The Skeptics Guide to Emergency Medicine

Date: July 13th, 2020 Guest Skeptic: Dr. Justin Morgenstern is an emergency physician and the creator of the excellent #FOAMed project called First10EM.com. He has a great new blog post about increasing diversity in medicine using something called the BSAP approach and an interesting Broome Doc podcast with Dr. Casey Parker called EBM 2.0.   Reference: Ebell et al. Accuracy of Signs and Symptoms for the Diagnosis of Community‐acquired Pneumonia: A Meta‐analysis. AEM July 2020 Case: A 67-year-old woman with no previous health problems presents with fever, cough, and myalgias. You are working with a medical student on their very first rotation, and you want to spend some time teaching them about the history and physical exam. However, being an evidence-based medicine enthusiast, you wonder what aspects of the patient’s presentation are going to be truly helpful in making a diagnosis.  Background: Depending on the time of year, fever and cough can be one of the most common presentations seen in the emergency department. It is important not to miss pneumonia in the sea of viral illnesses. We have covered various aspects of this issue a number of times on the SGEM: SGEM#287: Difficult to Breathe – It Could Be Pneumonia SGEM#286: Behind the Mask – Does it need to be an N95 mask? SGEM#263: Please Stop, Prescribing – Antibiotics for Viral Acute Respiratory Infections SGEM#216: Pump It Up – Corticosteroids for Patients with Pneumonia Admitted to Hospital SGEM#120: One Thing or Two for Community Acquired Pneumonia? Antibiotic overuse is a significant problem, and ordering chest x-rays (CXR) on everyone is inefficient, expensive, and adds potentially unnecessary risk from radiation. Thus, it is important to know how accurate the history and physical exam is for identifying patients with pneumonia. A prior meta-analysis demonstrated that the combination of normal vital signs and normal lung exam effectively rules out pneumonia (Marchellow eat al JABFM 2019), and that a physician’s overall clinical impression is moderately accurate (Dale et al BrJGP 2019). However, there has not been a meta-analysis looking at the evidence for individual signs and symptoms for pneumonia in the last decade. Clinical Question: What is the accuracy of individual signs and symptoms for diagnosing community acquired pneumonia? Reference: Ebell et al. Accuracy of Signs and Symptoms for the Diagnosis of Community‐acquired Pneumonia: A Meta‐analysis. AEM July 2020 Population: Adolescents and adults presenting with symptoms of respiratory infection or clinically suspected pneumonia in the outpatient setting Intervention: Any clinical sign or symptom (including vital signs) for pneumonia Comparison: Outcome: Radiologically confirmed pneumonia (using CXR as the gold standard) Dr. Mark Ebell This is an SGEMHOP episode which means we have the lead author on the show.  Dr. Mark Ebell is a Family Physician and Professor at the University of Georgia in Athens. He is a co-founder of POEMs, editor-in-chief of Essential Evidence, deputy editor of American Family Physician, and co-host of the podcast Primary Care Update and POEM of the Week.   Authors’ Conclusions: “While most individual signs and symptoms were unhelpful, selected individual signs and symptoms are of value for diagnosing CAP. Teaching and performing these high value elements of the physical examination should be prioritized, with the goal of better targeting chest radiographs and ultimately antibiotics. Quality Checklist for Systematic Review Diagnostic Studies: The diagnostic question is clinically relevant with an established criterion standard. Unsure. The search for studies was detailed and exhaustive. Yes The methodological quality of primary studies were assessed for common forms of diagnostic research bias. Yes The assessment of studies were reproducible. Yes There was low heterogeneity for estimates of sensitivity or specificity. Yes/No The summary diagnostic accuracy is sufficiently precise to improve upon existing clinical decision-making models. No Key Results: They identified 16 studies that met their inclusion and exclusion criteria. Seven studies were based in the emergency department and nine in a primary care setting. The number of participants ranged from 52 to 2850. The mean age ranged from 32 to 62 years, and between 48% and 60% of the participants were female. A CXR was used as the gold standard in all studies. The risk of bias was assessed as low in 12 studies and moderate in five. The prevalence of pneumonia was 10% in the primary care studies and 20% in emergency department studies. No individual sign or symptom was good enough to independently rule in or rule out pneumonia. The most helpful indicator was “overall clinical impression”, with a positive likelihood ratio of 6.32 (the highest of any finding) (95% CI 3.58-10.5) and a negative likelihood ratio of 0.54 (95% CI 0.46-0.64). Although a number of symptoms and signs were associated with pneumonia, the low positive likelihood ratios - generally less than 2 – mean that none of these factors are even close to diagnostic on their own. Examples include subjective fever, dyspnea, chest pain, dullness to percussion, crackles, confusion, and toxic or ill appearance. The negative likelihood ratios were even less helpful. We will include a full table with the results in the show notes. The finding with the best test characteristic to rule in pneumonia was egophony, with a positive likelihood ratio of 6.17 (95% 1.34-18.0) when present, although the negative likelihood ratio was only 0.96 (0.93-0.99) The absence of any abnormal vital sign was the best finding for ruling out pneumonia, with a negative likelihood ratio of 0.25 (95% CI 0.11-0.48) 1. Exclusions: You excluded patients from skilled nursing facilities, with chronic lung disease, and immunosuppressed patients. From a pure diagnostic standpoint, that makes sense. However, these are probably the patients in whom it’s most important not to miss a diagnosis of pneumonia. Based on your results, how do you approach the diagnosis in these patients? 2. Other Databases: You limited your search to the Medline databases, whereas we often see systematic reviews search multiple databases to ensure the results aren’t biased by missing published studies. Can you explain for the listeners why a researcher might decide to search one database versus multiple, and whether you think it could significantly affect the results? 3. Imperfect Gold Standard: The signs and symptoms were compared to CXR. We know that a CXR is less accurate in diagnosing CAP than a CT scan. How do you think that could have impacted the results? 4. Prevalence and Possible Selection Bias: Perhaps it is just the community I work in, where everyone wants their viral illness checked in the emergency department, but a 20% prevalence of pneumonia in the emergency department seems quite high to me. Could this represent selection bias, and if so how might that impact the results? 5. Spectrum Bias: In general, these studies included patients in whom the clinician suspected pneumonia, and so presumably are a sicker cohort than all comers with cough. The negative likelihood ratios would probably look better if we included all comers, and we might be misled into over-testing if we try to apply these results to every patient presenting with a cough. 6. Verification Bias: You mention in your methods that you only included studies in which imaging was either performed on all patients, or all high-risk patients with a random sampling of low risk patients, in order to avoid verification bias. Can you explain verification bias to our listeners, and why it might be important when considering this type of literature? 7. Sensitivity vs. Specificity: The only finding with a moderate sensitivity for ruling out pneumonia was the absence of any abnormal vital signs. I worry that people will hear that result and interpret it as if the patient has an abnormal vital sign, they must get imaging. However, the specificity is going to be pretty low – basically every influenza patient is mildly tachycardic. Can you talk about sensitivity, specificity, and how these numbers actually drive your clinical practice? 8. Limited Utility vs. No Utility: It would be pretty easy to look at these numbers and get a little nihilistic. Is the physical exam even necessary? However, there is a difference between a single criterion having limited impact independently, and it having no impact at all. Presumably, the overall clinician’s impression – which was the most accurate finding – included many of these individual findings, so they may add up to more than the sum of their parts. 9. Clinically Significance : A positive CXR does not mean a patient has a bacterial pneumonia. Prescribing antibiotics to a patient with a viral pneumonia is unlikely to have a patient-oriented outcome (POO). Do you think this disease-oriented outcome (DOO) and not a POO is a problem? 10. Are All Clinicians the Same? Overall clinical judgement was the most accurate for diagnosing pneumonia, but I wonder whether all clinicians are equally good. First, do we know what level of training the participants in these studies were. Second, do you think there are ways that we can improve our own clinical judgement when it comes to pneumonia? Comment on Authors’ Conclusion Compared to SGEM Conclusion: We agree with the authors’ conclusion that most individual signs and symptoms are unhelpful on their own, but there are a few high value findings, like normal vital signs, or egophony. These findings can be used to teach the physical exam and may help make better decisions about imaging and antibiotic use. SGEM Bottom Line: No individual sign or symptom is good enough to either rule in or rule out community acquired pneumonia.

Date: June 30th, 2020 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 Royal Perth Hospital. Reference: Alper et al. Thrombolysis with alteplase 3–4.5 hours after acute ischaemic stroke: trial reanalysis adjusted for baseline imbalances. BMJ Evidence Based Medicine 2020 Case: A 65-year-old man arrives from home to the emergency department by EMS with right-sided weakness beginning three hours prior. Advance neuroimaging demonstrates he does not qualify for endovascular clot retrieval. He has an NIHSS score of 11 and no contra-indications for systemic thrombolysis. Background: Thrombolysis for acute ischemic stroke has to be one of, if not the most, controversial subjects of my career. The debate dates back to the classic NINDS paper published in the NEJM in 1995. We reviewed that publication with Dr. Anand Swaminathan on SGEM#70. Some people might argue that it’s less relevant now because of endovascular clot retrieval, but it’s a living example of issues with research methodology, critical appraisal, bias, conflicts of interest, etc. These elements are continuously present in medicine – look at all the COVID-19 literature – made worse by the preprint archives of non-peer reviewed papers. Thrombolysis in acute ischaemic stroke. The Lancet 2012 Truth, thinking and thrombolysis. EMA 2016 Response from Prof. Fatovich to Stroke thrombolysis: Leaving the past, understanding the present and moving forward. EMA 2013 The “Fragility” of Stroke Thrombolysis. TMJ 2020 Believing is seeing: Stroke thrombolysis remains unproven after the third international stroke trial (IST-3). EMA 2012 Don't Just Do Something, Stand There! The Value and Art of Deliberate Clinical Inertia. EMA 2018 Dr. Jerome Hoffman It was Dr. Jerome Hoffman that introduced me to this issue and was a basis of my skepticism. I used to think if the study was published in a high-impact journal it must be true. His mentorship and teaching are why I consider Dr. Hoffman a legend of emergency medicine. We have covered the issue of thrombolysis for acute ischemic stroke a number of times on the SGEM. I have also published a review on the topic of thrombolytics for stroke beyond three hours (Carpenter et al JEM 2011). More recently, I published a pro/con debate on the subject with Dr. Eddy Lange looking at the evidence (Milne et al CJEM 2020). SGEM#29: Stroke Me, Stroke Me SGEM Xtra: Walk of Life SGEM Xtra: No Retreat, No Surrender SGEM#269: Pre-Hospital Nitroglycerin for Acute Stroke Patients? SGEM#290: Neurologist Led Stroke Teams – Working 9 to 5 There has been a lot of skepticism around thrombolysis in acute ischemic stroke since the beginning. A reanalysis of the NINDS data by Dr. Hoffman and Dr. Schriger was published in Annals of Emergency Medicine in 2009. At least one other reanalysis has questioned the 2009 reanalysis (Saver et al Ann Emerg Med 2010).  Thus, there is a degree of uncertainty in the NINDS-II results. The major takeaway from this reanalysis was that the baseline imbalance in stroke severity led to the difference in outcomes. If tPA really works, we should see a bigger change in the NIHSS score in the tPA group vs. the placebo group. Yet the difference was 0.0. People can forget that a clinical trial has internal validity if and only if the imbalance between groups, bias in the assessment of outcome, and chance, have been excluded as possible explanations for the difference in outcomes. Baseline imbalance is a recurring theme. So, replication studies are hugely important. It was the NINDS trial that changed guidelines and practices to provide thrombolysis in patients with stroke symptoms less than three hours after onset. This despite the multiple other trials that did not show efficacy and reported an increase in harm (bleeding). The increase in adverse events prompting some to be stopped early (SGEM Xtra:Thrombolysis for Acute Stroke). The only other randomized control trial claiming benefit for the primary outcome was ECASS III (Hacke et al NEJM 2008). ECASS I and II did not show a benefit with thrombolysis. ECASS III reported a 7% absolute benefit of improved mRS at 90 days compared to placebo, 9% increase in intracranial hemorrhage, 2% increase in symptomatic intracranial hemorrhage and no significant difference in mortality. The American College of Emergency Physicians (ACEP) is the largest organization of EM physicians in the world. ACEP has a clinical policy statement on the issue (Brown et al AEM 2015). They looked at the <3 hour time frame and the 3-4.5 hour time frame. ACEP made no level “A” recommendations but did make level B and C recommendations. Is IV tPA safe and effective for patients with acute ischemic stroke if given within 3 hours of symptom onset? Level B Recommendations: With a goal to improve functional outcomes, IV tPA should be offered and may be given to selected patients with acute ischemic stroke within 3 hours after symptom onset at institutions where systems are in place to safely administer the medication. The increased risk of symptomatic intracerebral hemorrhage (sICH) should be considered when deciding whether to administer IV tPA to patients with acute ischemic stroke. Level C Recommendations: When feasible, shared decision-making between the patient (and/or his or her surrogate) and a member of the health care team should include a discussion of potential benefits and harms prior to the decision whether to administer IV tPA for acute ischemic stroke. (Consensus recommendation) Is IV tPA safe and effective for patients with acute ischemic stroke treated between 3 to 4.5 hours after symptom onset? Level B Recommendations: Despite the known risk of sICH and the variability in the degree of benefit in functional outcomes, IV tPA may be offered and may be given to carefully selected patients with acute ischemic stroke within 3 to 4.5 hours after symptom onset at institutions where systems are in place to safely administer the medication. Level C Recommendations: When feasible, shared decision-making between the patient (and/or his or her surrogate) and a member of the health care team should include a discussion of potential benefits and harms prior to the decision whether to administer IV tPA for acute ischemic stroke. (Consensus recommendation) ECASS III was published in 2008. Now, 12 years later there is a reanalysis of the trial similar to the reanalysis of the NINDS 14 years after it was published. Clinical Question: Is thrombolysis for acute ischaemic stroke in the 3-4.5 hour time frame post symptom onset, safe and effective? Reference: Alper et al. Thrombolysis with alteplase 3–4.5 hours after acute ischaemic stroke: trial reanalysis adjusted for baseline imbalances. BMJ Evidence Based Medicine 2020 Population: Adult patients age 18-80 years of age with at least 30 minutes of acute ischemic stroke symptoms presenting between 3-4.5 hours after onset of symptoms with no significant improvement. Main Exclusion: Intracranial hemorrhage, time of symptom onset unknown, symptoms rapidly improving or only minor before start of infusion, severe stroke as assessed clinically (e.g., NIHSS score >25) or by appropriate imaging techniques*, seizure at the onset of stroke, stroke or serious head trauma within the previous 3 months, combination of previous stroke and diabetes mellitus, administration of heparin within the 48 hours preceding the onset of stroke, with an activated partial-thromboplastin time at presentation exceeding the upper limit of the normal range, platelet count of <100,000/mm2, systolic >185 mmHg or diastolic pressure >110 mmHg, or aggressive treatment (IV medication) necessary to reduce BP to these limits. blood glucose < 50 mg/dL or > 400 mg/dL, symptoms suggestive of subarachnoid hemorrhage, even if CT scan was normal, oral anticoagulant treatment, major surgery or severe trauma within the previous 3 months or other major disorders associated with an increased risk of bleeding. Intervention: tPA 0.9 mg/kg; initial 10% bolus, remainder over 60 minutes Comparison: Placebo Outcome: Primary Outcome: Modified Rankin Scale (mRS) score 0-1 (favourable) vs. 2-6 (unfavourable) at 90 days Secondary Outcomes: Global outcome measure that combined 90 day outcomes of mRS 0-1, >=95 Barthel index, NIHSS score 0-1, score of 1 GOS; mortality at 90 days; any ICH, symptomatic ICH, symptomatic edema (defined as brain edema with mass effect as the predominant cause of clinical deterioration), and other serious adverse events. Authors’ Conclusions: “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 policy makers should reconsider interpretations and decisions regarding management of acute ischaemic stroke that were based on ECASS III results.” 2008 ECASS III Conclusions: “As compared with placebo, intravenous alteplase administered between 3 and 4.5 hours after the onset of symptoms significantly improved clinical outcomes in patients with acute ischemic stroke; alteplase was more frequently associated with symptomatic intracranial hemorrhage.” 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

Date: June 27th, 2020 I had the pleasure of presenting at the Northern Constellation Faculty Development Conference 2020 on May 8th. This was the 9th annual conference put on by the Northern School of Medicine (NOSM). Dr. Sarah McIsaac was kind enough to invite me to present at the Northern Constellation Conference. She is an anesthesiologist/intensivist at Health Sciences North, Assistant Professor and Medical Director of Faculty Development for NOSM. This presentation is available to watch on the SGEM YouTube Channel or listened to on the SGEM podcast. All of the slides can also be downloaded from this link. I was asked to give a presentation about evidence-based medicine (EBM), critical appraisal and relate it back to COVID. Certainly there has been a lot of information coming out on the topic and it can seem like you are drinking from a fire hose at times. The presentation was broken down into three parts: Evidence-Based Medicine (EBM), critical appraisal and the Peltzman Effect (risk compensation): Part I: Evidence-Based Medicine (EBM) It is always good to define terms at the beginning of any discussion. I used the original definition of EBM given by Dr. David Sackett: “The conscientious, explicit and judicious use of current best evidence in making decisions about the care of individual patients.”  (Sackett et al BMJ 1996) There are three pillars to EBM than can be represented in a Venn diagram. People often make the mistake of thinking that EBM is just about the scientific literature. This is not true. The evidence informs and guides our care but it does not dictate our care. EBM also needs your clinical judgement based on your experience. We also need to engage with patients and ask them about their preferences and values. These three components make up EBM: The literature, our judgement and the patients values.  There is a hierarchy to the evidence and we want to use the best evidence so patients get the best care.  The hierarch is usually described as a pyramid with the lowest form of evidence being expert opinion and the highest level being a systematic review. This is an over simplification of the levels of evidence. A good randomized control trial (RCT) can be more informative than a systematic review (SR) that only includes low quality study (GIGO - garbage in, garbage out). There are arguments against EBM and it does have limitations. One that is often pointed out is that it would be unethical to do an RCT on harm. The 2003 Smith and Pell parachute trial is usually pointed to as an example (BMJ 2003). This could be considered a straw man argument because most medical practices are not parachutes (Hayes et al CMAJ 2018). In addition, a randomized control trial has been done assessing the efficacy of parachutes to prevent gravitationally related morbidity and mortality and was reviewed on SGEM#284. Five alternatives to EBM were discussed (Adapted from Isaacs and Fitzgerald BMJ 1999) : Eminence-Based Medicine (EmBM): The more senior the colleague, the less importance he or she placed on the need for anything as mundane as evidence. Experience, it seems, is worth any amount of evidence. These colleagues have a touching faith in clinical experience, which has been defined as ‘‘making the same mistakes with increasing confidence over an impressive number of years.” The eminent physician’s white hair and balding pate are called the “halo” effect. Vehemence-Based Medicine (VBM): The substitution of volume for evidence is an effective technique for brow beating your more timorous colleagues and for convincing relatives of your ability. Eloquence-Based Medicine (ElBM): The year round suntan, silk tie, Armani suit, and tongue should all be equally smooth. Sartorial elegance and verbal eloquence are powerful substitutes for evidence. Nervousness-Based Medicine (NBM): Fear of litigation is a powerful stimulus to over investigation and over treatment. This may be a greater factor in the US while in Canada it might be more of being shamed or reported to the College. In an atmosphere of litigation/shame phobia, the only bad test is the test you didn’t think of ordering. Confidence-Based Medicine (CBM): This is restricted to surgeons. EBM is like democracy, it is the worst form of medicine except all the others that have been tried. Part II: Five Steps of Critical Appraisal Step 1: Use a PICO (population, intervention, comparison/control and outcome) to formulate the clinical question you are trying to answer Step 2: Search for the best evidence (try the TRIP Database) Step 3: Find the least bias evidence (bias is something that systematically moves us away from the “truth” not just noise in the data) Step 4: Critically appraise the literature using a quality check list (SGEM Make it So) Step 5: Decide if it is practice changing (consider the number needed to treat for benefit [NNTB] and the number needed to treat for harm [NNTH]) Then once you have done all that you can discuss it with the patient in front of you to ask about their preferences and what they value. There is an excellent video summarizing this process made by Dr. James McCormick and called Viva La Evidence. Part III: The Peltzman Effect (Risk Compensation) Sam Peltzman was a professor at the University of Chicago in the 1970’s. He wrote this classic paper about seatbelt regulations for cars. The lab data (tech studies) implied annual highway deaths would be 20% greater without mandating seatbelt in all cars. He argued that these benefits would be offset by more pedestrian deaths and more nonfatal accidents because of “driving intensity”. This was driving faster and more recklessly with the security of the safety belt. Ultimately, Dr. Peltzman hypothesis about seat bests was shown to be wrong and they do have a net benefit. However, the idea of risk compensation where people adjust their behaviour in response to the perceived level of risk has been named The Peltzman Effect. There are example of where an intervention did have a positive outcome (seat belts and bike helmets) but there are other examples where it did not (parachutes and electronic health records). A good article on risk compensation in medicine is by Prasad and Jena 2014. COVID19 Management Strategies The presentation ended with a discussion around COVID19. Clinicians and researchers have been throwing the kitchen sink at the disease. Medication include: Azithromycin, Steroids, Famotidine, IL-6 inhibitors, Chloroquine/Hydroxychloroquine, Remdesivir, Vitamin C, Zinc, etc. Non-pharmacologic strategies to address this terrible global pandemic were also mentioned. this included the recommendation of universal mandatory mask wearing in public and the orders to shelter at home. Some of the unintended consequences of these strategies were raised. The precautionary principle was also briefly mentioned as part of this section.A shout out to Dr. T. Greenhalgh who has been promoting this approach in the medical literature (Greenhalgh et al BMJ 2020). A rapid response to this article and the precautionary principle was published (Martin et al BMJ 2020). There has even been a rebuttal to the response (Greenhalgh J Clin Eval Prac 2020). Will these social measures have a net positive impact on COVID19? I don't know. The strength of any of our recommendations should at least be in part proportional to the evidence. Any intervention can have potential benefits and potential harms. It is a cognitive bias that we over estimate benefit and underestimate harm. Anyone who says they know what the net impact of these social policy is expressing some hubris. My position is "I don't know" and it was Dr. Richard Feynman who famously said "it's ok to say...I don't know". The audience was then encouraged not to forget our past mistakes from a previous global pandemic. Jeanned Lenzer and Shannon Brownlee wrote a wonderful article about how pandemic science is out of control. Here is just the first paragraph from their article: "On September 14, 1918, in the midst of the worst pandemic in modern history, an article in the New York Times quoted Dr. Rupert Blue, then surgeon general of the US Public Health Service. Blue reported that doctors in many countries were treating their influenza patients with digitalis and the antimalaria drug quinine. There was no evidence that the two drugs were any more effective than folk remedies being used by patients, including cinnamon, goose grease poultices, and salt stuffed up the nose, but doctors were desperate and willing to try just about anything. They would eventually abandon quinine and digitalis as treatments for flu when studies showed they were not only ineffective but caused serious and sometimes deadly side effects." The New England Journal of Medicine also published an excellent article by Zagury-Orly and Schwartzstein called "COVID19 - A Reminder to Reason". The last paragraph was very poignant. “We are living through an unprecedented biopsychosocial crisis; physicians must be the voice of reason and lead by example. We must reason critically and reflect on the biases that may influence our thinking processes, critically appraise evidence in deciding how to treat patients, and use anecdotal observations only to generate hypotheses for trials that can be conducted with clinical equipoise. We must act swiftly but carefully, with caution and reason." The presentation ended with a reminder that it can feel like health care workers and essential service workers have the weight of the world on their shoulders. It is OK not to be OK. You do not need to be a super hero. Asking for help is a sign of strength and insight and not a weakness. Take good care of yourself so you can take good care of the patients.

Date: June 14th, 2020 Guest Skeptic: Dr. Dennis Ren is a Pediatric Emergency Medicine fellow at Children’s National Hospital in Washington, DC. Reference: Kuppermann et al. A Clinical Prediction Rule to Identify Febrile Infants 60 Days and Younger at Low Risk for Serious Bacterial Infections. JAMA Pediatr. 2019. Case: A 5-week-old full term female presents to the Emergency Department (ED) for fever with rectal temp of 100.6F (38.1C). Her mother states that she has been fussier today. She also seems “congested” and is not feeding as well. She continues to have the usual number of wet diapers. The mother is worried about her sick baby. She wants to know if they will need a spinal tap, be placed on antibiotics or will need to be admitted to the hospital? Background: Fever without source in infants less than three months old represents a significant diagnostic dilemma for clinicians. Several criteria have been developed previously, including the Rochester (Jaskiewicz et al 1994), Boston (Baskin et al 1992) and Philadelphia (Baker et al 1993) criteria to help clinicians stratify the risk of serious bacterial infections (SBI). Febrile infants commonly present to the emergency department. It is estimated 8-13% may have SBI that may include urinary tract infections, bacteremia, and bacterial meningitis. It is difficult to identify which infants have SBI by clinical examination alone. There are serious consequences from missed SBI. Workup for SBI may include lumbar puncture, antibiotics, and hospitalization. These criteria (Rochester, Boston and Philadelphia) could be considered out of date in our current era of vaccinations. We covered a new protocol called the Step-by-Step approach on SGEM#171. The “Step-by-Step”rule combined both clinical factors and laboratory factors in febrile infants aged 22 to 90 days. It had a sensitivity of 98.9% to detect all SBIs. The SGEM Bottom Line #171: “If you have availability of serum procalcitonin measurement in a clinically-relevant time frame, the Step-by-Step approach to fever without source in infants 90 days old or younger is better than using the Rochester criteria or Lab-score methods. With the caveat that you should be careful with infants between 22-28 days old or those who present within two hours of fever onset.” It is important to balance the consequences of missing an SBI with performing unnecessary procedures (lumbar punctures), exposing infants to antibiotics, and prolonging hospital stay. The new study proposes a novel way of identifying low risk febrile infants 29-60 days based on three objective lab criteria. Clinical Question: Can a clinical prediction rule (tool) using laboratory data identify febrile infants under 60 days of age who are at low risk for serious bacterial infection (urinary tract infection, bacteremia, and bacterial meningitis) and reduce unnecessary lumbar punctures, antibiotic exposure, and hospitalization? Reference: Kuppermann et al. A Clinical Prediction Rule to Identify Febrile Infants 60 Days and Younger at Low Risk for Serious Bacterial Infections. JAMA Pediatr. 2019. Population: Febrile infants <60 days of age who look good and whose blood cultures were obtained to rule out SBI (fever was a rectal temperature of at least 38C) Excluded: Infants who looked critically ill, had antibiotics in the previous 48 hours, history of prematurity (≤36 weeks’ gestation), pre-existing medical conditions, indwelling devices or soft tissue infections. Intervention: Derivation and validation of accurate clinical prediction rule (tool) for infants at low risk of SBI using a negative urinalysis, ANC <4,090/uL, and procalcitonin 1.71 ng/ml or less Comparison: Pre-existing algorithms combining subjective clinical findings and lab markers Outcome: Accuracy of the prediction rule to identify infants at low risk for SBI (sensitivity, specificity, negative prediction value and negative likelihood ratio). SBI was defined as bacterial meningitis, bacteremia or UTI. UTI was defined as growth of a single urine pathogen with at least 1,000 cfu/ml on culture obtained by suprapubic aspiration, at least 50,000 cfu/ml from catheterized specimens or 10,000-50,000 cfu/ml from catheterized specimens in association with an abnormal urinalysis (presences of leukocytes esterase, nitrite or pyuria). Authors’ Conclusions:“We derived and validated an accurate prediction rule to identify febrile infants 60 days and younger at low risk for SBIs using the urinalysis, ANC, and procalcitonin levels. Once further validated on an independent cohort, clinical application of the rule has the potential to decrease unnecessary lumbar punctures, antibiotic administration, and hospitalizations.” Quality Checklist for Clinical Decision Tools: The study population included or focused on those in the ED. Yes The patients were representative of those with the problem. Yes All important predictor variables and outcomes were explicitly specified. Yes This is a prospective, multicenter study including a broad spectrum of patients and clinicians (level II). Yes Clinicians interpret individual predictor variables and score the clinical decision rule reliably and accurately. Yes This is an impact analysis of a previously validated CDR (level I). No For Level I studies, impact on clinician behavior and patient-centric outcomes is reported. N/A The follow-up was sufficiently long and complete. Unsure The effect was large enough and precise enough to be clinically significant. Unsure. Key Results: The study included 1,821 febrile infants <60 days of age who had blood cultures collected. The mean age was 36 days old, 42% female, 2/3 had a fever of <12 hours prior to the ED visit, median YOS was 6.0 and SBI positive in 9.3% (7.7% from UTI alone). Low risk prediction rule was derived based on three variables: Normal urinalysis Absolute Neutrophil Count (ANC) ≤4,090/µL Serum procalcitonin ≤1.71 ng/ml Sensitivity of 97.7%, specificity of 60%, NPV of 99.6% and LR- of 0.04. No infants with bacterial meningitis were missed. There were 1,266 infants >28 days of age. The clinical prediction rule stratified 776/1,266 (61.3%) as low risk for SBI. Of that low risk subgroup, 523/776 (67.4%) had lumbar punctures performed. This is the number of lumbar punctures that could possibly be avoided in this age group for low-risk patients. Overall, this is a very well-executed study with practice changing potential. The PECARN group does some great research. We covered the very important paper by Kupperman et al (NEJM 2018) looking at fluid infusion rates for children with diabetic ketoacidosis on SGEM#255. 1) Procalcitonin: This study lost a portion of eligible participants due to procalcitonin sample issues (41%). It is difficult to say whether or not this would have changed the results or analysis. The authors state that this group was similar to those with the procalcitonin measurements. There is a slight difference in SBI positive percentage in those who have procalcitonin test results available compared to those who did not (9.3% vs. 12%). Laboratory tests besides procalcitonin like CRP, band counts and viral studies were not included. Past studies demonstrate concurrent viral infections may decrease risk of SBI but does not exclude SBI. The procalcitonin samples were centrifuged and frozen at -80C, batched, and all sent to a central laboratory. This can increase the precision of the results by decreasing variability. Having 26 different laboratories running the procalcitonin levels could introduce more variability into the results. This would potentially decrease the precision by increasing the 95% confidence interval around the point estimate for the diagnostic accuracy of the clinical prediction rule. To avoid over-fitting the data, they rounded off the ANC to 4,000/uL but more significantly decreased the procalcitonin level from 1.71 ng/ml to 0.5 ng/ml to see what would happen to the diagnostic accuracy. The sensitivity remained identical and the specificity decreased a little with rounding off the ANC and decreasing the procalcitonin level. 2) Urinary Tract Infection: The definition used in this study followed the AAP guidelines that we detailed in the PICO. However, they did use a lower threshold for colony forming units.The reason for including this lower threshold was to account for lower colonies of bacteria sometimes found in urine of younger infants. This definition makes the prediction rule a bit more conservative. 3) Younger vs Older Infants: There was a difference between the two subgroup of infants identified a priori. Overall, 9.3% had SBIs but it was 13% in younger infants (≤28 days of age) vs. 7.7% in the older population (infants >28 days of age). Most of the SBI were UTI. Five infants had bacteremia and meningitis. Ten infants had UTI and bacteremia. One poor infant in the ≤28-day age group had UTI, bacteremia, and meningitis. 4) Number of Cases: We need to be careful about just considering negative predictive value (NPV). NPV is dependent on prevalence of disease while likelihood ratios are not dependant on prevalence of disease. They identified 170 infants with SBI (9.3%) which gives a fairly tight 95% CI for NPV. However, there were only four cases of bacterial meningitis alone (0.2%) which can make the NPV look pretty good (100%) but with very wide 95% CI. We cannot just consider the number of cases identified but also the number of missed cases. In this study there were three missed cases of SBI using the clinical prediction rule.  Two of the missed patients had culture positive urine without pyuria (E. coli and Pseudomonas) were in validation set. One patient with positive blood culture for Enterobacter cloacae was in derivation set but repeat blood cultures prior to antibiotics were never positive.

Date: June 9th, 2020 Guest Skeptic: Dr. Chris Bond is an Emergency Medicine Physician and Assistant Professor at the University of Calgary. He is also an avid FOAM supporter/producer through various online outlets including TheSGEM. Reference: Westafer et al. Provider Perspectives on the Use of Evidence-based Risk Stratification Tools in the Evaluation of Pulmonary Embolism: A Qualitative Study. AEM June 2020. Case: A 63-year-old female presents to the emergency department (ED) with chest pain for the past eight hours. It is pleuritic, worse with certain movements and associated with some shortness of breath. Her vital signs are within normal limits and oxygen saturation is 95% on room air. An ECG, chest x-ray and troponin are all within normal limits and she has no calf swelling or tenderness. She does have a previous history of DVT/PE 12 years ago after returning from a transatlantic flight. She has also been doing more work around the house and lifting the past few weeks because of COVID and has some mild chest wall tenderness on palpation. The remainder of her Wells’ criteria are unremarkable. How do you proceed in evaluating this patient for pulmonary embolism (PE)? Background: Pulmonary embolism is a common ED diagnosis with an estimated 1-2% of all patients presenting to United States EDs undergoing CT for suspected PE (1). However, less than 10% of these scans show PE (2-4). We have covered the topic of PE frequently on the SGEM. SGEM#51: Home (Discharging Patients with Acute Pulmonary Emboli Home from the Emergency Department) SGEM#118: I Hope you Had a Negative D-dimer (ADJUST PE Study) SGEM#126: Take me to the Rivaroxaban – Outpatient treatment of VTE SGEM#163: Shuffle off to Buffalo to Talk Thrombolysis for Acute Pulmonary Embolism SGEM#219: Shout, Shout, PERC Rule Them Out SGEM#277: In the Pregnant YEARS – Diagnosing Pulmonary Embolism SGEM#282: It’s All ‘bout that Bayes, ‘Bout that Bayes- No Trouble – In Diagnosing Pulmonary Embolism There are multiple validated risk stratification tools to evaluate for PE and reduce inappropriate testing, including the Pulmonary Embolism Rule Out Criteria (PERC), Wells’score, YEARS algorithm and D-Dimer testing (5-7). There have also been more recent adjustments to D-Dimer threshold based on clinical probability as calculated by a trichotomized Wells score (8). Unfortunately, clinician uptake of these validated tools has been incomplete, with some ED studies finding 25% of patients who warranted no laboratory or imaging studies still received testing (4, 9-12.) Low-value testing increases costs, ED length of stay and subjects patients to unnecessary ionizing radiation and risk of anaphylaxis from intravenous contrast dye (13-14).  Moreover, false positives CT scans are common and estimated to be between 10-26%, resulting in unnecessary anti-coagulation and risk to patients (15-17). This can ultimately lead to over-testing, over-diagnosing and over-treating. The American Board of Internal Medicine (ABIM) started the project called Choosing Wisely to try and mitigate this problem. The SGEM looked at this imitative on an SGEM Xtra. The American College of Emergency Physicians (ACEP) is part of the Choosing Wisely program and has a number of recommendations. One of the recommendations is on CT scans for ruling out PE. They have encouraged physicians to” “Avoid CT pulmonary angiography in emergency department patients with a low-pretest probability of pulmonary embolism and either a negative Pulmonary Embolism Rule-Out Criteria (PERC) or a negative D-dimer.” ACEP 2014 The Right Care Alliance (RCA) was established in 2015. Certainly, patients at times need less care but they also at times need more care. This group’s goal is to advocate for the goldilocks zone of care, not too much but also not too little (SGEM Xtra). Clinical Question: What are the barriers and facilitators to the uptake of evidence-based practice in the ED evaluation for pulmonary embolism? Reference: Westafer et al. Provider Perspectives on the Use of Evidence-based Risk Stratification Tools in the Evaluation of Pulmonary Embolism: A Qualitative Study. AEM June 2020. Dr. Lauren Westafer As this is a qualitative study, we will use a modified PICO question Population: Emergency physicians Interest: The use of evidence-based risk stratification tools Context: The evaluation of acute pulmonary embolism This is an SGEMHOP episode and we have the lead author of this quantitative study, Dr. Lauren Westafer. Lauren is an emergency medicine physician practicing in Massachusetts, and avid FOAM producer. Authors’ Conclusions: “Our findings suggest that common barriers exist to the use of risk stratification tools in the evaluation of pulmonary embolism in the ED and provide insight into where to focus efforts for future implementation endeavors. Overall, provider-level factors such as risk avoidance and lack of knowledge of the tools dominated as barriers, while inner-setting factors were identified as facilitators. Future efforts to improve evidence based diagnosis of pulmonary embolism should focus on implementation strategies targeting these domains.” CASP Checklist for Qualitative Research Was there a clear statement of the aims of the research? Yes Is a qualitative methodology appropriate? Yes Was the research design appropriate to address the aims of the research? Yes Was the recruitment strategy appropriate to the aims of the research? No. Emails were sent to a purposive sample of physicians, many of whom were colleagues of the principal investigators and thus there would be bias as to those physicians potentially known practice patterns and potential responses. We do know that two physicians declined, and an effort was made to have a cross-section experience (years in practice), gender and practice setting (academic vs. community based). Was the data collected in a way that addressed the research issue? Yes Has the relationship between researcher and participants been adequately considered? Unsure. As before, the researcher was a colleague with six of the 23 study participants, this will introduce some bias. Have ethical issues been taken into consideration? Yes Was the data analysis sufficiently rigorous? Yes Is there a clear statement of findings? Yes How valuable is the research? The external validity of this study is seriously questionable given the small number of participants and practice setting of four Northeastern US emergency settings. There may be generalizability to the American practice setting, but I question its applicability in Canada, Europe, the ANZACS and other areas of the world. That said, there is value in recognizing what barriers and facilitators practicing physicians find for the use of any clinical decision making or decision instrument. The same themes often emerge regardless of where you are in the world. For example, fear, anxiety, uncertainty, knowledge gaps and medicolegal risk are all barriers that need to be addressed when working up patients for any disease process. The study also identifies that physicians are more comfortable making decisions that are clearly aligned with institutional goals/policies as well as in line with their colleagues practice patterns. Audit and feedback were also identified as a helpful tool by some physicians. Audit and feedback can be an extremely powerful tool if delivered well, I will encourage those who are interested to read the following paper. “Audit and Feedback for individual practitioners in the Emergency Department: An Evidence-based and Practical Approach” was recently published in CJEM and covers critical elements of implementing an ED based audit and feedback program (Dowling et al CJEM 2020). Key Results: They had 23 physicians from a total of 12 academic and community hospitals in New England were interviewed. Two potential participants declined. Participants had a median of 14 years in practice, 48% practiced solely in an academic setting, 20% practiced exclusively in a community ED and the remaining 32% practiced in a combination of academic and community EDs. All clinicians reported some familiarity and some use of risk-stratification tools, particularly PERC in the workup of PE. Barriers: Clinician-level barriers to use of risk-stratification tools centered on knowledge, belief about consequences and emotions. There was a lack of knowledge regarding validated cutoffs for the Wells score, lack of knowledge of a trichotomized Wells threshold, and most providers would only use a D-dimer for patients with a Wells score less than or equal to 3. Providers reported more confidence in their gestalt than risk stratification tools. They commonly reported that if a patient satisfied “PE is the most likely diagnosis” or there was a prior history of venous thromboembolism (VTE) or had active malignancy, the patient would automatically be too high risk to order a D-Dimer. Beliefs about consequences of using the tools, particularly risk avoidance and fear of missing PE were also common provider-level barriers. Nearly all participants were unaware of existing professional guidelines on PE. Facilitators: Study participants reported facilitators primarily at the level of the institutional setting. All clinicians felt that institutional support and a clear easy-to-follow algorithm endorsed by their hospital or group would facilitate their use of evidence-based approaches. This would also need to be easily accessible on shift. They also felt this would provide perceived medicolegal protection and establish a cultural norm of practice, and cited peer pressure as a root cause to motivate them to change practice. Clinicians felt that simplicity of PERC facilitated its use, while the element of gestalt incorporated into Wells made it more challenging to use.

Date: June 2nd, 2020 Reference: Permpikul et al. Early Use of Norepinephrine in Septic Shock Resuscitation (CENSER): A Randomized Trial. Respir Crit Care Med 2019. Guest Skeptic: Dr. Max Hockstein trained as an Emergency Medicine physician at University of Texas Southwestern and is finishing his Intensive Care fellowship at Emory. Max is then going to Georgetown to be an attending in both EM and ICU. Case: It’s another day in your emergency department (ED).  Six hours into your shift, you finish dispo’ing the “really quick sign-out” from the night before.  The triage nurse places a 61 year-old-man with fever, hypotension, cough into the smallest room in the ED.  You scan through the EMR and see the blood pressure is 60/40.  Being an astute emergency physician, you surmise that this value is one number column short of normal.  It’s uncomfortably low – is it time to start a norepinephrine infusion? Background: I think we have covered sepsis more often than any other topic on the SGEM. It was the landmark paper published 19 years ago by Dr. Emanuel Rivers on early goal directed therapy in the treatment of severe sepsis and septic shock that sensitized the medical community (Rivers et al NEJM 2001). SGEM#44: Pause (Etomidate and Rapid Sequence Intubation in Sepsis) SGEM#69: Cry Me A River (Early Goal Directed Therapy) ProCESS Trial SGEM#90: Hunting High and Low (Best MAP for Sepsis Patients) SGEM#92: ARISE Up, ARISE Up (EGDT vs. Usual Care for Sepsis) SGEM#113: EGDT – ProMISe(s) ProMISe(s) SGEM#174: Don’t Believe the Hype – Vitamin C Cocktail for Sepsis SGEM#207: Ahh (Don’t) Push It – Pre-Hospital IV Antibiotics for Sepsis. One of the goals of the early treatment of septic shock is to restore end-organ perfusion.  Significant effort has been placed on the administration of IV crystalloids to address concerns for hypovolemia in septic shock.  However, it has become evident that patients are often over-resuscitated with IV fluids which adversely impacts outcome.  As such, the idea of the early norepinephrine administration to restore end-organ perfusion in septic shock has been suggested. Monitor-Oriented Outcomes (MOOs) Trials that examine outcomes in shock, historically, have examined two types of outcomes: patient-oriented outcomes (POOs) and monitor-oriented outcomes (MOOs).  POOs focus on occurrences that matter to patients while MOOs do not.  Many trials examining vasoactive infusions use MOOs as an endpoint(s) targeted to the medication’s intended use (i.e. increase in MAP).  Much like titrating a therapy to an outcome, MOOs are frequently easier to monitor (ex: blood pressure, heart rate, mean arterial pressure, oxygen saturation, etc). An old adage in resuscitating the hypotensive patient “first, fill the tank” has gone largely unchallenged over the past several years.  Oddly enough, however, shortening the duration of shock time-to-shock-resolution hasn’t translated to any measurably better outcomes. Clinical Question: Does starting norepinephrine earlier in septic shock lead to earlier shock control? Reference: Permpikul et al.Early Use of Norepinephrine in Septic Shock Resuscitation (CENSER): A Randomized Trial. Respir Crit Care Med 2019. Population: Adult patients (18 year of age and older) presenting to the ED with a mean arterial pressure (MAP) < 65 mmHg. Infection needed to be the suspected cause of the hypotension. Patients also had to meet 2012 surviving sepsis diagnostic criteria. Exclusions: Acute cardiac and cerebral conditions, pulmonary edema, status asthmaticus, gastrointestinal bleeding, pregnancy, burn, drug overdose, trauma, need immediate surgery and cancer. Intervention: Early norepinephrine adjusted to 0.05ug/kg/min for 24hrs plus usual care Comparison: Placebo plus usual care (intravenous fluids, appropriate antibiotics, source control and organ support as directed by the attending physician) Outcome: Primary Outcome: Shock control (sustained MAP > 65mmHg) by six hours after diagnosis of sepsis with hypotension together with adequate tissue perfusion (urine flow >0.5ml/kg/h for two consecutive hours or a decrease in serum lactate by > 10% from the initial lactate level). Secondary Outcomes: 28-day mortality and hospital mortality, time from initial treatment to achieving target MAP and tissue perfusion goal (and within six hours), urine output within six hours, rate of respiratory failure requiring mechanical ventilator support, rate of renal failure requiring renal replacement therapy, lactate clearance, and number of organ support-free days to day 28 were also recorded. Authors’ Conclusions: “Early norepinephrine was significantly associated with increased shock control by 6 hours. Further studies are needed before this approach is introduced in clinical resuscitation practice.”       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. Yes All participants (patients, clinicians, outcome assessors) were unaware of group allocation. Unsure 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. Yes The treatment effect was large enough and precise enough to be clinically significant. Unsure Key Results: There were 310 patients included in the trial. The median age was in the late 60’s with slightly more females. The main sources of infections were urinary tract 30%, pneumonia 25%, intra-abdominal 20%, skin and soft tissue 10%. Shock control was significantly higher in early norepinephrine group Primary Outcome: Shock control by six hours was 76.1% in early norepinephrine group vs. 48.4% in the control group. 1) Time-to-Shock-Control: Intuitively, you would think that the less time that people spend in hemodynamic "shambles", the better they would do. Think of all the trials that tried to improve time-to-shock-control like the CORTICUS trial.ed This probably has something to do with our evolution and the human ability to withstand wide ranges of hemodynamic derangements.  Regardless, no study has been able to show that the less time patients spend in shock, the better they will do. The metric they used for shock-control (urine output and lactate clearance) were suboptimal. Neither of these clearly demonstrates shock control.  Lactate clearance is unreliable and can be misleading- especially in patients that are receiving therapies that increase the concentration of glycolytic intermediates or increase their clearance. 2) Blinding: There is a possibility that the study was unblinded. This is because the norepinephrine gives a rapid rise blood pressure which could be noticed by the treating clinician. The unblinding could have introduced some bias into the trial. The researchers could have checked on this by asking the clinicians to guess patient group allocation. 3) MOOs and POOs: Do you really think patients care how long it took them to get shock-control, what their lactate level or urine output is per hour or what was their MAP? These are monitor-oriented outcomes (MOOs). What patients care about more is being dead or alive (80’s tune Dead or Alive) which would be a patient- oriented outcome (POO). An even better POO would be alive and physically well. 4) Intravenous Fluids: Early norepinephrine use didn’t decrease the amount of volume people received. So, maybe, despite having earlier shock control, the tendency was to complete 30 mL/kg mandate.  It is a weird predicament we’ve placed ourselves into where we have to think about a catecholamine as a “fluid-sparing agent.”  Our goal should be to stop people from going from raisin to grape, so we don’t have to take them from grape to raisin later (if we get the chance). 5) Adverse Events: The observed adverse events in this trial also told us what we already know: skin necrosis rates were equal between the two groups. Also note that half of the patients got norepinephrine through a peripheral line.  There was less cardiogenic pulmonary edema in the early norepinephrine group, however, this was puzzling since the groups received approximately the same amount of IV fluid.  This may be because of the (trivial) beta-1 effects of the norepinephrine.  There were also less new-onset arrhythmias in the early norepinephrine group. Comment on Authors’ Conclusion Compared to SGEM Conclusion: We agree with the authors that norepinephrine raises blood pressure, MAP, urinary output and lactate clearance.  However, we did not need a study to tell us that information.  This makes the paper’s conclusion no better than the ATHOS-3 trial.  This paper showed that giving NE early is feasible and not unreasonable. SGEM Bottom Line: Early norepinephrine can change some MOOs (MAP, lactate, urinary output) but does not seem to change any POOs  (in-hospital or 28-day mortality) in adult patients with septic shock. Case Resolution: While a bag of isotonic crystalloid of choice is being infused through one peripheral IV, fixed-dose norepinephrine at 0.05 ug/kg/min is started through the other.  The patient is then taken to the intensive care unit where he makes a full recovery after three days of treatment for his community acquired pneumonia. Dr. Max Hockstein Clinical Application: This trial does not change anything for me. Hypotension is an emergency and as emergency physicians, we are good at treating it.

Date: May 29th, 2020 Reference: Erramouspe et al. Mortality and Complication Rates in Adult Trauma Patients Receiving Tranexamic Acid: A Single-center Experience in the Post–CRASH-2 Era. AEM May 2020 Guest Skeptic: Dr. Corey Heitz is an emergency physician in Roanoke, Virginia. He is also the CME editor for Academic Emergency Medicine. Case: A 44-year-old male presents to your level 1 trauma center by EMS after a motor vehicle collision. He is hypotensive and tachycardic. You suspect abdomen and pelvic trauma and calculate his injury severity score (ISS) to be 22. Your hospital protocol is to give tranexamic acid (TXA) 1g IV over 10 minutes followed by a 1g infusion over eight hours. You wonder what his over-all chance of dying or developing a thromboembolic event when treated with TXA. Background: TXA is synthetic derivative of lysine that controls bleeding by inhibiting fibrinolysis and thus stabilizing clots that are formed.  We have covered TXA as a treatment modality a number of times on the SGEM. The evidence for TXA providing a patient-oriented outcome (POO) has been mixed. It seems to work for epistaxis (SGEM#53 and SGEM#210), failed to demonstrate a decrease in all-cause mortality in post-partum hemorrhage (SGEM#214), and did not result in an improved neurologic outcome in hemorrhagic strokes (SGEM#236). REBEL EM has looked at using TXA for those conditions plus a few others (we will include a table in the show notes). It is unclear if it provides a benefit for gastrointestinal bleeds (GIB). Nebulized TXA shows promise for both post-tonsillectomy bleeding and hemoptysis. However, better studies are needed to confirm these observations. Dr. Anand Swaminathan and I covered the classic CRASH-2 Trial (SGEM#80). This study published in 2010 showed an absolute mortality reduction of 1.5% in adult trauma patients giving a number needed to treat to prevent one death of 67 (Shakur et al. Lancet 2010) CRASH-3 was a well-designed, large, multi-centred randomized placebo controlled trial published in October 2019 (The Lancet). It asked if TXA had a mortality benefit in patients with isolated head trauma (SGEM#270)? While there was a suggestion of benefit in a secondary subgroup analysis, the primary outcome demonstrated no statistical difference in head-injury related mortality with TXA compared to placebo (18.5% TXA vs. 19.8% placebo, RR 0.94 [95% CI 0.86 to 1.02]). One of the limitations to both CRASH-2 and CRASH-3 was the external validity. The majority of sites involved were in middle to low income countries. CRASH-3 had one Canadian site and the USA had no participating centres. Transfusion practices and identification of adverse events may differ in developing countries compared to the USA. Clinical Question: What is the mortality and thromboembolic events in adult trauma patients receiving TXA an American Level 1 Trauma Center? Reference: Erramouspe et al. Mortality and Complication Rates in Adult Trauma Patients Receiving Tranexamic Acid: A Single-center Experience in the Post–CRASH-2 Era. AEM May 2020 Population: Adults (18 years or older) who received TXA after an acute traumatic injury Excluded: Patients who received oral TXA, received it for elective surgery or nontrauma indications, received TXA 8 hours or longer after the injury, and patients with cardiac arrest at time of ED arrival. Intervention: TXA 1g IV over 10 minutes and maintenance infusion of 1g IV over 8 hours Comparison: None Outcome: Primary Outcome: In-hospital mortality Safety Outcome: Thromboembolic event within 28 day Dr. Erramousepe This is an SGEMHOP episode and we are pleased to have both the lead author and senior author on the episode. Dr. Joaquin Erramouspe is a medical doctor, who finished medical school in Uruguay, moved to the USA for further training and research, and now, is working as a researcher at Queensland University of Technology while obtaining his masters in science. Dr. Daniel Nishijima Dr. Daniel Nishijima is an emergency medicine physician at University of California Davis. His research focus is on trauma and neurological emergencies, particularly those with coagulation disorders. Authors’ Conclusions: “Adult trauma patients receiving TXA had similar incidences of death but higher incidences of thromboembolic events compared to the CRASH-2 trial. Variation in patient characteristics, injury severity, TXA dosing, and surgery and transfusion rates could explain these observed differences. Further research is necessary to provide additional insight into the incidence and risk factors of thromboembolic events in TXA use.” Quality Checklist for Observational Study: 1. Did the study address a clearly focused issue? Yes 2. Did the authors use an appropriate method to answer their question? Yes 3. Was the cohort recruited in an acceptable way? Yes 4. Was the exposure accurately measured to minimize bias? Yes 5. Was the outcome accurately measured to minimize bias? Yes 6. Have the authors identified all-important confounding factors? Yes 7. Was the follow up of subjects complete enough? Yes 8. How precise are the results? Fairly precise 9. Do you believe the results? Yes 10. Can the results be applied to the local population? Unsure 11. Do the results of this study fit with other available evidence? Yes Key Results: This retrospective study included 273 patients with a mean age of 43.8 years and 74% male. All-cause mortality was 12.8% and thromboembolic events were 6.6% Difference between the current study and the previously published CRASH-2 study. We have five nerdy question to ask Joaquin and Daniel to better understand their teams study. Listen to the podcast on iTunes to hear his responses. 1) Chart Review: You referenced Kaji et al. Looking through the retro-spectoscope: reducing bias in emergency medicine chart review studies (Annals of EM 2014). What additional benefit does this publication add to the quality check list for observational studies published by my EBM mentor Dr. Andrew Worster? (Annals of EM 2005). 2) External Validity: This study was conducted at a single Level 1 trauma center. How do you think it would compare to other Level 1 Trauma Centers in the USA? None of our trauma centres in Canada see the volumes that you do in the large US trauma centres. This is because of the lack of penetrating trauma. I have worked full time for 25 years in an ED and never seen a gunshot injury. Most of the trauma we see is from blunt force injury. Do you think the results would be similar in a Canadian trauma centre? What about non-level 1 trauma centers in the USA? I thought that CRASH-2 and CRASH-3 had a lot of external validity to where I work in a rural/critical access hospital. We don’t have a CT scanner or a surgeon and our massive transfusion protocol is both units of O-negative blood. We usually give TXA to our trauma patients but transfer them quickly to our local trauma centre. Did your study include or exclude patients transferred to your hospital who had TXA provided prior to arrival? 3) Lack of Control: There was no control group in this study, but you did compare your results to the CRASH-2 study. Let’s go through some of the differences and comment on how that may have impacted your results or explain your findings: Demographic Differences – The patients were older and there were less men in your cohort. Mortality Differences – There was less all-cause mortality and less bleeding mortality in your study compared to CRASH-2. Differences in Any Surgeries and Blood Products Transfused – You had more patients taken to the operating room for surgery and more transfusions of blood products. Thromboembolism – Previous studies have reassured that the risk of thromboembolism is low. However, in your study you had more than three times the events as CRASH-2 (6.6% vs 2.0%). Is this because you had better methods to detect these adverse events using your EMR or is it some other reason? 4) Comparison Group: There were 31/321 (10%) of patients who did not receive TXA. Do you have any more information on why they did not receive TXA and who they did clinically? 5) Next Steps: What are the unanswered questions you have about TXA use in adult trauma patients? Comment on Authors’ Conclusion Compared to SGEM Conclusion: We generally agree with the authors’ conclusions. SGEM Bottom Line: The evidence supports the use of TXA in the treatment of adult patients with blunt trauma, but the increased risk of thromboembolism is concerning. Case Resolution: The patient is intubated; his pelvis is placed in a binder and you start your hospital’s massive transfusion protocol. A FAST exam is positive, and the surgeons start debating whether to get more advanced imaging or take the patient directly to operating room for an exploratory laparotomy. You step out of the room and make a mental note to look up the patient tomorrow on your next shift. Dr. Corey Heitz Clinical Application: TXA has an absolute mortality benefit of 1.5% in CRASH-2. This new retrospective study will not change my practice but does increase our concern about thromboembolic events. What Do I Tell My Patient? It looks like you have internal bleeding. We are going to give you blood products as well as a medicine called TXA. This can help stop the bleeding and improve your chance of survival. There is a low risk of increasing blood clotting. The surgeons will take to more about taking you to the operating room. Keener Kontest: Last weeks' winner was Dr. Kirby Black an EM physician from Oneida, New York. He know Hippocrates first described strokes over 2,400 years ago. Listen to the SGEM podcast to hear this weeks’ question. Send your answer to TheSGEM@gmail.com with “keener” in the subject line. The first correct answer will receive a cool skeptical prize.

Date: May 19th, 2020 Reference: Yang P et al. Endovascular thrombectomy with or without intravenous alteplase in acute stroke. NJEM 2020. Guest Skeptic: Dr. Anand Swaminathan is an Assistant Professor of Emergency Medicine at St. Joseph’s Regional Medical Center in Paterson, NJ. Managing editor of EM:RAP and Associate Editor at REBEL EM. Case: A 53-year-old previously healthy man presents with 1.5 hours of right sided weakness as well as slurred speech. A rapid bedside assessment gives you a National Institute of Health Stroke Score/Scale (NIHSS) of 9 and you are concerned about a large vessel occlusion (LVO) based on the high NIHSS as well as the presence of both an upper extremity drift and the speech abnormality. A non-contrast CT shows no evidence of intracranial hemorrhage. A CT angiogram plus CT perfusion demonstrate a clot in the left proximal middle cerebral artery (MCA) with a small infarcted area and a large penumbra. Based on your institution’s current guidelines, the patient is a candidate for endovascular therapy, but they are also within the current window for the administration of alteplase. You wonder if you should give the alteplase while waiting for your neurointerventional team? Background: The issue of thrombolytics for stroke has been debated since at least 1995. This is the year that the famous NINDS trial was published. We cover this as an SGEM classic that all EM physicians should know about on SGEM#70. Our bottom line was that we were skeptical thrombolysis has a net patient-oriented benefit for acute ischemic strokes. We have covered this issue of thrombolysis for acute ischemic stroke a number of times on the SGEM SGEM#29: Stroke Me, Stroke Me SGEM Xtra:Thrombolysis for Acute Stroke SGEM#290: Neurologist Led Stroke Teams – Working 9 to 5 You also had the Legend of Emergency Medicine, Dr. Jerome Hoffman on to reflect upon the last 25 years and the thrombolysis for acute ischemic stroke debate (No Retreat, No Surrender) I also invited my EBM friend, Dr. Eddy Lang onto the SGEM to discuss his perspective on the issue (SGEM Xtra). This led to a pro/con publication in the Canadian Journal of Emergency Medicine (CJEM) tPA should be the initial treatment in eligible patients presenting with an acute ischemic stroke (Milne et al CJEM April 2020). The publication of the MR CLEAN trial in January 2015 changed the face of ischemic stroke care. This was the first study demonstrating a benefit to endovascular treatment of a specific subset of ischemic stroke patients: those with LVOpresenting within sixhours of symptom onset. MR CLEAN was followed by a flurry of publications seeking to replicate and refine treatment as well as expand the window for treatment. The REBEL EM team reviewed this literature back in 2018 and, with the help of Dr. Evie Marcolini, created the below workflow: One major component of LVO management is the use of systemic thrombolytics in patients presenting within the current thrombolytic treatment window prior to endovascular intervention. However, it’s unclear if systemic thrombolytic administration results in better outcomes or if it simply exposes the patient to increased risks at a higher cost. Limited evidence questions the utility of the current approach with thrombolytics plus endovascular therapy (Phan 2017, Rai 2018). There is a clear need for further research into systemic thrombolytics dosing and use. Clinical Question: Is endovascular therapy alone non-inferior to endovascular therapy plus systemic thrombolytics in the treatment of patients with large vessel occlusion strokes presenting within 4.5 hours of onset? Reference: Yang P et al. Endovascular thrombectomy with or without intravenous alteplase in acute stroke. NJEM 2020. Population: Adult patients (18 years of age or older) presenting within 4.5 hours of ischemic stroke symptom onset and with cerebral vascular occlusion on CT angiography of the intracranial internal carotid artery or middle cerebral artery (first and/or second segments) and an NIHSS > 1 and if endovascular thrombectomy was intended to be performed. Exclusions: Disability from a previous stroke or contraindication to IV alteplase and any contra-indication for thrombolysis according to American Heart Association (AHA) guidelines. Intervention: Endovascular thrombectomy alone Comparison: Endovascular thrombectomy + systemic alteplase 0.9 mg/kg Outcomes: Primary Outcome: Modified Rankin Scale (mRS) score assessed at 90 days after randomization looking for non-inferiority (defined as a lower end of the odds ratio > 0.80) Secondary Outcomes: Death from any cause at 90 days, successful reperfusion before thrombectomy, recanalization at 24-72 hours (assessed by CTA), NIHSS score at 24 hours, and 5-7 days, final lesion volume on CT and mRS comparisons Safety Outcomes: All hemorrhages and symptomatic intracranial hemorrhages according to the Heidelberg criteria, occurrence of pseudoaneurysm and groin hematoma at the site of arterial puncture used for thrombectomy, cerebral infarction in a new vascular territory at five to seven days, and mortality within 90 days. Authors’ Conclusions: “In Chinese patients with acute ischemic stroke from large-vessel occlusion, endovascular thrombectomy alone was noninferior with regard to functional outcome, within a 20% margin of confidence, to endovascular thrombectomy preceded by intravenous alteplase administered within 4.5 hours after symptom onset.” Quality Checklist for Randomized Clinical Trials: The study population included or focused on those in the emergency department. Unsure 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). Unsure 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. No Key Results: They screened 1,586 patients for eligibility and 654 were included in the final analysis. The median age was 69 years and slightly more were male. The median NIHSS score was 17. Primary Outcome: Adjusted odds ratio for the mRS aOR = 1.07 (95% CI 0.81 TO 1.40) Demonstrates non-inferiority as lower limit of non-inferiority was set at 0.80 Secondary Outcomes:  1) Consecutive Patients and External Validity – The manuscript did not explicitly say patients were recruited consecutively. Without this information it is hard to comment on whether or not there was selection bias. We are also concerned about the external validity of a stroke trial conducted in China compared to the care provided in the USA. 2) Declined to Participate – Of eligible patients, 15% (240/1,586) declined to participate. There was no information provided on this group in the published paper or supplementary material. Patients deciding to participate could have been different from those who decided not to participate. This too could have introduced some selection bias. 3) Lack of Blinding: The treating physicians and study participants were not blinded to group allocation. This could have biased the study towards the EVT alone if that hypothesis was known to these two groups. 4) Intention-To-Treat (ITT): You will often hear us comment about whether or not the trial has used an ITT analysis. This is a quality indicator for superiority designs. However, for non-interiority trials a per-protocol analysis is the more conservative approach to minimize bias.Using an ITT can bias the results toward the null hypothesis. The per-protocol analysis could only be found in the supplemental appendix. A non-inferiority design seeks to establish a novel treatment is not worse than a standard treatment by more than a predetermined acceptable amount. The null hypothesis for a non-inferiority study states for a given outcome, treatment A (a novel treatment) is worse than treatment B (an accepted, validated treatment) by more than a non-inferiority margin called the delta (∆). In contrast, the alternate hypothesis states for a given outcome, treatment A is not worse than treatment B by more than ∆.This type of study design is often used when two circumstances are met:  a placebo trial would be unethical, due to the existence of a treatment proven superior to placebo, and the novel treatment offers other advantages (e.g., cost, ease of use, less invasiveness, fewer adverse effects, etc.). Setting the non-inferiority margin should be specified a priori. It can be set at a statistically significant difference or a clinically significant difference. Subjectivity can be introduced when determining what is considered clinically significant. A number of guidelines exist like the CONSORT extension statement to help researcher properly design non-inferiority trials. 5) Outcomes: Outcome data was obtained via interviews performed in person or by phone. Phone interviews are suboptimal for assessing functionality. This could add more statistical noise into the data and bias the results to finding non-inferiority. We could not find how many assessments were done in person and how many were done by phone. It would be interesting to see if there were any differences in outcome that could be attributed to the method of assessing the outcome. Comment on Authors’ Conclusion Compared to SGEM Conclusion: We generally agree with the authors’ conclusions.

Date: May 18th, 2020 I was asked to participate in a debate regarding the issue of Masks4All in Canada by the people involved in the COVID Information for Canadian Physicians Facebook group. This is a private group ~22,000 physicians, residents, students and nurse practitioners from around the world. Dr. Joe Vipond I was reluctant to participate but was convinced after having a good conversation with the organizers and Dr. Vipond. They assured me it would be respectful, focus on the evidence and be an educational experience for the audience. These are stressful times and we all want the best recommendation for patients, based on the best evidence to ensure community well-being. Arguing for the affirmative position was Dr. Joe Vipond. He is an emergency physician at the Rockyview General Hospital and a clinical assistant professor at the University of Calgary. He has generously made available his notes from the debate that include links to more information. I argued against the resolution. This does not mean I am against wearing a cloth mask in public. Those who know my not so secret identity (BatDoc) know that I am often seen in public wearing a mask. This is not the type of mask Dr. Vipond and I were debating. We were not talking about wearing medical masks, surgical masks, N95 masks or respirators by healthcare providers on the front lines of COVID19. The debate also did not include symptomatic people or those caring for high-risk people. We were only debating the issue of universal cloth Masks4All in public. To be very clear, I am not anti-mask wearing in public. My position is "it all depends" as taught by my evidence-based medicine (EBM) mentor Dr. Andrew Worster from BEEM.  I am just not in favour of a mandatory universal Masks4All in public in Canada. You can watch the Mask4All debate on YouTube. Resolution: Be it resolved that a mandatory universal mask for all to prevent transmission of COVID19 be recommended for Canadians. Dr. Kashif Pirzada We were each given four minutes for an opening statement, three minutes for a rebuttal, four more minutes for a second affirmative statement and finished with three minutes for another rebuttal and closing statement. We had two moderators for this debate. Dr. Kashif Pirzada is an emergency physician in Toronto with an interest in startups and innovation.  He is also a co-founder of Conquer-Covid19, a charity that sources personal protection equipment for frontline health workers. Dr. Jennifer Kwan Dr. Jennifer Kwan is a family physician in Burlington, Ontario. She is known for COVID19 data visualizations on Twitter (@jkwan_md) along with the HowsMyFlattening team, and is an advocate for #Masks4Canada and personal protection equipment donations with Halton Regional Chinese Canadian Association. I am not against wearing a cloth mask in public. My position is that I am not convinced that a mandatory Masks4All in public by people that are practicing physical distancing will prevent transmission of clinical disease (COVID19). This is an important distinction. Dr. Samir Grover Questions on the Facebook feed were moderated by Dr. Samir Grover. He is an associate professor and program director for gastroenterology at the University of Toronto. Kashif and Samir have a podcast about COVID-19 called "The Medicine Club" which can be accessed on Twitter @TheMedClubTO It is important in any discussion to be clear on the terms being used. Mandatory: Required by a law or rule : OBLIGATORY. Universal: Including or covering all or a whole collectively or distributivity without limit or exception. Public: All public places (not to private places) Clinical Disease: There is a difference between a DOO (Disease Oriented Outcome- detection of COVID19 RNA) and a POO (Patient-Oriented Outcome - clinical disease). As a clinician, I am more interested in POOs and less interested in  DOOs. Epistemology: The study or a theory of the nature and grounds of knowledge especially with reference to its limits and validity I want to accept positions for good reasons not because it is someone’s opinion.  Just because someone is a gifted clinician and an excellent advocate for the environment does not mean they are an expert in clinical epidemiology, biostatistics and critical appraisal. This brings up the possibility of a Dunning-Kruger Effect. Here is a link to a great video made by Dr. Rohin Francis (@MedLifeCrisis). It is a satirical ad for Dunning-Kruger Alcohol and uses humour as a COVID19 coping strategy. “The Dunning-Kruger effect is a cognitive bias in which people wrongly overestimate their knowledge or ability in a specific area. This tends to occur because a lack of self-awareness prevents them from accurately assessing their skills.” My credentials included 37 years of medical research, Senior Editor of Academic Emergency Medicine (AEM), advance training in clinical epidemiology, biostatistics and critical appraisal.  I teach these skills and cognitive bias and logical fallacies to MSc and PhD students in the Department of Epidemiology. I have published dozens of critical appraisals which are considered a higher level of evidence than a randomized control trial on the EBM pyramid of evidence.  Basically, I am an uber nerd. This does NOT make my position of the evidence on cloth Masks4All correct or an argument from authority. The information is presented as evidence of my expertise and to support my claim that this is my lane. In the scientific method we start with the null hypothesis. The null would be that there is no statistical difference between universal/mandatory cloth masks4all and not wearing a cloth mask in public. The burden of proof is on those making the claim that cloth masks4all in public is superior in preventing transmission of clinical disease (POO) in those physically distancing. Without sufficient evidence we should not accept the claim. Therefore, we should accept the null hypothesis of no superiority. Everyone will have a different level of evidence required to accept a claim. I want patients to get the best recommendation, based on the best evidence. Without evidence people are providing an opinion. Christopher Hitchens famously said "that which can be asserted without evidence, can be dismissed without evidence." (Hitchens’ Razor) Peltzman Effect: Risk Compensation and Risk Homeostasis Prof Sam Peltzman Sam Peltzman was a professor who wrote a paper in 1975 about seatbelt regulations (The Effects of Automobile Safety Regulation, J Political Economy 1975). Professor Peltzman argued that the benefits of seatbelt would be offset by more pedestrian deaths and more nonfatal accidents because of “driving intensity”. This was driving faster and more recklessly with the security of the safety belt. His hypothesis was proven to be wrong and seatbelts were a net benefit but it did open a field of risk compensation. Bill Booth There are examples where an intervention did have a positive outcome (seat belts in cars and helmets when cycling) but there are other examples where the theoretical benefits did not materialize in the real world. This includes parachute equipment advancements to prevent morbidity and mortality from jumping out of a plane. Bill Booth was a person who designed safety equipment for parachutes. They should have decreased morbidity and mortality of jumping out of plane. The data showed it did not. There was risk compensation and it did not have the impact he hoped (Booth’s Second Law). "The safer skydiving gear becomes, the more chances skydivers will take, in order to keep the fatality rate constant."  Condoms Another example is condoms to prevent HIV virus transmission during that pandemic. The no glove, no love was thought to be a “no brainer”. It was widely felt that condoms could help prevent the spread of the HIV epidemic. However, the impact of condoms alone was mitigated during a global pandemic due to risk compensation/homeostasis. There are a significant portion of people who dislike using condoms, use is often irregular, and condoms seem to give a sense of security. This can lead to disinhibition, in which people may engage in risky sex with condoms (Shelton JD. Ten myths and one truth about generalized HIV epidemics, Lancet 2006). Risk compensation/homeostasis (Peltzman Effect) can also be seen in the unintended behavioral responses by patients and physicians to health care interventions. This may explain why certain health care interventions that seem logical and foolproof fail to demonstrate real-world benefits (Prasad and Jena Healthc Amst 2014). EHR and Burnout Electronic Health Records (EHRs) is just one newer example of the risk compensation hypothesis. One of the claimed benefits of introducing EHRs was to decrease medication errors. While they did demonstrate fewer of these errors they increased other errors. It is also unclear if the type of medication errors that were reduced had an important POO. EHRs also have been shown to negatively impact emergency department efficiency. They have been blamed for contributing to physician burnout. Burnout is associated with worse patient care. Gray A et al. The impact of computerized provider order entry on emergency department flow. CJEM 2016. Shanafelt et al Changes in Burnout and Satisfaction With Work-Life Balance in Physicians and the General US Working Population Between 2011 and 2014. Mayo Clin Proc. 2015;90(12):1600-1613 West CP, Huschka MM, Novotny PJ, et al. Association of perceived medical errors with resident distress and empathy: a prospective longitudinal study. JAMA. 2006; 296(9):1071-1078. Shanafelt TD, Balch CM, Bechamps G, et al. Burnout and medical errors among American surgeons. Ann Surg. 2010;251(6): 995-1000. Firth-Cozens J, Greenhalgh J. Doctors’ perceptions of the links between stress and lowered clinical care.

Date: May 9th, 2020 Guest Skeptic: Dr. Sean Moore is an Assistant Professor at the Northern Ontario School of Medicine (NOSM), Chief of Emergency Services at Lake of the Woods Hospital in Kenora, Medical director with Ornge, and Associate Medical Director with CritiCall Ontario. CAEP Town Hall We had the pleasure of presenting for the Canadian Association of Emergency Physicians (CAEP) COVID-19 Town Hall this week.  CAEP is the national voice of emergency medicine (EM) in Canada and provides continuing medical education, advocates on behalf of emergency physicians and their patients, supports research and strengthens the EM community. In co-operation with other specialties and committees, CAEP also plays a vital role in the development of national standards and clinical guidelines. Our CAEP COVID-19 Town Hall presentation is available to watch on the CAEP website. It has also been uploaded to CAEP's YouTube channel. All of the the CAEP COVID-19 Town Halls talks are available free open access. Copies of our slides can be downloaded at this link. Dr. Sean Moore Dr. Moore and I were asked to speak about the treatments being used for COVID-19. In this global pandemic, clinicians and researchers have been throwing multiple different treatments at this new corona virus hoping something will work. This includes things like: Azithromycin, Steroids, Famotidine, IL-6 inhibitors, Chloroquine, Hydroxychloroquine, Remdesivir, Vitamin C, and Zinc.   We narrowed our presentation down to five treatments and the evidence behind those treatments. These are listed below with links to the references mentioned in the presentation. Chloroquine / Hydroxychloroquine Dr. Didier Raoult Gautret et al. Clinical and microbiological effect of a combination of hydroxychloroquine and azithromycin in 80 COVID-19 patients with at least a six-day follow up: A pilot observational study. Travel Med Infect Dis. April 11th, 2020 Tang et al. Hydroxychloroquine in patients with COVID-19: an open-label, randomized, controlled trial. MedRxIV April 14th, 2020 Chowdhury et al. A Rapid Systematic Review of Clinical Trials Utilizing  Chloroquine and Hydroxychloroquine as a Treatment for COVID‐19. AEM May 2020. We cannot recommend hydroxychloroquine or chloroquine based on the available evidence. Steroids Surviving Sepsis Campaign: guidelines on the management of critically ill adults with Coronavirus Disease 2019 (COVID-19). Intensive Care Med. 2020 Mar 28. Steroids Wilson et al. COVID‐19: Interim Guidance on Management Pending Empirical Evidence. From an American Thoracic Society‐led International Task Force. Thoracic April 3rd, 2020 Villar et al. Dexamethasone treatment for the acute respiratory distress syndrome: a multicentre, randomised controlled trial. Lancet Resp Med Feb 7th, 2020 Wu et al. Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China. JAMA Int Med March 13th, 2020 We cannot recommend the use of steroids outside of an RCT. However, steroids should be considered when patients have other indications like COPD or asthma. Remdesivir Grein et al. Compassionate Use of Remdesivir for Patients with Severe Covid-19. NEJM April 10th, 2020 Wang et al. Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial. The Lancet April 29th, 2020 Fauchi A. Adaptive COVID-19 Treatment Trial (ACTT). Press Conference April 29th, 2020 We cannot recommend the routine use of remdesivir based on the available evidence. Convalescent Plasma Convalescent plasma is being investigated but there is very little information on this treatment modality. Currently the CONCOR Trial is underway in Canada using 200-500 ml of plasma. Researchers from across the country are involved including Drs. Donald Arnold, Philippe Begin and Jeannie Callum. Plasma collection was started in April. We cannot recommend the use of convalescent plasma outside of a research study. Vaccines Much work is being done on developing a COVID19 vaccine but that is a least months if not years away. My position on vaccines is that the evidence for potential benefit is much greater than the evidence for potential harm. Vaccines are safe and effective for the vast majority of people. SGEM#20 with guest skeptic Dr. Lauren Westafer (@LWestafer) from FOAMCast discussed the issue of flu shots for healthcare workers. We do not know how effective a vaccine will be, it's safety or how long the immunity would last at this time. George Santayana Dr. Moore and I continued the presentation with a reminder that we should remember our history. We have made mistakes in the past by adopting new technology or treatments too soon in medicine. There are examples of when the treatment was properly studied it was found not to work or even worse, increase mobility or mortality. It was George Santayana who said "those who cannot remember the past are condemned to repeat it".  An excellent article was written by Jeaane Lenzer and Shannon Brownlee and published in Issues in Science and Technology. It was titled Pandemic Science Out of Control: A toxic legacy of poor-quality research, media hype, lax regulatory oversight, and vicious partisanship has come home to roost in the search for effective treatments for COVID-19. I would encourage people to read at least the first paragraph. "On September 14, 1918, in the midst of the worst pandemic in modern history, an article in the New York Times quoted Dr. Rupert Blue, then surgeon general of the US Public Health Service. Blue reported that doctors in many countries were treating their influenza patients with digitalis and the antimalaria drug quinine. There was no evidence that the two drugs were any more effective than folk remedies being used by patients, including cinnamon, goose grease poultices, and salt stuffed up the nose, but doctors were desperate and willing to try just about anything. They would eventually abandon quinine and digitalis as treatments for flu when studies showed they were not only ineffective but caused serious and sometimes deadly side effects." Dr. Rob Leeper I took us back over 200 hundred years to give an example of why it is important to conduct randomized controlled trials rather than relying upon clinical experience and observational data. The study was conducted by Scottish medical student Alexander Hamilton who in 1809 challenged the standard of care, blood letting, for camp fever. He demonstrated that the number needed to treat for harm (NNT) was four. The primary outcome (harm) in this case was death. More details about blood letting and the importance of randomization can be found on the SGEM Xtra with Dr. Rob Leeper. The CAEP Town Hall on COVID-19 Treatments ended with an excellent article from the NEJM. It was a perspective piece written by Zagury-Orly and Schwartzstein called: A Reminder to Reason. I would highly suggest reading the entire article but the last paragraph gives a powerful statement. "We are living through an unprecedented biopsychosocial crisis; physicians must be the voice of reason and lead by example. We must reason critically and reflect on the biases that may influence our thinking processes, critically appraise evidence in deciding how to treat patients, and use anecdotal observations only to generate hypotheses for trials that can be conducted with clinical equipoise. We must act swiftly but carefully, with caution and reason." 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 ten years to less than one year using the power of social media. Ultimately we want 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. Other #FOAMed Resources on COVID19 First10EM with Dr. Justin Morgenstern PulmCrit with Dr. Josh Farkas EMCases with Dr. Anton Helman St. Emlyn's Dr. Simon Carley and the Team REBEL EM with Dr. Salim Rezaie and Team EMRAP with Dr. Mel Herber and Team