Preclinical Large Animal In-Vivo Experiments for Surgically Implanted Atrioventricular Valve: Reappraisal and Systematic Review.

BACKGROUND: The development of atrioventricular bioprosthesis has witnessed an increasing drive toward clinical translation over the last few decades. A significant challenge in the clinical translation of an atrioventricular bioprosthesis from bench to bedside is the appropriate choice of a large animal model to test the safety and effectiveness of the device. METHODS: We conducted a systematic review of pre-clinical in vivo studies that would enable us to synthesize a recommended framework. PRISMA (Preferred Reporting Items for Systematic Reviews and MetaAnalyses) guidelines were followed to identify and extract relevant articles. RESULTS: Sheep was the most common choice of animal, with nine out of the 12 included studies being conducted on sheep. There were acute and chronic studies based on our search criteria. An average of ~20 and 5 animals were used for chronic and acute studies. One out of three acute studies and eight out of nine chronic studies were on stented heart valve bioprosthesis. All analyses were conducted on the implantation of atrioventricular valves with trileaflet, except for one chronic study on unileaflet valves and one chronic and acute study on bileaflet valves. CONCLUSION: Understanding the variance in past pre-clinical study designs may increase the appropriate utilization of large animal models. This synthesized evidence provides a pre-clinical in vivo studies framework for future research on an atrioventricular bioprosthesis.

Development of a Standardized Assessment of Simulation-based Extracorporeal Membrane Oxygenation Educational Courses.

Background: In 2020, the Extracorporeal Life Support Organization education task force identified seven extracorporeal membrane oxygenation (ECMO) educational domains that would benefit from international collaborative efforts. These included research efforts to delineate the impact and outcomes of ECMO courses. Objective: Development of a standardized online assessment tool to evaluate the effectiveness of didactic and simulation-based ECMO courses on participants' confidence, knowledge, and simulation-based skills; participant satisfaction; and course educational benefits. Methods: We performed a prospective multicenter observational study of five different U.S. academic institution-based adult ECMO courses that met Extracorporeal Life Support Organization endorsement requirements for course structure, educational content, and objectives. Standardized online forms were developed and administered before and after courses, assessing demographics, self-assessment regarding ECMO management, and knowledge examination (15 simple-recall multiple-choice questions). Psychomotor skill assessment was performed during the course (time to complete prespecified critical actions during simulation scenarios). Self-assessment evaluated cognitive, behavioral, and technical aspects of ECMO; course satisfaction; and educational benefits. Results: Out of 211 participants, 107 completed both pre- and postcourse self-assessment forms (97 completed both pre- and postcourse knowledge forms). Fifty-three percent of respondents were physician intensivists, with most (51%) practicing at academic hospitals and with less than 1 year of ECMO experience (50%). After the course, participants reported significant increases in confidence across all domains (cognitive, technical, and behavioral, P < 0.0001, 95% confidence interval [CI], 1.2-1.5; P < 0.0001, 95% CI, 2.2-2.6; and P = 0.002, 95% CI, 1.7-2.1, respectively) with an increase in knowledge scores (P < 0.001; 95% CI, 1.4-2.5). These findings were most significant in participants with less ECMO experience. There were also significant reductions in times to critical actions in three of the four scored simulation scenarios. The results demonstrated participants' satisfaction with most course aspects, with more than 95% expressing that courses met their educational goals. Conclusion: We developed and tested a structured ECMO course assessment tool, demonstrating participants' self-reported benefit as well as improvement in psychomotor skill acquisition, course satisfaction, and educational benefits. Course evaluation is feasible and potentially provides important information to improve ECMO courses. Future steps could include national implementation, addition of questions targeting clinical decision making to further assess knowledge gain, and multilanguage translation for implementation in international courses.

Predictors and outcomes of high-flow nasal cannula failure following extubation: A multicentre observational study

INTRODUCTION@#Despite adhering to criteria for extubation, up to 20% of intensive care patients require re-intubation, even with use of post-extubation high-flow nasal cannula (HFNC). This study aims to identify independent predictors and outcomes of extubation failure in patients who failed post-extubation HFNC.@*METHODS@#We conducted a multicentre observational study involving 9 adult intensive care units (ICUs) across 5 public hospitals in Singapore. We included patients extubated to HFNC following spontaneous breathing trials. We compared patients who were successfully weaned off HFNC with those who failed HFNC (defined as re-intubation ≤7 days following extubation). Generalised additive logistic regression analysis was used to identify independent risk factors for failed HFNC.@*RESULTS@#Among 244 patients (mean age: 63.92±15.51 years, 65.2% male, median APACHE II score 23.55±7.35), 41 (16.8%) failed HFNC; hypoxia, hypercapnia and excessive secretions were primary reasons. Stroke was an independent predictor of HFNC failure (odds ratio 2.48, 95% confidence interval 1.83-3.37). Failed HFNC, as compared to successful HFNC, was associated with increased median ICU length of stay (14 versus 7 days, @*CONCLUSION@#Post-extubation HFNC failure, especially in patients with stroke as a comorbidity, remains a clinical challenge and predicts poorer clinical outcomes. Our observational study highlights the need for future prospective trials to better identify patients at high risk of post-extubation HFNC failure.

Severe COVID-19 and coagulopathy: A systematic review and meta-analysis

INTRODUCTION@#Coronavirus disease 2019 (COVID-19)-induced coagulopathy (CIC) has been widely reported in the literature. However, the spectrum of abnormalities associated with CIC has been highly variable.@*METHODS@#We conducted a systematic review of the literature (until 1 June 2020) to assess CIC and disease severity during the early COVID-19 pandemic. Primary outcomes were pooled mean differences in platelet count, D-dimer level, prothrombin time, activated partial thromboplastin time (aPTT) and fibrinogen level between non-severe and severe patients, stratified by degree of hypoxaemia or those who died. The risk factors for CIC were analysed. Random-effects meta-analyses and meta-regression were performed using R version 3.6.1, and certainty of evidence was rated using the Grading of Recommendation, Assessment, Development, and Evaluation approach.@*RESULTS@#Of the included 5,243 adult COVID-19 patients, patients with severe COVID-19 had a significantly lower platelet count, and higher D-dimer level, prothrombin time and fibrinogen level than non-severe patients. Pooled mean differences in platelet count (-19.7×109/L, 95% confidence interval [CI] -31.7 to -7.6), D-dimer level (0.8μg/mL, 95% CI 0.5-1.1), prothrombin time (0.4 second, 95% CI 0.2-0.6) and fibrinogen level (0.6g/L, 95% CI 0.3-0.8) were significant between the groups. Platelet count and D-dimer level were significant predictors of disease severity on meta-regression analysis. Older men had higher risks of severe coagulopathic disease.@*CONCLUSION@#Significant variability in CIC exists between non-severe and severe patients, with platelet count and D-dimer level correlating with disease severity. Routine monitoring of all coagulation parameters may help to assess CIC and decide on the appropriate management.

Prone positioning of non-intubated patients with COVID-19 - A Systematic Review and Meta-analysis

PurposeSeveral studies have reported adopting prone positioning (PP) in non-intubated patients with COVID-19-related hypoxaemic respiratory failure. This systematic review and meta-analysis evaluated the impact of PP on oxygenation and clinical outcomes. MethodsWe searched PubMed, Embase and COVID-19 living systematic review from December1st 2019 to July23rd 2020. We included studies that reported using PP in hypoxaemic, non-intubated adult COVID-19 patients. Primary outcome measure was the weighted mean difference (MD) in oxygenation parameters (PaO2/FiO2, PaO2 or SpO2) pre and post-PP. ResultsFifteen single arm observational studies reporting PP in 449 patients were included. Substantial heterogeneity was noted in terms of, location within hospital where PP was instituted, respiratory supports, frequency and duration of PP. Significant improvement in oxygenation was reported post-PP: PaO2/FiO2, (MD 37.6, 95%CI 18.8, 56.5); PaO2, (MD 30.4 mmHg, 95%CI 10.9, 49.9); and SpO2, (MD 5.8%, 95%CI 3.7, 7.9). Patients with a pre-PP PaO2/FiO2 [≤]150 experienced greater oxygenation improvements compared with those with a pre-PP PaO2/FiO2 >150 (MD 40.5, 95%CI -3.5, 84.6) vs. 37, 95%CI 17.1, 56.9). Respiratory rate decreased post-PP (MD -2.9, 95%CI -5.4, -0.4). Overall intubation and mortality rates were 21% (90/426) and 26% (101/390) respectively. No major adverse events were reported. ConclusionsDespite significant variability in frequency and duration of PP and respiratory supports, PP was associated with improvements in oxygenation parameters without any reported serious adverse events. Major limitation being lack of control arm and adjustment for confounders. Clinical trials are required to determine the effect of awake PP on patient-centred outcomes. Systematic review registrationRegistration/protocol in PROSPERO (CRD42020194080). What is the key question?Is the novel approach of prone positioning in non-intubated patients associated with improvement in oxygenation? What is the bottom line?Prone position in non-intubated severe COIVD 19 suffers is associated with improvement of oxygenation while the short- and long-term patient centred out comes in this awake prone patient need more investigation. Why read on?Our study is first of its kind (Systematic review and Meta-analysis) summarising the evidence surrounding the less invasive innovate technique of prone position in non-intubated COVID-19 patients.

Development and validation of a tool to appraise guidelines on SARS-CoV-2 infection prevention strategies in healthcare workers

BackgroundClinical guidelines on infection prevention strategies in healthcare workers (HCWs) play an important role in protecting them during the SARS-CoV-2 pandemic. Poorly constructed guidelines that are not comprehensive and are ambiguous may compromise HCWs safety. We aimed to develop and validate a tool to appraise guidelines on infection prevention strategies in HCWs. MethodsA 3-stage, web-based, Delphi consensus-building process among a panel of diverse HCWs and healthcare managers was utilised. We validated the tool by appraising 40 international, specialty-specific and procedure-specific guidelines along with national guidelines from countries with a wide range of gross national income. ResultsOverall consensus ([≥]75%) was reached at the end of three rounds for all six domains included in the tool. The chosen domains allowed appraisal of guidelines in relation to general characteristics (domain-1), recommendations on engineering (domain-2) and administrative aspects (domain 4-6) of infection prevention, as well as personal protection equipment (PPE) use (domain-3). The appraisal tool performed well across all domains and inter-rater agreement was excellent. All included guidelines performed relatively better in domains 1-3 compared with domains 4-6 and this was more evident in guidelines originating from lower income countries. ConclusionThe guideline appraisal tool was robust and easy to use. Recommendations on engineering aspects of infection prevention, administrative measures that promote optimal PPE use and HCW wellbeing were generally lacking in assessed guidelines. This tool may enable health systems to adopt high quality HCW infection prevention guidelines during SARS-CoV-2 pandemic and may also provide a framework for future guideline development. FundingNo funding received. Key SummaryWe developed and validated a guideline-appraisal tool by appraising 40 different guidelines from countries with varying GNI. This tool may help healthcare systems to adopt high-quality HCW infection-prevention guidelines during COVID-19 pandemic and may also provide a guideline development framework.

Variations in Personal Protective Equipment Preparedness in Intensive Care Units during the COVID-19 Pandemic: A Survey of Asia-Pacific Countries

ObjectivesTo evaluate PPE-preparedness across intensive care units (ICUs) in 6 Asia-Pacific countries. PPE-preparedness was defined as the adherence to guidelines, training HCWs, procuring PPE stocks and responding appropriately to a suspected case (transportation and admission to hospital). DesignCross-sectional web-based survey. SettingICUs in Australia, New Zealand (NZ), Singapore, Hong Kong (HK), India and Philippines with a 24/7 Emergency/Casualty Department, and capable of mechanically ventilating patients for >24 hours. InterventionsQuestionnaire sent to intensivists in 633 Level ll/lll ICUs in 6 Asia-Pacific countries by email, WhatsApp and text messaging. Main outcome measures263 intensivists responded, of whom 231 were eligible for analysis. Response rates were 68%-100% in all countries except India, where it was 24%. 97% either conformed to or exceeded WHO recommendations for PPE-practice. 59% employed airborne precautions irrespective of aerosol-generation-procedures. There were variations in negative-pressure room use (highest in HK/Singapore), training (best in NZ), and PPE stock-awareness (best in HK/Singapore/NZ). High-flow-nasal-oxygenation and non-invasive ventilation were not options in most HK (66.7%, 83.3% respectively) and Singapore ICUs (50%, 80% respectively), but were considered in other countries to a greater extent. 38% reported not having specialized airway teams. Showering and "buddy-systems" were underutilized. Clinical waste disposal training was suboptimal (38%). ConclusionsMost intensivists from six Asia-Pacific countries appeared to be aware of the WHO PPE-guidelines by either conforming to/exceeding the recommendations. Despite this, there were widespread variabilities across ICUs and countries in several domains, particularly related to PPE-training and preparedness. Standardising PPE guidelines may translate to better training, better compliance and policies that improve HCW safety. Adopting low-cost approaches such as buddy-systems should be encouraged. More importantly, better pandemic preparedness and building systems with deeply embedded culture of safety is essential to ensure the safety and well-being of HCWs during such pandemics. Author Contributorship O_TBL View this table: org.highwire.dtl.DTLVardef@1f291aorg.highwire.dtl.DTLVardef@1c388ccorg.highwire.dtl.DTLVardef@4a1a65org.highwire.dtl.DTLVardef@10af39aorg.highwire.dtl.DTLVardef@1ff1eaa_HPS_FORMAT_FIGEXP M_TBL C_TBL Summary BoxO_ST_ABSWhat is already known on this topicC_ST_ABSO_LIPersonal-protective equipment (PPE) is the cornerstone to preventing HCW- infections. A search was done on March 23, 2020 on PubMed, Embase or Google Scholar using the mesh terms "personal protective equipment", "PPE", "preparedness OR practice OR training". It revealed no previous studies on PPE preparedness in intensive care units (ICUs). No filters were used for the search. C_LIO_LISeveral guidelines/recommendations issued by health organisations on PPE practice exist C_LI What are the new findingsO_LIAs the first study to evaluate PPE-preparedness in ICUs, it demonstrated major concerns on PPE-preparedness across several ICUs, particularly in Australia, India and Philippines. There was suboptimal PPE-training, under-utilisation of low-cost interventions such as buddy-systems/team-training, and stock-awareness. C_LIO_LIThe guidelines by health organisations on PPE practice have several conflicting recommendations. C_LI How might it impact on clinical practice in the foreseeable futureO_LIStandardising PPE guidelines by health organisations may translate to better training, better compliance and policies that improve HCW safety. C_LIO_LITo ensure the safety and well-being of HCWs, urgent measures are needed to improve PPE-preparedness and building systems with deeply embedded culture of safety. By helping ICUs evaluate and improve their current state of PPE preparedness, the study may help prevent healthcare worker infections and save lives. C_LI

Multidisciplinary Extubation Protocol in Cardiac Surgical Patients Reduces Ventilation Time and Length of Stay in the Intensive Care Unit.

BACKGROUND: Protocolized care bundles may improve patient care by reducing medical errors, minimizing practice variability, and reducing mortality. We hypothesized that the introduction of a multidisciplinary extubation protocol would reduce duration of mechanical ventilation and intensive care unit length of stay in a tertiary cardiothoracic intensive care unit. METHODS: A multidisciplinary extubation protocol was created. The protocol was applied to all elective postoperative cardiac surgery patients. Data were collected 3 months before and 3 months after protocol initiation. Patients were excluded if they experienced events that contraindicated application of the protocol. RESULTS: Two hundred one patients undergoing elective open cardiac surgery were included: 99 patients before protocol implementation (preprotocol) and 102 patients after implementation (postprotocol). Median extubation time was reduced by 35% (620 minutes versus 405 minutes; p < 0.001), whereas adjusted extubation time remained significantly reduced by 144 minutes (p < 0.001). Intensive care unit length of stay was reduced from 2 days preprotocol to 1 day postprotocol (p < 0.001). Reintubation rate was the same in both groups (2.06% versus 1.96%; p = 1.0). CONCLUSIONS: A simple multidisciplinary extubation protocol is safe and associated with a significant reduction in the duration of mechanical ventilation and intensive care unit length of stay after elective cardiac surgery.

Delayed presentation of ACE inhibitor-induced angio-oedema.

We report two probable cases of delayed presentation of ACE inhibitor (ACEi)-induced angio-oedema. The first patient was on ACEi for more than 10 years while the second one was on it for 7 years. Both the patients presented with initial unilateral swelling of the tongue which progressed further to involve the soft tissues of the oropharynx, head and neck leading to a compromised airway needing awake fibreoptic intubation and were managed successfully in the intensive care unit (ICU). C1 esterase inhibitor and mast cell tryptase level was normal for both patients. Both were treated with intravenous antihistamines and corticosteroids in the ICU. Both patients were successfully extubated within 72 h and transferred to a medical ward. Age above 65 years, atopy and non-steroidal anti-inflammatory drug use may have been the predisposing factors. Both patients made a full recovery with no complications and the ACEi was ceased.