Prescription opioids and economic hardship in France.

This paper studies how opioid analgesic sales are empirically related to socioeconomic disparities in France, with a focus on poverty. This analysis is made possible using the OpenHealth database, which provides retail sales data for opioid analgesics available on the French market. We exploit firm-level data for each of the 94 departments in Metropolitan France between 2008 and 2017. We show that increases in the poverty rate are associated with increases in sales: a one percentage point increase in poverty is associated with approximately a 5% increase in mild opioid sales. Our analysis further shows that opioid sales are positively related to the share of middle-aged people and individuals with basic education only, while they are negatively related to population density. The granularity and longitudinal nature of these data allow us to control for a large pool of potential confounding factors. Our results suggest that additional interventions should be more intensively addressed toward the most deprived areas. We conclude that a combination of policies aimed at improving economic prospects and strictly monitoring access to opioid medications would be beneficial for reducing opioid-related harm.

The Safety of Anti-SARS-CoV-2 Vaccines: Vigilance Is Still Required.

The opinion I put forward in this paper is that attention must continue to be paid to clinical observations compatible with a detrimental effect of anti-SARS-CoV-2 in certain diseases of immunological nature. Using the example of the atypical thrombocytopenic thromboses caused by adenoviral-vector-based vaccines, I argue that usual post-marketing pharmacovigilance programs may fail in identifying very rare vaccine-related disorders. Since the robust protective immunity induced by mRNA vaccines is related to their distinct capacity to induce strong stimulation of T follicular helper cells, I suggest that the safety of mRNA vaccines should be further assessed by appropriately designed epidemiological and mechanistic studies focusing on lymphoproliferative and autoimmune diseases in which T follicular helper cells were found to play a key role.

Autoantibodies and SARS-CoV2 infection: The spectrum from association to clinical implication: Report of the 15th Dresden Symposium on Autoantibodies.

The relation between infections and autoimmune diseases has been extensively investigated. Multiple studies suggest a causal relation between these two entities with molecular mimicry, hyperstimulation and dysregulation of the immune system as plausible mechanisms. The recent pandemic with a new virus, i.e., SARS-CoV-2, has resulted in numerous studies addressing the potential of this virus to induce autoimmunity and, eventually, autoimmune disease. In addition, it has also revealed that pre-existing auto-immunity (auto-Abs neutralizing type I IFNs) could cause life-threatening disease. Therefore, the topic of the 15th Dresden Symposium on Autoantibodies was focused on autoimmunity in the SARS-CoV-2 era. This report is a collection and distillation of the topics presented at this meeting.

Rapid Progression of Angioimmunoblastic T Cell Lymphoma Following BNT162b2 mRNA Vaccine Booster Shot: A Case Report.

Since nucleoside-modified mRNA vaccines strongly activate T follicular helper cells, it is important to explore the possible impact of approved SARS-CoV-2 mRNA vaccines on neoplasms affecting this cell type. Herein, we report and discuss unexpected rapid progression of lymphomatous lesions after administration of a BNT162b2 mRNA vaccine booster in a man recently diagnosed with AITL.

Patient preferences for gene therapy in haemophilia: Results from the PAVING threshold technique survey.

OBJECTIVES: The aim of the Patient preferences to Assess Value IN Gene therapies (PAVING) study was to investigate trade-offs that adult Belgian people with haemophilia (PWH) A and B are willing to make when choosing between prophylactic factor replacement therapy (PFRT) and gene therapy. METHODS: The threshold technique was used to quantify the minimum acceptable benefit (MAB) of a switch from PFRT to gene therapy in terms of 'Annual bleeding rate' (ABR), 'Chance to stop prophylaxis' (STOP), and 'Quality of life' (QOL). The design was supported by stakeholder involvement and included an educational tool on gene therapy. Threshold intervals were analysed using interval regression models in Stata 16. RESULTS: A total of 117 PWH completed the survey. Mean thresholds were identified for all benefits, but substantial preference heterogeneity was observed; especially for the STOP thresholds, where the distribution of preferences was bimodal. Time spent on the educational tool and residence were found to impact MAB thresholds. The most accepted (88% of PWH) gene therapy profile investigated in this study comprised of zero bleeds per year (vs. six for PFRT), 90% chance to stop prophylaxis, no impact on QoL, and 10 years of follow-up on side effects (vs. 30 for PFRT). CONCLUSIONS: Results from this study proved the value of educating patients on novel treatments. Moreover, preference heterogeneity for novel treatments was confirmed in this study. In gene therapy decision-making, preference heterogeneity and the impact of patient education on acceptance should be considered.

Thrombotic thrombocytopenia associated with COVID-19 infection or vaccination: Possible paths to platelet factor 4 autoimmunity.

Michel Goldman and Cédric Hermans discuss thrombotic mechanisms in COVID-19 and rare adverse reactions to SARS-CoV-2 vaccinations.

Patient Preferences to Assess Value IN Gene Therapies: Protocol Development for the PAVING Study in Hemophilia.

Introduction: Gene therapies are innovative therapies that are increasingly being developed. However, health technology assessment (HTA) and payer decision making on these therapies is impeded by uncertainties, especially regarding long-term outcomes. Through measuring patient preferences regarding gene therapies, the importance of unique elements that go beyond health gain can be quantified and inform value assessments. We designed a study, namely the Patient preferences to Assess Value IN Gene therapies (PAVING) study, that can inform HTA and payers by investigating trade-offs that adult Belgian hemophilia A and B patients are willing to make when asked to choose between a standard of care and gene therapy. Methods and Analysis: An eight-step approach was taken to establish the protocol for this study: (1) stated preference method selection, (2) initial attributes identification, (3) stakeholder (HTA and payer) needs identification, (4) patient relevant attributes and information needs identification, (5) level identification and choice task construction, (6) educational tool design, (7) survey integration, and (8) piloting and pretesting. In the end, a threshold technique survey was designed using the attributes "Annual bleeding rate," "Chance to stop prophylaxis," "Time that side effects have been studied," and "Quality of Life." Ethics and Dissemination: The Medical Ethics Committee of UZ KU Leuven/Research approved the study. Results from the study will be presented to stakeholders and patients at conferences and in peer-reviewed journals. We hope that results from the PAVING study can inform decision makers on the acceptability of uncertainties and the value of gene therapies to patients.

Prioritization of Surgery in Cancer Patients During the COVID-19 Pandemic: Lessons From a Failed Balancing Act.

The prioritization of surgical oncology over other elective interventions during COVID-19 has failed to preserve the quality of care in oncology and will likely lead to an increase of cancer-related mortality in the coming years. We propose five components for systems to improve the organization of surgical oncology during future crises, namely (1) a multidisciplinary governance structure employing predictive models and risk/benefit evaluations, (2) predefined quality objectives based on measurable markers (regularly reviewed and adapted), (3) temporary flexibility in therapeutic algorithms and authorization procedures (with associated safeguards), (4) systems to ensure access to transparent, apolitical information, and (5) explicit, dedicated logistical surgical capacities to optimize coordination and resource allocation.

Patient perspectives regarding gene therapy in haemophilia: Interviews from the PAVING study.

INTRODUCTION: Exploring patient perceptions regarding gene therapies may provide insights about their acceptability to patients. OBJECTIVE: To investigate opinions of people with haemophilia (PWH) regarding gene therapies. Moreover, this study aimed to identify patient-relevant attributes (treatment features) that influence PWH's treatment choices. METHODS: Semi-structured individual interviews were conducted with Belgian PWH, types A and B. A predefined interview guide included information sections and open, attribute ranking and case questions. Qualitative data were organized using NVivo 12 and analysed following framework analysis. Sum totals of scores obtained in the ranking exercise were calculated per attribute. RESULTS: In total, 20 PWH participated in the interviews. Most participants demonstrated a positive attitude towards gene therapy and were very willing (40%; n = 8) or willing (35%; n = 7) to receive this treatment. The following five attributes were identified as most important to PWH in making their choice: annual bleeding rate, factor level, uncertainty of long-term risks, impact on daily life, and probability that prophylaxis can be stopped. While participants were concerned about the uncertainty regarding long-term safety, most participants were less concerned about uncertainty regarding long-term efficacy. CONCLUSIONS: This qualitative study showed that most PWH have a positive attitude towards gene therapy and that besides efficacy, safety and the related uncertainties, also impact on daily life is important to patients. The identified patient-relevant attributes may be used by regulators, health technology assessment bodies and payers in their evaluation of gene therapies for haemophilia. Moreover, they may inform clinical trial design, pay-for-performance schemes and real-world evidence studies.

Reflections on the Collaborative Fight Against COVID-19.

Clinical trials to identify efficient treatments against COVID-19 flourish worldwide without much attention to patients' voice so far. As therapeutic interventions in the early phase of the disease are attracting more and more interest, we argue that now is the time to involve patients' organizations in the design of clinical protocols in order to define the most relevant end-points and assess the risk-benefit balance of new therapies.

[Jules Bordet, a man of conviction. Centenary of his Nobel Prize]. / Jules Bordet, un homme de conviction - Centenaire de l'attribution de son prix Nobel.

Jules Bordet came to the Institut Pasteur soon after his MD graduation at the Université libre de Bruxelles, thanks to a grant from the Belgian government. He joined there the laboratory of Elie Metchnikoff, the father of phagocytes and cellular immunity. Amazingly, he will decipher there some of the key mechanisms of humoral immunity initially discovered by the German school against which his mentor was fighting. He described the mechanisms that govern bacteriolysis and hemolysis, following the action of immune sera. Even if he favored the term alexin coined by Hans Buchner, he is indeed one of the founding fathers of the complement system (term coined by Paul Ehrlich). It is for these works that he was awarded in October 1920 the 1919 Nobel Prize. Back in Belgium, he became the director of Institut Pasteur du Brabant and made another landmark discovery, namely the identification of the bacillus of whooping cough, now named Bordetella pertussis.

TITLE: Jules Bordet, un homme de conviction - Centenaire de l'attribution de son prix Nobel. ABSTRACT: Docteur en médecine, bénéficiant d'une bourse du gouvernement belge, Jules Bordet vint se former au sein du laboratoire du père de l'immunité cellulaire, Elie Metchnikoff, à l'Institut Pasteur. Paradoxalement, il va y déchiffrer certains des mécanismes clés de l'immunité humorale, initialement découverte par l'école allemande. Il y décrit notamment les mécanismes qui aboutissent à la bactériolyse et l'hémolyse par l'action d'immunsérums. Même s'il favorisa le terme d'alexine, créé par Hans Buchner, c'est bien le système du complément (terme inventé par Paul Ehrlich) dont il est un des pères fondateurs. C'est pour ces travaux qu'il se verra attribué en octobre 1920 le prix Nobel de physiologie ou médecine millésimé 1919. Il identifia aussi le bacille de la coqueluche, qui porte son nom Bordetella pertussis.

Online Information of Vaccines: Information Quality, Not Only Privacy, Is an Ethical Responsibility of Search Engines.

The fact that Internet companies may record our personal data and track our online behavior for commercial or political purpose has emphasized aspects related to online privacy. This has also led to the development of search engines that promise no tracking and privacy. Search engines also have a major role in spreading low-quality health information such as that of anti-vaccine websites. This study investigates the relationship between search engines' approach to privacy and the scientific quality of the information they return. We analyzed the first 30 webpages returned searching "vaccines autism" in English, Spanish, Italian, and French. The results show that not only "alternative" search engines (Duckduckgo, Ecosia, Qwant, Swisscows, and Mojeek) but also other commercial engines (Bing, Yahoo) often return more anti-vaccine pages (10-53%) than Google.com (0%). Some localized versions of Google, however, returned more anti-vaccine webpages (up to 10%) than Google.com. Health information returned by search engines has an impact on public health and, specifically, in the acceptance of vaccines. The issue of information quality when seeking information for making health-related decisions also impact the ethical aspect represented by the right to an informed consent. Our study suggests that designing a search engine that is privacy savvy and avoids issues with filter bubbles that can result from user-tracking is necessary but insufficient; instead, mechanisms should be developed to test search engines from the perspective of information quality (particularly for health-related webpages) before they can be deemed trustworthy providers of public health information.