Using contextual factors to elicit placebo and nocebo effects: An online survey of healthcare providers' practice

Contextual factor use by healthcare professionals has been studied mainly among nurses and physiotherapists. Preliminary results show that healthcare professionals use contextual factors without specifically labelling them as such. The main objective of this study was to evaluate knowledge and explore voluntary contextual factor use among various healthcare professions. The results aim to facilitate hypothesis-generation, to better position further research to explain and characterise contextual factor use. We conducted a web-based questionnaire cross-sectional observational study on a non-probabilistic convenience sample. Face and content validity were tested through cognitive interviews. Data were analysed descriptively. The target population was the main healthcare profession, or final year students, defined by the French public health law. The countries of distribution of the questionnaire were the French-speaking European countries. Among our 1236 participants, use of contextual factors was widespread. Those relating to the therapeutic relationship (e.g., communication) and patient characteristics (e.g., past experiences) were reportedly the most used. Meanwhile, contextual factors related to the healthcare providers' characteristics and their own beliefs were reported as less used. Despite high variability, respondents suggested contextual effects contribute to approximately half of the overall effect in healthcare and were perceived as more effective on children and elderly adults. Conceptual variations that exist in the literature are also present in the way healthcare providers consider contextual effects. Interestingly, there seems to be common ground between how physiotherapists, nurses and physicians use different contextual factors. Finally, in the present study we also observed that while there are similarities across usage, there is lack of both an epistemological and ethical consensus among healthcare providers with respect to contextual factors

‘It's not my greengrocer, it's someone from the medical profession’: A qualitative study regarding acceptability of deceptive and open‐label placebo prescribing in France

International audienceObjectives: To explore participants' views regarding clinical use of deceptive placebo (DP) and open-label placebo (OLP) treatments.Design: Qualitative thematic analysis.Methods: We conducted eight semi-structured interviews with healthy participants in an experimental trial comparing the efficacy of OLP and DP (Clinical trials n°NCT03934138). Interviewees' opinions were solicited following administration of placebos during the trial. Interviews were analysed using data-driven analysis.Results: We identified three themes. First, participants considered trust central in judging a placebo treatment to be acceptable. They expressed the importance of an implicit trust both in their health care professionals' (HCPs') competency as well as in the profession at large. A second theme was the perception of how placebo treatments might solve health problems. Acceptability of both types of placebo treatments was dependent on the perception patients had about the treatment solving their problem and/or doubts regarding the effectiveness of placebos The third theme encompassed perceived risks associated with placebo prescribing. Some comments viewed placebos positively as facilitating reduced medication intake. However, participants also identified the potential of placebos to generate adverse side effects.Conclusions: Treatment acceptability by patients is a pre-requisite, alongside effectiveness, to harness OLPs in clinical care. Our study identified the importance of trust in HCPs prescribing placebos, the clinical effectiveness of placebos and the potential risks of these interventions in assessing their acceptability. Future research is needed to explore the contexts in which placebos might be used, and how best to communicate information about placebo intervention

Chimeric peptidomimetic antibiotics against Gram-negative bacteria

There is an urgent need for new antibiotics against Gram-negative pathogens that are resistant to carbapenem and third-generation cephalosporins, against which antibiotics of last resort have lost most of their efficacy. Here we describe a class of synthetic antibiotics inspired by scaffolds derived from natural products. These chimeric antibiotics contain a β-hairpin peptide macrocycle linked to the macrocycle found in the polymyxin and colistin family of natural products. They are bactericidal and have a mechanism of action that involves binding to both lipopolysaccharide and the main component (BamA) of the β-barrel folding complex (BAM) that is required for the folding and insertion of β-barrel proteins into the outer membrane of Gram-negative bacteria. Extensively optimized derivatives show potent activity against multidrug-resistant pathogens, including all of the Gram-negative members of the ESKAPE pathogens$^{1}$. These derivatives also show favourable drug properties and overcome colistin resistance, both in vitro and in vivo. The lead candidate is currently in preclinical toxicology studies that-if successful-will allow progress into clinical studies that have the potential to address life-threatening infections by the Gram-negative pathogens, and thus to resolve a considerable unmet medical need

Importance of Baseline Prognostic Factors With Increasing Time Since Initiation of Highly Active Antiretroviral Therapy: Collaborative Analysis of Cohorts of HIV-1-Infected Patients

Background: The extent to which the prognosis for AIDS and death of patients initiating highly active antiretroviral therapy (HAART) continues to be affected by their characteristics at the time of initiation (baseline) is unclear. Methods: We analyzed data on 20,379 treatment-naive HIV-1- infected adults who started HAART in 1 of 12 cohort studies in Europe and North America (61,798 person-years of follow-up, 1844 AIDS events, and 1005 deaths). Results: Although baseline CD4 cell count became less prognostic with time, individuals with a baseline CD4 count 350 cells/μL (hazard ratio for AIDS = 2.3, 95% confidence interval [CI]: 1.0 to 2.3; mortality hazard ratio = 2.5, 95% CI: 1.2 to 5.5, 4 to 6 years after starting HAART). Rates of AIDS were persistently higher in individuals who had experienced an AIDS event before starting HAART. Individuals with presumed transmission by means of injection drug use experienced substantially higher rates of AIDS and death than other individuals throughout follow-up (AIDS hazard ratio = 1.6, 95% CI: 0.8 to 3.0; mortality hazard ratio = 3.5, 95% CI: 2.2 to 5.5, 4 to 6 years after starting HAART). Conclusions: Compared with other patient groups, injection drug users and patients with advanced immunodeficiency at baseline experience substantially increased rates of AIDS and death up to 6 years after starting HAART