Colony stimulating factor-1 producing endothelial cells and mesenchymal stromal cells maintain monocytes within a perivascular bone marrow niche.

Macrophage colony stimulating factor-1 (CSF-1) plays a critical role in maintaining myeloid lineage cells. However, congenital global deficiency of CSF-1 (Csf1op/op) causes severe musculoskeletal defects that may indirectly affect hematopoiesis. Indeed, we show here that osteolineage-derived Csf1 prevented developmental abnormalities but had no effect on monopoiesis in adulthood. However, ubiquitous deletion of Csf1 conditionally in adulthood decreased monocyte survival, differentiation, and migration, independent of its effects on bone development. Bone histology revealed that monocytes reside near sinusoidal endothelial cells (ECs) and leptin receptor (Lepr)-expressing perivascular mesenchymal stromal cells (MSCs). Targeted deletion of Csf1 from sinusoidal ECs selectively reduced Ly6C- monocytes, whereas combined depletion of Csf1 from ECs and MSCs further decreased Ly6Chi cells. Moreover, EC-derived CSF-1 facilitated recovery of Ly6C- monocytes and protected mice from weight loss following induction of polymicrobial sepsis. Thus, monocytes are supported by distinct cellular sources of CSF-1 within a perivascular BM niche.

Self-renewing resident arterial macrophages arise from embryonic CX3CR1(+) precursors and circulating monocytes immediately after birth.

Resident macrophages densely populate the normal arterial wall, yet their origins and the mechanisms that sustain them are poorly understood. Here we use gene-expression profiling to show that arterial macrophages constitute a distinct population among macrophages. Using multiple fate-mapping approaches, we show that arterial macrophages arise embryonically from CX3CR1(+) precursors and postnatally from bone marrow-derived monocytes that colonize the tissue immediately after birth. In adulthood, proliferation (rather than monocyte recruitment) sustains arterial macrophages in the steady state and after severe depletion following sepsis. After infection, arterial macrophages return rapidly to functional homeostasis. Finally, survival of resident arterial macrophages depends on a CX3CR1-CX3CL1 axis within the vascular niche.

A qualitative co-design-based approach to identify sources of workplace-related distress and develop well-being strategies for cardiovascular nurses, allied health professionals, and physicians.

OBJECTIVE: Clinician distress is a multidimensional condition that includes burnout, decreased meaning in work, severe fatigue, poor work-life integration, reduced quality of life, and suicidal ideation. It has negative impacts on patients, providers, and healthcare systems. In this three-phase qualitative investigation, we identified workplace-related factors that drive clinician distress and co-designed actionable interventions with inter-professional cardiovascular clinicians to decrease their distress and improve well-being within a Canadian quaternary hospital network. METHODS: Between October 2021 and May 2022, we invited nurses, allied health professionals, and physicians to participate in a three-phase qualitative investigation. Phases 1 and 2 included individual interviews and focus groups to identify workplace-related factors contributing to distress. Phase 3 involved co-design workshops that engaged inter-professional clinicians to develop interventions addressing drivers of distress identified. Qualitative information was analyzed using descriptive thematic analysis. RESULTS: Fifty-one clinicians (24 nurses, 10 allied health professionals, and 17 physicians) participated. Insights from Phases 1 and 2 identified five key thematic drivers of distress: inadequate support within inter-professional teams, decreased joy in work, unsustainable workloads, limited opportunities for learning and professional growth, and a lack of transparent leadership communication. Phase 3 co-design workshops yielded four actionable interventions to mitigate clinician distress in the workplace: re-designing daily safety huddles, formalizing a nursing coaching and mentorship program, creating a value-added program e-newsletter, and implementing an employee experience platform. CONCLUSION: This study increases our understanding on workplace-related factors that contribute to clinician distress, as shared by inter-professional clinicians specializing in cardiovascular care. Healthcare organizations can develop effective interventions to mitigate clinician distress by actively engaging healthcare workers in identifying workplace drivers of distress and collaboratively designing tailored, practical interventions that directly address these challenges.

Ethical decision making during a healthcare crisis: a resource allocation framework and tool.

The COVID-19 pandemic has strained healthcare resources the world over, requiring healthcare providers to make resource allocation decisions under extraordinary pressures. A year later, our understanding of COVID-19 has advanced, but our process for making ethical decisions surrounding resource allocation has not. During the first wave of the pandemic, our institution uniformly ramped-down clinical activity to accommodate the anticipated demands of COVID-19, resulting in resource waste and inefficiency. In preparation for the second wave, we sought to make such ramp down decisions more prudently and ethically. We report the development of a tool that can be used to make fair and ethical decisions in times of resource scarcity. We formed an interprofessional team to develop and use this tool to ensure that a diverse range of stakeholder perspectives were represented in this development process. This team, called the clinical activity recovery team, established institutional objectives that were combined with well-established procedural values, substantive ethical principles and decision-making criteria by using a variation on the well-known accountability for reasonableness ethical framework. The result of this is a stepwise, semiquantitative, ethical decision tool that can be applied to resource allocation challenges in order to reach fair and ethically defensible decisions. This ethical decision tool can be applied in various contexts and may prove useful at both the institutional and the departmental level; indeed this is how it is applied at our centre. As the second wave of COVID-19 strains healthcare resources, this tool can help clinical leaders to make fair decisions.

The psychological burden of waiting for procedures and patient-centred strategies that could support the mental health of wait-listed patients and caregivers during the COVID-19 pandemic: A scoping review.

BACKGROUND: Waiting for procedures delayed by COVID-19 may cause anxiety and related adverse consequences. OBJECTIVE: To synthesize research on the mental health impact of waiting and patient-centred mitigation strategies that could be applied in the COVID-19 context. METHODS: Using a scoping review approach, we searched 9 databases for studies on waiting lists and mental health and reported study characteristics, impacts and intervention attributes and outcomes. RESULTS: We included 51 studies that focussed on organ transplant (60.8%), surgery (21.6%) or cancer management (13.7%). Most patients and caregivers reported anxiety, depression and poor quality of life, which deteriorated with increasing wait time. The impact of waiting on mental health was greater among women and new immigrants, and those of younger age, lower socio-economic status, or with less-positive coping ability. Six studies evaluated educational strategies to develop coping skills: 2 reduced depression (2 did not), 1 reduced anxiety (2 did not) and 2 improved quality of life (2 did not). In contrast, patients desired acknowledgement of concerns, peer support, and periodic communication about wait-list position, prioritization criteria and anticipated procedure date. CONCLUSIONS: Findings revealed patient-centred strategies to alleviate the mental health impact of waiting for procedures. Ongoing research should explore how to optimize the impact of those strategies for diverse patients and caregivers, particularly in the COVID-19 context. PATIENT OR PUBLIC CONTRIBUTION: Six patients and four caregivers waiting for COVID-19-delayed procedures helped to establish eligibility criteria, plan data extraction and review a draft and final report.

Myocardial infarction accelerates atherosclerosis.

During progression of atherosclerosis, myeloid cells destabilize lipid-rich plaques in the arterial wall and cause their rupture, thus triggering myocardial infarction and stroke. Survivors of acute coronary syndromes have a high risk of recurrent events for unknown reasons. Here we show that the systemic response to ischaemic injury aggravates chronic atherosclerosis. After myocardial infarction or stroke, Apoe-/- mice developed larger atherosclerotic lesions with a more advanced morphology. This disease acceleration persisted over many weeks and was associated with markedly increased monocyte recruitment. Seeking the source of surplus monocytes in plaques, we found that myocardial infarction liberated haematopoietic stem and progenitor cells from bone marrow niches via sympathetic nervous system signalling. The progenitors then seeded the spleen, yielding a sustained boost in monocyte production. These observations provide new mechanistic insight into atherogenesis and provide a novel therapeutic opportunity to mitigate disease progression.

Innate response activator B cells aggravate atherosclerosis by stimulating T helper-1 adaptive immunity.

BACKGROUND: Atherosclerotic lesions grow via the accumulation of leukocytes and oxidized lipoproteins in the vessel wall. Leukocytes can attenuate or augment atherosclerosis through the release of cytokines, chemokines, and other mediators. Deciphering how leukocytes develop, oppose, and complement each other's function and shape the course of disease can illuminate our understanding of atherosclerosis. Innate response activator (IRA) B cells are a recently described population of granulocyte macrophage colony-stimulating factor-secreting cells of hitherto unknown function in atherosclerosis. METHODS AND RESULTS: Here, we show that IRA B cells arise during atherosclerosis in mice and humans. In response to a high-cholesterol diet, IRA B cell numbers increase preferentially in secondary lymphoid organs via Myd88-dependent signaling. Mixed chimeric mice lacking B cell-derived granulocyte macrophage colony-stimulating factor develop smaller lesions with fewer macrophages and effector T cells. Mechanistically, IRA B cells promote the expansion of classic dendritic cells, which then generate interferon γ-producing T helper-1 cells. This IRA B cell-dependent T helper-1 skewing manifests in an IgG1-to-IgG2c isotype switch in the immunoglobulin response against oxidized lipoproteins. CONCLUSIONS: Granulocyte macrophage colony-stimulating factor-producing IRA B cells alter adaptive immune processes and shift the leukocyte response toward a T helper-1-associated milieu that aggravates atherosclerosis.

The in-hospital costs of treating high-risk patients with fenestrated and branched endografts.

OBJECTIVE: This study determined the 30-day morbidity and mortality and in-hospital costs of elective fenestrated (fEVAR) and branched (bEVAR) endovascular aneurysm repairs at a single academic institution and determined factors that influence them. METHODS: All elective fEVAR or bEVAR patients treated between November 2007 and March 2014 in a Canadian academic hospital were included. Procedural details, 30-day morbidity and mortality rates, and cost of hospitalization were analyzed. Nonparametric bootstrap analysis was used to compare means between groups and calculate confidence intervals (CIs). RESULTS: There were 84 consecutive fEVAR (n = 61) and bEVAR (n = 23) procedures. The 30-day mortality was 3.3% for fEVAR and 4.3% for bEVAR. Mean hospital stay was 7.2 ± 0.8 days for fEVAR and 12.6 ± 2.2 days for bEVAR. The mean cost of the index hospitalization was $57,000 for fEVAR and $91,000 for bEVAR. Device-related costs accounted for 55% of the total costs. The occurrence of intraoperative or postoperative events were used to further divide each of the fEVAR and bEVAR groups into "complicated hospitalization" (fEVAR, n = 10; bEVAR, n = 13) and "uncomplicated hospitalization" (fEVAR, n = 51; bEVAR, n = 10) groups. Device-related costs were not significantly different between the complicated and uncomplicated hospitalization groups (mean difference [95% CI] fEVAR: $3383 [-$3405 to $9809], P = .3; and bEVAR: $1930 [-$7892 to $11,288], P = .68). However, there were significant differences between the complicated and uncomplicated hospitalization groups in hospital length of stay (mean difference [95% CI] fEVAR: 8.1 [3.0-13.2] days, P = .001; and bEVAR: 10.8 [5.9-19.9] days, P = .002) and nondevice-related costs (mean difference [95% CI,] fEVAR: $25,843 [$11,689-$43,247], P = .001; and bEVAR; $20,326 [$9362-$36,615], P = .002). CONCLUSIONS: bEVAR and fEVAR are expensive interventions. Intraoperative adverse events and postoperative systemic complications dramatically increase costs and length of stay. Measures to minimize complications will reduce hospitalization costs and improve patient outcomes.

Management of acute limb ischemia in the pediatric population.

OBJECTIVE: Acute limb ischemia (ALI) in pediatric patients is rare but may lead to limb loss and life-long complications. This study reviewed the experience of a Canadian tertiary pediatric center with the medical and operative management of ALI. METHODS: The medical records of inpatients diagnosed with ALI of the upper or lower limb between 1999 and 2012 were reviewed. Patient demographics, arterial clot site and etiology, intervention, anticoagulation type and duration, and short-term and long-term complications were analyzed. RESULTS: A total of 151 patients (45% female) presented with signs of limb ischemia, of whom 38% were aged <30 days, 46% were between 1 and 12 months, and 16% were between 1 and 18 years. Ninety-four percent of those injuries involved the lower limbs. Ninety-one percent were due to vessel catheterization, 5% were idiopathic, 1% were congenital, and 4% traumatic. Ninety-four percent were managed nonoperatively. Patients were treated with a combination of thrombolysis, unfractionated or low-molecular-weight heparin, aspirin or warfarin, or both (duration, 1 day-13 years). All patients were monitored after discharge at our institution or at their referring hospital (average, 3.4 ± 2.8 years). Fifteen percent had complications related to ALI or anticoagulation (most commonly limb length or thigh circumference discrepancy, or intracranial hemorrhage). Nineteen percent of patients died of unrelated causes (sepsis, multiorgan dysfunction, or cardiac failure). CONCLUSIONS: In contrast with adults, ALI in children can generally be managed nonoperatively with anticoagulation, likely because of their greater ability to develop arterial collaterals. Long-term follow-up by a multidisciplinary team of pediatric and surgical specialists and allied health professionals is integral to achieving a successful outcome in children with ALI.

Prevalence and drivers of nurse and physician distress in cardiovascular and oncology programmes at a Canadian quaternary hospital network during the COVID-19 pandemic: a quality improvement initiative.

OBJECTIVES: To assess the prevalence and drivers of distress, a composite of burnout, decreased meaning in work, severe fatigue, poor work-life integration and quality of life, and suicidal ideation, among nurses and physicians during the COVID-19 pandemic. DESIGN: Cross-sectional design to evaluate distress levels of nurses and physicians during the COVID-19 pandemic between June and August 2021. SETTING: Cardiovascular and oncology care settings at a Canadian quaternary hospital network. PARTICIPANTS: 261 nurses and 167 physicians working in cardiovascular or oncology care. Response rate was 29% (428 of 1480). OUTCOME MEASURES: Survey tool to measure clinician distress using the Well-Being Index (WBI) and additional questions about workplace-related and COVID-19 pandemic-related factors. RESULTS: Among 428 respondents, nurses (82%, 214 of 261) and physicians (62%, 104 of 167) reported high distress on the WBI survey. Higher WBI scores (≥2) in nurses were associated with perceived inadequate staffing (174 (86%) vs 28 (64%), p=0.003), unfair treatment, (105 (52%) vs 11 (25%), p=0.005), and pandemic-related impact at work (162 (80%) vs 22 (50%), p<0.001) and in their personal life (135 (67%) vs 11 (25%), p<0.001), interfering with job performance. Higher WBI scores (≥3) in physicians were associated with perceived inadequate staffing (81 (79%) vs 32 (52%), p=0.001), unfair treatment (44 (43%) vs 13 (21%), p=0.02), professional dissatisfaction (29 (28%) vs 5 (8%), p=0.008), and pandemic-related impact at work (84 (82%) vs 35 (56%), p=0.001) and in their personal life (56 (54%) vs 24 (39%), p=0.014), interfering with job performance. CONCLUSION: High distress was common among nurses and physicians working in cardiovascular and oncology care settings during the pandemic and linked to factors within and beyond the workplace. These results underscore the complex and contextual aspects of clinician distress, and the need to develop targeted approaches to effectively address this problem.

Lack of microsomal prostaglandin E(2) synthase-1 in bone marrow-derived myeloid cells impairs left ventricular function and increases mortality after acute myocardial infarction.

BACKGROUND: Microsomal prostaglandin E(2) synthase-1 (mPGES-1), encoded by the Ptges gene, catalyzes prostaglandin E(2) biosynthesis and is expressed by leukocytes, cardiac myocytes, and cardiac fibroblasts. Ptges(-/-) mice develop more left ventricle (LV) dilation, worse LV contractile function, and higher LV end-diastolic pressure than Ptges(+/+) mice after myocardial infarction. In this study, we define the role of mPGES-1 in bone marrow-derived leukocytes in the recovery of LV function after coronary ligation. METHODS AND RESULTS: Cardiac structure and function in Ptges(+/+) mice with Ptges(+/+) bone marrow (BM(+/+)) and Ptges(+/+) mice with Ptges(-/-) BM (BM(-/-)) were assessed by morphometric analysis, echocardiography, and invasive hemodynamics before and 7 and 28 days after myocardial infarction. Prostaglandin levels and prostaglandin biosynthetic enzyme gene expression were measured by liquid chromatography-tandem mass spectrometry and real-time polymerase chain reaction, immunoblotting, immunohistochemistry, and immunofluorescence microscopy, respectively. After myocardial infarction, BM(-/-) mice had more LV dilation, worse LV systolic and diastolic function, higher LV end-diastolic pressure, more cardiomyocyte hypertrophy, and higher mortality but similar infarct size and pulmonary edema compared with BM(+/+) mice. BM(-/-) mice also had higher levels of COX-1 protein and more leukocytes in the infarct, but not the viable LV, than BM(+/+) mice. Levels of prostaglandin E(2) were higher in the infarct and viable myocardium of BM(-/-) mice than in BM(+/+) mice. CONCLUSIONS: Lack of mPGES-1 in bone marrow-derived leukocytes negatively regulates COX-1 expression, prostaglandin E(2) biosynthesis, and inflammation in the infarct and leads to impaired LV function, adverse LV remodeling, and decreased survival after acute myocardial infarction.

Differential pathological and immune responses in newly weaned ferrets are associated with a mild clinical outcome of pandemic 2009 H1N1 infection.

Young children are typically considered a high-risk group for disease associated with influenza virus infection. Interestingly, recent clinical reports suggested that young children were the smallest group of cases with severe pandemic 2009 H1N1 (H1N1pdm) influenza virus infection. Here we established a newly weaned ferret model for the investigation of H1N1pdm infection in young age groups compared to adults. We found that young ferrets had a significantly milder fever and less weight loss than adult ferrets, which paralleled the mild clinical symptoms in the younger humans. Although there was no significant difference in viral clearance, disease severity was associated with pulmonary pathology, where newly weaned ferrets had an earlier pathology improvement. We examined the immune responses associated with protection of the young age group during H1N1pdm infection. We found that interferon and regulatory interleukin-10 responses were more robust in the lungs of young ferrets. In contrast, myeloperoxidase and major histocompatibility complex responses were persistently higher in the adult lungs; as well, the numbers of inflammation-prone granulocytes were highly elevated in the adult peripheral blood. Importantly, we observed that H1N1pdm infection triggered formation of lung structures that resembled inducible bronchus-associated lymphoid tissues (iBALTs) in young ferrets which were associated with high levels of homeostatic chemokines CCL19 and CXCL13, but these were not seen in the adult ferrets with severe disease. These results may be extrapolated to a model of the mild disease seen in human children. Furthermore, these mechanistic analyses provide significant new insight into the developing immune system and effective strategies for intervention and vaccination against respiratory viruses.

Association Between the Incidence of Hospitalizations for Acute Cardiovascular Events, Weather, and Air Pollution.

Background: The incidence of hospitalizations for cardiovascular events has been associated with specific weather conditions and air pollution. A comprehensive model including the interactions between various environmental factors remains to be developed. Objectives: The purpose of this study was to develop a comprehensive model of the association between weather patterns and the incidence of cardiovascular events and use this model to forecast near-term spatiotemporal risk. Methods: We present a spatiotemporal analysis of the association between atmospheric data and the incidence rate of hospital admissions related to heart failure (922,132 episodes), myocardial infarction (521,988 episodes), and ischemic stroke (263,529 episodes) in ∼24 million people in Canada between 2007 and 2017. Our hierarchical Bayesian model captured the spatiotemporal distribution of hospitalizations and identified weather and air pollution-related factors that could partially explain fluctuations in incidence. Results: Models that included weather and air pollution variables outperformed models without those covariates for most event types. Our results suggest that environmental factors may interact in complex ways on human physiology. The impact of environmental factors was magnified with increasing age. The weather and air pollution variables included in our models were predictive of the future incidence of heart failure, myocardial infarction, and ischemic strokes. Conclusions: The increasing importance of environmental factors on cardiovascular events with increasing age raises the need for the development of educational materials for older patients to recognize environmental conditions where exacerbations are more likely. This model could be the basis of a forecasting system used for local, short-term clinical resource planning based on the anticipated incidence of events.

Anti-inflammatory role of microsomal prostaglandin E synthase-1 in a model of neuroinflammation.

A major immunological response during neuroinflammation is the activation of microglia, which subsequently release proinflammatory mediators such as prostaglandin E(2) (PGE(2)). Besides its proinflammatory properties, cyclooxygenase-2 (COX-2)-derived PGE(2) has been shown to exhibit anti-inflammatory effects on innate immune responses. Here, we investigated the role of microsomal PGE(2) synthase-1 (mPGES-1), which is functionally coupled to COX-2, in immune responses using a model of lipopolysaccharide (LPS)-induced spinal neuroinflammation. Interestingly, we found that activation of E-prostanoid (EP)2 and EP4 receptors, but not EP1, EP3, PGI(2) receptor (IP), thromboxane A(2) receptor (TP), PGD(2) receptor (DP), and PGF(2) receptor (FP), efficiently blocked LPS-induced tumor necrosis factor α (TNFα) synthesis and COX-2 and mPGES-1 induction as well as prostaglandin synthesis in spinal cultures. In vivo, spinal EP2 receptors were up-regulated in microglia in response to intrathecally injected LPS. Accordingly, LPS priming reduced spinal synthesis of TNFα, interleukin 1ß (IL-1ß), and prostaglandins in response to a second intrathecal LPS injection. Importantly, this reduction was only seen in wild-type but not in mPGES-1-deficient mice. Furthermore, intrathecal application of EP2 and EP4 agonists as well as genetic deletion of EP2 significantly reduced spinal TNFα and IL-1ß synthesis in mPGES-1 knock-out mice after LPS priming. These data suggest that initial inflammation prepares the spinal cord for a negative feedback regulation by mPGES-1-derived PGE(2) followed by EP2 activation, which limits the synthesis of inflammatory mediators during chronic inflammation. Thus, our data suggest a role of mPGES-1-derived PGE(2) in resolution of neuroinflammation.

Group V phospholipase A2 in bone marrow-derived myeloid cells and bronchial epithelial cells promotes bacterial clearance after Escherichia coli pneumonia.

Group V-secreted phospholipase A(2) (GV sPLA(2)) hydrolyzes bacterial phospholipids and initiates eicosanoid biosynthesis. Here, we elucidate the role of GV sPLA(2) in the pathophysiology of Escherichia coli pneumonia. Inflammatory cells and bronchial epithelial cells both express GV sPLA(2) after pulmonary E. coli infection. GV(-/-) mice accumulate fewer polymorphonuclear leukocytes in alveoli, have higher levels of E. coli in bronchoalveolar lavage fluid and lung, and develop respiratory acidosis, more severe hypothermia, and higher IL-6, IL-10, and TNF-α levels than GV(+/+) mice after pulmonary E. coli infection. Eicosanoid levels in bronchoalveolar lavage are similar in GV(+/+) and GV(-/-) mice after lung E. coli infection. In contrast, GV(+/+) mice have higher levels of prostaglandin D(2) (PGD(2)), PGF(2α), and 15-keto-PGE(2) in lung and express higher levels of ICAM-1 and PECAM-1 on pulmonary endothelial cells than GV(-/-) mice after lung infection with E. coli. Selective deletion of GV sPLA(2) in non-myeloid cells impairs leukocyte accumulation after pulmonary E. coli infection, and lack of GV sPLA(2) in either bone marrow-derived myeloid cells or non-myeloid cells attenuates E. coli clearance from the alveolar space and the lung parenchyma. These observations show that GV sPLA(2) in bone marrow-derived myeloid cells as well as non-myeloid cells, which are likely bronchial epithelial cells, participate in the regulation of the innate immune response to pulmonary infection with E. coli.

Factors associated with SARS-CoV-2 test positivity in long-term care homes: A population-based cohort analysis using machine learning.

BACKGROUND: SARS-Cov-2 infection rates are high among residents of long-term care (LTC) homes. We used machine learning to identify resident and community characteristics predictive of SARS-Cov-2 infection. METHODS: We linked 26 population-based health and administrative databases to identify the population of all LTC residents tested for SARS-Cov-2 infection in Ontario, Canada. Using ensemble-based algorithms, we examined 484 factors, including individual-level demographics, healthcare use, comorbidities, functional status, and laboratory results; and community-level characteristics to identify factors predictive of infection. Analyses were performed separately for January to April (early wave 1) and May to August (late wave 1). FINDINGS: Among 80,784 LTC residents, 64,757 (80.2%) were tested for SARS-Cov-2 (median age 86 (78-91) years, 30.6% male), of whom 10.2% of 33,519 and 5.2% of 31,238 tested positive in early and late wave 1, respectively. In the late phase (when restriction of visitors, closure of communal spaces, and universal masking in LTC were routine), regional-level characteristics comprised 33 of the top 50 factors associated with testing positive, while laboratory values and comorbidities were also predictive. The c-index of the final model was 0.934, and sensitivity was 0.887. In the highest versus lowest risk quartiles, the odds ratio for infection was 114.3 (95% CI 38.6-557.3). LTC-related geographic variations existed in the distribution of observed infection rates and the proportion of residents at highest risk. INTERPRETATION: Machine learning informed evaluation of predicted and observed risks of SARS-CoV-2 infection at the resident and LTC levels, and may inform initiatives to improve care quality in this setting. FUNDING: Funded by a Canadian Institutes of Health Research, COVID-19 Rapid Research Funding Opportunity grant (# VR4 172736) and a Peter Munk Cardiac Centre Innovation Grant. Dr. D. Lee is the Ted Rogers Chair in Heart Function Outcomes, University Health Network, University of Toronto. Dr. Austin is supported by a Mid-Career investigator award from the Heart and Stroke Foundation. Dr. McAlister is supported by an Alberta Health Services Chair in Cardiovascular Outcomes Research. Dr. Kaul is the CIHR Sex and Gender Science Chair and the Heart & Stroke Chair in Cardiovascular Research. Dr. Rochon holds the RTO/ERO Chair in Geriatric Medicine from the University of Toronto. Dr. B. Wang holds a CIFAR AI chair at the Vector Institute.

Iliac branch graft in the treatment of complex aortoiliac aneurysms: early results from a North American institution.

PURPOSE: To describe early experience with the use of iliac branch grafts (IBGs) in aortoiliac aneurysm repair. MATERIALS AND METHODS: From July 2007 to August 2009 (25 months), 14 patients (13 men, one woman) with a mean age of 70.1 years (range, 59.3-80.0 y) were treated with IBGs. Indications were abdominal aneurysm with common iliac artery (CIA) involvement (n = 11), juxtarenal aortic aneurysm with CIA involvement (n = 1), and bilateral CIA and internal iliac artery (IIA) aneurysms (n = 1). Postoperative endoleaks and patency rate were determined with computed tomography within 1 month of implantation and 1 year thereafter, with concurrent clinical evaluation for pelvic ischemia. Mean follow-up period was 18.7 months (range, 6-35 mo). RESULTS: Technical success rate, as defined by successful implantation of IBG with no intraprocedural type I or type III endoleak, was 86% (12 of 14). A total of 14 IBGs were successfully deployed in 12 patients. Two cases of technical failure were related to excessive iliac tortuosity. The mean hospitalization duration was 6.5 days (range, 3-14 d), with zero mortality at 30 days. There were two cases of type II endoleak treated conservatively and a single case of IBG-related type III endoleak that required repeat intervention. The rest of the stent-implanted aortic and iliac aneurysms remained stable in size, with no aneurysm rupture or death recorded. All stent-implanted iliac branches remained patent on follow-up. None of the patients who received IBGs had new symptoms of pelvic ischemia. CONCLUSIONS: Iliac branch graft placement is a feasible technique with excellent short-term results in the treatment of aortoiliac aneurysms.

Burnout and distress among physicians in a cardiovascular centre of a quaternary hospital network: a cross-sectional survey.

BACKGROUND: Burnout and distress have a negative impact on physicians and the treatment they provide. Our aim was to measure the prevalence of burnout and distress among physicians in a cardiovascular centre of a quaternary hospital network in Canada, and compare these outcomes to those for physicians at academic health science centres (AHSCs) in the United States. METHODS: We conducted a survey of physicians practising in a cardiovascular centre at 2 quaternary referral hospitals in Toronto, Ontario, between Nov. 27, 2018, and Jan. 31, 2019. The survey tool included the Well-Being Index (WBI), which measures fatigue, depression, burnout, anxiety or stress, mental and physical quality of life, work-life integration, meaning in work and distress; a score of 3 or higher indicated high distress. We also evaluated physicians' perception of the adequacy of staffing levels and of fair treatment in the workplace, and satisfaction with the electronic health record. We carried out standard univariate statistical comparisons using the χ2, Fisher exact or Kruskal-Wallis test as appropriate to perform univariate comparisons in the sample of respondents. We assessed the relation between a WBI score of 3 or higher and demographic characteristics. We compared univariate associations among WBI data for physicians at AHSCs in the US who completed the WBI to responses from our participants. RESULTS: The response rate to the survey was 84.1% (127/151). Of the 127 respondents, 83 (65.4%) reported burnout in the previous month, and 68 (53.5%) reported emotional problems. Sixty-nine respondents (54.3%) had a WBI score of 3 or higher. Respondents were more likely to have a WBI score of 3 or higher versus a score less than 3 if they perceived insufficient staffing levels (52/69 [75%] v. 26/58 [45%], p = 0.02) or unfair treatment (23/69 [33%] v. 8/58 [14%], p = 0.03), or were anesthesiologists (26/35 [74%] v. 43/92 [47%] for other specialists, p = 0.005). Compared to 21 594 physicians in practice at AHSCs in the US, our respondents had a higher mean WBI score (2.4 v. 1.8, p = 0.004) and reported a higher prevalence of burnout (65.4% v. 56.6%, p = 0.048). INTERPRETATION: Physicians in this study had high levels of burnout and distress, driven by the perception of inadequate staffing levels and being treated unfairly in the workplace. Addressing these institutional factors may improve physicians' work experience and patient outcomes.

Burnout and distress among nurses in a cardiovascular centre of a quaternary hospital network: a cross-sectional survey.

BACKGROUND: Burnout and distress have a negative impact on nurses and the treatment they provide. Our aim was to measure the prevalence of burnout and distress among nurses in a cardiovascular centre at 2 quaternary referral hospitals in Canada, and compare these outcomes to those for nurses at academic health science centres (AHSCs) in the United States. METHODS: We conducted a survey of nurses practising in a cardiovascular centre at 2 quaternary referral hospitals in Toronto, Ontario, between Nov. 27, 2018, and Jan. 31, 2019. The survey tool included the Well-Being Index (WBI), which measures fatigue, depression, burnout, anxiety or stress, mental and physical quality of life, work-life integration, meaning in work and distress; a score of 2 or higher on the WBI indicated high distress. We also evaluated nurses' perception of the adequacy of staffing levels and of fair treatment in the workplace, and satisfaction with the electronic health record. We carried out standard univariate statistical comparisons using the χ2, Fisher exact or Kruskal-Wallis test as appropriate to perform univariate comparisons in the sample of respondents. We assessed the relation between a WBI score of 2 or higher and demographic characteristics. We compared univariate associations among WBI data for nurses at AHSCs in the US who completed the WBI to responses from our participants. RESULTS: The response rate to the survey was 49.1% (242/493). Of the 242 respondents, 188 (77.7%) reported burnout in the previous month; 189 (78.1%) had a WBI score of 2 or higher, and 132 (54.5%) had a score of 4 or higher (indicative of severe distress). Ordinal multivariable analysis showed that lower WBI scores were associated with satisfaction with staffing levels (odds ratio [OR] 0.33, 95% confidence interval [CI] 0.16-0.69) and the perception of fair treatment in the workplace (OR 0.41, 95% CI 0.23-0.74). Higher proportions of our respondents than nurses at AHSCs in the US reported burnout (77.7% v. 60.5%, p < 0.001) and had a WBI score of 2 or higher (78.1% v. 57.0%) or 4 or higher (54.5% v. 32.0%) (both p < 0.001). INTERPRETATION: Although levels of burnout and distress were high among nurses, their perceptions of adequate staffing and fair treatment were associated with lower distress. Addressing inadequate staffing and unfair treatment may decrease burnout and other dimensions of distress among nurses, and improve their work experience and patient outcomes.