Objectives Target trial emulation is an approach that is increasingly used to improve transparency in observational studies and help mitigate biases. For studies declaring that they emulated a target trial, we aimed to evaluate the specification of the target trial, examine its consistency with the observational emulation and assess the risk of bias in the observational analysis.Design Methodological systematic review reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement.Data sources The database MEDLINE (Medical Literature Analysis and Retrieval System Online) was interrogated for all studies published from 1 January 2021 to 3 July 2022. We performed an additional manual search of 20 general medical and specialised journals that spanned the same period.Eligibility criteria All studies that declared emulating a hypothetical or real randomised trial were eligible.Data extraction and synthesis Two independent reviewers performed the whole systematic review process (screening and selection of studies, data extraction and risk of bias assessment). The main outcomes were the definition of the key protocol components of the target trial and its emulation, consistency between the target trial and its emulation and risk of bias according to the ROBINS-I (Risk Of Bias In Non-randomised Studies - of Interventions) tool.Results Among the selected sample of 100 studies, 24 (24%) did not specify the target trial. Only 40 studies (40%) provided detailed information on all components of the target trial protocol. Eligibility criteria, intervention strategies and outcomes were consistent between the target trial and its emulation in 35 studies (46% of those specifying the target trial). Overall, 28 studies (28%) exhibited serious risk of bias and 41 (41%) had misalignments in the timing of eligibility assessment, treatment assignment and the start of follow-up (time-zero). As compared with studies that did not specify the target trial, those that did specify the trial less frequently seemed to have both time-zero issues (39% vs 52%) and serious risk of bias (26% vs 33%).Conclusions One-quarter of studies declaring that they emulated a target trial did not specify the trial. Target trials and their emulations were particularly inconsistent for studies emulating a real randomised trial. Risk of methodological issues seemed lower in observational analyses that specified versus did not specify the target trial.

BACKGROUND AND AIMSA recent single-center study reported a significant increase in acute myeloid leukaemia (AML) cases, including mixed-phenotype acute leukaemia (MPAL), after exposure to direct acting agents (DAA). We investigated whether DAA use increased the risk of AML in patients with chronic hepatitis C virus (HCV) infection.METHODSWe conducted a disproportionality analysis of the WHO Pharmacovigilance database Vigibase up to 2020. Queries focused on all DAAs, subclasses, combinations or each DAA separately as well as interferon and ribavirin as negative controls. The primary outcome was AML. Secondary outcomes were AML without MPAL, MPAL, acute lymphoid leukemia (ALL) and acute leukemia (AL, high-level term encompassing AML, ALL, MPAL and unspecified acute leukemia [UAL]). The information component (IC0.25) and proportional reporting ratio (PRR0.25) were computed to assess a potential pharmacovigilance signal.RESULTSWe identified 49 notifications reporting any AL occurrence after anti-HCV treatments from June 1997 to December 2020: 23 (47%) involved a DAA, 24 (49%) interferon and 12 (24%) ribavirin. The DAAs sofosbuvir and ledipasvir were suspected in 74% (n=17) and 39% (n=9) of cases. The events reported were AML (n=22), ALL (n=11), AML and ALL (n=1) and UAL (n=15) and no MPAL. DAA, interferon or ribavirin were not significantly associated with AML, ALL or AL.CONCLUSIONThis study did not find any association between DAA exposure and the occurrence of AML. Nevertheless, vigilance should remain, particularly for MPAL, which may not have been well captured in our study because of its rareness and high risk of misclassification.

Background: After several cases of peculiar hematological malignancies following introduction of new oral anti-hepatitis C virus (HCV) treatments in our recent practice, we aimed to systematically identify all cases of hematological malignancies (HM) in patients with chronic HCV infection and to compare them according to the prescription of oral anti-HCV Direct Acting Antivirals (DAA) treatment or not. Material/methods: In this single-center retrospective observational study, we included all patients with confirmed HM and chronic HCV infection managed between 2010 and 2019 in the Pitie-Salpetriere hospital, Paris. Non-inclusion criteria were a benign hematological disorder, an & nbsp;HM preceding chronic HCV infection and HCV acute infection. We compared characteristics of patients who received DAA before HM diagnosis to those with no DAA before HM. Results: Over the 10 years, 61 cases of HM among HCV infected patients were identified (female 29%, median age of 58.0 years [IQR 17]). Twenty-one received DAA before the onset of HM (Group DAA+) and 40 did not (Group DAA-) including 22 having received DAA after HM. In the DAA+ group, oral NS5B, NS5A and NS3A inhibitors were used in 90, 76 and 29% respectively. HM developed in the two years following DAA initiation in 76%. Eight (38%) had Non-Hodgkin Lymphoma, 5 (24%) had an Acute Myeloid Leukaemia (AML) including two with a mixed phenotype, 2 each had Hodg-kin Lymphoma, Multiple Myeloma or a myeloproliferative disorder and one each had a chronic Lymphocytic Leukaemia or AL Amyloidosis. In the Group DAA-, HM were NHL in 20(50%) patients, Myeloproliferative neoplasms in 7 (17%), Multiple Myeloma in 5, Hodgkin Lymphoma in 3, Myelo-dysplastic syndrome and AML in 2 (5%) each and Acute Lymphoblastic Leukaemia in one. No sig-nificant difference between the groups DAA + and -was found according to age, sex, HCV genotype, viral load, co-infection or type and exposition of previous HCV treatments. AML, liver transplantation and cirrhosis were significantly more frequent in the DAA+ group (p = 0.020, 0.045 and 0.032, respectively). Conclusion: AML seemed more frequent after using DAA treatments, notably in severe HCV patients including cirrhotic and/or liver transplanted patients. A multicentric observational study is ongoing to confirm and explore the results. (c) 2022 Elsevier Masson SAS. All rights reserved.

La place de la témocilline dans le traitement des infections à entérobactéries productrices de béta-lactamase à spectre étendu (EBLSE) reste à définir. Nous décrivons l'utilisation de la témocilline, son efficacité clinique et sa tolérance dans différentes situations. Nous avons inclus rétrospectivement tous les patients ayant reçu ≥ 24 h de témocilline pour une infection à EBLSE dans deux hôpitaux universitaires du 1er janvier au 15 décembre 2016. L'échec clinique était défini par la persistance des symptômes plus de 72 h après l'initiation de la témocilline, la récidive des symptômes (fièvre, signes fonctionnels en rapport avec l'organe atteint), un élargissement du spectre de l'antibiothérapie du fait d'une dégradation clinique, un décès, lorsque la témocilline était utilisée en curatif ; la persistance du germe à l'ECBU de contrôle d'une bactériurie asymptomatique en pré-opératoire. Nous avons défini comme guérison, l'absence de récidive documentée pendant toute la durée du suivi post-thérapeutique. Vingt-neuf patients ont été inclus, âge moyen 58 ans, prédominance masculine (18/11). Vingt patients avaient reçu la témocilline en relais d'une antibiothérapie probabiliste pendant 3,2 jours en moyenne (carbapénèmes n = 14, céphalosporines de 3e génération n = 4, uréidopénicillines n = 1, fluoroquinolones n = 1) pour respectivement 7 infections urinaires masculines (IUM), 7 pyélonéphrites aiguës (PNA), 2 pneumopathies, 2 infections multi-sites, une bactériémie sur thrombose septique, 1 bactériémie sur cathéter. Neuf patients ont reçu la Témocilline en première ligne après obtention de la CMI pour 4 IUM, 3 bactériuries asymptomatiques, 1 PNA, 1 septicémie sur translocation digestive. Les espèces isolées étaient les suivantes : E. coli (n = 9), K. pneumoniae (n = 7), E. cloacae (n = 6), E. aerogenes (n = 1). Pour 6 patients, l'infection était polymicrobienne. Dans tous les cas, la CMI était ≤ 8 mg/L sauf pour une souche de K. pneumoniae (CMI = 12 mg/L) conduisant à un échec. La guérison était obtenue chez 11/20 patients dans le groupe « relais » et 8/9 patients dans le groupe « première ligne ». Les succès étaient les suivants : infections urinaires (14/19), pneumopathies (1/2), infections multi-sites (1/3), bactériuries pré-opératoires (2/3), infections associées à une bactériémie (5/9). Douze sur 17 patients avec un score SOFA ≤ 2 ont évolué favorablement (70 %). La durée médiane d'antibiothérapie était de 14 jours (Min-Max : 3–28). Le suivi médian post-antibiotique était de 39 jours (Min-Max : 0–180). Aucun effet indésirable n'a été rapporté. On note une efficacité probable de la témocilline en relais ou en première ligne chez les malades non graves (SOFA ≤ 2) si la CMI du germe en cause est ≤ 8 mg/L. Nous observons plus d'échecs chez les patients en réanimation ainsi que ceux ayant une infection à E. aerogenes ou polymicrobienne.

Background. - Diphtheria is re-emerging in Europe. A total of 36 cases were reported in Europe in 2015 versus 53 cases between 2000 and 2009. Patients. - We report two cases of Corynebacterium diphtheriae infection in a French hospital in 2016: a cutaneous infection with negative toxin testing in a French traveller, and a respiratory diphtheria carriage with positive toxin testing in an Afghan refugee diagnosed with pulmonary tuberculosis. The vaccination history of the Afghan patient could not be retrieved. (C) 2018 Elsevier Masson SAS. All rights reserved.