Progressing From Disparity to Equity: Untangling the Complexities of Timely Care and the Rural Cancer Experience.

Richard L. Martin III, MD, MPH, and Stephen Schleicher, MD, MBA, share a perspective on rural cancer care.

Risk and protective factors for severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infection among healthcare workers: A test-negative case-control study in Québec, Canada.

OBJECTIVES: In Québec, Canada, we evaluated the risk of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infection associated with (1) the demographic and employment characteristics among healthcare workers (HCWs) and (2) the workplace and household exposures and the infection prevention and control (IPC) measures among patient-facing HCWs. DESIGN: Test-negative case-control study. SETTING: Provincial health system. PARTICIPANTS: HCWs with PCR-confirmed coronavirus disease 2019 (COVID-19) diagnosed between November 15, 2020, and May 29, 2021 (ie, cases), were compared to HCWs with compatible symptoms who tested negative during the same period (ie, controls). METHODS: Adjusted odds ratios (aORs) of infection were estimated using regression logistic models evaluating demographic and employment characteristics (all 4,919 cases and 4,803 controls) or household and workplace exposures and IPC measures (2,046 patient-facing cases and 1,362 controls). RESULTS: COVID-19 risk was associated with working as housekeeping staff (aOR, 3.6), as a patient-support assistant (aOR, 1.9), and as nursing staff (aOR, 1.4), compared to administrative staff. Other risk factors included being unexperienced (aOR, 1.5) and working in private seniors' homes (aOR, 2.1) or long-term care facilities (aOR, 1.5), compared to acute-care hospitals. Among patient-facing HCWs, exposure to a household contact was reported by 9% of cases and was associated with the highest risk of infection (aOR, 7.8). Most infections were likely attributable to more frequent exposure to infected patients (aOR, 2.7) and coworkers (aOR, 2.2). Wearing an N95 respirator during contacts with COVID-19 patients (aOR, 0.7) and vaccination (aOR, 0.2) were the measures associated with risk reduction. CONCLUSION: In the context of the everchanging SARS-CoV-2 virus with increasing transmissibility, measures to ensure HCW protection, including vaccination and respiratory protection, and patient safety will require ongoing evaluation.

Prostate cancer-Exercise and Metformin Trial (Pre-EMpT): study protocol for a feasibility factorial randomized controlled trial in men with localised or locally advanced prostate cancer.

BACKGROUND: Evidence from observational studies have shown that moderate intensity physical activity can reduce risk of progression and cancer-specific mortality in participants with prostate cancer. Epidemiological studies have also shown participants taking metformin to have a reduced risk of prostate cancer. However, data from randomised controlled trials supporting the use of these interventions are limited. The Prostate cancer-Exercise and Metformin Trial examines that feasibility of randomising participants diagnosed with localised or locally advanced prostate cancer to interventions that modify physical activity and blood glucose levels. The primary outcomes are randomisation rates and adherence to the interventions over 6 months. The secondary outcomes include intervention tolerability and retention rates, measures of insulin-like growth factor I, prostate-specific antigen, physical activity, symptom-reporting, and quality of life. METHODS: Participants are randomised in a 2 × 2 factorial design to both a physical activity (brisk walking or control) and a pharmacological (metformin or control) intervention. Participants perform the interventions for 6 months with final measures collected at 12 months follow-up. DISCUSSION: Our trial will determine whether participants diagnosed with localised or locally advanced prostate cancer, who are scheduled for radical treatments or being monitored for signs of cancer progression, can be randomised to a 6 months physical activity and metformin intervention. The findings from our trial will inform a larger trial powered to examine the clinical benefits of these interventions. TRIAL REGISTRATION: Prostate Cancer Exercise and Metformin Trial (Pre-EMpT) is registered on the ISRCTN registry, reference number ISRCTN13543667 . Date of registration 2nd August 2018-retrospectively registered. First participant was recruited on 11th September 2018.

Forming the Hematology-Oncology Collaborative Videoconferencing (CO-VID) Learning Initiative: Experiential Lessons Learned From a Novel Trainee-Led Multidisciplinary Virtual Learning Platform.

PURPOSE: COVID-19 challenged medical practice and graduate medical education. Building on previous initiatives, we describe and reflect on the formative process and goals of the Hematology-Oncology Collaborative Videoconferencing Learning Initiative, a trainee-led multi-institutional virtual COVID-19 learning model. METHODS: Clinical fellows and faculty from 13 US training institutions developed consensus needs, goals, and objectives, recruited presenters, and generated a multidisciplinary COVID-19 curriculum. Weekly Zoom conferences consisted of two trainee-led instructional segments and a trainee-moderated faculty Q&A panel. Hematology-oncology training program faculty and trainees were the targeted audience. Leadership evaluations consisted of anonymized baseline and concluding mixed methods surveys. Presenter evaluations consisted of session debriefs and two structured focus groups. Conference evaluations consisted of attendance, demographics, and pre- or postmultiple-choice questions on topic learning objectives. RESULTS: In 6 weeks, the initiative produced five conferences: antivirals, anticoagulation, pulmonology, provider resilience, and resource scarcity ethics. The average attendance was 100 (range 57-185). Among attendees providing both pre- and postconference data, group-level knowledge appeared to increase: antiviral (n = 46) pre-/postcorrect 82.6%/97.8% and incorrect 10.9%/2.2%, anticoagulation (n = 60) pre-/postcorrect 75%/93.3% and incorrect 15%/6.7%, and pulmonary (n = 21) pre-/postcorrect 66.7%/95.2% and incorrect 33.3%/4.8%. Although pulmonary management comfort appeared to increase, comfort managing of antivirals and anticoagulation was unchanged. At the conclusion of the pilot, leadership trainees reported improved self-confidence organizing multi-institutional collaborations, median (interquartile range) 58.5 (50-64) compared with baseline 34 (26-39), but did not report improved confidence in other educational or leadership skills. CONCLUSION: During crisis, trainees built a multi-institutional virtual education platform for the purposes of sharing pandemic experiences and knowledge. Accomplishment of initiative goals was mixed. Lessons learned from the process and goals may improve future disaster educational initiatives.

Upgrades to intensive care: The effects of COVID-19 on decision-making in the emergency department.

INTRODUCTION: The initial surge of critically ill patients in the COVID-19 pandemic severely disrupted processes at acute care hospitals. This study examines the frequency and causes for patients upgraded to intensive care unit (ICU) level care following admission from the emergency department (ED) to non-critical care units. METHODS: The number of ICU upgrades per month was determined, including the percentage of upgrades noted to have non-concordant diagnoses. Charts with non-concordant diagnoses were examined in detail as to the ED medical decision-making, clinical circumstances surrounding the upgrade, and presence of a diagnosis of COVID-19. For each case, a cognitive bias was assigned. RESULTS: The percentage of upgraded cases with non-concordant diagnoses increased from a baseline range of 14-20% to 41.3%. The majority of upgrades were due to premature closure (72.2%), anchoring (61.1%), and confirmation bias (55.6%). CONCLUSION: Consistent with the behavioral literature, this suggests that stressful ambient conditions affect cognitive reasoning processes.

Characterization and evolution of infection control practices among severe acute respiratory coronavirus virus 2 (SARS-CoV-2)-infected healthcare workers in acute-care hospitals and long-term care facilities in Québec, Canada, Spring 2020.

OBJECTIVES: In this study, we aimed to (1) estimate the severe acute respiratory coronavirus 2 (SARS-CoV-2) infection rate and the secondary attack rate among healthcare workers (HCWs) in Québec, the most affected province of Canada during the first wave; (2) describe the evolution of work-related exposures and infection prevention and control (IPC) practices in infected HCWs; and (3) compare the exposures and practices between acute-care hospitals (ACHs) and long-term care facilities (LTCFs). DESIGN: Survey of cases. PARTICIPANTS: The study included Québec HCWs from private and public institutions with laboratory-confirmed coronavirus disease 2019 (COVID-19) diagnosed between March 1 and June 14, 2020. HCWs aged ≥18 years who worked during the exposure period and survived their illness were eligible for the survey. METHODS: After obtaining consent, 4,542 HCWs completed a standardized questionnaire. COVID-19 rates and proportions of exposures and practices were estimated and compared between ACHs and LTCFs. RESULTS: HCWs represented 13,726 (25%) of 54,005 reported COVID-19 cases in Québec and had an 11-times greater rate of COVID-19 than non-HCWs. Their secondary household attack rate was 30%. Most affected occupations were healthcare support workers, nurses and nurse assistants working in LTCFs (45%) and ACHs (30%). Compared to ACHs, HCWs in LTCFs had less training, higher staff mobility between working sites, similar PPE use, and better self-reported compliance with at-work physical distancing. Suboptimal IPC practices declined over time but were still present at the end of the first wave. CONCLUSION: Québec HCWs and their families were severely affected during the first wave of COVID-19. Insufficient pandemic preparedness and suboptimal IPC practices likely contributed to high transmission in both LTCFs and ACHs.

The Use of Primary Care Big Data in Understanding the Pharmacoepidemiology of COVID-19: A Consensus Statement From the COVID-19 Primary Care Database Consortium.

The use of big data containing millions of primary care medical records provides an opportunity for rapid research to help inform patient care and policy decisions during the first and subsequent waves of the coronavirus disease 2019 (COVID-19) pandemic. Routinely collected primary care data have previously been used for national pandemic surveillance, quantifying associations between exposures and outcomes, identifying high risk populations, and examining the effects of interventions at scale, but there is no consensus on how to effectively conduct or report these data for COVID-19 research. A COVID-19 primary care database consortium was established in April 2020 and its researchers have ongoing COVID-19 projects in overlapping data sets with over 40 million primary care records in the United Kingdom that are variously linked to public health, secondary care, and vital status records. This consensus agreement is aimed at facilitating transparency and rigor in methodological approaches, and consistency in defining and reporting cases, exposures, confounders, stratification variables, and outcomes in relation to the pharmacoepidemiology of COVID-19. This will facilitate comparison, validation, and meta-analyses of research during and after the pandemic.

The Integrated RNA Landscape of Renal Preconditioning against Ischemia-Reperfusion Injury.

BACKGROUND: Although AKI lacks effective therapeutic approaches, preventive strategies using preconditioning protocols, including caloric restriction and hypoxic preconditioning, have been shown to prevent injury in animal models. A better understanding of the molecular mechanisms that underlie the enhanced resistance to AKI conferred by such approaches is needed to facilitate clinical use. We hypothesized that these preconditioning strategies use similar pathways to augment cellular stress resistance. METHODS: To identify genes and pathways shared by caloric restriction and hypoxic preconditioning, we used RNA-sequencing transcriptome profiling to compare the transcriptional response with both modes of preconditioning in mice before and after renal ischemia-reperfusion injury. RESULTS: The gene expression signatures induced by both preconditioning strategies involve distinct common genes and pathways that overlap significantly with the transcriptional changes observed after ischemia-reperfusion injury. These changes primarily affect oxidation-reduction processes and have a major effect on mitochondrial processes. We found that 16 of the genes differentially regulated by both modes of preconditioning were strongly correlated with clinical outcome; most of these genes had not previously been directly linked to AKI. CONCLUSIONS: This comparative analysis of the gene expression signatures in preconditioning strategies shows overlapping patterns in caloric restriction and hypoxic preconditioning, pointing toward common molecular mechanisms. Our analysis identified a limited set of target genes not previously known to be associated with AKI; further study of their potential to provide the basis for novel preventive strategies is warranted. To allow for optimal interactive usability of the data by the kidney research community, we provide an online interface for user-defined interrogation of the gene expression datasets (http://shiny.cecad.uni-koeln.de:3838/IRaP/).

Ivermectin: An Anthelmintic, an Insecticide, and Much More.

Here we tell the story of ivermectin, describing its anthelmintic and insecticidal actions and recent studies that have sought to reposition ivermectin for the treatment of other diseases that are not caused by helminth and insect parasites. The standard theory of its anthelmintic and insecticidal mode of action is that it is a selective positive allosteric modulator of glutamate-gated chloride channels found in nematodes and insects. At higher concentrations, ivermectin also acts as an allosteric modulator of ion channels found in host central nervous systems. In addition, in tissue culture, at concentrations higher than anthelmintic concentrations, ivermectin shows antiviral, antimalarial, antimetabolic, and anticancer effects. Caution is required before extrapolating from these preliminary repositioning experiments to clinical use, particularly for Covid-19 treatment, because of the high concentrations of ivermectin used in tissue-culture experiments.

Agent-Based Simulation for Evaluation of Contact-Tracing Policies Against the Spread of SARS-CoV-2 (preprint)

The decline of active COVID-19 cases in many countries in the world has proved that lockdown policies are indeed a very effective measure to stop the exponential spread of the virus. Still, the danger of a second wave of infections is omnipresent and it is clear, that every policy of the lockdown has to be carefully evaluated and possibly replaced by a different, less restrictive policy, before it can be lifted. Tracing of contacts and consequential tracing and breaking of infection-chains is a promising and comparably straightforward strategy to help containing the disease, although its precise impact on the epidemic is unknown. In order to quantify the benefits of tracing and similar policies we developed an agent-based model that not only validly depicts the spread of the disease, but allows for exploratory analysis of containment policies. We will describe our model and perform case studies in which we use the model to quantify impact of contact tracing in different characteristics and draw valuable conclusions about contact tracing policies in general.