Limitation of life-sustaining therapies in critically ill patients with COVID-19: a descriptive epidemiological investigation from the COVID-ICU study.

BACKGROUND: Limitations of life-sustaining therapies (LST) practices are frequent and vary among intensive care units (ICUs). However, scarce data were available during the COVID-19 pandemic when ICUs were under intense pressure. We aimed to investigate the prevalence, cumulative incidence, timing, modalities, and factors associated with LST decisions in critically ill COVID-19 patients. METHODS: We did an ancillary analysis of the European multicentre COVID-ICU study, which collected data from 163 ICUs in France, Belgium and Switzerland. ICU load, a parameter reflecting stress on ICU capacities, was calculated at the patient level using daily ICU bed occupancy data from official country epidemiological reports. Mixed effects logistic regression was used to assess the association of variables with LST limitation decisions. RESULTS: Among 4671 severe COVID-19 patients admitted from February 25 to May 4, 2020, the prevalence of in-ICU LST limitations was 14.5%, with a nearly six-fold variability between centres. Overall 28-day cumulative incidence of LST limitations was 12.4%, which occurred at a median of 8 days (3-21). Median ICU load at the patient level was 126%. Age, clinical frailty scale score, and respiratory severity were associated with LST limitations, while ICU load was not. In-ICU death occurred in 74% and 95% of patients, respectively, after LST withholding and withdrawal, while median survival time was 3 days (1-11) after LST limitations. CONCLUSIONS: In this study, LST limitations frequently preceded death, with a major impact on time of death. In contrast to ICU load, older age, frailty, and the severity of respiratory failure during the first 24 h were the main factors associated with decisions of LST limitations.

A qualitative study of professionals' perspectives on the ethics of medically-delivered safer injection education for people who inject drugs.

BACKGROUND: In this qualitative analysis we aimed to explore addiction physicians' perspectives on safer injection education for people who inject drugs, especially: (1) on possible means of introducing safer injection education in the medical environment, (2) on the compatibility of safer injection education with each physician's core values and goals, and (3) on possible reasons for the ethical dilemma in safer injection education. METHODS: We conducted semi-structured interviews with eleven physicians practicing addiction medicine in France in clinical and harm reduction settings. RESULTS: All participants were in favor of educational interventions for people who inject drugs. Nonetheless, these interventions varied from simple advice to injection supervision and they were seen as less acceptable when they concerned the practical and material aspects of injection. Some participants found that physicians practicing in clinical settings, where patients consult mostly to stop their drug use, should not practice safer injection education. On the contrary, other participants claimed that safer injection education was essential in all settings and was not a choice but rather a duty for addiction physicians. The ethical dilemma of such intervention when delivered by medical staff was viewed as a complex phenomenon, related to the representations of intravenous drug use and to societal expectations from physicians. CONCLUSION: Physicians' views on safer injection education for people who inject drugs reveal an emotionally charged subject related to the structural organization of addiction management in France. Such education is marked by an arduous history of harm reduction policies in France. IRB REGISTRATION: #00011928.

Acceptability of and Willingness to Take Digital Pills by Patients, the Public, and Health Care Professionals: Qualitative Content Analysis of a Large Online Survey.

BACKGROUND: Digital pills are pills combined with a sensor, which sends a signal to a patch connected to a smartphone when the pills are ingested. Health care professionals can access patient data from digital pills online via their own interface, thus allowing them to check whether a patient took the drug. Digital pills were developed for the stated goal of improving treatment adherence. The US Food and Drug Administration approved the first digital pills in November 2017, but the manufacturer withdrew its application to the European Medicines Agency in July 2020 because of insufficient evaluation. OBJECTIVE: As recommended for the evaluation of health technologies, this study assesses the prospective acceptability of and willingness to take digital pills among patients, the public, and health care professionals. METHODS: Participants were patients who were receiving long-term treatment for a chronic condition, public participants (both groups recruited from a representative sample), and health care professionals. Participants answered 5 open-ended questions regarding the acceptability of digital pills and 1 close-ended question regarding the willingness to take digital pills, which were developed in a preliminary qualitative study. We explored the 5 theoretical dimensions of acceptability by performing an abductive qualitative content analysis of all free-text responses. We assessed data saturation with mathematical models. We fitted a multivariate logistic regression model to identify the sociodemographic and health characteristics associated with the willingness to take digital pills. RESULTS: Between January 29, 2020, and April 18, 2020, 767 patients, 1238 public participants, and 246 health care professionals provided 11,451 free-text responses. We identified 98 codes related to the acceptability of digital pills: 29 codes on perceived clinical effectiveness (eg, sensor safety cited by 66/2251 participants, 29.5%), 6 on perceived burden (eg, increased doctors' workload, 164/2251 participants, 7.3%), 25 on perceived ethicality (eg, policing, 345/2251 participants, 15.3%), 30 codes on perceived opportunity (eg, exclusively negative perception, 690/2251 participants, 30.7%), and 8 on affective attitude (eg, anger, 541/2251, 24%). Overall, 271/767 (35.3%) patients, 376/1238 (30.4%) public participants, and 39/246 (15.8%) health care professionals reported willingness to take digital pills. This willingness was associated with male sex (odds ratio 1.98, 95% CI 1.62-2.43) and current use of a connected device to record health settings (with a dose-response relationship). CONCLUSIONS: The prospective acceptability of and willingness to take digital pills were limited by clinical and ethical concerns both at the individual and societal level. Our results suggest that digital pills should not be considered a mere change in the form of drug administration but a complex intervention requiring specific evaluation before extended use in clinical routine practice as well as an ethical and legal framework to ensure safe and ethical collection and use of health data through a patient-centered approach.

The contribution of French patient and consumer groups to health technology assessments over a 2-year period: an observational retrospective study.

BACKGROUND: In 2017, The French National Authority for Health (HAS) created an open, online, systematic contribution process to enable patient and consumer groups (PCGs) to contribute to health technology assessment (HTA) carried out to aid public authorities in reimbursement and pricing decision making. OBJECTIVES: This retrospective study analyzes how French PCGs contributed to the HTA process within the HAS for the first 2 years of this new mechanism. METHODS: PCG contributions received between 01 January 2017 and 31 December 2018 and the recording of deliberations leading to reports of the corresponding HTAs were included. Analysis grids were designed by the investigators with 5 rounds of refinement tests on 10 random PCG contributions and the reports. Systematic data extraction was then performed separately by two investigators. PCG answers to the open-question templates and the related final HTA report published by the HAS were analyzed. RESULTS: Seventy-nine contributions from 44 PCGs were received and analyzed by the HAS for 78 out of the 592 HTAs performed for drugs or medical devices during the 2-year period. Twenty-five percent of the HTAs performed for drugs received at least one contribution. The contributions covered quality-of-life aspects, access to care, and personal and family impact. Membership and budget of the contributing PCGs varied greatly. CONCLUSIONS: The experience gained in the first 2 years demonstrates the feasibility of the process and the fact that PCG contribution actually provides relevant input on the patient perspective for HTAs used for reimbursement decisions. The challenges identified on the side of PCGs were time constraints and human resources.

Facing new challenges to informed consent processes in the context of translational research: the case in CARPEM consortium.

BACKGROUND: In the context of translational research, researchers have increasingly been using biological samples and data in fundamental research phases. To explore informed consent practices, we conducted a retrospective study on informed consent documents that were used for CARPEM's translational research programs. This review focused on detailing their form, their informational content, and the adequacy of these documents with the international ethical principles and participants' rights. METHODS: Informed consent forms (ICFs) were collected from CARPEM investigators. A content analysis focused on information related to biological samples and data treatment (context of sampling and collect, aims, reuse, consent renewal), including the type of consent. An automatic assessment of the readability of the ICFs were performed with the IT program "Flesch Score". RESULTS: 29 ICFs from 25 of 49 studies were analyzed after selection criteria were applied. Three types of consent were identified: 11 broad consents, six specific consents, and two opt-out consents. The Flesch Scores showed that most of the documents were too complex to be fully understood by most of the potential research participants. Most of the biological samples were collected during the healthcare routine, but the information content about secondary use of biological samples varied between ICFs. All documents mentioned personal data treatment but information about their reuse was not standardized in the ICFs. CONCLUSIONS: Our review of current IC procedures of CARPEM showed that practices could be improved considering new translational research methods. "Old fashion written ICFs" should be adapted to the translational research approach, to better respect individual rights and international research ethics principles. In this context, theoretically, a digital tool allowing dynamic information and consent of participants, through an electronic interactive platform may be a good way to promote more active participation in research. Nevertheless, its feasibility in the complex environment of biological samples and data research remains to prove. The way of a combination of a broad consent followed by dynamic information may be alternatively tested.

How to strengthen the presence of patients in health technology assessments conducted by the health authorities.

The constant development of health technologies, combined with the increase in the cost of treatment, means that States must continually make choices about the introduction of new technologies into their healthcare system and how they are to be funded. In France, the systematic participation of patients in these processes is one of the targets to be met in terms of healthcare democracy. Although, on an international level, patient involvement in these assessments is constantly growing, it is difficult to define due to the presence of unstabilised elements in terms of both terminology and assessment methods. As a result, patient and public involvement in health technology assessments varies considerably from one country to the next, from one field to the next and even from one type of technology to the next. Several types of involvement exist, ranging from studies conducted to collect patient "insight" (experience, perception, needs, preferences, attitudes to treatment and health, etc.) to processes aimed at including patients in assessments (as individuals, as representatives of associations, etc.). Given the scope and complexity of the subject, and the difficulty involved in understanding all the different aspects of health technologies and innovations, the members of the Round Table chose to concentrate on health technology assessments (medicinal products and medical devices) to develop national recommendations on all possible types of patient involvement in the health technology assessment processes conducted by the health authorities in France.

Partnering with patients in translational oncology research: ethical approach.

BACKGROUND: The research program CARPEM (cancer research and personalized medicine) brings together the expertise of researchers and hospital-based oncologists to develop translational research in the context of personalized or "precision" medicine for cancer. There is recognition that patient involvement can help to take into account their needs and priorities in the development of this emerging practice but there is currently no consensus about how this can be achieved. In this study, we developed an empirical ethical research action aiming to improve patient representatives' involvement in the development of the translational research program together with health professionals. The aim is to promote common understanding and sharing of knowledge between all parties and to establish a long-term partnership integrating patient's expectations. METHODS: Two distinct committees were settled in CARPEM: an "Expert Committee", gathering healthcare and research professionals, and a "Patient Committee", gathering patients and patient representatives. A multidisciplinary team trained in medical ethics research ensured communication between the two committees as well as analysis of discussions, minutes and outputs from all stakeholders. RESULTS: The results highlight the efficiency of the transfer of knowledge between interested parties. Patient representatives and professionals were able to identify new ethical challenges and co-elaborate new procedures to gather information and consent forms for adapting to practices and recommendations developed during the process. Moreover, included patient representatives became full partners and participated in the transfer of knowledge to the public via conferences and publications. CONCLUSIONS: Empirical ethical research based on a patient-centered approach could help in establishing a fair model for coordination and support actions during cancer research, striking a balance between the regulatory framework, researcher needs and patient expectations. Our approach addresses the concept of translational ethics as a way to handle the main remaining gap between combining care and research activities in the medical pathway and the existing framework.

Sirolimus therapy may cause cardiac tamponade.

The side-effects associated with the immunosuppressive drug sirolimus are numerous and constitute a major limitation for its use in renal transplantation. In this study, we describe two cases of renal transplant recipients treated with sirolimus who developed pericardial tamponade associated with interstitial pneumonia, proteinuria, microcytic anemia and, in one case, lymphocytic meningitidis. An extensive search for infectious agents was negative, and all symptoms disappeared after sirolimus interruption. Therefore, this case demonstrates for the first time that sirolimus can cause pericardial tamponade as well as lymphocytic meningitidis.

Clinical and microbial impact of screening kidney allograft preservative solution for bacterial contamination with high-sensitivity methods.

The clinical and bacteriological consequences of routinely performing highly sensitive bacterial screening of kidney transplant preservation solution (PS) are not known. To evaluate the clinical and microbiological impacts of this strategy, we retrospectively analyzed 200 consecutive kidney allograft recipients from March 2009 to February 2011 for whom PS samples were routinely screened. PS were inoculated into aerobic and anaerobic blood culture bottles, as well as blood agar plates. A rectal swab for extended-spectrum ß-lactamase-producing Enterobacteriaceae (EBSL-PE) faecal carriage was also routinely obtained from each patient at admission and every 7 days until hospital discharge. In addition, a standard culture of drain fluid was collected on the day after kidney transplantation. Complete samples and cultures of PS were performed in 165 cases (82.5%), and 62 (37.6%) had positive blood culture results. The most frequent microbial agent isolated was coagulase-negative staphylococci (51.8%). Of these 62 positive samples, only seven (11.3%) were confirmed to contain the same organism by the standard culture method. Drain fluid and PS culture positivity with the same microorganism occurred in only two patients. Of the 62 patients with positive PS cultures, 26 (41.9%) received pre-emptive antibiotic therapy initiated within 48 h post-transplant. During the hospitalization period, patients with a positive PS culture, regardless of whether they received pre-emptive antibiotic therapy, did not exhibit any invasive infections (urinary, blood, peritoneal or wound) related to the microorganisms isolated in the PS. Patients with positive PS cultures who were treated with antibiotic therapy acquired significantly more colonizing ESBL-PE than patients who did not receive antibiotics (53.8% vs. 16.6%; P = 0.01); these patients also developed more clinical infections related to the ESBL-PE (23.1% vs. 5.2%; P < 0.01). The use of antibiotics for patients with positive PS cultures was an independent risk factor for ESBL-PE acquisition in both univariate and multivariate analyses. In conclusion, the use of more sensitive culture methods increases the rate of bacterial contamination of PS and is associated with an increased prescription of antibiotics and increased ESBL-PE carriage and related infections. Therefore, the systematic use of PS blood bottle cultures in kidney transplantation may have no benefit and might increase the rate of ESBL-PE emergence.

Team-family conflicts over end-of-life decisions in ICU: A survey of French physicians' beliefs.

INTRODUCTION: Conflicts between relatives and physicians may arise when decisions are being made about limiting life-sustaining therapies (LST). The aim of this study was to describe the motives for, and management of team-family conflicts surrounding LST limitation decisions in French adult ICUs. METHODS: Between June and October 2021, French ICU physicians were invited to answer a questionnaire. The development of the questionnaire followed a validated methodology with the collaboration of consultants in clinical ethics, a sociologist, a statistician and ICU clinicians. RESULTS: Among 186 physicians contacted, 160 (86%) answered all the questions. Conflicts over LST limitation decisions were mainly related to requests by relatives to continue treatments considered to be unreasonably obstinate by ICU physicians. The absence of advance directives, a lack of communication, a multitude of relatives, and religious or cultural issues were frequently mentioned as factors contributing to conflicts. Iterative interviews with relatives and proposal of psychological support were the most widely used tools in attempting to resolve conflict, while the intervention of a palliative care team, a local ethics resource or the hospital mediator were rarely solicited. In most cases, the decision was suspended at least temporarily. Possible consequences include stress and psychological exhaustion among caregivers. Improving communication and anticipation by knowing the patient's wishes would help avoid these conflicts. CONCLUSION: Team-family conflicts during LST limitation decisions are mainly related to requests from relatives to continue treatments deemed unreasonable by physicians. Reflection on the role of relatives in the decision-making process seems essential for the future.

Effects of cinacalcet in renal transplant patients with hyperparathyroidism.

BACKGROUND: Cinacalcet decreases serum parathyroid hormone (PTH) and calcium concentrations in kidney transplant recipients with autonomous hyperparathyroidism. Long-term treatment with cinacalcet may increase urinary calcium excretion and the risk of renal calcium deposits and may alter renal graft function. METHODS: We studied 71 renal recipients with hypercalcemic hyperparathyroidism. Of these patients, 34 received cinacalcet between month 3 and month 12 after renal transplantation. We compared phosphate calcium balance, measured glomerular filtration rate (GFR) and renal biopsies in cinacalcet-treated and non-cinacalcet-treated patients. Measurements were performed before initiating cinacalcet treatment (month 3) and at month 12. RESULTS: Patients treated with cinacalcet had more severe hyperparathyroidism. Serum PTH concentration decreased in both groups between months 3 and 12, but the decrease was much more important in cinacalcet-treated patients. Urinary calcium excretion significantly increased under cinacalcet treatment and was more than twice as high at month 12 as in patients who did not receive cinacalcet treatment. However, the hypercalciuria was not associated with an increase in calcium deposits on renal biopsies or an alteration of measured GFR. CONCLUSIONS: Despite sustained and marked hypercalciuria induced by cinacalcet treatment, cinacalcet does not have adverse effects on GFR or on renal graft calcium deposits in the first year following renal transplantation.

[Questioning the informed consent for conservation and research use of human biospecimens]. / Le consentement éclairé en question dans le cadre de collections en biobanque.

The availability for research of biobanked human biological materials and their derived data is submitted to several legal regulations, including informed consent. Empirical research about the understanding of the information disclosed is limited. The purpose of this paper is to analyze the appropriation of the oral and written information provided when the Informed Consent is collected for participation in tumor collection. Two materials have been collected: the description of the context of consent collecting based on interviews with different actors of one of the hospital sites concerned by the biobank and the analysis of consent forms by a group of individuals in poverty situations, using focus-group method. The description of the context shows the emotional situation related to the announcement of cancer and therefore difficulties understanding complex information in that very moment. They also pointed out the question of the patient's autonomy to give consent in the context of doctor-patient relationships in cancerology. The group insisted on the difficulty to understand the information disclosed, because of numerous and complex words and acronyms. On another hand, essential information isn't provided about risks and data sharing. Consulting a group of people in poverty situation is an issue of social justice: if patients with a low level of health literacy are able to take ownership of those questions, all the patients would be able to do it.

Entropy as the main justification for research in medical ethics.

Ethics is an unconventional field of research for a surgeon, as ethics in surgery owns several specificities and surgery is considered an aggressive specialty. Therefore, the interest of research in medical ethics is sometimes unclear.In this short essay, we discussed the interest of research in medical ethics using a comparison to thermodynamics and mainly, entropy. During the transformation of a figure from one state to another, some energy is released or absorbed; yet, a part of this energy is wasted because of "unordered" (and unsuccessful) reactions: it is Entropy.This "wasted energy" exists in Medical practice and justifies research in Medical ethics.

Ethical Aspects of Artificial Intelligence in Radiation Oncology.

Radiation oncology is a field that heavily relies on new technology. Data science and artificial intelligence will have an important role in the entire radiotherapy workflow. A new paradigm of routine healthcare data reuse to automate treatments and provide decision support is emerging. This review will discuss the ethical aspects of the use of artificial intelligence (AI) in radiation oncology. More specifically, the review will discuss the evolution of work through the ages, as well as the impact AI will have on it. We will then explain why AI opens a new technical era for the field and we will conclude on the challenges in the years to come.

AP-HP Health Data Space (AHDS) to the Test of the Covid-19 Pandemic.

Sharing observational and interventional health data within a common data space enables university hospitals to leverage such data for biomedical discovery and moving towards a learning health system. OBJECTIVE: To describe the AP-HP Health Data Space (AHDS) and the IT services supporting piloting, research, innovation and patient care. METHODS: Built on three pillars - governance and ethics, technology and valorization - the AHDS and its major component, the Clinical Data Warehouse (CDW) have been developed since 2015. RESULTS: The AP-HP CDW has been made available at scale to AP-HP both healthcare professionals and public or private partners in January 2017. Supported by an institutional secured and high-performance cloud and an ecosystem of tools, mostly open source, the AHDS integrates a large amount of massive healthcare data collected during care and research activities. As of December 2021, the AHDS operates the electronic data capture for almost +840 clinical trials sponsored by AP-HP, the CDW is enabling the processing of health data from more than 11 million patients and generated +200 secondary data marts from IRB authorized research projects. During the Covid-19 pandemic, AHDS has had to evolve quickly to support administrative professionals and caregivers heavily involved in the reorganization of both patient care and biomedical research. CONCLUSION: The AP-HP Data Space is a key facilitator for data-driven evidence generation and making the health system more efficient and personalized.

Mycobacterium genavense as a cause of subacute pneumonia in patients with severe cellular immunodeficiency.

BACKGROUND: Mycobacterium genavense is a rare nontuberculous mycobacteria (NTM). Human infections are mostly disseminated in the setting of the AIDS epidemic or the use of aggressive immunosuppressive treatments. M. genavense culture is fastidious, requiring supplemented media. Pulmonary involvement rarely occurs as a primary localization. CASES PRESENTATION: We report here two patients with pneumonia as the predominant manifestation of M. genavense infection: one kidney transplanted patient and one HIV-infected patient. Both patients were initially treated with anti-tuberculous drugs before the identification of M. genavense on sputum or broncho-alveolar lavage fluid culture. A four-drug regimen including clarithromycin and rifabutin was started. Gamma interferon has been helpful in addition to antimycobacterial treatment for one patient. CONCLUSION: Clinicians should be aware that M. genavense could be the etiologic agent of sub-acute pneumonia mimicking tuberculosis in patients with cellular immunodeficiency status.

COVID-19 Health Crisis and Chronic Illness: Protocol for a Qualitative Study.

BACKGROUND: The acute nature of the COVID-19 pandemic has put a strain on health resources that are usually dedicated to chronic illnesses. Resulting changes in care practices and networks have had major repercussions on the experience of people with chronic disorders. OBJECTIVE: This paper presents the protocol of the Parcours, Associations, Réseau, Chronicité, Organisation, Usagers, Retour d'expérience, Soins (PARCOURS)-COVID study. The aim of this study is to evaluate the effects of reorganization of the health system on the usual care network of patients with chronic illness, which fosters and qualifies the quality and continuum of care provided. The first objective of this study is to document these patients' experiences through transformations and adaptations of their network, both in the practical dimension (ie, daily life and care) and subjective dimension (ie, psychosocial experience of illness and relationship to the health system). The second objective of the study is to understand and acknowledge these reorganizations during the COVID-19 lockdown and postlockdown periods. The third objective is to produce better adapted recommendations for patients with chronic illness and value their experience for the management of future health crisis. METHODS: The PARCOURS-COVID study is a qualitative and participatory research involving patient organizations as research partners and members of these organizations as part of the research team. Three group of chronic diseases have been selected regarding the specificities of the care network they mobilize: (1) cystic fibrosis and kidney disease, (2) hemophilia, and (3) mental health disorders. Four consecutive phases will be conducted, including (1) preparatory interviews with medical or associative actors of each pathology field; (2) in-depth individual interviews with patients of each pathology, analyzed using the qualitative method of thematic analysis; (3) results of both these phases will then be triangulated through interviews with members of each patient's care ecosystem; and finally, (4) focus groups will be organized to discuss the results with research participants (ie, representatives of chronic disease associations; patients; and actors of the medical, psychosocial, and family care network) in a research-action framework. RESULTS: The protocol study has undergone a peer review by the French National Research Agency's scientific committee and has been approved by the research ethical committee of the University of Paris (registration number: IRB 00012020-59, June 28, 2020). The project received funding from August 2020 through April 2021. Expected results will be disseminated in 2021 and 2022. CONCLUSIONS: Our findings will better inform the stakes of the current health crisis on the management of patients with chronic illness and, more broadly, any future crisis for a population deemed to be at risk. They will also improve health democracy by supporting better transferability of knowledge between the scientific and citizen communities. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/28728.