Thrombolytic therapy of pulmonary embolism A meta-analysis

AbstractObjectivesWe sought to assess the efficacy and safety of thrombolytic therapy in patients with an acute pulmonary embolism (PE).BackgroundThrombolytic therapy is approved for the treatment of acute PE; however, the safety and efficacy of this therapy remain debated.MethodsA meta-analysis of randomized, controlled trials comparing thrombolytic agents with intravenous heparin in patients with acute PE was performed. Trials were identified through a combined search of the MEDLINE, EMBASE, and Current Contents databases. Three outcome measures were assessed: 1) mortality, 2) recurrence of PE, and 3) major hemorrhage.ResultsNine trials including 461 patients were identified. Compared with intravenous heparin, thrombolytic therapy had no significant effect on mortality (relative risk [RR] 0.63, 95% confidence interval [CI] 0.32 to 1.23) or the recurrence of PE (RR 0.59, 95% CI 0.30 to 1.18), but was associated with an increased risk of major hemorrhage (RR 1.76, 95% CI 1.04 to 2.98). These results were homogeneous and largely unaffected by the formulation of thrombolytic agent, the clinical severity of PE, the extent of vascular obstruction determined radiologically, or the methodologic quality of the included trials.ConclusionsCompared with intravenous heparin, thrombolytic therapy does not appear to have therapeutic benefit in unselected patients with acute PE, but it is associated with an increased risk of major hemorrhage. Given the small number of patients included in the randomized trials thus far, the negative results in terms of the efficacy outcomes should be interpreted with caution. Definitive evidence of the utility of thrombolytic therapy in this setting requires a large, randomized, controlled trial

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Efficacité du mélange equimolaire protoxyde d'azote-oxygène sur la tolérance de la fibroscopie oeso-gastro-duodénale : essai randomisé, en double aveugle, versus placebo

REIMS-BU Santé (514542104) / SudocSudocFranceF

Overlap syndrome and connective tissue diseases.

International audienc

Impact of liver disease severity and etiology on the occurrence of diabetes mellitus in patients with liver cirrhosis

International audienceThe association between liver cirrhosis (LC) and diabetes mellitus (DM) is well known. However, the impact of the severity or etiology of LC on the occurrence of DM is relatively unknown. We aimed to determine the prevalence and clinical correlates of DM in a large cohort of patients with cirrhosis. A total of 1,068 patients with LC were included in this cross sectional study (CIRCE study). The diagnosis of cirrhosis irrespective of its etiology was based on histological confirmation by liver biopsy or, in the absence of biopsy, on typical clinical, morphological and biological data. Data related to the cirrhosis etiology: alcohol, viral markers of hepatitis B, C, iron load parameters and autoimmune markers were collected for each patient. Venous blood samples were taken in the morning after 12-h overnight fasting. There were 383 patients with cirrhosis associated with hepatocellular carcinoma (HCC). DM was found in 412 (39.7 %) patients. Patients with DM were older and more likely to be overweight and male, with a family history of DM and a diagnosis of HCC. DM was not associated with a history of stroke or myocardial infarction. Cirrhosis secondary to hepatitis infection was less strongly associated with DM than with NASH or alcoholic cirrhosis. The severity of LC was not associated with DM. In multivariate analysis, the factors associated with DM were age, BMI, a family history of DM, and statin use. There was a significant interaction between HCC and cirrhosis etiology for the risk of DM. Cirrhosis secondary to hepatitis was associated with a lesser presence of DM only in patients with HCC (interaction p = 0.0015). LC was strongly associated with DM, with around 40 % of diabetic patients. In the group of patients with LC without HCC, diabetes was not associated with the etiology of cirrhosis

Sustained Remission After Treatment Withdrawal in Autoimmune Hepatitis: A Multicenter Retrospective Study

International audienceIn patients with autoimmune hepatitis (AIH), relapse rates between 25 and 100% after treatment withdrawal have been reported. The optimal strategy for immunosuppressive treatment withdrawal is controversial

COMBINATION OF AMOXICILLIN/CLAVULANATE AND PREDNISOLONE IN SEVERE ALCOHOLIC HEPATITIS: RESULTS OF THE ANTIBIOCOR RANDOMIZED CONTROLLED TRIAL.

International audienc

Effect of Prophylactic Antibiotics on Mortality in Severe Alcohol-Related Hepatitis

International audienceImportance The benefits of prophylactic antibiotics for hospitalized patients with severe alcohol-related hepatitis are unclear. Objective To determine the efficacy of amoxicillin-clavulanate, compared with placebo, on mortality in patients hospitalized with severe alcohol-related hepatitis and treated with prednisolone. Design, Setting, and Participants Multicenter, randomized, double-blind clinical trial among patients with biopsy-proven severe alcohol-related hepatitis (Maddrey function score ≥32 and Model for End-stage Liver Disease [MELD] score ≥21) from June 13, 2015, to May 24, 2019, in 25 centers in France and Belgium. All patients were followed up for 180 days. Final follow-up occurred on November 19, 2019. Intervention Patients were randomly assigned (1:1 allocation) to receive prednisolone combined with amoxicillin-clavulanate (n = 145) or prednisolone combined with placebo (n = 147). Main Outcome and Measures The primary outcome was all-cause mortality at 60 days. Secondary outcomes were all-cause mortality at 90 and 180 days; incidence of infection, incidence of hepatorenal syndrome, and proportion of participants with a MELD score less than 17 at 60 days; and proportion of patients with a Lille score less than 0.45 at 7 days. Results Among 292 randomized patients (mean age, 52.8 [SD, 9.2] years; 80 [27.4%] women) 284 (97%) were analyzed. There was no significant difference in 60-day mortality between participants randomized to amoxicillin-clavulanate and those randomized to placebo (17.3% in the amoxicillin-clavulanate group and 21.3% in the placebo group [ P = .33]; between-group difference, −4.7% [95% CI, −14.0% to 4.7%]; hazard ratio, 0.77 [95% CI, 0.45-1.31]). Infection rates at 60 days were significantly lower in the amoxicillin-clavulanate group (29.7% vs 41.5%; mean difference, −11.8% [95% CI, −23.0% to −0.7%]; subhazard ratio, 0.62; [95% CI, 0.41-0.91]; P = .02). There were no significant differences in any of the remaining 3 secondary outcomes. The most common serious adverse events were related to liver failure (25 in the amoxicillin-clavulanate group and 20 in the placebo group), infections (23 in the amoxicillin-clavulanate group and 46 in the placebo group), and gastrointestinal disorders (15 in the amoxicillin-clavulanate group and 21 in the placebo group). Conclusion and Relevance In patients hospitalized with severe alcohol-related hepatitis, amoxicillin-clavulanate combined with prednisolone did not improve 2-month survival compared with prednisolone alone. These results do not support prophylactic antibiotics to improve survival in patients hospitalized with severe alcohol-related hepatitis. Trial Registration ClinicalTrials.gov Identifier: NCT0228192