Background Coronaviruses can induce the production of interleukin (IL)-1β, IL-6, tumour necrosis factor, and other cytokines implicated in autoinflammatory disorders. It has been postulated that anakinra, a recombinant IL-1 receptor antagonist, might help to neutralise the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related hyperinflammatory state, which is considered to be one cause of acute respiratory distress among patients with COVID-19. We aimed to assess the off-label use of anakinra in patients who were admitted to hospital for severe forms of COVID-19 with symptoms indicative of worsening respiratory function.Methods The Ana-COVID study included a prospective cohort from Groupe Hospitalier Paris Saint-Joseph (Paris, France) and a historical control cohort retrospectively selected from the Groupe Hospitalier Paris Saint-Joseph COVID cohort, which began on March 18, 2020. Patients were included in the prospective cohort if they were aged 18 years or older and admitted to Groupe Hospitalier Paris Saint-Joseph with severe COVID-19-related bilateral pneumonia on chest x-ray or lung CT scan. The other inclusion criteria were either laboratory-confirmed SARS-CoV-2 or typical lung infiltrates on a lung CT scan, and either an oxygen saturation of 93% or less under oxygen 6 L/min or more, or aggravation (saturation ≤93% under oxygen 3 L/min) with a loss of 3% of oxygen saturation in ambient air over the previous 24 h. The historical control group of patients had the same inclusion criteria. Patients in the anakinra group were treated with subcutaneous anakinra (100 mg twice a day for 72 h, then 100 mg daily for 7 days) as well as the standard treatments at the institution at the time. Patients in the historical group received standard treatments and supportive care. The main outcome was a composite of either admission to the intensive care unit (ICU) for invasive mechanical ventilation or death.The main analysis was done on an intention-to-treat basis (including all patients in the anakinra group who received at least one injection of anakinra). FindingsFrom March 24 to April 6, 2020, 52 consecutive patients were included in the anakinra group and 44 historical patients were identified in the Groupe Hospitalier Paris Saint-Joseph COVID cohort study. Admission to the ICU for invasive mechanical ventilation or death occurred in 13 (25%) patients in the anakinra group and 32 (73%) patients in the historical group (hazard ratio [HR] 0•22 [95% CI 0•11-0•41; p<0•0001). The treatment effect of anakinra remained significant in the multivariate analysis (HR 0•22 [95% CI 0•10-0•49]; p=0•0002). An increase in liver aminotransferases occurred in seven (13%) patients in the anakinra group and four (9%) patients in the historical group.Interpretation Anakinra reduced both need for invasive mechanical ventilation in the ICU and mortality among patients with severe forms of COVID-19, without serious side-effects. Confirmation of efficacy will require con trolled trials.

Among candidate drugs to treat coronavirus disease 2019 , the combination of hydroxychloroquine (HCQ) and azithromycin (AZ) has received intense worldwide attention. Even as the efficacy of this combination is under evaluation, clinicians have begun to use it largely. As these medications are known to prolong the QT interval, we analyzed serial electrocardiograms recorded in patients hospitalized for COVID-19 pneumonia and treated with HCQ þ AZ. Fifty consecutive patients received the combination of HCQ (600 mg/d for 10 days) and AZ (500 mg/d on day 1 and 250 mg/d from day 2 to day 5). Twelve-lead electrocardiograms were recorded before treatment, at day 3, at day 5, and at discharge. The median age of patients was 68 years (interquartile range, 53-81 years); 28 (56%) were men. The main comorbidities were hypertension (36%; n¼18) and diabetes (16%; n¼8). The mean corrected QT (QTc) interval was 408 ms at baseline and increased up to 437 ms at day 3 and to 456 ms at day 5. Thirty-eight patients (76%) presented short-term modifications of the QTc duration (>30 ms). Treatment discontinuation was decided in 6 patients (12%), leading to QTc normalization in 5 of them. No deaths and no cardiac arrhythmic events were observed in this cohort. Our report confirms that a short duration treatment with HCQ þ AZ modifies the QTc interval. The treatment had to be discontinued for QTc modifications in 12% of patients. Nevertheless, in inpatients hospitalized for COVID-19, we did not observe any clinically relevant consequences of these transitory modifications. In conclusion, when patients are treated with HCQ þ AZ, cardiac monitoring should be regularly performed and hospital settings allow monitoring under in safe conditions.

During the SARS-CoV-2 pandemic, a variety of dermatological conditions were reported by physicians. Given the context, these lesions have been labeled as secondary to SARS-CoV-2 infection. We report the case of a recurrence of herpes zoster in a patient hospitalized with an SARS-CoV-2 infection. The rash occurred on the 15th day of hospitalization while the patient was recovering from a severe form. Local swab showed the presence of varicella-zoster virus within the vesicles. Dermatological symptoms secondary to COVID-19 have been frequently described. This is the first case that demonstrates the recurrence of herpes zoster during a SARS-CoV-2 infection.

Background: Ceftriaxone and cefotaxime share a similar antibacterial spectrum and similar indications but have different pharmacokinetic characteristics. Ceftriaxone is administered once daily and 40% of its clearance is by biliary elimination, whereas cefotaxime requires three administrations per day and shows less than 10% biliary elimination. The high biliary elimination of ceftriaxone suggests a greater impact of this antibiotic on the gut microbiota than cefotaxime. The objective of this study was to compare the impact of ceftriaxone and cefotaxime on the gut microbiota. Methods: A prospective clinical trial was performed that included 55 patients treated with intravenous ceftriaxone (1 g/24 h) or cefotaxime (1 g/8 h) for at least 3 days. Three fresh stool samples were collected from each patient (days 0, 3, and 7 or at the end of intravenous treatment) to assess the emergence of third-generation cephalosporin (3GC)-resistant Enterobacteriaceae, carbapenem-resistant Enterobacteriaceae, Pseudomonas aeruginosa, toxigenic Clostridioides difficile, and vancomycin-resistant enterococci. Results: The emergence of 3GC-resistant gram-negative enteric bacilli (Enterobacteriaceae) (5.9% vs 4.7%, p > 0.99), Enterococcus spp, and non-commensal microorganisms did not differ significantly between the groups. Both antibiotics reduced the counts of total gram-negative enteric bacilli and decreased the cultivable diversity of the microbiota, but the differences between the groups were not significant. Conclusion: No significant difference was observed between ceftriaxone and cefotaxime in terms of the emergence of resistance.

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Objective:Hypertension (HT) is the leading reason for visits to general practitioners (GPs). The diagnosis of HT and the decision to initiate drug treatment form an integral part of their natural field of practice. The recent national and international guidelines have made proposals that are specifically dedicated to this sequence of care. The objective of this study is to analyse the prescribing behaviours of GPs when initiating treatment for patients newly diagnosed with hypertension.Design and method:Data from the IQVIA Longitudinal Patient Database (LPD) France were used. LPD France is a permanent observatory to which a nationally representative panel of physicians – including GPs (n = 1200) – contribute anonymised electronic medical records (EMR). This analysis included all antihypertensive drug prescriptions made by the GPs from July 2020 to June 2021, which were then extrapolated to the entire population of mainland France. Initiation was defined by the establishment of an antihypertensive treatment for a patient already registered with the GP and who was receiving antihypertensive treatment for the first time in 24 months.Results:Over the 12-month period analysed, 869 283 patients had received an initial antihypertensive drug prescription following consultation with a GP. Monotherapy was prescribed in 71.5% of cases (versus 67.3% the previous year) and dual therapy in 21.5% of cases (versus 23.2% the previous year). Fixed-dose combinations accounted for 62% of the dual therapies.The therapeu tic classes of the prescribed monotherapies were distributed as follows:Conclusions:These findings reveal prescriptions that appeared to be consistent with the latest guidelines in which the first-line use of renin-angiotensin system blockers and calcium channel blockers is preferred. It is also interesting to note that treatment initiation with dual therapies was much less common, with a use rate of fixed-dose combinations slightly higher than that of the free-dose combinations.*IQVIA EMR LPD Médecins Généralistes / Cardiologues Libéraux’. EMR = Electronic Medical Records, LPD = Longitudinal Patient Data

Objective: Several well-designed randomized controlled trials (RCTs) have been conducted to evaluate the cardiovascular and renal effects of Glucagon-Like Peptide receptor agonists (GLP1) in type 2 diabetes. Their results have largely influenced the most recent dedicated therapeutic recommendations. Traditionally, p-values and confidence intervals have been used to denote the statistical significance of RCT results. However, even with a p-value and a confidence interval, the clinician cannot immediately discern how likely the study, if repeated, would yield a different and potentially conflicting result. The Fragility Index (FI) was developed as a novel metric to further assess the quality of statistically significant results and assist with the interpretation and clinical applicability of RCT findings, by providing the absolute number of patients or events from an RCT whose alternate outcome would have resulted in the study no longer being statistically significant. To date, there have been no studies evaluating the statistical fragility of GLP1 agonists RCTs. Design and method: We performed a systematic review of GLP1 cardiovascular outcomes trials using the PubMed database and calculate the FI for the specified primary endpoint, non-fatal myocardial infarction, non-fatal stroke, cardiovascular and all-cause death and renal outcomes as defined for each trial. The larger the FI the better (more robust) a trial's data are. A FI index reported as ‘0’ clearly emphasizes the lack of robustness of the data. Results: Results: We identified and included 7 trials, that involved 6 different molecules. The results are depicted in the following figure. Conclusions: Conclusion: In trials reported to date, the CV and renal benefits of GLP-1 agonists are not consistent across this class of medications. The Fragility Index may help clinicians to identify how easily a particular RCTs statistical significance may be overturned and to choose the molecule with the more robust expected benefit.