The Skeptics Guide to Emergency Medicine

Date: November 26th, 2022 Reference: James et al. Emergency Department Condition Acuity, Length of Stay, and Revisits Among Deaf and Hard-of-Hearing Patients: A Retrospective Chart Review. AEM November 2022 Guest Skeptic: Dr. Corey Heitz is an emergency physician in Roanoke, Virginia. He is also the CME editor for Academic Emergency Medicine. Click on the LINK for a transcript of the podcast Case: One night you grab the next patient on the board, and upon entering the room introduce yourself as you normally would. The patient waves at you and gestures to a friend in the room, who explains that the patient is deaf and needs a sign language interpreter. You know from your brief look at the triage report that the patient’s vitals are stable and their chief complaint isn’t likely to be immediately life threatening, so you politely explain you’ll be back, and go find the charge nurse to obtain interpreter services. Background: The emergency department sees anyone at anytime for anything. This includes some patients who have difficulty accessing the healthcare system due to social determinants of health, race, gender, mental health, substance use disorder, and physical difficulties. Deaf and hard-of-hearing (DHH) experience disparities in social outcomes as well as health inequities (1), likely due to audism, which creates privilege for non-DHH people in our society (2). DHH patients are more likely to use the ED than non-DHH patients, but little research has been done to compare ED-focused outcomes for these groups of patients (1, 3-4). DHH patients are heterogenous, with adult-onset DHH patients being less likely to use American Sign Language (ASL) with proficiency (5). DHH ASL users may have delays due to interpreter availability, potentially resulting in care discrepancies (1, 6). Clinical Question: How do deaf and hard-of-hearing (DHH) American Sign Language speakers and DHH English speakers utilize the ED, specifically regarding acuity of complaints and pain, what is their ED length of stay and what is the prevalence of acute revisits? Reference: James et al. Emergency Department Condition Acuity, Length of Stay, and Revisits Among Deaf and Hard-of-Hearing Patients: A Retrospective Chart Review, AEM November 2022 Population: All DHH-American Sign Language, DHH-English speakers, non-DHH English speakers users who had used a single academic center for care Excluded: Patients who had not had an ED visit during the time period Intervention: None Comparison: Non-DHH English speakers were compared to DHH ASL-users and DHH English speakers Outcomes: Primary Outcome: Emergency Severity Index (ESI), triage pain score, ED length of stay (LOS), and acute ED revisit (defined as within 9 days) Type of Study: Retrospective chart review of a single health care system Dr. Tyler James This is an SGEMHOP episode which means we have the lead author on the show Dr. Tyler James. Dr. James is a Postdoctoral Research Fellow in the Department of Family Medicine at the University of Michigan Medical School. His research focuses on healthcare access, utilization, and delivery for people with disabilities, with specific interest in working with people with sensory disabilities. He is also a mixed methods research methodologist, and serves as Associate Editor for Media Reviews of the Journal of Mixed Methods Research. Authors’ Conclusions: Our study identified that DHH ASL-users have longer ED LOS than non-DHH English-speakers. Additional research is needed to further explain the association between DHH status and ED care outcomes (including ED LOS, and acute revisit), which may be used to identify intervention targets to improve health equity. Quality Checklist for Observational Study: Did the study address a clearly focused issue? Yes Did the authors use an appropriate method to answer their question? Yes Was the cohort recruited in an acceptable way? Yes Was the exposure accurately measured to minimize bias? Yes Was the outcome accurately measured to minimize bias? Yes Have the authors identified all important confounding factors? Yes Was the follow up of subjects complete enough? Yes How precise are the results? Fairly precise Do you believe the results? Yes Can the results be applied to the local population? Unsure Do the results of this study fit with other available evidence? Yes Funding of the Study: Agency for Healthcare Research and Quality, and the National Center for Advancing Translational Sciences of the National Institutes of Health under University of Florida Clinical and Translational Science Results: The sample included 100% of DHH-ASL people (n=277). This was compared to 1,000 randomly sampled DHH English speakers, and 1,000 randomly sampled non-DHH English speakers. Of this total sample, 39%, 36% and 30% had an ED visit during the study time frame and were analyzed. The Mean age was mid to late 40’s, ~55% were women and about two-thirds identified as white. Key Result: There were no statistical differences in ESI, triage pain score, or acute ED visits but DHH ASL patients had longer ED LOS. Primary Outcome: Emergency Severity Index (ESI): When compared to non-DHH English speakers, neither DHH ASL users nor DHH English speakers had higher odds of being classified into lower-acuity ESI levels. Triage Pain Score: On a scale of 0 to 10 the mean score was 5.8 and the median was 7. Neither of the DHH patient groups had pain scale ratings significantly different than non-DHH English speakers. Acute ED Revisit: This was defined as a return within nine days. Ten percent of patients had acute revisits to the ED. There was no statistical difference between the groups for this metric. Length of Stay: DHH ASL-using patients stayed in the ED 9% longer than non-DHH English-speaking patients (IRR 1.09, 95% CI 1.05 to 1.13, P = 0.016). On average, this equated to approximately 30 min longer ED LOS (95% CI 17 to 44 min). There were no significant differences between DHH English-speaking patients and non-DHH English speakers For a transcript of this podcast and all of Tyler's responses to our nerdy questions clinic on this LINK. 1. Selecting the Cohort: Can you explain the decision to start with the cohort of patients who utilized any of the medical center facilities and then select those who presented to the ED, as opposed to just isolating DHH patients from all ED visits? 2. Return Visit: Often in ED literature, we see 72-hour return visits or seven-day returns. In addition, two weeks is sometimes used or even one month. Why did you decide to use nine days for your acute ED revisit metric? 3. Patient Level Data: I understand how it’s important to look at patient-level and encounter-level data, as a small subset of patients may have many encounters. However, how is this used for revisits, as that measurement seems to me to be a patient-specific outcome? 4. Length of Stay: The only metric measured that was statistically different was the ED LOS. It was 30 minutes longer in DHH ASL-using patients or approximately 9% compared to non-DHH English-speaking patients. Do you think this is clinically significant and we should be cautious not to over-interpret a single-centre retrospective observational data? 5. Any Thing Else: Is there any other data or themes that you want to highlight from this publication? Comment on Authors’ Conclusion Compared to SGEM Conclusion: We agree with the authors’ cautious conclusions. SGEM Bottom Line: Deaf and hard-of-hearing (DHH) patients present to the ED with similar acuity levels, triage pain scores and had no significant difference in acute ED revisits compared to non-DHH English speaking patients. However, there was an association observed between DHH-ASL patients and longer ED LOS comparted to non-DHH English speaking patients. Dr. Corey Heitz Case Resolution: Fortunately, your ED has on-site interpreter ASL services that can be accessed quickly and efficiently. This service is preferred to an online, remote interpreter system due to technical difficulties, lack of staff training, which can lead to poor patient-provider communication (7). Clinical Application: Deaf and hard of hearing patients should be triaged and treated with the same level of concern and care. Use of interpreter services is essential as with any non-English speaking patient. What Do I Tell the Patient? Thank you for your patience while we obtained interpreter services. How may we help you today? Keener Kontest: Last weeks’ winner was a repeat win for Dr. Cindy Bitter. She knew acute pancreatitis was first described in 1652 by Dutch anatomist Nicholas Tulp. Listen to the podcast this week to hear the trivia question. Send your answer to TheSGEM@gmail.com with "Keener" in the subject line. The first correct answer will receive a cool skeptical prize. SGEMHOP: Now it is your turn SGEMers. What do you think of this episode on DHH in the ED? What questions do you have for Tyler and this team? Tweet your comments using #SGEMHOP or post your feedback on the SGEM blog. The best social media feedback will be published in AEM. Remember to be skeptical of anything you learn, even if you heard it on the Skeptics’ Guide to Emergency Medicine. References: James TG, Varnes JR, Sullivan MK, et al. Conceptual model of emergency department utilization among deaf and hard-of-hearing patients: A critical review. Int J Environ Res Public Health [Internet] 2021 [cited 2021 Dec 9];18(24):12901. Available from: https://www.mdpi.com/1660-4601/18/24/12901 Bauman H-DL. Audism: Exploring the metaphysics of oppression. J Deaf Stud Deaf Educ 2004;9(2):239–46. McKee MM, Winters PC, Sen A, Zazove P, Fiscella K. Emergency department utilization among deaf American Sign Language users. Disabil Health J 2015;8(4):573–8.

Date: November 19th, 2022 Reference: Khatib N, and Sampsel K. CAEP Position Statement Executive Summary: Where is the love? Intimate partner violence (IPV) in the Emergency Department (ED). CJE.M 2022 Nov Dr. Nour Khatib Guest Skeptics: Dr. Nour Khatib is an emergency physician in Toronto working in community sites Markham Stouffville Hospital and Lakeridge health. Dr. Khatib also works in remote Northern communities in the Northwest Territories and Nunavut. She is currently the professional development and education lead at Lakeridge Health and lead preceptor for Lakeridge Health learners. She is the VP of Finance of a not-for-profit emergency education organization creating educational events for community emergency doctors. Prior to her career in medicine, she was a financial analyst for Pratt & Whitney Canada and has a background in Finance and an MBA. Her unique work and life experiences have fueled her passion for leadership, patient education, and quality improvement. Dr. Kari Sampsel Dr. Kari Sampsel is a staff Emergency Physician and Medical Director of the Sexual Assault and Partner Abuse Care Program at the Ottawa Hospital and an Assistant Professor at the University of Ottawa. She has been active in the fields of forensic medicine and medical education, with multiple international conference presentations, publications and committee work. She has been honored with a number of national awards in recognition of her commitment to education and awareness. She has founded a technology/consultancy company to assist organizations in policy development, staff training, investigation and prevention of sexual harassment and assault. She is also an avid CrossFitter and believes that strength and advocacy are the way to a better world. This is an SGEM Xtra episode. The Canadian Association of Emergency Physicians (CAEP) put out a position statement on intimate partner violence (IPV) on November 2, 2022.  CAEP has several position statements including homelessness, violence in the ED, gender equity, opioid use disorder and other topics. We did an SGEM Xtra episode covering the CAEP position statement on Access to Dental Care. The key message is that CAEP believes that every Canadian should have affordable, timely, and equitable access to dental care. TRIGGER WARNING: As a warning to those listening to the podcast or reading the blog post, there may be some things discussed about IPV that could be upsetting. The SGEM is free and open access trying to cut the knowledge translation down to less than one year. It is intended for clinicians providing care to emergency patients, so they get the best care, based on the best evidence. Some of the IPV material we are going to be talking about on the show could trigger some strong emotions. If you are feeling upset by the content, then please stop listening or reading. There will be resources listed at the end of the blog for those looking for assistance. The rate of women murdered by a current or ex-partner in Canada has increased from 1 in every 6 days, to one in every 36 hours in 2022. Canada’s Emergency Departments are where survivors of violence most often seek care, and where the violence against them is not always recognized. A new position statement from the Canadian Association of Emergency Physicians, published in November 2022, during Domestic Violence Awareness Month, aims to guide Emergency Department staff in the recognition and care of survivors of violence. This statement helps guide clinicians and emergency departments on how to implement processes to identify, treat and keep survivors of intimate partner violence safe. Questions for Dr. Khatib and Dr. Sampsel Nour and Kari were asked a number of questions about IPV and the CAEP Position Statement. Please listen to the SGEM Xtra podcast on iTunes to hear their answers and for more details. How do you define IPV? IPV refers to any behaviour within an intimate relationship that causes physical, psychological or sexual harm to those in the relationship. This is often an issue of power and control and could be in current or past relationships. Why did CAEP decide to put out a position statement on IPV? IPV patients are being seen daily in our EDs and CAEP saw the value in ensuring that this vulnerable trauma population was recognized and received good care when they came to see us. Why did you two decide to take the lead on this issue? Nour had presented an award-winning Grand Rounds on IPV where she noted that CAEP didn’t have a statement yet on this, despite IPV patients being seen most often in an ED setting.  In my experience working in this field, I noticed that emerg docs were really comfortable with caring for trauma patients, but were less comfortable with this subset of trauma.  So we decided to write a document to help our colleagues across the country. How prevalent is IPV and what impact does it have on those exposed to IPV World Health Organization (WHO) estimates the prevalence to be 1 in 3 women worldwide, with no significant difference between continents (WHO). Women exposed to IPV are twice more likely to suffer from depression and alcohol use disorders and 38% of all murders of women worldwide are IPV-related. In fact, a woman is murdered in Canada every 36 hours by a current or ex-partner. Who suffer from IPV? Women 1 in 3, men 1 in 8, but also LGBTQ+ The true rate for IPV in men is unknown given low reporting for various complex reasons Populations who are vulnerable such as indigenous and LGBTQ+ IPV transcends economic status, gender, borders It’s an everybody problem Minorities Has the COVID-19 global pandemic had an impact on IPV prevalence? The COVID-19 pandemic has worsened the prevalence of IPV with shelter-at-home orders, increased calls to police and community support, and decreased recognized presentations in the ED. My research and that of others found that the stressors of the pandemic mirror the stressors that worsen IPV and that home can be an unsafe place for those affected by IPV.  What role does the ED have in this issue of IPV?  A 2008 study found 44% of women murdered by their intimate partner had visited an ED in the last year; 93% of these victims visited specifically for IPV-related injury. ED physicians identified 5% of IPV cases; only 13% asked about domestic violence, despite almost 40% of females presenting with violent injuries. These patients are being seen in our EDs every day but we aren’t tuned to look for this like we are for so many other disease entities. We are that port in the storm for patients seeking care or even escaping IPV because we are always open. Can you help dispel the stereotype of the "battered woman"? The stereotypical “battered woman” is often the only image that comes to mind when thinking of IPV, when it can encompass things like stalking, threats to take away their children, workplace sabotage, or blackmail. Additionally, multiple visits for the same presentation, chronic pain syndromes, mental health concerns and substance use are highly associated with IPV. Also, IPV affects all races, socioeconomic classes, educational levels, so for all these reasons, it may not look like that “battered woman”. What are the Canadian statistics on IPV and do you think the incidence is over or under estimated? Vastly underestimated. Best estimates state that one in 10 survivors of violence seek care.  Even with that, Statistics Canada identified that IPV accounted for 1 in 4 police-reported crimes in 2011. Among these, ex-partners were involved 30% of the time. Between 2009 and 2017, there were a total of 22,323 incidents of police-reported same-sex intimate partner violence in Canada—that is, violence among same-sex spouses, boyfriends, girlfriends, or individuals in other intimate partnerships. This represented approximately 3% of all police-reported incidents of IPV over this time period. There is an increased risk of homicide after separation; leaving is the riskiest action patients take and they often find refuge in the emergency department during this transition period. A 2009 General Social Survey found 22% of victims report incidents to police; thus the IPV statistics discussed are significant underestimations. And like we had mentioned, a woman is murdered in Canada every 36h. Is IPV a reportable event in Canada that emergency physicians must call the police? In Canada, you cannot call the Police without the express consent of the patient, even if you are concerned for their safety. The only way you are allowed to break confidentiality is in cases where children are in the home (even if they are not victims of the abuse), elder abuse in a long-term care setting or gunshot wounds. We are there for the survivor of violence, to help them with what they need at the time, even if it can be difficult for us as ED physicians not to have this reported to police. What is the economic impact of IPV? Estimating the economic impact of a social phenomena naturally would help policy-makers with resource allocation and program funding. A Justice Canada costing study published in 2012 estimated the cost of IPV to be $7.4 billion dollars. The study estimated the cost of ED IPV-related visits were 30 x more costly than Family practice visits, and patients are three times more likely to visit the ED than their own family doctor for IPV-related health concerns. Why is that? We are always open. You can come to the ED and no one will find out. In and out anonymously. At your family doctors office this might not be the case. So the ED is where most IPV patients seek refuge/medical care. Comparatively, $7.4 billion dollars is equivalent to the Gross Domestic Product (GDP) of Bahamas and is more than what is spent on care of congestive heart failure patients in Canada. So clearly this is having a significant impact on the Canadian population,

Date: November 10th, 2022 Reference: de-Madaria E et al. Aggressive or Moderate Fluid Resuscitation in Acute Pancreatitis (WATERFALL). NEJM 2022. Guest Skeptic: Dr. Salim R. Rezaie completed his medical school training at Texas A&M Health Science Center and continued his medical education with a combined Emergency Medicine/Internal Medicine residency at East Carolina University. Currently, Salim works as a community emergency physician at Greater San Antonio Emergency Physicians (GSEP), where he is the director of clinical education. Salim is also the creator and founder of REBEL EM and REBEL Cast, a free, critical appraisal blog and podcast that try to cut down knowledge translation gaps of research to bedside clinical practice. Case: A 38-year-old male presents to the emergency department (ED) with acute mid epigastric abdominal pain with nausea and vomiting.  As part of the patient’s workup, he has an elevated lipase, and a CT abdomen and pelvis ultimately shows the patient to have acute pancreatitis. You remember a new trial was just published on whether to use aggressive versus nonaggressive goal-directed fluid resuscitation in the early phase of acute pancreatitis and wonder which would be better for this patient. Background: It’s interesting to see how fluid resuscitation has been debated over the years. This includes fluid type and rate for things like renal colic (SGEM#32), pediatric diabetic ketoacidosis  (SGEM#255), hyponatremia (SGEM#326), trauma (SGEM#369), and critically ill adults (SGEM#347 and SGEM#368). Standard management of acute pancreatitis has focused mainly on hydration, analgesia, and investigation for an underlying cause.  Recent evidence has challenged the routine use of aggressive large volume fluid resuscitation with the potential to increase the severity of pancreatitis as well as fluid overload.  High-quality evidence demonstrating harms of aggressive fluid resuscitation in acute pancreatitis have been lacking. Clinical Question: Does the use of a moderate fluid resuscitation strategy in acute pancreatitis decrease the rate of progression to moderate/severe pancreatitis in comparison to aggressive fluid resuscitation? Reference: de-Madaria E et al. Aggressive or Moderate Fluid Resuscitation in Acute Pancreatitis (WATERFALL). NEJM 2022. Population: Adult patients (≥18 years of age) diagnosed with acute pancreatitis based on the Revised Atlanta Classification (Requires 2 of 3: Typical abdominal pain, serum amylase or lipase level higher than three times the upper limit of normal, or signs of acute pancreatitis on imaging) that presented within 24 hours of pain onset Exclusions: Patients who met the criteria for moderately severe or severe disease at baseline (shock, respiratory failure, and renal failure) or who had baseline heart failure (NYHA II, III, or IV), uncontrolled arterial hypertension, electrolyte disturbances (hypernatremia, hyponatremia, hyperkalemia, hypercalcemia), an estimated life expectancy of <1 year, chronic pancreatitis, chronic renal failure, or decompensated cirrhosis Intervention: Moderate fluid resuscitation (bolus of 10 cc/kg lactated Ringer’s [LR] over two hours in patients with hypovolemia or no bolus in those with normovolemia followed by 1.5 cc/kg/hour of LR) Comparison: Aggressive fluid resuscitation (bolus of 20 cc/kg LR over two hours regardless of fluid status followed by 3.0 cc/kg/hour of LR) Outcome: Primary Outcome: Progression to moderately severe or severe acute pancreatitis (according to the Revised Atlanta Classification). Secondary Outcomes: Organ failure, local complications, persistent organ failure, respiratory Failure, hospital length of stay (LOS), ICU admission, and ICU LOS Safety Endpoint: Fluid Overload defined by 2 of the following 3: Criterion 1: Non-invasive evidence of heart failure (ie echo), radiographic evidence of pulmonary congestion, invasive cardiac Cath suggesting heart failure. Criterion 2: Dyspnea Criterion 3: Heart failure signs: peripheral edema, pulmonary rales, increased jugular venous pressure (JVP) or hepatojugular reflex Type of Study: Multicenter, multinational, open-label, parallel-group, randomized, controlled, superiority trial at 18 centers across four countries (India, Italy, Mexico, and Spain) Authors’ Conclusions: “In this randomized trial involving patients with acute pancreatitis, early aggressive fluid resuscitation resulted in a higher incidence of fluid overload without improvement in clinical outcomes.” Quality Checklist for Randomized Clinical Trials: The study population included or focused on those in the emergency department. Yes The patients were adequately randomized. Yes The randomization process was concealed. Yes The patients were analyzed in the groups to which they were randomized. Yes The study patients were recruited consecutively (i.e. no selection bias). Yes The patients in both groups were similar with respect to prognostic factors. No All participants (patients, clinicians, outcome assessors) were unaware of group allocation. No All groups were treated equally except for the intervention. Unsure Follow-up was complete (i.e. at least 80% for both groups). Yes All patient-important outcomes were considered. Yes The treatment effect was large enough and precise enough to be clinically significant. No Financial conflicts of interest. No Results: They screened 676 patients with acute pancreatitis for inclusion. The final cohort consisted of 249 patients randomly assigned (127 moderate and 122 aggressive). Mean age was 57 years. It was about a 50/50 male female split but 9.2% more females were in the aggressive group. There was also about a 10% difference in gallstone causes of pancreatitis (65.6% aggressive vs 55.9% moderate). The aggressive group got more fluid in the first 48 hours (7.8L vs 5.5L). Key Result: In adult patients with non-severe acute pancreatitis, there was a lack of benefit with aggressive fluid resuscitation but there was an increase in harm. Primary Outcome: Progression to moderate/severe pancreatitis Moderate 17.3% vs Aggressive 22.1% Absolute Difference 4.8%; aRR 1.30 (95% CI, 0.78 to 2.18) Secondary Outcomes:  No statistical difference in organ failure, local complications, persistent organ failure or respiratory failure between groups Primary Safety Outcome: Fluid overload Moderate 6.3% vs Aggressive 20.5% Absolute Difference: 14.2%; aRR 2.85 (95% CI, 1.36 to 5.94) NNH 7 1. Trial Stopped Early: This trial was stopped early due to an interim analysis demonstrating a significantly higher rate of fluid overload in the aggressive hydration group. We have discussed the issues around stopping trials early before on the SGEM. Guyatt et al published an article in the BMJ 2012 describing the dangers of stopping trials early for benefit and Veile et al covered the issue in JAMA 2016. This trial was stopped early for harm after about 1/3 of the power calculation to include 744 participants. The investigators a priori specified what conditions would trigger the trial to be stopped in a publication by Bolando et al Front Med 2020. a between-group difference in the primary outcome with a two-sided P value of less than 0.0002 at the first interim analysis less than 0.012 at the second interim analysis clear evidence of harm in one trial group over the other (safety) as adjudicated by the data and safety monitoring board, slow recruitment rate At the time the trial was stopped, there was a 4.8% non-statistically significant difference in the primary outcome (favoring moderate fluid resuscitation), which was smaller than the pre-set criteria of 5% difference.  However, given the statistically significant difference in the primary safety outcome, a larger study shouldn’t be necessary to change practice. 2. Open-Label Trial: Patients and investigators were aware of group allocation while the outcome assessors were blinded. Blinding to group allocation is an important method to mitigate potential bias. A good primer on the importance of blinding can be found on the Cochrane website Students 4 Best Evidence.. Sometimes it is not possible to blind trials, and this can introduce a potential risk of bias.  This is particularly important as the safety outcome (fluid overload) in the Waterfall trial has some subjectivity to it and means we should be more skeptical of this result. 3. Statistically Significant vs Clinically Significant: We have often mentioned the difference between statistical and clinical significance. Although none of the secondary outcomes reached statistical significance, all of them had numeric trends toward harm in the aggressive fluid group. Normally secondary outcomes are hypothesis generating, however given the worsened primary safety outcome of fluid overload, we need to consider this clinical information carefully. 4. Volume of Fluids: The authors did achieve separation between groups when looking at median fluids received in the first 48 hours. It was 7.8L in the aggressive group (range 6.5 to 9.8L) and 5.5L in the moderate group (range 4.09 to 6.8L) Not sure what point you are making?? 5. Exclusion Criteria: There was a fairly extensive list of exclusion criteria which excluded most patients that were approached for enrollment. Of the 676 patients assessed only 249 met inclusion/exclusion criteria (39%). Some of the exclusion criteria seemed questionable (i.e. HTN, electrolyte abnormalities) which resulted in 96 patients (14%) being excluded. Comment on Authors’ Conclusion Compared to SGEM Conclusion: We agree with the authors’ conclusion that an aggressive fluid resuscitation strategy led to more fluid overload without improvement in other clinical outcomes.

Date: October 24, 2022 Guest Skeptic: Dr. Damian Roland is a Consultant at the University of Leicester NHS Trust and Honorary Professor for the University of Leicester’s SAPPHIRE group. He specializes in Pediatric Emergency Medicine and is a passionate believer and advocate of FOAMed. Damian is also part of the Don’t Forget the Bubbles team. Dr. Damian Roland I sent Damian a message on Twitter after he posted about his pre-print paper, “Concomitant infection of COVID19 & Serious Bacterial infection in Infants <90 Days Old during Omicron Surge.”  It was a rapid evaluation under the remit of the Public Health/Disease Control so did not require review by a Research Ethics Committee (REC). Unfortunately, journals, do not typically accept this and want to see ethics derogation. This led to a conversation about research ethics and governance. It is important to acknowledge that historically, the medical community has not always conducted research ethically. We took advantage of vulnerable and minority populations as evidenced by Nazi medical experimentation in the concentration camps, the Tuskegee Syphilis Study, or the HeLa cells of Henrietta Lacks. We recognize the importance of research oversight and ethical research, but our world is changing… How have emerging pandemics, technology, and social media impacted the way we conduct and disseminate research? We covered five topics: Ethics of Research in Pandemics Maintaining Research Quality Deferred Consent Big Data Sharing Research on Social Media Ethics of Research in Pandemics Many processes that govern research were scaled back to enable rapid translation of ideas. Some of this was good (ex. steroids in Covid, vaccines) but some had some potentially detrimental consequences (think pre-prints) [1]. It was much easier (in the UK) to access national data sets, and this enabled real-time research to take place. During pandemics, we need to be nimble but governed when conducting research. For example, when a new disease process (ex. PIMS TS or MIS-C) is of such a public health importance that we need to understand it as fast as possible, it is difficult to do so under stringent ethics and governance practices. For the next pandemic, we need to have systems in place for research studies to be pre-approved and ready to go as soon as a pandemic hits. Maintaining Research Quality At one point there were over 100 articles being published per day about COVID-19 [2]. Not all of them were useful or high quality. Keep in mind the words of Professor Altman, “we need less research, better research, and research done for the right reasons.”[3] It is possible to have well-governed research that is poor quality but finds itself through poor review, disseminated widely in a high-quality journal. Conversely, there can be well-governed research that is high-quality, but journals disagree, and that research has less impact because it is not perceived by journals to be good. The issue of ethical review should be separate from quality and governance. Does ethical review encompass the standard or quality of research or the mechanism of ensuring that the research is ethically performed? A randomized control trial is always going to have ethical review whereas an observational study may not. Should research that is well thought out and robust but lacking ethical approval be excluded from journals because editors perceive it does not meet the standard for high-quality research? We separated 1) the governance of conducting research 2) the process of research, and 3) the publication of research and 4) the application of research findings. There are many factors that come into in play when making clinical decisions while facing the pressures of a novel pandemic. Dr. Simon Carley on SGEM Xtra: EBM and the Changingman discussed his publication, Evidence-based medicine and COVID-19: what to believe and when to change. [4] Deferred Consent This is not a new concept but has been historically difficult to get through an ethics committee. We have seen this with seizure studies such as Emergency treatment with Levetiracetam or Phenytoin in Status Epilepticus in children (EcLiPSE)[5] and Levetiracetam versus phenytoin for second-line treatment of convulsive status epilepticus in children (ConSEPT)[6]. Parents did not want to have the burden of consenting to a study during a stressful time, so these patients were randomized and consent was obtained later. Most of the hesitation about this approach did not come from the patients or parents but the clinicians. These studies are now a couple of years old, but deferred consent is being increasingly used in a variety of pediatric studies. Should deferred consent become the standard? Some still think that consent should be obtained prior, if possible, out of respect for patient autonomy and principle of respect for persons. Maybe there are exceptional circumstances when deferred consent is appropriate such as situations where there is clinical equipoise, and the patient is in critical condition or unable to provide consent [7]. When we are conducting research on pediatric patients, we are often obtaining consent from the legal guardians and assent from the child (if possible). We are relying on a proxy consent which may or may not align with the preferences of the patient [8]. In the UK, there is patient and public involvement (PPI) with studies so that research becomes a collaboration between researchers and patients, including children right from the beginning. This is critical as patient/family values and preferences is one of the pillars of evidence-based medicine. Big Data The recently published EPISODES study (Presentations of children to emergency departments across Europe and the COVID-19 pandemic: A multinational observational study | PLOS Medicine) [9] highlights the power of bringing multiple hospitals together. This is an opportunity to standardize reporting outcomes and comparing them in reliable and objective ways to see how care is provided globally. There are many global emergency medicine research networks. The results from these multi-center studies may be more generalizable. However, we should still be applying a critical and skeptical lens to these studies as disease prevalence and phenotypes may vary depending on location. We still need to determine whether the findings from big data studies can be applied to the local population. Sharing Research Findings via Social Media COVID-19 saw some savage attacks by scientists on each other which probably detracted from the original research (and obscured good papers and falsely elevated poor ones). There can be various interpretations of the evidence. Scientists are realizing that social media is a great mechanism for knowledge dissemination and translation. We need to be wary of crowdsourcing “facts” [10]. We enjoy being around like-minded people so it is easy to create communities in social media that are echo chambers. Confronting a perspective different from our own is uncomfortable. It is possible to have a civil conversation or debate and still disagree without being unkind to one another. It’s okay to change our minds! People were critical of health organizations changing recommendations during the pandemic, but that’s science! Damian encouraged us to maintain a professional tone and try to be objective as we can when sharing information on social media, acknowledge when we are wrong, and admit when we do not know.   The SGEM will be back next episode doing a structured critical appraisal of a recent publication. Trying to cut the knowledge translation window down from over 10 years to less than 1 year using the power of social media. Our goal is for patients to get the best care, based on the best evidence. Remember to be skeptical of anything you learn, even if you heard it on the Skeptics’ Guide to Emergency Medicine. References: Nabavi Nouri S, Cohen YA, Madhavan MV, Slomka PJ, Iskandrian AE, Einstein AJ. Preprint manuscripts and servers in the era of coronavirus disease 2019. J Eval Clin Pract. 2021;27(1):16-21. Teixeira da Silva JA, Tsigaris P, Erfanmanesh M. Publishing volumes in major databases related to Covid-19. Scientometrics. 2021;126(1):831-842. Altman DG. The scandal of poor medical research. BMJ. 1994;308(6924):283-284. Carley S, Horner D, Body R, Mackway-Jones K. Evidence-based medicine and COVID-19: what to believe and when to change. Emerg Med J. 2020;37(9):572-575. Woolfall K, Roper L, Humphreys A, et al. Enhancing practitioners’ confidence in recruitment and consent in the EcLiPSE trial: a mixed-method evaluation of site training - a Paediatric Emergency Research in the United Kingdom and Ireland (Peruki) study. Trials. 2019;20(1):181. Dalziel SR, Borland ML, Furyk J, et al. Levetiracetam versus phenytoin for second-line treatment of convulsive status epilepticus in children (Consept): an open-label, multicentre, randomised controlled trial. Lancet. 2019;393(10186):2135-2145. McRae AD, Weijer C. Lessons from everyday lives: a moral justification for acute care research. Crit Care Med. 2002;30(5):1146-1151. Jansen TC, Kompanje EJO, Druml C, Menon DK, Wiedermann CJ, Bakker J. Deferred consent in emergency intensive care research: what if the patient dies early? Use the data or not? Intensive Care Med. 2007;33(5):894-900. Nijman RG, Honeyford K, Farrugia R, et al. Presentations of children to emergency departments across Europe and the COVID-19 pandemic: A multinational observational study. PLoS Med. 2022;19(8):e1003974. Baron RJ, Ejnes YD. Physicians spreading misinformation on social media - do right and wrong answers still exist in medicine? N Engl J Med. 2022;387(1):1-3.

Date: October 27th, 2022 Reference: Hayashi et al. Comparative efficacy of sedation or analgesia methods for reduction of anterior shoulder dislocation: A systematic review and network meta-analysis. AEM October 2022 Guest Skeptic: Dr. Justin Morgenstern is an emergency physician and the creator of the #FOAMed project called First10EM.com   Case: A 19-year-old man presents to the emergency department (ED) with his first time anterior should dislocation after trying to recreate one of his favourite scenes in the movie Lethal Weapon. He is in significant pain, but your charge nurse informs us that, like most days since the pandemic started, the department is completely full of admitted patients, and there is nowhere safe to perform a procedural sedation, let alone have the staff to do it. The patient asks, through clenched teeth, whether there are any other options to get his shoulder back in. Background: We have covered shoulder issues a few times on the SGEM. There was an episode looking at diagnosing rotator cuff injuries (SGEM#74), the best position post-dislocation immobilization (SGEM#121) and using point of care ultrasound (POCUS) to diagnose shoulder dislocations (SGEM#288). The shoulder joint has the widest range of motion of any joint in the human body. This makes it very useful and very susceptible being dislocated. The vast majority of shoulder dislocations are anterior. Young active men are at greatest risk for dislocating their shoulder. There is also a wide range of options to diagnose shoulder dislocations (clinically, POCUS, x-ray) and dozens of reduction techniques. Some clinicians perform reductions without any analgesics at all, while others choose from a variety of options, including peripheral nerve blocks, intra-articular anesthesia, and full procedural sedation. Procedural sedation might represent one of the greatest advancements for the practice of emergency medicine, allowing us to perform a large variety of necessary but painful procedures without causing our patients pain. Although minor adverse events, such as brief apnea or hypoxia, are common, significant adverse events are very rare, and the benefits are clear (Bellolio 2016). However, for most departments, procedural sedation represents a logistical challenge that can increase a patient’s length of stay. Peripheral nerve blocks (PNBs) can be very effective at controlling pain, but require a degree of practitioner skill. The use of ultrasound to guide these procedures has increased their popularity in recent years. There have been a few randomized control trials (RCTs) of peripheral nerve blocks for shoulder dislocation, but without definitive results (Raeyat Doost 2017; Blaivas 2011). Intra-articular anesthetic (IAA) injections are another option, and seem like they should be incredibly easy, considering that the humeral head is not sitting in the glenoid fossa, and so the joint is wide open and supposedly easy to access. Intra-articular injection has been compared with procedural sedation (PS) for shoulder dislocation, with some potential benefits (Wakai 2011).  However, in one study, emergency physicians missed the joint space almost half the time when performing landmark-based shoulder injections (Omer 2021). Therefore, uncertainty remains about the ideal technique to provide analgesia and/or sedation for the reduction of anterior shoulder dislocations. Clinical Question: What is the safety and efficacy of intravenous sedation, intra-articular injection, and peripheral nerve block for the reduction of anterior shoulder dislocations. Reference: Hayashi et al. Comparative efficacy of sedation or analgesia methods for reduction of anterior shoulder dislocation: A systematic review and network meta-analysis. AEM October 2022 Population: RCTs that assessed sedation of analgesia methods for the reduction of anterior shoulder dislocations diagnosed on either physical exam or x-ray in patients older than 15 years of age. Exclusions: Allergies to study medications, multiple traumas, fractures (except Hill-Sachs and Bankart lesions), hemodynamic instability, or respiratory distress. Intervention: Intravenous (IV) sedation, intra-articular anesthetic (IAA) injection, and peripheral nerve blocks (PNB). Comparison: Patients who received either a placebo or no sedation. Outcome: Primary Outcome: There were three primary outcomes - Immediate success rate, patient satisfaction, and ED length of stay (LOS) Secondary Outcomes: Adverse events, pain score, time required for reduction, number of reduction attempts, and total success rate of the reduction. This is an SGEMHOP episode. Normally we have one of the authors on the show. This time we have the corresponding author who is an orthopedic trauma surgeon in Japan. Dr. Yamamoto was kind enough to give a shout out to his co-investigators and send responses to our ten nerdy questions. I can understand how hard it would be to talk nerdy in another language. Dr. Yamamoto's co-authors incliuded Minoru Hayashi, Kenichi Kano, Naoto Kuroda, Akihiro Shiroshita and Yuki Kataoka who are member of Scientific Research WorkS Peer Support Group (SRWS-PSG). SRWS-PSG is a scientific research group mainly conducting systematic reviews Authors’ Conclusions: “The results of our NMA indicated that three sedation or analgesia methods (IVS, IAA, and PNB) might result in little to no difference in the success rate of reduction and patient satisfaction. IAA and PNB had no adverse respiratory events.” Quality Checklist for Therapeutic Systematic Reviews: The clinical question is sensible and answerable. Yes The search for studies was detailed and exhaustive. Yes The primary studies were of high methodological quality. No The assessment of studies were reproducible. Yes The outcomes were clinically relevant. Yes There was low statistical heterogeneity for the primary outcomes. Unsure The treatment effect was large enough and precise enough to be clinically significant. No Results: After full-text review, they identified 16 RCTs that fulfilled their inclusion and exclusion criteria. These trials encompass a total of 957 patients. Of the 16 studies, 11 compared IV sedation to intra-articular injection, four compared nerve blocks to sedation, and one compared intra-articular injection to nothing. Key Result: There were no statistical differences in immediate success rate between techniques, uncertainty regarding patient satisfaction and intra-articular anesthetic had the shortest length-of-stay. Primary Outcomes: Immediate Success: There were no statistical differences IAA vs IVS: RR 0.93, 95% CI 0.84 to 1.02 PNB vs IVS: RR 1.13, 95% CI 0.84 to 1.52 Patient Satisfaction: The evidence was uncertain, with no statistical differences IAA vs IVS: SMD -0.47, 95% CI -1.41 to 0.48 PNB vs IVS: SMD -0.60, 95% CI -1.43 to 0.23 ED Length of Stay: The evidence was classified as very uncertain, but IAA had statistically shorter length of stays than IVS, whereas there was not a statistical difference between PNB and IVS IAA vs IVS: MD -107 minutes, 95% CI -203 to -13 PNB vs IVS: SMD -26 minutes, 95% CI -149 to 96 Secondary Outcomes: Adverse events: Two of the studies reported no adverse events. Respiratory events were the most common in the IVS group. Psychological agitation and drowsiness were reported in the IAA group, and mild local anesthetic systemic toxicity was reported in the PNB group. Pain score: IAA might be lower than PNB (SMD -1.8), but there were not differences noted between either IAA or PNB and IVS. Time for reduction: Both IAA and PNB might take longer than IVS (by 5 and 15 minutes respectively). Number of reduction attempts: Very uncertain, but no clear differences between the groups. Total success rate of reduction: No clear differences. We asked Dr. Yamamoto and his team of co-authors ten nerdy questions. They sent their written responses which are listed below: 1) Uncertainty: Rather than just focusing on statistical significance, you use the language of uncertainty throughout your results, with almost all the results being very uncertain. This language is not used in all meta-analyses. Can you comment on why you phrased your results this way? It is a very important point. We used “uncertain” as a result of evaluating the confidence of the evidence using the CINeMA tool. The confidence is the credibility of results from NMA and covers six domains: (i) within-study bias, (ii) reporting bias, (iii) indirectness, (iv) imprecision, (v) heterogeneity, and (vi) incoherence [Nikolakopoulou et al PLoS Med 2020]. The concept of imprecision includes statistical significance. We believe that our evaluation using confidence is more appropriate in assessing the credibility of the evidence. Dr. Yamamoto Considering both certainty of evidence and effect size are important for readers. Therefore, clinicians should not judge the effectiveness of interventions based on effect size alone, but should also consider the certainty of the evidence. 2) Accounting for Bias in the Meta-Analyses: I always find it difficult to appropriately account for the potential bias of individual studies when reading a meta-analysis. If I wouldn’t trust the results of a single RCT, it doesn’t help to mix it in with a bunch of other trials with similar methodologic issues. This is the classic GIGO – garbage in garbage out – problem. You perform a secondary analysis that focuses only on studies with the lowest risk of bias, and in that analysis IV sedation actually was statistically better than intra-articular injections. How do you account for bias in a meta-analysis, and which of these outcomes do you trust? A meta-analysis including only RCTs with low risk of bias is more reliable than the others. However,

Date: October 18th, 2022 Reference: Moore et al. Head and thorax elevation during cardiopulmonary resuscitation using circulatory adjuncts is associated with improved survival. Resuscitation 2022 Guest Skeptic: Clay Odell is a Paramedic, Firefighter, and registered nurse (RN). Case: You are the Chief of your local Fire and EMS Department, and an individual contacts you saying he saw a piece on TV about a “Heads Up” CPR device, and he wants to donate half the cost and has his checkbook out. Background: We have covered Out of Hospital Cardiac Arrests (OHCAs) many, many times on the SGEM. This includes epinephrine for OHCA, target temperature management, mechanical CPR, supraglottic airways, steroids, hands on defibrillation and many more topics. SGEM#50: Under Pressure Journal Club: Vasopressin, Steroids and Epinephrine in Cardiac Arrest SGEM#54: Baby It’s Cold Outside: Pre-hospital Therapeutic Hypothermia in Out of Hospital Cardiac Arrest SGEM#59: Can I Get a Witness: Family Members Present During CPR SGEM#64: Classic EM Paper: OPALS Study SGEM#107: Can’t Touch This: Hands on Defibrillation SGEM#136: CPR – Man or Machine? SGEM#143: Call Me Maybe for Bystander CPR SGEM#152: Movin’ on Up – Higher Floors, Lower Survival for OHCA SGEM#162: Not Stayin’ Alive More Often with Amiodarone or Lidocaine in OHCA SGEM#189: Bring Me To Life in OHCA SGEM#238: The Epi Don’t Work for OHCA SGEM#247: Supraglottic Airways Gonna Save You for an OHCA? SGEM#275: 10th Avenue Freeze Out - Therapeutic Hypothermia after Non-Shockable Cardiac Arrest SGEM#306: Fire Brigade and the Staying Alive APP for OHCAs in Paris SGEM#314: OHCA – Should you Take ‘em on the Run Baby if you Don’t get ROSC? SGEM#329: Will Corticosteroids Help if...I Will Survive a Cardiac Arrest? SGEM#336: You Can’t Always Get What You Want – TTM2 Trial SGEM#344: We Will...We Will Cath You – But should We After An OHCA Without ST Elevations? SGEM#353: At the COCA, COCA for OHCA Overall, the success rate of resuscitation of out of hospital cardiac arrest – or OHCA’s – is pretty dismal and efforts to improve resuscitation rates are absolutely vital. Animal research has suggested that elevating the head during CPR improves success rates. The proposed physiology includes decreased intracranial pressure and improved return of venous blood from the head and neck to the thorax. Pathophysiology has been used to justify practice many times in medicine. There are examples of medical reversal when properly conducted studies are performed to confirm the hypotheses. The time to accept a claim is when there is sufficient evidence. This study is an attempt to confirm (or refute) the pathophysiology and the animal research into human subjects. Clinical Question: Does the rapid use of an automated head up device as part of a CPR bundle improve survival from OHCA? Reference: Moore et al. Head and thorax elevation during cardiopulmonary resuscitation using circulatory adjuncts is associated with improved survival. Resuscitation 2022 Population: Adults 18 years of age and older with OHCA (ventricular fibrillation [VF] or ventricular tachycardia [VT], pulseless electrical activity [PEA], or asystole; routine and consistent treatment with ACE-CPR within the participating pre-hospital system; and routine and consistent recording of the 911 call receipt to placement of the APPD [automated controlled head and thorax patient positioning device] time interval. Excluded: Children, prisoners, women known to be pregnant, patients >175kg and patients without documentation of 911 call to start of EMS CPR time interval. Intervention: Automated controlled elevation of the head and thorax CPR (ACE-CPR) with an impedance threshold device (ITD) and active compression decompression (ACD-CPR) or LUCAS manual compression device Comparison: Conventional CPR (C-CPR) with or without ITD Outcome: Primary Outcome: Survival to hospital discharge Secondary Outcomes: Return of spontaneous circulation (ROSC) at any time, “favorable neurological function” defined as a Cerebral Performance Category (CPC) of 1 or 2 or “neurologically favorable function” defined as a modified Rankin Scale (mRS) score ≤ 3 Type of Study: Multi-centre, prospective observational study Authors’ Conclusions: “Compared with C-CPR controls, rapid initiation of ACE-CPR was associated with a higher likelihood of survival to hospital discharge after OHCA.” Quality Checklist for Observational Study: Did the study address a clearly focused issue? Yes Did the authors use an appropriate method to answer their question? Yes Was the cohort recruited in an acceptable way? Yes Was the exposure accurately measured to minimize bias? Yes Was the outcome accurately measured to minimize bias? Yes Have the authors identified all-important confounding factors? Unsure Was the follow up of subjects complete enough? Yes How precise are the results? Not very Do you believe the results? Unsure Can the results be applied to the local population? Unsure Do the results of this study fit with other available evidence? Yes Funding of the Study: ACE-CPR device manufacturer “Advanced CPR Solutions” Results: They included 227 patients from the ACE-CPR registry data who were propensity score matched to 860 C-CPR patients. The mean age was 64 years, 68% were male, 7% were EMS witness, 43% bystander CPR attempted, 17% in ventricular fibrillation or pulseless ventricular tachycardia. Key Result: When all the patients in the study were considered, ACE-CPR was not associated with improved survival to discharge for the adult patients with OHCA. Primary Outcome: Survival to hospital discharge ACE-CPR 9.5% vs. C-CPR 6.7%, OR 1.44 (95% CI, 0.86 to 2.44) Subgroup analysis of those treated from 911 call to ACE-CPR within 11 minutes and 18 minutes had an improved odds ratio of survival Secondary Outcomes: ROSC at any time (no statistical difference): ACE-CPR 33% vs. C-CPR 33%, OR 1.02 (95% CI, 0.75 to 1.49) Survival to hospital discharge with favorable neurological status (no statistical difference): ACE-CPR vs C-CPR 9% vs 4.1%, OR, 1.47, 95% CI, 0.76–2.82),   1) Association Is Not Causation: It is good to remember that this study design (prospective observational) cannot be used to conclude causation. While it is interesting that there was an association between rapid ACE-CPR use and mortality, causation would need to be demonstrated in a properly designed RCT. A search of ClinicalTrial.gov did not find any RCTs. However, there is another observational study (before-after design) currently underway in Europe called GRAVITY. 2) Propensity Score Matching: The authors compared their own data to patient data from other studies. Propensity score matching is a mathematical technique used in observational studies to try to minimize confounders. It can potentially improve the accuracy of minimizing some of the biases. However, it cannot address unmeasured confounders and get to the level of a randomized controlled trial. Peter C. Austin published a paper in 2011 that gives a reasonable introduction to propensity score matching. 3) Time to Treatment: We know that certain things can be important in patients with OHCA. This includes early high-quality CPR and having a shockable rhythm. Time is another important factor. This study showed that earlier ACE-CPR application from 911 dispatch had a greater odds ratio than those treated in a similar time frame with C-CPR. We must be careful not to over-interpret these results. It could also be that those using these fancy new devices were performing at a higher level for other important aspects correlated to survival. Of course, randomization to early vs. late CPR would be unethical. They also highlighted <11min and <18min in a subgroup analysis. Why were these times picked and was it done a priori? We could not find that this study was registered or published their methodology in advance. 4) Generalizability: This study included six sites which were characterized as early adopters. Are there any differences between those locations that embraced this technology sooner compared to those that did not? Perhaps it is those traits that lead to faster care and ultimately better outcomes? And not necessarily the head elevation? 5) Conflicts of Interest: The study was funded by the manufacturer of the ACE-CPR device. Co-author Bayert Salverda received payment from AdvancedCPR Solutions on contract basis for data collection services. He was listed as “data curation”. Another co-author, Keith Lurie, is a co-founder of AdvancedCPR Solutions, owns a significant equity position in this company and serves as its Chief Medical Officer. None of the other co-authors declared any relationship with industry or other relevant entities, financial or otherwise that might pose a conflict of interest with the publication. As we have pointed out before, industry funding does not negate results, but it should make us more skeptical. Comment on Authors’ Conclusion Compared to SGEM Conclusion: We agree that there was an association between rapid application of ACE-CPR and lower mortality. SGEM Bottom Line: We cannot recommend the purchase of an ACE-CPR device at this time. Case Resolution: The generous offer to help purchase an ACE-CPR device is declined. Clay Odell Clinical Application: Current research has not adequately shown a difference in outcomes between high-quality conventional CPR and ACE-CPR. There is a potential that earlier application of the ACE-CPR device, along with ITD and ACD-CPR or mechanical CPR may improve outcomes. However, it is too soon to adopt this technology. The authors mention further studies being conducted and we look forward to critically appraising those publications when available.

Date: October 5th, 2022 Reference: Top Gun 1986 Guest Skeptic: Dr. Chris Carpenter is Professor of Emergency Medicine in the Department of Emergency Medicine at Washington University in St. Louis and co-wrote the book on "Evidence-Based Emergency Care: Diagnostic Testing and Clinical Decision Rules".  Chris will be moving to Rochester, Minnesota soon to become the Vice Chair of Implementation and Innovation at the Mayo Clinic. This is an SGEM Xtra episode about what we learned from the 1986 movie Top Gun. It is similar to the episode with kindness guru, Dr. Brian Goldman, on how Star Trek made us better physicians. When Top Gun Maverick was released on Memorial Day Weekend May 27th, 2022, I hosted a weekend extravaganza. This involved watching the original movie, playing beach volleyball and then seeing Top Gun Maverick. It was an epic weekend with friends from around the world. Chris Bond from Standing on the Corner Minding My Own Business (SOCMOB) and I even stood up and sang She’s Lost that Lovin’ Feeling at the local movie theatre. You can click on this LINK to see the performance. Chris Carpenter was booked to attend the Top Gun long weekend but COVID had other ideas. He tested positive a few days before the extravaganza. Chris did not want to become a  citizen of Canada for two-weeks in isolation, so he stayed home and missed the fun. We were back together again at ACEP22 in San Francisco. Each year we co-present at the Rural Section meeting. This year we reviewed ten recent publications, provided some critical appraisal of the studies and then discussed if the evidence would be applied differently in a rural or critical access hospital compared to a tertiary or urban centre. You can download a copy of our slides at this LINK. Being together again for the first time since 2019 was a great opportunity to record the Top Gun SGEM Xtra episode. There are so many different lessons/takeaways from the movie and we covered eleven (my second favourite number). Lessons Learned from Top Gun 1) Be Prepared To Fail: Lieutenant Pete Mitchell (Maverick) takes risks and sometimes they work and sometimes they do not work. He dropped below the hard deck to get the kill shot during a training session but was reprimanded. Maverick also took a chance in the bar and tried to sing She’s Lost that Loving Feeling. Lieutenant Commander Rick Heatherly (Jester): "That was some of the best flying I've seen to date — right up to the part where you got killed." Working in the emergency department mean you will fail (make some mistakes). You need to learn from these experiences and not let previous failures prevent you from trying. It's not the falling down that is the most important, but rather the picking ourselves up. 2) Never Leave Your Wingman: Maverick comes into Top Gun a bit of a loner. Only real friend is Lieutenant Nick Bradshaw Goose. He needs to learn to work together in a team. Have your team’s back (RNs, techs, docs, admin, etc). Early in the movie he helps a fellow pilot land his plane. Commander Tom Jardian (Stinger): "Maverick, you just did an incredibly brave thing. (Pause) What you should have done was land your plane! Maverick also leaves his wingman at one point at Top Gun while in a training session and loses. Later in the movie he stays with his wingman in combat and is successful.  This leads to the exchange between Iceman and Maverick Lieutenant Tom Kazansky (Iceman): "You can be my wingman any time." Maverick: "Bull----! You can be mine." Working in an emergency department takes teamwork and you need to be there for each other. This will be discussed further. 3) Asking for Permission: Sometimes it is better to ask forgiveness than permission. Maverick asks for permission to buzz the tower. He is told no but does it anyway. Maverick: "Requesting permission for flyby". Air Boss Johnson: "That’s a negative Ghostrider, the pattern is full." Maverick and Goose get in trouble for this and learns another valuable lesson. Don’t disobey orders. Remember to put patient care at the centre of your decision making. This means at times you might be treating first and asking for permission from administration later. 4) Lack of Knowledge or Attitude: What gets us into trouble is often not our lack of medical knowledge (or our capacity to absorb new knowledge into our clinical armamentarium), but rather our attitude. Iceman: "Maverick, it's not your flying, it's your attitude. The enemy's dangerous, but right now you're worse. Dangerous and foolish. You may not like who's flying with you, but whose side are you on?" As clinicians, scientists and healthcare leaders, we need to have an attitude that we are a team working together for patients. 5) Time to Think: Often in EM we do not have time to think. We need to make life and death decisions at times quickly on limited information. This is why training and high-fidelity SIM training can be helpful. Maverick: “You don't have time to think up there. If you think, you're dead." 6) Thrive in a Chaotic Environment: The emergency department is often a very chaotic environment. Multiple things happening at the same time can distract us from a patient-centered and empathetic approach to care. Constantly being interrupted. Density of decision making. Cognitive load. An ever-expanding tethering to computers to document more in the electronic health record.  The pressure (personally, professionally, legally) to be correct all the time. But we love it. Charlotte Blackwood (Charlie): "You're not going to be happy unless you're going Mach 2 with your hair on fire." 7) Back Story: Everyone has a back story. We know little about each other. Everyone is potentially fighting a battle we know nothing about. It could help explain and understand certain behaviors. Maverick was struggling with many things but one of them was living in the shadow of his father’s reputation as a navy pilot. Goose: "Every time we go up there, it's like you're flying with a ghost." 8) Teamwork: Optimal emergency care requires a great team working together. This is what was demonstrated in Top Gun. It is not only the pilots that need to perform at a high level but also all the team members that get them in the air, stay in the air and land safety. We could not do what we do without nurses, techs, support staff, etc. And the mission of Skeptics' Guides to shorten the Knowledge Translation (KT) window also requires an exceptional team of medical educators, local opinion leaders, researchers, and Implementation Science experts to be successful. You can learn more about the power of teamwork in Dr. Brian Goldman's book on the subject. 9) Communication: Good communication is such an important aspect of a highly functional team. Maverick: “Talk to me Goose” 10) Clinical Judgment: Where it exists, this is the evidence that informs our care and guides our care, but it should not dictate our care. We need to assess the potential benefits and potential harms and apply the evidence using our clinical judgement and in the context of the situation and the individual patient’s priorities and preferences. Charlie: "A rolling reversal would work well in that situation." Maverick: "If I reverse on a hard cross I could immediately go to guns on him". Charlie: "Yeah, but at that speed it's too fast... a little bit too aggressive." 11) People Still Die: You can do everything right and still patients will die. This is an important lesson to learn in medicine. We try to do our best but everyone will eventually die and you might be the last physician to have contact with that person. Doing the right thing and not committing any errors can still result in a patient dying. This is what happened when Goose died and Maverick was cleared of any wrongdoing. Anything else you learned from watching Top Gun in 1986 compared to re-watching it in 2022? Lt. Chris (EBM) Carpenter I was able to see Top Gun Maverick on Father’s Day when my college-age children were in town for the weekend.  They fooled me by telling me that we were going to see a Pixar movie and then walked me into the Top Gun theater.  As I sat there on Father’s Day 2022, I noticed a philosophical tear emerging from me emotionally.  I had seen Top Gun as a soon-to-be college Freshman in 1986 at a time when I felt young and certain of my worldly knowledge – and completely invincible.  Maverick was me and he was always on the moral high ground in every scene. Fast forward to 2022 and I saw Maverick realizing that he had at times been unnecessarily careless and wanted his students to learn from his mistakes.  With great power comes great responsibility and sometimes that means deviating from the norm, taking a different path that may be less fun or a little more arduous.  Stinger, Jester, and Viper were not trying to hold Maverick back or suppress his talents, they were trying to keep him alive and help him to see that the squadron working as a team was stronger than any individual on that team.  As an older pilot in Top Gun Maverick, he had realized those lessons and helped the team survive impossible odds to succeed. Top Gun Maverick is ultimately a movie about maturing into adulthood and finding redemption for our past mistakes. None of us wants to be wrong, but all of us sometimes are.  That’s life.  While we still have today, we should absorb those lessons, take a deep breath and step into tomorrow with courage, humility, and the ideals that we value.  Carpe diem. The SGEM will be back next episode trying to cut the knowledge translation window down from over ten years to less than one year using the power of social media. The ultimate goal being for patients to get the best care, based upon the best evidence. Remember to be skeptical of anything you learn, even if you heard it on the Skeptics' Guide to Emergency Medicine.

Date: September 15, 2022 Reference:  Ramnarayan P et al. Effect of high-flow nasal cannula therapy vs continuous positive airway pressure therapy on liberation from respiratory support in acutely ill children admitted to pediatric critical care units: a randomized clinical trial. JAMA July 2022 Dr. Spyridon Karageorgos Guest Skeptic: Dr. Spyridon Karageorgos is a Pediatric Resident at Aghia Sophia Childrens’ Hospital, Athens, Greece and a MSc student in Pediatric Emergency Medicine at Queen Mary University London. Case: A 10-month-old male infant presents to the emergency department (ED) with a low-grade fever, rhinorrhea and reduced feeding during the last two days. On exam, you notice increased work of breathing, nasal flaring, grunting with subcostal and intercostal retractions. He’s breathing at a rate of 75 per minute with oxygen saturations of 86% on room air. You make a clinical diagnosis of severe bronchiolitis. You start with low-flow O2 therapy but there is no clinical improvement. You discuss with the family the possibility that the child may need to be admitted in the pediatric intensive care unit (PICU) and require escalation of respiratory support with another modality of non-invasive ventilation. Parents look worried and ask you what kind of non-invasive support are you planning to start? Background: The use of High-Flow Nasal Cannula (HFNC) has increased in both PICU and in the Pediatric ED, especially for infants presenting acutely ill with respiratory distress requiring non-invasive ventilation (NIV). Despite the rise in popularity, there is a lack of high-quality evidence surrounding the use of high flow nasal cannula. Most studies are observational studies rather than randomized control trials (RCTs) [1-3]. Randomized control trials performed demonstrated that the early initiation of high flow nasal cannula led to lower rates of treatment failure/escalation…to high flow nasal cannula[4]. Even results from meta-analyses are mixed [5-6]. The SGEM covered the use of high flow nasal oxygen for bronchiolitis with Dr. Ben Lawton on SGEM #228. The bottom line for that episode was: "High flow oxygen therapy is not required for every child in hospital with bronchiolitis. It will continue to have a role in supporting those with more severe disease, but the potential benefits and harms will need to be considered within the context of where it is being used." There are a few proposed mechanisms for HFNC: Positive pressure Reduced upper airway resistance Washout of dead space in the nasopharynx More comfort from humidified air However, data regarding the clinical effectiveness of HFNC compared to continuous positive airway pressure (CPAP) is limited. In 2018, Ramnarayan et al. performed a multicentre pilot randomised controlled trial of HFNC vs CPAP in paediatric critical care that confirmed the feasibility of performing a large multicenter trial on HFNC vs CPAP in PICU [7]. The FIRST-ABC master protocol included two RCTs, one in acutely ill children requiring respiratory support (Step-Up RCT) and one in children requiring respiratory support after extubation from invasive ventilation (Step-Down RCT), with the aim of assessing the clinical and cost-effectiveness of HFNC as the first-line mode of non-invasive respiratory support in critically ill children. We’re focusing on the Step-Up RCT for today’s episode. Clinical Question: In acutely ill pediatric patients requiring non-invasive ventilation in the PICU, is High Flow Nasal Cannula (HFNC) noninferior to Continuous Positive Airway Pressure (CPAP) in terms of time to liberation from all forms of respiratory support? Reference:  Ramnarayan P et al. Effect of high-flow nasal cannula therapy vs continuous positive airway pressure therapy on liberation from respiratory support in acutely ill children admitted to pediatric critical care units: a randomized clinical trial. JAMA July 2022 Population: Children between 36 weeks (corrected gestational age) and less than 16 years requiring non-invasive respiratory support for acute illness from 24 PICUs and HDUs in the UK between August 2019 and November 2021 Exclusion: Clinical decision to initiate other mode of ventilation (intubation, invasive ventilation), tracheostomy in place, receipt of CPAP or HFNC for >2 hours in the prior to randomization, supplemented O2 at home, presence of air-leak, midfacial/craniofacial anomalies, previously recruited to the FIRST-ABC trial Intervention: HFNC based on body weight Comparison: CPAP of 7 to 8 cm H2 Outcome: Primary Outcome: Time from randomization to liberation from respiratory support which was defined as the start of the 48-hour period during which the child was free from any respiratory support, excluding supplemental oxygen. Secondary Outcomes: Mortality at critical care discharge Rate of intubation at 48 hours Duration of critical care and acute hospital stay Patient comfort Sedation during noninvasive respiratory support Parental stress Adverse events up to 48 hours after liberation from respiratory support Trial: unblinded, multicenter, parallel-group, randomized, non-inferiority trial. Authors’ Conclusions: “Among acutely ill children clinically assessed to require non-invasive respiratory support in a pediatric critical care unit, HFNC compared with CPAP met the criterion for noninferiority for time to liberation from respiratory support” Quality Checklist for Randomized Clinical Trials: The study population included or focused on those in the emergency department. No The patients were adequately randomized. Yes The randomization process was concealed. Yes The patients were analyzed in the groups to which they were randomized. Yes The study patients were recruited consecutively (i.e. no selection bias). No The patients in both groups were similar with respect to prognostic factors. Yes. All participants (patients, clinicians, outcome assessors) were unaware of group allocation. No All groups were treated equally except for the intervention. Unsure. Follow-up was complete (i.e. at least 80% for both groups). Yes All patient-important outcomes were considered. Yes The treatment effect was large enough and precise enough to be clinically significant. Unsure. Financial conflicts of interest. The lead author reported receiving personal fees from two healthcare companies, but we do not think this impacted the results of the article. Results: 600 children (41% of those eligible) were randomized. 573 children (HFNC: 295; CPAP: 278) were included in the primary analysis. 533 children (HFNC: 288; CPAP: 245) were included in the per-protocol analysis. Median age for both groups was around 9 months and 40% were female. Key Result: There were no statistical differences between the HFNC and CPAP groups with regards to time from randomization to liberation from respiratory support. Primary Outcome: The median time to liberation in the HFNC group was 52.7 hours (95% CI, 45.0-60.1 hours) vs 45.4 hours (95% CI, 40.2-53.7 hours) in the CPAP group Absolute difference, 7.3 hours [95% CI –7.3 to 22.2 hours] Adjusted hazard ratio 1.03 [0.86-1.2] Secondary Outcomes:  There was no difference between groups regarding mortality at critical care discharge, patient comfort and parental stress scale. Sedation use was lower in the HFNC group compared to the CPAP group (28% vs 39.2%) Non-invasive Ventilation Devices: This study was attempting to compare HFNC versus CPAP across multiple institutions. However, not all institutions used the same device or interface of delivering HFNC or CPAP. There were 7 different types of devices used across the institutions to deliver HFNC or CPAP. There were 5 or 6 difference CPAP interfaces used. It is hard to guarantee that with this variation, the patients received the same or consistent respiratory support within the same group. The modality of CPAP used may also have impacted patient comfort and decision to switch modalities. Heterogeneous Disease Processes: While most previous HFNC studies have looked specifically at application to children with bronchiolitis, this study includes a patient population with a variety of disease processes including upper airway problems, asthma, cardiac, neurologic, or sepsis/infection. This both a strength and weakness of this study. Including a heterogeneous group may make the results more generalizable. However, it leaves much more (appropriate) flexibility on behalf of the clinician as to what modality of NIV to use. For example, a patient for whom we may want to optimize preload, we may prefer a modality that avoids excessive positive pressure, leading to decrease systemic venous return. Disclaimer: I am skeptical of the ability for HFNC to deliver consistent PEEP especially in children, given that it is an open system, variability to size of cannula and nares, and little control over whether a pediatric patient keeps their mouth open or closed.[8] Selection Bias: As mentioned prior only 41% of eligible patients were randomized in the study. Of the group of that were eligible but not randomized, 35% (325 out of 849) were due to “clinical decision.” The authors cite reasons including preference for HFNC or CPAP, unavailability of PICU (could not initiate CPAP), availability of CPAP masks, cardiac disease, wheeze and unsuitability of CPAP, or unspecified reasons. This may have led to selection bias. Switching between HFNC and CPAP: The decision to switch from HFNC and CPAP and vice versa was based on clinician’s judgement. Even though there were specific criteria for switching, a high rate of patients initially randomized to CPAP group were switched to HFNC (31%), mainly due to discomfort.

Date: September 28th, 2022 Reference: Hartford et al. Disparities in the emergency department management of pediatric migraine by race, ethnicity, and language preference. AEM September 2022. Guest Skeptic: Dr. Lauren Westafer is an Assistant Professor in the Department of Emergency Medicine at the University of Massachusetts Medical School – Baystate. She is the cofounder of FOAMcast and is a pulmonary embolism and implementation science researcher. Case: A 15-year-old patient presents to the Emergency Department with a unilateral pounding headache. The headache is similar to prior migraine headaches. They have photophobia but no vision changes, weakness, numbness, tingling, or neurologic deficits. They took 400 mg ibuprofen at home without relief. The patient and their mother ask what the next steps will be and what type of medication will be administered. Background: We have looked at migraine treatment a few times on the SGEM. That includes an episode on steroids to prevent bounce back visits to the ED (SGEM#28), ketorolac for acute treatment (SGEM#66), acupuncture for prophylaxis (SGEM#211) and a calcitonin gene-related peptide antagonist (SGEM#279). Patients with migraines often present to the ED looking for pain relief. There are many therapeutic options available to clinicians to address their pain. Unfortunately, poor pain control persists despite the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) making pain “the fifth vital sign” in 2001 to raise the awareness of oligoanalgesia in the ED. Despite the limitation of having a subjective measure as a vital sign, the problem of oligoanalgesia (poor pain management) persists (Motov and Khan). Some groups of patients who are at greater risk than others (elderly, women, mentally ill, certain ethnic groups, and insurance status). Children represent one group that is less likely to receive adequate analgesia. (Brown et al, Selbst and Clark). It is not well documented, whether gaps in pain assessment and treatment exist in conditions in which opioids are not indicated, such as migraine headaches. It is hypothesized that race, ethnicity and language (REaL) could also be independently associated with pain control. Clinical Question: Is there an association between patient demographics (race, ethnicity, and language) and pain management among pediatric ED patients presenting with migraine headaches? Reference: Hartford et al. Disparities in the emergency department management of pediatric migraine by race, ethnicity, and language preference. AEM September 2022. Population: All patients treated in a single pediatric ED with at least one migraine-relevant medication using an ED migraine pathway from pathway inception (October 14, 2016) through February 28, 2020. Excluded: Repeat encounters Intervention: Intravenous (IV) medications +/- oral (PO)/intranasal (IN) Comparison: Oral or intranasal medications only Outcome: Primary Outcome: Treatment group assignment according to race, ethnicity and language (REaL) categories. Secondary Outcomes: Pain intensity scores using the age-appropriate scale (FACES or 0-10 pain scale), ED length of stay, ED charges (billing data) Dr. Emily Hartford This is an SGEMHOP episode which means we have the lead author on the show. Dr. Emily Hartford is as assistant professor in Pediatric Emergency Medicine at the University of Washington and Seattle Children’s Hospital.  She works to improve equity for patients of diverse backgrounds in the ED as well as in global partnerships to improve pediatric emergency education. This study was part of a quality improvement project that involved a migraine protocol (see below). Authors’ Conclusions: “In this retrospective analysis of pediatric migraine patients in the ED, we found that race/ethnicity and language for care were significantly associated with odds of receiving intravenous therapies compared to oral or intranasal treatments.” Quality Checklist for Observational Study: Did the study address a clearly focused issue? Yes Did the authors use an appropriate method to answer their question? Yes Was the cohort recruited in an acceptable way? Yes Was the exposure accurately measured to minimize bias? Yes Was the outcome accurately measured to minimize bias? Yes Have the authors identified all-important confounding? Unsure Was the follow up of subjects complete enough? Yes How precise are the results? Somewhat Do you believe the results? Yes Can the results be applied to the local population? Unsure Do the results of this study fit with other available evidence? Yes Conflicts of Interest? None Results: They included 833 pediatric ED patients with migraine in the study. The median age was 14.8 years and two-thirds were female. There were 51% non-Hispanic White (nHW), 23% Hispanic, 8.3% Black or African American, 4.3% Asian.  Of the 833 patients, 546 (65.5%) received intravenous (IV) medications. Key Result: There were differences in the treatment of pain associations with race, ethnicity, and language in pediatric migraine patients. Primary Outcome: Treatment group assignment according to REaL categories. The adjusted odds of receiving IV medication by race/ethnicity was highest among those who identified as non-Hispanic White race with an adjusted odds ratio (aOR) of 1.38 (95% CI 1.02-1.87) and lower among those who self-identified as Asian, Black or African American, or Hispanic. The aOR of receiving IV medication was 1.41 (95% CI 1.13 -1.77) in those who spoke English compared to 0.71 (95% CI 0.57-0.89) in those who spoke a language other than English. Secondary Outcomes: Pain intensity scores using the age-appropriate scale (FACES or 0-10 pain scale), ED length of stay, ED charges (billing data) The change in pain intensity scores over time were similar between PO only treatment and IV treatment groups. However, there was somewhat greater improvement in the IV group. Median LOS was 3.4 hours in the PO only group and 5.2 hours in the IV ± PO group. This gave a median difference of 1.8 hours (95% CI 1.6–2.0). However, there was not any statistically significant differences in this metric based upon race/ethnicity. Median charges were $1,173 for the PO only group and significantly higher at $3,199 for the IV group. They assessed charges for the IV group only because PO/IN charges were likely based on static CPT values by billing coders and had no variability, and reported no statistical differences. 1. Sample Size in Racial Groups: In this study, the majority (51%) of the patients self-identified as non-Hispanic White, with < 5% identifying as Asian (4.2%), 2 or more races (4.6%), or Black/African-American (8.3%). How confident in these comparisons and associations should we be? While the percentage of several REaL groups was indeed small, we did capture every individual patient that presented to our ED on the migraine pathway over the study timespan, so the results reflect what actually happened. Measurements of uncertainty, such as confidence intervals, reflect what might have happened under the same data-generating process as we experienced, and could reflect predictive/future patterns had we not subsequently started an intervention to address these disparities. While our results may or may not generalize to other institutions, they definitely reflect our own experiences, and as such we’re quite confident that the results suggest a need to improve. 2. Selection of Covariates: In your models, covariates included race/ethnicity groups, language type, and insurance type (public/private). Typically, in analyses, we adjust for covariates based on literature or theory. Why were only these included? Are there other important variables that you would have liked to include? There’s a rough statistical rule of thumb that states you need a sample size of about 96 to usefully estimate the intercept (i.e. overall prevalence) in a logistic regression. So even with more than 800 patients in our study, we were still constrained by n size in including either additional variables or estimating interactions (the latter of which typically require an n size 4x higher than non-interaction analyses). You might expect that insurance type and race/ethnicity would have some statistical interactions in the United States, for example, but we did not have the n to estimate that. In addition, insurance type is a rough surrogate for SES in the absence of any other ways to measure SES status of patients; more direct measures of SES would have been nice to include, were they available.   3. Patient-Oriented Outcomes: Your outcomes included IV vs PO/IN, pain intensity, LOS, and charges. Did you collect data on patient preferences or satisfaction with treatment? At the time of our analysis, we did not have access to patient satisfaction data than spanned our timeline, as our hospital had changed survey vendors and had not yet updated the data warehouse with those newer results. In addition, it could be difficult to compare results from two different vendors asking two different sets of patient satisfaction questions. It is an interesting question, however, and it would be nice to know more about that outcome. 4. Generalizability: This was conducted at a single freestanding academic pediatric hospital ED in the US. As a result, patient demographics may be different in other geographic locations and practices may vary at community EDs and those not affiliated with freestanding pediatric hospitals. In addition, REaL is not as “real” in other countries like UK, Europe, Canada, Australia, NZ, Different countries have different ways of measuring and understanding variables such as race and ethnicity. 5.

Date: September 20th, 2022 Reference: Menon et al. Intravenous tenecteplase compared with alteplase for acute ischaemic stroke in Canada (AcT): a pragmatic, multicentre, open-label, registry-linked, randomised, controlled, non-inferiority trial. The Lancet 2022 Guest Skeptic: Professor Daniel Fatovich is an emergency physician and clinical researcher based at Royal Perth Hospital, Western Australia. He is Head of the Centre for Clinical Research in Emergency Medicine, Harry Perkins Institute of Medical Research; Professor of Emergency Medicine, University of Western Australia; and Director of Research for East Metropolitan Health Service. Case: A 74-year-old man arrives from home by private vehicle complaining of right-sided weakness and dysarthria beginning two hours prior to arrival. Advance neuroimaging demonstrates no bleed and no large vessel occlusion. His NIHSS score is calculated to be 10 and he has no absolute contra-indications for systemic thrombolysis. Background: A lot has happened since you were on the SGEM last time discussing stroke (SGEM#325). This includes the CADTH report on thrombolysis by Alteplase for acute ischemic stroke in less than 4.5 hours with a letter to the editor from some neurologists representing CSC expressing their serious concerns about the report. Neurologist Dr. Ravi Garg was on an SGEM Xtra discussing his publication analysing the 1995 NINDS study. He showed the study had a high risk of selection bias. Dr. Garg concluded that the baseline imbalances observed in the NINDS study were more likely due to randomization errors than random chance. His advice was treatment decisions and guideline recommendations based on the original treatment effect reported in the NINDS tPA study should be done cautiously. We also had stroke neurologist Dr. Jeff Saver on an SGEM Xtra discussing his SRMA using the fragility index. He holds a much different interpretation of the stroke literature than Dr. Garg. The conclusion to Dr. Saver’s publication was that intravenous alteplase given within three hours of symptom onset for acute ischemic stroke is one of the most robustly proven therapies in medicine. Besides the disagreement about the strength of the evidence for tPA, there are challenges with administering this medication. It involves giving an infusion of 0.9mg/kg IV to a maximum dose of 90mg. The infusion starts with 10% of the total dose given as a bolus administered in one minute. The remaining amount is infused over 60 minutes.  Tenecteplase (TNK) is a genetically modified variant of alteplase with greater fibrin specificity (15-fold higher) and longer plasma half-life (22 min vs 3.5 min). Because of its ease of use as a single bolus and more favourable benefit-to-risk profile, it is preferred over alteplase as the fibrinolytic agent of choice for acute myocardial infarction. Clinical Question: Is tenecteplase non-inferior to alteplase in treating acute ischemic stroke? Reference: Menon et al. Intravenous tenecteplase compared with alteplase for acute ischaemic stroke in Canada (AcT): a pragmatic, multicentre, open-label, registry-linked, randomised, controlled, non-inferiority trial. The Lancet 2022 Population: Adult patients aged 18 years and older with ischemic stroke who met eligibility criteria for alteplase (ischemic stroke causing disabling neurologic deficit, within 4.5 hours of onset). Patients eligible for endovascular thrombectomy in addition to intravenous thrombolysis were eligible for enrolment. Exclusions: Standard contraindications to IV thrombolysis Intervention: Tenecteplase (0.25 mg/kg) bolus Comparison: Alteplase (0.09 mg/kg bolus + 60 min infusion total 0.9 mg/kg to maximum of 90mg) Outcome: Primary Outcome: Proportion mRS 0-1 at 90 days, up to 120 days Secondary Outcomes: mRS 0-2 at 90-120 days; 90-120 day EQ-VAS & EQ-5D-5L, door to needle time, proportion given endovascular therapy, recanalization status at first angiographic acquisition, baseline CT to arterial puncture time, cognition assessment (online), hospital length of stay, discharge destination. SAFETY outcomes: sICH, oroligual angio-oedema, extracranial bleeding requiring blood transfusion, all < 24 hours of thrombolysis; 90-day all-cause mortality. Type of Trial: Investigator-initiated, multicentre (22 stroke centres), parallel-group, open label, registry linked, RCT with blinded outcome assessment. Authors’ Conclusions: “Intravenous tenecteplase (0.25 mg/kg) is a reasonable alternative to alteplase for all patients presenting with acute ischaemic stroke who meet standard criteria for thrombolysis.” Quality Checklist for Randomized Clinical Trials: The study population included or focused on those in the emergency department. Yes The patients were adequately randomized. Yes The randomization process was concealed. Yes The patients were analyzed in the groups to which they were randomized. Yes The study patients were recruited consecutively (i.e. no selection bias). No The patients in both groups were similar with respect to prognostic factors. No All participants (patients, clinicians, outcome assessors) were unaware of group allocation. No All groups were treated equally except for the intervention. Yes Follow-up was complete (i.e. at least 80% for both groups). Yes All patient-important outcomes were considered. No The treatment effect was large enough and precise enough to be clinically significant. No Financial conflicts of interest. Some authors report a relationship to the manufacturer. Results: They recruited 1,577 patients into the trial. The median age was 74 years and 48% were female. The median baseline NIHSS score was 10. Key Result: Tenecteplase was non-inferior to alteplase in stroke patients treated within 4.5 hours of symptom onset. Primary Outcome: The primary outcome (90–120 day mRS score of 0–1) 36.9% tenecteplase group vs 34.8% alteplase group Unadjusted risk difference 2.1% (95% CI –2.6 to 6.9). The lower bound 95% CI of the difference in primary outcome rate (-2.6%) was greater than -5%, thus meeting the prespecified non-inferiority threshold. Secondary Outcomes: See Table 2 mRS 0-2 at 90-120 days: tenecteplase 56.4% vs 55.6% alteplase; sICH Tenecteplase 3.4% vs alteplase 3.2% (but only recorded to 24 hrs); death within 90 days: tenecteplase 15.3% vs alteplase 15.4%). NB mortality in NINDS was 21% placebo, alteplase 17%; ECASS III: 8.4% placebo, 7.7% alteplase). Extended Thrombolysis in Cerebral Infarction (eTICI) score ≥ 2b on initial angiography of EVT was 10.2% tenecteplase and 10.5% alteplase (n=502). Revised Arterial Occlusive Lesion Score (rAOL) score of ≥  2b on initial angiography of EVT was 19% tenecteplase and 16.3% alteplase (n = 499). 1) Open Label: Open label studies can advantage the new intervention. Blinding treatment allocation is a fundamental element of reducing bias in a clinical trial. The trial participants and clinicians were not blinded to the treatment allocation in AcT. Therefore, the trial was liable to ascertainment bias, sometimes referred to as detection bias. Ascertainment bias is the systematic distortion of the assessment of outcome measures by the investigators or trial participants because they are aware of treatment allocation. It results in an exaggerated difference between the treatments in outcome. Knowledge of the treatment may influence the way in which staff and investigators manage patients during the study and influence the perspectives of patients. Previous studies have attempted to quantify this. Schulz et al (1995) report that ORs were exaggerated by 41% for inadequately concealed trials. [1] Nunan (2018) reports it can overestimate effect size by up to 30% - 40%. [2] Using blinded outcome assessments is an attempt to ameliorate this bias. However, the modified Rankin scale, despite its widespread use as an outcome instrument, shows a wide inter-rater variability that adds to the uncertainty.[3] Bias becomes a critical problem in any open label or poorly blinded trial of thrombolysis. [4]  Considering this bias might lead one to conclude that tenecteplase is not non-inferior to alteplase. 2) Comparison to Other Studies: In NINDS Part 2 (alteplase < 3 hours), a mRS 0-1 was reported as 26% placebo and 39% alteplase. Some argue the result reflected placebo doing badly rather than alteplase being good. In ECASS III (alteplase 3-4.5 hours), the original report for mRS 0-1 was 45.2% placebo and 52.4% alteplase. Subsequent re-analyses of these two foundational trials report different results: NINDS was due to a baseline imbalance in stroke severity favouring alteplase [5]. Saver et al [6] does not agree with the reanalysis by Hoffman and Schriger; in ECASS III the re-analysis concludes “Reanalysis of the ECASS III trial data with multiple approaches adjusting for baseline imbalances does not support any significant benefits and continues to support harms for the use of alteplase 3–4.5 hours after stroke onset. Clinicians, patients and policymakers should reconsider interpretations and decisions regarding management of acute ischaemic stroke that were based on ECASS III results.” [7] In the AcT open label study, they report 36.9% tenecteplase vs 34.8% alteplase (for mRS 0-1) which is obviously for all patients within 4.5 hrs (kind of a combination of NINDS and ECASS III). Comparing results between studies is problematic due to unknown confounders. Also, NINDS was published in 1995 and ECASS III in 2008. Stroke care has evolved over time, and one would have thought that the AcT result would be much better than the ~35% result they got which was a long way short of placebo in ECASS III (45.2%). 3) Outcome Measure: The outcome in this study was the mRS score obtained by telephone interview. There are problems with the inter-rater reliability of the mRS.