Exploring pandemic metaphors in educational contexts: a survey on the language of teachers and educators in Reggio Emilia, Italy.

This study aimed to explore how metaphors were used to interpret the pandemic and to address its challenges in primary and secondary schools in Reggio Emilia, Italy. A questionnaire was administered to educators and teachers to understand how languages, images, and metaphors were used by themselves and their students to talk about the pandemic and their experiences of living with it. The goal of the questionnaire was to guide critical reflection and encourage more informed language choices. While the existing literature points out the alleged overuse of war metaphors and military frames in public discourse, our findings show that war metaphors are relatively frequent, with other metaphorical frames widely used by teachers and educators to foster resilient attitudes in students. Moreover, in their professional contexts, teachers and educators mostly use metaphorical frames involving resilient attitudes. Our interpretation of the results supports the hypothesis that the purposeful use and deliberate production of metaphors support the choice of metaphors with positive, constructive implications. Finally, some implications of these findings on the theory of metaphor and the methodology of the research are discussed.

Critical discourse studies and 'times of crisis': a proposal for re-existences based on Critical Aquilombage and Pragmatic Networks perspectives

The purpose of this reflection is to contribute to the debate on Critical Discourse Studies, through the presentation of original theoretical-methodological possibilities of anti-colonial nature, attentive and committed to the citizen struggle. Therefore, as a scenario of reflection and potential epistemological and methodological application, the concept of Critical Aquilombage – CA – (SANTOS, 2019;2021;2022) is described and applied in intersection with the concept of Pragmatic Networks – PR – (SANTOS, 2017;2019);the 'discourse of crisis' (located in the context of the Covid-19 pandemic in Brazil) is used as illustration for the analysis. In the text, theoretical-methodological understandings related to discourse are developed, as well as the critical discourse analysis (FAIRCLOUGH, 2003;2010;RESENDE, 2019) oriented to the consolidation of reexistence movements (SOUZA, 2009;2011). In this way, a critical reflection and potential application of the epistemological-methodological-ontological enterprise CA-PR are presented, approaching them to the problematization of the term 'crisis'. Finally, it is possible to argue that the term ‘crisis' has been strategically used by social representants of symbolic and material power to operate the existential emptiness of Black People, operating the non-existence process (that is, sophisticated discursive movements in which existences are affected and erased, to the detriment of few others – which ones, for centuries, have continued to manipulate language and society in order to maintain places of social privilege and prestige): on the other hand, the critical-reflective use of texts can point to new modes of resistance. © 2022 Thesaurus Editora de Brasilia Ltda.. All rights reserved.

COVID-19 vaccine short-term adverse events in the real-life family practice in Krakow, Poland.

BACKGROUND: In manufacturers' trials, vaccination against COVID-19 proved to be safe and effective. The officially reported frequency of vaccine adverse events (VAEs) in Poland is lower than that declared by the manufacturers. The anti-vaccination activists questioned the trustworthiness of official data. OBJECTIVES: The aim was to explore the real-life prevalence of VAEs in general practice settings and the factors that may influence it. METHODS: In this pragmatic, mixed prospective and retrospective study, patients vaccinated against COVID-19 between May and October 2021 in three GP practices in Krakow, Poland, were enrolled. Their demographic (age, sex, level of education) and clinical data (weight and height, smoking status, history of allergies, COVID-19 and chronic diseases) were collected. Then, they were interviewed about VAEs they experienced. RESULTS: Out of 1530 patients invited to participate, 1051 (69%) agreed and were eligible for analyses. Only 8.8% did not report any VAE. Pain at the injection site was the most frequently reported reaction (800, 76.2%). The most prevalent systemic ones were excessive fatigue/lethargy (527, 50.6%), sleep/circadian rhythm disturbances (433, 41.6%) and headache (399, 38.3%). Fifty required medical assistance - 39 experienced presyncope (3.7%) and 11 loss of consciousness (1.1%). Only two others were hospitalised. Females, younger adults, those with higher education and with a history of COVID-19 reported systemic VAEs more frequently, while those who were older and obese were less likely to report local reactions. CONCLUSION: Although more than 90% of patients vaccinated against COVID-19 in general practice settings may experience VAEs, in short-term observation, the vast majority are localised and mild.

The clinical evaluation of Basti along with Rasayana on symptoms of post-COVID-19 syndrome: an open-labeled proof of concept pragmatic study-a study protocol.

BACKGROUND: Post-COVID-19 syndrome is a result of triggering various immune pathways and metabolic disturbances. Basti is an important per rectal Ayurveda-based treatment having multi-targeted actions. Basti and Rasayana treatment modulate immune responses by regulating pro-inflammatory cytokines, immune globulins, and functional properties of T cell. We propose to study the clinical evaluation of Basti along with Rasayana (rejuvenation therapy) on symptoms of post-COVID 19 syndrome. METHODS AND ANALYSIS: We designed a prospective, open-labeled proof of concept pragmatic study. The study duration is 18 months, and the intervention period are 35 days from the day of enrollment of the patients. The patients will be treated on the basis of Ayurvedic classification of Santarpanottha (over nutrition) symptoms and Apatarpanottha (lack of nutrition) symptoms. The Santarpanottha group will be treated within 3-5 days of oral Guggulu Tiktak Kashayam followed by 8 days of Yog Basti treatment and then 21 days of Rasayana therapy with Brahma Rasayan. The Apatarpanottha group will be treated within 3-5 days of oral Laghumalini Vasant, followed by 8 days of Yog Basti treatment and then 21 days of Kalyanak Ghrit. The outcome measures of this study will be to evaluate the changes in fatigue severity scale, MMRC dyspnea chest pain scale, pain score assessed by VAS scale, smell and taste scale, WOMAC scale, Hamilton depression scale, Hamilton anxiety scale, Insomnia Severity Index, change in Cough Severity Index, facial aging scale, dizziness scale, Pittsburgh Sleep Severity Quality Index, functional status scale, and heart palpitation scale. All adverse events will be monitored at each time throughout the study visit time. A total of 24 participants will be recruited to demonstrate with 95% confidence interval and 80% power. DISCUSSION: Ayurveda treats Santarpanottha (originated from over nutrition) symptoms and Apatarpanottha (symptoms originated from undernutrition) symptoms differently; hence, inspite of the same disease or symptom management, changes depend upon the type of the origin. This pragmatic clinical study is developed on the fundamental grounds of Ayurveda. ETHICS AND DISSEMINATION: Ethics approval was obtained through the Institutional Ethics Committees of Government Ayurved College and Hospital on 23 July 2021. TRIAL REGISTRATION: The trial is prospectively registered with the Clinical Trial Registry of India on 17 August 2021 [CTRI/2021/08/035732] after the Institutional Ethics Committee approval [GACN/PGS/Synopsis/800/2021 Date 23/7/2021].

Effect of hospital-at-home vs. traditional brick-and-mortar hospital care in acutely ill adults: study protocol for a pragmatic randomized controlled trial.

BACKGROUND: Delivering acute hospital care to patients at home might reduce costs and improve patient experience. Mayo Clinic's Advanced Care at Home (ACH) program is a novel virtual hybrid model of "Hospital at Home." This pragmatic randomized controlled non-inferiority trial aims to compare two acute care delivery models: ACH vs. traditional brick-and-mortar hospital care in acutely ill patients. METHODS: We aim to enroll 360 acutely ill adult patients (≥18 years) who are admitted to three hospitals in Arizona, Florida, and Wisconsin, two of which are academic medical centers and one is a community-based practice. The eligibility criteria will follow what is used in routine practice determined by local clinical teams, including clinical stability, social stability, health insurance plans, and zip codes. Patients will be randomized 1:1 to ACH or traditional inpatient care, stratified by site. The primary outcome is a composite outcome of all-cause mortality and 30-day readmission. Secondary outcomes include individual outcomes in the composite endpoint, fall with injury, medication errors, emergency room visit, transfer to intensive care unit (ICU), cost, the number of days alive out of hospital, and patient-reported quality of life. A mixed-methods study will be conducted with patients, clinicians, and other staff to investigate their experience. DISCUSSION: The pragmatic trial will examine a novel virtual hybrid model for delivering high-acuity medical care at home. The findings will inform patient selection and future large-scale implementation. TRIAL REGISTRATION: ClinicalTrials.gov NCT05212077. Registered on 27 January 2022.

Increasing patient participation in oncology clinical trials.

AIM: Timely recruitment of eligible participants is essential for the success of clinical trials, with insufficient accrual being the leading cause for premature termination of both oncology and non-oncology trials. METHODS: In this paper we further elaborate on the challenges for patient participation in oncology trials from physician, patient, healthcare system, and some trial-related perspectives. RESULTS: We present strategies such as use of digital healthcare technologies, real-world data and real-world evidence, decentralized clinical trials, pragmatic trial designs, and supportive services to increase patient participation. CONCLUSIONS: Multifaceted measures are necessary to increase patient participation, especially for those who are under-represented in cancer trials.

Impact of COVID-19 pandemic on nonpharmacological pain management trials in military and veteran healthcare settings: an evaluation informed by implementation science.

The coronavirus disease (COVID-19) pandemic disrupted healthcare and clinical research, including a suite of 11 pragmatic clinical trials (PCTs), across clinics within the Department of Veterans Affairs (VA) and the Department of Defense (DOD). These PCTs were designed to evaluate an array of nonpharmacological treatments and models of care for treatment of patients with pain and co-occurring conditions. The aims of the study are to (a) describe modifications to PCTs and interventions to address the evolving pandemic and (b) describe the application of implementation science methods for evaluation of those PCT modifications. The project used a two-phase, sequential, mixed-methods design. In Phase I, we captured PCT disruptions and modifications via a Research Electronic Data Capture questionnaire, using Periodic Reflections methods as a guide. In Phase II, we utilized the Framework for Reporting Adaptations and Modifications-Expanded (FRAME) taxonomy to develop a focus group interview guide and checklist that would provide more in-depth data than Phase I. Data were analyzed using directed content analysis. Phase I revealed that all PCTs made between two and six trial modifications. Phase II, FRAME-guided analyses showed that the key goals for modifying interventions were increasing treatment feasibility and decreasing patient exposure to COVID-19, while preserving intervention core elements. Context (format) modifications led eight PCTs to modify parts of the interventions for virtual delivery. Content modifications added elements to enhance patient safety; tailored interventions for virtual delivery (counseling, exercise, mindfulness); and modified interventions involving manual therapies. Implementation science methods identified near-real-time disruptions and modifications to PCTs focused on pain management in veteran and military healthcare settings.

Active-duty personnel and veterans often report pain and seek treatment in military and veteran healthcare settings. Nondrug treatments, such as self-care, counseling, exercise, and manual therapy, are recommended for most patients with chronic pain. The COVID-19 pandemic has affected clinical trials of these nondrug treatments in military and veteran populations. In this study, we explored how 11 research teams adapted study trials on pain to address COVID-19. Team members completed online questions, brief checklists, and a one-time focus group about how they modified their trials. Each of the 11 trials made 2 to 6 changes to their studies. Most paused or delayed recruitment efforts. Many shifted parts of the study to a virtual format. Goals for adapting treatments included improved feasibility and decreased patient exposure to COVID-19. Context or format changes increased virtual delivery of study treatments. Content changes focused on patient safety, tailoring treatments for virtual delivery, and offering varied manual therapies. Provider concerns about technology and patient willingness to seek in-person care during the pandemic also were factors driving changes. These findings may support the increased use of virtual care for pain management in military and veteran health settings.

The impact of COVID-19 on a large pragmatic clinical trial embedded in primary care.

INTRODUCTION: The COVID-19 pandemic had significant impact on clinical care and clinical trial operations, but the impact on decentralized pragmatic trials is unclear. The Diuretic Comparison Project (DCP) is a Point-of Care (POC) pragmatic trial testing whether chlorthalidone is superior to hydrochlorothiazide in preventing major cardiovascular (CV) events and non-cancer death. DCP utilized telephone consent, data collection from the electronic health record and Medicare, forwent study visits, and limited provider commitment beyond usual care. We assessed the impact of COVID-19 on recruitment, follow-up, data collection, and outcome ascertainment in DCP. METHODS: We compared data from two 8-month periods: Pre-Pandemic (July 2019-February 2020) and Mid-Pandemic (July 2020-February 2021). Consent and randomization rates, diuretic adherence, blood pressure (BP) and electrolyte follow-up rates, records of CV events, hospitalization, and death rates were compared. RESULTS: Providers participated at a lower rate mid-pandemic (65%) than pre-pandemic (71%), but more patients were contacted (7622 vs. 5363) and consented (3718 vs. 3048) mid-pandemic than pre-pandemic. Patients refilled medications and remained on their randomized diuretic equally (90%) in both periods. Overall, rates of BP, electrolyte measurements, and hospitalizations decreased mid-pandemic while deaths increased. CONCLUSIONS: While recruitment, enrollment, and adherence did not suffer during the pandemic, documented blood pressure checks and laboratory evaluations decreased, likely due to fewer in-person visits. VA hospitalizations decreased, despite a considerable number of COVID-related hospitalizations. This suggests changes in clinical care during the pandemic, but the limited impact on DCP's operations during a global pandemic is an important strength of POC trials. CLINICAL TRIAL REGISTRATION: NCT02185417.

Implementation Challenges for a Multisite Advance Care Planning Pragmatic Trial: Lessons Learned.

BACKGROUND/PROBLEM: Advance care planning (ACP) pragmatic trials are needed. PROPOSED SOLUTION: We determined key system-level activities to implement ACP interventions for a cluster-randomized pragmatic trial. We identified patients with serious illness from 50 primary care clinics across three University of California health systems using a validated algorithm. If patients lacked documented ACP within the last 3 years, they were eligible for an intervention: (Arm 1) an advance directive (AD); (Arm 2) AD + PREPAREforYourCare.org; (Arm 3) AD + PREPARE + lay health navigator outreach. Triggered by an appointment, we mailed and sent interventions through automated electronic health record (EHR) messaging. We collaborated with patients/caregivers, clinicians, payors, and national/health system leader advisors. We are currently finalizing 24 months follow-up data. OUTCOMES/METHODS: We used the Consolidated Framework for Implementation Research (CFIR) and Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) frameworks to track secular trends and implementation efforts. KEY MESSAGE/RESULTS: Required multisite, system-level activities: 1) obtaining leadership, legal/privacy, and EHR approvals; 2) standardizing ACP documentation; 3) providing clinician education; 3) validating an automated serious illness identification algorithm; 4) standardizing ACP messaging with input from over 100 key advisors; 5) monitoring secular trends (e.g., COVID); and 6) standardizing ACP workflows (e.g., scanned ADs). Of 8707 patients with serious illness, 6883 were eligible for an intervention. Across all arms, 99% received the mailed intervention, 78.3% had an active patient portal (64.2% opened intervention), and 90.5% of arm three patients (n = 2243) received navigator outreach. LESSONS LEARNED: Implementing a multisite health system-wide ACP program and pragmatic trial, with automated EHR-based cohort identification and intervention delivery, requires a high level of multidisciplinary key advisor engagement, standardization, and monitoring. These activities provide guidance for the implementation of other large-scale, population-based ACP efforts.

Using a Single Irb for Nih-Funded Multisite Trials

As clinical trials evolve, the oversight by Institutional Review Boards (IRBs) has also evolved to meet everexpanding needs for both efficiency and changing regulatory requirements in the protection of human subjects. The most significant regulatory change to occur was the change to the Revised Common Rule Research Provision (45 CFR 46.114(b)) that went into effect on 20 January 2020, requiring all cooperative research subject to the Common Rule to use a single Institutional Review Board (sIRB) to review the research. Since the Common Rule affects all federally funded research, clinical trialists performing multicenter trials using federal grants are now required to use an sIRB instead of individual IRBs at each research site in their trials. For those multicenter trialists, using an sIRB offers efficiencies in time and effort which can aid in bringing trial results to fruition both faster and at a lower cost while still providing protection to human subjects. While commercial sIRBs have been available for many years, sIRBs placed at academic institutions and health care systems are relatively new. They can offer the benefit of lower cost for trialists within an institution, and better overall trial management by having more frequent communication and discussion regarding trial issues as well as improved safety management through aggregate safety review. They can also offer increased speed of research review with cooperative planning between trialist and the sIRB representatives. This session will focus on the use of sIRBs from various perspectives to give the view from an academic sIRB, from end users of both an academic sIRB and a health system IRB, and guidance from a clinical regulatory specialist regarding maintaining a trial master file while using an sIRB. Mr. Jarrod Feld from the University of Iowa will present from his perspective as the External IRB Coordinator at the University of Iowa. Mr. Feld coordinates reliance and compliance for University of Iowa human research studies which use the University of Iowa Institutional Review Board as their sIRB, and studies where Iowa relies on another institutional IRB. Mr. Feld also provides guidance to investigators on using an sIRB. Using his experience, Mr. Feld will outline the nature of reliance agreements, discuss working with a range of local IRBs to develop understanding regarding the reliance program and outline best practices for using an sIRB, and discuss enhanced safety management oversight when using an sIRB for large multisite trial. Ms. Tina Neill-Hudson from the University of Iowa will present from her experience as the sIRB Liaison for both the Acute to Chronic Pain Signature (A2CPS) Consortium, an NIH (National Institutes of Health)- funded multisite observational trial, and the Fibromyalgia and TENS in Physical Therapy Study (FM TIPS) study, an NIH-funded embedded pragmatic clinical trial. Ms. Neill-Hudson works with relying sites on completing the necessary regulatory documents needed for reliance agreements and sIRB approval. Ms. Neill-Hudson will discuss the process for obtaining reliance for institutions who may or may not have local IRB oversight and provide examples of specific steps and procedures for obtaining sIRB approval in a timely manner. Ms. Neill-Hudson will speak to the importance of having an sIRB liaison on the study team and the use of SMART IRB. Ms. Catherine Gladden from MassGeneral Brigham will present on using an sIRB for multicenter NIHfunded trials. Ms. Gladden will discuss the use of a Consortium-level reliance agreement and role of the local IRBs. Ms. Gladden oversees the sIRB liaison team at the Coordinating Center for the NeuroNEXT Network and works with the sIRB and local IRBs to ensure local policies and requirements are followed while maintaining compliance with the sIRB and the NeuroNEXT reliance agreement. Ms. Gladden will be discussing best practices for using an sIRB in a multicenter trial and discuss the experience of using an sIRB in the safety management plan. Ms. Cynthia Diltz from the University of Iowa wi l present on the topic of managing a trial master file while using an sIRB. Ms. Diltz will speak on her experience with electronic trial master files versus hard copy master files, and in using commercial software for trial master file management. Using an electronic trial master file is a necessity in the scheme of using an sIRB to assist sponsors and individual clinical research sites to view Institutional Review Board documents in real time and to provide a single storage location for documentation of Institutional Review Board approvals and activities such as continuing review. This session is timely due to the change to the Common Rule mandating the use of an sIRB for all research subject to the Common Rule, which has the most significant impact on trialists at academic institutions and health care systems. In an era of the need for timely study results for use in addressing urgent public health policy concerns, using an sIRB is becoming a necessity. The speed with which clinical trials need to be managed by an IRB has accelerated during recent public health care crises, notably the COVID-19 pandemic. In addition, it is likely that there will be changes to local IRBs as the norm becomes using an sIRB for any research subject to the Common Rule. Investigators and clinical site staff will require education on the evolution of human subject's protection and research review happening at an sIRB instead of within their local IRBs, and assistance in understanding the process and planning for success will be crucial.

The self-society duality in volunteer tourism: An analytical framework for the (post-)pandemic era

Volunteer tourism straddles the intersection of two seemingly conflicting nonwork activities: traveling, with largely self-serving aspects, and volunteering, with society-serving aspects. This self–society duality is a defining feature of the practice, which carries moral ambiguities and may undermine the volunteer's moral self-worth. However, little is known about how volunteers account for this duality and maintain their moral self-worth. Exploring volunteers' perceptions of this duality is more important than ever in "the new present” under COVID-19, where a personal quest for pleasure runs counter to public health and the common good, and the self–society duality in volunteer tourism may be intensified. Drawing on pragmatic sociology and in-depth interviews with volunteer tourists, this article shows that volunteer tourists comprise narratives that intertwine the self-serving aspects of volunteering and multiple beliefs about the common good. Through these narratives, interviewees move between self-serving and society-serving aspects, overcome moral ambiguity, and deem themselves as living up to moral standards. The different elements that comprise the interviewees' narratives reveal a narrative form about moral good particular to tourism. Highlighting these elements, this article proposes an analytical framework through which volunteer tourists' moral views and the relation between self-serving and society-serving in volunteer tourism can be explored. © 2023 The Authors

Accommodating ''History Effects'' in Long Duration, Multisite Clinical Trials to Ensure Relevant and Compelling Evidence

Over the course of a clinical trial, changes in the practice environment have the potential to reduce internal and external validity and impact change in patient outcomes. Such ''history effects''1 can take the form of changes in standard of care, clinical guidelines and recommendations, new drug/device availability in the marketplace, testing and screening procedures, and, as recently experienced, a global pandemic. Clinical trials conducted over many years are particularly susceptible to history effects. Such effects can impact foundational ability to continue a trial, including clinician equipoise and ability to implement trial interventions, necessitating awareness and action planning. For example, Curtis et al.2 acknowledged challenges with clinical guideline history effects and issued recommendations for addressing them such as consideration of participant wellbeing, stakeholder engagement, safety monitoring, review of guideline and policy changes, and development of rules for protocol changes. This session will explore how four multisite clinical trials conducted with VA Cooperative Studies Program sponsorship and coordination have weathered history effects during prolonged periods of enrollment. Topics to be covered include the implementation of pragmatic designs, monitoring of clinical guidelines, assessing control group treatment conditions, modifying protocols, adjusting quality assurance procedures, refining recruitment pathways, and training site investigators. The speakers, Study Chairs, will describe best practices and provide recommendations for navigating history effects in prolonged multisite clinical trials that can ensure outcomes remain relevant and compelling to inform public health at trial commencement. The CSP 2008/PTXRx study is a pragmatic, randomized, double-blind, placebo-controlled, multicenter clinical trial of Veteran patients with diabetic kidney disease (DKD) examining whether pentoxifylline (PTX), when added to usual care, can delay time to end-stage renal disease or death. Enrollment for the study began in 2019, and it is anticipated that 9 years of follow-up will be required to observe the required number of primary events. Given the long duration of the study, changes in clinical guidelines were anticipated and have occurred, including the approval of new DKD therapies and introduction of a new formula for estimated glomerular filtration rate (eGFR) calculation. In anticipation of these changes, the study design allows for whatever standard of care is extant at any time during the course of the study. PTXR's pragmatic trial design and protocol leverage the VA's research infrastructure and remote platforms allowing the study to be responsive to external changes and to safely continue during a global pandemic. The CSP 596/OPTION study is a randomized, double- blind, multicenter trial of Veteran patients with a first or second recurrent Clostridium difficile infection (CDI) comparing (1) fidaxomicin and (2) vancomycin, followed by a taper and pulse to (3) a standard vancomycin regimen. Since enrollment began in 2016, significant changes in CDI epidemiology and clinical management have impacted the study. The COVID-19 pandemic also resulted in an administrative hold on all trial activity followed by staggered reopening of sites due to variable COVID-19 activity and clinical priorities. Many clinical laboratories switched to algorithms that included free toxin assays in addition to polymerase chain reaction (PCR) tests out of concern for overdiagnosis based on PCR testing alone, reducing the number of potentially enrollable cases. There has been increased empirical vancomycin treatment for recurrent CDI without confirmation by stool testing, a requirement for enrollment, and a recruitment strategy for identifying potential cases. Finally, conflicting clinical guidelines for recurrent CDI has created potential equipoise when considering enrollment. Ongoing educational efforts have been made to clarify the protocol and emphasize the validity of the research question as well as protoco changes to allow safe enrollment and follow-up of participants in the face of the ongoing COVID-19 pandemic. The CSP 2005/VALOR is a phase III randomized, open label, multicenter clinical trial of Veteran patients with operable stage I non-small cell lung cancer that compares stereotactic radiotherapy and anatomic pulmonary resection with a primary outcome measure of overall survival. The study was activated in 2017 and recruitment to the trial has been affected by ongoing changes in public and clinician perceptions about stereotactic radiotherapy and surgery that have interfered with equipoise and willingness of participants to enroll. The study team perpetually addresses this challenge through group conversations with local site investigators, study coordinators, and other research personnel to preserve group equipoise across the study. Since the study's activation, new safety information about stereotactic radiotherapy has emerged necessitating protocol modifications while aiming to preserve internal and external validity. The includes modifying standard operating procedures for the study's centralized quality assurance program that has had to adapt its process to remain contemporary. STARPORT, funded by VA CSRD with CSP collaboration, is a randomized, open label, multicenter clinical trial of Veteran patients with oligorecurrent prostate cancer comparing the effects of standard systemic therapy (SST) alone or with PET-directed local therapy using surgery or radiation. Although enrollment was initiated in 2021, changes are already evident in clinical practice guidelines regarding the use of imaging in workup in this patient population. Shortly before the start of accrual, 18F-DCFPyL PSMA PET/CT received FDA-approval. Consequently, it is being rapidly adopted at the STARPORT VA medical centers and the use of conventional imaging using CT or bone scan prior to PET/CT imaging-part of the original eligibility criteria-quickly is falling out of favor. Furthermore, shortly after the start of enrollment, NCCN guidelines adopted the stance that conventional imaging was no longer required in the setting of PSMA PET/CT imaging, solidifying the transition away from conventional imaging. Thus, the protocol is being amended to remove the requirement for conventional imaging as part of workup for oligorecurrence. In addition, to be generalizable, the study is designed to integrate future PSMA radiotracers that are incorporated into practice as well as changes in SST regimens over the time of the study.

The evolving landscape of pulmonary arterial hypertension clinical trials

Although it is a rare disease, the number of available therapeutic options for treating pulmonary arterial hypertension has increased since the late 1990s, with multiple drugs developed that are shown to be effective in phase 3 randomised controlled trials. Despite considerable advancements in pulmonary arterial hypertension treatment, prognosis remains poor. Existing therapies target pulmonary endothelial dysfunction with vasodilation and anti-proliferative effects. Novel therapies that target proliferative vascular remodelling and affect important outcomes are urgently needed. There is need for additional innovations in clinical trial design so that all emerging candidate therapies can be rigorously studied. Pulmonary arterial hypertension trial design has shifted from short-term submaximal exercise capacity as a primary endpoint, to larger clinical event-driven trial outcomes. Event-driven pulmonary arterial hypertension trials could face feasibility and efficiency issues in the future because increasing sample sizes and longer follow-up durations are needed, which would be problematic in such a rare disease. Enrichment strategies, innovative and alternative trial designs, and novel trial endpoints are potential solutions that could improve the efficiency of future pulmonary arterial hypertension trials while maintaining robustness and clinically meaningful evidence.Copyright © 2022 Elsevier Ltd

Optimizing Precision Medicine Cancer Clinical Trials

With the advent of precision medicine, getting the right treatment for the right patient at the right time has illuminated a variety of challenges and opportunities for innovation in trial design and conduct. Although there is no onesize- fits-all approach to precision medicine, a number of approaches, particularly basket and umbrella trial platforms that permit simultaneous evaluation of multiple treatments in multiple patient cohorts, have evolved to improve trial efficiency. The novel coronavirus pandemic has illuminated the need for, and feasibility of, conducting trials with fewer requirements, greater flexibility, and more decentralization. Through the lens of precision medicine cancer clinical trials, successes and challenges will be discussed to share practical solutions of how to improve evidence generation in the era of precision medicine. Through discussion of precision medicine cancer clinical trials within the United States, this session will provide an overview of how best to optimize these clinical trials. This session comprises the following three main topic areas: matching treatments to patients, including the use of novel patient identification strategies, genomic matching rules, molecular tumor boards (MTBs), decision-support tools, incorporating precision medicine trials into a research portfolio, and how to overcome challenges;accelerating evidence development, including the use of adaptive trial designs, cohort management strategies and data sharing plans;and improving diversity of trial participants and increasing generalizability of study results through expanded eligibility criteria and site selection strategies. This topic will be explored through 90 min of invited talks and a panel discussion with Q&A. Moderator and session chair, Richard L Schilsky, MD, FACP, FSCT, FASCO, will introduce the session and speakers and provide an introduction on the basics of precision oncology. Timothy Cannon, MD, a medical oncologist and clinical trial researcher, will present a case study of two patients with the same alteration and discuss how the care for each differed based on access to a precision medicine cancer clinical trial. Dr. Cannon will also discuss how to implement precision medicine trials within a research portfolio and how to identify patients at a site. Christine Walko, PharmD, BCOP, FCCP, a pharmacist and researcher, will then discuss the basics of matching therapies to genomics, how to use decision support tools, the role of an MTB, and identifying therapeutic options for patients. Edward S Kim, MD, MBA, FACP, FASCO, a medical oncologist, will talk about MTBs from a clinician perspective and precision medicine cancer clinical trials from a community practice perspective. Dr. Kim will also speak about how to extend the research team to create an adequate community research portfolio and about using broader eligibility criteria that might facilitate enrollment of diverse populations. Jane Perlmutter, PhD, MBA, FASCO, a cancer survivor and patient advocate, will discuss what pragmatic trials are, how they increase the opportunity for diversity and generalizability, and patient perspectives regarding pragmatic and precision cancer clinical trials. Susan Halabi, PhD, FASCO, FSCT, a researcher and professor of biostatistics and bioinformatics, will talk about the best ways to design an adaptive trial, especially its role in real-world settings, how these types of designs can be used for efficient signal finding in rare populations, and how these trials can create opportunities for data sharing and collaboration. Pam K Mangat, MS, a research scientist and the Director of Clinical Research for American Society of Clinical Oncology's (ASCO) Targeted Agent and Profiling Utilization Registry (TAPUR) Study, will discuss the operations behind a precision medicine study, advantages and disadvantages of a pragmatic trial, cohort closing and collapsing rules to help with management of large numbers of small cohorts, and contributing knowledge to other trials. The session will conclude with a panel di cussion moderated by session chair, Richard L Schilsky, MD, FACP, FSCT, FASCO, for approximately 10 min, with 5 min for a Q&A session.

Characterizing modifications to a comparative effectiveness research study: the OPTIMIZE trial-using the Framework for Reporting Adaptations and Modifications to Evidence-based Interventions (FRAME).

BACKGROUND: The OPTIMIZE trial is a multi-site, comparative effectiveness research (CER) study that uses a Sequential Multiple Assessment Randomized Trial (SMART) designed to examine the effectiveness of complex health interventions (cognitive behavioral therapy, physical therapy, and mindfulness) for adults with chronic low back pain. Modifications are anticipated when implementing complex interventions in CER. Disruptions due to COVID have created unanticipated challenges also requiring modifications. Recent methodologic standards for CER studies emphasize that fully characterizing modifications made is necessary to interpret and implement trial results. The purpose of this paper is to outline the modifications made to the OPTIMIZE trial using the Framework for Reporting Adaptations and Modifications to Evidence-Based Interventions (FRAME) to characterize modifications to the OPTIMIZE trial in response to the COVID pandemic and other challenges encountered. METHODS: The FRAME outlines a strategy to identify and report modifications to evidence-based interventions or implementation strategies, whether planned or unplanned. We use the FRAME to characterize the process used to modify the aspects of the OPTIMIZE trial. Modifications were made to improve lower-than-anticipated rates of treatment initiation and COVID-related restrictions. Contextual modifications were made to permit telehealth delivery of treatments originally designed for in-person delivery. Training modifications were made with study personnel to provide more detailed information to potential participants, use motivational interviewing communication techniques to clarify potential participants' motivation and possible barriers to initiating treatment, and provide greater assistance with scheduling of assigned treatments. RESULTS: Modifications were developed with input from the trial's patient and stakeholder advisory panels. The goals of the modifications were to improve trial feasibility without compromising the interventions' core functions. Modifications were approved by the study funder and the trial steering committee. CONCLUSIONS: Full and transparent reporting of modifications to clinical trials, whether planned or unplanned, is critical for interpreting the trial's eventual results and considering future implementation efforts. TRIAL REGISTRATION: ClinicalTrials.gov NCT03859713. Registered on March 1, 2019.

Analysis of Semantic Shift before and after COVID-19 in Spanish Diachronic Word Embeddings

Words can shift their meaning across time. This case study shows the results obtained by the exploratory analysis of the semantic shifting on Spanish vocabulary using Diachronic Words Embeddings. Diachronic data consists of a 2018 Spanish corpus, before the COVID-19 outbreak, and a second corpus with documents from 2021. We focused on the semantic shift of three of the topics: COVID-19, masks and vaccines. This paper addresses the construction of the diachronic Spanish word embeddings model, as well as the results obtained by the analysis using a non-supervised distance vector technique. The results allowed to identify shifts related to increase in COVID-19 content. © 2022 IEEE.

Pragmatic Municipalism: Privatization and Remunicipalisation in the US

At the local government level in the US, the process of privatisation has been a dynamic one of experimentation with market delivery and return to public delivery when privatisation fails to deliver. National survey data show what drives this experimentation are pragmatic concerns with service cost and quality. Service and market characteristics, local government capacity and regulatory framework matter. In contrast to current international debates about the potential of remunicipalization to be a political reassertion of the public sector, for US local governments it is primarily a process of pragmatic municipalism. While some shifts in private finance and state regulatory environment favour private actors at the expense of local government, federal investments since COVID-19 provide funding and policy preference for maintaining a public role.

Re-Existence in the Post-Pandemic World: Critical Discursive Considerations About Citizenship, Technology and Pragmatic Networks

Aiming to reflect on possible horizons for social transformation, the present work brings together some ontological, epistemological and methodological considerations regarding critical work with language connected to the citizen issue. It is, therefore, an invitation to an open dialogue about discourse and mobilization based on Critical Discourse Studies (RESENDE, 2008;PARDO, 2011;SANTOS, 2017;2019). Thus, some observations are shared based on the comprehension of discourse, through some original concepts (i.e., Critical Aquilombage (Santos, 2019;2021) and Pragmatic Networks (SANTOS, 2017;2019), and on the necessity of a discursive-oriented practice in times of crisis - which are mediated by digital technologies, new spaces of struggle for the power that influences social groups in the maintenance and erasure of their social existences.

Elements for successful implementation of a clinic-based health literacy intervention.

Improving health literacy is a national public health priority. Given the context of the COVID-19 pandemic, it is even more critical for health and medical information to be clear and understandable for patients and their families. Clinic-based programs to improve health literacy need to be pragmatic, feasible, and helpful for the implementing clinic and patients. This paper describes the development, implementation, and evaluation of a pragmatic, clinic-based health literacy intervention in a safety-net clinic that serves uninsured and indigent patients. Study methods are guided by a previous pilot study and components recommended for pragmatic interventions. An electronic readiness assessment was distributed to out-patient clinics affiliated with a statewide hospital association. The AskMe3 tool was used for the intervention as it is evidence informed and relatively easy to implement. Implementation included ongoing dialogue between the clinic and the academic research team. Within the implementing clinic, data collected from patients via verbally administered questionnaires was analyzed using descriptive statistics and chi-squares. Interview data collected from the clinic director was analyzed qualitatively for themes. The implementing clinic had some of the lowest average scores of the 34 clinics who participated in the initial readiness assessment. Despite this, they were able to successfully implement the health literacy intervention during a global pandemic. Eighty-eight participants completed patient questionnaires at this clinic. Most patients (96%) agreed the AskMe3 questions helped them talk with the doctor or nurse at their current appointment. Most (99%) also perceived the AskMe3 tool to be very helpful when used in a clinical setting. The clinic director offered that the staff initially thought the intervention would be difficult to implement. However, implementation by clinic volunteers with encouragement and prioritization of health literacy by the clinic director contributed to success. When considering interventions for clinical settings, a pragmatic approach can help with selection and implementation of a program that fits with the realities on the ground. Further, frequent technical assistance can help resolve implementation barriers. Interventions utilizing tools such as AskMe3, because of their simplicity, allow creative solutions to capacity issues for clinics who see a need for health literacy improvements.