Gender bias in academic medicine: a resumé study.

BACKGROUND: Minimising the effects of unconscious bias in selection for clinical academic training is essential to ensure that allocation of training posts is based on merit. We looked at the effect of anonymising applications to a training programme for junior doctors on the scores of the applications and on gender balance; and whether female candidates were more likely to seek gender-concordant mentors. METHODS: Applications to the training programme were reviewed and scored independently by reviewers who received either an anonymised or named copy. Scores were compared using a paired t-test, and differences in scores compared by gender. The gender of named supervisors for male and female candidates was compared. RESULTS: Scores of 101 applications were reviewed. When their identity was known, male candidates scored 1.72% higher and female candidates scored 0.74% higher, but these findings were not statistically significant (p value = 0.279 and 0.579). Following introduction of anonymisation, the proportion of successful female candidates increased from 27 to 46%. Female candidates were more likely to name a female supervisor compared to male (41% vs. 25% of supervisors). CONCLUSIONS: Anonymising applications did not significantly change scores, although gender balance improved. Gender-concordant mentoring initiatives should consider effects on mentors as well as mentees.

Nursing home staff mental health during the Covid-19 pandemic in the Republic of Ireland.

BACKGROUND: Nursing homes for older adults have been disproportionately affected by the Covid-19 pandemic with increased mortality of residents and staff distress. OBJECTIVE: To quantify the mental health of nursing home staff during the Covid-19 pandemic in the Republic of Ireland. DESIGN/METHODS: Cross-sectional anonymous study of Republic of Ireland nursing home staff (n = 390) during the third wave of the Covid-19 pandemic. Online survey collecting demographic information, Covid-19 exposure history and mental health measures. RESULTS: There were significant differences between nurses, healthcare assistants (HCA) and non-clinical staff history in age, ethnicity, years' experience, history of Covid-19 infection and contact with Covid-19 positive acquaintances. Moderate-severe post-traumatic stress disorder symptoms were found in 45.1% (95% confidence interval [CI] 40.2%-50.1%) of all staff. A World Health Organisation-5 (WHO-5) wellbeing index score ≤32, indicating low mood, was reported by 38.7% (95% CI, 33.9%-43.5%) of staff; significantly more nurses reported low mood. Suicidal ideation and suicide planning were reported, respectively, by 13.8% (95% CI, 10.4%-17.3%) and 9.2% (95% CI, 6.4%-12.1%) of participants with no between-group differences. HCAs reported a significantly higher degree of moral injury than non-clinical staff. Nurses were more likely to use approach coping styles than non-clinical staff. Work ability was insufficient in 24.6% (95% CI 20.3%-28.9%) of staff. CONCLUSION: Nursing home staff report high levels of post-traumatic stress, mood disturbance and moral injury during the Covid-19 pandemic. Differences in degree of moral injury, wellbeing and coping styles were found between staff groups, which need to be incorporated into planning supports for this neglected workforce.

Assessment of an electronic patient record system on discharge prescribing errors in a Tertiary University Hospital.

BACKGROUND: Prescribing error represent a significant source of preventable harm to patients. Prescribing errors at discharge, including omission of pre-admission medications (PAM), are particularly harmful as they frequently propagate following discharge. This study assesses the impact of an educational intervention and introduction of an electronic patient record (EPR) in the same centre on omission of PAM at discharge using a pragmatic design. A survey of newly qualified doctors is used to contextualise findings. METHODS: Discharge prescriptions and discharge summaries were reviewed at discharge, and compared to admission medicine lists, using a paper-based chart system. Discrepancies were noted, using Health Information and Quality Authority guidelines for discharge prescribing. An educational intervention was conducted. Further review of discharge prescriptions and discharge summaries took place. Following introduction of an EPR, review of discharge summaries and discharge prescriptions was repeated. A survey was administered to recently qualified doctors (interns), and analysed using descriptive statistics and thematic analysis. RESULTS: Omission of PAM as prescribed or discontinued items at discharge occurs frequently. An educational intervention did not significantly change prescribing error rates (U = 1255.5, p = 0.206). EPR introduction did significantly reduce omission of PAM on discharge prescribing (U = 694, p < 0.001), however there was also a reduction in the rate of deliberate discontinuation of PAM at discharge (U = 1237.5, p = 0.007). Survey results demonstrated that multiple sources are required to develop a discharge prescription. Time pressure, access to documentation and lack of admission medicine reconciliation are frequently cited causes of discharge prescribing error. CONCLUSION: This study verified passive educational interventions alone do not improve discharge prescribing. Introduction of EPR improved discharge prescribing, but negatively impacted deliberate discontinuation of PAM at discharge. This is attributable to reduced access to key sources of information used in formulating discharge prescriptions, and separation of the discontinuation function from the prescribing function on the EPR discharge application.

Ireland's medical brain drain: migration intentions of Irish medical students.

BACKGROUND: To provide the optimum level of healthcare, it is important that the supply of well-trained doctors meets the demand. However, despite many initiatives, Ireland continues to have a shortfall of physicians, which has been projected to persist. Our study aimed to investigate the migration intentions of Irish medical students and identify the factors that influence their decisions in order to design appropriate interventions to sustain the supply of trained doctors in order to maintain a viable medical system. METHODS: An online cross-sectional survey was undertaken of all Irish medical students studying in the Republic of Ireland. The survey included nominal, ordinal, and scale items to determine migration intentions, factors influencing their decisions, and understanding of the Irish healthcare system. RESULTS: A total of 2 273 medical students responded (37% response rate), of whom 1 519 were classified as Irish medical students (having completed secondary school in Ireland). Of these, 88% indicated they were either definitely migrating or contemplating migrating following graduation or completion of the pre-registration intern year. Forty percent expressed an intention of returning to Ireland within 5 years. The factors most influencing their decision to leave were career opportunities (85%), working conditions (83%), and lifestyle (80%). CONCLUSION: The migration intentions expressed in this study predict an immediate and severe threat to the sustainability of the Irish healthcare service. Urgent interventions such as providing information about career options and specialty training pathways are required. These must begin in the undergraduate phase and continue in postgraduate training and are needed to retain medical school graduates.

Risk Factors and Modifiers for Cardiovascular Disease Assessment of Patients with Heterozygous Familial Hypercholesterolaemia.

Background: The assessment of the risk of cardiovascular disease (CVD) in patients with heterozygous familial hypercholesterolemia (HeFH) is determined by conventional risk factors. However, factors modifying CVD, or risk modifiers, beyond conventional risk factors may inform their CVD risk assessment and the subsequent use of new therapies. This work identifies and characterises patients within a lipid clinic cohort with regards to conventional CVD risk factors and risk modifiers with a focus on those with HeFH. Methods: A study of consecutive adult patients attending our specialist lipid clinic was performed over a six-month period. The patient data recorded included demographics, clinical characteristics, risk factors and risk modifiers, biochemical profiles and genetic testing results. Risk modifiers were identified based on ESC/EAS guidance, and those with HeFH were compared to those without. Results: A total of 370 patients were included. Of these, 98 HeFH patients were identified (26%). Then, 52% of HeFH patients were stratified into the very-high risk category due to the presence of CVD risk factors. Risk modifiers were present in 73%. These included a family history of premature CVD (56%), obesity (28%), a sedentary lifestyle (13%) and a major psychiatric disorder (12%). Compared to the rest of the cohort, those with HeFH were less likely to have hypertension and more likely to have a family history of premature CVD. Conclusions: Half of patients with HeFH are categorised as having very high CV risk. Consideration of risk modifiers, particularly a family history of premature CV disease, increases this very-high-risk category further. This may have implications for the clinical application and access to novel treatments.

The Effect of Semaglutide on Blood Pressure in Patients without Diabetes: A Systematic Review and Meta-Analysis.

(1) Background: Recent advances in the pharmacological treatment of obesity with glucagon-like peptide-1 receptor agonists (GLP-1 RA) highlight the potential to target excess body weight to improve blood pressure (BP). This review aimed to determine the BP reduction in trials of semaglutide for weight reduction in patients without diabetes. (2) Methods: Relevant studies were identified via a search of research databases. Studies were screened to include randomized controlled trials (RCTs) of semaglutide versus a placebo in adults. Pooled and sensitivity analyses were performed, and risk of bias was assessed. (3) Results: six RCTs, with 4744 participants, were included in the final analysis. At baseline, the cohorts in these studies had a mean BP in the normotensive range. The mean difference in systolic BP was -4.83 mmHg (95% CI: -5.65 to -4.02), while that for diastolic BP was -2.45 mmHg (95% CI: -3.65 to -1.24). All included studies were of a high methodological quality. (4) Conclusions: A clinically significant reduction in BP was evident following semaglutide treatment in normotensive populations without diabetes. The effect of semaglutide in those with obesity and hypertension is as yet undetermined. Targeting excess body weight may be a novel therapeutic strategy for these patients.

Dublin hospital workers' mental health during the peak of Ireland's COVID-19 pandemic.

BACKGROUND: Hospital-based healthcare workers have experienced significant psychological stressors during the COVID-19 pandemic. AIM: To evaluate the mental health of hospital workers during the third wave of the COVID-19 pandemic in Dublin, Ireland. METHODS: Cross-sectional anonymous online survey of hospital workers (n = 377; 181 doctors (48.0%), 166 nurses (44.0%), 30 radiographers (8.0%)), collecting demographic information, COVID-19 exposure history and mental health measures. RESULTS: There were significant differences between profession groups in gender, experience, COVID-19 infection history, exposure to COVID-19 positive acquaintances, and work areas. Moderate-severe post-traumatic stress disorder (PTSD) symptoms were found in 45.1% (95% CI 40.1-50.1%) of all participants; significantly fewer doctors reported moderate-severe PTSD symptoms (26%; 95% CI 22-36%). A World Health Organisation-5 Wellbeing Index (WHO-5) score ≤ 32, indicating low mood, was reported by 52% (95% CI 47-57%) of participants; significantly fewer doctors reported low mood (46%; 95% CI 39-53%). One-week suicidal ideation and planning were reported respectively by 13% (95% CI 10-16%) and 5% (95% CI 3-7%) of participants with no between-group differences. Doctors reported significantly less moral injury than other groups. There were no significant between-group differences regarding coping styles. Work ability was insufficient in 39% (95% CI 34-44%) of staff; no between-group differences. CONCLUSIONS: Dublin hospital workers reported high levels of PTSD symptoms, mood disturbance, and moral injury during the COVID-19 pandemic. Concerning levels of suicidal ideation and planning existed in this cohort. Differences in degrees of post-traumatic stress, moral injury, and wellbeing were found between profession groups, which should be considered when planning any supports.

A hospital to community exercise referral pathway: results of a pilot project.

BACKGROUND: People living with chronic disease should ideally engage with community-based exercise services following hospital-based rehabilitation. However, transition from hospital to community exercise settings is extremely challenging and strategies to support this transition are underdeveloped. AIMS: The aims of this study were to develop and explore the feasibility of a pilot exercise referral pathway between an acute hospital and community gyms for patients with chronic health conditions and to evaluate patient satisfaction with the exercise referral pathway. METHODS: A stakeholder-informed exercise referral pathway was developed and offered to patients following completion of a hospital-based exercise programme for a chronic health condition. The pathway was evaluated using a mixed-methods approach. Quantitative data examining participant engagement was used to examine feasibility. Quantitative survey data and qualitative data from semi-structured interviews examined satisfaction with the pathway. RESULTS: Forty-nine people living with chronic conditions (mean age 72 ± 7.8 years) participated (recruitment rate 59%). The average number of community gym visits over 4 months was 17.4 (range 0-51). Twenty-nine (78%) participants reported that they planned to continue their gym membership when the programme ended. Themed responses from participant interviews (n = 12) highlighted the benefits of a supported transition from hospital to gym membership and the need for more structured exercise support in community gyms. CONCLUSION: A structured exercise referral pathway to support exercise transition between hospital and community settings in populations with chronic health conditions appears feasible. Participants reported high levels of satisfaction with the referral pathway.

Room to improve: The diagnostic journey of Spinal Muscular Atrophy.

AIMS: To highlight the current diagnostic pathway for children with Spinal Muscular Atrophy (SMA) in Ireland. We look to identify points along the diagnostic pathway that may impede a timely diagnosis, and argue that newborn screening for SMA is the single best measure to remediate these delays. METHODS: Through retrospective chart review and an online questionnaire, we gathered SMA patient data outlining clinical characteristics and the route to diagnosis of the SMA cohort attending the National SMA Treatment centre at Children's Health Ireland. RESULTS: We found that 32 children were diagnosed with SMA in Ireland in the 15-years from 2007 to 2021, with twelve cases of SMA type I. Muscle weakness is the most commonly reported initial sign, and the GP is usually the first health provider to address parental concerns. Patients commonly experience delays in diagnosis due to factors such as varied SMA clinical phenotypes, and a lack of experience or awareness of SMA amongst community based health care practitioners. In spite of this, when patients do gain early access to tertiary diagnostics through prenatal or neonatal genetic testing, they then report rapid diagnosis and initiation of disease modifying therapy in the crucial pre-symptomatic window. CONCLUSION: We conclude that delays to diagnosis inherent within the current Irish system are pervasive and arise prior to engagement with tertiary services. All of these delays are remediable through the establishment of a dedicated SMA newborn screening programme.

Worsening of mental health outcomes in nursing home staff during the COVID-19 pandemic in Ireland.

BACKGROUND: Mental health issues in nursing home staff during the COVID-19 pandemic have been significant; however, it is not known if these issues persist following widespread vaccination and easing of restrictions. OBJECTIVE: To quantify the mental health of nursing home staff at different timepoints during the COVID-19 pandemic in the Republic of Ireland. DESIGN/METHODS: Two identical, online, cross-sectional, nationwide, anonymous surveys of Republic of Ireland nursing home staff at two timepoints (survey 1 (S1, n = 390): November 2020 to January 2021; survey 2 (S2, N = 229: November 2021 to February 2022) during the COVID-19 pandemic. Convenience sampling was used with staff self-selecting for participation. Methods included the World Health Organisation's Well-Being Index (WHO-5), the Impact of Events Scale-Revised (IES-R), the Moral Injury Events Scale (MIES), two Likert-scale items regarding suicidal ideation and planning, the Work Ability Score (WAS), the Brief Coping Orientation to Problems Experienced (Brief-COPE) Scale, and a 15-item questionnaire assessing perceptions of the outbreak with one additional Likert-scale item on altruism. Descriptive analysis examined differences between staff based on their classification in one of three groups: nurses, healthcare assistants (HCA) and nonclinical staff. Pseudonymous identifiers were used to link responses across surveys. RESULTS: An insufficient number of participants completed both surveys for linked analyses to be performed; therefore, we performed an ecological comparison between these two independent surveys. More staff reported moderate-severe post-traumatic stress symptoms (S1 45%; S2 65%), depression (S1: 39%; S2 57%), suicidal ideation (S1: 14%; S2 18%) and suicidal planning (S1: 9%; S2 15%) later in the pandemic. There was a higher degree of moral injury at S2 (S1: 20.8 standard deviation (SD) 9.1; S2: 25.7 SD (11.3)) and use of avoidant (maladaptive) coping styles at S2 (S1: 20.8 (6.3); S2 23.0 (6.3)) with no notable differences found in the use of approach (adaptive) coping styles. Staff reported more concerns at S2 regarding contracting COVID-19, social stigma, job stress, doubts about personal protective equipment and systems and processes. CONCLUSION: In comparison to our previous survey, mental health outcomes appear to have worsened, coping did not improve, and staff concerns, and worries appear to have increased as the pandemic progressed. Follow-up studies could help to clarify is there are any lingering problems and to assess if these issues are related to the pandemic and working conditions in nursing homes.

An exploration of the professional identity of clinical academics using repertory grid technique.

BACKGROUND: Clinicians who divide their time between clinical work and research have contributed to some of the most fundamental breakthroughs in medicine in recent history, yet their role is not always well-understood or valued. Understanding the factors which contribute to career success for clinical academics is critical for supporting this workforce. Social Cognitive Career Theory (SCCT) provides a conceptual framework for career success, incorporating personal and environmental factors. PURPOSE: The aim of this study is to explore clinical academics' construal of successful clinical academic practice and to contribute to a holistic view of the professional identity of the clinical academic. METHODOLOGY: Using a constructivist technique, repertory grid, the authors interviewed ten clinical academics at different career stages in one-to-one structured interviews conducted virtually between November 2020 and April 2021. Data from the interviews were analysed qualitatively and quantitatively. Common themes were identified, analysed, and ranked according to importance with respect to successful clinical academic practice. Using SCCT as a framework, constructs were categorised as personal factors, organisational factors, competencies and person-environment fit. A differential analysis between established/trainee and female/male participants was carried out. SUMMARY OF RESULTS: One hundred and thirty-three constructs were elicited and categorised into 20 themes (constructs). There was consensus among participants that 6 were of high importance with respect to successful clinical academic practice, 8 of intermediate and 4 of low importance, with no consensus on 2 constructs. Personal factors of high importance include innovation and integrity. Competencies including research and teaching skills are highly important, and ability to collaborate is also considered central to successful clinical academic practice. Female participants expressed greater concerns about the impact of familial responsibilities on career progression. DISCUSSION AND CONCLUSIONS: This study highlights the importance of interactions between the person and environment, and characterises the important attributes of successful clinical academics including personal factors such as integrity and innovation.

Exercise and chronic health conditions in the community: A qualitative Study of Patients and Fitness instructors.

Further information is needed on how community exercise facilities can be effectively utilised to engage people living with chronic health conditions in exercise. The aim of this study was to identify the exercise barriers, facilitators and needs of patients with chronic disease in the community; and to provide recommendations to support the transition from hospital-based to community-based exercise. Using a qualitative approach, four focus groups were conducted with patients who had completed hospital-based exercise programmes (n = 11) and fitness instructors (n = 10). Data were audio recorded, member checked and transcribed verbatim for thematic analysis using NVivo. The side effects of chronic health conditions, the gym environment and a need for support when joining/attending a gym were perceived as barriers to exercising in the community. In contrast, the presence of supportive staff was perceived by patients as a facilitator to engaging in exercise in the community. A total of three themes emerged from participants views on exercise needs in the community; the referral and induction process in community gyms, fitness instructor training and experience and creating a supportive exercise environment. Themes informed eight key recommendations to support patients to exercise in the community, including supportive gym referral and induction processes for patients with chronic conditions, increased professional training for fitness instructors in the area of chronic disease management and exercise prescription, and exercise support at regular intervals for those with chronic conditions attending community gyms. This study found that there is potential for community gyms to play a key role in promoting health among people with chronic conditions. However, more can be done to foster an inclusive atmosphere in this space. Patients living with chronic conditions need information and advice on exercising in their communities. Community gyms require further support to ensure that facilities meet the exercise needs of people with chronic conditions.

Collaboration, supervision and patient safety in the era of COVID-19: an analysis of medical wards and ICU.

AIMS: COVID-19 resulted in significant changes across medical wards and ICU in St James's Hospital Dublin. This included the implementation of ward-based medical teams (WBMT). The purpose of this study was to identify how these structural changes affected inter-professional collaboration, supervision and patient safety. METHODS: Questionnaires were distributed to doctors working on medical wards and ICU at the height of the first wave of COVID-19. The sense of collaboration, patient safety and supervision were assessed. RESULTS: Fifty-three doctors took part in the study. Thirty-three (62%) felt that collaboration was better than normal. Forty-six (87%) of participants described supervision as "good" or "excellent". Thirty-one out of 40 participants (77%) felt that patient safety was better than normal. DISCUSSION: Implementation of WBMT may result in improved sense of collaboration, supervision and patient safety during COVID-19; however, the increased sense of solidarity and comradery felt during the initial surge make drawing these conclusions challenging.

Clinical characteristics of two groups commonly referred to an Irish hypertension service-patients with resistant hypertension and young adults with hypertension.

BACKGROUND: The management of hypertension is primarily performed in primary care settings in many health systems. However, two groups of patients often require specialist input: patients with resistant hypertension (RH) and young adults with hypertension. AIMS: To elucidate these groups by examining the characteristics of patients attending an Irish hypertension service, thus informing future management of hypertension. METHODS: Patients were recruited at consecutive hypertension clinics at St James Hospital, Dublin from July to September 2019. Following patient consent, patient data were recorded to identify patient characteristics as well as the results of investigations, blood pressure (BP) measurements and the anti-hypertensive treatment of the study participants which were then analysed. RESULTS: Two hundred thirty-six patients were included in the study. Compared to those without RH, the RH group were more likely to be obese (OR 2.59 [95% CI 1.06 to 6.33]), to have cardiovascular disease (OR 3.07 [95% CI 1.56 to 6.02]) and to have a non-dipping BP pattern (OR 3.86 [95% CI 1.57 to 9.47]). Young adults comprised 27% of the cohort. Forty-seven percent of these patients were obese, 15.9% had hypertension in pregnancy and 22.2% had chronic headaches. Despite being prescribed less anti-hypertensives (1.41 vs 2.28; p < 0.05), the majority of young patients had a BP less than 140/90 mmHg, comparing favourably with older patients (OR 2.25 [95% CI 1.20 to 4.27]). CONCLUSION: This contemporary study highlights the high prevalence of obesity among RH patients and young adults with hypertension. Findings suggest that programs to combat hypertension must include interventions to address obesity.

Referrals to, and characteristics of patients attending a specialist hypertension clinic.

The management of hypertension is suboptimal in Ireland and internationally. The role of a specialist hypertension clinic is not always defined but an analysis of the reasons for referral are likely informative. Also, a description of the clinical characteristics of patients with hypertension will inform requirements for comprehensive hypertension management in the community and secondary care. Patients were recruited at consecutive hypertension clinics at St James Hospital, Dublin from July to September 2019. Reasons for referral, clinical characteristics of patients, their investigations and treatment were analyzed. 236 patients were included in the study. The majority of patients, 83%, were obese or overweight. A family history of hypertension was a frequent finding with 70.8% of patients reporting same. 26.7% of patients were under the age of 40. 78% of referrals were from primary care and the most referrals were to investigate secondary causes of hypertension or because the patient was ≤40 years of age. Calcium channel blockers were the treatment most frequently prescribed (51.7%). Clinic blood pressure for the cohort was 137/81 mmHg and this was replicated by their ambulatory BP. This insight into the contemporary management of hypertension highlights the frequency of obesity and a positive family history in those with hypertension. Most referrals were consistent with international guidance though deviations were evident. Findings suggest a national program for hypertension with greater focus on public health interventions and better resourcing of primary care is required.

Supervision and Care Quality as Perceived by Redeployed Attendings, Fellows, and Residents During a COVID-19 Surge: Lessons for the Future.

PURPOSE: To better prepare for potential future large-scale redeployments, this study examines quality of supervision and care as perceived by redeployed residents, fellows, and attendings during a COVID-19 surge. METHOD: During April and May 2020, attendings, fellows, and residents redeployed at 2 teaching hospitals were invited to participate in a survey, which included questions on respondents' prior experience; redeployed role; amount of supervision needed and received; and perceptions of quality of supervision, patient care, and interprofessional collaboration. Frequencies, means, and P values were calculated to compare perceptions by experience and trainee status. Narrative responses to 2 open-ended questions were independently coded; themes were constructed. RESULTS: Overall, 152 of 297 (51.2%) individuals responded, including 64 of 142 attendings (45.1%), 40 of 79 fellows (50.6%), and 48 of 76 residents (63.2%). Fellows and attendings, regardless of prior experience, perceived supervision as adequate. In contrast, experienced residents reported receiving more supervision than needed, while inexperienced residents reported receiving less supervision than needed and rated overall supervision as poor. Attendings, fellows, and experienced residents rated the overall quality of care as acceptable to good, whereas inexperienced residents perceived overall quality of care as worse to much worse, particularly when compared with baseline. CONCLUSIONS: Narrative themes indicated that the quality of supervision and care was buffered by strong camaraderie, a culture of informal consultation, team composition (mixing experienced with inexperienced), and clinical decision aids. The markedly negative view of inexperienced residents suggests a higher risk for disillusionment, perhaps even moral injury, during future redeployments. Implications for planning are explored.

A randomized, double-blind, placebo-controlled trial of intravenous alpha-1 antitrypsin for ARDS secondary to COVID-19.

Background: Patients with severe coronavirus disease 2019 (COVID-19) develop a febrile pro-inflammatory cytokinemia with accelerated progression to acute respiratory distress syndrome (ARDS). Here we report the results of a phase 2, multicenter, randomized, double-blind, placebo-controlled trial of intravenous (IV) plasma-purified alpha-1 antitrypsin (AAT) for moderate to severe ARDS secondary to COVID-19 (EudraCT 2020-001391-15). Methods: Patients (n = 36) were randomized to receive weekly placebo, weekly AAT (Prolastin, Grifols, S.A.; 120 mg/kg), or AAT once followed by weekly placebo. The primary endpoint was the change in plasma interleukin (IL)-6 concentration at 1 week. In addition to assessing safety and tolerability, changes in plasma levels of IL-1ß, IL-8, IL-10, and soluble tumor necrosis factor receptor 1 (sTNFR1) and clinical outcomes were assessed as secondary endpoints. Findings: Treatment with IV AAT resulted in decreased inflammation and was safe and well tolerated. The study met its primary endpoint, with decreased circulating IL-6 concentrations at 1 week in the treatment group. This was in contrast to the placebo group, where IL-6 was increased. Similarly, plasma sTNFR1 was substantially decreased in the treatment group while remaining unchanged in patients receiving placebo. IV AAT did not definitively reduce levels of IL-1ß, IL-8, and IL-10. No difference in mortality or ventilator-free days was observed between groups, although a trend toward decreased time on ventilator was observed in AAT-treated patients. Conclusions: In patients with COVID-19 and moderate to severe ARDS, treatment with IV AAT was safe, feasible, and biochemically efficacious. The data support progression to a phase 3 trial and prompt further investigation of AAT as an anti-inflammatory therapeutic. Funding: ECSA-2020-009; Elaine Galwey Research Bursary.

Severe COVID-19 is characterised by inflammation and immature myeloid cells early in disease progression.

SARS-CoV-2 infection causes a wide spectrum of disease severity. Identifying the immunological characteristics of severe disease and the risk factors for their development are important in the management of COVID-19. This study aimed to identify and rank clinical and immunological features associated with progression to severe COVID-19 in order to investigate an immunological signature of severe disease. One hundred and eight patients with positive SARS-CoV-2 PCR were recruited. Routine clinical and laboratory markers were measured, as well as myeloid and lymphoid whole-blood immunophenotyping and measurement of the pro-inflammatory cytokines IL-6 and soluble CD25. All analysis was carried out in a routine hospital diagnostic laboratory. Univariate analysis demonstrated that severe disease was most strongly associated with elevated CRP and IL-6, loss of DLA-DR expression on monocytes and CD10 expression on neutrophils. Unbiased machine learning demonstrated that these four features were strongly associated with severe disease, with an average prediction score for severe disease of 0.925. These results demonstrate that these four markers could be used to identify patients developing severe COVID-19 and allow timely delivery of therapeutics.

Study protocol for the St James's Hospital, Tallaght University Hospital, Trinity College Dublin Allied Researchers' (STTAR) Bioresource for COVID-19.

Background: The current coronavirus disease 2019 (COVID-19) pandemic began in Ireland with the first confirmed positive case in March 2020. In the early stages of the pandemic clinicians and researchers in two affiliated Dublin hospitals identified the need for a COVID-19 biobanking initiative to support and enhance research into the disease. Through large scale analysis of clinical, regional, and genetic characteristics of COVID-19 patients, biobanks have helped identify, and so protect, at risk patient groups The STTAR Bioresource has been created to collect and store data and linked biological samples from patients with SARS-CoV-2 infection and healthy and disease controls. Aim: The primary objective of this study is to build a biobank, to understand the clinical characteristics and natural history of COVID-19 infection with the long-term goal of research into improved disease understanding, diagnostic tests and treatments. Methods: This is a prospective dual-site cohort study across two tertiary acute university teaching hospitals. Patients are recruited from inpatient wards or outpatient clinics. Patients with confirmed COVID-19 infection as well as healthy and specific disease control groups are recruited.  Biological samples are collected and a case report form detailing demographic and medical background is entered into the bespoke secure online Dendrite database. Impact: The results of this study will be used to inform national and international strategy on health service provision and disease management related to COVID-19. In common with other biobanks, study end points  evolve over time as new research questions emerge. They currently include patient survival, occurrence of severe complications of the disease or its therapy, occurrence of persistent symptoms following recovery from the acute illness and vaccine responses.