Rethinking the pros and cons of randomized controlled trials and observational studies in the era of big data and advanced methods: a panel discussion.

Randomized controlled trials (RCTs) have traditionally been considered the gold standard for medical evidence. However, in light of emerging methodologies in data science, many experts question the role of RCTs. Within this context, experts in the USA and Canada came together to debate whether the primacy of RCTs as the gold standard for medical evidence, still holds in light of recent methodological advances in data science and in the era of big data. The purpose of this manuscript, aims to raise awareness of the pros and cons of RCTs and observational studies in order to help guide clinicians, researchers, students, and decision-makers in making informed decisions on the quality of medical evidence to support their work. In particular, new and underappreciated advantages and disadvantages of both designs are contrasted. Innovations taking place in both of these research methodologies, which can blur the lines between the two, are also discussed. Finally, practical guidance for clinicians and future directions in assessing the quality of evidence is offered.

Identify and classify interprofessional primary care performance indicators: a scoping review protocol.

INTRODUCTION: Measuring the performance of interprofessional primary care is needed to examine whether this model of care is achieving its desired outcomes on patient care and health system effectiveness as well as to guide quality improvement initiatives. The aim of this scoping review is to map the literature on primary care performance measurement indicators to determine the extent to which current indicators capture or could be adapted to capture processes, outputs and outcomes that reflect interprofessional primary care. METHODS AND ANALYSIS: The review will be guided by the six-stage framework by Arksey and O'Malley (2005). MEDLINE, Embase, CINAHL, grey literature and the reference list of key studies will be searched to identify any study, published in English or French between 2000 and 2022, related to the concepts of performance indicators, frameworks, interprofessional teams and primary care. Two reviewers will independently screen all abstracts and full-text studies for inclusion. Eligible indicators will be classified according to process, output and outcome domains proposed by two validated frameworks. This study started in November 2022 and is expected to be completed by July 2023. ETHICS AND DISSEMINATION: This review does not require ethical approval. The results will be disseminated through a peer-reviewed publication, conference presentations and presentations to stakeholders.

Radiosensitization of EMT6 mammary carcinoma cells by 2-benzoyl-3-phenyl-6,7-dichloroquinoxaline 1,4-dioxide.

BACKGROUND AND PURPOSE: Previously, we have reported that 2-benzoyl-3-phenyl-6,7-dichloroquinoxaline 1,4-dioxide (DCQ) is a radiosensitizer. Here, we investigate the mechanism of radiosensitization. MATERIALS AND METHODS: EMT6 cells were treated with DCQ for 4h prior to ionizing radiation (IR). Flow cytometry, clonogenic assay, TUNEL, and Western blotting were performed to assess the effect of treatment on cells. RESULTS: Propidium iodide staining of EMT6 cells treated with IR+/-DCQ revealed high numbers of cells with decreased DNA, consistent with an apoptotic response. TUNEL assay revealed apoptosis was 4%, 38%, and 49% 24h after treatment with IR alone, DCQ alone, and DCQ+IR, respectively. Clonogenic assays revealed that the survival of irradiated EMT6 cells was significantly reduced by DCQ treatment. DCQ treatment abrogated the radiation-induced expression of p21 and p53. The increased apoptosis observed in DCQ+IR-treated cells was correlated to suppression of radiation-induced phosphorylation of Akt and the expression of Bcl-X(L). DCQ also caused the phosphorylation of mitogen-activated protein kinases Erk and Jnk. CONCLUSIONS: The radiosensitization effect of DCQ occurs through enhancement of radiation-induced apoptosis, which correlates to the inhibition of p-Akt kinase and Bcl-X(L) and the activation of Erk and Jnk kinases, but appears independent of p53 induction or modulation of Bax/Bcl-2 gene expression. These data suggest DCQ should be tested as a radiosensitizer in vivo and has potential in the treatment of human solid tumors.