Effects of statins to reduce all-cause mortality in heart failure patients: findings from the epical2 cohort study

Introduction: The addition of statins to standard care in heart failure (HF) patients remains controversial in clinical practice. Large-scale clinical trials failed to show mortality benefits, but uncertainty persists in real-world settings.Objective: We evaluated whether the prescription of statins at hospital discharge is associated with a reduction in all-cause mortality at up to 1 year of follow-up in HF patients.Methods: We analyzed data from Epidémiologie et Pronostic de l’Insuffisance Cardiaque Aiguë en Lorraine (EPICAL2) cohort study of 2254 hospitalized acute HF patients who were admitted to 21 hospitals located in northeast France for acute HF between October 2011 and October 2012 and who received statins at discharge compared with patients who did not. We used propensity score matching and instrumental variable analyses to estimate the treatment effects of statins, and a multivariable Cox proportional- hazards model to examine survival with statin use, adjusting for patient demographics, HF characteristics, medical history, comorbidities, drug treatment and other known potential confounders. We plotted Kaplan–Meier survivor curves, and used log-rank test to determine the equality of survivor functions.Results: We included 2032 patients in this investigation: 919 (45%) in the statin-treated group and 1113 (55%) in the control group. The estimated average statin-treatment effects for all-cause mortality in HF failed to demonstrate a significant effect on mortality [Z = − 1.73, 95% confidence interval (CI) − 0.11 to 0.007, p value = 0.083, and Z = − 0.95, 95% CI − 1.34 to 0.46, p value = 0.34] for propensity score matching and instrumental variable analyses, respectively. Moreover, the Cox proportional-hazards model showed that statin prescription was not significantly associated with the rate of death (hazard ratio = 0.85, 95% CI 0.66–1.11, p value = 0.26), adjusted for all confounders.Conclusion: In patients with HF (and reduced or preserved ejection fraction), the prescription of statins did not appear to be associated with better survival after 1 year of follow-up in the EPICAL2 cohort. We cannot exclude that a subpopulation of HF patients may have some benefits compared with the whole HF population or that there might be a lack of power to show such effect

Modelling paralytic shellfish toxins (PST) accumulation in Crassostrea gigas by using Dynamic Energy Budgets (DEB)

As other filter-feeders, Crassostrea gigas can concentrate paralytic shellfish toxins (PST) by consuming dinoflagellate phytoplankton species like Alexandrium minutum. Intake of PST in oyster tissues mainly results from feeding processes, i.e. clearance rate, pre-ingestive sorting and ingestion that are directly influenced by environmental conditions (trophic sources, temperature). This study aimed to develop a mechanistic model coupling the kinetics of PST accumulation and bioenergetics in C. gigas based on Dynamic Energy Budget (DEB) theory. For the first time, the Synthesizing Units (SU) concept was applied to formalize the feeding preference of oysters between non-toxic and toxic microalgae. Toxin intake and accumulation were both dependent on the physiological status of oysters. The accumulation was modelled through the dynamics of two toxin compartments: (1) a compartment of ingested but non-assimilated toxins, with labile toxins within the digestive gland eliminated via faeces production; (2) a compartment of assimilated toxins with a rapid detoxification rate (within a few days). Firstly, the DEB-PST model was calibrated using data from two laboratory experiments where oysters have been exposed to A. minutum. Secondly, it was validated using data from another laboratory experiment and from three field surveys carried out in the Bay of Brest (France) from 2012 to 2014. To account for the variability in PST content of A. minutum cells, the saxitoxin (STX) amount per energy units in a toxic algae (ρPST) was adjusted for each dataset. Additionally, the effects of PST on the oyster bioenergetics were calibrated during the first laboratory experiment. However, these effects were shown to depend on the strain of A. minutum. Results of this study could be of great importance for monitoring agencies and decision makers to identify risky conditions (e.g. production areas, seawater temperature), to properly assess detoxification step (e.g. duration, modalities) before any commercialization or to improve predictions regarding closing of shellfish areas

Safety and efficacy of intra-arterial fibrinolytics as adjunct to mechanical thrombectomy : a systematic review and meta-analysis of observational data

Background Achieving the best possible reperfusion is a key determinant of clinical outcome after mechanical thrombectomy (MT). However, data on the safety and efficacy of intra-arterial (IA) fibrinolytics as an adjunct to MT with the intention to improve reperfusion are sparse. Methods We performed a PROSPERO-registered (CRD42020149124) systematic review and meta-analysis accessing MEDLINE, PubMed, and Embase from January 1, 2000 to January 1, 2020. A random-effect estimate (Mantel-Haenszel) was computed and summary OR with 95% CI were used as a measure of added IA fibrinolytics versus control on the risk of symptomatic intracranial hemorrhage (sICH) and secondary endpoints (modified Rankin ScalePeer reviewe

Penumbral imaging and functional outcome in patients with anterior circulation ischaemic stroke treated with endovascular thrombectomy versus medical therapy: a meta-analysis of individual patient-level data

Background: CT perfusion (CTP) and diffusion or perfusion MRI might assist patient selection for endovascular thrombectomy. We aimed to establish whether imaging assessments of irreversibly injured ischaemic core and potentially salvageable penumbra volumes were associated with functional outcome and whether they interacted with the treatment effect of endovascular thrombectomy on functional outcome. Methods: In this systematic review and meta-analysis, the HERMES collaboration pooled patient-level data from all randomised controlled trials that compared endovascular thrombectomy (predominantly using stent retrievers) with standard medical therapy in patients with anterior circulation ischaemic stroke, published in PubMed from Jan 1, 2010, to May 31, 2017. The primary endpoint was functional outcome, assessed by the modified Rankin Scale (mRS) at 90 days after stroke. Ischaemic core was estimated, before treatment with either endovascular thrombectomy or standard medical therapy, by CTP as relative cerebral blood flow less than 30% of normal brain blood flow or by MRI as an apparent diffusion coefficient less than 620 μm2/s. Critically hypoperfused tissue was estimated as the volume of tissue with a CTP time to maximum longer than 6 s. Mismatch volume (ie, the estimated penumbral volume) was calculated as critically hypoperfused tissue volume minus ischaemic core volume. The association of ischaemic core and penumbral volumes with 90-day mRS score was analysed with multivariable logistic regression (functional independence, defined as mRS score 0–2) and ordinal logistic regression (functional improvement by at least one mRS category) in all patients and in a subset of those with more than 50% endovascular reperfusion, adjusted for baseline prognostic variables. The meta-analysis was prospectively designed by the HERMES executive committee, but not registered. Findings: We identified seven studies with 1764 patients, all of which were included in the meta-analysis. CTP was available and assessable for 591 (34%) patients and diffusion MRI for 309 (18%) patients. Functional independence was worse in patients who had CTP versus those who had diffusion MRI, after adjustment for ischaemic core volume (odds ratio [OR] 0·47 [95% CI 0·30–0·72], p=0·0007), so the imaging modalities were not pooled. Increasing ischaemic core volume was associated with reduced likelihood of functional independence (CTP OR 0·77 [0·69–0·86] per 10 mL, pinteraction=0·29; diffusion MRI OR 0·87 [0·81–0·94] per 10 mL, pinteraction=0·94). Mismatch volume, examined only in the CTP group because of the small numbers of patients who had perfusion MRI, was not associated with either functional independence or functional improvement. In patients with CTP with more than 50% endovascular reperfusion (n=186), age, ischaemic core volume, and imaging-to-reperfusion time were independently associated with functional improvement. Risk of bias between studies was generally low. Interpretation: Estimated ischaemic core volume was independently associated with functional independence and functional improvement but did not modify the treatment benefit of endovascular thrombectomy over standard medical therapy for improved functional outcome. Combining ischaemic core volume with age and expected imaging-to-reperfusion time will improve assessment of prognosis and might inform endovascular thrombectomy treatment decisions. Funding: Medtronic

Safety and efficacy of intra-arterial fibrinolytics as adjunct to mechanical thrombectomy: A systematic review and meta-analysis of observational data

Background: Achieving the best possible reperfusion is a key determinant of clinical outcome after mechanical thrombectomy (MT). However, data on the safety and efficacy of intra-arterial (IA) fibrinolytics as an adjunct to MT with the intention to improve reperfusion are sparse. Methods: We performed a PROSPERO-registered (CRD42020149124) systematic review and meta-analysis accessing MEDLINE, PubMed, and Embase from January 1, 2000 to January 1, 2020. A random-effect estimate (Mantel-Haenszel) was computed and summary OR with 95% CI were used as a measure of added IA fibrinolytics versus control on the risk of symptomatic intracranial hemorrhage (sICH) and secondary endpoints (modified Rankin Scale ≤2, mortality at 90 days). Results: The search identified six observational cohort studies and three observational datasets of MT randomized-controlled trial data reporting on IA fibrinolytics with MT as compared with MT alone, including 2797 patients (405 with additional IA fibrinolytics (100 urokinase (uPA), 305 tissue plasminogen activator (tPA)) and 2392 patients without IA fibrinolytics). Of 405 MT patients treated with additional IA fibrinolytics, 209 (51.6%) received prior intravenous tPA. We did not observe an increased risk of sICH after administration of IA fibrinolytics as adjunct to MT (OR 1.06, 95% CI 0.64 to 1.76), nor excess mortality (0.81, 95% CI 0.60 to 1.08). Although the mode of reporting was heterogeneous, some studies observed improved reperfusion after IA fibrinolytics. Conclusion: The quality of evidence regarding peri-interventional administration of IA fibrinolytics in MT is low and limited to observational data. In highly selected patients, no increase in sICH was observed, but there is large uncertainty

Etude des motifs d'appels d'urgence par les maisons de retraite de l'agglomération Aixoise en période de permanence de soins sur une année (à propos de 360 cas)

INTRODUCTION: Identifier les différentes motifs d'urgence par les maisons de retraite (MDR) de l'agglomération Aixoise en période de permanence de soins (PDS) à la régulation des Bouches-du-Rhône. METHODE: Etude descriptive, multicentrique, transversale, rétrospective a été réalisée. 24 MDR sont recensées sur 1 an (de juin 2011 à juin 2012) en PDS (nuit de 18h à 19h et samedis, dimanches), soit 360 sujets (utilisation logiciel CENTAURE 15 et questionnaires MDR). Le critère de jugement principal a été l'étude des motifs dits urgents des MDR médicalisées ou pas. RESULTATS: 360 sujets ont donc été inclus. Deux groupes ont été réalisés: le 1er regroupant 17 MDR médicalisées soit 324 appels et le 2ème regroupant 7 MDR non médicalisées soit 36 appels. La prévalence des appels des MDR médicalisées est de 21% versus 7 % pour MDR non médicalisées. l'incidence des différents motifs d'appels est différents pour les 2 groupes: 30% pour motif traumatologique dans le groupe 1 versus 33% pour motif neurologique dans le groupe 2 (p=0.014). Après analyse en sous-groupes dans MDR médicalisées: protocoles d'urgences, médecin coordinateur formation du personnel soignant aux gestes d'urgence ont été globalement recensés. L'étude du nombre et du taux d'appels, du taux de transfert médicalisé, les différents calculs de ratio ont permis de souligner des problèmes d'ordre organisationnel et de soins (MDR n2 avec 44 appels, taux d'appels de 0,56 pour 78 patients avec GIRE médian 3,40 transferts hospitaliers dont 2 médicalisés, ratio 1 = 1.7 et ratio 2 = 14.7). CONCLUSION: En PDS, les motifs d'appels sont d'ordre traumatologique pour MDR médicalisée versus motifs médicaux pour MDR non médicalisées.AIX-MARSEILLE2-BU Méd/Odontol. (130552103) / SudocSudocFranceF

Performance of administrative databases for identifying individuals with multiple sclerosis

Abstract Administrative databases are an alternative to disease registries as a research tool to study multiple sclerosis. However, they are not initially designed to fulfill research purposes. Therefore, an evaluation of their performance is necessary. Our objective was to assess the performance of the French administrative database comprising hospital discharge records and national health insurance databases in identifying individuals with multiple sclerosis, in comparison with a registry that exhaustively compiles resident multiple sclerosis cases in Lorraine, northeastern France, as reference. We recorded all individuals residing in the Lorraine region who were identified by the administrative database or the registry as having multiple sclerosis from 2011 to 2016. We calculated the Matthews correlation coefficient and other concordance indicators. For identifying individuals with multiple sclerosis, the Matthews correlation coefficient by the administrative database was 0.79 (95% CI 0.78–0.80), reflecting moderate performance. The mean time to identification was 5.5 years earlier with the registry than the administrative database. Administrative databases, although useful to study multiple sclerosis, should be used with caution because results of studies based on them may be biased. Our study highlights the value of regional registries that allow for a more exhaustive and rapid identification of cases

Incertitudes des méthodes d’évaluation « eaux littorales » : utilisation de modèles linéaires dynamiques pour l’évaluation des incertitudes des paramètres contaminants chimiques dans le biote

L’incertitude associée à une mesure a pour origine d’une part la variabilité environnementale et d’autre part l’ensemble du processus d’acquisition depuis le prélèvement jusqu’à la saisie de la donnée dans une base. L’estimation de l’ensemble de cette variabilité est un exercice complexe à réaliser dans le cadre d’un plan d’expérience. En revanche, les longues séries temporelles de données présentent la caractéristique d’intégrer toutes les variabilités. L’analyse de ces séries en termes de signal et bruit doit permettre de quantifier l’amplitude des incertitudes. Toutefois, les séries temporelles d’observation présentent un ensemble de caractéristiques les rendant difficiles à analyser. Les modèles linaires dynamiques constituent une approche adaptée à l’analyse de ces données particulières en faisant l’hypothèse de paramètres variables dans le temps. L’objet du présent travail consiste à estimer les variances liées au processus d’observation à l’aide de modèles linéaires dynamiques. Les données étudiées sont des paramètres de contaminations chimiques (cadmium, cuivre, CB153, fluoranthène, mercure, plomb) mesurés dans les huîtres et les moules prélevées sur les lieux de surveillance de l’estuaire de la Seine (i.e. « Cap de la Hève », « Villerville »), en Gironde (i.e. « La Fosse »), dans le bassin d’Arcachon (i.e. « Les Jacquets », « Comprian »), dans le Golfe de Fos (i.e. « Pointe St. Gervais ») et dans la petite rade de Toulon (i.e. « Toulon Lazaret »). La pertinence des DLM entraîne généralement la validation de la nécessaire expertise thématique. Bien que la relation moyenne-variance n’ait pas été observée sans ambiguïté pour tous les modèles, le caractère log-normal des distributions des contaminants est très vraisemblable. Les contributions non-structurelles aux bornes des intervalles de confiance à 90 % des observations en pourcentage de la médiane varient globalement de −20 % à −30 % pour la borne inférieure et de 30 % à 60 % pour la borne supérieure pour les contaminants métalliques. Ces résultats sont compatibles avec l’expérience experte. Pour les courtes séries des contaminants organiques les valeurs sont de l’ordre de −35 % pour la borne inférieure et pour la borne supérieure, de 80 % à 96 % pour le CB153 et de 100 % à 198 % pour le fluoranthène. Pour ce dernier, la multiplication des  laboratoires et des méthodes impliquées est sans doute une cause de la grande variabilité