Evidence-Based Considerations for the Design of an Open-Source Ventilator: A Systematic Review

OBJECTIVE: To inform the design of open-source ventilators, we performed a systematic review of clinical practice guidelines (CPGs) to consolidate the evidence on mechanical ventilation strategies that result in improved patient-important outcomes for acute hypoxic respiratory failure. DATA SOURCES: We developed a search strategy to identify relevant CPGs from Ovid Medline, Ovid Medline In-Process & Other Non-Indexed Citations, Embase, the Cochrane Library, Mendeley, and Google scholar from 2010 to February 17, 2022. STUDY SELECTION: Using a two-step screening process with two independent reviewers, we included CPGs that made recommendations on mechanical ventilation strategies of interest. Guidelines that reported at least one recommendation about mechanical ventilation in ICU patients with acute hypoxic respiratory failure were included. DATA EXTRACTION: From the 13 eligible guidelines, we collected data on country, aim, patient population, impact on morbidity and mortality (effect size and CIs), recommendations, strength of Recommendation (as per Grading of Recommendations, Assessment, Development and Evaluations), and details of supporting evidence base. DATA SYNTHESIS: We identified three ventilation strategies that confer a mortality and morbidity benefit for ventilated patients with acute hypoxic respiratory failure: low-tidal volume ventilation, plateau pressures of less than 30 cm H2O, and higher positive end-expiratory pressure (PEEP). These moderate-to-strong recommendations were based on moderate-to-high certainty in evidence. We identified several other recommendations with no or minimal certainty in evidence. CONCLUSIONS: Our systematic review of international CPGs identified no recommendations favoring specific mode of ventilation and three ventilation strategies that confer mortality and morbidity benefits, backed by moderate-to-strong evidence. Ventilator design teams must include the ability to consistently provide and measure low-tidal volume ventilation, plateau pressures of less than 30 cm H2O, and higher PEEP into their designs. Based on our findings, we provide the first public framework for open-source ventilator design

A Pilot Study Comparing HPV-Positive and HPV-Negative Head and Neck Squamous Cell Carcinomas by Whole Exome Sequencing.

Background. Next-generation sequencing of cancers has identified important therapeutic targets and biomarkers. The goal of this pilot study was to compare the genetic changes in a human papillomavirus- (HPV-)positive and an HPV-negative head and neck tumor. Methods. DNA was extracted from the blood and primary tumor of a patient with an HPV-positive tonsillar cancer and those of a patient with an HPV-negative oral tongue tumor. Exome enrichment was performed using the Agilent SureSelect All Exon Kit, followed by sequencing on the ABI SOLiD platform. Results. Exome sequencing revealed slightly more mutations in the HPV-negative tumor (73) in contrast to the HPV-positive tumor (58). Multiple mutations were noted in zinc finger genes (ZNF3, 10, 229, 470, 543, 616, 664, 638, 716, and 799) and mucin genes (MUC4, 6, 12, and 16). Mutations were noted in MUC12 in both tumors. Conclusions. HPV-positive HNSCC is distinct from HPV-negative disease in terms of evidence of viral infection, p16 status, and frequency of mutations. Next-generation sequencing has the potential to identify novel therapeutic targets and biomarkers in HNSCC

Clinical characteristics, multiorgan dysfunction and outcomes of patients with COVID-19: a prospective case series

BACKGROUND: Characterizing the multiorgan manifestations and outcomes of patients hospitalized with COVID-19 will inform resource requirements to address the long-term burden of this disease. We conducted a descriptive analysis using prospectively collected data to describe the clinical characteristics and spectrum of organ dysfunction, and in-hospital and longer-term clinical outcomes of patients hospitalized with COVID-19 during the first wave of the pandemic at a Canadian centre. METHODS: We conducted a prospective case series involving adult patients (aged ≥ 18 yr) with COVID-19 admitted to 1 of 2 hospitals in London, Ontario, from Mar. 17 to June 18, 2020, during the first wave of the pandemic. We recorded patients\u27 baseline characteristics, physiologic parameters, measures of organ function and therapies administered during hospitalization among patients in the intensive care unit (ICU) and in non-ICU settings, and compared the characteristics of hospital survivors and nonsurvivors. Finally, we recorded follow-up thoracic computed tomography (CT) and echocardiographic findings after hospital discharge. RESULTS: We enrolled 100 consecutive patients (47 women) hospitalized with COVID-19, including 32 patients who received ICU care and 68 who received treatment in non-ICU settings. Respiratory sequelae were common: 23.0% received high-flow oxygen by nasal cannula, 9.0% received noninvasive ventilation, 24.0% received invasive mechanical ventilation and 2.0% received venovenous extracorporeal membrane oxygenation. Overall, 9.0% of patients had cerebrovascular events (3.0% ischemic stroke, 6.0% intracranial hemorrhage), and 6.0% had pulmonary embolism. After discharge, 11 of 19 patients had persistent abnormalities on CT thorax, and 6 of 15 had persistent cardiac dysfunction on echocardiography. INTERPRETATION: This study provides further evidence that COVID-19 is a multisystem disease involving neurologic, cardiac and thrombotic dysfunction, without evidence of hepatic dysfunction. Patients have persistent organ dysfunction after hospital discharge, underscoring the need for research on long-term outcomes of COVID-19 survivors

Doppler identified venous congestion in septic shock:protocol for an international, multi-centre prospective cohort study (Andromeda-VEXUS)

INTRODUCTION: Venous congestion is a pathophysiological state where high venous pressures cause organ oedema and dysfunction. Venous congestion is associated with worse outcomes, particularly acute kidney injury (AKI), for critically ill patients. Venous congestion can be measured by Doppler ultrasound at the bedside through interrogation of the inferior vena cava (IVC), hepatic vein (HV), portal vein (PV) and intrarenal veins (IRV). The objective of this study is to quantify the association between Doppler identified venous congestion and the need for renal replacement therapy (RRT) or death for patients with septic shock. METHODS AND ANALYSIS: This study is a prespecified substudy of the ANDROMEDA-SHOCK 2 (AS-2) randomised control trial (RCT) assessing haemodynamic resuscitation in septic shock and will enrol at least 350 patients across multiple sites. We will include adult patients within 4 hours of fulfilling septic shock definition according to Sepsis-3 consensus conference. Using Doppler ultrasound, physicians will interrogate the IVC, HV, PV and IRV 6-12 hours after randomisation. Study investigators will provide web-based educational sessions to ultrasound operators and adjudicate image acquisition and interpretation. The primary outcome will be RRT or death within 28 days of septic shock. We will assess the hazard of RRT or death as a function of venous congestion using a Cox proportional hazards model. Sub-distribution HRs will describe the hazard of RRT given the competing risk of death. ETHICS AND DISSEMINATION: We obtained ethics approval for the AS-2 RCT, including this observational substudy, from local ethics boards at all participating sites. We will report the findings of this study through open-access publication, presentation at international conferences, a coordinated dissemination strategy by investigators through social media, and an open-access workshop series in multiple languages. TRIAL REGISTRATION NUMBER: NCT05057611.</p

Coronavirus disease 2019 (COVID-19) excess mortality outcomes associated with pandemic effects study (COPES): A systematic review and meta-analysis

Background and aimWith the Coronavirus Disease 2019 (COVID-19) pandemic continuing to impact healthcare systems around the world, healthcare providers are attempting to balance resources devoted to COVID-19 patients while minimizing excess mortality overall (both COVID-19 and non-COVID-19 patients). To this end, we conducted a systematic review (SR) to describe the effect of the COVID-19 pandemic on all-cause excess mortality (COVID-19 and non-COVID-19) during the pandemic timeframe compared to non-pandemic times.MethodsWe searched EMBASE, Cochrane Database of SRs, MEDLINE, Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Cochrane Controlled Trials Register (CENTRAL), from inception (1948) to December 31, 2020. We used a two-stage review process to screen/extract data. We assessed risk of bias using Newcastle-Ottawa Scale (NOS). We used Critical Appraisal and Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology.ResultsOf 11,581 citations, 194 studies met eligibility. Of these studies, 31 had mortality comparisons (n = 433,196,345 participants). Compared to pre-pandemic times, during the COVID-19 pandemic, our meta-analysis demonstrated that COVID-19 mortality had an increased risk difference (RD) of 0.06% (95% CI: 0.06–0.06% p &lt; 0.00001). All-cause mortality also increased [relative risk (RR): 1.53, 95% confidence interval (CI): 1.38–1.70, p &lt; 0.00001] alongside non-COVID-19 mortality (RR: 1.18, 1.07–1.30, p &lt; 0.00001). There was “very low” certainty of evidence through GRADE assessment for all outcomes studied, demonstrating the evidence as uncertain.InterpretationThe COVID-19 pandemic may have caused significant increases in all-cause excess mortality, greater than those accounted for by increases due to COVID-19 mortality alone, although the evidence is uncertain.Systematic review registration[https://www.crd.york.ac.uk/prospero/#recordDetails], identifier [CRD42020201256]

Safety and Efficacy of Dexmedetomidine in Acutely Ill Adults Requiring Noninvasive Ventilation:A Systematic Review and Meta-analysis of Randomized Trials

BACKGROUND: Although clinical studies have evaluated dexmedetomidine as a strategy to improve noninvasive ventilation (NIV) comfort and tolerance in patients with acute respiratory failure (ARF), their results have not been summarized. RESEARCH QUESTION: Does dexmedetomidine, when compared with another sedative or placebo, reduce the risk of delirium, mortality, need for intubation and mechanical ventilation, or ICU length of stay (LOS) in adults with ARF initiated on NIV in the ICU? STUDY DESIGN AND METHODS: We electronically searched MEDLINE, EMBASE, and the Cochrane Library from inception through July 31, 2020, for randomized clinical trials (RCTs). We calculated pooled relative risks (RRs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes with the corresponding 95% CIs using a random-effect model. RESULTS: Twelve RCTs were included in our final analysis (n = 738 patients). The use of dexmedetomidine, compared with other sedation strategies or placebo, reduced the risk of intubation (RR, 0.54; 95% CI, 0.41-0.71; moderate certainty), delirium (RR, 0.34; 95% CI, 0.22-0.54; moderate certainty), and ICU LOS (MD, –2.40 days; 95% CI, –3.51 to –1.29 days; low certainty). Use of dexmedetomidine was associated with an increased risk of bradycardia (RR, 2.80; 95% CI, 1.92-4.07; moderate certainty) and hypotension (RR, 1.98; 95% CI, 1.32-2.98; moderate certainty). INTERPRETATION: Compared with any sedation strategy or placebo, dexmedetomidine reduced the risk of delirium and the need for mechanical ventilation while increasing the risk of bradycardia and hypotension. The results are limited by imprecision, and further large RCTs are needed. TRIAL REGISTRY: PROSPERO; No.: 175086; URL: www.crd.york.ac.uk/prospero

Development of a transoral robotic surgery program in Canada

Abstract Due to significant differences in healthcare structure between the United States and Canada, there are unique barriers to adopting new medical technology in Canada. In this article, we describe our experience developing a transoral robotic surgery (TORS) program at Western University. Specifically, we outline the steps that were necessary to obtain institutional and multidisciplinary team approval, financial support, as well as surgeon and allied healthcare personnel training. This experience can potentially be used as a roadmap for other Canadian institutions pursuing a TORS program

Needs Assessment Survey Identifying Research Processes Which may be Improved by Automation or Artificial Intelligence: ICU Community Modeling and Artificial Intelligence to Improve Efficiency (ICU-Comma)

Background: Critical care research in Canada is conducted primarily in academically-affiliated intensive care units with established research infrastructure, including research coordinators (RCs). Recently, efforts have been made to engage community hospital ICUs in research albeit with barriers. Automation or artificial intelligence (AI) could aid the performance of routine research tasks. It is unclear which research study processes might be improved through AI automation. Methods: We conducted a cross-sectional survey of Canadian ICU research personnel. The survey contained items characterizing opinions regarding research processes that may be amenable to AI automation. We distributed the questionnaire via email distribution lists of 3 Canadian research societies. Open-ended questions were analyzed using a thematic content analysis approach. Results: A total of 49 survey responses were received (response rate: 8%). Tasks that respondents felt were time-consuming/tedious/tiresome included: screening for potentially eligible patients (74%), inputting data into case report forms (65%), and preparing internal tracking logs (53%). Tasks that respondents felt could be performed by AI automation included: screening for eligible patients (59%), inputting data into case report forms (55%), preparing internal tracking logs (51%), and randomizing patients into studies (45%). Open-ended questions identified enthusiasm for AI automation to improve information accuracy and efficiency while freeing up RCs to perform tasks that require human interaction. This enthusiasm was tempered by the need for proper AI education and oversight. Conclusions: There were balanced supportive (increased efficiency and re-allocation of tasks) and challenges (informational accuracy and oversight) with regards to AI automation in ICU research

A Pilot Study Comparing HPV-Positive and HPV-Negative Head and Neck Squamous Cell Carcinomas by Whole Exome Sequencing.

Background. Next-generation sequencing of cancers has identified important therapeutic targets and biomarkers. The goal of this pilot study was to compare the genetic changes in a human papillomavirus- (HPV-)positive and an HPV-negative head and neck tumor. Methods. DNA was extracted from the blood and primary tumor of a patient with an HPV-positive tonsillar cancer and those of a patient with an HPV-negative oral tongue tumor. Exome enrichment was performed using the Agilent SureSelect All Exon Kit, followed by sequencing on the ABI SOLiD platform. Results. Exome sequencing revealed slightly more mutations in the HPV-negative tumor (73) in contrast to the HPV-positive tumor (58). Multiple mutations were noted in zinc finger genes (ZNF3, 10, 229, 470, 543, 616, 664, 638, 716, and 799) and mucin genes (MUC4, 6, 12, and 16). Mutations were noted in MUC12 in both tumors. Conclusions. HPV-positive HNSCC is distinct from HPV-negative disease in terms of evidence of viral infection, p16 status, and frequency of mutations. Next-generation sequencing has the potential to identify novel therapeutic targets and biomarkers in HNSCC