GPs' opinions of public and industrial information regarding drugs: a cross-sectional study

Background: General Practitioners {GP} in Sweden prescribe more than 50% of all prescriptions. Scientific knowledge on the opinions of GPs regarding drug information has been sparse. Such knowledge could be valuable when designing evidence-based drug information to GPs. GPs' opinions on public- and industry-provided drug information are presented in this article. Methods: A cross-sectional study using a questionnaire was answered by 368 GPs at 97 primary-health care centres {PHCC}. The centres were invited to participate by eight out of 29 drug and therapeutic committees {DTCs}. A multilevel model was used to analyse associations between opinions of GPs regarding drug information and whether the GPs worked in public sector or in a private enterprise, their age, sex, and work experience. PHCC and geographical area were included as random effects. Results: About 85% of the GPs perceived they received too much information from the industry, that the quality of public information was high and useful, and that the main task of public authorities was to increase the GPs' knowledge of drugs. Female GPs valued information from public authorities to a much greater extent than male GPs. Out of the GPs, 93% considered the main task of the industry was to promote sales. Differences between the GPs' opinions between PHCCs were generally more visible than differences between areas. Conclusions: Some kind of incentives could be considered for PHCCs that actively reduce drug promotion from the industry. That female GPs valued information from public authorities to a much greater extent than male GPs should be taken into consideration when designing evidence-based drug information from public authorities to make implementation easier

Intratumoral administration of the Toll-like receptor 7/8 agonist 3M-052 enhances interferon-driven tumor immunogenicity and suppresses metastatic spread in preclinical triple-negative breast cancer

Objectives: Loss of tumor-inherent type I interferon (IFN) signalling has been closely linked to accelerated metastatic progression via decreased immunogenicity and antitumor immunity. Previous studies in murine models of triple-negative breast cancer (TNBC) demonstrate that systemic IFN inducers are effective antimetastatic agents, via sustained antitumor CD8+ T-cell responses. Repeated systemic dosing with recombinant IFNs or IFN inducers is associated with significant toxicities; hence, the use of alternate intratumoral agents is an active area of investigation. It is critical to investigate the impact of intratumoral agents on subsequent metastatic spread to predict clinical impact. Methods: In this study, the local and systemic impact of the intratumoral Toll-like receptor (TLR) 7/8 agonist 3M-052 alone or in combination with anti-PD1 was evaluated in metastatic TNBC models. The IFN-α receptor (IFNAR1) blocking antibody, MAR1-5A3, along with immune-deficient mice and ex vivo assays are utilised to examine the key targets of this agent that are critical for an antimetastatic response. Results: Single intratumoral administration of 3M-052 reduced mammary tumor growth, induced a T-cell-inflamed tumor microenvironment (TME) and reduced metastatic spread to lung. Metastasis suppression was reliant on IFN signalling and an antitumor immune response, in contrast to primary tumor growth inhibition, which was retained in NSG and CD8+ T-cell-depleted mice. 3M-052 action was demonstrated via dendritic cell activation and production of type I IFN and other pro-inflammatory cytokines to initiate a T-cell-inflamed TME and promote tumor cell antigen presentation. Conclusion: This work supports neoadjuvant TLR agonist-based immunotherapeutics as realistic options for immune activation in the TME and long-term metastatic protection in TNBC