"Who am I to say that I'm not going to take it": patient perspectives on decisions about antithrombotic therapy in the context of advanced cancer

Introduction The decision to reconsider antithrombotic therapy (ATT) in cancer patients nearing the end of life is complex given the increasing risk of haemorrhage and thrombosis. A decision support tool (DST) is being developed to facilitate this process. Understanding patients' experiences, values, and perspectives are an essential component, yet remain largely unexplored. Aim To explore these patients' experiences, values and perspectives regarding ATT use. Methods Qualitative study using semi-structured interviews with patients with advanced cancer receiving ATT, across Denmark, France, Spain, and the United Kingdom. Data were analysed using Framework Analysis. Results Sixty patients and 13 relatives participated. Three major themes were generated: 1. ATT is important and lifelong: Deprescription was perceived as counterintuitive; continuation was preferred, providing a sense of security. 2. Varying perspectives regarding roles and responsibilities in ATT decision-making: Patients' views regarding their role varied. When a good relationship existed with their clinician, patients trusted them to lead on the decision. Relatives played a key supportive role. 3. Challenges in navigating ATT management in the context of advanced cancer and multiple comorbidities: Decisions relating to ATT were rarely made in isolation. Patients prioritised cancer management and described difficulties navigating multiple health concerns. Conclusion Patients found decision-making around ATT near the end of life multifaceted, occurring amid a myriad of competing priorities. While patients reported a reticence to discontinuing, ultimately many deferred such decisions to a clinician, whose role was highly valued. These findings support a need for a DST, to support informed and shared choices in ATT decisions

Developing a decision support tool for the continuation or deprescribing of antithrombotic therapy in patients receiving end-of-life care: Protocol for a European Delphi study

Introduction To develop a European shared decision support tool (SDST), a Delphi process will be used to reach consensus about aspects relating to the continuation or deprescribing of antithrombotic therapy (ATT) in cancer patients at the end of life. As part of the SERENITY project, this study corresponds to work package (WP) 4. Methods Findings from SERENITY WPs 1-3 (realist review, flash mob research, epidemiological and qualitative studies) informed the Delphi study. The WP4 steering committee had two objectives. (1) to build a representative expert panel comprising physicians, pharmacists, nurses and psychologists from eight European countries; and (2) to advise on the content of the Delphi form, divided into four sections: context, content, SDST design and trial outcomes. The form was reviewed by the SERENITY patient and public involvement group to ensure that it met patients’ needs. The Delphi study will take place in three rounds held at 6-week intervals, involving experts from eight countries. Consensus will be reached on items with at least 70% agreement. The steering committee will review and validate the results across the different rounds. Results Through this Delphi study, the following aspects will be defined: characterisation of candidate patients for discussion about ATT deprescribing; healthcare team roles in ATT decision-making; specific information and communication requirements for patients when making deprescribing decisions; SDST content priorities; and optimal outcomes for the planned clinical trial. Conclusion This study will feed directly into the development and evaluation of the SDST, aimed at reducing complications and improving quality-of-life in end-of-life cancer patients receiving ATT

Neurological manifestations of COVID-19 in adults and children

Different neurological manifestations of coronavirus disease 2019 (COVID-19) in adults and children and their impact have not been well characterized. We aimed to determine the prevalence of neurological manifestations and in-hospital complications among hospitalized COVID-19 patients and ascertain differences between adults and children. We conducted a prospective multicentre observational study using the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) cohort across 1507 sites worldwide from 30 January 2020 to 25 May 2021. Analyses of neurological manifestations and neurological complications considered unadjusted prevalence estimates for predefined patient subgroups, and adjusted estimates as a function of patient age and time of hospitalization using generalized linear models. Overall, 161 239 patients (158 267 adults; 2972 children) hospitalized with COVID-19 and assessed for neurological manifestations and complications were included. In adults and children, the most frequent neurological manifestations at admission were fatigue (adults: 37.4%; children: 20.4%), altered consciousness (20.9%; 6.8%), myalgia (16.9%; 7.6%), dysgeusia (7.4%; 1.9%), anosmia (6.0%; 2.2%) and seizure (1.1%; 5.2%). In adults, the most frequent in-hospital neurological complications were stroke (1.5%), seizure (1%) and CNS infection (0.2%). Each occurred more frequently in intensive care unit (ICU) than in non-ICU patients. In children, seizure was the only neurological complication to occur more frequently in ICU versus non-ICU (7.1% versus 2.3%, P < 0.001). Stroke prevalence increased with increasing age, while CNS infection and seizure steadily decreased with age. There was a dramatic decrease in stroke over time during the pandemic. Hypertension, chronic neurological disease and the use of extracorporeal membrane oxygenation were associated with increased risk of stroke. Altered consciousness was associated with CNS infection, seizure and stroke. All in-hospital neurological complications were associated with increased odds of death. The likelihood of death rose with increasing age, especially after 25 years of age. In conclusion, adults and children have different neurological manifestations and in-hospital complications associated with COVID-19. Stroke risk increased with increasing age, while CNS infection and seizure risk decreased with age

HLA-class II haplotypes and Autism Spectrum Disorders

AbstractInfections and autoimmunity are associated with autism spectrum disorders (ASD), with both strongly influenced by the genetic regulation of the human leukocyte antigen (HLA) system. The relationship between ASD and the HLA genetic diversity requires further investigation. Using a case control design, the distribution of HLA class II-DRB1 and DQB1 alleles, genotypes and haplotypes were investigated in ASD patients, versus healthy controls (HC). ASD patients meeting DSM-IV TR criteria and HC (474 and 350 respectively) were genotyped at medium resolution using a Luminex-based SSO technology. Comparisons of genotypes, allele frequencies associated with a haplotype analysis were performed. Results indicate: (i) the HLA-DRB1 *11-DQB1*07 haplotype was more prevalent in ASD patients, versus HC (Pc = 0.001), partially replicating previous data and possibly linking to gastro-intestinal (GI)-related pro-inflammatory processes, given that this haplotype associates with pediatric celiac disorders; (ii) the HLA-DRB1 *17-DQB1*02 haplotype was higher in HC, versus ASD patients (Pc = 0.002), indicating that this is a protective haplotype. Using the Autism Diagnostic Interview to assess clinical dimensions, higher scores on social (Pc = 0.006) and non-verbal functioning (Pc = 0.004) associated with the DRB1 *11 DQB1*07 haplotype. Our results support HLA involvement in ASD, with possible relevance to GI and gut-brain axis dysregulation.</jats:p

Prospective external validation of a new non‐invasive test for the diagnosis of non‐alcoholic steatohepatitis in patients with type 2 diabetes

International audienceBackgroundOne of the unmet needs in patients with type 2 diabetes mellitus (T2DM) is the prediction of non-alcoholic liver disease by non-invasive blood tests, for each of the three main histological features, fibrosis, non-alcoholic steatohepatitis (NASH) and steatosis.AimsTo validate externally the performances of a recent panel, Nash-FibroTest, for the assessment of the severity of fibrosis stages, NASH grades and steatosis grades.MethodsWe prospectively analysed 272 patients with T2DM. Standard definitions of stages and grades were used, and analyses were centralised and blinded. The performances of the FibroTest, NashTest-2 and SteatoTest-2 were assessed using the Obuchowski measure (OM), the main outcome recommended as a summary measure of accuracy includeing all pairwise stages and grades comparisons, which is not provided par the extensively used binary area under the ROC curve.ResultsThe diagnostic performance of each component of the panel was significant. OM (SE; significance) of the FibroTest, the NashTest-2 and the SteatoTest-2 was 0.862 (0.012; P < 0.001), 0.827 (0.015; P < 0.001) and 0.794 (0.020; P < 0.01), respectively. For ballooning and lobular inflammation, OM was 0.794 (0.021; P < 0.001) and 0.821 (0.017; P < 0.001), respectively. In a post hoc analysis the FibroTest outperformed VCTE by 4.1% (2.5-6.5; P < 0.001) for reliability, with a non-significant difference for OM for fibrosis staging, 0.859 (0.012) for FibroTest vs 0.870 (0.009) for VCTE.ConclusionsFrom a single blood sample, the panel provides non-invasive diagnosis of the stages of fibrosis, and the grades of NASH and steatosis in patients with T2DM

Protocol for venoarterial ExtraCorporeal Membrane Oxygenation to reduce morbidity and mortality following bilateral lung TransPlantation: the ECMOToP randomised controlled trial

Introduction Lung transplantation (LTx) aims at improving survival and quality of life for patients with end-stage lung diseases. Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is used as intraoperative support for LTx, despite no precise guidelines for its initiation. We aim to evaluate two strategies of VA-ECMO initiation in the perioperative period in patients with obstructive or restrictive lung disease requiring bilateral LTx. In the control ‘on-demand’ arm, high haemodynamic and respiratory needs will dictate VA-ECMO initiation; in the experimental ‘systematic’ arm, VA-ECMO will be pre-emptively initiated. We hypothesise a ‘systematic’ strategy will increase the number of ventilatory-free days at day 28.Methods and analysis We designed a multicentre randomised controlled trial in parallel groups. Adult patients with obstructive or restrictive lung disease requiring bilateral LTx, without a formal indication for pre-emptive VA-ECMO before LTx, will be included. Patients with preoperative pulmonary hypertension with haemodynamic collapse, ECMO as a bridge to transplantation, severe hypoxaemia or hypercarbia will be secondarily excluded. In the systematic group, VA-ECMO will be systematically implanted before the first pulmonary artery cross-clamp. In the on-demand group, VA-ECMO will be implanted intraoperatively if haemodynamic or respiratory indices meet preplanned criteria. Non-inclusion, secondary exclusion and VA-ECMO initiation criteria were validated by a Delphi process among investigators. Postoperative weaning of ECMO and mechanical ventilation will be managed according to best practice guidelines. The number of ventilator-free days at 28 days (primary endpoint) will be compared between the two groups in the intention-to-treat population. Secondary endpoints encompass organ failure occurrence, day 28, day 90 and year 1 vital status, and adverse events.Ethics and dissemination The sponsor is the Assistance Publique–Hôpitaux de Paris. The ECMOToP protocol version 2.1 was approved by Comité de Protection des Personnes Ile de France VIII. Results will be published in international peer-reviewed medical journals.Trial registration number NCT05664204

Sera Neutralizing Activities Against Severe Acute Respiratory Syndrome Coronavirus 2 and Multiple Variants 6 Months After Hospitalization for Coronavirus Disease 2019

Abstract Background Humoral response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) occurs within the first weeks after coronavirus disease 2019 (COVID-19). Those antibodies exert a neutralizing activity against SARS-CoV-2, whose evolution over time after COVID-19 as well as efficiency against novel variants are poorly characterized. Methods In this prospective study, sera of 107 patients hospitalized with COVID-19 were collected at 3 and 6 months postinfection. We performed quantitative neutralization experiments on top of high-throughput serological assays evaluating anti-spike (S) and anti-nucleocapsid (NP) immunoglobulin G (IgG). Results Levels of seroneutralization and IgG rates against the ancestral strain decreased significantly over time. After 6 months, 2.8% of the patients had a negative serological status for both anti-S and anti-NP IgG. However, all sera had a persistent and effective neutralizing effect against SARS-CoV-2. IgG levels correlated with seroneutralization, and this correlation was stronger for anti-S than for anti-NP antibodies. The level of seroneutralization quantified at 6 months correlated with markers of initial severity, notably admission to intensive care units and the need for mechanical invasive ventilation. In addition, sera collected at 6 months were tested against multiple SARS-CoV-2 variants and showed efficient neutralizing effects against the D614G, B.1.1.7, and P.1 variants but significantly weaker activity against the B.1.351 variant. Conclusions Decrease in IgG rates and serological assays becoming negative did not imply loss of neutralizing capacity. Our results indicate a sustained humoral response against the ancestral strain and the D614G, B.1.1.7, and P.1 variants for at least 6 months in patients previously hospitalized for COVID-19. A weaker protection was, however, observed for the B.1.351 variant. </jats:sec

Impact on disease mortality of clinical, biological, and virological characteristics at hospital admission and overtime in COVID‐19 patients

International audienc