Maintenance therapy in advanced non-small cell lung cancer: A prime-time for change?

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Integrated strategic and tactical optimization of animal-waste sourced biopower supply chains

International audience—Many models have been recently developed for the optimization of biomass related supply chains. However, models for biopower supply chains powered by animal waste have not received much attention yet. In this paper, we propose a mixed integer linear programming model for supplier selection and procurement planning for a biopower plant. The model integrates time window constraints for the collection of animal waste as well as inventory constraints. We show that the model is intractable with a state-of-the art commercial solver and propose a heuristic approach based on the Adaptive Large Neighbourhood Search (ALNS) framework. We show the efficiency of this approach on a case study in central France

Stereotactic ablative radiotherapy for medically inoperable early stage lung cancer: early outcomes

Objective To evaluate the clinical outcome and safety of stereotactic ablative radiotherapy for medically inoperable stage I non- small-cell lung carcinoma. Design Retrospective case series. Setting Pamela Youde Nethersole Eastern Hospital, Hong Kong. Patients All patients with medically inoperable stage I non-small-cell lung carcinoma receiving stereotactic ablative radiotherapy since its establishment in 2008. Main outcome measures Disease control rate, overall survival, and treatment toxicities. Results Sixteen stage I non-small-cell lung carcinoma patients underwent the procedure from June 2008 to November 2011. The median patient age was 82 years and the majority (81%) had moderate-tosevere co-morbidity based on the Adult Comorbidity Evaluation 27 index. With a median follow-up of 22 months, the 2-year primary tumour control rate, disease-free survival and overall survival rates were 91%, 71% and 87%, respectively. No grade 3 (National Cancer Institute Common Terminology Criteria for Adverse Events) or higher treatment-related complications were reported. Conclusion Stereotactic ablative radiotherapy can achieve a high degree of local control safely in medically inoperable patients with early lung cancer.published_or_final_versio

An evaluation of the mental health impact of SARS-CoV-2 on patients, general public and healthcare professionals:A systematic review and meta-analysis

BACKGROUND: The global impact of COVID-19 pandemic continues to affect the lives of billions of people with recurrent waves. Healthcare systems are struggling to manage pre-existing patient care and recurring covid-19 demands. As a result, we evaluated the mental health impact using systematic review and meta-analysis.METHODS: A comprehensive search was undertaken from April 2020 to 22nd January 2021 using multiple electronic databases. A systematic review protocol was developed and published on PROSPERO registration; CRD42020181481. A random-effects model was used to compute pooled estimates of anxiety, depression, PTSD, insomnia and suicidal thoughts.FINDINGS: Our search yielded 11,295 studies and of those 287 met the inclusion criteria. The meta-analysis of 206 studies revealed minimal differences in prevalence of anxiety, depression, and PTSD among HCPs compared with the public during the pandemic but higher prevalence of suicidal thoughts/ideation or self-harm (11% vs 5.8%) and lower prevalence of wellbeing (28.2% vs 52.6%) among the public compared to HCPs.INTERPRETATION: The pandemic has led to a high mental health burden especially amongst HCPs and higher suicidal ideation and lower wellbeing in general public which warrants further investigation and management globally. These findings highlight an emerging critical public health issue that requires urgent solutions.</p

Cardiovascular outcomes and hospitalizations in Asian patients receiving immune checkpoint inhibitors: a population-based study.

Immune checkpoint inhibitors (ICI) have known associations with cardiotoxicity. However, a representative quantification of the adverse cardiovascular events and cardiovascular attendances amongst Asian users of ICI has been lacking. This retrospective cohort study identified all ICI users in Hong Kong, China, between 2013-2021. All patients were followed up until the end of 2021 for the primary outcome of major adverse cardiovascular event (MACE; a composite of cardiovascular mortality, myocardial infarction, heart failure, and stroke). Patients with prior diagnosis of any component of MACE were excluded from all MACE analyses. In total, 4324 patients were analysed (2905 (67.2%) males; median age 63.5 years old (interquartile range 55.4-70.7 years old); median follow-up 1.0 year (interquartile range 0.4-2.3 years)), of whom 153 were excluded from MACE analyses due to prior events. MACE occurred in 116 (2.8%) with an incidence rate (IR) of 1.7 [95% confidence interval: 1.4, 2.0] events per 100 patient-years; IR was higher within the first year of follow-up (2.9 [2.3, 3.5] events per 100 patient-years). Cardiovascular hospitalization(s) occurred in 188 (4.4%) with 254 episodes (0.5% of all episodes) and 1555 days of hospitalization (1.3% of all hospitalized days), for whom the IR of cardiovascular hospitalization was 5.6 [4.6, 6.9] episodes per 100 person-years with 52.9 [39.8, 70.3] days' stay per 100 person-years. Amongst Asian users of ICI, MACE was uncommon, and a small proportion of hospitalizations was cardiovascular in nature. Most MACE and cardiovascular hospitalizations occurred during the first year after initiating ICI. [Abstract copyright: Copyright © 2022. Published by Elsevier Inc.

Effect of natalizumab on disease progression in secondary progressive multiple sclerosis (ASCEND). a phase 3, randomised, double-blind, placebo-controlled trial with an open-label extension

Background: Although several disease-modifying treatments are available for relapsing multiple sclerosis, treatment effects have been more modest in progressive multiple sclerosis and have been observed particularly in actively relapsing subgroups or those with lesion activity on imaging. We sought to assess whether natalizumab slows disease progression in secondary progressive multiple sclerosis, independent of relapses. Methods: ASCEND was a phase 3, randomised, double-blind, placebo-controlled trial (part 1) with an optional 2 year open-label extension (part 2). Enrolled patients aged 18–58 years were natalizumab-naive and had secondary progressive multiple sclerosis for 2 years or more, disability progression unrelated to relapses in the previous year, and Expanded Disability Status Scale (EDSS) scores of 3·0–6·5. In part 1, patients from 163 sites in 17 countries were randomly assigned (1:1) to receive 300 mg intravenous natalizumab or placebo every 4 weeks for 2 years. Patients were stratified by site and by EDSS score (3·0–5·5 vs 6·0–6·5). Patients completing part 1 could enrol in part 2, in which all patients received natalizumab every 4 weeks until the end of the study. Throughout both parts, patients and staff were masked to the treatment received in part 1. The primary outcome in part 1 was the proportion of patients with sustained disability progression, assessed by one or more of three measures: the EDSS, Timed 25-Foot Walk (T25FW), and 9-Hole Peg Test (9HPT). The primary outcome in part 2 was the incidence of adverse events and serious adverse events. Efficacy and safety analyses were done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01416181. Findings: Between Sept 13, 2011, and July 16, 2015, 889 patients were randomly assigned (n=440 to the natalizumab group, n=449 to the placebo group). In part 1, 195 (44%) of 439 natalizumab-treated patients and 214 (48%) of 448 placebo-treated patients had confirmed disability progression (odds ratio [OR] 0·86; 95% CI 0·66–1·13; p=0·287). No treatment effect was observed on the EDSS (OR 1·06, 95% CI 0·74–1·53; nominal p=0·753) or the T25FW (0·98, 0·74–1·30; nominal p=0·914) components of the primary outcome. However, natalizumab treatment reduced 9HPT progression (OR 0·56, 95% CI 0·40–0·80; nominal p=0·001). In part 1, 100 (22%) placebo-treated and 90 (20%) natalizumab-treated patients had serious adverse events. In part 2, 291 natalizumab-continuing patients and 274 natalizumab-naive patients received natalizumab (median follow-up 160 weeks [range 108–221]). Serious adverse events occurred in 39 (13%) patients continuing natalizumab and in 24 (9%) patients initiating natalizumab. Two deaths occurred in part 1, neither of which was considered related to study treatment. No progressive multifocal leukoencephalopathy occurred. Interpretation: Natalizumab treatment for secondary progressive multiple sclerosis did not reduce progression on the primary multicomponent disability endpoint in part 1, but it did reduce progression on its upper-limb component. Longer-term trials are needed to assess whether treatment of secondary progressive multiple sclerosis might produce benefits on additional disability components. Funding: Biogen

The Atacama Large Millimeter/submillimeter Array (ALMA) Band-1 Receiver

The Atacama Large Millimeter/submillimeter Array(ALMA) Band 1 receiver covers the 35-50 GHz frequency band. Development of prototype receivers, including the key components and subsystems has been completed and two sets of prototype receivers were fully tested. We will provide an overview of the ALMA Band 1 science goals, and its requirements and design for use on the ALMA. The receiver development status will also be discussed and the infrastructure, integration, evaluation of fully-assembled band 1 receiver system will be covered. Finally, a discussion of the technical and management challenges encountered will be presented

Cardiovascular outcomes and hospitalizations in Asian patients receiving immune checkpoint inhibitors: A population-based study

Immune checkpoint inhibitors (ICI) have known associations with cardiotoxicity. However, a representative quantification of the adverse cardiovascular events and cardiovascular attendances amongst Asian users of ICI has been lacking. This retrospective cohort study identified all ICI users in Hong Kong, China, between 2013 and 2021. All patients were followed up until the end of 2021 for the primary outcome of major adverse cardiovascular event (MACE; a composite of cardiovascular mortality, myocardial infarction, heart failure, and stroke). Patients with prior diagnosis of any component of MACE were excluded from all MACE analyses. In total, 4324 patients were analyzed (2905 (67.2%) males; median age 63.5 years old (interquartile range 55.4-70.7 years old); median follow-up 1.0 year (interquartile range 0.4-2.3 years)), of whom 153 were excluded from MACE analyses due to prior events. MACE occurred in 116 (2.8%) with an incidence rate (IR) of 1.7 [95% confidence interval: 1.4, 2.0] events per 100 patient-years; IR was higher within the first year of follow-up (2.9 [2.3, 3.5] events per 100 patient-years). Cardiovascular hospitalization(s) occurred in 188 (4.4%) with 254 episodes (0.5% of all episodes) and 1555 days of hospitalization (1.3% of all hospitalized days), for whom the IR of cardiovascular hospitalization was 5.6 [4.6, 6.9] episodes per 100 person-years with 52.9 [39.8, 70.3] days’ stay per 100 person-years. Amongst Asian users of ICI, MACE was uncommon, and a small proportion of hospitalizations were cardiovascular in nature. Most MACE and cardiovascular hospitalizations occurred during the first year after initiating ICI

The replication crisis has led to positive structural, procedural, and community changes

The emergence of large-scale replication projects yielding successful rates substantially lower than expected caused the behavioural, cognitive, and social sciences to experience a so-called ‘replication crisis’. In this Perspective, we reframe this ‘crisis’ through the lens of a credibility revolution, focusing on positive structural, procedural and community-driven changes. Second, we outline a path to expand ongoing advances and improvements. The credibility revolution has been an impetus to several substantive changes which will have a positive, long-term impact on our research environment

The replication crisis has led to positive structural, procedural, and community changes

In response to large-scale replication projects yielding successful replication rates substantially lower than expected, the behavioural, cognitive and social sciences have found themselves amidst a ‘replication crisis’. In this narrative review, we reframe this ’crisis’ through the lens of a credibility revolution, focusing on positive structural, procedural and community-driven changes. Second, we outline a path to expand ongoing advances and improvements. The credibility revolution has been an impetus to several substantive changes which will have a positive, long-term impact upon our research environment