Implementing a randomised controlled trial through community pharmacies to support people living with severe and persistent mental illness: Lessons learnt during the COVID-19 pandemic.

Public health orders were introduced in many countries, including Australia, during the COVID-19 pandemic to reduce the spread of the virus. However, for many people this led to an exacerbation of mental health symptoms, particularly those living with severe or persistent mental illness (SPMI). Additionally, the conduct of clinical research was severely impacted during the pandemic, with many difficulties encountered in the conduct of clinical trials. This paper describes the COVID-related impacts experienced during the implementation of a randomised controlled trial (RCT) testing the effectiveness of a community pharmacist-led support service for people living with SPMI in Australia (the PharMIbridge RCT), and the strategies used to successfully implement the RCT. Australian public health orders led to interstate border closures, stay-at-home orders and work-from-home requirements, resulting in necessary changes to allow for the continuation of the RCT including; changes to trial regions, transferring some training materials online while delaying face-to-face (F2F) training components, delays in pharmacy and consumer recruitment, encouraging telehealth service delivery and extensions to timelines with existing funding. Having a solution-focussed and flexible approach, while still ensuring critical trial protocol elements were adhered to, such as providing opportunities for F2F skills-based training for pharmacists, as well as F2F site visits from researchers and mentors to support trial implementation, resulted in high pharmacy and consumer participant retention through to trial conclusion. Future planning for RCTs should consider possible pandemic-related risks and rapid responses from approval bodies to ensure researchers can be agile and adapt to ensure successful trial completion.

The impact of COVID-19 on clinical research at Australian and New Zealand universities: A qualitative study.

Background: The COVID-19 pandemic resulted in the implementation of social distancing measures, travel restrictions, and infection control measures that introduced a myriad of disruptions in the conduct of clinical research worldwide. As a result, many aspects of clinical research were variably impacted. Aim: To explore the impact of the first 18 months of the COVID-19 pandemic on clinical research across accredited nursing, pharmacy, and medicine program providers in Australian and New Zealand universities. Methods: Representatives from all program providers across Australian and New Zealand universities, with publicly available contact information, were invited to participate in this qualitative study, whereby semi-structured interviews were completed with participants who held senior research or leadership positions within their institution. Interviews were transcribed verbatim and inductively analysed using thematic content analysis. Findings: Interviews were conducted with 16 participants between August and October 2021. Two major themes were identified (Immediate Research Impact and Broader Research Impact) with six subthemes: Prioritisation, Continuation, and Dissemination of Research; Modifications to Research; Funding and Changes to Research Focus; Collaboration; Research Workforce; Context-specific Impacts. Discussion: The impact on clinical research in Australian and New Zealand universities included changes to data collection methods, a perceived decreased quality of research, changes to collaboration, neglect of basic disease research, and loss of the research workforce. Conclusion: This study highlights the impact of the COVID-19 pandemic on clinical research within the Australian and New Zealand university context. Implications of these impacts should be considered to ensure long-term sustainability of research and preparedness for future disruptions.

Guidance on the Conduct of Clinical Research within OECD Countries during the Early Stages of the COVID-19 Pandemic: A Systematic Review.

BACKGROUND: In response to the COVID-19 pandemic, member countries of the Organisation for Economic Co-operation and Development (OECD) rapidly published guidance regarding the conduct of clinical research. A systematic review was conducted to explore the recommendations issued in relation to the commencement, continuation and termination of clinical research during the early phases of the pandemic. METHODS: Searches consisting of the terms "COVID-19", "clinical research", and "guidance", were conducted in PubMed, Embase, MEDLINE, Trip, Guidelines International Network, and Google in April-May 2021 (up to 4 May 2021). Data were extracted from guidance published from OECD member countries and mapped to inductively-developed categories. RESULTS: 9419 references were systematically screened, resulting in the inclusion of 46 publications from 27 OECD countries. Thirty-three sources made recommendations regarding monitoring, risk-benefit assessments and information technology. There was limited specific recommendations made in relation to personal protective equipment (PPE) in the included guidance. Findings demonstrate that guidance differed by publication date demonstrating the rapidly evolving environment within which research was conducted. Importantly, many organisations opted to endorse existing guidance published by the United States' Food and Drug Administration and the European Medicines Agency rather than develop their own recommendations. CONCLUSIONS: Given the rapidly evolving nature of the pandemic, particularly in the early stages, findings demonstrate the global response in relation to clinical research conduct, thereby providing important insights for future public health emergencies.

A training programme for community pharmacists to support people living with severe and persistent mental illness: Intervention mapping in the context of a pandemic

Objective: The Bridging the Gap Between Physical and Mental Illness in Community Pharmacy (PharMIbridge) randomised controlled trial (RCT) aims to test the effectiveness of a pharmacist-led support service in improving medication adherence, and the physical and mental health of people living with severe and persistent mental illness compared to a standard medication review service. Method: Using the six-step intervention mapping (IM) framework, this paper describes the development and content of the PharMIbridge pharmacist training programme, an integral part of the RCT implementation, and continuous adaptations made to the process to keep pace with the evolving severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic in Australia. A Training Working Group comprising health educators, practitioners, mental health consumers and researchers, refined the programme objectives and assisted with developing content and troubleshooting issues related to training delivery for pharmacists randomised to the RCT intervention arm. Results: A 2-day training programme was developed, which included Mental Health First Aid, simulated patient role-plays, and four pre-recorded modules using lectures, demonstration case vignettes, role-play activities and discussion. The programme, co-facilitated by project team members and mentors (pharmacist and consumer educators), aims to enhance pharmacists' mental health literacy, skills and confidence and empower them to engage with this vulnerable population using a strengths-based approach. Pre- and post-training questionnaires and interviews will be used to evaluate the impact of the PharMIbridge training programme. Conclusion: The systematic stepwise method provided by the IM framework highlights the solution-focused approach adopted by the project team and characteristics including adaptability and resilience which enabled training development and implementation across four Australian regions during the SARS-CoV-2 pandemic.

Post-Intensive Care COVID Survivorship Clinic: A Single-Center Experience.

Patients discharged from the ICU post-COVID-19 pneumonitis may experience long-term morbidity related to their critical illness, the treatment for this and the ICU environment. The aim of this study was to characterize the cognitive, psychologic, and physical consequences of COVID-19 in patients admitted to the ICU and discharged alive. DESIGN: Prospective cohort study. SETTING: Post-intensive care syndrome (PICS) follow-up clinic at Tallaght University Hospital, a tertiary referral center with a 16-bed mixed medical-surgical ICU, including critical care physicians, a psychologist, a physiotherapist, and a research nurse. PATIENTS: Patients who had been admitted to the ICU in our tertiary referral center with COVID-19 pneumonitis 6 months earlier. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 22 patients attended the 6-month PICS follow-up clinic following admission to ICU with COVID-19 pneumonitis. Mean grip strength was low at the 6-month follow-up at 24.1 pounds (sd 9.8) with a minimally active median metabolic equivalent (MET) of 970 METs/wk (interquartile range, 0-7,794 METs/wk). Only 59% of patients were independent with regard to their activities of daily living. Eight of 14 patients (57%) had returned to work by 6 months post-ICU discharge. Their mean Intensive Care Psychological Assessment Tool (IPAT) score was 6.6 (sd 4.6) with a Post-Traumatic Stress Disorder Checklist for Diagnostic and Statistical Manual of Mental Disorders-5th Edition (PCL-5) score of 21.1 (sd 17.5) and a mean Montreal Cognitive Assessment (MoCA) score of 24 (sd 8.4); suggestive of mild cognitive impairment. In a multivariable regression model, only Acute Physiology and Chronic Health Evaluation II score was significantly independently associated with MoCA score as a cognitive PICS outcome (beta-coefficient, -1.6; se, 0.6; p = 0.04). None of the predictor variables were significantly independently associated with IPAT and PCL-5 as psychologic outcomes, nor with International Physical Activity Questionnaire-Short Form as a physical PICS outcome. CONCLUSIONS: In this single-center prospective cohort study, we found that patients have a high burden of physical and psychologic impairment at 6 months following ICU discharge post-COVID-19 pneumonitis; in many cases requiring specialist referrals for long-term input. We advocate for increased resources for this much needed follow-up multidisciplinary intervention for an ever-growing population of patients.

Severe COVID-19 Is Characterized by an Impaired Type I Interferon Response and Elevated Levels of Arginase Producing Granulocytic Myeloid Derived Suppressor Cells.

COVID-19 ranges from asymptomatic in 35% of cases to severe in 20% of patients. Differences in the type and degree of inflammation appear to determine the severity of the disease. Recent reports show an increase in circulating monocytic-myeloid-derived suppressor cells (M-MDSC) in severe COVID 19 that deplete arginine but are not associated with respiratory complications. Our data shows that differences in the type, function and transcriptome of granulocytic-MDSC (G-MDSC) may in part explain the severity COVID-19, in particular the association with pulmonary complications. Large infiltrates by Arginase 1+ G-MDSC (Arg+G-MDSC), expressing NOX-1 and NOX-2 (important for production of reactive oxygen species) were found in the lungs of patients who died from COVID-19 complications. Increased circulating Arg+G-MDSC depleted arginine, which impaired T cell receptor and endothelial cell function. Transcriptomic signatures of G-MDSC from patients with different stages of COVID-19, revealed that asymptomatic patients had increased expression of pathways and genes associated with type I interferon (IFN), while patients with severe COVID-19 had increased expression of genes associated with arginase production, and granulocyte degranulation and function. These results suggest that asymptomatic patients develop a protective type I IFN response, while patients with severe COVID-19 have an increased inflammatory response that depletes arginine, impairs T cell and endothelial cell function, and causes extensive pulmonary damage. Therefore, inhibition of arginase-1 and/or replenishment of arginine may be important in preventing/treating severe COVID-19.