Fostering the exchange of real world data across different countries to answer primary care research questions: an UNLOCK study from the IPCRG

There is growing awareness amongst healthcare planners, providers and researchers of the need to make better use of routinely collected health data by translating it into actionable information that improves efficiency of healthcare and patient outcomes. There is also increased acceptance of the importance of real world research that recruits patients representative of primary care populations and evaluates interventions realistically delivered by primary care professionals. The UNLOCK Group is an international collaboration of primary care researchers and practitioners from 15 countries. It has coordinated and shared datasets of diagnostic and prognostic variables for COPD and asthma to answer research questions meaningful to professionals working in primary care over a 6-year period. Over this time the UNLOCK Group has undertaken several studies using data from unselected primary care populations from diverse contexts to evaluate the burden of disease, multiple morbidities, treatment and follow-up. However, practical and structural constraints have hampered the UNLOCK Group's ability to translate research ideas into studies. This study explored the constraints, challenges and successes experienced by the UNLOCK Group and its participants' learning as researchers and primary care practitioners collaborating to answer primary care research questions. The study identified lessons for future studies and collaborations that require data sharing across borders. It also explored specific challenges to fostering the exchange of primary care data in comparison to other datasets such as public health, prescribing or hospital data and mechanisms that may be used to overcome these.The IPCRG provided funding for this research project as an UNLOCK Group study for which the funding was obtained through an unrestricted grant by Novartis AG, Basel, Switzerland. Novartis has no role in study design, data collection and analysis, decision to publish, or preparation of the manuscriptinfo:eu-repo/semantics/publishedVersio

How Does Reasoning (Fail to) Contribute to Moral Judgment? Dumbfounding and Disengagement

Recent experiments in moral psychology have been taken to imply that moral reasoning only serves to reaffirm prior moral intuitions. More specifically, Jonathan Haidt concludes from his moral dumbfounding experiments, in which people condemn other people’s behavior, that moral reasoning is biased and ineffective, as it rarely makes people change their mind. I present complementary evidence pertaining to self-directed reasoning about what to do. More specifically, Albert Bandura’s experiments concerning moral disengagement reveal that moral reasoning often does contribute effectively to the formation of moral judgments. And such reasoning need not be biased. Once this evidence is taken into account, it becomes clear that both cognition and affect can play a destructive as well as a constructive role in the formation of moral judgments

The role of APOBEC3B in lung tumor evolution and targeted cancer therapy resistance

In this study, the impact of the apolipoprotein B mRNA-editing catalytic subunit-like (APOBEC) enzyme APOBEC3B (A3B) on epidermal growth factor receptor (EGFR)-driven lung cancer was assessed. A3B expression in EGFR mutant (EGFRmut) non-small-cell lung cancer (NSCLC) mouse models constrained tumorigenesis, while A3B expression in tumors treated with EGFR-targeted cancer therapy was associated with treatment resistance. Analyses of human NSCLC models treated with EGFR-targeted therapy showed upregulation of A3B and revealed therapy-induced activation of nuclear factor kappa B (NF-κB) as an inducer of A3B expression. Significantly reduced viability was observed with A3B deficiency, and A3B was required for the enrichment of APOBEC mutation signatures, in targeted therapy-treated human NSCLC preclinical models. Upregulation of A3B was confirmed in patients with NSCLC treated with EGFR-targeted therapy. This study uncovers the multifaceted roles of A3B in NSCLC and identifies A3B as a potential target for more durable responses to targeted cancer therapy.</p

Lopinavir/Ritonavir and Darunavir/Cobicistat in Hospitalized COVID-19 Patients: Findings From the Multicenter Italian CORIST Study

Background: Protease inhibitors have been considered as possible therapeutic agents for COVID-19 patients. Objectives: To describe the association between lopinavir/ritonavir (LPV/r) or darunavir/cobicistat (DRV/c) use and in-hospital mortality in COVID-19 patients. Study Design: Multicenter observational study of COVID-19 patients admitted in 33 Italian hospitals. Medications, preexisting conditions, clinical measures, and outcomes were extracted from medical records. Patients were retrospectively divided in three groups, according to use of LPV/r, DRV/c or none of them. Primary outcome in a time-to event analysis was death. We used Cox proportional-hazards models with inverse probability of treatment weighting by multinomial propensity scores. Results: Out of 3,451 patients, 33.3% LPV/r and 13.9% received DRV/c. Patients receiving LPV/r or DRV/c were more likely younger, men, had higher C-reactive protein levels while less likely had hypertension, cardiovascular, pulmonary or kidney disease. After adjustment for propensity scores, LPV/r use was not associated with mortality (HR = 0.94, 95% CI 0.78 to 1.13), whereas treatment with DRV/c was associated with a higher death risk (HR = 1.89, 1.53 to 2.34, E-value = 2.43). This increased risk was more marked in women, in elderly, in patients with higher severity of COVID-19 and in patients receiving other COVID-19 drugs. Conclusions: In a large cohort of Italian patients hospitalized for COVID-19 in a real-life setting, the use of LPV/r treatment did not change death rate, while DRV/c was associated with increased mortality. Within the limits of an observational study, these data do not support the use of LPV/r or DRV/c in COVID-19 patients