Secondary impacts of the COVID-19 pandemic at a tertiary children's hospital in Canada: a mixed-methods study.

OBJECTIVES: Decisions to pause all non-essential paediatric hospital activities during the initial phase of the COVID-19 pandemic may have led to significant delays, deferrals and disruptions in medical care. This study explores clinical cases where the care of children was perceived by hospital clinicians to have been negatively impacted because of the changes in healthcare delivery attributing to the restrictions placed resulting from the COVID-19 pandemic. DESIGN AND SETTING: This study used a mixed-methods approach using the following: (1) a quantitative analysis of overall descriptive hospital activity between May and August 2020, and utilisation of data during the study period was performed, and (2) a qualitative multiple-case study design with descriptive thematic analysis of clinician-reported consequences of the COVID-19 pandemic on care provided at a tertiary children's hospital. RESULTS: Hospital-level utilisation and activity patterns revealed a substantial change to hospital activity including an initial reduction in emergency department attendance by 38% and an increase in ambulatory virtual care from 4% before COVID-19 to 67% between May and August 2020. Two hundred and twelve clinicians reported a total of 116 unique cases. Themes including (1) timeliness of care, (2) disruption of patient-centred care, (3) new pressures in the provision of safe and efficient care and (4) inequity in the experience of the COVID-19 pandemic emerged, each impacting patients, their families and healthcare providers. CONCLUSION: Being aware of the breadth of the impact of the COVID-19 pandemic across all of the identified themes is important to enable the delivery of timely, safe, high-quality, family-centred paediatric care moving forward.

The Prevalence and Predictors of Compassion Satisfaction, Burnout and Secondary Traumatic Stress in Registered Nurses in an Eastern Canadian Province: A Cross-Sectional Study.

BACKGROUND: The quality of Registered Nurses' worklife is impacting nurses' mental health, and the standard of care received by clients. Contributing factors to nurses' stress are the trauma of continuous caring for those in great suffering, and adverse working conditions. OBJECTIVES: i) to explore the prevalence of work-related stress in a provincial sample of Registered Nurses; ii) to compare the levels of compassion satisfaction, burnout and secondary traumatic stress reported by nurses in hospital, community, non-direct care settings, and, iii) to identify factors that predict levels of nursing work stress. METHODS: A descriptive, predictive study with a self-report survey containing demographic questions and the Professional Quality of Life Scale was emailed to over 3,300 Registered Nurses. The scale measured the prevalence of three worklife indicators, compassion satisfaction, burnout and secondary traumatic stress. Multiple linear regression identified factors that predicted the levels of the three indicators. A subgroup analysis explored the quality of worklife based on three practice environments. FINDINGS: Nurses (n = 661) reported moderate compassion satisfaction, burnout, and secondary traumatic stress. The strongest predictor, satisfaction with one's current job, predicted high compassion satisfaction and lower burnout and secondary stress. The subgroup analysis identified hospital nurses as having the most work-related stress and the lowest level of compassion satisfaction. CONCLUSION: Innovative, collaborative action can transform nurses' practice environments. Organizational support is essential to bring about needed improvements.

Characterization of p73 functional domains necessary for transactivation and growth suppression.

p73, a p53 family member, is highly similar to p53 in both structure and function. Like p53, the p73 protein contains an N-terminal activation domain, a DNA-binding domain, a tetramerization domain, and several PXXP motifs. Previously, we and others have shown that some functional domains in p53, such as the DNA-binding and tetramerization domains, are required for inducing both cell cycle arrest and apoptosis whereas others, such as the second activation domain, the proline-rich domain, and the C-terminal basic domain, are only required for inducing apoptosis. To determine the activity of p73 functional domains, we have generated stable inducible cell lines that express p73beta and various mutants deficient in one or more functional domains. We found that in addition to the DNA-binding domain, p73-mediated growth suppression requires the N-terminal activation domain and the tetramerization domain. However, unlike p53, p73-mediated apoptosis does not require the region adjacent to the activation domain or the entire C-terminal region. Interestingly, while the N- or the C-terminal PXXP motifs are dispensable for p73 function, deletion of both the N- and the C-terminal PXXP motifs renders p73 inactive in transactivation. In addition, we found that substitution of two conserved tandem hydrophobic residues with two hydrophilic ones, which can abrogate the activity of the first activation domain in p53, has no effect on p73 transcriptional activity. Together, we showed that the p73 protein has its own unique determinants for transactivation and growth suppression.

The PERK eukaryotic initiation factor 2 alpha kinase is required for the development of the skeletal system, postnatal growth, and the function and viability of the pancreas.

Phosphorylation of eukaryotic initiation factor 2 alpha (eIF-2 alpha) is typically associated with stress responses and causes a reduction in protein synthesis. However, we found high phosphorylated eIF-2 alpha (eIF-2 alpha[P]) levels in nonstressed pancreata of mice. Administration of glucose stimulated a rapid dephosphorylation of eIF-2 alpha. Among the four eIF-2 alpha kinases present in mammals, PERK is most highly expressed in the pancreas, suggesting that it may be responsible for the high eIF-2 alpha[P] levels found therein. We describe a Perk knockout mutation in mice. Pancreata of Perk(-/-) mice are morphologically and functionally normal at birth, but the islets of Langerhans progressively degenerate, resulting in loss of insulin-secreting beta cells and development of diabetes mellitus, followed later by loss of glucagon-secreting alpha cells. The exocrine pancreas exhibits a reduction in the synthesis of several major digestive enzymes and succumbs to massive apoptosis after the fourth postnatal week. Perk(-/-) mice also exhibit skeletal dysplasias at birth and postnatal growth retardation. Skeletal defects include deficient mineralization, osteoporosis, and abnormal compact bone development. The skeletal and pancreatic defects are associated with defects in the rough endoplasmic reticulum of the major secretory cells that comprise the skeletal system and pancreas. The skeletal, pancreatic, and growth defects are similar to those seen in human Wolcott-Rallison syndrome.