The Skeptics Guide to Emergency Medicine

Date: October 21st, 2020 Guest Skeptic: Dr. Justin Morgenstern is an emergency physician, creator of the excellent #FOAMed project called First10EM.com and a member of the #SGEMHOP team. Reference: Derkenne et al. Mobile Smartphone Technology Is Associated With Out-of-hospital Cardiac Arrest Survival Improvement: The First Year "Greater Paris Fire Brigade" Experience. AEM Oct 2020. Case: You are waiting in line for coffee, discussing the latest SGEM Hot Off the Press episode on twitter, when an alert pops up on your phone. It says that someone in the grocery store next door has suffered a cardiac arrest and needs your help. You remember installing this app at a conference last year, but this is the first time you have seen an alert. You abandon your coffee order and quickly head next-door, where you are able to start cardiopulmonary resuscitation (CPR) and direct a bystander to find the store’s automated external defibrillator (AED) while waiting for emergency medical services (EMS) to arrive. After the paramedics take over, you wonder about the evidence for this seemingly miraculous intervention. Background: Out of hospital cardiac arrest (OHCA) is something that we have covered many times on the SGEM. SGEM#64: Classic EM Papers (OPALS Study) SGEM#136: CPR – Man or Machine? SGEM#143: Call Me Maybe for Bystander CPR SGEM#152: Movin’ on Up – Higher Floors, Lower Survival for OHCA SGEM#162: Not Stayin’ Alive More Often with Amiodarone or Lidocaine in OHCA SGEM#189: Bring Me to Life in OHCA SGEM#231: You’re So Vein – IO vs. IV Access for OHCA SGEM#238: The Epi Don’t Work for OHCA SGEM#247: Supraglottic Airways Gonna Save You for an OHCA? SGEM#275: 10th Avenue Freeze Out – Therapeutic Hypothermia after Non-Shockable Cardiac Arrest The American Heart Association promotes the “Chain-of-Survival”. There are five steps in the Chain-of-Survival for OHCA: Step One – Recognition and activation of the emergency response system Step Two – Immediate high-quality cardiopulmonary resuscitation Step Three – Rapid defibrillation Step Four – Basic and advanced emergency medical services Step Five – Advanced life support and post arrest care Bystander CPR and early defibrillation are key components of the out of hospital cardiac arrest chain of survival. Unfortunately, most patients don’t receive these crucial interventions. Many people are trained in CPR but never use their skills, because it is unlikely that they will happen to be in exactly the right place at the right time. They may be willing and able to help, but if the patient in need is one block over, they may never know about it. The advent of the smart phone with GPS capability means that we should be better able to direct individuals trained in basic life support (BLS) to those in need around them. We should also be able to use smart phones to more easily identify the closest AEDs. Over the last decade, numerous apps have been developed to do exactly that, but the impact of those apps on clinical outcomes is still unclear. Clinical Question: Is the use of a smart phone app that can match trained responders to cardiac arrest victims and indicate the closest available AEDs associated with better clinical outcomes? Reference: Derkenne et al. Mobile Smartphone Technology Is Associated With Out-of-hospital Cardiac Arrest Survival Improvement: The First Year "Greater Paris Fire Brigade" Experience. AEM Oct 2020. Population: Cardiac arrests from a single emergency medical service (EMS) agency in Paris, France that were called through the central dispatch center and occurred while the chief dispatcher was available to participate, occurred in a public area, and in which there was not obvious environmental danger. Intervention: Alerts were sent through the Staying Alive app to volunteers trained in BLS who were within 500 meters of the reported cardiac arrest. The intervention group is the group of patients for whom someone responded to the alert and provided BLS treatment. Comparison: The control group consisted of patients in whom no volunteer was within 500 meters at the time of the arrest, for whom no volunteer responded to the alert, or for whom the volunteer responded to the alert but did not perform BLS. Outcomes: Return of spontaneous circulation (ROSC) upon hospital admission, survival outcomes upon hospital discharge and impact of first responders (commonly referred to as“Bons Samaritains”[BS]) on survival outcomes. Dr. Clementt Derkenne This is an SGEMHOP episode which means we usually have the lead author on the show.  Dr. Clement Derkenne is an emergency physician in the Emergency Medical Department, Paris Fire Brigade, Clamart, France. He did not feel comfortable doing a podcast in English which we completely understand. Authors’ Conclusions: “We report for the that mobile smartphone technology was associated with OHCA survival through accelerated initiation of efficient cardiopulmonary resuscitation by first responders in a large urban area.” Quality Checklist for Observational Study: Did the study address a clearly focused issue? Yes Did the authors use an appropriate method to answer their question? Unsure Was the cohort recruited in an acceptable way? Was the exposure accurately measured to minimize bias? Yes Was the outcome accurately measured to minimize bias? Yes and Unsure Have the authors identified all-important confounding factors? Unsure Was the follow up of subjects complete enough? Yes How precise are the results? Moderate Do you believe the results? Probably Can the results be applied to the local population? Unsure Do the results of this study fit with other available evidence? Unsure Key Results: They recorded 4,107 OHCA in 2018. The mean age was in the mid 50’s, ~75% were male, 91% were medical cardiac arrests and most arrests took place outside the home. The Staying Alive app was activated 366 times (9.8% of the total arrests). There were 46 patents in the intervention group (24 received CPR only, 18 AED only and 4 both) and 320 in the control group (97 cases where no volunteer responded to the notification, and 226 who responded to the notification but either couldn’t locate the patient or failed to start BLS). Getting treatment as a result of the Staying Alive App was associated with more ROSC and more survival to hospital discharge. ROSC: 48% SA vs. 23% control, p<0.001 Survival to Hospital Discharge: 35% SA vs 16% control, p=0.004 Adjusted Odds Ratio = 5.9 (95% CI; 2.1 to 16.5), p < 0.001 1. External Validity: This study looked at the large urban area of Paris, France. It is unclear if this would translate to smaller urban centres or rural communities. 2. Control Group: In the conclusion for this paper, the authors say that smartphone technology is associated with out of hospital cardiac arrest survival. However, they didn’t compare a group of patients who had smart phone technology available to a group of patients who didn’t have such technology. What they actually compared is a group of patients who got treatment – CPR or and AEDs – to a group of patients who didn’t get treatment, even though the app was activated. I think this data only shows us that there is an association between CPR and AED use and survival – but we already knew that. In order to see an association with the app, we need a control group who didn’t have the app available – maybe a different city that isn’t using an app, or maybe a different time period, like historical controls in a before and after study. But as it stands, I don’t think control group tells us anything about the app itself. 3. Excluded Patients: More than 90% (3,737/4,107) of the OHCA patients were not included in this study. There were many differences between those included and those not included. It would be interesting to know what the outcomes were for this group and compare them to the intervention and control groups. 4. Primary Outcome: When critically appraising studies, it is very important to know the primary outcome in order to interpret the reported statistics. The authors' looked at a number of very important outcomes, but we didn’t see a primary outcome explicitly reported in the manuscript. 5. All-Patient Oriented Outcomes: We have seen many studies that have a primary outcome of ROSC, admission to hospital, or survival to hospital discharge. A better patient-oriented outcome (POO) is survival to hospital discharge with good neurologic function. 6. Generalizability and Cost Effectiveness: Out of 4,107 arrests, only 46 patients received treatment through the app. This very small number could result in selection bias that would affect the generalizability of these results. Further, the fact that the app only resulted in treatment for a small number of cases may indicate that the costs of the app and training might overshadow its benefits. 7. Confounders: This is observational data, so we are limited to finding associations. There were many differences between patients with OHCA where the app was activated and the patients with OHCA while the app was not activated. There was another dichotomy between when a volunteer responded and when they did not respond. We wonder what various factors might have influenced whether a patient ended up in the control or intervention group? For example, people might be less likely to respond to an arrest in a poorer area of town, but patients in a poorer area might have worse outcomes, confounding these results. 8. Harms and Unintended Consequences: These apps make a lot of intrinsic sense. However, nothing in life is free. If the app is going to be used at scale, there will be some cost in development, advertising, and training. The use of an app could also take attention away from other important interventions,

Date: October 21st, 2020 This is an SGEM Xtra episode. I had the honour of presenting at the Department of Family Medicine's Grand Rounds at the Schulich School of Medicine and Dentistry. The title of the talk was: How to think, not what to think. The presentation is available to watch on YouTube, listen to on iTunes and all the slides can be downloaded from this LINK. Five Objectives: Discuss what is science Talk about who has the burden of proof Discuss Evidence-based medicine (EBM), limitations and alternatives Provide a five step approach to critical appraisal Briefly talk about COVID19 and the importance of EBM What is Science? It is the most reliable method for exploring the natural world. There are a number of qualities of science: Iterative, falsifiable, self-correcting and proportional. What science isn’t is “certain”. We can have confidence around a point estimate of an observed effect size and our confidence should be in part proportional to the strength of the evidence. Science also does not make “truth” claims. Scientists do make mistakes, are flawed and susceptible to cognitive biases. Physicians took on the image of a scientist by co-opting the white coat. Traditionally, scientists wore beige and physicians wore black to signify the somber nature of their work (like the clergy). Then came along the germ theory of disease and other scientific knowledge. It was the Flexner Report in 1910 that fundamentally changed medical education and improved standards. You could get a medical degree in only one year before the Flexner Report. The white coat was now a symbol of scientific rigour separating physicians from “snake oil salesman”.  Many medical schools still have white coat ceremonies. However, only 1 in 8 physicians still report wearing a white lab coat today (Globe and Mail). Science is Usually Iterative: Sometimes science takes giants leaps forward, but usually it takes baby steps. You probably have heard the phrase "standing on the shoulders of giants"? In Greek mythology, the blind giant Orion carried his servant Cedalion on his shoulders to act as the giant's eyes. The more familiar expression is attributed to Sir Isaac Newton, "If I have seen further it is by standing on the shoulders of Giants.” It has been suggested that Newton may have been throwing shade at Robert Hooke. Hooke was the first head of the Royal Society in England. Hooke was described as being a small man and not very attractive. The rivalry between Newton and Hooke is well documented. The comments about seeing farther because of being on the shoulders of giants was thought to be a dig at Hooke's short stature. However, this seems to be gossip and has not been proven. Science is Falsifiable:  If it is not falsifiable it is outside the realm/dominion of science. This philosophy of science was put forth by Karl Popper in 1934. A great example of falsifiability was the claim that all swans are white. All it takes is one black swan to falsify the claim.  Science and Proportionality: The evidence required to accept a claim should be in part proportional to the claim itself. The classic example was given by the famous scientist Carl Sagan (astronomer, astrophysicist and science communicator). Did the TV series Cosmos and wrote a number of popular science books (The Dragons of Eden). Sagan made the claim that there was a “fire-breathing dragon that lives in his garage”. How much evidence would it take for you to accept the claim about the dragon? His word, pictures, videos, bones, other biological evidence, how about knowing any other dragons or dragons that breathe fire? Compare that to if I said we just got a new puppy and it’s in the garage. You would probably take my word for it. There is nothing extraordinary about the claim. Most of you should be familiar and have had experience with a puppy at some point in your life.  So the quality of evidence to convince you of something should be in part proportional to the claim being asserted. The summary is the famous quote by Carl Sagan that "extraordinary claims require extraordinary evidence".  Science is Self-Correcting: Because science is iterative and falsifiable it is also self correcting. Science gets updated. We hopefully learn and get closer to the “truth” over time. Medical reversal is a thing and there is a great book and by Drs. Prasad and Cifu on this issue called Ending Medical Reversal: Improving Outcomes, Saving Lives. Burden of Proof: Those making the claim have the burden of proof. It is called a burden because it hard - not because it is easy. We start with the null hypothesis (no superiority). Evidence is presented to convince us to reject the null and accept there is superiority to their claim. If the evidence is convincing we should reject the null. If the evidence is not convincing we need to accept the null hypothesis. It is a logical fallacy to shift the burden of proof onto those who say they do not accept the claim. They do not have to prove something wrong but rather not be convinced that the claim is valid/“true” and this is an important distinction in epistemology. Real World Example: Probiotics have been promoted for acute gastroenteritis (AGE) in children. Previous work in this area has been described as being “underpowered or had methodology problems related to the trial design and choice of appropriate end points.” Schnadower et al. did a randomized control trial (RCT) of Lactobacillus rhamnosus GG vs. placebo for AGE in children (NEJM 2018). They included children 3 months to 4 years of age with gastroenteritis. The trial enrolled 971 children who to took the probiotic twice a day for five days or placebo.  The results showed no statistical difference between the two groups for their primary outcome. We covered this RCT on SGEM#254: Probiotics for Pediatric Gastroenteritis. Can we say probiotics don’t work? No that would shift the burden of proof. However, without sufficient evidence of superiority we should accept the null hypothesis. This study was limited to only the probiotic tested in the trial. However, Freedman et al in this same 2018 NEJM edition had similar trial looking at L. rhamnosus and L. helveticus found the same thing (no superiority of probiotics vs placebo). It should be noted that there is some weak evidence for probiotic efficacy in antibiotic associated diarrhea (Goldenberg et al 2015). The bottom line is that probiotics cannot be routinely recommended at this time for acute gastroenteritis in children (SGEM# Evidence-Based Medicine (EBM): This was defined by Dr. David Sackett over 20 years ago (Sackett et al BMJ 1996). He defined EBM as “The conscientious, explicit and judicious use of current best evidence in making decisions about the care of individual patients.”  I really like this definition, and the only tweak I would have added would be to include the word "shared".   The definition of EBM can be visually displayed as a Venn diagram. There are three components: The literature, our clinical judgement, and the patients values/preferences. Many people make the mistake of thinking that EBM is just about the scientific literature. This is not true. You need to know about the relevant scientific information. The literature should inform our care but not dictate our care. Clinical judgement is very important. Sometimes you will have lots of experience and other times you may have very limited experience. The third component of EBM is the patient. We need to ask them what they value and prefer. The easiest way to do this is to ask the patient. It should start with patients care and it ends with patient care. We all want patients to get the best care, based on the best evidence.  Levels of Evidence: There is a hierarchy to the evidence and we want to use the best evidence to inform our patient care. The levels of evidence is usually described using a pyramid. The lowest level is expert opinion. the middle of the hierarchy is a randomized control trial and the top is considered a systematic review. The systematic review +/- a meta-analysis is put on the top of the EBM level of evidence pyramid. However, we need to watch out for garbage in, garbage out (GIGO). This means if you take a number of crappy little studies (CLS), mash them all up into a meat grinder and spit out a point estimate down to the 5th decimal place that results is some impressive p-value is an illusion of certainty when certainty does not exist. EBM Limitations: Harm and the parachutes Smith and Pell BMJ 2003 Hayes et al CMAJ 2018 Yeh et al BMJ 2018 Most published research findings are false Ioannidis PLoS 2005 Guidelines are just cookbook medicine Good evidence is ignored  Too busy for EBM Five Alternatives to EBM: This was adapted from a paper by Isaacs and Fitzgerald BMJ 1999. To paraphrase Sir Winston Churchill, EBM is the worst form of medicine except for all the others that have been tried. Eminence Based Medicine - 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 are the senior physicians on staff that make the "same mistakes with increasing confidence over an impressive number of years.” Vehemence Based Bedicine - The substitution of volume for evidence as an effective technique for brow beating your colleagues and for convincing relatives of your ability. The quality of the evidence is more important than the quantity of evidence. Eloquence Based Medicine - This is the physician with the year round suntan, Armani suit, pocket handkerchief and tongue that is as silky smooth as his silk tie. Sartorial and verbal eloquence should be no substitute for high-quality,

Date: October 14th, 2020 Guest Skeptic: Dr.Salim Rezaie is a community emergency physician at Greater San Antonio Emergency Physicians (GSEP), where he is the director of clinical education.  Salim is probably better known as the creator and founder of the wonderful knowledge translation project called REBEL EM. It is a free, critical appraisal blog and podcast that try to cut down knowledge translation gaps of research to bedside clinical practice. Reference: Rowell et al. Effect of Out-of-Hospital Tranexamic Acid vs Placebo on 6-Month Functional Neurologic Outcomes in Patients With Moderate or Severe Traumatic Brain Injury. JAMA 2020.  Case: A 42-year-old helmeted bicycle rider is involved in an accident where he hits his head on the ground.  At the time of emergency medical services (EMS) arrival, the patient is alert but seems a bit confused.  The accident was within one hour of injury and his Glasgow Coma Scale (GSC) score was 12. Vital signs show a slight tachycardia but otherwise normal. Pupils were both equal and reactive and he doesn’t appear to have any other traumatic injuries, or focal neurologic deficits. Other injuries appear minimal with some abrasions from the fall. Background: The CRASH-2 trial, published in 2010, showed a 1.5% mortality benefit (NNT 67) for patients with traumatic hemorrhage who received tranexamic acid (TXA) compared to placebo. Dr. Anand Swaminathan and I covered that classic paper on SGEM#80. TXA has become standard practice in many settings as a result of this data.  However, patients with significant head injury were excluded in this study and it was unclear of the effect of TXA in this group. CRASH-3 Fast forward to October 2019, when CRASH-3 was published. This large, very well-done randomized placebo-controlled trial examined the use of TXA in patients with traumatic brain injuries (TBIs) with GCS score of 12 or lower or any intracranial bleed on CT scan and no extracranial bleeding treated within 3 hours of injury. The authors reported no statistical superiority of TXA compared to placebo for the primary outcome of head injury-related deaths within 28 days. We reviewed that article published in the Lancet in SGEM#270. Subgroup analysis did demonstrate that certain patients (GCS 9 to 15 and ICH on baseline CT) showed a mortality benefit with TXA. While very interesting and potentially clinically significant, we need to be careful not to over-interpret this subgroup analysis. We did express concern over the possibility that this subgroup would be highlighted and “spun”. Unfortunately, that did happen with a subsequent media blitz and a misleading infographic. Further data is clearly needed to elucidate the role of TXA in patients with TBI. Clinical Question: Does pre-hospital administration of TXA to patients with moderate or severe traumatic brain injury improve neurologic outcomes at 6 months? Reference: Rowell et al. Effect of Out-of-Hospital Tranexamic Acid vs Placebo on 6-Month Functional Neurologic Outcomes in Patients With Moderate or Severe Traumatic Brain Injury. JAMA 2020. Population: Patients 15 years of age or older with moderate or severe blunt or penetrating TBI. Moderate to severe TBI was defined as a GCS 3 to 12, at least one reactive pupil, systolic blood pressure ≥90mmHg prior to randomization, able to receive intervention or placebo within two hours from injury, and destination to a participating trauma center. Exclusions: Prehospital GCS=3 with no reactive pupil, start of study drug bolus dose greater than two hours from injury, unknown time of injury, clinical suspicion by EMS of seizure activity, acute MI or stroke, or known history, of seizures, thromboembolic disorders or renal dialysis, CPR by EMS prior to randomization, burns > 20% total body surface area, suspected or known prisoners, suspected or known pregnancy), prehospital TXA or other pro-coagulant drug given prior to randomization or subjects who have activated the “opt-out” process. Interventions: They had two intervention groups. The Bolus Maintenance Group received an out-of-hospital TXA 1g intravenous (IV) bolus and in-hospital TXA 1g IV 8-hour infusion. The Bolus Only Group received an out-of-hospital TXA 2g IV and in-hospital placebo 8-hour IV infusion. Comparison: The Placebo Group received Out-of-hospital saline IV bolus and in-hospital saline 8-hour infusion. Outcome: Primary Outcome: Favorable neurologic function at 6 months (defined as Glasgow Outcome Scale-Extended Score >4 which is considered moderate disability or good recovery) Secondary Outcomes: There were 18 secondary endpoints, of which 5 reported statistical analysis in this trial 28 day mortality 6-Month Disability Rating Scale Score (0 equals no disability and 30 equals death) Progression of intracranial hemorrhage (Defined as >33% increase in the combined volume of hemorrhage) Incidence of seizures Incidence of thromboembolic events Authors’ Conclusions: “Among patients with moderate to severe TBI, out-of-hospital tranexamic acid administration within 2 hours of injury compared with placebo did not significantly improve 6-month neurologic outcome as measured by the Glasgow Outcome Scale-Extended.” Quality Checklist for Randomized Clinical Trials: The study population included or focused on those in the emergency department. Yes and No The patients were adequately randomized. Yes The randomization process was concealed. Yes The patients were analyzed in the groups to which they were randomized. No 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. Yes All groups were treated equally except for the intervention. Yes Follow-up was complete (i.e. at least 80% for both groups). Unsure All patient-important outcomes were considered. Yes The treatment effect was large enough and precise enough to be clinically significant. No Key Results: They enrolled and randomized 1,063 patients with 966 patients included in the primary analysis group. The mean age was in the late 30’s, ¾ were male, the vast majority (>95%) of patients had blunt trauma, mean out-of-hospital GCS score was 8 and the mean time from injury to out-of-hospital study drug administration was just over just over 40 minutes. No statistical difference in favorable neurologic function at 6 months with TXA compared to placebo. Primary Outcome: Favorable Neurologic Function at 6 Months 65% TXA groups vs. 63% Placebo group Difference 3.5% (90% 1-sided confidence limit for benefit, −0.9%); P = 0.16 Secondary Outcomes:  28 Day Mortality: No statistical difference between groups (14% vs. 17%) Disability Rating Scale Score: No statistical difference between groups (6.8 vs. 7.6) Progression of Intracranial Hemorrhage: No statistical difference between groups (16% vs. 20%) Incidence of Seizures: Bolus Only (5%), Bolus Maintenance (2%) and placebo (2%). Not statistically significant. Thrombotic Events: Bolus Only (9%), Bolus Maintenance (4%) and placebo (10%) 1. Survival Bias: When a selection process of a trial favors certain individuals who make it past a certain point in time and ignores the individuals who did not. In other words, patients who die shortly after the start of follow-up may not have had an opportunity to become exposed and will not have their results recorded. This introduces an artificial survival advantage associated with the exposed subjects regardless of treatment effectiveness. When survivor treatment selection is not addressed, ineffective treatment may appear to prolong survival or worsen adverse events. Severely injured patients who survive longer in the bolus only group may have lived long enough to experience more complications and only those who survive out to 6 months can have an outcome recorded. 2. Glasgow Coma Scale (GCS) Score: The GCS has limitations including inter rater reliability (IRR) issues. This could have contributed to 20% of patients originally given a score of <13 in the pre-hospital setting arrived at the hospital with a GCS of 13 or greater.  Another concern is that the GCS is not a diagnostic tool. It cannot reliably discriminate between CNS depressed states (intoxication, hypoglycemia, sedation, shock, seizure, etc) and intracranial hemorrhages. 3. Few Intracranial Hemorrhages (ICHs): This trial ultimately only had a small number of patients with ICH (58%). This means many patients without ICH were given TXA and were included in the analysis. While being practical it could dilute any potential treatment benefit of TXA in patients with isolated TBI.  4. Loss to Follow-Up: Depending on how you define and calculate loss to follow-up. It was at least 15% and could have been as high as 23%. I usually get concerned when the loss to follow-up is larger than the difference in the primary outcome. This is more important when the authors are claiming superiority which they are not doing in this case. The authors correctly do not conclude superiority but that does not mean we should conclude TXA given pre-hospital does not work in patients with isolated TBI. However, this trial does not support that TXA does work but, given the limitations we have discussed, it is still a reasonable hypothesis that it may work and merits further testing. 5. Minimal Clinically Important Difference (Statistical vs Clinical Significance): Although the study was not powered to detect a difference in mortality (secondary outcome), in this trial we see a ≈3.0% difference in 28-day mortality (not statistically significant) which could be clinically important at a population level. If we assume an estimated 56,

Date: October 9th, 2020 Guest Skeptic: Dr. Sergey Motov is an Emergency Physician in the Department of Emergency Medicine, Maimonides Medical Center in New York City. He is also one of the world’s leading researchers on pain management in the emergency department, specifically the use of ketamine. His twitter handle is @PainFreeED. Reference: Friedman et al. Ibuprofen Plus Acetaminophen Versus Ibuprofen Alone for Acute Low Back Pain: An Emergency Department-based Randomized Study. AEM 2020. Case: A 41-year-old man without a significant past medical history presents to the emergency department (ED) with a chief complaint of lower back pain that started 48 hours prior to the ED visits after attempting to move a couch in his house. He describes the pain as sharp, constant, non-radiating, and 6/10 in intensity. Pain gets worse with movement and minimal bending. The pain is limiting his usual activities included his ability to go to work. He denies weakness or numbness of the legs as well as bowel or bladder dysfunctions. You perform a physical exam and note prominent tender area to palpation at the right lumbar region. You explain to the patient the most likely diagnosis is a muscle strain. Your usual approach is to treat this type of case scenario with Ibuprofen. The patient asked you if Ibuprofen alone will be strong enough to control his pain. Background: Pain is one of the most frequent reasons to attend an ED. Low back pain (LBP) is responsible for 2.3% of all ED visits resulting in 2.6 million visits each year in the USA (Friedman et al Spine 2010). We have covered back pain a number of times on the SGEM. SGEM#87: Let Your Back Bone Slide (Paracetamol for Low-Back Pain) SGEM#173: Diazepam Won’t Get Back Pain Down SGEM#240: I Can’t Get No Satisfaction for My Chronic Non-Cancer Pain The SGEM bottom line from SGEM#240 was: There appears to be no long-term analgesics benefits from prescribing opioids for chronic non-cancer pain (nociceptive and neuropathic). However, their use is associated with increased adverse events. The American College of Emergency Physicians (ACEP) has updated their clinical policy on prescribing opioids for adult ED patients. There are no Level A recommendations, one Level B recommendation and multiple Level C recommendations (ACEP June 2020) In adult patients experiencing opioid withdrawal, is emergency department-administered buprenorphine as effective for the management of opioid withdrawal compared with alternative management strategies? Level B Recommendations: When possible, treat opioid withdrawal in the emergency department with buprenorphine or methadone as a more effective option compared with nonopioid-based management strategies such as the combination of α2-adrenergic agonists and antiemetics Many other pharmaceutical treatments besides opioids have been tried to address acute LBP pain with limited success. These include: acetaminophen (Williams et al Lancet 2014), muscle relaxants (Friedman et al JAMA 2015), NSAIDs (Machado et al Ann Rheum Dis 2017), steroids (Balakrishnamoorthy et al Emerg Med J 2014) and benzodiazepines (Friedman et al Ann Emerg Med 2017). Pain outcomes for patients with LBP are generally poor; One week after an ED visit in an unselected LBP population, 70% of patients report persistent back pain–related functional impairment and 69% report continued analgesic use (Friedman et al AEM 2012). There are a number of non-pharmaceutical treatment modalities that have also been tried to treat low back pain. They include: CBT and mindfulness (Cherkin et al JAMA 2016), chiropractic (Paige et al JAMA 2017), physical therapy (Paolucci et al J Pain Research 2018) and acupuncture (Colquhoun and Novella Anesthesia and Analgesia 2013). None of these other treatments has high-quality evidence supporting their use. Nonsteroidal anti-inflammatory drugs (NSAIDs) are recommended as first-line medication therapy for patients with acute LBP.  Acetaminophen is often used for acute LBP, although it is unlikely to be effective when used as monotherapy. Whether or not combining an NSAID with acetaminophen can improve patient outcomes is unknown. Clinical Question: Is the addition of acetaminophen to ibuprofen better than ibuprofen alone in treating ED patients with acute, non-traumatic, non-radicular low back pain? Reference: Friedman et al. Ibuprofen Plus Acetaminophen Versus Ibuprofen Alone for Acute Low Back Pain: An Emergency Department-based Randomized Study. AEM 2020. Population: Adults aged 21 to 69 years who presented to the ED primarily for management of acute non-traumatic, non-radicular, musculoskeletal LBP with Roland Morris Disability Questionnaire (RMDQ)score of >5. The RMDQ is a 24-item questionnaire commonly used to measure LBP and related functional impairment. The scale goes from 0 (no impairment) to 24 (maximum impairment). Exclusions: “non- musculoskeletal etiology of low back, such as urinary tract infection or influenza-like illness; radicular pain, defined as pain radiating below the gluteal folds in a dermatomal distribution; pain duration > 2 weeks (336 hours); or a baseline LBP frequency of once per month or more frequently. Patients with substantial, direct trauma to the back within the previous month were excluded as were those who were unavailable for follow-up, those who were pregnant or breastfeeding, patients with a chronic pain syndrome defined as use of any analgesic medication on a daily or near-daily basis, and those who were allergic to or intolerant of the investigational medications.” Intervention: Combination ofibuprofen 600mg plus acetaminophen 500 to 1000mg, orally, every 6 hours. Comparison: Monotherapy of Ibuprofen 600mg plus placebo,orally, every 6 hours. Outcome: Primary Outcome: Improvement of LBP on the RMDQ between ED discharge and the 7-day telephone follow-up.  Secondary Outcomes: 1 week and 48 hours after ED discharge were as follows: 1) participants’ worst LBP during the previous 24 hours, using a four-item ordinal scale (severe, moderate, mild, or none); 2) the frequency of LBP during the previous 24 hours using a five-item scale (not at all, rarely, sometimes, usually, always); 3) the frequency of any analgesic or LBP medication use during the previous 24 hours; 4) satisfaction with treatment, as measured by response to the question, “The next time you have back pain, do you want to take the same medications you’ve been taking this past week?”; 5) the day post–ED discharge the participant was able to return to usual activities; and 6) the frequency of visits to any health care provider. Authors’ Conclusions: “Among ED patients with acute, nontraumatic, non-radicular LBP, adding acetaminophen to ibuprofen does not improve outcomes within 1 week.” 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. Yes 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. No Key Results: They screened 605 patients for eligibility and were able to randomize 120. The mean age was 41 years, 52% were men, mean duration of symptoms was 48 hours and 80% were working at least 30 hours a week. No statistical difference between ibuprofen plus acetaminophen and ibuprofen alone in back pain improvement at one week. Primary Outcome: Mean improvement of RMDQ (+/-SD) at 1 week Combo 11.1 (+/- 10.7) vs Mono 11.9 (+/- 9.7) Between group difference 0.8 (95% CI -3.0 to 4.7) Secondary Outcomes:  Participants’ worst LBP during the previous 24 hours, using a four-item ordinal scale (severe, moderate, mild, or none): No statistical difference Frequency of LBP during the previous 24 hours using a five-item scale (not at all, rarely, sometimes, usually, always): More frequent in combination group Frequency of any analgesic or LBP medication use during the previous 24 hours: No statistical difference Satisfaction with treatment, as measured by response to the question, “The next time you have back pain, do you want to take the same medications you’ve been taking this past week?” No statistical difference How many days post–ED discharge the participant was able to return to usual activities: No statistical difference Frequency of visits to any health care provider: No statistical difference 1. Ibuprofen Dosing: They used 600mg of ibuprofen in this trial rather than 400mg. Unlike opioid analgesics, NSAID dosing is limited by their “analgesic ceiling”, meaning there is a dose-analgesic response. Above certain doses, NSAIDs produce more side effects or harms without providing additional analgesia. Our team has published evidence supporting this on both ibuprofen (Motov et al Ann Emerg Med 2019) and ketorolac (Motov et al Ann Emerg Med 2017). The ketorolac paper was covered on SGEM#175. 2. External Validity: This study was conducted in two urban EDs serving a socioeconomically depressed population. Socioeconomic factors have been shown to be associated with an increased risk of pain (Poleshuckand Green Pain 2008). It is unclear if this data could be applied to other populations. 3.

Date: September 28th, 2020 Guest Skeptic: Dr.Michelle Cohen (@DocMCohen). She is a rural Family Physician, writer (CBC News, Toronto Star and McLean’s Magazine), Assistant Professor Queens University and the Co-Chair of the Advocacy Committee of Canadian Women in Medicine. Dr. Michell Cohen This is an SGEM Xtra episode based on an article by Dr. Cohen and Dr. Kiran published in the Canadian Medical Association Journal (CMAJ). The article was called Closing the gender pay gap in Canadian medicine. Please listen to the SGEM podcast to hear Dr. Cohen answer five questions and discuss the issue of gender pay inequity.   Five Questions about the Gender Pay Gap Is the gender pay gap real? Do women just work less (or less efficiently) than men? What are some of the root causes of the gender pay gap? What can we learn from other jurisdictions? What can be done to close the gender pay gap in Canadian medicine? The CMAJ article fits with the evidence presented at FIX19. It also is consistent with the study published a year ago that showed Ontario female surgeons made 24% less per hour than male surgeons. This pay gap persisted even after adjusting for various factors (Dossa et al JAMA 2019). The Ontario Medical Association (OMA) has published a report called Understanding Gender Pay Gaps Among Ontario Physicians from their Human Resources Committee. It found that male physicians on average bill 15.6% more than female physicians even after controlling for a number of variables. There was a recent study that looked at the 194 countries and the gender of the national leader (Garikipati and Kambhampati 2020). They found that countries led by women were associated with better COVID-outcomes. This is low quality evidence because it is an observational study that is pre-print (not peer reviewed) and we should not over-interpret the results. This association between women leaders and good COVID responses was discussed in a debate about masks back in the spring of this year (SGEM Xtra Masks4All). There was a stronger association between women leaders and good COVID responses than to mandatory universal masking policies. Conclusions to the CMAJ Article “Women continue to be paid less than men in medicine. The gender pay gap exists within every specialty and also between specialties, with physicians in male­dominated specialties receiving higher payments. The gap is not explained by women working less but, rather, relates more to systemic bias in medical school, hiring, pro­motion, clinical care arrangements, mechanisms used to pay physicians and societal structures more broadly. Progress in Canada will require a commitment from medical associations and governments to close the pay gap, starting with transparent reporting of physician payments stratified by gender. We need to go further as a professionto understand how gender, race, disability and other identi­ties intersect to affect gaps in pay and then take action to address these gaps to realize the vision of pay equity for all in medicine.” We need to ensure that everyone gets the emergency care they need, regardless of whether they identify as a man or woman. The emergency department is like a lighthouse. It is the one place in the house of medicine where the light is always on and will treat anyone at any time for anything. The gender inequity discussion does dichotomize things into men and women. This is a false dichotomy. There are people who do not identify as a man or women. Gender is complex and on a spectrum. There is how a person identifies, expresses themselves, the sex assigned at birth, who they are physically attracted to and who they are emotionally attracted to. I would suggest that FBM is just the starting point and we need to take it one step further to Gender-Based Medicine (GBM). The Gender Unicorn is a graphic representation demonstrating the complexity of gender and sexuality. We need to make sure that the house of medicine is not just inclusive and tolerant but accepting and welcoming to everyone regardless of how they identify. The progression, in my opinion, should be from Evidence-Based Medicine (male dominated) to Feminist-Based Medicine (recognizing gender inequity) to Gender-Based Medicine (more inclusive) and ultimately to Humanist-Based Medicine (HBM). There are other inequities in medicine besides just gender. There are problems with race, religion, socioeconomic status, mental health, physical ability, etc. In order to provide patients with the best care, based on the best evidence we need high-quality, clinically relevant research that is inclusive and representative of everyone; remove inequities for those who generate research and provide care at the bedside; and finally, recognize everyone has value and should expect and deserve great care. 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. So, patients 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.

Date: October 2nd, 2020 Guest Skeptic: Dr.Barbra Backus is an emergency physician at the Emergency Department of the Erasmus University Medical Center in Rotterdam, the Netherlands. She is the creator of the HEART Score and an enthusiastic researcher. Reference: Claiborne Johnston S et al. Ticagrelor and Aspirin or Aspirin Alone in Acute Ischemic Stroke or TIA. NEJM July 2020 Case:  A 65-year-old man with a history of well controlled hypertension presents to the emergency department and is diagnosed with a mild stroke (NIHSS score 3). He is a non-smoker, not diabetic and has never had a stroke before. The only medicine he takes is an angiotensin converting enzyme inhibitor. You are wondering if he should be discharged on just aspirin or aspirin plus another antiplatelet agent like ticagrelor. Background: Acute ischemic strokes are the leading cause of disability in our society and the third most common cause of death. Aspirin has been used to prevent a subsequent stroke in patients who suffered an acute ischemic stroke (AIS) or transient ischemic attack (TIA), which occur in approximately 5-10% of patients in the first few months after their primary event. Trials have shown mixed results with the combination of aspirin with clopidogrel in this population. SGEM#24 reviewed a randomized controlled trial (RCT) of aspirin vs. aspirin + clopidogrel in patients with recent symptomatic lacunar infarcts identified by MRI (Benavente et al NEJM 2012). Adding clopidogrel to aspirin did not reduce recurrent strokes but did increase risk of bleed and death. The study was stopped early due to harm and lack of efficacy. An RCT done in China on patients with minor strokes or TIAs who were treated within 24 hours after the onset of symptoms showed that aspirin plus clopidogrel is superior to aspirin alone for reducing the risk of stroke in the first 90 days and does not increase the risk of hemorrhage (Wang et al NEJM 2013). A third RCT assigned patients with minor ischemic stroke or high-risk TIA to ASA alone or the combination of both aspirin and clopidogrel. This trial was also stopped early because of lower risk of major ischemic events but higher risk of major hemorrhage with the combination therapy compared to aspirin alone (Johnston et al NEJM 2018). As an antiplatelet agent that blocks the P2Y12 receptor, clopidogrel requires hepatic conversion to its active form through a pathway that is ineffective in 25% of white and 60% of Asian patients; efficacy is therefore uncertain in these patients (Pan et al Circulation 2017). Ticagrelor is a direct-acting antiplatelet agent that does not depend on metabolic activation. A trial of ticagrelor alone did not show a benefit over aspirin in preventing subsequent cardiovascular events (Johnston et al NEJM 2016). The effect of the combination of ticagrelor and aspirin on prevention of stroke has not been well studied. Clinical Question: Is the combination of ticagrelor and aspirin superior to aspirin alone in reducing the risk of subsequent stroke or death among patients with acute non-cardioembolic cerebral ischemia? Reference:Claiborne Johnston S et al. Ticagrelor and Aspirin or Aspirin Alone in Acute Ischemic Stroke or TIA. NEJM July 2020 Population: Patients 40 years and older who experience a mild-to-moderate acute noncardioembolic ischemic stroke (NIHSS score of 5 or less), or high-risk TIA (ABCD2>5) or symptomatic intracranial or extracranial arterial stenosis (>50% lumen narrowing accounting for the TIA) Excluded: Thrombolysis or EVT was planned <24 hours before randomization or if there was planned use of anticoagulation or specific anti-platelet therapy other than ASA. Patients were also not eligible if they had “hypersensitivity to ticagrelor or ASA, a history of atrial fibrillation or ventricular aneurysm or a suspicion of a cardioembolic cause of the TIA or stroke, planned carotid endarterectomy that required discontinuation of the trial medication within 3 days after randomization, a known bleeding diathesis or coagulation disorder, a history of intracerebral hemorrhage, gastrointestinal bleeding within the past 6 months, or major surgery within 30 days before randomization.” Intervention: 30-day regimen of ticagrelor (180-mg loading dose followed by 90 mg twice daily) plus aspirin (300 to 325 mg on the first day followed by 75 to 100 mg daily). Comparison: 30-day regimen of matching placebo plus aspirin. Outcomes: Primary Outcome: Composite of stroke or death within 30 days. Secondary Outcomes: First subsequent ischemic stroke, incidence of disability within 30 days and adverse events. Authors’ Conclusions: “Among patients with a mild-to-moderate acute noncardioembolic ischemic stroke (NIHSS score ≤5) or TIA who were not undergoing intravenous or endovascular thrombolysis, the risk of the composite of stroke or death within 30 days was lower with ticagrelor–aspirin than with aspirin alone, but the incidence of disability did not differ significantly between the two groups. Severe bleeding was more frequent with ticagrelor.” 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. Yes All groups were treated equally except for the intervention. Yes Follow-up was complete (i.e. at least 80% for both groups). Yes All patient-important outcomes were considered. No The treatment effect was large enough and precise enough to be clinically significant. Yes Key Results: 11,016 patients underwent randomization (5,523 to ticagrelor-aspirin and 5,493 to placebo plus aspirin). The average participant was 65 years old, more than 60% were male, more than 75% had a history of hypertension and 91% presented with ischemic strokes. Thirteen percent of the patients were taking aspirin before the initial index stroke or TIA. Less strokes and more bleeds in the combination group with no statistical difference between the two groups for a good neurologic outcome. Primary Outcome: Stroke or death within 30 days 5% in combo group vs. 6.6% in aspirin alone (HR, 0.83; 95% CI, 0.71 to 0.96) p=0.02 Secondary Outcomes:  Subsequent ischemic stroke 5.0% vs. 6.3% (HR, 0.79; 95% CI, 0.68 to 0.93) P=0.004 Incidence of disability was not statistically different 23.8 vs. 24.1% (P=0.61) Severe bleeding was greater in the combo group: 5% vs. 0.1% in the aspirin group (P=0.001) 1) Industry Funded: This trial was sponsored by the maker of ticagrelor and multiple authors reported financial conflicts of interest. A Cochrane SRMA has reported that industry funded studies have more favorable efficacy results and conclusions compared to non-industry funded studies. These differences cannot be explained by standard risk of bias assessment tools (Lundh et al 2017). 2) Low AIS and High TIAs: These are a very select group of patients with many exclusion criteria. This makes it difficult to apply the results to all low AIS and high-risk TIA patients. 3) Composite Outcome: There can be only one…primary outcome. Their primary outcome was stroke or death within 30 days. While they did find a statistical difference between the combination therapy and aspirin alone, the difference was driven by stroke. There was no statistical difference in death between the two groups 6% vs 0.5% (HR 1.33, 95% CI, 0.81 to 2.19). 4) Relative vs. Absolute Reduction: They demonstrated a 17% relative reduction in their composite primary outcome or a 1.1% absolute reduction. This gives an NNTB of 90 for a disease-oriented outcome (DOO) of stroke because there was no difference in death or disability which are patient oriented outcomes (POO). For Serious adverse events there as a 500% relative increase in severe bleeding which as only a 0.4% absolute increase. This gives a NNTH of 250 for a POO. 5) Length of Treatment: They only looked at 30 days for their outcomes. Patients with small strokes or high risk TIAs are going to be on antiplatelet drugs indefinitely. It would have been helpful to see longer term outcomes of at least 90 days like many stroke studies or even better years. Questions include: Does the efficacy continue? Would mortality benefit become statistically significant? Would the severe adverse event rate increase with time? It is interesting that the premature discontinuation rate was four times higher in the combination group (2.6% vs 0.6%) due to bleeding. This does not address the additional cost of ticagrelor ($360/month vs $1/month). Comment on Authors’ Conclusion Compared to SGEM Conclusion: We generally agree with the authors’ conclusions. SGEM Bottom Line: Ticagrelor in combination with aspirin cannot be routinely recommended at this time. The decrease in subsequent strokes comes at a cost of increased serious bleeding and no increase in a good neurologic outcome. A risk assessment and shared decision making is encouraged. Case Resolution: You discharge the patient home with aspirin alone with an Urgent TIA/Stroke Clinic follow-up in the next 24 to 48 hours. Dr. Barbra Backus Clinical Application: With antiplatelet drugs and anticoagulants there is always a trade-off. While adding another antiplatelet drug to aspirin has the potential to increase efficacy it also increases the potential harm.

Date: September 22nd, 2020 Guest Skeptic: Dr. Chris Bond is an emergency medicine physician in Calgary. He is also an avid FOAM supporter/producer through various online outlets including TheSGEM. Reference: Warren et al. Antacid monotherapy is more effective in relieving epigastric pain than in combination with lidocaine. A randomized double-blind clinical trial. AEM Sept 2020. Case: A 34-year-old male presents to the emergency department with burning epigastric pain after eating two hours ago. He says he gets this from time to time but this is the worst it has ever been. He denies chest pain, shortness of breath, fever and vomiting. His vital signs are within normal limits and his abdominal exam reveals mild epigastric and left upper quadrant tenderness with no peritonitis. Pink Lady Cocktail Background: Patients presenting to emergency departments (EDs) with epigastric pain are typically treated with an antacid, either alone or combined with other medications. Such medications include viscous lidocaine, an antihistamine, a proton pump inhibitor, or an anticholinergic (1,2). In Canada we often use an antacid plus viscous lidocaine referred to as a “Pink Lady”. This is different than the alcoholic cocktail called a Pink Lady. In the US, combination treatment is often called a “GI Cocktail”. There are mixed results from studies with varying methodological quality looking at acute dyspepsia management in the ED. One single-blind study comparing 30 mL of antacid with or without 15 mL of viscous lidocaine found the addition of lidocaine significantly increased pain relief, decreasing patient pain score by 40 mm compared to 9 mm with antacid monotherapy (3). Another single-blind RCT comparing antacid plus either benzocaine solution or viscous lidocaine found no statistical difference between the two interventions, however, there was no antacid monotherapy group (4). A larger, double-blind RCT of 113 patients compared 30 mL of antacid monotherapy, antacid with 10 mL of an anticholinergic, and antacid with anticholinergic and 10 mL of 2% viscous lidocaine. This study found all treatments had clinical efficacy and there was no statistical difference in pain relief between the three treatment groups. The conclusion from Berman et al was to recommend antacid monotherapy (5). Clinical Question: Is antacid monotherapy more effective in relieving epigastric pain than in combination with lidocaine? Reference: Warren et al. Antacid monotherapy is more effective in relieving epigastric pain than in combination with lidocaine. A randomized double-blind clinical trial. AEM Sept 2020. Population: Adult patients with epigastric pain or dyspepsia presenting to the emergency department. Excluded: Patients unable to consent or under 18 years of age. Intervention:  Arm 1 (Viscous): Received 10 mL oral lidocaine 2% viscous gel plus 10 mL antacid (traditional antacid/lidocaine mixture) Comparison: Arm 2 (Solution): Received 10 mL lidocaine 2% solution plus 10 mL antacid Arm 3 (Antacid): Received 20 mL antacid alone Outcome: Primary Outcome: Change in pain scores on 100mm visual analog scale (VAS) at 30 minutes after treatment. Secondary Outcomes: Medication palatability (taste, bitterness, texture, and overall acceptability) using a VAS, change in pain score 60 minutes post administration and adverse events. Dr. Jamie Warren This is an SGEMHOP episode which means we have the lead author on the show, Dr. Jaimee Warren. She is a first-year doctor at the Royal Melbourne Hospital and an aspiring emergency and retrieval physician. She hopes to one day work in rural and extreme environments. Authors’ Conclusions: “A 20 mL dose of antacid alone is no different in analgesic efficacy than a 20 mL mixture of antacid and lidocaine (viscous or solution). Antacid monotherapy was more palatable and acceptable to patients. A change in practice is therefore recommended to cease adding lidocaine to antacid for management of dyspepsia and epigastric pain in the ED.” Quality Checklist for Randomized Clinical Trials: The study population included or focused on those in the emergency department. Yes The study participants were adequately randomized. Yes The randomization process was concealed. Yes The participants were analyzed in the groups to which they were randomized. Yes The study participants were recruited consecutively (i.e. no selection bias). No The participants in both groups were similar with respect to prognostic factors. Unsure All participants were unaware of group allocation. No All groups were treated equally except for the intervention. Yes Follow-up was complete (i.e. at least 80% for both groups). Yes All patient-important outcomes were considered. Yes The treatment effect was large enough and precise enough to be clinically significant. Yes Key Results: The trial enrolled 94 patients and 89 could be analyzed (30 viscous, 31 solution and 28 antacid group). The mean age was in the early 40’s, with around 2/3 female and 80% of patients were discharged with a gastrointestinal diagnosis.  All three treatments (viscous, solution or antacid monotherapy) worked and there was no statistical difference between groups. Primary Outcome: The lidocaine solution with antacid and antacid monotherapy provided clinically important (>13 mm) analgesia at 30 minutes (17mm and 20mm), viscous lidocaine with antacid did not (9mm). However, this still did not result in a statistically significant difference between treatments. Secondary Outcomes: At 60 minutes, all treatment groups (viscous, solution and antacid monotherapy) experienced additional pain relief. The change in median pain scores was clinically significant (>13 mm) for all three arms (21mm, 26mm, and 32mm). The most frequent adverse effect was oral numbness (lidocaine viscous 20% and lidocaine solution 26%). Two patients in the viscous arm reported dizziness and tiredness (7%), and four patients in the solution arm reported cough, nausea, and dizziness (13%). One patient in the antacid arm reported a dry mouth (4%). Participants found antacid monotherapy to be the most palatable solution, with statistically significant differences in taste, bitterness, and overall acceptability. Listen to the podcast on iTunes to hear Jaimee's responses to our ten nerdy questions. 1. Inclusion Criteria: Patients were enrolled prospectively based on the clinician providing an antacid therapy. This resulted in a large group of patients having non-GI causes of pain. Why not enroll patients for whom the final diagnosis was dyspepsia or epigastric pain after ED workup? 2. Selection Bias: Why were patients that presented overnight excluded from enrolment (funding for research staff 24/7)? Are these patients potentially different (eg. more severe presentations of alcohol related gastritis, large meals for dinner followed by lying down or other reasons)? 3. Unbalanced Groups: In Table 1, it appears that more patients in the lidocaine arms had prior proton pump inhibitor (PPI) use and more prior upper GI related diagnoses (eg. Peptic ulcer disease/gastritis/gastroesophageal reflux disease). It also appears the viscous group received more rescue analgesics in the ED. Can you confirm these are all non-statistically significant differences between groups as the p-values are not documented? 4. Blinding of Staff: The solutions were not made to look identical. This could have unblinded the trial to the nursing staff. Do you think that could have impacted the results and did you consider asking the nurses which group they felt the participant was randomized? 5. Placebo Effect: The patients may also have been unblinded and susceptible to a placebo effect. Lidocaine has a bitter taste and can cause oral numbness. It has been demonstrated that bitter tasting treatments can increase the placebo effect. Wright et al. If it Tastes Bad it Must Be Good: Consumer Naïve Theories and the Marketing Placebo Effect. Intern. J. of Research in Marketing 2013 Kihlstrom. Placebo: Feeling Better, Getting Better, and the Problems of Mind and Body. Mcgill J Med. 2008 Evans FJ. The placebo response in pain reduction. In: Bonica JJ, editor. Advances in Neurology. New York: Raven; 1974 6. Diagnosis: Do you think that the effectiveness of antacid monotherapy is the same whether the diagnosis is dyspepsia vs. GERD vs. gastritis vs. PUD? 7. Primary Outcome: Your primary outcome was a change in 100mm VAS at 30 min. While that is an important patient-oriented outcome (POO) what about length of relief? Your secondary outcome was 60min. What about a longer time frame or return to ED within 24hrs? 8. Other Comparisons: Can you comment on how use of these medications compares with H2 receptor antagonists and PPIs in terms of efficacy for treating dyspepsia and epigastric pain in the ED? 9. Down Under: This was a single centre study conducted in Melbourne, Australia. Patient expectations can be different depending on the country. What are your thoughts to the external validity to other countries (UK, USA, Canada, Europe, etc)? Do you think you would find similar results? 10. Anything Else: Is there anything else you’d like to comment on about your paper that we have not asked, or you think is important for the SGEMers to know? Comment on Authors’ Conclusion Compared to SGEM Conclusion: We generally agree with the authors’ conclusions but would say that a change in practice should be “considered” rather than “recommended”. SGEM Bottom Line: Consider using antacid monotherapy in place of lidocaine/antacid combination therapy for patients with dyspepsia. Case Resolution: You give your patient 20 mL of antacid and his epigastric pain improves.

Date: September 16th, 2020 Guest Skeptics: Dr. Robert Goulden and Dr. Audrey Marcotte are Chief Residents from the Royal College of Emergency Medicine Program at McGill University. Robert’s academic interests include research and evidence-based medicine. Alongside his EM residency, he is doing a PhD in epidemiology. Audrey’s academic interests include trauma and resuscitation. Outside of medicine, Audrey likes to play rugby and run. Reference: Roberts et al. Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial. The Lancet 2020 This was an SGEM Journal Club episode recorded live at McGill University Grand Rounds. This was the third time coming to McGill University Department of Emergency Medicine to give Grand Rounds. The first visit was back in 2013 for SGEM#50: Under Pressure - Vasopressin, Steroids and Epinephrine in Cardiac Arrest. The bottom line was this was interesting, but VSE protocol was not ready for routine use. The second visit was SGEM#176: Somebody’s Watching Me – Cardiac Monitoring for Chest Pain. We were trying to answer the question: Do all patients presenting to the emergency department with chest pain need to be placed on cardiac monitoring or could some be safely removed? The SGEM Bottom Line was that for some patients presenting with chest pain who are chest pain free and have normal/non-specific ECG findings could potentially be safely removed from cardiac monitoring using the Ottawa CPCM Rule. Five Rules of SGEM-JC Case:A 58-year-old man presents with hypotension, tachycardia, and pallor. He vomits a large amount of bloody emesis and has epigastric discomfort. He is not taking any anti-coagulants. He remains hemodynamically unstable despite initial resuscitation and has another episode of hematemesis in front of you. While waiting for your consultant to answer the phone, you consider treating him with tranexamic acid (TXA), but wonder if it will prevent death from gastrointestinal (GI) bleeding. Background: We have covered the use of TXA a number of times on the SGEM. TXA is an anti-fibrinolytic agent that inhibits clot breakdown and has demonstrated mixed results in different clinical settings. The CRASH-2 trial showed a 1.5% absolute mortality benefit with TXA in adult trauma patients compared to placebo (SGEM#80). TXA also seems to improve patient-oriented outcomes in epistaxis (SGEM#53 and SGEM#210). However, TXA did not show a statistically significant difference for the primary outcome in post-partum hemorrhage (SGEM#214) WOMAN Trial, hemorrhagic stroke (SGEM#236) or traumatic intracranial hemorrhage (SGEM#270) CRASH-3. A Cochrane systematic review and meta-analysis of eight smaller trials (n=1,701) using TXA in gastrointestinal bleeding suggested a large (40%) risk reduction in all-cause mortality (Bennett et al 2014). However, even a meta-analysis is prone to bias and is only as good as the quality of the included trials. When all participants in the intervention group with missing outcome data were included as treatment failures, or when the analysis was limited to trials with low risk of attrition bias the mortality benefit of TXA disappeared. Clinical Question: Does treatment with TXA reduce the mortality of patients with upper or lower GI bleeds? Reference: Roberts et al. Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial. The Lancet 2020 Population: Adult patients (16 years of age or 18 years of age and older depending on country) with significant upper or lower GI bleed. Significant bleed was defined clinically (judged at risk of bleeding to death, hypotension <90 mmHg systolic, tachycardia, signs of shock, needing transfusion, urgent endoscopy or surgery). Exclusion: Any patient whom the clinician felt had a clear indication or clear contraindication for TXA Intervention: Intravenous TXA, 1g loading dose over 10 minutes followed by 3g maintenance over 24 hours Comparison: Matching placebo (Sodium chloride 0.9% IV) Outcome:  Primary Outcome: Death due to gastrointestinal (GI) bleeding within five days Secondary Outcomes: Death due to gastrointestinal bleeding within 24h and within 28 days All-cause and cause specific mortality at 28 days Rebleeding within 24h, 5 days, 28 days Surgical or radiological intervention Blood product transfusion Thromboembolic events (deep vein thrombosis, pulmonary embolism, stroke, myocardial infarction) Seizures and other complications (sepsis, pneumonia, renal and liver failure, cardiac event) Days in intensive care unit Functional status (Katz index of Independence in activities of daily living) Authors’ Conclusions: “We found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a randomised trial.” 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). 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. Yes 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. No Key Results: Mean age 58 years, two-thirds male, nine out of ten were upper GI bleeds, half were thought to be due to varices and about 9% were known to be on anti-coagulants. No statistically significant difference in mortality from GI bleed. Primary Outcome: Mortality from GI bleed within five days 3.7% (TXA) vs. 3.8% (placebo), RR 0·99 (0·82–1·18) Secondary Outcomes:  No significant difference in all-cause mortality at 28 days, 9.5% (TXA) vs. 9.2% (Placebo), RR 1·03 (95% CI; 0·92–1·16) Statistically significant increase in venous thromboembolism (VTE), 0.8% (TXA) vs. 0.4% (Placebo). RR 1.85 (95% CI; 1.15-2.98). This effect was more marked in those with suspected variceal bleeding than in those with non-variceal bleeding (p=0.035 for heterogeneity). No significant difference in all other secondary outcomes including rebleed and death due to rebleed at multiple time points, need for additional interventions, and other safety outcomes 1) Consistency in Results: This trial is definitively and unambiguously “negative” - it’s actually rare that we get a trial result that is so clear cut. All of the different outcomes lined up as showing no statistical benefit, and there were no subgroups in which that differed. In contrast, think of CRASH-3 (TXA for intracranial hemorrhage) or PARAMEDIC-2 (epinephrine for out-of-hospital cardiac arrest), other well-conducted large RCTs, where the fact that some outcomes were “positive” and others “negative” have left people still debating how to interpret them. 2) Changing the Primary Outcome: Switching the outcome midway through a trial is a red flag for potential statistical shenanigans, as there is a risk that investigators are aware of partial results and are switching from a non-significant to a significant outcome. However, in this case the decision to switch was made and published with a justification before unblinding. However, they did shift from a reliable, unambiguous, patient-centred outcome - all-cause mortality at 28 days - to a much less patient and clinically important outcome - mortality from GI bleeding at five days. Patients (and clinicians) don’t usually care what they die of - they care whether they die or not. It’s also much more challenging to reliably determine the cause of death as compared to determining ifsomeone is dead or not. Imagine if TXA decreased GI bleeding death by 2% but increased VTE death by 4%. Should that be considered a positive trial?! In the end, it doesn’t matter as the original primary outcome of all-cause mortality at 28 days - which I think should be the outcome we are most interested in - was also not significantly different. “The sample size calculation was initially based on all­ cause mortality as the primary outcome since we expected that most deaths would be due to bleeding. However, while the trial was underway, we observed that over half of all deaths were due to non­bleeding causes. Accumulating evidence from other large trials of tranexamic acid showed no apparent effect on non­bleeding deaths." "The primary outcome was therefore changed to death due to bleeding within 5 days of randomisation on Nov 21, 2018. Based on the amended primary outcome, assuming a risk of death due to bleeding of 4%, a study with 12000 patients has about 85% power (two-­sided α of 5%) to detect a clinically important 25% relative reduction in death due to bleeding from 4% to 3%”. 3) Secondary Outcomes:  The finding of increased VTE risk is interesting. It may be a chance finding since there were lots of secondary analyses and by random chance alone, we would expect a few to be statistically different. However, this was a safety outcome for which there was a reasonable prior belief in potential harm, and their point estimate (RR 1.

Date: September 11th, 2020 This is an SGEM Xtra episode. I was invited by the College of Physicians and Surgeons of Ontario (CPSO) to give a talk at their council meeting on burnout. It was an opportunity to share my journey and give an important message about kindness. I have discussed burnout and wellness a number of times on the SGEM: SGEM#289: I Want a Dog to Relieve My Stress in the Emergency Department SGEM Xtra: CAEP Wellness Week 2019 SGEM Xtra: On the Edge of Burnout SGEM Xtra: Don’t Give Up – The Power of Kindness SGEM#178: Mindfulness – It’s not Better to Burnout than it is to Rust SGEM Xtra: Five Tips to Avoid Emergency Medicine Burnout Burnout vs. Moral Injury The word burnout was coined by Herbert Freudenberger in 1974. He defined it as “a state of fatigue or frustration that resulted from professional relationships that failed to produce the expected rewards”. A distinction between burnout and moral injury was made during the presentation. Moral injury has been defined as: “perpetrating, failing to prevent, bearing witness to, or learning about acts that transgress deeply held moral beliefs and expectations". This was originally described in soldiers’ responses to their actions during war. Journalist Diane Silver described moral injury in her State News article as “a deep soul wound that pierces a person’s identity, sense of morality, and relationship to society.” The moral injury of physicians is being unable to provide high-quality care they want to provide to their patients. My struggle with Burnout My struggle with burnout included the death of my father (Dr. Ken Milne Sr.) in November of 2018, the sudden death of my "little" brother Scottie (The Moose) in February 2020 and the unexpected death our family dog Moxy (best dog every) this summer. Much of this taking place in the context of the COVID19 global pandemic. All the slides from this CPSO presentation can be downloaded and shared from this link. The CPSO video recorded the presentation and it should be available soon. There are also a number of references for further information on burnout. 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 Shanafelt et al. Relationship Between Clerical Burden and Characteristics of the Electronic Environment With Physician Burnout and Professional Satisfaction. Mayo Clin Proc 2016 West et al. Interventions to prevent and reduce physician burnout: a systematic review and meta-analysis. Lancet 2016  Dr. Goldman & BatDoc One of the big lessons I have learned over the last two years is to be kinder. This was taught to me by my kindness mentor Dr. Brian Goldman from CBC show White Coat Black Art. He has published a book called The Power of Kindness: Why Empathy Is Essential in Everyday Life. I had the honour of interviewing Dr. Goldman on an SGEM Xtra. We need to try to be kinder to ourselves, kinder to each other and kinder to each other. In a world where you can be anything, be kind.   College of Physicians and Surgeons of Ontario The CPSO has recognized that our health care system is facing pressures and the COVID19 pandemic has made things even worse. The June 2020 eDialogue highlighted five things the college is doing to mitigate this increase in stress. Introduced Alternative Dispute Resolution mech as an option for the handling of low-risk matters Decreased the time to complete a complaint by 47% in 2019, compared to 2018 Promoted connectedness through the quality improvement’s (QI) emphasis on peer interactions Encouraged professionalism to flourish by developing a QI framework that allows physicians to self-direct their learning Redesigned policies that allow physicians to immediately understand and access College expectations Pills that can be hard to swallow - but can help a lot   Admitting that you're not okay Asking for help Allowing yourself to feel your emotions Removing toxic people, habits and belief systems Learning to accept change You can listen to the SGEM Podcast on iTunes or GooglePlay to hear more about my journey.  Telling my personal burnout story is not to get sympathy or pity. Rather it is to remind you that everyone has a story. Everyone can be fighting a battle you know nothing about. My story is only unique because it is my story, everyone will have their own story, and we all can struggle facing our personal difficulties.   While it can feel like we have the weight of the world on our shoulders right now please remember 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 not a weakness. And don’t panic, this too shall pass.There are a number of resources available if you are struggling with burnout: Physician Health Program ACEM Member Wellbeing ACEP Wellness Section CAEP Resident Wellness EMRA Wellness Committee The SGEM will be back next episode with a 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 (FOAMed). Our ultimate goal is for patients to get the best care, based on the best evidence. REMEMBER TO BE SKEPTICAL OF ANYTHING YOU LEARN, EVEN IF YOU HEARD IT ON THE SKEPTICS’ GUIDE TO EMERGENCY MEDICINE.

Date: August 27th, 2020 Guest Skeptic: Dr. Malthaner is the Chair/Chief of the Division of Thoracic Surgery, Director of Thoracic Surgery Research and Simulation, and Professor in the Departments of Surgery, Oncology, and Epidemiology and Biostatistics at the Schulich School of Medicine and Dentistry and Western University. Rick is also the founder of Western University’s Department of Surgery Journal Club and runs The Skeptik Thoracik Journal Club. Reference: Brown et al. Conservative versus Interventional Treatment for Spontaneous Pneumothorax. NEJM 2020 Case: A 49-year-old healthy male electrician presents to the emergency room with right chest pain and dyspnea. The work-up reveals a diagnosis of a right pneumothorax confirmed by chest x-ray (CXR). What do you do? Background: A patient with a pneumothorax is a common presentation to the emergency department. Pneumothoraxes can be broken down into either primary or secondary. Primary pneumothorax occurs in healthy people. Secondary pneumothoraxes are associated with underlying lung disease. There is considerable heterogeneity in the management of primary spontaneous pneumothoraxes, but the most common treatment is interventional drainage, sometimes progressing to surgical intervention. However, the insertion of a chest tube is often painful and can cause organ injury, bleeding, and infection. An alternative approach is conservative management, with intervention reserved for patients for whom the pneumothorax becomes physiologically significant. I covered in the Skeptik Thoracik Journal Club which can be viewed on YouTube. Clinical Question: Does everyone with a large first-time spontaneous pneumothorax need a chest tube? Reference: Brown et al. Conservative versus Interventional Treatment for Spontaneous Pneumothorax. NEJM 2020 Population: Patients 14 to 50 years of age with a unilateral primary spontaneous pneumothorax of 32% or more on chest radiography according to the Collins method. Exclusion: Previous primary spontaneous pneumothorax on the same side Secondary pneumothorax (defined as occurring in the setting of acute trauma or underlying lung disease including asthma with preventive medications or symptoms in the preceding two years) Coexistent hemothorax Bilateral pneumothorax “Tension’ pneumothorax” (systolic BP <90 mmHg, mean arterial pressure <65 mmHg, or shock index HR/SBP ≥1) Pregnancy at time of enrolment Social circumstances (inadequate support after discharge to re-attend hospital if required or unlikely to present for study follow up) Planned air travel within the following 12 weeks Intervention: A small chest tube (≤12 French) was inserted and attached to an underwater seal, without suction and a CXR was obtained one hour later. If the lung had re-expanded and the underwater drain no longer bubbled, the drain was closed with the use of a three-way stopcock. Four hours later, if the patient’s condition was stable and a repeat CXR showed that the pneumothorax had not recurred, the drain was removed, and the patient was discharged. If the initial drain insertion did not result in resolution on CXR or if the pneumothorax recurred under observation, the stopcock was opened, the underwater seal drainage was recommenced, and the patient was admitted. Subsequent interventions were at the discretion of the attending clinician. Comparison: Patients were observed for a minimum of four hours before a repeat CXR was obtained.After observation, if patients did not receive supplementary oxygen and were walking comfortably, they were discharged with analgesia and written instructions. Interventions were allowed in the conservative-management protocol under five conditions: Clinically significant symptoms persisted despite adequate analgesia; Chest pain or dyspnea prevented mobilization; Patient was unwilling to continue with conservative treatment; Patient’s condition became physiologically unstable (systolic blood pressure of <90 mm Hg, heart rate in beats per minute greater than or equal to systolic blood pressure in millimeters of mercury, respiratory rate of >30 breaths per minute, Spo2 of <90% while the patient was breathing ambient air or a repeat chest radiograph showed an enlarging pneumothorax along with physiological instability. In these situations, subsequent interventions were at the discretion of the attending clinician. Outcome: Primary Outcome: Complete radiographic resolution of primary spontaneous pneumothorax (full lung re-expansion), as determined by the treating physician, within eight weeks after randomization. Secondary Outcomes: Per-protocol analysis of the primary outcome. Time to radiographic resolution. Time to symptom resolution of symptoms. Pneumothorax recurrence 24 hours or later after chest tube removal. Adverse events. Length of stay (LOS) in the hospital in the first eight weeks. Number of invasive procedures. Number of radiologic investigations. Number of days off from work. Chest-tube drainage for equal to or greater than 72 hours. Patient satisfaction. Two sensitivity analyses of the primary outcome. Authors’ Conclusions: “Although the primary outcome was not statistically robust to conservative assumptions about missing data, the trial provides modest evidence that conservative management of primary spontaneous pneumothorax was noninferior to interventional management, with a lower risk of serious adverse events.” 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). 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. No 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: The cohort of patients analyzed was 256 (154 intervention group and 162 conservative group). The mean age was 26 years and the mean pneumothorax size was about 65% based on the Collins formula. Conservative management was shown to be non-inferior to placing a chest tube in a patient with a large first-time spontaneous pneumothorax.  Primary Outcome: Re-Expansion within Eight Weeks Intervention Group 98.5% vs. Conservative Group 94.4% Risk Difference -4.1% (95% CI; -8.6% to 0.5%) p=0.02 which meets the pre-specified non-inferiority margin of -9% Secondary Outcomes:  Sensitivity Analysis: Worst Case Intervention Group 93.5% vs. Conservative Group 82.5% Risk Difference -11.0% (95% CI; -19.4% to -1.5%) which does not meet pre-specified non-inferiority margin of -9% 1. Missing Data: An important thing to look at when critically appraising a study is how did the authors manage missing data? In this study, what happened when the data on patients in whom the 8-week visit occurred after 56 days? Were treated as missing, unless a later CXR showed a persisting pneumothorax, thereby confirming treatment failure. Two sensitivity analyses were undertaken in this trial. In one analysis, the 8-week window was extended to 63 days and data on patients in whom the 8-week visit occurred after 63 days were treated as missing, unless a later CXR showed a persisting pneumothorax, thereby confirming treatment failure. In the other analysis, data on patients in whom the 8-week clinic visit occurred after 56 days were imputed as failure (worst case scenario). 2. Per-Protocol vs. Intention-to-Treat (ITT) Analysis: Their primary outcome used an ITT analysis. It is better in non-inferiority trials to use a per-protocol analysis. This is because the ITT will bias towards finding non-inferiority while a per-protocol is a more conservative approach. Their secondary outcomes did include a per-protocolanalysis of the primary outcome (complete lung re-expansion within 8 weeks, as reviewed by two radiologists who were unaware of the trial-group assignments). In the per-protocol analysis, 98.4% in the intervention group had resolution within 8 weeks as compared with 94.6% in the conservative group (RD, −3.8% [95% CI; −8.3 to 0.7]). 3. Satisfaction Scale: They used a 6- point Likert scale to assess patient satisfaction at eight weeks. While the scale has face validity, we are not aware that this specific instrument has been validated in this disease specific condition. I don’t think one exits and this may be a minor nerdy point. 4. Adaptive Biased-Coin Randomization: The urn randomization is the most widely known type of the adaptive biased-coin randomization. They are a compromise between designs that yield perfect balance in treatment assignments and complete randomization which addresses experimental bias. The urn design forces a small-sized trial to be balanced but approaches complete randomization as the size of the trial (n) increases (Wei and Lachin 1988). In an adaptive biased-coin randomization the probability of being assigned to a group decreases if the group is overrepresented and increases if the group is underrepresented. This special less common method of randomization is thought to be less affected by selection bias than permuted-block randomization. We talked about Cluster Randomization on SGEM#:247. Rather than randomizing the individual patients, it randomizes groups of patients to the intervention or control.