Reduced-Dose Intravenous Thrombolysis for Acute Intermediate-High-risk Pulmonary Embolism: Rationale and Design of the Pulmonary Embolism International THrOmbolysis (PEITHO)-3 trial

Intermediate-high-risk pulmonary embolism (PE) is characterized by right ventricular (RV) dysfunction and elevated circulating cardiac troponin levels despite apparent hemodynamic stability at presentation. In these patients, full-dose systemic thrombolysis reduced the risk of hemodynamic decompensation or death but increased the risk of life-threatening bleeding. Reduced-dose thrombolysis may be capable of improving safety while maintaining reperfusion efficacy. The Pulmonary Embolism International THrOmbolysis (PEITHO)-3 study (ClinicalTrials.gov Identifier: NCT04430569) is a randomized, placebo-controlled, double-blind, multicenter, multinational trial with long-term follow-up. We will compare the efficacy and safety of a reduced-dose alteplase regimen with standard heparin anticoagulation. Patients with intermediate-high-risk PE will also fulfill at least one clinical criterion of severity: systolic blood pressure ≤110 mm Hg, respiratory rate >20 breaths/min, or history of heart failure. The primary efficacy outcome is the composite of all-cause death, hemodynamic decompensation, or PE recurrence within 30 days of randomization. Key secondary outcomes, to be included in hierarchical analysis, are fatal or GUSTO severe or life-threatening bleeding; net clinical benefit (primary efficacy outcome plus severe or life-threatening bleeding); and all-cause death, all within 30 days. All outcomes will be adjudicated by an independent committee. Further outcomes include PE-related death, hemodynamic decompensation, or stroke within 30 days; dyspnea, functional limitation, or RV dysfunction at 6 months and 2 years; and utilization of health care resources within 30 days and 2 years. The study is planned to enroll 650 patients. The results are expected to have a major impact on risk-adjusted treatment of acute PE and inform guideline recommendations

How to Capitalize on the Retest Effect in Future Trials on Huntington's Disease

The retest effect-improvement of performance on second exposure to a task-may impede the detection of cognitive decline in clinical trials for neurodegenerative diseases. We assessed the impact of the retest effect in Huntington\u27s disease trials, and investigated its possible neutralization. We enrolled 54 patients in the Multicentric Intracerebral Grafting in Huntington\u27s Disease (MIG-HD) trial and 39 in the placebo arm of the Riluzole trial in Huntington\u27s Disease (RIL-HD). All were assessed with the Unified Huntington\u27s Disease Rating Scale (UHDRS) plus additional cognitive tasks at baseline (A1), shortly after baseline (A2) and one year later (A3). We used paired t-tests to analyze the retest effect between A1 and A2. For each task of the MIG-HD study, we used a stepwise algorithm to design models predictive of patient performance at A3, which we applied to the RIL-HD trial for external validation. We observed a retest effect in most cognitive tasks. A decline in performance at one year was detected in 3 of the 15 cognitive tasks with A1 as the baseline, and 9 of the 15 cognitive tasks with A2 as the baseline. We also included the retest effect in performance modeling and showed that it facilitated performance prediction one year later for 14 of the 15 cognitive tasks. The retest effect may mask cognitive decline in patients with neurodegenerative diseases. The dual baseline can improve clinical trial design, and better prediction should homogenize patient groups, resulting in smaller numbers of participants being required

Confinement national lors de la crise sanitaire liée au Sars-Cov2 : quels impacts sur l'activité et la mortalité des résections digestives électives ?

International audienceIntroductionUn confinement national a été déclaré par les autorités gouvernementales le 12 mars 2020 pour limiter les risques de propagation du virus Sars-Cov2. L'activité au bloc opératoire a été annulée pour libérer des équipes paramédicales et médicales pour les réorienter vers les soins liés à la pandémie COVID19. Le but de cette étude était d’évaluer la baisse d'activité et la mortalité pendant le confinement, liées à la Covid-19.MéthodesTous les patients opérés en France d'une résection élective (oesophagectomie, gastrectomie, colectomie, proctectomie, pancréatectomie et hépatectomie) entre les 11ème-19ème semaines de 2019 et 2020 (période de confinement) ont été inclus via le PMSI. L'activité chirurgicale et la mortalité intra-hospitalière ont été étudiées. Les groupes 2019 et 2020 ont été appariés sur un score de propension, la région et l'acte chirurgical. Le calcul du score de propension intégrait l’âge, le sexe, le score de charleston, le statut nutritionnel, le diagnostic de cancer, un traitement néoadjuvant, et le volume d'activité du centre. Une analyse multivariée sur la mortalité a été réalisée incluant l'année et le statut COVID (symptomatique, asymptomatique, non-infecté).RésultatsEn 2019, 9801 résections ont été réalisées, contre 6008 en 2020 (-39 %). Cette diminution d'activité était plus marquée dans les zones de circulation du virus (rouge=-48 %, verte=-33 %). Les oesophagectomies étaient la chirurgie la plus touchées (-48 %), suivi des hépatectomies (-45 %), des proctectomies (-38 %), des colectomies (-37 %), et des gastrectomies (-33 %). La mortalité était de 2,5 % en 2019 et de 2,9 % en 2020. Après ajustement, il n'y avait pas d'augmentation de la mortalité pendant le confinement (OR=1,11 [0,87-1,41], p=0,391). La mortalité était significativement augmentée en cas d'infection COVID-19 qu'elle soit asymptomatique (OR=1,94 [1,23-2,95], p=0,003) ou symptomatique (OR=10,44 [5,32-19,18], p<0,001). La morbidité globale postopératoire augmentait en cas d'infection COVID-19 notamment les complications pulmonaires, les infections du site opératoires et les pathologies thromboemboliques.Discussion/ConclusionLa chirurgie digestive élective a baissé de 40 % pendant le confinement. La mortalité n’était pas augmentée, sauf en cas d'infection COVID-19

Bone-patellar tendon-bone autografts versus hamstring autografts for reconstruction of anterior cruciate ligament: meta-analysis

Objectives To compare bone-patellar tendon-bone autografts with hamstring autografts for reconstruction of the anterior cruciate ligament. Data sources Medline, WebSPIRS, Science Citation Index, Current Contents databases, and Cochrane Central Register of Controlled Trials. Review methods All randomised controlled trials reporting one or more outcome related to stability (instrumented measurement of knee laxity, Lachman test, or pivot shift test) and morbidity (anterior knee pain, kneeling test, loss of extension, or graft failure). Study quality was assessed by using a 5 point scale. Random effect models were used to pool the data. Heterogeneity in the effect of treatment was tested on the basis of study quality, randomisation status, and number of tendon strands used. Results 24 trials of 18 cohorts (1512 patients) met the inclusion criteria. Study quality was poor for nine studies and fair for nine studies. The weighted mean difference of the instrumented measurement of knee laxity was 0.36 (95% confidence interval 0.01 to 0.71; P = 0.04). Relative risk of a positive Lachman test was 1.22 (1.01 to 1.47; P = 0.04), of anterior knee pain 0.57 (0.44 to 0.74; P < 0.0001), of a positive kneeling test 0.26 (0.14 to 0.48; P < 0.0001), and of loss of extension 0.52 (0.34 to 0.80; P = 0.003). Other results were not significant. Conclusion Morbidity was lower for hamstring autografts than for patellar tendon autografts. Evidence that patellar tendon autografts offer better stability was weak. The poor quality of the studies calls into question the robustness of the analyses