Crisis Response in Higher Education

This open access book explores the impact of Covid-19 on universities, and how students, staff, faculty and academic leaders have adapted to and dealt with the impact of the pandemic. Drawing on experiences from Britain, Australia and Sweden, it showcases how Covid has challenged routines and procedures in universities, and thrown them into a disarray of ever-changing events and short-term adaptations. The authors pay particular attention to how students, staff, faculty, and leaders have coped with Covid, through a series of autobiographical portraits of their strains but also heroic efforts in the harshest of circumstances. This important book explores the exceptional ramifications of the pandemic but also how universities may contribute to a fairer and more robust society and concludes with a set of prescriptions for universities that aim to be proactive and resilient forces in society. It will be of interest to scholars interested in higher education, governance and organizational studies. This is an open access book

Synergism between the Two Membranes of the Blood-brain Barrier: Glucose and Amino Acid Transport

Brain capillary endothelial cells, which are connected by extensive tight junctions and are polarized into luminal (blood-facing) and abluminal (brain-facing) plasma membrane domains, form the blood-brain barrier (BBB). The polar distribution of transport proteins mediates glucose and amino acid (AA) homeostasis in the brain. The ability to isolate the luminal and abluminal membranes has permitted the study of each side of the BBB separately in vitro and yielded new information on BBB function. The two membranes have different characteristics. Facilitative transporters were found on both membranes in a position to permit the bidirectional transport of glucose, almost all amino acids and taurine. Na+-dependent transporters were only found on abluminal membranes. The Na+-dependent transporters on the abluminal side are capable of removing virtually all amino acids including acidic AA from the extracellular fluid of brain (ECF). The presence of Na+-dependent carriers on the abluminal membrane provides a mechanism by which the concentrations of AA, glucose and taurine in the ECF of brain may be maintained at optimal levels under physiological and pathophysiological circumstances. Facilitative carriers for glutamine (n) and glutamate (xg-) are found only in the luminal membrane of the BBB. This organization allows the net removal of acidic and nitrogen-rich AA from brain, and explains the low rate of glutamate and glutamine penetration into the central nervous system. The presence of a g-glutamyl cycle at the luminal membrane and Na+-dependent AA transporters at the abluminal membrane may serve to modulate movement of AA from blood to brain. The g-glutamyl cycle is expected to generate pyroglutamate within the endothelial cells. Pyroglutamate stimulates Na+-dependent AA transporters at the abluminal membrane thereby reducing net influx of AA the to brain. It is now clear the BBB may actively participate in the regulation of the AA content of the brain as well as contributing to the control of brain osmolarity

Reduced Kidney Function is Associated with Poorer Domain‐Specific Cognitive Performance in Community‐Dwelling Older Adults

OBJECTIVES: Whilst chronic kidney disease has been associated with cognitive impairment, the association between reduced estimated Glomerular Filtration Rate (eGFR) and domain‐specific cognitive performance is less clear and may represent an important target for the promotion of optimal brain health in older adults. METHODS: Participants aged >60 years from the Trinity‐Ulster‐Department of Agriculture study underwent detailed cognitive assessment using the Mini‐Mental State Examination (Mini‐Mental State Examination (MMSE)), Frontal Assessment Battery (FAB) and Repeatable Battery for Assessment of Neuropsychological Status (RBANS). Poisson and linear regression models assessed the relationship between eGFR strata and cognitive performance. RESULTS: In 4887 older adults (73.9 ± 8.3 years; 67.7% female), declining eGFR strata was associated with greater likelihood of error on the MMSE/FAB and poorer overall performance on the RBANS. Following robust covariate adjustment, findings were greatest for GFR 80 years. CONCLUSIONS: Reduced kidney function was associated with poorer global and domain‐specific neuropsychological performance. Associations were strongest with eGFR <45 ml/min/1.73 m(2) and in those aged 60–70 years, suggesting that this population may potentially benefit from potential multi‐domain interventions aimed at promoting optimal brain health in older adults

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Arrhythmia and death following percutaneous revascularization in ischemic left ventricular dysfunction: Prespecified analyses from the REVIVED-BCIS2 trial

BACKGROUND: Ventricular arrhythmia is an important cause of mortality in patients with ischemic left ventricular dysfunction. Revascularization with coronary artery bypass graft or percutaneous coronary intervention is often recommended for these patients before implantation of a cardiac defibrillator because it is assumed that this may reduce the incidence of fatal and potentially fatal ventricular arrhythmias, although this premise has not been evaluated in a randomized trial to date. METHODS: Patients with severe left ventricular dysfunction, extensive coronary disease, and viable myocardium were randomly assigned to receive either percutaneous coronary intervention (PCI) plus optimal medical and device therapy (OMT) or OMT alone. The composite primary outcome was all-cause death or aborted sudden death (defined as an appropriate implantable cardioverter defibrillator therapy or a resuscitated cardiac arrest) at a minimum of 24 months, analyzed as time to first event on an intention-to-treat basis. Secondary outcomes included cardiovascular death or aborted sudden death, appropriate implantable cardioverter defibrillator (ICD) therapy or sustained ventricular arrhythmia, and number of appropriate ICD therapies. RESULTS: Between August 28, 2013, and March 19, 2020, 700 patients were enrolled across 40 centers in the United Kingdom. A total of 347 patients were assigned to the PCI+OMT group and 353 to the OMT alone group. The mean age of participants was 69 years; 88% were male; 56% had hypertension; 41% had diabetes; and 53% had a clinical history of myocardial infarction. The median left ventricular ejection fraction was 28%; 53.1% had an implantable defibrillator inserted before randomization or during follow-up. All-cause death or aborted sudden death occurred in 144 patients (41.6%) in the PCI group and 142 patients (40.2%) in the OMT group (hazard ratio, 1.03 [95% CI, 0.82–1.30]; P =0.80). There was no between-group difference in the occurrence of any of the secondary outcomes. CONCLUSIONS: PCI was not associated with a reduction in all-cause mortality or aborted sudden death. In patients with ischemic cardiomyopathy, PCI is not beneficial solely for the purpose of reducing potentially fatal ventricular arrhythmias. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01920048

Percutaneous revascularization for ischemic left ventricular dysfunction: Cost-effectiveness analysis of the REVIVED-BCIS2 trial

BACKGROUND: Percutaneous coronary intervention (PCI) is frequently undertaken in patients with ischemic left ventricular systolic dysfunction. The REVIVED (Revascularization for Ischemic Ventricular Dysfunction)-BCIS2 (British Cardiovascular Society-2) trial concluded that PCI did not reduce the incidence of all-cause death or heart failure hospitalization; however, patients assigned to PCI reported better initial health-related quality of life than those assigned to optimal medical therapy (OMT) alone. The aim of this study was to assess the cost-effectiveness of PCI+OMT compared with OMT alone. METHODS: REVIVED-BCIS2 was a prospective, multicenter UK trial, which randomized patients with severe ischemic left ventricular systolic dysfunction to either PCI+OMT or OMT alone. Health care resource use (including planned and unplanned revascularizations, medication, device implantation, and heart failure hospitalizations) and health outcomes data (EuroQol 5-dimension 5-level questionnaire) on each patient were collected at baseline and up to 8 years post-randomization. Resource use was costed using publicly available national unit costs. Within the trial, mean total costs and quality-adjusted life-years (QALYs) were estimated from the perspective of the UK health system. Cost-effectiveness was evaluated using estimated mean costs and QALYs in both groups. Regression analysis was used to adjust for clinically relevant predictors. RESULTS: Between 2013 and 2020, 700 patients were recruited (mean age: PCI+OMT=70 years, OMT=68 years; male (%): PCI+OMT=87, OMT=88); median follow-up was 3.4 years. Over all follow-ups, patients undergoing PCI yielded similar health benefits at higher costs compared with OMT alone (PCI+OMT: 4.14 QALYs, £22 352; OMT alone: 4.16 QALYs, £15 569; difference: −0.015, £6782). For both groups, most health resource consumption occurred in the first 2 years post-randomization. Probabilistic results showed that the probability of PCI being cost-effective was 0. CONCLUSIONS: A minimal difference in total QALYs was identified between arms, and PCI+OMT was not cost-effective compared with OMT, given its additional cost. A strategy of routine PCI to treat ischemic left ventricular systolic dysfunction does not seem to be a justifiable use of health care resources in the United Kingdom

Biomolecule Damage (DNA and Lipid) is Elevated in Patients with Type 1 Diabetes with and without Diabetic Complications

There is strong evidence that oxidative stress is involved in the aetiology and pathogenesis of diabetes and its complications. Increased production of reactive oxygen species in vivo can lead to cellular biomolecule damage, such as lipid peroxidation and DNA damage.The aim of this study was to determine the extent of this damage by measuring in vivo antioxidant status, levels of lipid peroxidation, and levels of neutrophil DNA damage in 50 participants with type 1 diabetes and 50 age- and sex-matched, healthy controls.Gylcaemic control (%HbA1c) was relatively good with a group mean of 7.71% which increased to 8.12 % in those with complications. Compared to the control group there were significantly elevated levels of neutrophil DNA damage (% tail DNA, p&lt;0.0001) and plasma MDA levels (p&lt;0.05) in the Type 1 group as a whole, this significance rose to p&lt;0.01 in those with complications. There were significant alterations in markers of antioxidant status including, reduced levels of superoxide dismutase (p&lt;0.0001), uric acid (p&lt;0.05) and Vitamin C (p&lt;0.05) and elevated levels of catalase (p&lt;0.001).These results indicate that even with acceptable glycaemic control significant oxidative damage still occurs and this damage increases, in some indices, with the onset of complications

A national stakeholder consensus study of challenges and priorities for clinical learning environments in postgraduate medical education

Background: High quality clinical learning environments (CLE) are critical to postgraduate medical education (PGME). The understaffed and overcrowded environments in which many residents work present a significant challenge to learning. The purpose of this study was to develop a national expert group consensus amongst stakeholders in PGME to; (i) identify important barriers and facilitators of learning in CLEs and (ii) indicate priority areas for improvement. Our objective was to provide information to focus efforts to provide high quality CLEs. Methods: Group Concept Mapping (GCM) is an integrated mixed methods approach to generating expert group consensus. A multi-disciplinary group of experts were invited to participate in the GCM process via an online platform. Multi-dimensional scaling and hierarchical cluster analysis were used to analyse participant inputs in regard to barriers, facilitators and priorities. Results: Participants identified facilitators and barriers in ten domains within clinical learning environments. Domains rated most important were those which related to residents’ connection to and engagement with more senior doctors. Organisation and conditions of work and Time to learn with senior doctors during patient care were rated as the most difficult areas in which to make improvements. Conclusions: High quality PGME requires that residents engage and connect with senior doctors during patient care, and that they are valued and supported both as learners and service providers. Academic medicine and health service managers must work together to protect these elements of CLEs, which not only shape learning, but impact quality of care and patient safety