-texts, 25 studies were included. The 25 studies reported on several potential effects, including the patient-physician relationship (3 studies), defensive medicine (14 studies), anxiety (8 studies), depression (8 studies), one’s identity as a physician (5 studies), and anger (5 studies). Generally, the effects evaluated in the included studies were negative. Although the existing literature covered a range of possible effects, few studies assessed the same effects via different methods, and in different regions and contexts. The findings of this scoping review suggest that complaints processes can have negative effects on physicians.

Speed reading is a requisite skill in reading comprehension among adolescent learners. It allows them to process information quickly and meaningfully. Since reading has been a major concern of the Philippine education despite efforts exerted for years, this study aimed to determine whether reading interest itself among adolescent learners correlates with speed reading, particularly grade 11 science, technology, engineering, and mathematics (STEM) learners from a private university in City of Koronadal, South Cotabato. A descriptive-correlational design was used in the study, utilizing an adopted survey questionnaire to assess the level of reading interest and a reading comprehension test to assess the speed reading of the respondents. The data were analyzed using descriptive statistics such as weighted mean to describe the level of reading interest; an effective reading rate (EER) to assess speed reading; and a Pearson correlation coefficient (r) to determine the relationship between reading interest and speed reading. It was found that the level of reading interest of the respondents was high; their speed reading was classified as above average; and thus, there was a high positive correlation between the level of reading interest and speed reading among the respondents, signifying that efforts should be made as well toward intensifying love for reading among Filipino learners. [ABSTRACT FROM AUTHOR]

Background: General medicine is an integral part of health services, yet there is little data highlighting their contribution to acute hospital care in Australia. Aims: To utilise the Victorian Department of Health's administrative dataset for hospital admissions to evaluate the relative contribution and trends over time of general medical services to acute multiday inpatient hospital separations in the Victorian public healthcare system. Methods: A retrospective time‐series study of general medical activity compared to other major specialties using hospital‐level data provided by the Department of Health: (i) extrapolation from diagnosis‐related group (DRG) activity data (2011–2021) and, (ii) directly reported discharge unit‐based activity (available from 2018). Acute multiday separations of all patients aged ≥18 years from all metropolitan and rural Victorian public hospitals were included. Results: Using the DRG‐based data, general medicine ranked as the largest care provider of all specialties studied, accounting for 12.1% of separations. Despite the largest increase at a rate of 2831 separations/year (0.336%/year of total, P < 0.001) compared to others, mean length of stay declined by 0.08 days/year (P < 0.001). These findings were significant for metropolitan and rural hospitals. The use of directly reported discharge unit‐based data also ranked general medicine as the largest care provider accounting for 32.9% of total separations, with rural hospital general medical services contributing nearly 50% of all multiday separations. Conclusions: Both DRG‐based data and discharge unit‐based data indicate that general medicine is the largest provider of acute multiday inpatient care in Victorian hospitals. The estimate of contribution of general medicine differed between the two datasets as DRG data likely over‐represents the role of other specialties possibly due to assumptions regarding specialty management of varying groups of diagnoses. [ABSTRACT FROM AUTHOR]

ONC201 is a first-in-class, orally active antitumor agent that upregulates cytotoxic TRAIL pathway signaling in cancer cells. ONC201 has demonstrated safety and preliminary efficacy in a first-in-human trial in which patients were dosed every 3 weeks. We hypothesized that dose intensification of ONC201 may impact antitumor efficacy. We discovered that ONC201 exerts dose--and schedule-dependent effects on tumor progression and cell death signaling in vivo. With dose intensification, we note a potent anti-metastasis effect and inhibition of cancer cell migration and invasion. Our preclinical results prompted a change in ONC201 dosing in all open clinical trials. We observed accumulation of activated [NK.sup.+] and [CD3.sup.+] cells within ONC201-treated tumors and that NK cell depletion inhibits ONC201 efficacy in vivo, including against TRAIL/ONC201-resistant [Box.sup.-/-] tumors. Immunocompetent NCR1-GFP mice, in which NK cells express GFP, demonstrated [GFP.sup.+] NK cell infiltration of syngeneic MC38 colorectal tumors. Activation of primary human NK cells and increased degranulation occurred in response to ONC201. Coculture experiments identified a role for TRAIL in human NK-mediated antitumor cytotoxicity. Preclinical results indicate the potential utility for ONC201 plus anti-PD-1 therapy. We observed an increase in activated TRAIL-secreting NK cells in the peripheral blood of patients after ONC201 treatment. The results offer what we believe to be a unique pathway of immune stimulation for cancer therapy., Introduction We previously identified ONC201/TIC10 as a small molecule that upregulates endogenous TNF-related apoptosis-inducing ligand (TRAIL) in tumor and normal cells, and restores autocrine and paracrine antitumor activity within tumor [...]