Patient, Neighborhood, and Spatial Determinants of Out-of-Hospital Cardiac Arrest Outcomes Throughout the Chain of Survival: A Community-Oriented Multilevel Analysis.

Objective: Global and national trends of out-of-hospital cardiac arrest (OHCA) have been examined; however, geographic variation and socioeconomic disparities of OHCA outcomes in the community setting are less understood. We developed and tested a replicable, community-oriented assessment strategy aimed to identify spatial variations in OHCA outcomes using socioeconomic, prehospital, and in-hospital factors. Methods: Emergency medical service (EMS) records of adult, non-traumatic OHCA within Alachua County, FL (2012-2017) were retrospectively reviewed and matched to corresponding medical records at the University of Florida (UF). Incidence of cardiac arrest was geocoded to census tracts and connected to U.S. census socioeconomic attribute data. Primary outcomes include survival to emergency department (ED), hospital admission, discharge, and discharge to home. Multilevel mixed-effects logistic regression models were developed to assess sub-county geographic variance, probabilities of survival, and prehospital risk factors. Getis-Ord Gi statistic and Moran's I-test was applied to assess spatial clustering in outcome survival rates. Results: Of the 1562 OHCA cases extracted from EMS records, 1,335 (85.5%) were included with 372 transported to study site. Predicted probability of survival to ED was 57.0% (95CI: 51.3-62.3%). Of transported cases to study site ED, predicted probabilities of survival was to 41.7% (95CI: 36.1-47.6%) for hospital admission, 16.1% (95CI: 10.7-23.5%) for hospital discharge, and 7.1% (95CI: 3.7-13.3%) for home discharge. Census tracts accounted for significant variability in survival to ED (p < 0.001), discharge (p = 0.031), and home discharge outcomes (p = 0.036). There was no significant geographic variation in survival to admission outcome. Neighborhood-level factors significantly improved model fit for survival to ED, discharge, and discharge home outcomes. Multiple modifiable patient- and neighborhood-level variables of interest were identified, including rural-urban differences. Conclusion: We identified important geographic disparities that exist in OHCA outcomes at the community level. By using a replicable schematic, this variation can be explained through community-oriented modifiable socioeconomic and prehospital factors.

Public perception towards bystander cardiopulmonary resuscitation.

OBJECTIVE: Bystander cardiopulmonary resuscitation (CPR) after out-of-hospital cardiac arrest (OHCA) improves survival and neurological outcomes. Nonetheless, many OHCA patients do not receive bystander CPR during a witnessed arrest. Our aim was to identify potential barriers to bystander CPR. METHODS: Participants at CPR training events conducted in the USA between February and May 2018 answered a 14-question survey prior to training. Respondents were asked about their overall comfort level performing CPR, and about potential concerns specific to performing CPR on a middle-aged female, a geriatric male, and male and female adolescent patients. Open-ended responses were analysed qualitatively by categorising responses into themes. RESULTS: Of the 677 participants, 582 (86.0%) completed the survey, with 509 (88.1%) between 18 and 29 years of age, 341 (58.6%) without prior CPR training and 556 (96.0%) without prior CPR experience. Across all four scenarios of patients in cardiac arrest, less than 65% of respondents reported that they would be 'Extremely Likely' (20.6%-29.1%) or 'Moderately Likely' (26.9%-34.8%) to initiate CPR. The leading concerns were 'causing injury to patient' for geriatric (n=193, 63.1%), female (n=51, 20.5%) and adolescent (n=148, 50.9%) patients. Lack of appropriate skills was the second leading concern when the victim was a geriatric (n=41, 13.4%) or adolescent (n=68, 23.4%) patient, whereas for female patients, 35 (14.1%) were concerned about exposing the patient or the patient's breasts interfering with performance of CPR and 15 (6.0%) were concerned about being accused of sexual assault. Significant differences were observed in race, ethnicity and age regarding the likelihood of starting to perform CPR on female and adolescent patients. CONCLUSIONS: Participants at CPR training events have multiple concerns and fears related to performing bystander CPR. Causing additional harm and lack of skills were among the leading reservations reported. These findings should be considered for improved CPR training and public education.

A novel approach to maintain gut mucosal integrity using an oral enzyme supplement.

OBJECTIVE: To determine the role of intestinal alkaline phosphatase (IAP) in enteral starvation-induced gut barrier dysfunction and to study its therapeutic effect as a supplement to prevent gut-derived sepsis. BACKGROUND: Critically ill patients are at increased risk for systemic sepsis and, in some cases, multiorgan failure leading to death. Years ago, the gut was identified as a major source for this systemic sepsis syndrome. Previously, we have shown that IAP detoxifies bacterial toxins, prevents endotoxemia, and preserves intestinal microbiotal homeostasis. METHODS: WT and IAP-KO mice were used to examine gut barrier function and tight junction protein levels during 48-hour starvation and fed states. Human ileal fluid samples were collected from 20 patients postileostomy and IAP levels were compared between fasted and fed states. To study the effect of IAP supplementation on starvation-induced gut barrier dysfunction, WT mice were fasted for 48 hours +/- IAP supplementation in the drinking water. RESULTS: The loss of IAP expression is associated with decreased expression of intestinal junctional proteins and impaired barrier function. For the first time, we demonstrate that IAP expression is also decreased in humans who are deprived of enteral feeding. Finally, our data demonstrate that IAP supplementation reverses the gut barrier dysfunction and tight junction protein losses due to a lack of enteral feeding. CONCLUSIONS: IAP is a major regulator of gut mucosal permeability and is able to ameliorate starvation-induced gut barrier dysfunction. Enteral IAP supplementation may represent a novel approach to maintain bowel integrity in critically ill patients.

Cardiac arrest: An interdisciplinary scoping review of clinical literature from 2020.

Objectives: The Interdisciplinary Cardiac Arrest Research Review (ICARE) group was formed in 2018 to conduct an annual search of peer-reviewed literature relevant to cardiac arrest. Now in its third year, the goals of the review are to highlight annual updates in the interdisciplinary world of clinical cardiac arrest research with a focus on clinically relevant and impactful clinical and population-level studies from 2020. Methods: A search of PubMed using keywords related to clinical research in cardiac arrest was conducted. Titles and abstracts were screened for relevance and sorted into 7 categories: Epidemiology & Public Health Initiatives; Prehospital Resuscitation, Technology & Care; In-Hospital Resuscitation & Post-Arrest Care; Prognostication & Outcomes; Pediatrics; Interdisciplinary Guidelines & Reviews; and a new section dedicated to the coronavirus disease 2019 (COVID-19) pandemic. Screened manuscripts underwent standardized scoring of methodological quality and impact on the respective fields by reviewer teams lead by a subject matter expert editor. Articles scoring higher than 99 percentiles by category were selected for full critique. Systematic differences between editors' and reviewers' scores were assessed using Wilcoxon signed-rank test. Results: A total of 3594 articles were identified on initial search; of these, 1026 were scored after screening for relevance and deduplication, and 51 underwent full critique. The leading category was Prehospital Resuscitation, Technology & Care representing 35% (18/51) of fully reviewed articles. Four COVID-19 related articles were included for formal review that was attributed to a relative lack of high-quality data concerning cardiac arrest and COVID-19 specifically by the end of the 2020 calendar year. No significant differences between editor and reviewer scoring were found among review articles (P = 0.697). Among original research articles, section editors scored a median 1 point (interquartile range, 0-3; P < 0.01) less than reviewers. Conclusions: Several clinically relevant studies have added to the evidence base for the management of cardiac arrest patients including methods for prognostication of neurologic outcome following arrest, airway management strategy, timing of coronary intervention, and methods to improve expeditious performance of key components of resuscitation such as chest compressions in adults and children.

Cardiac arrest: An interdisciplinary review of the literature from 2018.

OBJECTIVES: The Interdisciplinary Cardiac Arrest Research Review (ICARE) group was formed in 2018 to conduct a systematic annual search of peer-reviewed literature relevant to cardiac arrest (CA). The goals of the review are to illustrate best practices and help reduce knowledge silos by disseminating clinically relevant advances in the field of CA across disciplines. METHODS: An electronic search of PubMed using keywords related to CA was conducted. Title and abstracts retrieved by these searches were screened for relevancy, separated by article type (original research or review), and sorted into 7 categories. Screened manuscripts underwent standardized scoring of overall methodological quality and importance. Articles scoring higher than 99 percentiles by category-type were selected for full critique. Systematic differences between editors and reviewer scores were assessed using Wilcoxon signed-rank test. RESULTS: A total of 9119 articles were identified on initial search; of these, 1214 were scored after screening for relevance and deduplication, and 80 underwent full critique. Prognostication & Outcomes category comprised 25% and Epidemiology & Public Health 17.5% of fully reviewed articles. There were no differences between editor and reviewer scoring. CONCLUSIONS: The total number of articles demonstrates the need for an accessible source summarizing high-quality research findings to serve as a high-yield reference for clinicians and scientists seeking to absorb the ever-growing body of CA-related literature. This may promote further development of the unique and interdisciplinary field of CA medicine.

Cardiac arrest: An interdisciplinary scoping review of the literature from 2019.

OBJECTIVES: The Interdisciplinary Cardiac Arrest Research Review (ICARE) group was formed in 2018 to conduct a systematic annual search of peer-reviewed literature relevant to cardiac arrest. Now in its second year, the goals of the review are to illustrate best practices in research and help reduce compartmentalization of knowledge by disseminating clinically relevant advances in the field of cardiac arrest across disciplines. METHODS: An electronic search of PubMed using keywords related to cardiac arrest was conducted. Title and abstracts retrieved by these searches were screened for relevance, classified by article type (original research or review), and sorted into 7 categories. Screened manuscripts underwent standardized scoring of overall methodological quality and impact on the categorized fields of study by reviewer teams lead by a subject-matter expert editor. Articles scoring higher than 99 percentiles by category-type were selected for full critique. Systematic differences between editors' and reviewers' scores were assessed using Wilcoxon signed-rank test. RESULTS: A total of 3348 articles were identified on initial search; of these, 1364 were scored after screening for relevance and deduplication, and forty-five underwent full critique. Epidemiology & Public Health represented 24% of fully reviewed articles with Prehospital Resuscitation, Technology & Care, and In-Hospital Resuscitation & Post-Arrest Care Categories both representing 20% of fully reviewed articles. There were no significant differences between editor and reviewer scoring. CONCLUSIONS: The sheer number of articles screened is a testament to the need for an accessible source calling attention to high-quality and impactful research and serving as a high-yield reference for clinicians and scientists seeking to follow the ever-growing body of cardiac arrest-related literature. This will promote further development of the unique and interdisciplinary field of cardiac arrest medicine.

Patterns of emergency department utilization for LVAD patients compared with non-LVAD patients.

BACKGROUND: Left ventricular assist device (LVAD) patients are vulnerable to over-utilization of resources. METHODS AND RESULTS: We explored the pattern of emergency department (ED) presentations of LVAD patients and their costs compared with non-LVAD heart failure patients. ED visits between 7/2008 and 7/2017 were reviewed to identify 145 LVAD patients, and 435 patients with known heart failure were selected using propensity score matching for age and sex. ED evaluation metrics, hospitalization cost, and length of stay (LOS) were analyzed. Although the most common ED presentations and their frequency differed between groups, few were LVAD specific. LVAD patients were more likely to have taken personal vehicles or be flown to the ED. They had similar times to triage, rooming, and physician evaluation compared with non-LVAD patients. However, LVAD patients were noted to have a shorter time from physician assessment to disposition (109.8 min vs. 177.0 min, p < 0.001) and, overall, LVAD patients had shorter ED LOS (6.33 vs. 9.82 hrs, p = 0.0001). For patients admitted, no significant difference was found between groups in hospital LOS (6.67 vs 6.58 days, p = 0.928) or total cost ($28,766 vs $21,524, p = 0.087). CONCLUSION: Shorter disposition times without increases in LOS or costs may identify a created healthcare disparity among LVAD patients.

MicroRNAs as potential prognosticators of neurological outcome in out-of-hospital cardiac arrest patients.

Out-of-hospital cardiac arrest survival rates have increased due to advancement in resuscitative measures, yet approximately 90% of survivors ultimately die or have severe neurologic dysfunction caused by ischemic injury. Currently, there are few early prognostic indicators of which patients have possibility of meaningful recovery. This leads to uncertainty for families and clinicians, as well as aggressive, invasive and expensive treatments despite medical futility. Several biomarkers investigated in traumatic brain injury have shown prognostication potential in ischemic brain injury. miRNAs, small noncoding RNAs responsible for gene regulation, have been studied in cardiovascular diseases, and have shown prognostication potential due to tissue specificity and stability in circulation. This review discusses available evidence on miRNAs prognosticating neurological outcomes after out-of-hospital cardiac arrest.

Inhibition of the gut enzyme intestinal alkaline phosphatase may explain how aspartame promotes glucose intolerance and obesity in mice.

Diet soda consumption has not been associated with tangible weight loss. Aspartame (ASP) commonly substitutes sugar and one of its breakdown products is phenylalanine (PHE), a known inhibitor of intestinal alkaline phosphatase (IAP), a gut enzyme shown to prevent metabolic syndrome in mice. We hypothesized that ASP consumption might contribute to the development of metabolic syndrome based on PHE's inhibition of endogenous IAP. The design of the study was such that for the in vitro model, IAP was added to diet and regular soda, and IAP activity was measured. For the acute model, a closed bowel loop was created in mice. ASP or water was instilled into it and IAP activity was measured. For the chronic model, mice were fed chow or high-fat diet (HFD) with/without ASP in the drinking water for 18 weeks. The results were that for the in vitro study, IAP activity was lower (p < 0.05) in solutions containing ASP compared with controls. For the acute model, endogenous IAP activity was reduced by 50% in the ASP group compared with controls (0.2 ± 0.03 vs 0.4 ± 0.24) (p = 0.02). For the chronic model, mice in the HFD + ASP group gained more weight compared with the HFD + water group (48.1 ± 1.6 vs 42.4 ± 3.1, p = 0.0001). Significant difference in glucose intolerance between the HFD ± ASP groups (53 913 ± 4000.58 (mg·min)/dL vs 42 003.75 ± 5331.61 (mg·min)/dL, respectively, p = 0.02). Fasting glucose and serum tumor necrosis factor-alpha levels were significantly higher in the HFD + ASP group (1.23- and 0.87-fold increases, respectively, p = 0.006 and p = 0.01). In conclusion, endogenous IAP's protective effects in regard to the metabolic syndrome may be inhibited by PHE, a metabolite of ASP, perhaps explaining the lack of expected weight loss and metabolic improvements associated with diet drinks.

Intestinal Alkaline Phosphatase Regulates Tight Junction Protein Levels.

BACKGROUND: Intestinal alkaline phosphatase (IAP) plays a pivotal role in maintaining gut health and well-being. Oral supplementation with IAP in mice improves gut barrier function and prevents luminal proinflammatory factors from gaining access to the circulation. In this study, we sought to explore the relationship between IAP and tight junction protein (TJP) expression and function. STUDY DESIGN: The effect of IAP deletion on TJP levels was studied in mouse embryonic fibroblasts (MEFs) generated from IAP-knockout and wild type mice. Regulation of TJPs by IAP was assayed in the human colon cancer Caco-2 and T84 cells by overexpressing the human IAP gene. Tight junction protein levels and localization were measured by using RT q-PCR and antibodies targeting the specific TJPs. Finally, the effect of IAP on inflammation-induced intestinal permeability was measured by in vitro trans-well epithelial electrical resistance (TEER). RESULTS: Intestinal alkaline phosphatase gene deletion in MEFs resulted in significantly lower levels of ZO-1, ZO-2, and Occludin compared with levels in wild-type control cells; IAP overexpression in Caco-2 and T84 cells resulted in approximate 2-fold increases in the mRNA levels of ZO-1 and ZO-2. The IAP treatment ameliorated lipopolysaccharide-induced increased permeability in the Caco-2 trans-well system. Furthermore, IAP treatment preserved the localization of the ZO-1 and Occludin proteins during inflammation and was also associated with improved epithelial barrier function. CONCLUSIONS: Intestinal alkaline phosphatase is a major regulator of gut mucosal permeability and appears to work at least partly through improving TJP levels and localization. These data provide a strong foundation to develop IAP as a novel therapy to maintain gut barrier function.