During refractory cardiogenic shock and cardiac arrest, veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is used to restore a circulatory output. However, it also impacts significantly arterial oxygenation. Recent guidelines of the Extracorporeal Life Support Organization (ELSO) recommend targeting postoxygenator partial pressure of oxygen (P POST O 2 ) around 150 mmHg. In this narrative review, we intend to summarize the rationale and evidence for this P POST O 2 target recommendation. Because this is the most used configuration, we focus on peripheral VA-ECMO. To date, clinicians do not know how to set the sweep gas oxygen fraction (F S O 2 ). Because of the oxygenator’s performance, arterial hyperoxemia is common during VA-ECMO support. Interpretation of oxygenation is complex in this setting because of the dual circulation phenomenon, depending on both the native cardiac output and the VA-ECMO blood flow. Such dual circulation results in dual oxygenation, with heterogeneous oxygen partial pressure (PO 2 ) along the aorta, and heterogeneous oxygenation between organs, depending on the mixing zone location. Data regarding oxygenation during VA-ECMO are scarce, but several observational studies have reported an association between hyperoxemia and mortality, especially after refractory cardiac arrest. While hyperoxemia should be avoided, there are also more and more studies in non-ECMO patients suggesting the harm of a too restrictive oxygenation strategy. Finally, setting F S O 2 to target strict normoxemia is challenging because continuous monitoring of postoxygenator oxygen saturation is not widely available. The threshold of P POST O 2 around 150 mmHg is supported by limited evidence but aims at respecting a safe margin, avoiding both hypoxemia and severe hyperoxemia.
Background: Describe the characteristics, patterns of care, and predictive geriatric factors of elderly patients with IDHm high-grade glioma (HGG) included in the French POLA network. Material and methods: The characteristics of elderly (≥70 years) patients IDHm HGG were compared to those of younger patients IDHm HGG (<70 years) and of elderly patients IDHwt HGG. Geriatric features were collected. Results: Out of 1433 HGG patients included, 119 (8.3%) were ≥70 years. Among them, 39 presented with IDHm HGG. The main characteristics of elderly IDHm HGG were different from those of elderly IDHwt HGG but similar to those of younger IDHm HGG. In contrast, their therapeutic management was different from those of younger IDHm HGG with less frequent gross total resection and radiotherapy. The median progression-free survival (PFS) and overall survival (OS) were longer for elderly patients IDHm HGG (29.3 months and 62.1 months) than elderly patients IDHwt HGG (8.3 months and 13.3 months) but shorter than those of younger patients IDHm HGG (69.1 months and not reached). Geriatric factors associated with PFS and OS were mobility, neuropsychological disorders, body mass index, and autonomy. Geriatric factors associated with PFS and OS were mobility, neuropsychological disorders, and body mass index, and autonomy. Conclusion: the outcome of IDHm HGG in elderly patients is better than that of IDHwt HGG. Geriatric assessment may be particularly important to optimally manage these patients.
Background: BRAFV600E mutations occur in 8%-12% of metastatic colorectal cancer (mCRC) cases and are associated with poor survival. European guidelines recommend combination (doublet or triplet) chemotherapy plus bevacizumab in first line. However, an unmet need remains for more effective treatments for these patients. Patients and methods: CAPSTAN CRC is a European, retrospective, multicenter, observational study evaluating real-world treatment practices for patients with BRAFV600E-mutant mCRC treated between 1 January 2016 and 31 January 2020. The primary objective was to describe first-line treatment patterns. Secondary objectives included describing baseline demographics, mutational testing procedures, treatment effectiveness, and safety. Results: In total, 255 patients (median age 66.0 years; 58.4% female) with BRAFV600E-mutant unresectable mCRC from seven countries were included. Most had right-sided tumors (52.5%) and presented with synchronous disease at diagnosis (66.4%). Chemotherapy plus targeted therapy (68.7%) was preferred at first line over chemotherapy alone (31.3%). The main first-line treatments were FOLFOX plus bevacizumab (27.1%) and FOLFOXIRI (folinic acid, 5-fluorouracil, oxaliplatin, irinotecan) with/without bevacizumab (27.1%/19.2%). Median duration of first-line treatment was 4.9 months. Overall, 52.5% received second-line treatment. Across all first-line regimens, progression-free survival (PFS) and overall survival were 6.0 [95% confidence interval (CI) 5.3-6.7] months and 12.9 (95% CI 11.6-14.1) months, respectively. Triplet plus targeted therapy was associated with more adverse events (75.0%) compared with triplet chemotherapy alone (50.0%) and doublet chemotherapy alone (36.1%). Multivariate analysis identified low body mass index and presence of three or more metastatic sites as significant prognostic factors for PFS. Conclusions: This study is, to date, the largest real-world analysis of patients with BRAFV600E-mutant mCRC, providing valuable insights into routine first-line treatment practices for these patients. The data highlight the intrinsic aggressiveness of this disease subgroup, confirming results from previous real-world studies and clinical trials, and stressing the urgent need for more effective treatment options in this setting.
Many signaling pathways, molecular and cellular actors which are critical for wound healing have been implicated in cancer metastasis. These two conditions are a complex succession of cellular biological events and accurate regulation of these events is essential. Apart from inflammation, macrophages-released ROS arise as major regulators of these processes. But, whatever the pathology concerned, oxidative stress is a complicated phenomenon to control and requires a finely tuned balance over the different stages and responding cells. This review provides an overview of the pivotal role of oxidative stress in both wound healing and metastasis, encompassing the contribution of macrophages. Indeed, macrophages are major ROS producers but also appear as their targets since ROS interfere with their differentiation and function. Elucidating ROS functions in wound healing and metastatic spread may allow the development of innovative therapeutic strategies involving redox modulators.
Background There is no specific guideline for the treatment of locally advanced rectal cancers in the elderly. Here we compared R0 resection rate and degradation of autonomy based on the IADL score between neoadjuvant, short course radiotherapy, and chemoradiotherapy in this specific population. Patients and methods Patients ≥75 years with resectable T3-T4 rectal adenocarcinoma within 12 cm of the anal verge or T2 of the very low rectum, were randomised between short course radiotherapy (5x5 Gy in one week) and chemoradiotherapy (50 Gy, 2 Gy/f, 5 weeks with capecitabine: 800 mg/m² twice daily, 5 days per week), with delayed surgery 7 ± 1 weeks for the two arms. Results One hundred and three eligible patients were enrolled between January 2016 and Decembre 2019 when the trial was closed due to poor accrual. The R0 resection rate (first coprimary objective) was 84.3%; CI95% [73.26 - 94.18] in the short course group and 88%; CI95% [77.77 - 96.60] in the chemoradiotherapy group (non inferiority p=0.28). The deterioration of the IADL score was not different during the pre-operative phase, it was significantly more deteriorated in the chemoradiotherapy group at 3 months post-operative (44.8% vs 14.8%; p= 0.032), but was not different at 12 months post-operative (second co-primary objective). During pre-operative phase, 9.8% of patients in short course group and 22% of patients in chemoradiotherapy group presented a serious adverse event, but we observed no difference during the post-operative phase between the two groups. Conclusion Although the main objectives of the study were not achieved, the short course radiotherapy followed by delayed surgery could represent a preferred treatment option in patients ≥75 years with locally advanced rectal cancer; a new study must be performed to confirm the improvement in overall and specific survival results.
Introduction: Several studies in COPD have shown a significant and early increase in the risk of cardiovascular mortality attributable to inhaled bronchodilators including long acting β2 agonists (LABAs) and muscarinic antagonists (LAMAs). Cardiac autonomic system impairment may be a potential mechanism involved. Methods: We performed a phase 4, investigator-initiated, prospective, randomized, blinded, cross-over trial (LAB-Card trial - NCT02872090) to evaluate the effect of two LAMAs and one LABA on the cardiac autonomic system in patients with COPD by using three major assessment approaches: heart rate variability (HRV, a predictor of cardiovascular death), baroreflex sensitivity (BRS) and autonomic function (tilt test). Results: 34 patients attended four visits to receive either tiotropium 18µg, glycopyrronium 44µg, indacaterol 150 µg or placebo (lactose) in a randomized order followed by the assessment of HRV and BRS in supine position and after passive rising. Neither LAMAs (tiotropium or glycopyrronium) nor LABA (indacaterol) induced a higher LF/HF ratio (reflect of sympathetic/parasympathetic balance) measured in supine position at rest compared to placebo (primary outcome). Solely indacaterol induced an increase in heart rate compared to placebo. No significant differences were observed for HRV and BRS between active drugs and placebo in supine position or after passive rising. Conclusion: We did not found evidence of a deleterious effect of 2 LAMAs and one LABA on the autonomic cardiovascular control in COPD patients. Further investigations are needed to explore mechanisms by which long-acting bronchodilators may increase cardiovascular events in COPD.
Background: Outcomes are poor in patients with HER2-negative, advanced gastric or gastro-oesophageal junction adenocarcinomas. In this study, we investigated efficacy and safety of the first-in-class, afucosylated, humanised IgG1 anti-fibroblast growth factor receptor 2 isoform IIb (FGFR2b) monoclonal antibody bemarituzumab with modified 5-fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) in patients with FGFR2b-selected gastric or gastro-oesophageal junction adenocarcinoma. Methods: In the randomised, double-blind, placebo-controlled phase 2 trial (FIGHT), patients aged 18 years and older with HER2 non-positive, FGFR2b-selected gastric or gastro-oesophageal junction adenocarcinoma, and an Eastern Cooperative Oncology Group performance status of 0-1 were recruited from 144 clinical sites across 17 countries. Patients with previous treatment with any selective inhibitor of the FGF-FGFR pathway were excluded. Eligible patients were randomly assigned (1:1), using permuted-block randomisation (block size of four) and a central interactive voice-web-based response system, stratified by geographical region, previous treatment with curative intent, and administration of mFOLFOX6 while being screened for FGFR2b status, to either bemarituzumab (15 mg/kg of bodyweight) or matched placebo intravenously every 2 weeks. All patients also received mFOLFOX6 (oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, and 5-fluorouracil as a 400 mg/m2 bolus followed by 2400 mg/m2 over approximately 46 h) intravenously every 2 weeks. Patients were given treatment until disease progression (defined by Response Evaluation Criteria in Solid Tumours [RECIST] version 1.1), unacceptable toxicity, withdrawal of consent, or death. The primary endpoint was progression-free survival in the intention-to-treat population (defined as all patients randomly assigned to treatment). Safety was assessed in all patients who received at least one dose of assigned treatment. This study is registered with ClinicalTrials.gov, NCT03694522, and is now complete. Findings: Between Nov 14, 2017, and May 8, 2020, 910 patients were screened and 155 were randomly assigned to the bemarituzumab (n=77) or placebo group (n=78). Median age was 60·0 years (IQR 51·0-67·0), 44 (28%) participants were women, 111 (72%) were men, 89 (57%) were Asian, and 61 (39%) were White. At the time of the primary analysis and at a median follow-up of 10·9 months (IQR 6·3-14·2), median progression-free survival was 9·5 months (95% CI 7·3-12·9) in the bemarituzumab group and 7·4 months (5·8-8·4) in the placebo group (hazard ratio [HR] 0·68 [95% CI 0·44-1·04; p=0·073). Common grade 3 or worse adverse events were decreased neutrophil count (23 [30%] of 76 in the bemarituzumab group vs 27 [35%] of 77 in the placebo group), cornea disorder (18 [24%] vs none), neutropenia (ten [13%] vs seven [9%]), stomatitis (seven [9%] vs one [1%]), and anaemia (six [8%] vs ten [13%]). Serious treatment-emergent adverse events were reported in 24 (32%) patients in the bemarituzumab group and 28 (36%) in the placebo group. Serious mFOLFOX6 treatment-related adverse events occurred in nine (12%) patients in the bemarituzumab group and in 15 (19%) patients in the placebo group. All-grade corneal events (adverse events of special interest) occurred in 51 (67%) patients in the bemarituzumab group and eight (10%) in the placebo group; grade 3 corneal events were reported only in 18 (24%) patients in the bemarituzumab group. Treatment-related deaths occurred in three patients in the bemarituzumab group (two due to sepsis, one due to pneumonia) and none in the placebo group. Interpretation: In this exploratory phase 2 study, despite no statistically significant improvement in progression-free survival, treatment with bemarituzumab showed promising clinical efficacy. Confirmatory phase 3 trials of bemarituzumab plus mFOLFOX6 powered to demonstrate statistical significance are being investigated in patients with previously untreated, FGFR2b-overexpressing, advanced gastric or gastro-oesophageal junction adenocarcinoma. Funding: Five Prime Therapeutics.
Background Little is known on headaches long-term persistence after bacterial meningitis and on their impact on patients’ quality of life. Methods In an ancillary study of the French national prospective cohort of community-acquired bacterial meningitis in adults (COMBAT) conducted between February 2013 and July 2015, we collected self-reported headaches before, at onset, and 12 months (M12) after meningitis. Determinants of persistent headache (PH) at M12, their association with M12 quality of life (SF 12), depression (Center for Epidemiologic Studies Depression Scale) and neuro-functional disability were analysed. Results Among the 277 alive patients at M12 87/274 (31.8%), 213/271 (78.6%) and 86/277 (31.0%) reported headaches before, at the onset, and at M12, respectively. In multivariate analysis, female sex (OR: 2.75 [1.54–4.90]; p < 0.001), pre-existing headaches before meningitis (OR: 2.38 [1.32–4.30]; p < 0.01), higher neutrophilic polynuclei percentage in the CSF of the initial lumbar puncture (OR: 1.02 [1.00-1.04]; p < 0.05), and brain abscess during the initial hospitalisation (OR: 8.32 [1.97–35.16]; p < 0.01) were associated with M12 persistent headaches. Neither the responsible microorganism, nor the corticoids use were associated with M12 persistent headaches. M12 neuro-functional disability (altered Glasgow Outcome Scale; p < 0.01), M12 physical handicap (altered modified Rankin score; p < 0.001), M12 depressive symptoms (p < 0.0001), and M12 altered physical (p < 0.05) and mental (p < 0.0001) qualities of life were associated with M12 headaches. Conclusion Persistent headaches are frequent one year after meningitis and are associated with quality of life alteration.
Background PAOLA-1/ENGOT-ov25 (NCT02477644) demonstrated a significant progression-free survival (PFS) benefit with maintenance olaparib plus bevacizumab versus placebo plus bevacizumab in newly diagnosed, advanced ovarian cancer. We report the prespecified main second progression-free survival (PFS2) analysis for PAOLA-1. Methods This randomised, double-blind, phase III trial was conducted in 11 countries. Eligible patients had newly diagnosed, advanced, high-grade ovarian cancer and were in response after first-line platinum-based chemotherapy plus bevacizumab. Patients were randomised 2:1 to olaparib (300 mg twice daily) or placebo for up to 24 months; all patients received bevacizumab (15 mg/kg every 3 weeks) for up to 15 months. Primary PFS end-point was reported previously. Time from randomisation to second disease progression or death was a key secondary end-point included in the hierarchical-testing procedure. Results After a median follow-up of 35.5 months and 36.5 months, respectively, median PFS2 was 36.5 months (olaparib plus bevacizumab) and 32.6 months (placebo plus bevacizumab), hazard ratio 0.78; 95% confidence interval (CI) 0.64–0.95; P = 0.0125. Median time to second subsequent therapy or death was 38.2 months (olaparib plus bevacizumab) and 31.5 months (placebo plus bevacizumab), hazard ratio 0.78; 95% CI 0.64–0.95; P = 0.0115. Seventy-two (27%) patients in the placebo plus bevacizumab group received a poly(ADP-ribose) polymerase inhibitor as first subsequent therapy. No new safety signals were observed for olaparib plus bevacizumab. Conclusion In newly diagnosed, advanced ovarian cancer, maintenance olaparib plus bevacizumab provided continued benefit beyond first progression, with a significant PFS2 improvement and a time to second subsequent therapy or death delay versus placebo plus bevacizumab.
Context: Blastic plasmacytoid dendritic cell neoplasm (BPDCN), an aggressive hematologic malignancy with poor prognosis, is characterized by clonal expansion of plasmacytoid dendritic tumor cells expressing specific markers including the interleukin-3 receptor alpha (CD123). Tagraxofusp (TAG) is a CD123-targeted therapy approved by the FDA and EMA. A global expanded access program (EAP) was implemented prior to TAG's EMA authorization to provide access to patients in real-world practice. Objective: Main objectives were rates of complete response and incidence/severity of capillary leak syndrome (CLS). Key secondary objectives included rate of patients bridged to transplantation, survival, safety, number of cycles administered. Design: Non-interventional, retrospective analysis of BPDCN patients enrolled in the European EAP from 08.2019-12.2021. Setting: 57 European centers (Germany, France, Italy, Switzerland, United Kingdom, Spain, Austria). Patients: 76 adult (median age 64 years, range 21-85 years) and 4 pediatric patients with BPDCN confirmed by hematopathology with established marker panels (including CD123). Interventions: TAG 12 mcg/kg was administered intravenously once daily on days 1-5 (up to day 10 allowed) of a 21-day cycle. Hospitalization was required for the first cycle (subsequent cycles allowed outpatient administration). Main outcome measures: Review of case report forms and individual records of patients who met criteria for TAG prior to regulatory approval. Results: Most patients were male (78%), representing real-world distribution. Sixty-three patients received TAG first-line and 17 patients as second/or further line of treatment. The median number of cycles was 2.5 (range 1-8) in first-line and 2.6 (range 1-13) in second-line/further, respectively. No deaths due to CLS were reported. Adverse events (AEs) mainly occurred in cycle 1, with similar rates and severity in older vs younger patients. Analysis is ongoing; data on safety, efficacy, transplantation, and time-related parameters will be reported. Conclusions: The is the largest retrospective analysis of real-world clinical practice outside of a clinical trial in BPDCN patients treated with TAG. Adherence to the EAP and multidisciplinary training is thought to have positively affected prevention and management of CLS and other grade 3-4 AEs. These preliminary results confirm the feasibility and safety of TAG, including in elderly patients, with manageable safety.
The genes that encode CTX-M-type ESBLs have diffused extensively among Enterobacterales over the past decades.¹ Despite this epidemic success at the global level, few of these have been detected (blaCTX-M-1,-2,-3,-14,-15and-43) in the distantly related opportunistic pathogen Pseudomonas aeruginosa.1–4 The narrow host range of plasmids carrying the blaCTX-M determinants in Enterobacterales (mainly of incompatibility group IncF) plausibly accounts for the low prevalence of these resistance genes in P. aeruginosa.⁵ On the other hand, little is known about the mobile elements that enable the acquisition of CTX-M enzymes by clinical P. aeruginosa strains. One plasmid close to broad-host-range incompatibility group IncP2 has been found to carry the gene blaCTX-M-2, while another one belonging to IncQ harboured blaCTX-M-3.6,7 The present report describes the structure of a large conjugative plasmid determining a novel CTX-M variant, named CTX-M-206, and the genetic environment of a chromosomally located blaCTX-M-15 gene in a P. aeruginosa isolate present in a second strain.
Rational: Long-term outcomes of patients with COVID-19-related acute respiratory distress syndrome (ARDS) treated with extracorporeal membrane oxygenation (ECMO) are unknown. Methods: Multicenter, prospective study in patients who received ECMO for COVID-19 ARDS from March to June 2020 and survived hospital discharge. Physical examination, pulmonary function tests, anxiety, depression, post-traumatic stress disorders (PTSD), and quality of life (QoL) were assessed at 6 and 12 months after ECMO onset. Results: Of 80 eligible patients, 62 were enrolled in 7 French Intensive Care Units (ICU). ECMO and invasive mechanical ventilation duration were 18 (11-25) and 36 (27-62) days, respectively. All were alive but only 19/50 (38%) returned to work and 13/42 (31%) had recovered a normal sex drive at one year. Pulmonary function tests were almost normal at 6 months except for diffusing capacity for carbon monoxide which was still impaired at 12 months. Mental health, role-emotional, and role-physical were the most impaired domain compared to non-COVID ECMO patients. One year after ICU admission, 19/43 (44%) patients had significant anxiety, 18/43 (42%) had depression symptoms and 21/50 (42%) were at risk for PTSD. Conclusions: Despite the partial recovery of the lung function tests at one year, the physical and psychological function of this population remains impaired. Based on the comparison with long-term follow-up of non-COVID ECMO patients, poor mental and physical health may be more related to COVID-19 than to ECMO in itself, although this needs confirmation This article is open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
In March 2022, WHO, WOAH, FAO, and UNEP jointly advocated a rebalancing of the multiple components of One Health, explicitly including the notion of equity between sectors and disciplines, and a clearer ecological vision of the whole. Here we illustrate the vital need for this shift based on the multi-decadal experience of the authors in this field of research. We explain why One Health research still crucially requires the expansion of the current collaborations between disciplines and sectors to achieve its goals, and to release significant funding in each field for a successful transformational change. If not, ‘One Health’ will still stay as an aspiration and will not hit its promised targets. One Health Impact Statement In March 2022, WHO, WOAH, FAO, and UNEP jointly advocated a rebalancing of the multiple components of One Health, explicitly including the notion of equity between sectors and disciplines, and a clearer ecological vision of the whole. Here we illustrate the vital need for this shift based on the multi-decadal experience of the authors in this field of research. We explain why One Health research still crucially requires the expansion of the current collaborations between disciplines and sectors to achieve its goals, and to release significant funding in each field for a successful transformational change. If not, ‘One Health’ will still stay as an aspiration and will not hit its promised targets.
Background Results of this double-blind, phase 2 trial showed patients with metastatic castration-resistant prostate cancer given olaparib plus abiraterone versus placebo plus abiraterone had significantly improved progression-free survival. Here, we present an exploratory analysis of pain and health-related quality of life (HRQOL). Methods This double-blind, randomised, placebo-controlled, phase 2 trial was conducted across 41 urological oncology sites in 11 countries in Europe and North America. Eligible patients were aged 18 years or older, had metastatic castration-resistant prostate cancer, and had previously received docetaxel and up to one additional line of previous chemotherapy. Metastatic castration-resistant prostate cancer was defined as increasing prostate-specific antigen (PSA) concentration or other signs of disease progression despite androgen-deprivation therapy and serum testosterone concentrations at castrate levels (≤50 ng/dL), and with at least one metastatic lesion on bone scan, CT, or MRI. Eligible patients were randomly assigned (1:1) to receive oral olaparib (300 mg twice per day) plus oral abiraterone (1000 mg once a day) and oral prednisone or prednisolone (5 mg twice a day) or placebo plus abiraterone (1000 mg once a day) and prednisone or prednisolone (5 mg twice a day). Randomisation was done without stratification and by use of an interactive voice or web response system. A randomised treatment kit ID number was assigned sequentially to each patient as they became eligible. The primary endpoint (radiographic progression-free survival) has previously been reported. HRQOL was a prespecified exploratory patient-reported outcome. Patients were asked to complete the Brief Pain Inventory-Short Form (BPI-SF), single-item worst bone pain, Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire, and EuroQol-5 five-dimension five level (EQ-5D-5L) assessment at baseline, at weeks 4, 8, and 12, then every 12 weeks until treatment discontinuation. Prespecified outcomes were change from baseline in BPI-SF worst pain, single-item worst bone pain and FACT-P Total Outcome Index (TOI) scale scores, time to deterioration in BPI-SF worst pain and worst bone pain, and assessment of the EQ-5D-5L pain and discomfort domain. All analyses were exploratory and done in the full analysis set (all randomly assigned patients, including patients who were randomly assigned but did not subsequently go on to receive study treatment), with the exception of mean baseline and total change from baseline analyses, for which we used the population who had a valid baseline and at least one post-baseline assessment. This trial is registered with Clinicaltrials.gov, NCT01972217, and is no longer recruiting patients. Findings Between Nov 25, 2014, and July 14, 2015, 171 patients were assessed for eligibility. 29 patients were excluded, and 142 were enrolled and randomly assigned to receive olaparib and abiraterone (n=71) or placebo and abiraterone (n=71). Data cutoff was Sept 22, 2017. Median follow-up was 15·9 months (IQR 8·1–25·5) in the olaparib plus abiraterone group and 24·5 months (8·1–27·6) in the placebo plus abiraterone group. Questionnaire compliance was generally high (43–100%). Least-squares mean changes from baseline in BPI-SF worst pain, single-item worst bone pain, and FACT-P TOI remained stable across all visits for patients in both treatment groups. Adjusted mean change in FACT-P TOI from baseline across all visits was −0·10 (95% CI −2·50 to 2·71) in the olaparib plus abiraterone group and −1·20 (−4·15 to 1·74) in the placebo plus abiraterone group (difference 1·30, 95% CI −2·70 to 5·30; p=0·52). Time to deterioration in pain was similar in both groups (BPI-SF worst pain HR 0·90 [95% CI 0·62–1·32], p=0·30; worst bone pain HR 0·85 [0·59–1·22], p=0·18). Improvement rates in the pain and discomfort domain of the EQ-5D-5L were similar in both groups from baseline to week 48, beyond which a higher proportion of patients in the olaparib plus abiraterone arm reported an improvement compared to the placebo plus abiraterone group. Interpretation In these prespecified exploratory analyses, there was no significant difference in pain or HRQOL when olaparib was added to abiraterone. In this phase 2 trial, a statistically significant radiographic progression-free survival benefit was observed with the olaparib plus abiraterone combination. These results suggest that the improved survival benefits observed when combining olaparib with abiraterone does not result in different HRQOL compared with placebo plus abiraterone. Phase 3 studies are required to validate these results. Funding AstraZeneca and Merck Sharp & Dohme, a subsidiary of Merck & Co, Rahway, NJ, USA.
Résumé Le 31 mars 2021 est paru au Journal Officiel un décret relatif aux modalités de remise des certificats médicaux aux victimes de violences. Celles-ci peuvent désormais obtenir une copie du certificat réalisé par le médecin requis par les autorités judiciaires, ce qui concerne particulièrement le médecin légiste. But de l’étude L’objectif de notre étude était d’évaluer la demande de copie de certificats médico-légaux dans les premiers temps d’application de ce décret. Matériels et méthodes Il s’agissait d’une étude prospective menée auprès de trois services de médecine légale recevant des victimes en consultation, au moyen d’un questionnaire papier couplé aux données issues de Medlé, sur une période de trois mois. Résultats Sur les 1492 consultations réalisées durant la période d’étude, une copie du certificat n’a été remise à la victime que dans 13,1 % des consultations. Elle était demandée spontanément par la victime dans 15,2 % des cas, le plus souvent pour exercer ses droits (46,4 %). Il s’agissait principalement de consultations suite à un accident, à des violences psychologiques et à des coups et blessures. Cette copie était demandée spontanément par moins de 3 % des victimes de violences conjugales. Une certaine disparité existait entre les trois centres concernant le mineur victime. Conclusion Cette étude porte sur un faible échantillon sur une période courte. L’information des victimes, notamment de violences conjugales, sur l’accès à la copie du certificat médico-légal apparaît encore insuffisante, et le principe de remise, s’il peut aider la victime dans ses démarches, peut également être source de confusions.
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