Publications by authors named "Mark Levine"

299 Publications

Addressing silent hypoxemia with COVID-19: Implementation of an outpatient pulse oximetry program in Vermont.

Public Health Pract (Oxf) 2021 Nov 27;2:100186. Epub 2021 Aug 27.

Vermont Department of Health, Burlington, VT, USA.

Objectives: We initiated an outpatient pulse oximetry program to facilitate more rapid detection of clinical deterioration of persons with COVID-19.

Methods: Vermont residents in non-congregate settings with laboratory-confirmed SARS-CoV-2 infection were eligible for inclusion.

Results: Acceptance of pulse oximetry occurred more frequently among those who were older or symptomatic, spoke English, or who had underlying medical conditions.

Conclusions: We provide the first description of an outpatient pulse oximetry program for COVID-19 by a state health department in the U.S.
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http://dx.doi.org/10.1016/j.puhip.2021.100186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8390119PMC
November 2021

Metformin in Combination With Chemoradiotherapy in Locally Advanced Non-Small Cell Lung Cancer: The OCOG-ALMERA Randomized Clinical Trial.

JAMA Oncol 2021 Sep;7(9):1333-1341

Juravinski Cancer Center, Hamilton Health Science, Hamilton, Ontario, Canada.

Importance: Unresected locally advanced non-small cell lung cancer (LA-NSCLC) shows poor survival outcomes even after aggressive concurrent chemoradiotherapy. Whether metformin, a diabetes agent that inhibits the mitochondria oxidative phosphorylation chain, could improve radiotherapy and chemotherapy response in LA-NSCLC remains to be studied.

Objective: To examine whether metformin, given concurrently with chemoradiotherapy and as consolidation treatment, could improve outcomes in patients with LA-NSCLC.

Design, Setting, And Participants: The Ontario Clinical Oncology Group Advanced Lung Cancer Treatment With Metformin and Chemoradiotherapy (OCOG-ALMERA) study was a multicenter phase 2 randomized clinical trial. Patients were stratified for stage IIIA vs IIIB LA-NSCLC and use of consolidation chemotherapy. The trial was designed to enroll 96 patients with unresected LA-NSCLC who did not have diabetes. The trial was conducted from September 24, 2014, to March 8, 2019.

Interventions: Patients were randomized to platinum-based chemotherapy, concurrent with chest radiotherapy (60-63 Gy), with or without consolidation chemotherapy or the same treatment plus metformin, 2000 mg/d, during chemoradiotherapy and afterward for up to 12 months.

Main Outcomes And Measures: The primary outcome was the proportion of patients who experienced a failure event (ie, locoregional disease progression, distant metastases, death, and discontinuation of trial treatment or planned evaluations for any reason within 12 months). Proportions were compared using a 2-sided Fisher exact test. Conventional progression-free and overall survival were estimated using the Kaplan-Meier method. Adverse events were graded with Common Terminology Criteria for Adverse Events, version 4.03. All randomized patients were included in an intention-to-treat analysis.

Results: The trial was stopped early due to slow accrual. Between 2014 and 2019, 54 patients were randomized (26 in experimental arm and 28 in control arm). Participants included 30 women (55.6%); mean (SD) age was 65.6 (7.6) years. Treatment failure was detected in 18 patients (69.2%) receiving metformin within 1 year vs 12 (42.9%) control patients (P = .05). The 1-year progression-free survival rate was 34.8% (95% CI, 16.6%-53.7%) in the metformin arm and 63.0% (95% CI, 42.1%-78.1%) in the control arm (hazard ratio, 2.42; 95% CI, 1.14-5.10) The overall survival rates were 47.4% (95% CI, 26.3%-65.9%) in the metformin arm and 85.2% (95% CI, 65.2%-94.2%) in the control arm (hazard ratio, 3.80; 95% CI, 1.49-9.73). More patients in the experimental arm vs control arm (53.8% vs 25.0%) reported at least 1 grade 3 or higher adverse event.

Conclusions And Relevance: In this randomized clinical trial, the addition of metformin to chemoradiotherapy was associated with worse treatment efficacy and increased toxic effects compared with combined modality therapy alone. Metformin is not recommended in patients with LA-NSCLC who are candidates for chemoradiotherapy.

Trial Registration: ClinicalTrials.gov Identifier: NCT02115464.
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http://dx.doi.org/10.1001/jamaoncol.2021.2328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8323053PMC
September 2021

Metformin in Combination With Chemoradiotherapy in Locally Advanced Non-Small Cell Lung Cancer: The OCOG-ALMERA Randomized Clinical Trial.

JAMA Oncol 2021 Sep;7(9):1333-1341

Juravinski Cancer Center, Hamilton Health Science, Hamilton, Ontario, Canada.

Importance: Unresected locally advanced non-small cell lung cancer (LA-NSCLC) shows poor survival outcomes even after aggressive concurrent chemoradiotherapy. Whether metformin, a diabetes agent that inhibits the mitochondria oxidative phosphorylation chain, could improve radiotherapy and chemotherapy response in LA-NSCLC remains to be studied.

Objective: To examine whether metformin, given concurrently with chemoradiotherapy and as consolidation treatment, could improve outcomes in patients with LA-NSCLC.

Design, Setting, And Participants: The Ontario Clinical Oncology Group Advanced Lung Cancer Treatment With Metformin and Chemoradiotherapy (OCOG-ALMERA) study was a multicenter phase 2 randomized clinical trial. Patients were stratified for stage IIIA vs IIIB LA-NSCLC and use of consolidation chemotherapy. The trial was designed to enroll 96 patients with unresected LA-NSCLC who did not have diabetes. The trial was conducted from September 24, 2014, to March 8, 2019.

Interventions: Patients were randomized to platinum-based chemotherapy, concurrent with chest radiotherapy (60-63 Gy), with or without consolidation chemotherapy or the same treatment plus metformin, 2000 mg/d, during chemoradiotherapy and afterward for up to 12 months.

Main Outcomes And Measures: The primary outcome was the proportion of patients who experienced a failure event (ie, locoregional disease progression, distant metastases, death, and discontinuation of trial treatment or planned evaluations for any reason within 12 months). Proportions were compared using a 2-sided Fisher exact test. Conventional progression-free and overall survival were estimated using the Kaplan-Meier method. Adverse events were graded with Common Terminology Criteria for Adverse Events, version 4.03. All randomized patients were included in an intention-to-treat analysis.

Results: The trial was stopped early due to slow accrual. Between 2014 and 2019, 54 patients were randomized (26 in experimental arm and 28 in control arm). Participants included 30 women (55.6%); mean (SD) age was 65.6 (7.6) years. Treatment failure was detected in 18 patients (69.2%) receiving metformin within 1 year vs 12 (42.9%) control patients (P = .05). The 1-year progression-free survival rate was 34.8% (95% CI, 16.6%-53.7%) in the metformin arm and 63.0% (95% CI, 42.1%-78.1%) in the control arm (hazard ratio, 2.42; 95% CI, 1.14-5.10) The overall survival rates were 47.4% (95% CI, 26.3%-65.9%) in the metformin arm and 85.2% (95% CI, 65.2%-94.2%) in the control arm (hazard ratio, 3.80; 95% CI, 1.49-9.73). More patients in the experimental arm vs control arm (53.8% vs 25.0%) reported at least 1 grade 3 or higher adverse event.

Conclusions And Relevance: In this randomized clinical trial, the addition of metformin to chemoradiotherapy was associated with worse treatment efficacy and increased toxic effects compared with combined modality therapy alone. Metformin is not recommended in patients with LA-NSCLC who are candidates for chemoradiotherapy.

Trial Registration: ClinicalTrials.gov Identifier: NCT02115464.
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http://dx.doi.org/10.1001/jamaoncol.2021.2328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8323053PMC
September 2021

'Oh no, not a group!' The factors that lonely or isolated people report as barriers to joining groups for health and well-being.

Br J Health Psychol 2021 May 24. Epub 2021 May 24.

University of Exeter, Psychology, UK.

Objectives: Belonging to groups can significantly affect people's health and well-being for the better ('the social cure') or worse ('the social curse'). Encouraging people to join groups is a central component of the Social Prescribing movement; however, not everyone who might benefit from Social Prescribing aspires to participating in groups. This study aims to identify what barriers are preventing people from experiencing the associated health and well-being benefits of group belonging.

Method: Semi-structured interviews analysed using reflexive thematic analysis. Participants were 11 white British people (aged 48-86), 1 male and 10 female, recruited by a charity partner of a Social Prescribing project.

Results: The themes derived from the interviews are as follows: (1) 'The dread, the fear of being in a group': When groups do not meet needs; (2) 'I can remember as quite a young child backing out of things': Accumulative barriers over the lifetime, and (3) 'I'm singing away and feeling terribly miserable': the challenges of fitting in with others in groups. The themes reflect how people can feel deterred from social interaction, which interferes with their ability to derive a sense of belonging or shared identity associated with the 'social cure'.

Conclusions: A key challenge for Social Prescribing is to meet the social needs of people disinclined to join groups; groups can be detrimental to health and well-being if there are barriers to integration. Alternative ways of structuring groups or activities may be more effective and can still avail of the belonging and identity associated with 'the social cure'.
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http://dx.doi.org/10.1111/bjhp.12536DOI Listing
May 2021

Digital Detectives: Websleuthing Reduces Eyewitness Identification Accuracy in Police Lineups.

Front Psychol 2021 15;12:640513. Epub 2021 Apr 15.

School of Computing & Communications, The Open University, Milton Keynes, United Kingdom.

Eyewitnesses to crimes sometimes search for a culprit on social media before viewing a police lineup, but it is not known whether this affects subsequent lineup identification accuracy. The present online study was conducted to address this. Two hundred and eighty-five participants viewed a mock crime video, and after a 15-20 min delay either (i) viewed a mock social media site including the culprit, (ii) viewed a mock social media site including a lookalike, or (iii) completed a filler task. A week later, participants made an identification from a photo lineup. It was predicted that searching for a culprit on social media containing the lookalike (rather than the culprit) would reduce lineup identification accuracy. There was a significant association between social media exposure and lineup accuracy for the Target Present lineup (30% more of the participants who saw the lookalike on social media failed to positively identify the culprit than participants in the other conditions), but for the Target Absent lineup (which also included the lookalike) there was no significant association with lineup identification accuracy. The results suggest that if an eyewitness sees a lookalike (where they are expecting to see the culprit) when conducting a self-directed search on social media, they are less likely to subsequently identify the culprit in the formal ID procedure.
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http://dx.doi.org/10.3389/fpsyg.2021.640513DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8081957PMC
April 2021

Integrating Sleep Knowledge Into the Anesthesiology Curriculum.

Anesth Analg 2021 05;132(5):1296-1305

Division of Pulmonary, Critical Care and Sleep Medicine, MetroHealth Medical Center, Case Western Reserve University, Cleveland, Ohio.

There is common ground between the specialties of anesthesiology and sleep medicine. Traditional sleep medicine curriculum for anesthesiology trainees has revolved around the discussion of obstructive sleep apnea (OSA) and its perioperative management. However, it is time to include a broader scope of sleep medicine-related topics that overlap these specialties into the core anesthesia residency curriculum. Five main core competency domains are proposed, including SLeep physiology; Evaluation of sleep health; Evaluation for sleep disorders and clinical implications; Professional and academic roles; and WELLness (SLEEP WELL). The range of topics include not only the basics of the physiology of sleep and sleep-disordered breathing (eg, OSA and central sleep apnea) but also insomnia, sleep-related movement disorders (eg, restless legs syndrome), and disorders of daytime hypersomnolence (eg, narcolepsy) in the perioperative and chronic pain settings. Awareness of these topics is relevant to the scope of knowledge of anesthesiologists as perioperative physicians as well as to optimal sleep health and physician wellness and increase consideration among current anesthesiology trainees for the value of dual credentialing in both these specialties.
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http://dx.doi.org/10.1213/ANE.0000000000005490DOI Listing
May 2021

Effect of Vitamin C, Thiamine, and Hydrocortisone on Ventilator- and Vasopressor-Free Days in Patients With Sepsis: The VICTAS Randomized Clinical Trial.

JAMA 2021 02;325(8):742-750

Department of Emergency Medicine, Johns Hopkins University, Baltimore, Maryland.

Importance: Sepsis is a common syndrome with substantial morbidity and mortality. A combination of vitamin C, thiamine, and corticosteroids has been proposed as a potential treatment for patients with sepsis.

Objective: To determine whether a combination of vitamin C, thiamine, and hydrocortisone every 6 hours increases ventilator- and vasopressor-free days compared with placebo in patients with sepsis.

Design, Setting, And Participants: Multicenter, randomized, double-blind, adaptive-sample-size, placebo-controlled trial conducted in adult patients with sepsis-induced respiratory and/or cardiovascular dysfunction. Participants were enrolled in the emergency departments or intensive care units at 43 hospitals in the United States between August 2018 and July 2019. After enrollment of 501 participants, funding was withheld, leading to an administrative termination of the trial. All study-related follow-up was completed by January 2020.

Interventions: Participants were randomized to receive intravenous vitamin C (1.5 g), thiamine (100 mg), and hydrocortisone (50 mg) every 6 hours (n = 252) or matching placebo (n = 249) for 96 hours or until discharge from the intensive care unit or death. Participants could be treated with open-label corticosteroids by the clinical team, with study hydrocortisone or matching placebo withheld if the total daily dose was greater or equal to the equivalent of 200 mg of hydrocortisone.

Main Outcomes And Measures: The primary outcome was the number of consecutive ventilator- and vasopressor-free days in the first 30 days following the day of randomization. The key secondary outcome was 30-day mortality.

Results: Among 501 participants randomized (median age, 62 [interquartile range {IQR}, 50-70] years; 46% female; 30% Black; median Acute Physiology and Chronic Health Evaluation II score, 27 [IQR, 20.8-33.0]; median Sequential Organ Failure Assessment score, 9 [IQR, 7-12]), all completed the trial. Open-label corticosteroids were prescribed to 33% and 32% of the intervention and control groups, respectively. Ventilator- and vasopressor-free days were a median of 25 days (IQR, 0-29 days) in the intervention group and 26 days (IQR, 0-28 days) in the placebo group, with a median difference of -1 day (95% CI, -4 to 2 days; P = .85). Thirty-day mortality was 22% in the intervention group and 24% in the placebo group.

Conclusions And Relevance: Among critically ill patients with sepsis, treatment with vitamin C, thiamine, and hydrocortisone, compared with placebo, did not significantly increase ventilator- and vasopressor-free days within 30 days. However, the trial was terminated early for administrative reasons and may have been underpowered to detect a clinically important difference.

Trial Registration: ClinicalTrials.gov Identifier: NCT03509350.
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http://dx.doi.org/10.1001/jama.2020.24505DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7903252PMC
February 2021

ASIA: Automated Social Identity Assessment using linguistic style.

Behav Res Methods 2021 08 11;53(4):1762-1781. Epub 2021 Feb 11.

Department of Psychology, University of Exeter, Washington Singer Laboratories, Exeter, EX4 4QG, UK.

The various group and category memberships that we hold are at the heart of who we are. They have been shown to affect our thoughts, emotions, behavior, and social relations in a variety of social contexts, and have more recently been linked to our mental and physical well-being. Questions remain, however, over the dynamics between different group memberships and the ways in which we cognitively and emotionally acquire these. In particular, current assessment methods are missing that can be applied to naturally occurring data, such as online interactions, to better understand the dynamics and impact of group memberships in naturalistic settings. To provide researchers with a method for assessing specific group memberships of interest, we have developed ASIA (Automated Social Identity Assessment), an analytical protocol that uses linguistic style indicators in text to infer which group membership is salient in a given moment, accompanied by an in-depth open-source Jupyter Notebook tutorial ( https://github.com/Identity-lab/Tutorial-on-salient-social-Identity-detection-model ). Here, we first discuss the challenges in the study of salient group memberships, and how ASIA can address some of these. We then demonstrate how our analytical protocol can be used to create a method for assessing which of two specific group memberships-parents and feminists-is salient using online forum data, and how the quality (validity) of the measurement and its interpretation can be tested using two further corpora as well as an experimental study. We conclude by discussing future developments in the field.
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http://dx.doi.org/10.3758/s13428-020-01511-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8367904PMC
August 2021

Teaching Health Professions Students About the Holocaust.

AMA J Ethics 2021 01 1;23(1):E26-30. Epub 2021 Jan 1.

Project manager for the Holocaust Genocide and Contemporary Bioethics Program at the University of Colorado Center for Bioethics and Humanities in Aurora.

The legacy of health professionals' roles in the Holocaust is fundamental to understanding modern health care ethics, but teaching it is difficult. The University of Colorado Center for Bioethics and Humanities has developed a program that addresses 4 main pedagogical challenges of this content. This article identifies 3 core lessons and proposes 5 specific learning objectives related to health professionals' involvement in the Holocaust for any health professional training program.
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http://dx.doi.org/10.1001/amajethics.2021.26DOI Listing
January 2021

Assessment of Day-7 Postexposure Testing of Asymptomatic Contacts of COVID-19 Patients to Evaluate Early Release from Quarantine - Vermont, May-November 2020.

MMWR Morb Mortal Wkly Rep 2021 Jan 8;70(1):12-13. Epub 2021 Jan 8.

Vermont Department of Health.

On May 8, 2020, the Vermont Department of Health (VDH) issued a Health Update* recommending shortening the duration of quarantine for persons exposed to SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19). Exposed persons who were in quarantine could be tested by polymerase chain reaction (PCR) on or after quarantine day 7. Those who had remained asymptomatic throughout quarantine and who received a negative SARS-CoV-2 PCR test result on or after day 7 could end quarantine. This policy was based on a report suggesting that symptom onset occurs within this time frame in approximately three quarters of COVID-19 cases (1) and on consultation of the Vermont Health Commissioner with the U.S. Surgeon General. VDH implemented this policy to minimize restrictions on state residents, recognizing that some reduction could occur in the prevention benefit of quarantine to contain the spread of SARS-CoV-2. State-run SARS-CoV-2 testing sites were made available to increase access to no-cost testing and facilitate implementation of this policy. During August 1-December 1, among persons seeking testing at a VDH SARS-CoV-2 testing site, 36% stated that their reason for seeking testing was to end quarantine early (VDH, unpublished data, December 7, 2020), indicating that persons were aware of and following the policy and using the testing services provided. To assess the effectiveness of this policy, VDH analyzed testing data for contacts of persons with a COVID-19 diagnosis. During May 8-November 16, VDH identified 8,798 exposed contacts of COVID-19 patients; 3,983 (45%) had sought testing within 14 days of their exposure, with day 0 defined as the date of last exposure noted in the case investigation record. Among these persons, 2,200 (55%) who received testing on days 7-10 were included in this analysis; 977 (44.9%) of these contacts had a specimen collected for testing on day 7. Among these, 34 (3%) had test results that were positive, 940 (96%) had results that were negative, and three (<1%) had results that were indeterminate (Table). Among the 34 contacts who received a positive SARS-CoV-2 PCR test result on day 7 after exposure, 12 (35%) were asymptomatic. The remaining 22 contacts with positive test results were symptomatic at the time of testing; approximately one half had developed symptoms on days 4-7 after exposure. Among the 940 contacts who received negative test results on specimens collected on day 7 after exposure, 154 (16%) had a subsequent test within the next 7 days (i.e., days 8-14); among these, 152 (99%) had tests that remained negative, and two (1%) had results that were indeterminate.
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http://dx.doi.org/10.15585/mmwr.mm7001a3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790157PMC
January 2021

Jobs, Housing, and Mask Wearing: Cross-Sectional Study of Risk Factors for COVID-19.

JMIR Public Health Surveill 2021 01 11;7(1):e24320. Epub 2021 Jan 11.

Department of Medicine, Larner College of Medicine, University of Vermont, Burlington, VT, United States.

Background: Many studies have focused on the characteristics of symptomatic patients with COVID-19 and clinical risk factors. This study reports the prevalence of COVID-19 in an asymptomatic population of a hospital service area (HSA) and identifies factors that affect exposure to the virus.

Objective: The aim of this study is to measure the prevalence of COVID-19 in an HSA, identify factors that may increase or decrease the risk of infection, and analyze factors that increase the number of daily contacts.

Methods: This study surveyed 1694 patients between April 30 and May 13, 2020, about their work and living situations, income, behavior, sociodemographic characteristics, and prepandemic health characteristics. This data was linked to testing data for 454 of these patients, including polymerase chain reaction test results and two different serologic assays. Positivity rate was used to calculate approximate prevalence, hospitalization rate, and infection fatality rate (IFR). Survey data was used to analyze risk factors, including the number of contacts reported by study participants. The data was also used to identify factors increasing the number of daily contacts, such as mask wearing and living environment.

Results: We found a positivity rate of 2.2%, a hospitalization rate of 1.2%, and an adjusted IFR of 0.55%. A higher number of daily contacts with adults and older adults increases the probability of becoming infected. Occupation, living in an apartment versus a house, and wearing a face mask outside work increased the number of daily contacts.

Conclusions: Studying prevalence in an asymptomatic population revealed estimates of unreported COVID-19 cases. Occupational, living situation, and behavioral data about COVID-19-protective behaviors such as wearing a mask may aid in the identification of nonclinical factors affecting the number of daily contacts, which may increase SARS-CoV-2 exposure.
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http://dx.doi.org/10.2196/24320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7800904PMC
January 2021

"Building the Threads of Connection that We Already Have": The Nature of Connections via Technology for Older People.

Clin Gerontol 2021 Jul-Sep;44(4):406-417. Epub 2020 Dec 2.

Centre for Research in Ageing and Cognitive Health, University of Exeter, Exeter, UK.

: The social connectedness of older people is of increasing concern. Technology has been suggested for enhancing social inclusion. This study aimed to explore the nature and quality of connections via technology.: Qualitative exploration of experiences, stories, and needs was undertaken through semi-structured interviews with older (7) and middle-aged (3) adults with rich experience of connections via technology in Australia and England. Core aspects of connections through technology were constructed through interpretive description analysis.: Four key aspects were: 1. : descriptions of a range of subjective quality of connections and characteristics of good connections; 2. Experiences of poor connection () including descriptions of experiences creating isolation; 3. described the purposes of technology-based connections including connecting with others, themselves and places important to them; 4. described active strategies to enhance connection.: Using technology is part of the social engagement of many people. Considering the related feelings of connection and support strategies and needs could enhance future research and practice with older people.: The different characteristics and potential positive and negative experiences of connection via technology need consideration in measuring social isolation and supporting older adults.
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http://dx.doi.org/10.1080/07317115.2020.1852638DOI Listing
August 2021

Vitamin E catabolism in women, as modulated by food and by fat, studied using 2 deuterium-labeled α-tocopherols in a 3-phase, nonrandomized crossover study.

Am J Clin Nutr 2020 Nov 12. Epub 2020 Nov 12.

Molecular and Clinical Nutrition Section, Intramural Research Program, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD, USA.

Background: Human vitamin E (α-tocopherol) catabolism is a mechanism for regulating whole-body α-tocopherol.

Objectives: To determine the roles of the intestine and liver on α-tocopherol catabolism as affected by fat or fasting, 2 deuterium-labeled (intravenous d6- and oral d3-) forms of α-tocopherol were used.

Methods: Healthy women received intravenous d6-α-tocopherol and consumed d3-α-tocopherol with a 600-kcal defined liquid meal (DLM; 40% or 0% fat, n = 10) followed by controlled meals; or the 0% fat DLM (n = 7) followed by a 12-h fast (0% fat-fast), then controlled meals ≤72 h. The order of the 3-phase crossover design was not randomized and there was no blinding. Samples were analyzed by LC/MS to determine the α-tocopherol catabolites and α-carboxyethyl hydroxychromanol (α-CEHC) in urine, feces, and plasma that were catabolized from administered oral d3- and intravenous d6-α-tocopherols.

Results: Urinary and plasma d3- and d6-α-CEHC concentrations varied differently with the interventions. Mean ± SEM cumulative urinary d6-α-CEHC derived from the intravenous dose excreted over 72 h during the 40% fat (2.50 ± 0.37 μmol/g creatinine) and 0% fat (2.37 ± 0.37 μmol/g creatinine) interventions were similar, but a ∼50% decrease was observed during the 0% fat-fast (1.05 ± 0.39 μmol/g creatinine) intervention (compared with 0% fat, P = 0.0005). Cumulative urinary d3-α-CEHC excretion was not significantly changed by any intervention. Total urinary and fecal excretion of catabolites accounted for <5% of each of the administered doses.

Conclusions: Differential catabolism of the intravenous d6-α-tocopherol and oral d3-α-tocopherol doses shows both liver and intestine have roles in α-tocopherol catabolism. During the 40% fat intervention, >90% of urinary d3-α-CEHC excretion was estimated to be liver-derived, whereas during fasting <50% was from the liver with the remainder from the intestine, suggesting that there was increased intestinal α-tocopherol catabolism while d3-α-tocopherol was retained in the intestine in the absence of adequate fat/food for α-tocopherol absorption.This trial was registered at clinicaltrials.gov as NCT00862433.
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http://dx.doi.org/10.1093/ajcn/nqaa298DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7779232PMC
November 2020

Virtual Cancer Care During the COVID-19 Pandemic and Beyond: A Call for Evaluation.

JMIR Cancer 2020 Nov 24;6(2):e24222. Epub 2020 Nov 24.

Department of Oncology, McMaster University, Hamilton, ON, Canada.

The interplay of virtual care and cancer care in the context of the COVID-19 pandemic is unique and unprecedented. Patients with cancer are at increased risk of SARS-CoV-2 infection and have worse outcomes than patients with COVID-19 who do not have cancer. Virtual care has been introduced quickly and extemporaneously in cancer treatment centers worldwide to maintain COVID-19-free zones. The outbreak of COVID-19 in a cancer center could have devastating consequences. The virtual care intervention that was first used in our cancer center, as well as many others, was a landline telephone in an office or clinic that connected a clinician with a patient. There is a lack of virtual care evaluation from the perspectives of patients and oncology health care providers. A number of factors for assessing oncology care delivered through a virtual care intervention have been described, including patient rapport, frailty, delicate conversations, team-based care, resident education, patient safety, technical effectiveness, privacy, operational effectiveness, and resource utilization. These factors are organized according to the National Quality Forum framework for the assessment of telehealth in oncology. This includes the following 4 domains of assessing outcomes: experience, access to care, effectiveness, and financial impact or cost. In terms of virtual care and oncology, the pandemic has opened the door to change. The lessons learned during the initial period of the pandemic have given rise to opportunities for the evolution of long-term virtual care. The opportunity to evaluate and improve virtual care should be seized upon.
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http://dx.doi.org/10.2196/24222DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7717920PMC
November 2020

Pericardial disease as a rare complication of pediatric appendicitis: a systematic literature search.

JA Clin Rep 2020 Nov 9;6(1):89. Epub 2020 Nov 9.

Department of Anesthesia and Pain Medicine, The Hospital for Sick Children, 555 University Ave, #2211, Toronto, ON, M5G 1X8, Canada.

Background: Classic symptoms of acute appendicitis are well known but are uncommon and often misinterpreted in pediatric patients, potentially delaying diagnosis and resulting in rare sequelae.

Methods: We conducted a comprehensive systematic literature search of case reports detailing pericardial disease as a rare complication of pediatric appendicitis through MEDLINE, Embase, and Cochrane Databases. Inclusion criteria was that the patient must be < 18 years old and present with both pericardial disease and appendicitis.

Results: Our search yielded 7 cases with an average age of 10.3 ± 3.9 years old. The cases involved cardiac tamponade, pericarditis, and/or pericardial effusion. Five cases were diagnosed with appendicitis before complicated by pericardial disease. Most cases had an infectious component, but a majority had negative pericardial fluid cultures. Pleural effusion and abdominal abscesses were other common complications of pediatric appendicitis.

Conclusion: Awareness of this uncommon relationship may have prognostic value as this may facilitate appropriate management of pericardial effusions, tamponade, and/or appendicitis.
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http://dx.doi.org/10.1186/s40981-020-00395-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7652975PMC
November 2020

Vitamin E treatment in NAFLD patients demonstrates that oxidative stress drives steatosis through upregulation of de-novo lipogenesis.

Redox Biol 2020 10 1;37:101710. Epub 2020 Sep 1.

Liver and Energy Metabolism Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA; Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA. Electronic address:

Oxidative stress (OS) in non-alcoholic fatty liver disease (NAFLD) promotes liver injury and inflammation. Treatment with vitamin E (α-tocopherol, αT), a lipid-soluble antioxidant, improves liver injury but also decreases steatosis, thought to be upstream of OS, through an unknown mechanism. To elucidate the mechanism, we combined a mechanistic human trial interrogating pathways of intrahepatic triglyceride (IHTG) accumulation and in vitro experiments. 50% of NAFLD patients (n = 20) treated with αT (200-800 IU/d) for 24 weeks had a ≥ 25% relative decrease in IHTG by magnetic resonance spectroscopy. Paired liver biopsies at baseline and week 4 of treatment revealed a decrease in markers of hepatic de novo lipogenesis (DNL) that strongly predicted week 24 response. In vitro, using HepG2 cells and primary human hepatocytes, αT inhibited glucose-induced DNL by decreasing SREBP-1 processing and lipogenic gene expression. This mechanism is dependent on the antioxidant capacity of αT, as redox-silenced methoxy-αT is unable to inhibit DNL in vitro. OS by itself was sufficient to increase S2P expression in vitro, and S2P is upregulated in NAFLD livers. In summary, we utilized αT to demonstrate a vicious cycle in which NAFLD generates OS, which feeds back to augment DNL and increases steatosis. Clinicaltrials.gov: NCT01792115.
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http://dx.doi.org/10.1016/j.redox.2020.101710DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7494510PMC
October 2020

What Works in Violence Prevention Among Young People?: A Systematic Review of Reviews.

Trauma Violence Abuse 2020 Jul 17:1524838020939130. Epub 2020 Jul 17.

University of Exeter, United Kingdom.

Violence prevention programs aim to raise awareness, change attitudes, normative beliefs, motivation, and behavioral responses. Many programs have been developed and evaluated, and optimistic claims about effectiveness made. Yet comprehensive guidance on program design, implementation, and evaluation is limited. The aim of this study was to provide an up-to-date review of evidence on what works for whom. A systematic search of PsycINFO, MEDLINE, ERIC, and Sociology Collection ProQuest identified 40 reviews and meta-analyses reporting on the effectiveness of violence prevention programs among young people (age 15-30) in educational institutions, published before October 2018. These included reviews of programs designed to reduce (i) bullying, (ii) dating and relationship violence, (iii) sexual assault, and (iv) antisocial behavior. Only evaluations that reported on behavioral outcomes such as perpetration, victimization, and bystander behavior were included. The reviewed evaluations reported on programs that were mainly implemented in high-income countries in Europe and North America. The majority found small effects on violence reduction and victimization and increases in self-reported bystander behavior. Our findings expose critical gaps in evaluation research in this area and provide recommendations on how to optimize the effectiveness of future programs.
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http://dx.doi.org/10.1177/1524838020939130DOI Listing
July 2020

Hypofractionated Breast Irradiation: What's Next?

J Clin Oncol 2020 10 14;38(28):3245-3247. Epub 2020 Jul 14.

McMaster University, Department of Oncology, Hamilton, Ontario, Canada.

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http://dx.doi.org/10.1200/JCO.20.01243DOI Listing
October 2020

Anesthesia environmental sustainability programs-a survey of Canadian department chiefs and residency program directors.

Can J Anaesth 2020 09 11;67(9):1190-1200. Epub 2020 Jun 11.

Department of Anesthesia, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.

Introduction: Anesthesia-related activities contribute to operating room waste impacting climate change. The aim of this study was to ascertain 1) the current existence and scope of department and education programs concerned with anesthesia "green" practice; and 2) perceived barriers to environmental sustainability efforts among Canadian anesthesia department chiefs and residency program directors.

Methods: Association of Canadian University Departments of Anesthesia-affiliated anesthesiology department chiefs (n = 113) were invited to complete an online survey ascertaining current efforts in, and barriers to, environmentally sustainable anesthesia practice. Similarly, Canadian anesthesiology residency program directors (n = 17) were invited to complete an online survey delineating current educational programs on environmental sustainability and identifying interest in, and barriers to, developing a Canada-wide curriculum.

Results: The response rates for department chiefs and program directors were 23% (26/113) and 41% (7/17), respectively. Department chiefs indicated that their departments participate in sustainability efforts such as donating medical equipment (65%) and recycling (58%). Despite interest in environmental sustainability, department chiefs identified inadequate funding (72%), lack of a mandate (64%), and inadequate knowledge (60%) as barriers to implementing environmentally sustainable practices. Only 29% of responding Canadian anesthesiology programs include environmental sustainability in their curriculum. Responding residency program directors believe residents would benefit from more teaching on the topic (86%) but identified barriers including a lack of faculty expertise (100%) and time constraints (71%). Respondents (71%) also indicated an interest in developing a Canadian curriculum on the topic.

Conclusion: Our results highlight current attitudes, gaps, and barriers to environmentally sustainable anesthesiology practice among departmental and educational leadership. Furthermore, this study identifies potential opportunities to develop cross-Canada collaborative educational programs in this field.
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http://dx.doi.org/10.1007/s12630-020-01738-wDOI Listing
September 2020

Vermont's comprehensive public health framework for tobacco control and prevention.

Prev Med 2020 11 27;140:106152. Epub 2020 May 27.

Vermont Department of Health, Burlington, VT, USA. Electronic address:

When the Centers for Disease Control and Prevention published the Best Practices Guide for Comprehensive Tobacco Control - 2014 it provided an opportunity for Vermont's Tobacco Control Program to create a new state plan. Bringing together partner agencies, advocates and health organizations, the workgroup faced a challenge: there wasn't consensus around focusing on e-cigarettes. There was concern that if too much emphasis was placed on addressing this emerging product, it would be at the cost of reducing combustible use. Youth smoking rates were declining while adult smoking prevalence in Vermont remained stagnant and difficult to move downward. Through applying the lens of best practice and examining the data, the workgroup determined that an ambitious state plan was necessary. Adopting a set of principles grounded in public health and performance measurement, the plan's five goals are to reduce use of all tobacco products among youth and adults. The state plan established a vision of a Vermont free of tobacco use for the program and partners to use, emphasizing data-driven interventions and advancing policymaking, including addressing flavored tobacco products. The tobacco control and regulatory framework in Vermont has worked consistently at the state and local level on strategies involving youth engagement, coalition prevention activities, counter marketing and enforcement. Vermont's framework has evolved to recognize that no matter where a Vermonter is living or working, the protections and services provided by a tobacco program should be equitable. Future application of the public health framework includes exploring innovative policy approaches to curtail the vaping epidemic.
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http://dx.doi.org/10.1016/j.ypmed.2020.106152DOI Listing
November 2020

Fundamental Research in Oncology and Thrombosis 2 (FRONTLINE 2): A Follow-Up Survey.

Oncologist 2020 07 8;25(7):e1091-e1097. Epub 2020 May 8.

McMaster University, Hamilton, Ontario, Canada.

Background: Fundamental Research in Oncology and Thrombosis (FRONTLINE) is a global survey of physicians' perceptions and practice in the management of venous thromboembolism (VTE) in patients with cancer.

Materials And Methods: The present survey, FRONTLINE 2, follows the original FRONTLINE survey (published in The Oncologist in 2003) and provides insights into how physicians perceive risk of VTE in cancer and approach its prophylaxis and treatment.

Results: Between November 2015 and February 2016, 5,233 respondents participated, representing cancer physicians and surgeons. Most believed that less than one in five patients with any cancer might be at risk of VTE, with a slightly higher risk in patients with brain, pancreatic, and lung tumors. The most frequently reported reasons for giving prophylaxis were prior history of VTE (74.6%), abnormal platelet count (62.0%), and obesity (59.5%). In surgical and medical cancer patients, low-molecular-weight heparin (LMWH) was the most popular prophylactic measure, used by 74.2% and 80.6%, respectively. Oral anticoagulants (OACs) were given in less than one fifth of cases. In surgical patients, prophylaxis was usually provided for 1 month postoperatively. Following a diagnosis of VTE, patients initially received treatment with LMWH and were maintained long term on OACs, primarily warfarin, dabigatran, and rivaroxaban. Most surgical and medical cancer patients underwent treatment of VTE for 3-6 months.

Conclusion: Compared with the original FRONTLINE survey, FRONTLINE 2 reveals some differences in the management of VTE in patients with cancer. Newer anticoagulants such as fondaparinux, dabigatran, and rivaroxaban are being incorporated into the contemporary management of VTE in patients with cancer.

Implications For Practice: This globally conducted survey of more than 5,000 cancer clinicians revealed a number of insights into the perceived risk for venous thromboembolism as well as contemporary approaches to its prevention and treatment. Although guidelines have consistently recommended anticoagulant medications for prevention and treatment of cancer-associated thrombosis, clinicians report substantial variation in their practice.
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http://dx.doi.org/10.1634/theoncologist.2019-0676DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7356678PMC
July 2020

In response: Letter on update to the Vitamin C, Thiamine and Steroids in Sepsis (VICTAS) protocol.

Trials 2020 Apr 22;21(1):351. Epub 2020 Apr 22.

Division of Pulmonary & Critical Care Medicine, Department of Medicine, Johns Hopkins University, 1800 Orleans Street, Suite 9121, Baltimore, MD, 21287, USA.

Trial Registration: ClinicalTrials.gov: NCT03509350. Registered on 26 April 2018.
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http://dx.doi.org/10.1186/s13063-020-04290-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7175511PMC
April 2020

Therapeutic Targeting of -Mutated Pheochromocytoma/Paraganglioma with Pharmacologic Ascorbic Acid.

Clin Cancer Res 2020 07 9;26(14):3868-3880. Epub 2020 Mar 9.

Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, Maryland.

Purpose: Pheochromocytomas and paragangliomas (PCPG) are usually benign neuroendocrine tumors. However, PCPGs with mutations in the succinate dehydrogenase B subunit () have a poor prognosis and frequently develop metastatic lesions. -mutated PCPGs exhibit dysregulation in oxygen metabolic pathways, including pseudohypoxia and formation of reactive oxygen species, suggesting that targeting the redox balance pathway could be a potential therapeutic approach.

Experimental Design: We studied the genetic alterations of cluster I PCPGs compared with cluster II PCPGs, which usually present as benign tumors. By targeting the signature molecular pathway, we investigated the therapeutic effect of ascorbic acid on PCPGs using and models.

Results: By investigating PCPG cells with low SDHB levels, we show that pseudohypoxia resulted in elevated expression of iron transport proteins, including transferrin (TF), transferrin receptor 2 (TFR2), and the divalent metal transporter 1 ( DMT1), leading to iron accumulation. This iron overload contributed to elevated oxidative stress. Ascorbic acid at pharmacologic concentrations disrupted redox homeostasis, inducing DNA oxidative damage and cell apoptosis in PCPG cells with low levels. Moreover, through a preclinical animal model with PCPG allografts, we demonstrated that pharmacologic ascorbic acid suppressed -low metastatic lesions and prolonged overall survival.

Conclusions: The data here demonstrate that targeting redox homeostasis as a cancer vulnerability with pharmacologic ascorbic acid is a promising therapeutic strategy for -mutated PCPGs.
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http://dx.doi.org/10.1158/1078-0432.CCR-19-2335DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7443979PMC
July 2020

The LISA randomized trial of a weight loss intervention in postmenopausal breast cancer.

NPJ Breast Cancer 2020 21;6. Epub 2020 Feb 21.

10Division of Medical Oncology & Hematology, Sunnybrook Odette Cancer Center, Ontario Clinical Oncology Group, University of Toronto, Toronto, ON Canada.

Obesity has been associated with poor breast cancer (BC) outcomes. We investigated whether a standardized, telephone-based weight loss lifestyle intervention in the adjuvant setting would impact BC outcomes. We conducted a multicenter trial randomizing women 1:1 to mail-based educational material alone (control) or combined with a standardized, telephone-based lifestyle intervention that focused on diet, physical activity, and behavior and involved 19 calls over 2 years to achieve up to 10% weight loss. In all, 338 (of 2150 planned) T1-3, N0-3, M0 hormone receptor positive BC patients with body mass index (BMI) ≥24 kg/m receiving adjuvant letrozole were randomized (enrolment ended due to funding loss). The primary outcome was disease-free survival (DFS); secondary outcome was Overall Survival (OS). At 8 years' median follow-up, in a planned analysis, DFS and OS were compared using the Kaplan-Meier method. Baseline BMI and other characteristics were similar between study arms. In all, 22 of 171 (12.9%) in the lifestyle intervention arm versus 30 of 167 (18.0%) in the education had DFS events; the hazard ratio (HR) was 0.71 (95% confidence interval [CI]: 0.41-1.24,  = 0.23). Although loss of funding reduced sample size, we view these hypothesis generating results as compatible with our hypothesis of a potential beneficial effect of a lifestyle intervention on DFS. They provide support for completion of ongoing randomized controlled trials of the effect of lifestyle interventions in BC outcomes.
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http://dx.doi.org/10.1038/s41523-020-0149-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7035359PMC
February 2020

Effect of PET-CT on disease recurrence and management in patients with potentially resectable colorectal cancer liver metastases. Long-term results of a randomized controlled trial.

J Surg Oncol 2020 May 7;121(6):1001-1006. Epub 2020 Feb 7.

Ontario Clinical Oncology Group, McMaster University, Hamilton, Ontario.

Background: Preoperative evaluation of resectable colorectal cancer liver metastases with positron emission tomography (PET) combined with computed tomography (PET-CT) is used extensively. The PETCAM trial evaluated the effect of PET-CT (intervention) vs no PET-CT (control) on surgical management. PET-CT resulted in 8% change in surgical management, therefore, we aimed to compare long-term outcomes (disease-free [DFS], overall survival [OS]).

Methods: Trial recruitment (2005-2010) had prospective follow-up until 2013. Events from 2013 to 2017 were collected retrospectively. Survival was described by the Kaplan-Meier method and compared with log-rank test. Oncologic risk factors were calculated using Cox proportional hazard models.

Results: Among 404 patients randomized, there were no differences in DFS (hazard ratio [HR] = 1.13; 95% confidence interval [CI], 0.89 to 1.43) or OS (HR, 1.02; 95% CI, 0.78-1.32) between groups. For all patients randomized, median DFS (PET-CT vs no PET-CT) was 16 months (95% CI, 13-18) and 15 months (95% CI, 11-22), P = .33. For patients who underwent liver resection (n = 368), DFS (17 vs 16 months, P = .51) and OS (58 months vs 52 months, P = .90) were similar between groups, respectively. Risk factors for DFS and OS were age, tumor size, node-positive disease, extrahepatic metastases and disease-free duration.

Conclusion: Preoperative PET-CT changes surgical management in a small percentage of cases, without effect on recurrence rates or long-term survival.
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http://dx.doi.org/10.1002/jso.25864DOI Listing
May 2020

Treatment of cancer-associated venous thromboembolism: 12-month outcomes of the placebo versus rivaroxaban randomization of the SELECT-D Trial (SELECT-D: 12m).

J Thromb Haemost 2020 04 26;18(4):905-915. Epub 2020 Feb 26.

Warwick Clinical Trials Unit, Warwick Medical School, University of Warwick, Coventry, UK.

Background: The Anticoagulation Therapy in Selected Cancer Patients at Risk of Recurrence of Venous Thromboembolism (SELECT-D) trial demonstrated reduction in recurrent venous thromboembolism (VTE) but increased bleeding with rivaroxaban compared with dalteparin for treatment of acute VTE in cancer patients, at 6 months. Uncertainty remains around optimal duration of anticoagulation.

Objectives: To assess VTE recurrence and bleeding, with anticoagulation or not, beyond 6 months.

Patients/methods: In SELECT-D, after 6 months of trial treatment for VTE, patients with active cancer and residual deep vein thrombosis (RDVT) or index pulmonary embolism (PE) were eligible for randomization to a further 6 months of rivaroxaban or placebo. Patients with no RDVT stopped anticoagulation. Primary outcome was VTE recurrence at 12 months. The second randomization closed prematurely because of low recruitment when 92 of the planned 300 patients were recruited.

Results: Ninety-two of 136 eligible patients were randomized to rivaroxaban or placebo. The cumulative VTE recurrence after 6 months from the second randomization was 14% with placebo and 4% with rivaroxaban (hazard ratio, 0.32; 95% confidence interval [CI], 0.06-1.58). The major and clinically relevant non-major bleeding rates were 0% and 0% with placebo; and 5% (95% CI, 1-18) and 4% (95% CI, 1-17) with rivaroxaban. In an exploratory analysis, 7 (15%) of 46 placebo patients with RDVT or an index PE experienced recurrent VTE compared to none in the 35 patients in the RDVT-negative cohort (P = .03).

Conclusion: The SELECT-D trial was underpowered to detect a statistically significant reduction in recurrent VTE with extended anticoagulation. The absence of RDVT and/or index PE, defined a population at low risk of recurrence.
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http://dx.doi.org/10.1111/jth.14752DOI Listing
April 2020

Contact Logger: Measuring everyday intergroup contact experiences in near-time.

Behav Res Methods 2020 08;52(4):1568-1586

Department of Psychology, University of Lancaster, Lancaster, UK.

Intergroup contact research has traditionally relied on retrospective accounts of intergroup encounters, mainly through survey-based or observational methods. This study introduces and tests the usability of a purpose-built, location-aware mobile application-the Contact Logger. This application enables the recording of interpersonal and intergroup encounters, in public and private spaces (both indoor and outdoor), in their here-and-now contexts. The main advantage of this approach, as compared to traditional methods, lies in its ability to collect repeated and timely (near-time) self-assessments of individuals' behaviors and experiences. It also allows for geographical location data to be logged. Usability testing was conducted in a real-world environment and took place over the course of seven days, during which participants (N = 12) logged every contact they had with an outgroup member (here, older people). Subsequently, participants completed a paper-and-pencil questionnaire, reporting on the usability and experience of using the Contact Logger. The results showed that the application is a viable and easy-to-use alternative to traditional methods. The information gathered aided the further development and optimization of the application. The outcomes of this development process are also briefly discussed.
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http://dx.doi.org/10.3758/s13428-019-01335-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7406530PMC
August 2020

High-dose ascorbic acid synergizes with anti-PD1 in a lymphoma mouse model.

Proc Natl Acad Sci U S A 2020 01 7;117(3):1666-1677. Epub 2020 Jan 7.

Department of Medicine (Oncology), Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY 10461;

Major efforts are underway to identify agents that can potentiate effects of immune checkpoint inhibition. Here, we show that ascorbic acid (AA) treatment caused genomewide demethylation and enhanced expression of endogenous retroviral elements in lymphoma cells. AA also increased 5-hydroxymethylcytosine (5hmC) levels of CD8+ T cells and enhanced their cytotoxic activity in a lymphoma coculture system. High-dose AA treatment synergized with anti-PD1 therapy in a syngeneic lymphoma mouse model, resulting in marked inhibition of tumor growth compared with either agent alone. Analysis of the intratumoral epigenome revealed increased 5hmC with AA treatment, consistent with in vitro findings. Analysis of the tumor immune microenvironment revealed that AA strikingly increased intratumoral infiltration of CD8+ T cells and macrophages, suggesting enhanced tumor immune recognition. The combination treatment markedly enhanced intratumoral infiltration of macrophages and CD8+ T lymphocytes, granzyme B production by cytotoxic cells (cytotoxic T cells and natural killer cells), and interleukin 12 production by antigen-presenting cells compared with single-agent anti-PD1. These data indicate that AA potentiates anti-PD1 checkpoint inhibition through synergistic mechanisms. The study provides compelling rationale for testing combinations of high-dose AA and anti-PD1 agents in patients with aggressive B cell lymphoma as well as in preclinical models of other malignancies.
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http://dx.doi.org/10.1073/pnas.1908158117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6983418PMC
January 2020
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