Showing papers by "Laval University published in 2021"

Health effects of climate change: an overview of systematic reviews.

Abstract: Objectives We aimed to develop a systematic synthesis of systematic reviews of health impacts of climate change, by synthesising studies’ characteristics, climate impacts, health outcomes and key findings. Design We conducted an overview of systematic reviews of health impacts of climate change. We registered our review in PROSPERO (CRD42019145972). No ethical approval was required since we used secondary data. Additional data are not available. Data sources On 22 June 2019, we searched Medline, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Embase, Cochrane and Web of Science. Eligibility criteria We included systematic reviews that explored at least one health impact of climate change. Data extraction and synthesis We organised systematic reviews according to their key characteristics, including geographical regions, year of publication and authors’ affiliations. We mapped the climate effects and health outcomes being studied and synthesised major findings. We used a modified version of A MeaSurement Tool to Assess systematic Reviews-2 (AMSTAR-2) to assess the quality of studies. Results We included 94 systematic reviews. Most were published after 2015 and approximately one-fifth contained meta-analyses. Reviews synthesised evidence about five categories of climate impacts; the two most common were meteorological and extreme weather events. Reviews covered 10 health outcome categories; the 3 most common were (1) infectious diseases, (2) mortality and (3) respiratory, cardiovascular or neurological outcomes. Most reviews suggested a deleterious impact of climate change on multiple adverse health outcomes, although the majority also called for more research. Conclusions Most systematic reviews suggest that climate change is associated with worse human health. This study provides a comprehensive higher order summary of research on health impacts of climate change. Study limitations include possible missed relevant reviews, no meta-meta-analyses, and no assessment of overlap. Future research could explore the potential explanations between these associations to propose adaptation and mitigation strategies and could include broader sociopsychological health impacts of climate change.

Attitudes of healthcare workers towards COVID-19 vaccination: a survey in France and French-speaking parts of Belgium and Canada, 2020.

Abstract: In October and November 2020, we conducted a survey of 2,678 healthcare workers (HCWs) involved in general population immunisation in France, French-speaking Belgium and Quebec, Canada to assess acceptance of future COVID-19 vaccines (i.e. willingness to receive or recommend these) and its determinants. Of the HCWs, 48.6% (n = 1,302) showed high acceptance, 23.0% (n = 616) moderate acceptance and 28.4% (n = 760) hesitancy/reluctance. Hesitancy was mostly driven by vaccine safety concerns. These must be addressed before/during upcoming vaccination campaigns.

Pembrolizumab alone or combined with chemotherapy versus chemotherapy as first-line therapy for advanced urothelial carcinoma (KEYNOTE-361): a randomised, open-label, phase 3 trial.

Abstract: Summary Background PD-1 and PD-L1 inhibitors are active in metastatic urothelial carcinoma, but positive randomised data supporting their use as a first-line treatment are lacking. In this study we assessed outcomes with first-line pembrolizumab alone or combined with chemotherapy versus chemotherapy for patients with previously untreated advanced urothelial carcinoma. Methods KEYNOTE-361 is a randomised, open-label, phase 3 trial of patients aged at least 18 years, with untreated, locally advanced, unresectable, or metastatic urothelial carcinoma, with an Eastern Cooperative Oncology Group performance status of up to 2. Eligible patients were enrolled from 201 medical centres in 21 countries and randomly allocated (1:1:1) via an interactive voice-web response system to intravenous pembrolizumab 200 mg every 3 weeks for a maximum of 35 cycles plus intravenous chemotherapy (gemcitabine [1000 mg/m2] on days 1 and 8 and investigator's choice of cisplatin [70 mg/m2] or carboplatin [area under the curve 5] on day 1 of every 3-week cycle) for a maximum of six cycles, pembrolizumab alone, or chemotherapy alone, stratified by choice of platinum therapy and PD-L1 combined positive score (CPS). Neither patients nor investigators were masked to the treatment assignment or CPS. At protocol-specified final analysis, sequential hypothesis testing began with superiority of pembrolizumab plus chemotherapy versus chemotherapy alone in the total population (all patients randomly allocated to a treatment) for the dual primary endpoints of progression-free survival (p value boundary 0·0019), assessed by masked, independent central review, and overall survival (p value boundary 0·0142), followed by non-inferiority and superiority of overall survival for pembrolizumab versus chemotherapy in the patient population with CPS of at least 10 and in the total population (also a primary endpoint). Safety was assessed in the as-treated population (all patients who received at least one dose of study treatment). This study is completed and is no longer enrolling patients, and is registered at ClinicalTrials.gov , number NCT02853305 . Findings Between Oct 19, 2016 and June 29, 2018, 1010 patients were enrolled and allocated to receive pembrolizumab plus chemotherapy (n=351), pembrolizumab monotherapy (n=307), or chemotherapy alone (n=352). Median follow-up was 31·7 months (IQR 27·7–36·0). Pembrolizumab plus chemotherapy versus chemotherapy did not significantly improve progression-free survival, with a median progression-free survival of 8·3 months (95% CI 7·5–8·5) in the pembrolizumab plus chemotherapy group versus 7·1 months (6·4–7·9) in the chemotherapy group (hazard ratio [HR] 0·78, 95% CI 0·65–0·93; p=0·0033), or overall survival, with a median overall survival of 17·0 months (14·5–19·5) in the pembrolizumab plus chemotherapy group versus 14·3 months (12·3–16·7) in the chemotherapy group (0·86, 0·72–1·02; p=0·0407). No further formal statistical hypothesis testing was done. In analyses of overall survival with pembrolizumab versus chemotherapy (now exploratory based on hierarchical statistical testing), overall survival was similar between these treatment groups, both in the total population (15·6 months [95% CI 12·1–17·9] with pembrolizumab vs 14·3 months [12·3–16·7] with chemotherapy; HR 0·92, 95% CI 0·77–1·11) and the population with CPS of at least 10 (16·1 months [13·6–19·9] with pembrolizumab vs 15·2 months [11·6–23·3] with chemotherapy; 1·01, 0·77–1·32). The most common grade 3 or 4 adverse event attributed to study treatment was anaemia with pembrolizumab plus chemotherapy (104 [30%] of 349 patients) or chemotherapy alone (112 [33%] of 342 patients), and diarrhoea, fatigue, and hyponatraemia (each affecting four [1%] of 302 patients) with pembrolizumab alone. Six (1%) of 1010 patients died due to an adverse event attributed to study treatment; two patients in each treatment group. One each occurred due to cardiac arrest and device-related sepsis in the pembrolizumab plus chemotherapy group, one each due to cardiac failure and malignant neoplasm progression in the pembrolizumab group, and one each due to myocardial infarction and ischaemic colitis in the chemotherapy group. Interpretation The addition of pembrolizumab to first-line platinum-based chemotherapy did not significantly improve efficacy and should not be widely adopted for treatment of advanced urothelial carcinoma. Funding Merck Sharp and Dohme, a subsidiary of Merck, Kenilworth, NJ, USA.

Nanoplastics are neither microplastics nor engineered nanoparticles

Abstract: Increasing concern and research on the subject of plastic pollution has engaged the community of scientists working on the environmental health and safety of nanomaterials. While many of the methods developed in nano environment, health and safety work have general applicability to the study of particulate plastics, the nanometric size range has important consequences for both the analytical challenges of studying nanoscale plastics and the environmental implications of these incidental nanomaterials. Related to their size, nanoplastics are distinguished from microplastics with respect to their transport properties, interactions with light and natural colloids, a high fraction of particle molecules on the surface, bioavailability and diffusion times for the release of plastic additives. Moreover, they are distinguished from engineered nanomaterials because of their high particle heterogeneity and their potential for rapid further fragmentation in the environment. These characteristics impact environmental fate, potential effects on biota and human health, sampling and analysis. Like microplastics, incidentally produced nanoplastics exhibit a diversity of compositions and morphologies and a heterogeneity that is typically absent from engineered nanomaterials. Therefore, nanoscale plastics must be considered as distinct from both microplastics and engineered nanomaterials.

Valve Academic Research Consortium 3: updated endpoint definitions for aortic valve clinical research

Abstract: Aims The Valve Academic Research Consortium (VARC), founded in 2010, was intended to (i) identify appropriate clinical endpoints and (ii) standardize definitions of these endpoints for transcatheter and surgical aortic valve clinical trials. Rapid evolution of the field, including the emergence of new complications, expanding clinical indications, and novel therapy strategies have mandated further refinement and expansion of these definitions to ensure clinical relevance. This document provides an update of the most appropriate clinical endpoint definitions to be used in the conduct of transcatheter and surgical aortic valve clinical research. Methods and results Several years after the publication of the VARC-2 manuscript, an in-person meeting was held involving over 50 independent clinical experts representing several professional societies, academic research organizations, the US Food and Drug Administration (FDA), and industry representatives to (i) evaluate utilization of VARC endpoint definitions in clinical research, (ii) discuss the scope of this focused update, and (iii) review and revise specific clinical endpoint definitions. A writing committee of independent experts was convened and subsequently met to further address outstanding issues. There were ongoing discussions with FDA and many experts to develop a new classification schema for bioprosthetic valve dysfunction and failure. Overall, this multi-disciplinary process has resulted in important recommendations for data reporting, clinical research methods, and updated endpoint definitions. New definitions or modifications of existing definitions are being proposed for repeat hospitalizations, access site-related complications, bleeding events, conduction disturbances, cardiac structural complications, and bioprosthetic valve dysfunction and failure (including valve leaflet thickening and thrombosis). A more granular 5-class grading scheme for paravalvular regurgitation (PVR) is being proposed to help refine the assessment of PVR. Finally, more specific recommendations on quality-of-life assessments have been included, which have been targeted to specific clinical study designs. Conclusions Acknowledging the dynamic and evolving nature of less-invasive aortic valve therapies, further refinements of clinical research processes are required. The adoption of these updated and newly proposed VARC-3 endpoints and definitions will ensure homogenous event reporting, accurate adjudication, and appropriate comparisons of clinical research studies involving devices and new therapeutic strategies.

Pandemics Throughout History

Abstract: The emergence and spread of infectious diseases with pandemic potential occurred regularly throughout history. Major pandemics and epidemics such as plague, cholera, flu, severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) have already afflicted humanity. The world is now facing the new coronavirus disease 2019 (COVID-19) pandemic. Many infectious diseases leading to pandemics are caused by zoonotic pathogens that were transmitted to humans due to increased contacts with animals through breeding, hunting and global trade activities. The understanding of the mechanisms of transmission of pathogens to humans allowed the establishment of methods to prevent and control infections. During centuries, implementation of public health measures such as isolation, quarantine and border control helped to contain the spread of infectious diseases and maintain the structure of the society. In the absence of pharmaceutical interventions, these containment methods have still been used nowadays to control COVID-19 pandemic. Global surveillance programs of water-borne pathogens, vector-borne diseases and zoonotic spillovers at the animal-human interface are of prime importance to rapidly detect the emergence of infectious threats. Novel technologies for rapid diagnostic testing, contact tracing, drug repurposing, biomarkers of disease severity as well as new platforms for the development and production of vaccines are needed for an effective response in case of pandemics.

The international EAACI/GA²LEN/EuroGuiDerm/APAAACI guideline for the definition, classification, diagnosis, and management of urticaria.

Abstract: This update and revision of the international guideline for urticaria was developed following the methods recommended by Cochrane and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group. It is a joint initiative of the Dermatology Section of the European Academy of Allergology and Clinical Immunology (EAACI), the Global Allergy and Asthma European Network (GA²LEN) and its Urticaria and Angioedema Centers of Reference and Excellence (UCAREs and ACAREs), the European Dermatology Forum (EDF; EuroGuiDerm), and the Asia Pacific Association of Allergy, Asthma and Clinical Immunology with the participation of 64 delegates of 50 national and international societies and from 31 countries. The consensus conference was held on 3 December 2020. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS). Urticaria is a frequent, mast cell-driven disease that presents with wheals, angioedema, or both. The lifetime prevalence for acute urticaria is approximately 20%. Chronic spontaneous or inducible urticaria is disabling, impairs quality of life, and affects performance at work and school. This updated version of the international guideline for urticaria covers the definition and classification of urticaria and outlines expert-guided and evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria.

Tralokinumab for moderate‐to‐severe atopic dermatitis: results from two 52‐week, randomized, double‐blind, multicentre, placebo‐controlled phase III trials (ECZTRA 1 and ECZTRA 2)*

Abstract: Background Tralokinumab, a fully human monoclonal antibody, specifically neutralizes interleukin-13, a key cytokine driving peripheral inflammation in atopic dermatitis (AD). In phase II studies, tralokinumab combined with topical corticosteroids provided early and sustained improvements in AD signs and symptoms. Objectives To evaluate the efficacy and safety of tralokinumab monotherapy in adults with moderate-to-severe AD who had an inadequate response to topical treatments. Methods In two, 52-week, randomized, double-blind, placebo-controlled, phase III trials, ECZTRA 1 and ECZTRA 2, adults with moderate-to-severe AD were randomized (3 : 1) to subcutaneous tralokinumab 300 mg every 2 weeks (Q2W), or placebo. Primary endpoints were IGA score of 0 or 1 at week 16 and EASI 75 at week 16. Patient achieving an IGA score of 0/1 and/or EASI 75 with tralokinumab at week 16 were rerandomized to tralokinumab Q2W or every 4 weeks or placebo, for 36 weeks. Results At week 16, more patients who received tralokinumab vs. placebo achieved an IGA score of 0/1: 15·8% vs. 7·1% in ECZTRA 1 [difference (95% CI) 8·6% (4·1-13·1); P = 0·002] and 22·2% vs. 10·9% in ECZTRA 2 [11·1% (5·8-16·4); P Conclusions Tralokinumab monotherapy was superior to placebo at 16 weeks of treatment and was well tolerated up to 52 weeks of treatment.

Bacteriocins as a new generation of antimicrobials: toxicity aspects and regulations

Abstract: In recent decades, bacteriocins have received substantial attention as antimicrobial compounds. Although bacteriocins have been predominantly exploited as food preservatives, they are now receiving increased attention as potential clinical antimicrobials and as possible immune-modulating agents. Infections caused by antibiotic-resistant bacteria have been declared as a global threat to public health. Bacteriocins represent a potential solution to this worldwide threat due to their broad- or narrow-spectrum activity against antibiotic-resistant bacteria. Notably, despite their role in food safety as natural alternatives to chemical preservatives, nisin remains the only bacteriocin legally approved by regulatory agencies as a food preservative. Moreover, insufficient data on the safety and toxicity of bacteriocins represent a barrier against the more widespread use of bacteriocins by the food and medical industry. Here, we focus on the most recent trends relating to the application of bacteriocins, their toxicity and impacts.

Key competencies in sustainability in higher education : toward an agreed-upon reference framework

Abstract: Hundreds of sustainability programs have emerged at universities and colleges around the world over the past 2 decades. A prime question for employers, students, educators, and program administrators is what competencies these programs develop in students. This study explores convergence on competencies for sustainability programs. We conducted a Delphi study with 14 international experts in sustainability education on the framework of key competencies in sustainability by Wiek et al. (Sustain Sci 6: 203–218, 2011), the most frequently cited framework to date. While experts generally agreed with the framework, they propose two additional competencies, suggest a hierarchy of competencies, and specify learning objectives for students interested in a career as sustainability researcher. The refined framework can inform program development, implementation, and evaluation to enhance employability of graduates and facilitate comparison of sustainability programs worldwide.

A proximity-dependent biotinylation map of a human cell.

Abstract: Compartmentalization is a defining characteristic of eukaryotic cells, and partitions distinct biochemical processes into discrete subcellular locations. Microscopy1 and biochemical fractionation coupled with mass spectrometry2–4 have defined the proteomes of a variety of different organelles, but many intracellular compartments have remained refractory to such approaches. Proximity-dependent biotinylation techniques such as BioID provide an alternative approach to define the composition of cellular compartments in living cells5–7. Here we present a BioID-based map of a human cell on the basis of 192 subcellular markers, and define the intracellular locations of 4,145 unique proteins in HEK293 cells. Our localization predictions exceed the specificity of previous approaches, and enabled the discovery of proteins at the interface between the mitochondrial outer membrane and the endoplasmic reticulum that are crucial for mitochondrial homeostasis. On the basis of this dataset, we created humancellmap.org as a community resource that provides online tools for localization analysis of user BioID data, and demonstrate how this resource can be used to understand BioID results better. A proximity-dependent biotinylation technique defines the location of more than 4,000 proteins in a human cell, and almost 36,000 proximal interactions between proteins, including those at the interface of the mitochondria and ER.

Sum Rate Maximization for IRS-Assisted Uplink NOMA

Abstract: An intelligent reflecting surface (IRS) consists of a large number of low-cost reflecting elements, which can steer the incident signal collaboratively by passive beamforming. This way, IRS reconfigures the wireless environment to boost the system performance. In this letter, we consider an IRS-assisted uplink non-orthogonal multiple access (NOMA) system. The objective is to maximize the sum rate of all users under individual power constraint. The considered problem requires a joint power control at the users and beamforming design at the IRS, and is non-convex. To handle it, semidefinite relaxation is employed, which provides a near-optimal solution. Presented numerical results show that the proposed NOMA-based scheme achieves a larger sum rate than orthogonal multiple access (OMA)-based one. Moreover, the impact of the number of reflecting elements on the sum rate is revealed.

Arterial and venous thromboembolism in COVID-19: a study-level meta-analysis.

Abstract: Background The prevalence of venous thromboembolic event (VTE) and arterial thromboembolic event (ATE) thromboembolic events in patients with COVID-19 remains largely unknown. Methods In this meta-analysis, we systematically searched for observational studies describing the prevalence of VTE and ATE in COVID-19 up to 30 September 2020. Results We analysed findings from 102 studies (64 503 patients). The frequency of COVID-19-related VTE was 14.7% (95% CI 12.1% to 17.6%, I2=94%; 56 studies; 16 507 patients). The overall prevalence rates of pulmonary embolism (PE) and leg deep vein thrombosis were 7.8% (95% CI 6.2% to 9.4%, I2=94%; 66 studies; 23 117 patients) and 11.2% (95% CI 8.4% to 14.3%, I2=95%; 48 studies; 13 824 patients), respectively. Few were isolated subsegmental PE. The VTE prevalence was significantly higher in intensive care unit (ICU) (23.2%, 95% CI 17.5% to 29.6%, I2=92%, vs 9.0%, 95% CI 6.9% to 11.4%, I2=95%; pinteraction Conclusions Patients admitted in the ICU for severe COVID-19 had a high risk of VTE. Conversely, further studies are needed to determine the specific effects of COVID-19 on the risk of ATE or VTE in less severe forms of the disease.

Widespread deoxygenation of temperate lakes

Abstract: The concentration of dissolved oxygen in aquatic systems helps to regulate biodiversity1,2, nutrient biogeochemistry3, greenhouse gas emissions4, and the quality of drinking water5. The long-term declines in dissolved oxygen concentrations in coastal and ocean waters have been linked to climate warming and human activity6,7, but little is known about the changes in dissolved oxygen concentrations in lakes. Although the solubility of dissolved oxygen decreases with increasing water temperatures, long-term lake trajectories are difficult to predict. Oxygen losses in warming lakes may be amplified by enhanced decomposition and stronger thermal stratification8,9 or oxygen may increase as a result of enhanced primary production10. Here we analyse a combined total of 45,148 dissolved oxygen and temperature profiles and calculate trends for 393 temperate lakes that span 1941 to 2017. We find that a decline in dissolved oxygen is widespread in surface and deep-water habitats. The decline in surface waters is primarily associated with reduced solubility under warmer water temperatures, although dissolved oxygen in surface waters increased in a subset of highly productive warming lakes, probably owing to increasing production of phytoplankton. By contrast, the decline in deep waters is associated with stronger thermal stratification and loss of water clarity, but not with changes in gas solubility. Our results suggest that climate change and declining water clarity have altered the physical and chemical environment of lakes. Declines in dissolved oxygen in freshwater are 2.75 to 9.3 times greater than observed in the world’s oceans6,7 and could threaten essential lake ecosystem services2,3,5,11. Analysis of temperate lakes finds a widespread decline in dissolved oxygen concentrations in surface and deep waters, which is associated with reduced solubility at warmer surface water temperatures and increased stratification at depth.

Convalescent plasma for hospitalized patients with COVID-19: an open-label, randomized controlled trial.

Abstract: The efficacy of convalescent plasma for coronavirus disease 2019 (COVID-19) is unclear. Although most randomized controlled trials have shown negative results, uncontrolled studies have suggested that the antibody content could influence patient outcomes. We conducted an open-label, randomized controlled trial of convalescent plasma for adults with COVID-19 receiving oxygen within 12 d of respiratory symptom onset ( NCT04348656 ). Patients were allocated 2:1 to 500 ml of convalescent plasma or standard of care. The composite primary outcome was intubation or death by 30 d. Exploratory analyses of the effect of convalescent plasma antibodies on the primary outcome was assessed by logistic regression. The trial was terminated at 78% of planned enrollment after meeting stopping criteria for futility. In total, 940 patients were randomized, and 921 patients were included in the intention-to-treat analysis. Intubation or death occurred in 199/614 (32.4%) patients in the convalescent plasma arm and 86/307 (28.0%) patients in the standard of care arm-relative risk (RR) = 1.16 (95% confidence interval (CI) 0.94-1.43, P = 0.18). Patients in the convalescent plasma arm had more serious adverse events (33.4% versus 26.4%; RR = 1.27, 95% CI 1.02-1.57, P = 0.034). The antibody content significantly modulated the therapeutic effect of convalescent plasma. In multivariate analysis, each standardized log increase in neutralization or antibody-dependent cellular cytotoxicity independently reduced the potential harmful effect of plasma (odds ratio (OR) = 0.74, 95% CI 0.57-0.95 and OR = 0.66, 95% CI 0.50-0.87, respectively), whereas IgG against the full transmembrane spike protein increased it (OR = 1.53, 95% CI 1.14-2.05). Convalescent plasma did not reduce the risk of intubation or death at 30 d in hospitalized patients with COVID-19. Transfusion of convalescent plasma with unfavorable antibody profiles could be associated with worse clinical outcomes compared to standard care.

2020 taxonomic update for phylum Negarnaviricota (Riboviria: Orthornavirae), including the large orders Bunyavirales and Mononegavirales

Abstract: In March 2020, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote on newly proposed taxa, the phylum Negarnaviricota was amended and emended. At the genus rank, 20 new genera were added, two were deleted, one was moved, and three were renamed. At the species rank, 160 species were added, four were deleted, ten were moved and renamed, and 30 species were renamed. This article presents the updated taxonomy of Negarnaviricota as now accepted by the ICTV.

Adjusting to epidemic-induced telework: empirical insights from teleworkers in France

Abstract: The covid-19 pandemic crisis presents unprecedented challenges and has profound implications for the way people live and work. Information and communication technologies have been playing a crucial...

Impact of the COVID-19 Pandemic on Older Adults: Rapid Review.

Abstract: Background: The COVID-19 pandemic has drastically changed the lives of countless members of the general population. Older adults are known to experience loneliness, age discrimination, and excessive worry. It is therefore reasonable to anticipate that they would experience greater negative outcomes related to the COVID-19 pandemic given their increased isolation and risk for complications than younger adults. Objective: This study aims to synthesize the existing research on the impact of the COVID-19 pandemic, and associated isolation and protective measures, on older adults. The secondary objective is to investigate the impact of the COVID-19 pandemic, and associated isolation and protective measures, on older adults with Alzheimer disease and related dementias. Methods: A rapid review of the published literature was conducted on October 6, 2020, through a search of 6 online databases to synthesize results from published original studies regarding the impact of the COVID-19 pandemic on older adults. The Human Development Model conceptual framework–Disability Creation Process was used to describe and understand interactions between personal factors, environmental factors, and life habits. Methods and results are reported following the Preferred Reporting Items for Systematic Reviews and Meta-analyses Statement. Results: A total of 135 records were included from the initial search strategy of 13,452 individual studies. Of these, 113 (83.7%) studies were determined to be of level 4 according to the levels of evidence classification by the Centre for Evidence-Based Medicine. The presence of psychological symptoms, exacerbation of ageism, and physical deterioration of aged populations were reported in the included studies. Decreased social life and fewer in-person social interactions reported during the COVID-19 pandemic were occasionally associated with reduced quality of life and increased depression. Difficulties accessing services, sleep disturbances, and a reduction of physical activity were also noted. Conclusions: Our results highlight the need for adequate isolation and protective measures. Older adults represent a heterogeneous group, which could explain the contradictory results found in the literature. Individual, organizational, and institutional strategies should be established to ensure that older adults are able to maintain social contacts, preserve family ties, and maintain the ability to give or receive help during the current pandemic. Future studies should focus on specific consequences and needs of more at-risk older adults to ensure their inclusion, both in public health recommendations and considerations made by policy makers.

Low-Bandgap Non-fullerene Acceptors Enabling High-Performance Organic Solar Cells

Abstract: Great progress in organic solar cells (OSCs) has been recently achieved owing to the advent of non-fullerene acceptors (NFAs). Indeed, low-bandgap NFAs ranging from 1.3 to 1.6 eV with broad absorpt...

Palbociclib with adjuvant endocrine therapy in early breast cancer (PALLAS): interim analysis of a multicentre, open-label, randomised, phase 3 study.

Abstract: Summary Background Palbociclib added to endocrine therapy improves progression-free survival in hormone-receptor-positive, HER2-negative, metastatic breast cancer. The PALLAS trial aimed to investigate whether the addition of 2 years of palbociclib to adjuvant endocrine therapy improves invasive disease-free survival over endocrine therapy alone in patients with hormone-receptor-positive, HER2-negative, early-stage breast cancer. Methods PALLAS is an ongoing multicentre, open-label, randomised, phase 3 study that enrolled patients at 406 cancer centres in 21 countries worldwide with stage II–III histologically confirmed hormone-receptor-positive, HER2-negative breast cancer, within 12 months of initial diagnosis. Eligible patients were aged 18 years or older with an Eastern Cooperative Oncology Group performance score of 0 or 1. Patients were randomly assigned (1:1) in permuted blocks of random size (4 or 6), stratified by anatomic stage, previous chemotherapy, age, and geographical region, by use of central telephone-based and web-based interactive response technology, to receive either 2 years of palbociclib (125 mg orally once daily on days 1–21 of a 28-day cycle) with ongoing standard provider or patient-choice adjuvant endocrine therapy (tamoxifen or aromatase inhibitor, with or without concurrent luteinising hormone-releasing hormone agonist), or endocrine therapy alone, without masking. The primary endpoint of the study was invasive disease-free survival in the intention-to-treat population. Safety was assessed in all randomly assigned patients who started palbociclib or endocrine therapy. This report presents results from the second pre-planned interim analysis triggered on Jan 9, 2020, when 67% of the total number of expected invasive disease-free survival events had been observed. The trial is registered with ClinicalTrials.gov (NCT02513394) and EudraCT (2014-005181-30). Findings Between Sept 1, 2015, and Nov 30, 2018, 5760 patients were randomly assigned to receive palbociclib plus endocrine therapy (n=2883) or endocrine therapy alone (n=2877). At the time of the planned second interim analysis, at a median follow-up of 23·7 months (IQR 16·9–29·2), 170 of 2883 patients assigned to palbociclib plus endocrine therapy and 181 of 2877 assigned to endocrine therapy alone had invasive disease-free survival events. 3-year invasive disease-free survival was 88·2% (95% CI 85·2–90·6) for palbociclib plus endocrine therapy and 88·5% (85·8–90·7) for endocrine therapy alone (hazard ratio 0·93 [95% CI 0·76–1·15]; log-rank p=0·51). As the test statistic comparing invasive disease-free survival between groups crossed the prespecified futility boundary, the independent data monitoring committee recommended discontinuation of palbociclib in patients still receiving palbociclib and endocrine therapy. The most common grade 3–4 adverse events were neutropenia (1742 [61·3%] of 2840 patients on palbociclib and endocrine therapy vs 11 [0·3%] of 2903 on endocrine therapy alone), leucopenia (857 [30·2%] vs three [0·1%]), and fatigue (60 [2·1%] vs ten [0·3%]). Serious adverse events occurred in 351 (12·4%) of 2840 patients on palbociclib plus endocrine therapy versus 220 (7·6%) of 2903 patients on endocrine therapy alone. There were no treatment-related deaths. Interpretation At the planned second interim analysis, addition of 2 years of adjuvant palbociclib to adjuvant endocrine therapy did not improve invasive disease-free survival compared with adjuvant endocrine therapy alone. On the basis of these findings, this regimen cannot be recommended in the adjuvant setting. Long-term follow-up of the PALLAS population and correlative studies are ongoing. Funding Pfizer.

Open-Label, Single-Arm, Phase II Study of Pembrolizumab Monotherapy as First-Line Therapy in Patients With Advanced Non-Clear Cell Renal Cell Carcinoma.

Abstract: PURPOSEPembrolizumab, a programmed death 1 inhibitor, demonstrated promising single-agent activity in untreated patients with various cancer types The phase II KEYNOTE-427 study evaluated efficacy

Polypill with or without Aspirin in Persons without Cardiovascular Disease.

Abstract: Background A polypill comprising statins, multiple blood-pressure–lowering drugs, and aspirin has been proposed to reduce the risk of cardiovascular disease. Methods Using a 2-by-2-by-2 fa...

Vaccine Hesitancy, Acceptance, and Anti-Vaccination: Trends and Future Prospects for Public Health.

Abstract: An often-stated public health comment is that "vaccination is a victim of its own success." While the scientific and medical consensus on the benefits of vaccination is clear and unambiguous, an increasing number of people are perceiving vaccines as unsafe and unnecessary. The World Health Organization identified "the reluctance or refusal to vaccinate despite availability of vaccines" as one of the 10 threats to global health in 2019. The negative influence of anti-vaccination movements is often named as a cause of increasing vaccine resistance in the public. In this review, we give an overview of the current literature on the topic, beginning by agreeing on terminology and concepts before looking at potential causes, consequences, and impacts of resistance to vaccination.

Student Motivation and Associated Outcomes: A Meta-Analysis From Self-Determination Theory:

Abstract: Student outcomes are influenced by different types of motivation that stem from external incentives, ego involvement, personal value, and intrinsic interest. The types of motivation described in self-determination theory each co-occur to different degrees and should lead to different consequences. The associations with outcomes are due in part to unique characteristics and in part to the degree of autonomy each entails. In the current meta-analysis, we examine these different types of motivation in 344 samples (223,209 participants) as they relate to 26 performance, well-being, goal orientation, and persistence-related student outcomes. Findings highlight that intrinsic motivation is related to student success and well-being, whereas personal value (identified regulation) is particularly highly related to persistence. Ego-involved motives (introjected regulation) were positively related to persistence and performance goals but also positively related with indicators of ill-being. Motivation driven by a desire to obtain rewards or avoid punishment (external regulation) was not associated with performance or persistence but was associated with decreased well-being. Finally, amotivation was related to poor outcomes. Relative weights analysis further estimates the degree to which motivation types uniquely predict outcomes, highlighting that identified regulation and intrinsic motivation are likely key factors for school adjustment.