Intra-aortic balloon pump protects against hydrostatic pulmonary oedema during peripheral venoarterial-extracorporeal membrane oxygenation

International audienceBackground: Increased left ventricular afterload during peripheral venoarterial-extracorporeal membrane oxygenation (VA-ECMO) support frequently causes hydrostatic pulmonary oedema. Because physiological studies demonstrated left ventricular afterload decrease during VA-ECMO assistance combined with the intra-aortic balloon pump (IABP), we progressively changed our standard practice systematically to associate an IABP with VA-ECMO. This study aimed to evaluate IABP efficacy in preventing pulmonary oedema in VA-ECMO-assisted patients. Methods: A retrospective single-centre study. Results: Among 259 VA-ECMO patients included, 104 received IABP. Weinberg radiological score-assessed pulmonary oedema was significantly lower in IABP + than IABP – patients at all times after ECMO implantation. This protection against pulmonary oedema persisted when death and switching to central ECMO were used as competing risks (subhazard ratio 0.49, 95% confidence interval (CI) 0.33–0.75; P<0.001). Multivariable analysis retained IABP as being independently associated with a lower risk of radiological pulmonary oedema (odds ratio (OR) 0.4, 95% CI 0.2–0.7; P=0.001) and a trend towards lower mortality (OR 0.54, 95% CI 0.29–1.01; P=0.06). Finally, the time on ECMO free from mechanical ventilation increased in IABP + patients (2.2±4.3 vs. 0.7±2.0 days; P=0.0003). Less frequent pulmonary oedema and more days off mechanical ventilation were also confirmed in 126 highly comparable IABP + and IABP – patients, propensity score matched for receiving an IABP. Conclusions: Associating an IABP with peripheral VA-ECMO was independently associated with a lower frequency of hydrostatic pulmonary oedema and more days off mechanical ventilation under ECMO

Intra-aortic balloon pump protects against hydrostatic pulmonary oedema during peripheral venoarterial-extracorporeal membrane oxygenation

International audienceBackground: Increased left ventricular afterload during peripheral venoarterial-extracorporeal membrane oxygenation (VA-ECMO) support frequently causes hydrostatic pulmonary oedema. Because physiological studies demonstrated left ventricular afterload decrease during VA-ECMO assistance combined with the intra-aortic balloon pump (IABP), we progressively changed our standard practice systematically to associate an IABP with VA-ECMO. This study aimed to evaluate IABP efficacy in preventing pulmonary oedema in VA-ECMO-assisted patients. Methods: A retrospective single-centre study. Results: Among 259 VA-ECMO patients included, 104 received IABP. Weinberg radiological score-assessed pulmonary oedema was significantly lower in IABP + than IABP – patients at all times after ECMO implantation. This protection against pulmonary oedema persisted when death and switching to central ECMO were used as competing risks (subhazard ratio 0.49, 95% confidence interval (CI) 0.33–0.75; P<0.001). Multivariable analysis retained IABP as being independently associated with a lower risk of radiological pulmonary oedema (odds ratio (OR) 0.4, 95% CI 0.2–0.7; P=0.001) and a trend towards lower mortality (OR 0.54, 95% CI 0.29–1.01; P=0.06). Finally, the time on ECMO free from mechanical ventilation increased in IABP + patients (2.2±4.3 vs. 0.7±2.0 days; P=0.0003). Less frequent pulmonary oedema and more days off mechanical ventilation were also confirmed in 126 highly comparable IABP + and IABP – patients, propensity score matched for receiving an IABP. Conclusions: Associating an IABP with peripheral VA-ECMO was independently associated with a lower frequency of hydrostatic pulmonary oedema and more days off mechanical ventilation under ECMO

Cost-effectiveness of acupuncture versus standard care for pelvic and low back pain in pregnancy: A randomized controlled trial

<div><p>Objective</p><p>To assess the cost-effectiveness of acupuncture for pelvic girdle and low back pain (PGLBP) during pregnancy.</p><p>Design</p><p>Pragmatic-open-label randomised controlled trial.</p><p>Setting</p><p>Five maternity hospitals</p><p>Population</p><p>Pregnant women with PGLBP</p><p>Method</p><p>1:1 randomization to standard care or standard care plus acupuncture (5 sessions by an acupuncturist midwife).</p><p>Main outcome measure</p><p>Efficacy: proportion of days with self-assessed pain by numerical rating scale (NRS) ≤ 4/10. Cost effectiveness (societal viewpoint, time horizon: pregnancy): incremental cost per days with NRS ≤ 4/10. Indirect non-healthcare costs included daily compensations for sick leave and productivity loss caused by absenteeism or presenteeism.</p><p>Results</p><p>96 women were allocated to acupuncture and 103 to standard care (total 199). The proportion of days with NRS ≤ 4/10 was greater in the acupuncture group than in the standard care group (61% vs 48%, p = 0.007). The mean Oswestry disability score was lower in the acupuncture group than with standard care alone (33 versus 38, Δ = 5, 95% CI: 0.8 to 9, p = 0.02). Average total costs were higher in the control group (€2947) than in the acupuncture group (€2635, Δ = —€312, 95% CI: -966 to +325), resulting from the higher indirect costs of absenteeism and presenteeism. Acupuncture was a dominant strategy when both healthcare and non-healthcare costs were included. Costs for the health system (employer and out-of-pocket costs excluded) were slightly higher for acupuncture (€1512 versus €1452, Δ = €60, 95% CI: -272 to +470).</p><p>Conclusion</p><p>Acupuncture was a dominant strategy when accounting for employer costs. A 100% probability of cost-effectiveness was obtained for a willingness to pay of €100 per days with pain NRS ≤ 4.</p></div

The European “Clinical Trial” Regulation; Relationship with the Jardé Act: a Giens Workshop

In May 2014, the European Union Parliament and Council published a new regulation on clinical trials on medicinal products for human use, which is designed to replace Directive 2001/20/EC. It will not come into effect until 2016. Nevertheless, it is essential to examine its relationship with national legislation, i.e. the Jardé Act, whose implementation has been delayed pending publication of the European regulation. The Giens workshop identified and examined the various issues that this relationship is bound to raise. In particular, it looked at trial methodology assessment procedures, the working relationship between the French National Agency of Drug Safety and Health Products (Agence Nationale de Sécurité du Médicament et des Produits de Santé, ANSM) and ethics committees during the authorization application evaluation phase, review of post-authorization/registration studies on medicinal products and medical devices, and data transparency. Abbreviations: see end of article

Le règlement européen «essais cliniques» : articulation avec la loi Jardé : un atelier de Giens

Le Parlement et le Conseil de l’Union Européenne ont publié en mai 2014 un nouveau règlement relatif aux essais cliniques de médicaments, destiné à remplacer la directive 2001/20/CE. Sa mise en application n’interviendra pas avant 2016. Néanmoins, il est essentiel de se préoccuper dès à présent de l’articulation de ce texte avec la législation nationale, c’est-à-dire de la loi Jardé dont la mise en œuvre a été retardée, précisément dans l’attente de la publication du règlement européen. L’atelier de Giens a listé et étudié les différents problèmes que cette articulation ne manquera pas de poser. Ont été particulièrement abordés : les modalités d’évaluation de la méthodologie des essais, l’articulation fonctionnelle entre l’Agence Nationale de Sécurité du Médicament et des Produits de Santé (ANSM) et les Comités de Protection des Personnes (CPP) pendant cette phase d’évaluation des demandes d’autorisation, l’évaluation des études post-autorisation/inscription des médicaments et des dispositions médicaux, la transparence des données. Abréviations : voir en fin d’article

Les essais plateformes

International audienc

Platform trials

International audienceFor the past few years, platform trials have experienced a significant increase, recently amplified by the COVID-19 pandemic. The implementation of a platform trial is par-ticularly useful in certain pathologies, particularly when there is a significant number of drug candidates to be assessed, a rapid evolution of the standard of care or in situations of urgent need for evaluation, during which the pooling of protocols and infrastructure optimizes the number of patients to be enrolled, the costs, and the deadlines for carrying out the investiga-tion. However, the specificity of platform trials raises methodological, ethical, and regulatory issues, which have been the subject of the round table and which are presented in this article. The round table was also an opportunity to discuss the complexity of sponsorship and data management related to the multiplicity of partners, funding, and governance of these trials, and the level of acceptability of their findings by the competent authorities

Prognosis value of a genetic score based on germline genetic variants in a prospective cohort of early triple negative breast cancer patients

International audienceBackground: Triple-negative breast cancers (TNBC) are a heterogeneous group of tumors with poor outcome. In this study, the association between germline genetic variants and invasive disease-free survival (iDFS) was analyzed in TNBC patients. Methods: A genome wide-association study (GWAS) aimed to identify variants (single nucleotide polymorphisms – SNPs) associated with prognosis in 1121 patients with TNBC in the SIGNAL prospective cohort. Associations between gene variants and iDFS were assessed in univariate Cox regression models. Variants were combined in a score to identify risk categories. A prognostic model based on breast cancer stage and genetic variants was estimated using a multivariate Cox regression. Interaction between stage and genetic score was tested. Discrimination of the model was assessed by the Harrell’s C statistic and internal validity by bootstrap method. Results: The characteristics of the 1121 patients were representative of a population with early TNBC. Four SNPs on chromosomes 9 and 2 were found significantly associated to iDFS in univariate Cox models. Homozygous status for the most frequent allele was associated with poorer iDFS for two SNPs and this status was present in 50% and 57% of the population. For the two other SNPs, the most frequent allele was associated with more favorable iDFS. Three prognostic categories were derived from the genetic score. The following table presents the results from the multivariate Cox model including genetic score and disease stage. Clinical trial information: RECF1098. Conclusions: In a prospective cohort of 1121 patients with early TNBC, 4 genetic variants (SNPs) were associated with iDFS. A score involving SNPs provided similar prognostic indications as breast cancer stages. A search assessing the function and the role of the involved genes is ongoing

The European “Clinical Trial” Regulation: Relationship with the Jardé Act: a Giens Workshop

In May 2014, the European Union Parliament and Council published a new regulation on clinical trials on medicinal products for human use, which is designed to replace Directive 2001/20/EC. It will not come into effect until 2016. Nevertheless, it is essential to examine its relationship with national legislation, i.e. the Jardé Act, whose implementation has been delayed pending publication of the European regulation. The Giens workshop identified and examined the various issues that this relationship is bound to raise. In particular, it looked at trial methodology assessment procedures, the working relationship between the French National Agency of Drug Safety and Health Products (Agence Nationale de Sécurité du Médicament et des Produits de Santé, ANSM) and ethics committees during the authorization application evaluation phase, review of post-authorization/registration studies on medicinal products and medical devices, and data transparency. Abbreviations: see end of article

Safety and efficacy of nivolumab, an anti-PD1 immunotherapy, in patients with advanced basal cell carcinoma, after failure or intolerance to sonic Hedgehog inhibitors: UNICANCER AcSé NIVOLUMAB trial

International audienceBasal cell carcinoma (BCC) is the most common human malignancy. In most cases, BCC has slow progression and can be definitively cured by surgery or radiotherapy. However, in rare cases, it can become locally advanced or, even more rarely, metastatic. The alternative recommended treatments are Sonic Hedgehog pathway inhibitors; however, the response is often short-lived.Methods: This was a phase 2 basket study (NCT03012581) evaluating the efficacy and safety of nivolumab in a cohort of 32 advanced BCC patients, enrolled after failure of Sonic Hedgehog inhibitors, including 29 laBCC (91%) and 3 mBCC (9%).Results: Compared to previously published studies, our population consisted of severe patients with a poor prognosis because they had already received multiple lines of treatment: all patients received previous Sonic Hedgehog inhibitors, 53% of patients already had chemotherapy and 75% radiotherapy. At 12 weeks, we reported 3.1% of complete responses, 18.8% of partial responses, and 43.8% of stable diseases. The best response rate to nivolumab reached 12.5% of complete responses (four patients), 18.8% of partial responses (three patients), and 43.8% of stable diseases (14 patients). Adverse events (AE) were mostly grade 2 or 3, slightly different to the adverse events observed in the treatment of metastatic melanoma (higher rate of diabetes, no thyroid dysfunction).Conclusion: Nivolumab is a relevant therapeutic option for patients with advanced relapsing/refractory BCC