Carboxymethyl cellulose-alginate interpenetrating hydroxy ethyl methacrylate crosslinked polyvinyl alcohol reinforced hybrid hydrogel templates with improved biological performance for cardiac tissue engineering.

Cardiac tissue engineering is an emerging approach for cardiac regeneration utilizing the inherent healing responses elicited by the surviving heart using biomaterial templates. In this study, we aimed to develop hydrogel scaffolds for cardiac tissue regeneration following myocardial infarction (MI). Two superabsorbent hydrogels, CAHA2A and CAHA2AP, were developed employing interpenetration chemistry. CAHA2A was constituted with alginate, carboxymethyl cellulose, (hydroxyethyl) methacrylate, and acrylic acid, where CAHA2AP was prepared by interpenetrated CAHA2A with polyvinyl alcohol. Both hydrogels displayed superior physiochemical characteristics, as determined by attenuated total reflection infrared spectroscopy spectral analysis, differential scanning calorimetry measurements, tensile testing, contact angle, water profiling, dye release, and conductivity. In vitro degradation of the hydrogels displayed acceptable weight composure and pH changes. Both hydrogels were hemocompatible, and biocompatible as evidenced by direct contact and MTT assays. The hydrogels promoted anterograde and retrograde migration as determined by the z-stack analysis using H9c2 cells grown with both gels. Additionally, the coculture of the hydrogels with swine epicardial adipose tissue cells and cardiac fibroblasts resulted in synchronous growth without any toxicity. Also, both hydrogels facilitated the production of extracellular matrix by the H9c2 cells. Overall, the findings support an appreciable in vitro performance of both hydrogels for cardiac tissue engineering applications.

Bioactive extracellular matrix fragments in tendon repair.

Tendinopathy is a common tendon disorder that causes pain, loss of strength and function, and local inflammation mainly characterized by hypoxia, collagen degradation, and extracellular matrix (ECM) disorganization. Generally, ECM degradation and remodeling is tightly regulated; however, hyperactivation of matrix metalloproteases (MMPs) contributes to excessive collagenolysis under pathologic conditions resulting in tendon ECM degradation. This review article focuses on the production, function, and signaling of matrikines for tendon regeneration following injury with insights into the expression, tissue compliance, and cell proliferation exhibited by various matrikines. Furthermore, the regenerative properties suggest translational significance of matrikines to improve the outcomes post-injury by assisting with tendon healing.

Study of the Effects of Epinephrine on Cerebral Oxygenation and Metabolism During Cardiac Arrest and Resuscitation by Hyperspectral Near-Infrared Spectroscopy.

OBJECTIVES: Epinephrine is routinely administered to sudden cardiac arrest patients during resuscitation, but the neurologic effects on patients treated with epinephrine are not well understood. This study aims to assess the cerebral oxygenation and metabolism during ventricular fibrillation cardiac arrest, cardiopulmonary resuscitation, and epinephrine administration. DESIGN: To investigate the effects of equal dosages of IV epinephrine administrated following sudden cardiac arrest as a continuous infusion or successive boluses during cardiopulmonary resuscitation, we monitored cerebral oxygenation and metabolism using hyperspectral near-infrared spectroscopy. SETTINGS: A randomized laboratory animal study. SUBJECTS: Nine healthy pigs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Our study showed that although continuous epinephrine administration had no significant impact on overall cerebral hemodynamics, epinephrine boluses transiently improved cerebral oxygenation (oxygenated hemoglobin) and metabolism (cytochrome c oxidase) by 15% ± 6.7% and 49% ± 18%, respectively (p < 0.05) compared with the baseline (untreated) ventricular fibrillation. Our results suggest that the effects of epinephrine diminish with successive boluses as the impact of the third bolus on brain oxygen metabolism was 24.6% ± 3.8% less than that of the first two boluses. CONCLUSIONS: Epinephrine administration by bolus resulted in transient improvements in cerebral oxygenation and metabolism, whereas continuous epinephrine infusion did not, compared with placebo. Future studies are needed to evaluate and optimize the use of epinephrine in cardiac arrest resuscitation, particularly the dose, timing, and mode of administration.

Impact of a peer-support programme to improve loneliness and social isolation due to COVID-19: does adding a secure, user friendly video-conference solution work better than telephone support alone? Protocol for a three-arm randomised clinical trial.

INTRODUCTION: The COVID-19 pandemic has forced the implementation of physical distancing and self-isolation strategies worldwide. However, these measures have significant potential to increase social isolation and loneliness. Among older people, loneliness has increased from 40% to 70% during COVID-19. Previous research indicates loneliness is strongly associated with increased mortality. Thus, strategies to mitigate the unintended consequences of social isolation and loneliness are urgently needed. Following the Obesity-Related Behavioural Intervention Trials model for complex behavioural interventions, we describe a protocol for a three-arm randomised clinical trial to reduce social isolation and loneliness. METHODS AND ANALYSIS: A multicentre, outcome assessor blinded, three-arm randomised controlled trial comparing 12 weeks of: (1) the HOspitals WoRking in Unity ('HOW R U?') weekly volunteer-peer support telephone intervention; (2) 'HOW R U?' deliver using a video-conferencing solution and (3) a standard care group. The study will follow Consolidated Standard of Reporting Trials guidelines.We will recruit 24-26 volunteers who will receive a previously tested half day lay-training session that emphasises a strength-based approach and safety procedures. We will recruit 141 participants ≥70 years of age discharged from two participating emergency departments or referred from hospital family medicine, geriatric or geriatric psychiatry clinics. Eligible participants will have probable baseline loneliness (score ≥2 on the de Jong six-item loneliness scale). We will measure change in loneliness, social isolation (Lubben social network scale), mood (Geriatric Depression Score) and quality of life (EQ-5D-5L) at 12-14 weeks postintervention initiation and again at 24-26 weeks. ETHICS AND DISSEMINATION: Approval has been granted by the participating research ethics boards. Participants randomised to standard care will be offered their choice of telephone or video-conferencing interventions after 12 weeks. Results will be disseminated through journal publications, conference presentations, social media and through the International Federation of Emergency Medicine. TRIAL REGISTRATION NUMBER: NCT05228782.

Impact of an intergenerational program to improve loneliness and social isolation in older adults initiated at the time of emergency department discharge: study protocol for a three-arm randomized clinical trial.

BACKGROUND: Social isolation and loneliness (SIL) worsens mortality and other outcomes among older adults as much as smoking. We previously tested the impact of the HOW R U? intervention using peer support from similar-aged volunteers and demonstrated reduced SIL among older adults discharged from the emergency department (ED). Generativity, defined as "the interest in establishing and guiding the next generation," can provide an alternative theoretical basis for reducing SIL via intergenerational programs between members of younger and older generations. The current protocol will examine the impact of younger intergenerational volunteers providing the HOW RU? METHODS: In this randomized clinical trial, we will compare the following three arms: (1) the standard same-generation peer support HOW R U? intervention, (2) HOW R U? intervention delivered by intergenerational volunteers, and (3) a common wait-list control group. Outcome assessors will be blinded to the intervention. Trained volunteers will deliver 12 weekly telephone support calls. We will recruit participants ≥ 70 years of age with baseline loneliness (six-item De Jong loneliness score of 2 or greater) from two EDs. Research staff will assess SIL, depression, quality of life, functional status, generativity, and perceived benefit at baseline, at 12 weeks, and 24 weeks post-intervention. DISCUSSION: We hypothesize participants receiving the intergenerational intervention will show improved outcomes compared to the control group and peer support HOW R U? INTERVENTION: We also hypothesize that participants with higher perceptions of generativity will have greater reductions in SIL than their lower generativity counterparts. Aging is experienced diversely, and social interventions combatting associated SIL should reflect that diversity. As part of a program of research following the Obesity-Related Behavioral Intervention Trials (ORBIT) model, the findings of this RCT will be used to define which intervention characteristics are most effective in reducing SIL. TRIAL REGISTRATION: ClinicalTrials.gov NCT05998343 Protocol ID:21-0074E. Registered on 24 July 2023.

The ability of machine learning algorithms to predict defibrillation success during cardiac arrest: A systematic review.

OBJECTIVE: To evaluate the existing knowledge on the effectiveness of machine learning (ML) algorithms inpredicting defibrillation success during in- and out-of-hospital cardiac arrest. METHODS: MEDLINE, Embase, CINAHL and Scopus were searched from inception to August 30, 2022. Studies were included that utilized ML algorithms for prediction of successful defibrillation, observed as return of spontaneous circulation (ROSC), survival to hospital or discharge, or neurological status at discharge.Studies were excluded if involving a trauma, an unknown underlying rhythm, an implanted cardiac defibrillator or if focused on the prediction or onset of cardiac arrest. Risk of bias was assessed using the PROBAST tool. RESULTS: There were 2399 studies identified, of which 107 full text articles were reviewed and 15 observational studies (n = 5680) were included for final analysis. 29 ECG waveform features were fed into 15 different ML combinations. The best performing ML model had an accuracy of 98.6 (98.5 - 98.7)%, with 4 second ECG intervals. An algorithm incorporating end-tidal CO2 reported an accuracy of 83.3% (no CI reported). Meta-analysis was not performed due to heterogeneity in study design, ROSC definitions, and characteristics. CONCLUSION: Machine learning algorithms, specifically Neural Networks, have been shown to have potential to predict defibrillation success for cardiac arrest with high sensitivity and specificity.Due to heterogeneity, inconsistent reporting, and high risk of bias, it is difficult to conclude which, if any, algorithm is optimal. Further clinical studies with standardized reporting of patient characteristics, outcomes, and appropriate algorithm validation are still required to elucidate this. PROSPERO 2020 CRD42020148912.

Going home positive: a qualitative study of the experiences of care for patients with COVID-19 who are not hospitalized.

BACKGROUND: Most Canadians diagnosed with COVID-19 have had mild symptoms not requiring hospitalization. We sought to understand the patient experience of care while being isolated at home after testing positive for SARS-CoV-2 infection. METHODS: We conducted a phenomenologically informed qualitative descriptive study using in-depth semistructured interviews to identify common themes of experience for patients sent home from hospital with a positive COVID-19 diagnosis. Between July and December 2020, we conducted interviews with patients who were followed by the North York General Hospital COVID Follow-Up Clinic. Patients with mild to moderate symptoms were interviewed 4 weeks after their COVID-19 diagnosis. We conducted the interviews and performed a thematic analysis of the data concurrently, in keeping with the iterative process of qualitative methodology. RESULTS: We conducted interviews with 26 patients. From our analysis, 3 themes were developed regarding participants' overall experience: lack of adequate communication, inconsistency of information from various sources, and the social implications of a COVID-19 diagnosis. The implications of a positive test for SARS-CoV-2 infection are substantial, even when symptoms are mild and patients self-isolate as recommended. Participants noted communication challenges and inconsistent information, leading to exacerbated stress. INTERPRETATION: Participants shared their experiences of the stigma of testing positive and the frustration of poor communication structures and inconsistent information. Experiencing care during self-isolation at home is an area of increasing importance, and these findings can inform improved support, ensuring access to equitable and safe COVID-19 care for these patients.

First-line Medications for the Outpatient Treatment of Alcohol Use Disorder: A Systematic Review of Perceived Barriers.

OBJECTIVES: Alcohol use disorder (AUD) is a common illness with significant health and economic consequences. Although three pharmacotherapeutic agents have been shown to decrease heavy drinking days among individuals with AUD, they are vastly underutilized in clinical practice. The objective of this review was to elucidate barriers that may prevent patients from obtaining medication for addiction treatment (MAT) for AUD in an outpatient or residential setting. METHODS: Electronic searches of Medline and EMBASE were conducted, and reference lists were hand-searched. All study designs which discussed the use of MAT for AUD in an outpatient or residential setting were eligible for inclusion. Two reviewers independently screened the search output to identify potentially eligible articles, the full texts of which were retrieved and assessed for inclusion. RESULTS: After eliminating duplicate citations and articles that did not meet eligibility criteria, 23 articles were included in the review. Perceived barriers to obtaining pharmacotherapy for the treatment of AUD in an outpatient or residential setting were grouped into 3 themes: lack of knowledge and concerns about efficacy and complexity of prescribing; treatment philosophy and stigma; medication accessibility including formulary restrictions, geographical and socioeconomic barriers. CONCLUSIONS: Although evidence-based pharmacotherapeutics have been approved for the treatment of AUD, our findings suggest patients continue to experience barriers to the use of these medications. Efforts should be made to increase rates of prescribing by providers and the use of medications by patients. More research is needed to further elucidate perceived barriers to MAT use, along with strategies to overcome them.

Towards quality assurance: implementation of a POCUS image archiving system in a high-volume community emergency department.

BACKGROUND: Quality assurance review is an integral part of point-of-care ultrasound (POCUS) programs but may not be routine practice in community hospitals. Lack of image acquisition and documentation can result in suboptimal patient care. In cases with an adverse outcome and no record of images, there is no mechanism for quality improvement. OBJECTIVES: Our goal was to implement a system of POCUS image archiving in a community hospital. Our SMART (Specific, Measurable, Actionable, Realistic, Timely) aim was to have > 50% of emergency department (ED) POCUS users archiving scans, and > 80% of all billed POCUS scans archived, measuring improvements bi-weekly over a period of 9 months. METHODS: The study was conducted at a single-community ED between August 2020 and April 2021. The POCUS archiving workflow was developed and refined through multiple plan-do-study-act (PDSA) cycles. Surveys, stakeholder meetings, audits, and feedback were used to generate and re-evaluate the interventions. These included introduction of QPathE© software, streamlining of the workflow process, strategic machine placement, POCUS rounds, use of a website for POCUS workflow instructions, and dissemination of audit results. Scans were tracked biweekly, and indexed by the number of scans billed. The primary outcome measure was the number of POCUS scans archived per 100 scans billed. RESULTS: Over a 9-month period, spanning 72,986 ED visits, 550 scans were archived. The percentage of POCUS users who changed practice to consistently archiving scans was 51%. The rate of POCUS scans archived per 100 scans billed was > 80%, compared to no archiving at baseline. CONCLUSION: We were able to transition from a system with entirely unarchived POCUS scanning, to one with > 80% of scans archived over a period of 9 months. This is the first published paper documenting implementation of a POCUS image archiving system in a Canadian Community ED.

RéSUMé: CONTEXTE: L'examen de l'assurance qualité fait partie intégrante des programmes d'échographie au point d'intervention (POCUS), peut ne pas être une pratique courante dans les hôpitaux communautaires. L'absence d'acquisition et de documentation d'images peut entraîner des soins sous-optimaux pour le patient. Dans les cas où l'issue est défavorable et où il n'y a pas d'enregistrement des images, il n'existe aucun mécanisme d'amélioration de la qualité. OBJECTIFS: Notre objectif était de mettre en place un système d'archivage des images POCUS dans un hôpital communautaire. Notre objectif SMART (Specific, Measurable, Actionable, Realistic, Timely) était de faire en sorte que > 50% des utilisateurs de POCUS aux urgences archivent les scans, et que > 80% de tous les scans POCUS facturés soient archivés, en mesurant les améliorations toutes les deux semaines sur une période de 9 mois. MéTHODES: L'étude a été menée dans une seule urgence communautaire entre août 2020 et avril 2021. Le flux de travail de l'archivage POCUS a été développé et affiné à travers de multiples cycles Planification- Exécution­Étude­Action (PEEA) [en anglais Plan-Do-Study-Act (PDSA)]. Des sondages, des réunions de parties prenantes, des audits et des commentaires ont été utilisés pour générer et réévaluer les interventions. Il s'agit notamment de l'introduction du logiciel QPathE©, de la rationalisation du processus de flux de travail, de l'emplacement stratégique des machines, des tournées POCUS, de l'utilisation d'un site web pour les instructions de flux de travail POCUS et de la diffusion des résultats des audits. Les scans étaient suivis toutes les deux semaines et indexés en fonction du nombre de scans facturés. Le principal critère d'évaluation était le nombre de scans POCUS archivés pour 100 scans facturés. RéSULTATS: Sur une période de 9 mois, couvrant 72 986 visites aux urgences, 550 scanners ont été archivés. Le pourcentage d'utilisateurs de POCUS qui ont changé de pratique pour archiver systématiquement les scans était de 51 %. Le taux de scanners POCUS archivés pour 100 scanners facturés était > 80%, par rapport à l'absence d'archivage au départ. CONCLUSION: Nous avons pu passer d'un système où les scanners POCUS n'étaient pas du tout archivés à un système où plus de 80% des scanners ont été archivés sur une période de 9 mois. Il s'agit du premier article publié sur la mise en œuvre d'un système d'archivage d'images POCUS dans une urgence communautaire canadienne.

Establishing a multicenter, preclinical consortium in resuscitation: A pilot experimental trial evaluating epinephrine in cardiac arrest.

BACKGROUND: Large animal studies are an important step in the translation pathway, but single laboratory experiments do not replicate the variability in patient populations. Our objective was to demonstrate the feasibility of performing a multicenter, preclinical, randomized, double-blinded, placebo-controlled cardiac arrest trial. We evaluated the effect of epinephrine on coronary perfusion pressure (CPP) as previous single laboratory studies have reported mixed results. METHODS: Forty-five swine from 5 different laboratories (Ann Arbor, MI; Baltimore, MD; Los Angeles, CA; Pittsburgh, PA; Toronto, ON) using a standard treatment protocol. Ventricular fibrillation was induced and left untreated for 6 min before starting continuous cardiopulmonary resuscitation (CPR). After 2 min of CPR, 9 animals from each lab were randomized to 1 of 3 interventions given over 12 minutes: (1) Continuous IV epinephrine infusion (0.00375 mg/kg/min) with placebo IV normal saline (NS) boluses every 4 min, (2) Continuous placebo IV NS infusion with IV epinephrine boluses (0.015 mg/kg) every 4 min or (3) Placebo IV NS for both infusion and boluses. The primary outcome was mean CPP during the 12 mins of drug therapy. RESULTS: There were no significant differences in mean CPP between the three groups: 14.4 ± 6.8 mmHg (epinephrine Infusion), 16.9 ± 5.9 mmHg (epinephrine bolus), and 14.4 ± 5.5 mmHg (placebo) (p = NS). Sensitivity analysis demonstrated inter-laboratory variability in the magnitude of the treatment effect (p = 0.004). CONCLUSION: This study demonstrated the feasibility of performing a multicenter, preclinical, randomized, double-blinded cardiac arrest trials. Standard dose epinephrine by bolus or continuous infusion did not increase coronary perfusion pressure during CPR when compared to placebo.

Altered Vascular Extracellular Matrix in the Pathogenesis of Atherosclerosis.

Cardiovascular disease continues to grow as a massive global health burden, with coronary artery disease being one of its most lethal varieties. The pathogenesis of atherosclerosis induces changes in the blood vessel and its extracellular matrix (ECM) in each vascular layer. The alteration of the ECM homeostasis has significant modulatory effects on the inflammatory response, the proliferation and migration of vascular smooth muscle cells, neointimal formation, and vascular fibrosis seen in atherosclerosis. In this literature review, the role of the ECM, the multitude of components, and alterations to these components in the pathogenesis of atherosclerosis are discussed with a focus on versatile cellular phenotypes in the structure of blood vessel. An understanding of the various effects of ECM alterations opens up a plethora of therapeutic options that would mitigate the substantial health toll of atherosclerosis on the global population.

Development of the Canadian COVID-19 Emergency Department Rapid Response Network population-based registry: a methodology study.

BACKGROUND: Emergency physicians lack high-quality evidence for many diagnostic and treatment decisions made for patients with suspected or confirmed coronavirus disease 2019 (COVID-19). Our objective is to describe the methods used to collect and ensure the data quality of a multicentre registry of patients presenting to the emergency department with suspected or confirmed COVID-19. METHODS: This methodology study describes a population-based registry that has been enrolling consecutive patients presenting to the emergency department with suspected or confirmed COVID-19 since Mar. 1, 2020. Most data are collected from retrospective chart review. Phone follow-up with patients at 30 days captures the World Health Organization clinical improvement scale and contextual, social and cultural variables. Phone follow-up also captures patient-reported quality of life using the Veterans Rand 12-Item Health Survey at 30 days, 60 days, 6 months and 12 months. Fifty participating emergency departments from 8 provinces in Canada currently enrol patients into the registry. INTERPRETATION: Data from the registry of the Canadian COVID-19 Emergency Department Rapid Response Network will be used to derive and validate clinical decision rules to inform clinical decision-making, describe the natural history of the disease, evaluate COVID-19 diagnostic tests and establish the real-world effectiveness of treatments and vaccines, including in populations that are excluded or underrepresented in clinical trials. This registry has the potential to generate scientific evidence to inform our pandemic response, and to serve as a model for the rapid implementation of population-based data collection protocols for future public health emergencies. TRIAL REGISTRATION: Clinicaltrials.gov, no. NCT04702945.

The impact of social media promotion with infographics and podcasts on research dissemination and readership.

OBJECTIVE: In 2015 and 2016, the Canadian Journal of Emergency Medicine (CJEM) Social Media (SoMe) Team collaborated with established medical websites to promote CJEM articles using podcasts and infographics while tracking dissemination and readership. METHODS: CJEM publications in the "Original Research" and "State of the Art" sections were selected by the SoMe Team for podcast and infographic promotion based on their perceived interest to emergency physicians. A control group was composed retrospectively of articles from the 2015 and 2016 issues with the highest Altmetric score that received standard Facebook and Twitter promotions. Studies on SoMe topics were excluded. Dissemination was quantified by January 1, 2017 Altmetric scores. Readership was measured by abstract and full-text views over a 3-month period. The number needed to view (NNV) was calculated by dividing abstract views by full-text views. RESULTS: Twenty-nine of 88 articles that met inclusion were included in the podcast (6), infographic (11), and control (12) groups. Descriptive statistics (mean, 95% confidence interval) were calculated for podcast (Altmetric: 61, 42-80; Abstract: 1795, 1135-2455; Full-text: 431, 0-1031), infographic (Altmetric: 31.5, 19-43; Abstract: 590, 361-819; Full-text: 65, 33-98), and control (Altmetric: 12, 8-15; Abstract: 257, 159-354; Full-Text: 73, 38-109) articles. The NNV was 4.2 for podcast, 9.0 for infographic, and 3.5 for control articles. Discussion Limitations included selection bias, the influence of SoMe promotion on the Altmetric scores, and a lack of generalizability to other journals. CONCLUSION: Collaboration with established SoMe websites using podcasts and infographics was associated with increased Altmetric scores and abstract views but not full-text article views.

The effect of an infographic promotion on research dissemination and readership: A randomized controlled trial.

OBJECTIVE: Journals use social media to increase the awareness of their publications. Infographics show research findings in a concise and visually appealing manner, well suited for dissemination on social media platforms. We hypothesized that infographic abstracts promoted on social media would increase the dissemination and online readership of the parent research articles. METHODS: Twenty-four articles were chosen from the six issues of CJEM published between July 2016 and June 2017 and randomized to infographic or control groups. All articles were disseminated through the journal's social media accounts (Twitter and Facebook). Control articles were promoted using a screen capture image of each article's abstract on the journal's social media accounts. Infographic articles were promoted similarly using a visual infographic. Infographics were also published and promoted on the CanadiEM.org's website and social media channels. Abstract views, full-text views, and the change in Altmetric score were compared between groups using unpaired two-tailed t-tests. RESULTS: There were no significant differences in the groups at baseline. Abstract views (mean, 95% CI) were higher in the infographics (379, 287-471) than the control group (176, 136-215, p<0.001). Mean change in Altmetric scores was higher in the infographics (26, 18-34) than in the control group (3, 2-4, p<0.0001). There was no difference in full-text views between the infographics (50, 0-101) and control groups (25, 18-32). CONCLUSION: The promotion of CJEM articles using infographics on social media and the CanadiEM.org website increased Altmetric scores and abstract views. Infographics may have a role in increasing awareness of medical literature.