IntroductionDelirium occurs frequently in critically ill patients and is associated with disease severity and infection. Although several pathways for delirium have been described, biomarkers associated with delirium in intensive care unit (ICU) patients is not well studied. We examined plasma biomarkers in delirious and nondelirious patients and the role of these biomarkers on long-term cognitive function.MethodsIn an exploratory observational study, we included 100 ICU patients with or without delirium and with ("inflamed") and without ("noninflamed") infection/systemic inflammatory response syndrome (SIRS). Delirium was diagnosed by using the confusion-assessment method-ICU (CAM-ICU). Within 24 hours after the onset of delirium, blood was obtained for biomarker analysis. No differences in patient characteristics were found between delirious and nondelirious patients. To determine associations between biomarkers and delirium, univariate and multivariate logistic regression analyses were performed. Eighteen months after ICU discharge, a cognitive-failure questionnaire was distributed to the ICU survivors.ResultsIn total, 50 delirious and 50 nondelirious patients were included. We found that IL-8, MCP-1, procalcitonin (PCT), cortisol, and S100-β were significantly associated with delirium in inflamed patients (n = 46). In the noninflamed group of patients (n = 54), IL-8, IL-1ra, IL-10 ratio Aβ1-42/40, and ratio AβN-42/40 were significantly associated with delirium. In multivariate regression analysis, IL-8 was independently associated (odds ratio, 9.0; 95% confidence interval (CI), 1.8 to 44.0) with delirium in inflamed patients and IL-10 (OR 2.6; 95% CI 1.1 to 5.9), and Aβ1-42/40 (OR, 0.03; 95% CI, 0.002 to 0.50) with delirium in noninflamed patients. Furthermore, levels of several amyloid-β forms, but not human Tau or S100-β, were significantly correlated with self-reported cognitive impairment 18 months after ICU discharge, whereas inflammatory markers were not correlated to impaired long-term cognitive function.ConclusionsIn inflamed patients, the proinflammatory cytokine IL-8 was associated with delirium, whereas in noninflamed patients, antiinflammatory cytokine IL-10 and Aβ1-42/40 were associated with delirium. This suggests that the underlying mechanism governing the development of delirium in inflamed patients differs from that in noninflamed patients. Finally, elevated levels of amyloid-β correlated with long-term subjective cognitive-impairment delirium may represent the first sign of a (subclinical) dementia process. Future studies must confirm these results.The study was registered in the Clinical Trial Register (NCT00604773).

IMPORTANCEThe evidence for palliative care exists predominantly for patients with cancer. The effect of palliative care on important end-of-life outcomes in patients with noncancer illness is unclear.OBJECTIVE To measure the association between palliative care and acute health care use, quality of life (QOL), and symptom burden in adults with chronic noncancer illnesses.

The traditional view of atherosclerosis has recently been expanded from a predominantly lipid retentive disease to a coupling of inflammatory mechanisms and dyslipidemia. Studies have suggested a novel role for polymorphonuclear neutrophil (PMN)-dominant inflammation in the development of atherosclerosis. Human neutrophil peptides (HNPs), also known as alpha-defensins, are secreted and released from PMN granules upon activation and are conventionally involved in microbial killing. Current evidence suggests an important immunomodulative role for these peptides. HNP levels are markedly increased in inflammatory diseases including sepsis and acute coronary syndromes. They have been found within the intima of human atherosclerotic arteries, and their deposition in the skin correlates with the severity of coronary artery diseases. HNPs form complexes with LDL in solution and increase LDL binding to the endothelial surface. HNPs have also been shown to contribute to endothelial dysfunction, lipid metabolism disorder, and the inhibition of fibrinolysis. Given the emerging relationship between PMN-dominant inflammation and atherosclerosis, HNPs may serve as a link between them and as a biological marker and potential therapeutic target in cardiovascular diseases including coronary artery diseases and acute coronary syndromes.

Abstract Objective To measure the associations between newly initiated palliative care in the last six months of life, healthcare use, and location of death in adults dying from non-cancer illness, and to compare these associations with those in adults who die from cancer at a population level. Design Population based matched cohort study. Setting Ontario, Canada between 2010 and 2015. Participants 113 540 adults dying from cancer and non-cancer illness who were given newly initiated physician delivered palliative care in the last six months of life administered across all healthcare settings. Linked health administrative data were used to directly match patients on cause of death, hospital frailty risk score, presence of metastatic cancer, residential location (according to 1 of 14 local health integration networks that organise all healthcare services in Ontario), and a propensity score to receive palliative care that was derived by using age and sex. Main outcome measures Rates of emergency department visits, admissions to hospital, and admissions to the intensive care unit, and odds of death at home versus in hospital after first palliative care visit, adjusted for patient characteristics (such as age, sex, and comorbidities). Results In patients dying from non-cancer illness related to chronic organ failure (such as heart failure, cirrhosis, and stroke), palliative care was associated with reduced rates of emergency department visits (crude rate 1.9 (standard deviation 6.2) v 2.9 (8.7) per person year; adjusted rate ratio 0.88, 95% confidence interval 0.85 to 0.91), admissions to hospital (crude rate 6.1 (standard deviation 10.2) v 8.7 (12.6) per person year; adjusted rate ratio 0.88, 95% confidence interval 0.86 to 0.91), and admissions to the intensive care unit (crude rate 1.4 (standard deviation 5.9) v 2.9 (8.7) per person year; adjusted rate ratio 0.59, 95% confidence interval 0.56 to 0.62) compared with those who did not receive palliative care. Additionally increased odds of dying at home or in a nursing home compared with dying in hospital were found in these patients (n=6936 (49.5%) v n=9526 (39.6%); adjusted odds ratio 1.67, 95% confidence interval 1.60 to 1.74). Overall, in patients dying from dementia, palliative care was associated with increased rates of emergency department visits (crude rate 1.2 (standard deviation 4.9) v 1.3 (5.5) per person year; adjusted rate ratio 1.06, 95% confidence interval 1.01 to 1.12) and admissions to hospital (crude rate 3.6 (standard deviation 8.2) v 2.8 (7.8) per person year; adjusted rate ratio 1.33, 95% confidence interval 1.27 to 1.39), and reduced odds of dying at home or in a nursing home (n=6667 (72.1%) v n=13 384 (83.5%); adjusted odds ratio 0.68, 95% confidence interval 0.64 to 0.73). However, these rates differed depending on whether patients dying with dementia lived in the community or in a nursing home. No association was found between healthcare use and palliative care for patients dying from dementia who lived in the community, and these patients had increased odds of dying at home. Conclusions These findings highlight the potential benefits of palliative care in some non-cancer illnesses. Increasing access to palliative care through sustained investment in physician training and current models of collaborative palliative care could improve end-of-life care, which might have important implications for health policy.

Background Although podcasts are increasingly being produced for medical education, their use and perceived impact in informal educational settings are understudied. Objective This study aimed to explore how and why physicians and medical learners listen to The Rounds Table (TRT), a medical podcast, as well as to determine the podcast’s perceived impact on learning and practice. Methods Web-based podcast analytics were used to collect TRT usage statistics. A total of 17 medical TRT listeners were then identified and interviewed through purposive and convenience sampling, using a semistructured guide and a thematic analysis, until theoretical sufficiency was achieved. Results The following four themes related to podcast listenership were identified: (1) participants thought that TRT increased efficiency, allowing them to multitask, predominantly using mobile listening platforms; (2) participants listened to the podcast for both education and entertainment, or “edutainment”; (3) participants thought that the podcast helped them keep up to date with medical literature; and (4) participants considered TRT to have an indirect effect on learning and clinical practice by increasing overall knowledge. Conclusions Our results highlight how a medical podcast, designed for continuing professional development, is often used informally to promote learning. These findings enhance our understanding of how and why listeners engage with a medical podcast, which may be used to inform the development and evaluation of other podcasts.

Background Palliative care is associated with improved symptom control and quality of life in people with heart failure. There is conflicting evidence as to whether it is associated with a greater likelihood of death at home in this population. The objective of this study was to describe the delivery of newly initiated palliative care services in adults who die with heart failure and measure the association between receipt of palliative care and death at home compared with those who did not receive palliative care. Methods and Results We performed a population‐based cohort study using linked health administrative data in Ontario, Canada of 74 986 community‐dwelling adults with heart failure who died between 2010 and 2015. Seventy‐five percent of community‐dwelling adults with heart failure died in a hospital. Patients who received any palliative care were twice as likely to die at home compared with those who did not receive it (adjusted odds ratio 2.12 [95% CI , 2.03–2.20]; P <0.01). Delivery of home‐based palliative care had a higher association with death at home (adjusted odds ratio 11.88 [95% CI , 9.34–15.11]; P <0.01), as did delivery during transitions of care between inpatient and outpatient care settings (adjusted odds ratio 8.12 [95% CI , 6.41–10.27]; P <0.01). Palliative care was most commonly initiated late in the course of a person's disease (≤30 days before death, 45.2% of subjects) and led by nonspecialist palliative care physicians 61% of the time. Conclusions Most adults with heart failure die in a hospital. Providing palliative care near the end‐of‐life was associated with an increased likelihood of dying at home. These findings suggest that scaling existing palliative care programs to increase access may improve end‐of‐life care in people dying with chronic noncancer illness.

Objective-Neutrophils

CLINICIAN'S CAPSULE What is known about the topic? Goals of care discussions (GOC) are critical to reflecting patients' preferences in the provision of acute care, yet these discussions can be challenging to have in the emergency department (ED) setting. What did this study ask? What are emergency physicians' perspectives on barriers and facilitators to GOC discussions? What did this study find? In this survey of emergency medicine attending and resident physicians, the majority reported feeling comfortable and adequately trained to conduct GOC discussions. However, they identified time constraints, environmental factors, and patient expectations as barriers. Fifty-four percent of respondents believed that it was primarily the responsibility of admitting services to conduct GOC discussions. Why does this study matter to clinicians? This study suggests that dedicated ED resources for palliative care, such as a palliative care ED pathway, and addressing structural factors, such as a way to dedicate time and private space to GOC discussions, would be promising avenues for improvement. Training did not appear to be a barrier.