GPs' practices when prescribing buprenorphine in primary care: A survey among the Sentinelles network.

INTRODUCTION: France is a leading country for opioid agonist treatment providing, with a predominance of buprenorphine. General practitioners (GPs) are the main prescribers of buprenorphine, but they seem to be less involved over the last 10 years. This work is the second part of a larger study analysing buprenorphine prescribing among French GPs working in primary care, and aims to describe GPs' practices when prescribing buprenorphine. METHODS: This is a cross-sectional study conducted in France from March to July 2021 among a sample of GPs in the Sentinelles network, a national epidemiologic surveillance system. Data about the last situations of initiation and renewal of buprenorphine were collected. RESULTS: Among the 237 participants (34.3% response rate), 156 responded to the questionnaire about the last situation of renewal and 41 about the last situation of initiation. The last initiation occurred more than 12 months earlier for 46.3% of respondents, whereas the last renewal occurred less than 1 month ago for 68.6%. There was an over-representation of the male gender among the patients who were consulting (initiation 70.7%, renewal 68.6%). A majority of patients had an illicit opioid use disorder (initiation 78.0%, renewal 82.7%). Overall, GPs were involved in the general care of patients with opioids use disorder and in opioids harm reduction (initiation 87.8% and 82.9%, renewal 88.5% and 51.9%). CONCLUSION: Among buprenorphine prescribers, initiations were infrequent unlike renewals and involved mainly illicit opioid users.

The French ecology of medical care. A nationwide population-based cross sectional study.

PURPOSE: Studies in the United States, Canada, Belgium, and Switzerland showed that the majority of health problems are managed within primary health care; however, the ecology of French medical care has not yet been described. METHODS: Nationwide, population-based, cross sectional study. In 2018, we included data from 576,125 beneficiaries from the General Sample of Beneficiaries database. We analysed the reimbursement of consultations with (i) a general practitioner (GP), (ii) an outpatient doctor other than a GP, (iii) a doctor from a university or non-university hospital; and the reimbursement of (iv) hospitalization in a private establishment, (v) general hospital, and (vi) university hospital. For each criterion, we calculated the average monthly number of reimbursements reported on 1,000 beneficiaries. For categorical variables, we used the χ2 test, and to compare means we used the z test. All tests were 2-tailed with a P-value < 5% considered significant. RESULTS: Each month, on average, 454 (out of 1,000) beneficiaries received at least 1 reimbursement, 235 consulted a GP, 74 consulted other outpatient doctors in ambulatory care and 24 in a hospital, 13 were hospitalized in a public non-university hospital and 10 in the private sector, and 5 were admitted to a university hospital. Independently of age, people consulted GPs twice as much as other specialists. The 13-25-year-old group consulted the least. Women consulted more than men. Individuals covered by complementary universal health insurance had more care. CONCLUSIONS: Our study on reimbursement data confirmed that, like in other countries, in France the majority of health problems are managed within primary health care.

Barriers and facilitators to the involvement of general practitioners in the prescription of buprenorphine.

INTRODUCTION: France has one of the highest opioid agonist treatment (OAT) coverage rates in the world. French general practitioners (GPs) are providing the majority of prescriptions. However, a fall in the number of GPs initiating buprenorphine has been observed over the last decade. METHODS: The objective of this study was to explore the obstacles and facilitators to the involvement of GPs in the prescription of buprenorphine. A qualitative study comprising 14 individual interviews and a focus group bringing together 5 GPs was conducted among GPs based in France between June 2021 and March 2022. We performed data analysis using a grounded theory methodology. RESULTS: The interviews showed a great diversity in the level of involvement of GPs, depending on their experience, their representations of patients with OUD, their mode of exercise, and their personal preferences. The negative representations of the patients associated with the feeling of physical and ethical endangerment, the feeling of powerlessness, the fear of a disruption of the practice and the feeling of incompetence appeared at the forefront of the difficulties stated. Conversely, the strengthening of initial training and the facilitation of access to self-training tools and multidisciplinarity, the consideration of opioid use disorder (OUD) as a chronic illness with the application of a patient-centered motivational approach, as well as the defining and respecting one's own limits when prescribing buprenorphine seem to be the keys to a balanced and fulfilling practice. CONCLUSION: Raising awareness of the frequency of OUD appeared to be an additional lever to enhance the interest of the GPs concerned. Additional studies focusing on the evolution of professional practices would be necessary to extend these findings.

Buprenorphine deregulation as an opioid crisis policy response - A comparative analysis between France and the United States.

BACKGROUND: In passing the Maintstreaming Addiction Treatment Act, the United States has abolished its federal X waiver, considered a major barrier to the wider buprenorphine prescribing needed to respond to opioid-related harms. Advocates for this policy have drawn on the French response of deregulating buprenorphine prescribing to address increasing overdose mortality around the turn of the millennium. So far, such policy advocacy has incompletely accounted for contextual and health system differences between the two countries. METHODS: Using the health system dynamics framework, this analysis compares France from 1995 to 2003 (the relevant period of buprenorphine reform) to the US from 2018 until today (the comparison period to explore potential impacts of reform). We used it to guide examination of a) contextual issues relating to opioid use epidemiology and b) health system factors including prescriber supply, sector organization, and insurance coverage for primary care to draw relevant policy learning for the contemporary US. RESULTS: We identified that the US had a 22.5-fold higher mortality rate and a 2.3-fold higher opioid use disorder (OUD) rate compared to France, despite having rates of prescribed buprenorphine per-capita higher than, and per-person with OUD comparable to, than that of France. These wide gulfs between the scales and nature of the problems between France and the US suggest that relaxing restrictions on buprenorphine prescribing through abolishing the X waiver will be insufficient for achieving hoped-for reductions in overdose mortality. CONCLUSION: Health system strengthening with a focus on improvements in primary care prescriber supply, coverage, and coordination are likely higher yield policy complements to relaxing buprenorphine regulation. Such an approach would better prepare the US to adapt to ongoing dynamics and uncertainties in the opioid crisis and to optimize the already relatively high levels of buprenorphine prescribing.

Identification of factors associated with non-adherence to recommended COVID-19 preventive behaviours: a cross-sectional study based on a survey among 1004 French primary care professionals.

OBJECTIVES: Since the beginning of the COVID-19 pandemic, adherence to preventive behaviours to limit virus spread has been a major issue. The study objective was to identify factors associated with non-adherence to preventive behaviours among general practitioners (GPs) during the COVID-19 pandemic using data from a questionnaire completed during the French National Congress of General Medicine in June 2021. DESIGN: This descriptive study relied on data collected with a questionnaire during the national congress on general medicine in Bordeaux, France, from 16-18 June 2021. SETTING: The study was conducted in primary care in France. PARTICIPANTS: Out of a total of 1004 GPs and GP trainees, 755 completed the questionnaire during conferences and 249 were contacted by mail. RESULTS: The questionnaire included questions on sociodemographic characteristics and COVID-19 related preventive behaviours, beliefs and experiences. Answers to questions that explored the Health Belief Model components were selected and then compared among participants who reported appropriate preventive behaviours (wearing face masks and social distancing) and participants who reported non-adherence. Analysis was based on multivariate logistic regression.The responders' mean age was 35.8 years; 61.64% were women, 61.9% were practising GPs and 37.2% were GP trainees. Moreover, 96.6% of participants had completed the COVID-19 vaccination schedule. Non-adherence (reported by 72/1004 participants) was more frequent among smokers (OR=2.57, 95% CI 1.29 to 4.83, p=0.005) and younger participants (OR=0.95, 95% CI 0.92 to 0.98, p=0.005). Complete COVID-19 vaccination or a previous infection was not associated with non-adherence and has been poorly described. CONCLUSION: More studies are needed to confirm the factors involved in the adoption of COVID-19 preventive behaviours by healthcare professionals and to explore the beliefs and barriers to the adoption of these behaviours.

A face-to-face national congress experience during the COVID-19 pandemic: A report focussing on the risk of COVID-19 contamination.

BACKGROUND: The Congress of the National College of Academic General Practitioners took place in France in June 2021. In total, 1300 participants were registered, provoking concerns about the risk of COVID-19 contamination. OBJECTIVES: The study objective was to report participation in the first French face-to-face medical congress after restrictions due to COVID-19 and whether it resulted in COVID-19 contamination. METHODS: We performed two web-based surveys of respectively 46 and 33 questions. The first questionnaire was sent to all congress participants during the congress (and to a panel of non-participants) and investigated demographic characteristics, medical conditions, behaviours related to COVID-19 contamination risk, and the interest of face-to-face congress as compared to virtual congress. Two weeks after the congress, a questionnaire was addressed to the same population and to university General Practice departments to identify incident COVID-19 cases among participants. RESULTS: A total of 1001 general practitioners and residents completed the first questionnaire; 752 participated in the congress. The respondents were mainly women (61.3%), with a mean age of 35 (SD 10) years, 96.2% had been vaccinated against SARS-CoV-2, and 11.4% considered themselves at risk for a severe form of COVID-19 for medical reasons. Concerning the interest in attending the congress face-to-face, mean score was 9 over 10 (SD 1.5). No case of COVID-19 was reported among participants according to the second questionnaire (449 respondents). CONCLUSION: During a world pandemic, even participants considering themselves at risk came to a medical congress, highlighting the networking and social aspects of a face-to-face congress.

[Misuse of paracetamol in primary care: Cross-sectional study in a French rural context]. / Mésusage du paracétamol en soins primaires : étude transversale dans un contexte rural français.

OBJECTIVE: To estimate the prevalence of the paracetamol use for a reason other than pain (qualitative misuse) during the last 12 months in patients consulting their general practitioner, as well as the reasons for this misuse. METHODS: Descriptive cross-sectional analysis, with gender weighting to estimate the prevalence of paracetamol misuse. RESULTS: In total, data from 209 patients were included in the analysis. Among them, 11 patients declared having taken paracetamol for a reason other than pain, i.e., a gender-weighted prevalence of 5.7% (95% CI: 3.0 to 10.4). Nearly two-thirds of these patients said they had done it to feel better. CONCLUSIONS: The paracetamol misuse is rare but real in general practice. Further studies are needed to better understand it, especially qualitative studies.

Real-Life Testing of the Prescription Opioid Misuse Index in French Primary Care.

Analgesic opioid (AO) misuse by patients ranges from 0% to 50%. General practitioners are the first prescribers of AO. Our objective was to validate the Prescription Opioid Misuse Index (POMI) in primary care. We conducted a psychometric study in patients with chronic pain who had been taking AOs for at least 3 months and were followed in general practice. Patients responded to the POMI at inclusion and after 2 weeks. The reference used was the DSM-V. Sixty-nine GPs included 160 patients (87 women, 54.4%), mean age 56.4 ± 15.2 years. The total POMI score was 1.50 ± 1.27, and 73/160 (45.6.0%) had a score ≥ 2 (misuse threshold). Internal validity was measured with the Kuder-Richardson coefficient, which was 0.44. Correlations between each item and the total score ranged from 0.06 to 0.35. Test-retest reliability was determined from 145 patients: Lin's concordance coefficient was 0.57 [0.46, 0.68]. Correlation with the DSM-V (Spearman's coefficient) was 0.52. The POMI does not have sufficient psychometric properties to be recommended as a tool to identify the misuse of AOs in primary care. This study clearly showed that there is a need to create a monitoring tool specific to primary care.

Prescribing buprenorphine for opioid use disorder in primary care: A survey of French general practitioners in the Sentinelles network.

INTRODUCTION: Although opioid substitution coverage in France is high and patient care with buprenorphine is mainly managed by general practitioners (GPs), buprenorphine sales have been decreasing since 2011, suggesting that French GPs are prescribing less buprenorphine. Yet this possible change in GP practices has not yet been investigated. This study aimed to examine primary care GPs' opinions about buprenorphine and habits related to prescribing buprenorphine. METHODS: The study team conducted a cross-sectional survey from March 2021 to July 2021 among a sample of GPs in the Sentinelles network, a French epidemiologic surveillance system based on primary care practitioners. The study collected information about substance use disorder (SUD) training, opinions on buprenorphine, and habits related to buprenorphine prescription were collected (initiation and renewal within the past two years). FINDINGS: Among the 237 participants (34 % response rate), 15.2 % reported having had specific training for SUD management. A majority reported a very positive (16 %) or positive (63.7 %) opinion of buprenorphine. Most participants agreed (61.2 %) or strongly agreed (31.2 %) that buprenorphine was efficacious in the treatment of illicit opioid use disorder. Of the 206 GPs who reported having treated patients with opioid use disorder in the past two years, 47 (22.8 %) had initiated a buprenorphine prescription, whereas 177 (85.9 %) had renewed a buprenorphine prescription. Previous SUD training was associated with initiating buprenorphine (OR 4.66; 95 % CI [2.15-10.08]), while female gender was associated with not initiating buprenorphine prescribing (OR 0.46; 95 % CI [0.22-0.98]). CONCLUSION: A sample of French GPs who work in primary care has a positive view of buprenorphine, but the absence of SUD training among this population may be a barrier to their prescribing buprenorphine.

Barriers and Expectations of Adolescents Regarding the Identification and Management of Their Psychoactive Substance Use by Their General Practitioner.

AIMS: General practitioners (GPs), who are the most frequently consulted health professionals by adolescents, play a key role in screening for psychoactive substance (PAS) use. The purpose of our study was to determine the barriers and expectations of adolescents regarding the identification and management of their PAS use by their general practitioner. METHODS: Descriptive, cross-sectional study of a population of adolescents aged 12 to 17 years, followed up in general practice in France. Adolescents were recruited from general practice offices by open-access questionnaires. An opaque box was provided to ensure the anonymity of the adolescents. RESULTS: A total of 277 adolescents were included: 155 girls, mean age 14.5 ± 1.7 years, 113 adolescents (41%) had used a PAS at least once in the past 12 months. Alcohol was the most used PAS, followed by tobacco and cannabis. Three groups were identified: the nonusers group (n = 134); the group of moderate users (n = 71); the group of users at risk of substance abuse or misusing (n = 38). Regardless of group, adolescents felt that their GP was attentive, responsive, competent, understanding, and took the time to ask the appropriate questions in their role. The at-risk group was less confident and less comfortable, and they felt more judged and more afraid of the GP telling their parents. Despite this, the at-risk group was the most willing to talk to their GP about their PAS. Almost half of the adolescents surveyed found it useful to use a questionnaire to discuss PAS. CONCLUSIONS: Reminding each consultation of the principles of the relationship of trust and confidentiality while maintaining an empathetic attitude would make it easier for GPs to remove adolescents' inhibitions about communicating about their PAS use.

No association of low-dose aspirin with severe COVID-19 in France: A cohort of 31.1 million people without cardiovascular disease.

Background: Aspirin at low doses has been reported to be a potential drug candidate to treat or prevent severe coronavirus disease 2019 (COVID-19). Objectives: We aimed to explore whether low-dose aspirin used for primary cardiovascular prevention was associated with a lower risk of severe COVID-19. Method: A large cohort of patients without known cardiovascular comorbidities was constructed from the entire French population registered in national health care databases. In total, 31.1 million patients aged ≥40 years, including 1.5 million reimbursed for low-dose aspirin at least at three time points during the 6 months before the epidemic, were followed until hospitalization with a COVID-19 diagnosis or intubation/death for hospitalized patients. Results: Cox models adjusted for age and sex showed a positive association between low-dose aspirin and the risk of hospitalization (hazard ratio [HR], 1.33; 95% confidence interval (CI), 1.29-1.37]) or death/intubation (HR, 1.40 [95% CI, 1.33-1.47]). In fully adjusted models, associations were close to null (HR, 1.03 [95% CI, 1.00-1.06] and 1.04 [95% CI, 0.98-1.10], respectively). Conclusion: There was no evidence for an effect of low-dose aspirin for primary cardiovascular prevention in reducing severe COVID-19.

Inhaled ciclesonide for outpatient treatment of COVID-19 in adults at risk of adverse outcomes: a randomised controlled trial (COVERAGE).

OBJECTIVES: To assess the efficacy of inhaled ciclesonide in reducing the risk of adverse outcomes in COVID-19 outpatients at risk of developing severe illness. METHODS: COVERAGE is an open-label, randomized controlled trial. Outpatients with documented COVID-19, risk factors for aggravation, symptoms for ≤7 days, and absence of criteria for hospitalization are randomly allocated to either a control arm or one of several experimental arms, including inhaled ciclesonide. The primary efficacy endpoint is COVID-19 worsening (hospitalization, oxygen therapy at home, or death) by Day 14. Other endpoints are adverse events, maximal follow-up score on the WHO Ordinal Scale for Clinical Improvement, sustained alleviation of symptoms, cure, and RT-PCR and blood parameter evolution at Day 7. The trial's Safety Monitoring Board reviewed the first interim analysis of the ciclesonide arm and recommended halting it for futility. The results of this analysis are reported here. RESULTS: The analysis involved 217 participants (control 107, ciclesonide 110), including 111 women and 106 men. Their median age was 63 years (interquartile range 59-68), and 157 of 217 (72.4%) had at least one comorbidity. The median time since first symptom was 4 days (interquartile range 3-5). During the 28-day follow-up, 2 participants died (control 2/107 [1.9%], ciclesonide 0), 4 received oxygen therapy at home and were not hospitalized (control 2/107 [1.9%], ciclesonide 2/110 [1.8%]), and 24 were hospitalized (control 10/107 [9.3%], ciclesonide 14/110 [12.7%]). In intent-to-treat analysis of observed data, 26 participants reached the composite primary endpoint by Day 14, including 12 of 106 (11.3%, 95% CI: 6.0%-18.9%) in the control arm and 14 of 106 (13.2%; 95% CI: 7.4-21.2%) in the ciclesonide arm. Secondary outcomes were similar for both arms. DISCUSSION: Our findings are consistent with the European Medicines Agency's COVID-19 task force statement that there is currently insufficient evidence that inhaled corticosteroids are beneficial for patients with COVID-19.

Perceived risk of opioid use disorder secondary to opioid analgesic medication use by the general population in France.

BACKGROUND: In Europe and France, the use of opioid analgesic drugs has become widespread as an option for pain management. However, their use can lead to nonmedical use and/or opioid use disorder (OUD). This work aimed to assess the perceived risk of OUD secondary to opioid analgesic drugs use by the general population. METHODS: We conducted a cross-sectional observational study using the GrippeNet web-based cohort, comprising about 10,000 French volunteers from the general population, using a self-administered questionnaire. The main outcome was the perceived risk of OUD secondary to opioid analgesic drugs use, assessed by a 4-item scale and modelled using logistic regression (backward procedure). RESULTS: Among 5046 French respondents, after adjustment, 65% believed that the use of analgesic drugs could likely or very likely lead to OUD. Factors associated with the perception of a higher risk were being over 50 and having heard about opioids in the media. Previous opioid use and a high level of education decreased the perception of the risk. Among those having used opioids in the past 2 years (N = 1770), 71.1% reported being not at all concerned by this risk. The majority of the sample perceived the risk of OUD but those having already used opioid analgesics drugs expressed no concern about this risk for themselves. CONCLUSIONS: This finding highlight the need to reinforce warning on the package insert documents, therapeutic education and collaborative care between the prescribing general practitioners and pharmacists to increase awareness of opioid medications users on the risk of OUD. SIGNIFICANCE: This study found that the risk of OUD secondary to opioid analgesics use is well perceived in the general population, but that those having already used opioid analgesics expressed little concern for themselves. This finding could potentially help to raise awareness of healthcare providers and policy makers on the lack of perceived risk regarding these drugs and the need to inform and identify at-risk patients in primary care.

Association of Opioid Agonist Treatment With All-Cause Mortality and Specific Causes of Death Among People With Opioid Dependence: A Systematic Review and Meta-analysis.

Importance: Mortality among people with opioid dependence is higher than that of the general population. Opioid agonist treatment (OAT) is an effective treatment for opioid dependence; however, there has not yet been a systematic review on the relationship between OAT and specific causes of mortality. Objective: To estimate the association of time receiving OAT with mortality. Data Sources: The Embase, MEDLINE, and PsycINFO databases were searched through February 18, 2020, including clinical trial registries and previous Cochrane reviews. Study Selection: All observational studies that collected data on all-cause or cause-specific mortality among people with opioid dependence while receiving and not receiving OAT were included. Randomized clinical trials (RCTs) were also included. Data Extraction and Synthesis: This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Data on study, participant, and treatment characteristics were extracted; person-years, all-cause mortality, and cause-specific mortality were calculated. Crude mortality rates and rate ratios (RRs) were pooled using random-effects meta-analyses. Main Outcomes and Measures: Overall all-cause and cause-specific mortality both by setting and by participant characteristics. Methadone and buprenorphine OAT were evaluated specifically. Results: Fifteen RCTs including 3852 participants and 36 primary cohort studies including 749 634 participants were analyzed. Among the cohort studies, the rate of all-cause mortality during OAT was more than half of the rate seen during time out of OAT (RR, 0.47; 95% CI, 0.42-0.53). This association was consistent regardless of patient sex, age, geographic location, HIV status, and hepatitis C virus status and whether drugs were taken through injection. Associations were not different for methadone (RR, 0.47; 95% CI, 0.41-0.54) vs buprenorphine (RR, 0.34; 95% CI, 0.26-0.45). There was lower risk of suicide (RR, 0.48; 95% CI, 0.37-0.61), cancer (RR, 0.72; 95% CI, 0.52-0.98), drug-related (RR, 0.41; 95% CI, 0.33-0.52), alcohol-related (RR, 0.59; 95% CI, 0.49-0.72), and cardiovascular-related (RR, 0.69; 95% CI, 0.60-0.79) mortality during OAT. In the first 4 weeks of methadone treatment, rates of all-cause mortality and drug-related poisoning were almost double the rates during the remainder of OAT (RR, 2.01; 95% CI, 1.55-5.09) but not for buprenorphine (RR, 0.58; 95% CI, 0.18-1.85). All-cause mortality was 6 times higher in the 4 weeks after OAT cessation (RR, 6.01; 95% CI, 4.32-8.36), remaining double the rate for the remainder of time not receiving OAT (RR, 1.81; 95% CI, 1.50-2.18). Opioid agonist treatment was associated with a lower risk of mortality during incarceration (RR, 0.06; 95% CI, 0.01-0.46) and after release from incarceration (RR, 0.09; 95% CI, 0.02-0.56). Conclusions and Relevance: This systematic review and meta-analysis found that OAT was associated with lower rates of mortality. However, access to OAT remains limited, and coverage of OAT remains low. Work to improve access globally may have important population-level benefits.

Perceptions, professional responsibility and management experiences of patients with alcohol, tobacco and opioid use disorder by residents in general practice and teaching general practitioners.

BACKGROUND: Substance use disorders (SUDs) are based on pathophysiological mechanisms common to all psychoactive substances. However, general practitioners (GPs) hold different views depending on the substance in question. OBJECTIVES: To determine whether the perceptions that teaching GPs and final-year residents in general practice have of patients with a SUD vary according to the substance involved and explore their professional responsibility and management experiences. METHODS: A cross-sectional observational study was carried out by asking residents and teaching GPs from eight faculties of medicine about their perceptions, professional responsibility and management experience of patients with tobacco, alcohol and opioid use disorders, using an online questionnaire between June and September 2017. RESULTS: The responses of 238 teaching GPs (mean age 50 years SD 3.5; 58% men) and 327 residents (mean age 28 years SD 9.9; 67% women) were analysed (response rates: 9 and 15% respectively). Tobacco smokers were considered to be more responsible for their acts than the other users. Teaching GPs and residents considered that it was their responsibility to discuss substance use. They did not feel able to manage alcohol and opioid use disorders. Tobacco cessation was mainly managed alone (78%). The results were quite similar among teaching GPs and residents. CONCLUSION: The majority of practitioners had no difficulty managing smoking cessation. During the management of alcohol and particularly opioid use disorders, practitioners did not feel competent. The gap between their perceived responsibility and competencies should be addressed by training and promoting collaborative care.

Reactivated world war two traumatic memories in COVID-19 lockdown period.

Some events that we can forget about can still have an impact on elderly people's health. Asking about patients' feelings and past experiences during such conditions may help them express their feelings, and they may ask for psychological help.

Home Treatment of Older People with Symptomatic SARS-CoV-2 Infection (COVID-19): A structured Summary of a Study Protocol for a Multi-Arm Multi-Stage (MAMS) Randomized Trial to Evaluate the Efficacy and Tolerability of Several Experimental Treatments to Reduce the Risk of Hospitalisation or Death in outpatients aged 65 years or older (COVERAGE trial).

OBJECTIVES: To assess the efficacy of several repurposed drugs to prevent hospitalisation or death in patients aged 65 or more with recent symptomatic SARS-CoV-2 infection (COVID-19) and no criteria for hospitalisation. TRIAL DESIGN: Phase III, multi-arm (5) and multi-stage (MAMS), randomized, open-label controlled superiority trial. Participants will be randomly allocated 1:1:1:1:1 to the following strategies: Arm 1: Control arm Arms 2 to 5: Experimental treatment arms Planned interim analyses will be conducted at regular intervals. Their results will be reviewed by an Independent Data and Safety Monitoring Board. Experimental arms may be terminated for futility, efficacy or toxicity before the end of the trial. New experimental arms may be added if new evidence suggests that other treatments should be tested. A feasibility and acceptability substudy as well as an immunological substudy will be conducted alongside the trial. PARTICIPANTS: Inclusion criteria are: 65-year-old or more; Positive test for SARS-CoV-2 on a nasopharyngeal swab; Symptoms onset within 3 days before diagnosis; No hospitalisation criteria; Signed informed consent; Health insurance. Exclusion criteria are: Inability to make an informed decision to participate (e.g.: dementia, guardianship); Rockwood Clinical Frailty Scale ≥7; Long QT syndrome; QTc interval > 500 ms; Heart rate <50/min; Kalaemia >5.5 mmol/L or <3.5 mmol/L; Ongoing treatment with piperaquine, halofantrine, dasatinib, nilotinib, hydroxyzine, domperidone, citalopram, escitalopram, potent inhibitors or inducers of cytochrome P450 CYP3A4 isoenzyme, repaglinide, azathioprine, 6-mercaptopurine, theophylline, pyrazinamide, warfarin; Known hypersensitivity to any of the trial drugs or to chloroquine and other 4-aminoquinolines, amodiaquine, mefloquine, glafenine, floctafenine, antrafenine, ARB; Hepatic porphyria; Liver failure (Child-Pugh stage ≥B); Stage 4 or 5 chronic kidney disease (GFR <30 mL/min/1.73 m²); Dialysis; Hypersentivity to lactose; Lactase deficiency; Abnormalities in galactose metabolism; Malabsorption syndrome; Glucose-6-phosphate dehydrogenase deficiency; Symptomatic hyperuricemia; Ileus; Colitis; Enterocolitis; Chronic hepatitis B virus disease. The trial is being conducted in France in the Bordeaux, Corse, Dijon, Nancy, Paris and Toulouse areas as well as in the Grand Duchy of Luxembourg. Participants are recruited either at home, nursing homes, general practices, primary care centres or hospital outpatient consultations. INTERVENTION AND COMPARATOR: The four experimental treatments planned in protocol version 1.2 (April 8th, 2020) are: (1) Hydroxychloroquine 200 mg, 2 tablets BID on day 0, 2 tablets QD from day 1 to 9; (2) Imatinib 400 mg, 1 tablet QD from day 0 to 9; (3) Favipiravir 200 mg, 12 tablets BID on day 0, 6 tablets BID from day 1 to 9; (4) Telmisartan 20 mg, 1 tablet QD from day 0 to 9. The comparator is a complex of vitamins and trace elements (AZINC Forme et Vitalité®), 1 capsule BID for 10 days, for which there is no reason to believe that they are active on the virus. In protocol version 1.2 (April 8th, 2020): People in the control arm will receive a combination of vitamins and trace elements; people in the experimental arms will receive hydroxychloroquine, or favipiravir, or imatinib, or telmisartan. MAIN OUTCOME: The primary outcome is the proportion of participants with an incidence of hospitalisation and/or death between inclusion and day 14 in each arm. RANDOMISATION: Participants are randomized in a 1:1:1:1:1 ratio to each arm using a web-based randomisation tool. Participants not treated with an ARB or ACEI prior to enrolment are randomized to receive the comparator or one of the four experimental drugs. Participants already treated with an ARB or ACEI are randomized to receive the comparator or one of the experimental drugs except telmisartan (i.e.: hydroxychloroquine, imatinib, or favipiravir). Randomisation is stratified on ACEI or ARBs treatment at inclusion and on the type of residence (personal home vs. nursing home). BLINDING (MASKING): This is an open-label trial. Participants, caregivers, investigators and statisticians are not blinded to group assignment. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): A total of 1057 participants will be enrolled if all arms are maintained until the final analysis and no additional arm is added. Three successive futility interim analyses are planned, when the number of participants reaches 30, 60 and 102 in the control arm. Two efficacy analyses (interim n°3 and final) will be performed successively. TRIAL STATUS: This describes the Version 1.2 (April 8th, 2020) of the COVERAGE protocol that was approved by the French regulatory authority and ethics committee. The trial was opened for enrolment on April 15th, 2020 in the Nouvelle Aquitaine region (South-West France). Given the current decline of the COVID-19 pandemic in France and its unforeseeable dynamic in the coming months, new trial sites in 5 other French regions and in Luxembourg are currently being opened. A revised version of the protocol was submitted to the regulatory authority and ethics committee on June 15th, 2020. It contains the following amendments: (i) Inclusion criteria: age ≥65 replaced by age ≥60; time since first symptoms <3 days replaced by time since first symptoms <5 days; (ii) Withdrawal of the hydroxychloroquine arm (due to external data); (iii) increase in the number of trial sites. TRIAL REGISTRATION: The trial was registered on Clinical Trials.gov on April 22nd, 2020 (Identifier: NCT04356495): and on EudraCT on April 10th, 2020 (Identifier: 2020-001435-27). FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).

Evolution of Reactions to Uncertainty Among Residents During a Clinical Rotation.

BACKGROUND AND OBJECTIVES: For residents, uncertainty can be a source of motivation, interest, and stimulation, but it can also cause fear and anxiety that can lead to burn-out. Considering the prevalence of uncertainty in family medicine and the potential reactions from residents, reactions to uncertainty constitute an important research topic. This study sought to measure the evolution of reactions to uncertainty of family medicine residents in their first and second year, during a 6-month clinical rotation in a family physician's office. METHODS: This study utilized a prospective epidemiological cohort design of first- and second-year family medicine residents during a 6-month clinical rotation in a family physician's office during the 2018-2019 academic year. Data were collected at the beginning and end of the clinical rotation for the entire student population using the Physicians' Reactions to Uncertainty (PRU) questionnaire. RESULTS: One hundred-two respondents were matched at the end of the clinical rotation and were included in the analysis. At baseline, there were no significant differences between first- and second-year residents in each dimension of the PRU. Anxiety due to uncertainty decreased significantly in residents of both years. Concern about bad outcomes decreased, but not significantly, in both years. Reluctance to disclose uncertainty to patients decreased in first-year residents. CONCLUSIONS: During a 6-month clinical rotation, anxiety due to uncertainty decreased in first- and second-year residents. The frequency and the type of uncertain situations residents encountered could be investigated in future studies to better understand residents' reactions to uncertainty.

Discussing alcohol use with the GP: a qualitative study.

BACKGROUND: Despite most GPs recognising their role in the early diagnosis of alcohol use disorder (AUD), only 23% of GPs routinely screen for alcohol use. One reason GPs report for not screening is their relationship with patients; questions regarding alcohol use are considered a disturbance of a relationship built on mutual trust. AIM: To analyse the feelings and experiences of patients with AUD concerning early screening for alcohol use by GPs. DESIGN & SETTING: A qualitative study of patients (n = 12) with AUD in remission or treatment, recruited from various medical settings. METHOD: Semi-structured interviews were conducted, audiorecorded, and transcribed verbatim. The authors conducted an inductive analysis based on grounded theory. The analysis was performed until theoretical data saturation was reached. RESULTS: The participants experienced AUD as a chronic, destructive, and shameful disease. The participants expected their GPs to play a primary role in addressing AUD by kind listening, and providing information and support. If the GPs expressed a non-judgmental attitude, the participants could confide in them; this moment was identified as a key milestone in their trajectory, allowing relief and a move toward treatment. The participants thought that any consultation could be an opportunity to discuss alcohol use and noted that such discussions required a psychological and benevolent approach. CONCLUSION: The participants felt fear or denial from the GPs, even though they felt that discussing alcohol use is part of the GP's job. The participants requested that GPs adopt non-judgmental attitudes and kindness when approaching the subject of alcohol use.