The Skeptics Guide to Emergency Medicine

Date: June 30th, 2022 Reference: McGinnis et al. Major adverse cardiac event rates in moderate-risk patients: Does prior coronary disease matter? AEM June 2022. Guest Skeptic: Dr. Corey Heitz is an emergency physician in Roanoke, Virginia. He is also the CME editor for Academic Emergency Medicine. Case: You are working a shift in your local community emergency department (ED) when a 47-year-old male presents with chest pain. His symptoms are moderately suspicious, he has a normal EKG, and a history of hypertension. His father had a minor heart attack at the age of 63. With a negative initial troponin, this gives him a HEART score of 4. He has no history of coronary artery disease. You have been reading about the overuse of objective cardiac testing (OCT) and wonder if this patient really needs admission to the hospital. Background: Chest pain is one of the most common presentations to the ED. Much ink has been spilled over the years on trying to find a way to safely rule-out acute coronary syndrome in these patients. Multiple clinical decision instruments have been created to risk stratify patients and guide clinicians (TIMI, GRACE, MAC, T-MAC, HE-MAC, ADAPT, VCPR, EDACS, etc). The HEART score was originally developed in 122 patients in the Netherlands and published in 2008. Backus and colleagues published their multi-centre validation of the HEART score in 2010. Since then, there have been several studies looking at this clinical decision instrument. We looked at a HEART Score Pathway that included a HEART Score and 0 and 3 hour cardiac troponin testing on SGEM#151 with our friend Salim Rezaie. The bottom line from that episode was that the HEART Pathway appears to have the potential to safely decrease objective cardiac testing, increase early discharge rates and cut median length of stay in low-risk chest pain patients presenting to the ED with suspicion of ACS. In prior decades nearly all patients presenting to EDs with chest pain were admitted to hospital. If we thought about ACS, we brought them in. This would be for objective cardiac testing including stress test, CT-angiography, and/or invasive angiography. However, all this recent research into clinical decision tools and pathways to risk-stratify these patients is reducing admissions and therefore ED and hospital overcrowding [1-5]. Many patients risk stratified as “non-low” risk are admitted, but the benefit of objective cardiac testing in this cohort is unclear in the absence of elevated troponins or abnormal EKGs [6-9]. The study we will be reviewing today seeks asks if the presence of known coronary artery disease is predictive of major adverse cardiac events (MACE) in a previously identified non-low risk group of patients. Clinical Question: What is the 30-day incidence of MACE in patients who are non-low risk but have known coronary artery disease? Reference: McGinnis et al. Major adverse cardiac event rates in moderate-risk patients: Does prior coronary disease matter? AEM June 2022. Population: Adult patients (age >21 years) with chest pain or suspected ACS, HEAR >4, elevated troponin, ischemic EKG or prior CAD Exclusions: Patients with evidence of an ST-segment elevated myocardial infarction and patients who were identified as low risk (HEAR < 4) by the HEART Pathway Intervention: Assessment of moderate-risk patients as described in the inclusion/exclusion criteria Comparison: None Outcome: Primary Outcome: 30-day MACE defined as the composite of all-cause death, MI, or coronary revascularization. Secondary Outcomes: Individual components of the MACE composite at the index visit Study Design: A preplanned subgroup analysis of non–low-risk patients in the HEART Pathway Implementation Study was conducted. The original study was a prospective interrupted time-series of accrued adults with possible ACS from three US sites (November 2013–January 2016). Dr. Henderson McGinnis This is an SGEMHOP episode, which means we have the lead author on the show. Dr. Henderson McGinnis is a Professor in the Dept of Emergency Medicine at Atrium Health Wake Forest Baptist. Henderson is the Medical Director for AirCare, the system’s critical care air and ground transport service. He is also the fellowship director of the Wilderness Medicine Fellowship at the Wake Forest EM Program. Authors’ Conclusions: “MACE rates at 30 days were low among moderate-risk patients but were significantly higher among those with prior CAD.” 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. Unsure This is a prospective, multicenter study including a broad spectrum of patients and clinicians (level II). No 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 7. For Level I studies, impact on clinician behavior and patient-centric outcomes is reported. N/A The follow-up was sufficiently long and complete. Yes 9. The effect was large enough and precise enough to be clinically significant. Yes Results: Out of the original cohort of patients, 37.7% (1,715/4,550) were classified as moderate risk with non-ischemic EKGs and negative serial troponins. Mean age was 61 years, 55% were women, and 29.6% had known coronary artery disease. Key Result: Moderate risk patients with known CAD had a higher risk of MACE than those without CAD. Primary Outcome: 30-day MACE defined as the composite of all-cause death, MI, or coronary revascularization. Moderate risk patients with known CAD: 7.1% (36/508) Moderate risk patients without CAD: 1.4% (17/1,207) LR- for 30-day MACE among moderate-risk patients without prior CAD was 0.08 (95% CI; 0.05 to 0.12). Secondary Outcomes: Individual components of the MACE composite at the index visit and 30-day Listen to the podcast to hear Henderson answer our 10 nerdy questions. 1. Secondary Analysis of a Subgroup – The biggest limitation which you identify up front is that this study is a secondary analysis of a subgroup of patients from the HEART Pathway Implementation Study. How cautious should we be in interpreting these results until a prospective study is done specifically looking at the patient population that could potentially be discharged home from the ED? 2. Prior Coronary Artery Disease (CAD): This study hinges in part on whether the patient had known CAD. In the methods section, there is no definition of prior known CAD. What entities does this encompass? 3. Objective Cardiac Testing (OCT): Often people were admitted to hospital for OCT (stress testing, coronary computed tomography angiography, or invasive coronary angiography). Our friend Dr. Morgenstern at First10EM has written multiple blog posts on why he does not order stress tests. What OCT are you doing at your centre and on whom? 4. HEAR Score: A lot of your discussion centers around what you term the “HEAR” score, or HEART without the "T". Can you discuss this concept for our listeners, and if and how you suggest using it clinically? 5. Not HS-Troponin: Since we are talking about the “T” in the HEART score this study did not use hs-sensitivity troponins. Many places are now switching over to this assay. What impact do you think it will have on managing these patients with moderate risk? 6. Pre/Post and Wash-In: In the method section you discuss the different phases of the study such as pre-implementation, post-implementation, and a wash-in period. You also excluded patients with another chest pain visit within a year. Can you explain how this influences the study population? 7. Two Percent Threshold: This gets back to my previous question about OCT. Moderate risk patients with no CAD has a 30-day MACE of 1.4%. This is below the pretest threshold of 2% which has been determined to be a reasonable cut off for getting OCT. 8. Primary Outcome: While the 30-day MACE of 1.4% is below 2% for OCT, it is still above the what most physicians consider acceptable [10-12]. 9. MACE Events: There were 17 MACE events that made up the 1.4% in the moderate-risk patients without known CAD. Included four deaths of which at least two were apparently due to noncardiac causes. In addition, two of the three missed MIs were due to serial troponin protocol violations. Recategorizing those patients would result in 12/1,207 (0.99%) that would be below both the 2% and 1% threshold. 10. Anything Else: Is there any other aspect of the trial that you would like to highlight or discuss in this talk nerdy section? Comment on Authors’ Conclusion Compared to SGEM Conclusion: We agree with the authors’ conclusion. SGEM Bottom Line: It may be reasonable, in patients who are moderate risk by the HEART score but do not have existing known CAD, to pursue outpatient follow up instead of urgent inpatient workup. Case Resolution: You discuss the situation with your patient, and offer him the option of pursuing admission, or close outpatient follow up. He elects discharge after serial troponins and will call his physician in the morning. Dr. Corey Heitz Clinical Application: The HEART Pathway Implementation Study is a well-designed study, of which this is a well-done subgroup analysis. The results are somewhat limited by the mis categorizations of the initial HEAR(T) score, but correct categorization would likely have further decreased the incidence of MACE for moderate risk patients without CAD. The LR- for moderate risk patients without CAD, compared to those with CAD and high-risk patients, was 0.08.

Date: June 18th, 2022 Reference: Crombie et al. Resuscitation with blood products in patients with trauma-related haemorrhagic shock receiving prehospital care (RePHILL): a multicentre, open-label, randomised, controlled, phase 3 trial. The Lancet Haematology 2022 Guest Skeptic: Dr. Casey Parker is a Rural Generalist that includes in his practice emergency medicine, anaesthesia and critical care. He is also now a fully fledged "sonologist". Casey currently splits his time between Broome, a small rural hospital in the remote Kimberley region of Western Australia, and a large tertiary ED in sunny Perth. Case: You are working in the emergency department (ED) and receive a call from the Advanced Care Paramedics who are at the scene of a stabbing. Apparently, two rival gangs (Jets and Sharks) had a rumble. The young man has been stabbed in the abdomen and lost a lot of blood. The patient is tachycardic (120 beats/minute), hypotensive (80/60 mmHg) and looks very pale. They have two large bore intravenous (IV) access and are planning to bring them to your ED as soon as possible. The paramedic asks you, “we have saline, and we also have red-cells and this fancy new lyophilised plasma.  Should we give our shocked patient saline or plasma / red cells en route to the ED?”  What do you advise him?  Background: The use of fluids in trauma resuscitation has been studied in a number of trials in recent years. A lot of observational data has been collected from the battlefields of Iraq and Afghanistan. The Control of Major Bleeding After Trauma (COMBAT) Trial was published in the Lancet in 2018. It was a pragmatic, randomised, single-centre trial done at the Denver looking at the use of plasma in the prehospital setting. This trial did not show a statistical mortality benefit within 28 days of injury. First10EM and REBEL EM both did a review of the COMBAT trial.  The Prehospital Air Medical Plasma (PAMPer) trial was published in NEJM, also in 2018.  The goal of this trial was to determine the efficacy and safety of prehospital administration of thawed plasma in injured patients who are at risk for hemorrhagic shock. This trial did report that prehospital administration of plasma was safe and resulted in lower 30-day mortality. PAMPer was reviewed by First10EM and The Bottom Line.  The traditional teaching in trauma is to replace blood with blood products, so we would expect that we should see a benefit if we used blood and plasma instead of saline alone for the initial resuscitation. Clinical Question: In the resuscitation of pre-hospital trauma patients with hemorrhagic shock is there a patient-oriented benefit to using blood and plasma over 0.9% saline? Reference: Crombie et al. Resuscitation with blood products in patients with trauma-related haemorrhagic shock receiving prehospital care (RePHILL): a multicentre, open-label, randomised, controlled, phase 3 trial. The Lancet Haematology 2022 Population: Adult patients 16 years of age or older suffering traumatic injury resulting in shock believed to be due to a traumatic haemorrhage. Shock was defined as a systolic BP less than 90 mmHg or an absent radial pulse.  Exclusions: Patients known to refuse blood produces, those who received transfusion of prehospital blood products before assessment for eligibility, pregnancy (known or apparent), isolated head injury without evidence of major haemorrhage, and prisoners.  Intervention: Up to four units of blood products boluses one unit at a time.  Units were alternating between units of O-negative packed red cells (PRBC) or or reconstituted lyophilised plasma to a maximum of two units of either. Comparison: Up to four boluses of 0.9% saline (250ml/bolus) Outcome:  Primary Outcome: Composite outcome of mortality from time of injury to hospital discharge or the failure to clear lactate by 20% within the first two hours after randomisation. Secondary Outcomes: Individual components of the composite primary outcome, fluid volumes, measures of coagulopathy, 30 day mortality and common side effects of transfusion such as reaction and adult respiratory distress syndrome (ARDS) Trial: This was a multi-centre, open-label, concealed, single-blinded, randomised controlled trail Authors’ Conclusions: “The trial did not show that prehospital PRBC–LyoPlas resuscitation was superior to 0.9% sodium chloride for adult patients with trauma related haemorrhagic shock. Further research is required to identify the characteristics of patients who might benefit from prehospital transfusion and to identify the optimal outcomes for transfusion trials in major trauma. The decision to commit to routine prehospital transfusion will require careful consideration by all stakeholders.” Quality Checklist for Randomized Clinical Trials: The study population included or focused on those in the emergency department. No The patients were adequately randomized. Yes The randomization process was concealed. Yes The patients were analyzed in the groups to which they were randomized. Yes The study patients were recruited consecutively (i.e. no selection bias). 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. Yes Follow-up was complete (i.e. at least 80% for both groups). Yes All patient-important outcomes were considered. Unsure The treatment effect was large enough and precise enough to be clinically significant. No Lack of financial conflicts of interest. Yes Results: The trial randomized 432 participants. Median age was 38 years, 82% were male and 62% of patients had blunt force trauma from a motor vehicle collision.  Key Result: Blood products were not superior to saline for the primary outcome. Primary Outcome: Composite outcome of mortality from time of injury to hospital discharge or the failure to clear lactate by 20% within the first two hours after randomisation. 64% in the blood product group vs 65% of the saline group  Adjusted risk difference –0·025% [95% CI –9.0 to 9.0], p=0·996) Adjusted risk ratio 1.01 [95% CI 0.88 to 1.17] Secondary Outcomes:  Mortality: 43% in the blood products group vs 45% in the saline group (Adjusted risk ratio 0.97 [95% CI 0.78 to 1.20]; p=0·75)  Failure to clear lactate: 50 vs 55% (Adjusted risk ratio 0.94 [95% CI 0.78 to 1.13]; p=0·52) None of the other secondary outcomes reported were statistically different Serious adverse events were similar between both groups 1. Mixing POOs and LOOs: Is it appropriate to place LOOs (lab-oriented outcomes) and POOs (patient-oriented outcomes) together in a composite primary? This trial used a composite primary outcome that included  mortality (a big POO) with lactate clearance (a lab-oriented outcome that may or may not be a surrogate marker for mortality).  Usually one might design a trial with softer LOOs if one were trying to detect a subtle difference in a population where hard patient-oriented outcomes are rare. However, in this trial nearly half of the patients died.  Mortality is very objective and important to patients, and it would therefore seem better to stick with a single primary outcome and power the recruitment to that end. 2. Dose: The RePHILL trial participants received less than a litre of fluid in total prior to arriving in hospital. That could either be all saline in the control group or a mixture of saline and blood products in the intervention group.  The fact that this was a “negative” trial may mean that there truly is no difference between saline and blood products in pre-hospital resuscitation. Or, it could mean that at this dosage there is no detectable potential benefit or potential harm observable. For example, If we only gave 10 mg of aspirin to patients with ST elevated myocardial infarction and observe no mortality benefit, but also no GI bleeds we could conclude that aspirin has no effect. However, we do have high-quality data showing that there is a benefit to giving 162.5mg of aspirin to STEMI patients with a small increase in harm (TheNNT.com). So is the RePHILL trial telling us there is no benefit, or that the doses are not adequate to give an effect that we can observe? This is why it is good to be cautious not to over or under-interpret the data. The most accurate conclusion is that the intervention provided in this cohort of trauma patients with shock did not demonstrate superiority over the control group. This is different than concluding blood products do not work for trauma patients in the prehospital setting.  3. External Validity: This trial used a team of pre-hospital physicians and critical care paramedics in the UK. The team traveled by helicopter or land based rapid response vehicles with a blood product that is relatively new and hard to come by (lyophilised plasma).  If RePHILL had been a positive trial and shown a clear benefit then we would be stuck with the issue of external validity, especially in rural areas like Canada and Australia which are much larger countries geographically.  We do not have the systems or access to this product. It would be very difficult to bring a physical-led plasma wielding team to the roadside in most parts of the world. Rural clinicians know about the tyranny of distance.  The goal should be to get the best medical care to rural patients which can be logistically tough at times. However, it should not be the knowledge of the team that results in lesser care. 4. Too Good to Be True: The original power calculation for RePHILL was based on the consensus that a 10% absolute difference in the primary outcome. This is a large difference for a complex disease like trauma using a simple intervention. However,

Date: June 12th, 2022 Reference: Finfer et al. Balanced Multielectrolyte Solution versus Saline in Critically Ill Adults. NEJM 2022. Guest Skeptic: Dr. Aaron Skolnik is an Assistant Professor of Emergency Medicine at the Mayo Clinic Alix School of Medicine and Consultant in the Department of Critical Care Medicine at Mayo Clinic Arizona.  He is board certified in Emergency Medicine, Medical Toxicology, Addiction Medicine, Internal Medicine-Critical Care, and Neurocritical Care.  Aaron is a full-time multidisciplinary intensivist.  He is the Medical Director of Respiratory Care for Mayo Clinic Arizona and is most proud of his position as medical student clerkship director for critical care. Case: A 62-year-old man is brought in by EMS from home with lethargy and hypotension.  Chest x-ray is clear, labs are remarkable for a leukocytosis of 16,000 with left shift; exam is notable for left flank pain and costovertebral tenderness.  Straight catheter urinalysis is grossly cloudy, and pyuria is present on microscopy.  Blood pressure is 85/50 mmHg.  You wonder which IV fluid should you order? Background:  There has been a longstanding debate about which intravenous fluid is the best for volume resuscitating critically ill patients.  We’ve known for some time that albumin is bad for injured brains, and that hydroxyethyl starch solutions have been associated with kidney injury and mortality.  Since then that debate has broadly centered on the choice between what we will call “abnormal saline” (0.9% sodium chloride), and balanced crystalloid solutions, meaning those with a chloride composition closer to plasma such as lactated ringer’s or Plasma Lyte 148. Early work suggested potential harm from 0.9% saline, that may be partly driven by kidney injury associated with the administration of high-chloride content IV fluids. In the last few years, the pendulum has swung back and forth.  Two large, cluster-randomized trials (SMARTand SALT-ED) showed a small benefit to the use of balanced crystalloids in preventing a composite outcome of Major Adverse Kidney Events within 30 days (aka MAKE-30). Then, the BaSICS trial (a multicentred RCT done in 75 Brazilian ICUs) came along and compared saline to Plasma-Lyte at what the authors deemed slow and fast infusion rates.  We reviewed that last time on SGEM#347. There was no interaction between fluid type or rate of infusion with the primary outcome of 90-day survival.  Among 19 secondary outcomes, which should only be considered hypothesis generating, SOFA scores and neuro SOFA scores at day seven were worse in the balanced crystalloid group. Now we have the PLUS trial, from Australia and New Zealand to add to the medical literature on this issue. Clinical Question: Is the 90-day mortality in critically ill adult patients lower with the use of Plasma-Lyte 148, a balanced crystalloid solution, for fluid resuscitation and therapy, than with the use of normal saline? Reference:  Finfer et al. Balanced Multielectrolyte Solution versus Saline in Critically Ill Adults. NEJM 2022. Population: Patients 18 years or older, admitted to 53 ANZ ICUs over 38 months, whom the treating clinician deemed to need fluid resuscitation and were expected to be in the ICU on three consecutive days. Exclusions: Patients with specific ICU fluid requirements, those who received disqualifying fluid prior to enrollment (> 500 mL in the ICU), those at imminent risk for death or with life expectancy < 90 days, and those at risk for cerebral edema. Intervention: Plasma-Lyte 148 for all resuscitation episodes while in ICU for up to 90 days after the first episode of fluid resuscitation Comparison: 0.9% saline for all resuscitation episodes while in ICU for up to 90 days after the first episode of fluid resuscitation Outcome: Primary Outcome: All-cause mortality within 90 days after randomization Secondary Outcomes: Peak serum creatinine level during the first seven days after randomization, the maximum increase in creatinine level during ICU stay, receipt of new renal-replacement therapy, receipt and duration of treatment with vasoactive drugs, duration of mechanical ventilation in the ICU, length of ICU and hospital stays, and death from any cause during ICU stay, during hospital stay, and within 28 days after randomization. Trial: Double-blind, parallel-group, randomized, controlled trial. Authors’ Conclusions: “We found no evidence that the risk of death or acute kidney injury among critically ill adults in the ICU was lower with the use of [Plasmalyte 148] than with saline.” 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. 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. Yes Financial conflicts of interest. Yes Results: They recruited 5,037 patients from 53 ICUs in Australia and New Zealand. The mean age was 62 years, 39% female, 76% had invasive mechanical ventilation, and a median APACHE score of 19. Key Result: No statistical difference in all-cause mortality within 90 days. Primary Outcome: All-cause mortality within 90 days after randomization 21.8% Plasma-Lyte 148 group vs 22.0% saline group Absolute difference of −0.15 percentage points (95% CI, −3.60 to 3.30; P=0.90) Odds Ratio of 0.99 (95% CI, 0.86 to 1.14) Secondary Outcomes: Over the first seven days after randomization, arterial blood pH was higher, and the serum chloride level was lower in the balanced crystalloid group. Both achieved statistical significance, though the absolute difference was probably not clinically meaningful.  Over that same time period, there were no significant differences in mean heart rate, mean arterial pressure, mean central venous pressure, creatinine, hemoglobin, and lactate between groups. Measures of organ failure including rise in creatinine and need for renal replacement therapy were similar between groups.  There was also no significant difference in days alive free of the vent, free of renal replacement, outside of the ICU, or outside of the hospital.  Adverse events did not differ between groups. We reached out to the lead author Dr. Simon Finfer. He was kind enough to send a brief responses to our five nerdy questions. 1) Recruitment: The trial was originally designed to recruit a sample size of 8,800 patients.  Due to COVID-19, the recruitment stopped at just over 5,000 patients.  Do you think this influenced the trial results in any meaningful way? “NO - this was covered in paper and supplementary figure S11 2) Fluids: More than half of the patients in the balanced crystalloid group received more than 500 mL of normal saline, mostly because of medications that could not be mixed in balanced solution.  How might this have swayed the trial result and what did the authors do to account for this? “We did several secondary analyses that did not alter the results. They are all in table 2 - see attached which is convincing that going on further to 8800 or even more would not have produced a different result” 3) Brain Injury: The authors didn’t test balanced crystalloid solution in TBI patients or others thought to be at risk for cerebral edema.  What do you think about balanced versus saline in this group?  Is this population the clinical stronghold of normal saline? “The BaSICS study validates our decision not to expose patients with TBI to PL148 which has higher tonicity than other balanced fluids but still lower than NS. Patients with TBI should get NS. 4) Small Effect Size: The trial is a “negative” one, but as the authors point out in their discussion, their results also allow for up to a 3% increase or decrease in the risk of death or new renal replacement associated with balanced crystalloid administration.  Is that an acceptable level of uncertainty about effect?  How do you apply those confidence intervals to patient care? “See answer to point 1 and below”  5) Other Evidence: There is a recent systematic review and meta-analysis published in NEJM Evidence examining 13 RCTs and over 35,000 patients comparing balanced crystalloid to saline in critically ill adults.  That SRMA concluded “The estimated effect of using balanced crystalloids versus saline in critically ill adults ranges from a 9% relative reduction to a 1% relative increase in the risk of death, with a high probability that the average effect of using balanced crystalloids is to reduce mortality.”  What do you think of the SRMA and how do you integrate all of this recent evidence into your clinical practice? “Well, as I am the corresponding author for that paper, I think it is quite good. The overall message is that balanced solutions are probably better overall, but the effect is small, for patients with a low risk of death the absolute effect is very small indeed. Patient with TBI and possibly other acute brain pathologies should get normal saline or a fluid of equal tonicity. We are conducting a patient level meta-analysis which will allow us to look at subgroups’ effects in more detail (I am the senior author for that as well). We have all the data and hope to publish by the end of this year.”

Date: May 24th, 2022 Reference: Broder et al. Guidelines for Reasonable and Appropriate Care in the Emergency Department (GRACE) 2: Low-Risk, Recurrent Abdominal Pain in the Emergency Department. AEM May 2022 Guest Skeptic: Dr. Justin Morgenstern is an emergency physician and the creator of the #FOAMed project called First10EM.com Case: A 33-year-old male presents to the emergency department (ED) complaining of abdominal pain. He states he has had the same pain for more than 10 years, and no one has ever been able to figure out what is going on. He doesn’t have any specific symptoms today, including no fever, vomiting, diarrhea, or urinary symptoms. His vital signs are normal. His abdomen is diffusely tender, but without any surgical findings. You review his chart and note that he has had five CTs performed in the last year at your hospital alone, all of which were negative. You are worried about the cumulative radiation dose he has received but find it hard to exclude significant pathology on history and physical. After all, even patients with chronic abdominal pain can develop a new acute issue like appendicitis. Background: The Society of Academic Emergency Medicine (SAEM) has launched an initiative called GRACE which stands for Guidelines for Reasonable and Appropriate Care in the Emergency Department. GRACE-1 The first GRACE publication looked at low risk chest pain, and in my opinion, they filled a very valuable role. Most guidelines focus on a single emergency visit in isolation, but a patient who presents to the emergency department recurrently with the same symptoms may require a different approach. In the context of recurrent chest pain, they made eight key recommendations. The SGEM bottom line was there is moderate level of evidence that ACS can be excluded in adult patients with recurrent, low-risk chest pain using a single hs-troponin below a validated threshold without further diagnostic testing in patients who have a CCTA within the past two years showing no coronary stenosis. The writing group of GRACE-2 wanted to look at clinically relevant questions to address the care of adult patients with low-risk, recurrent, previously undifferentiated abdominal pain in the ED. Through consensus, four questions were developed and then a systematic review of the literature was performed. This literature was then synthesized to come up with recommendations, following GRADE methodology. GRADE stands for Grading of Recommendations, Assessment, Development, and Evaluation, it was pioneered at McMaster University, in creating rigorous, transparent, and trustworthy guidelines on common clinical problems for EM physicians that are not always directly studied in EM research activities. There can be many presentations for low-risk abdominal pain. We have covered cannabis hyperemesis on SGEM#318 and SGEM#46 and pediatric gastroenteritis on SGEM#254. Clinical Question: What are the recommendations for managing patients with low-risk, recurrent, previously undifferentiated abdominal pain in the ED? Dr. Joshua Broder Reference: Broder et al. Guidelines for Reasonable and Appropriate Care in the Emergency Department (GRACE) 2: Low-Risk, Recurrent Abdominal Pain in the Emergency Department. AEM May 2022 This is an SGEMHOP episode which means we have the lead author on the show. Dr. Joshua Broder is the Residency Program Director and Vice Chief for Education In the Division of Emergency Medicine Duke University School of Medicine. Authors’ Conclusions: “No direct evidence exists to direct the care of patients with low-risk recurrent undifferentiated abdominal pain in the ED. Improved definitions are required to better define this population, and clinically relevant outcomes of interest should be described and studied with rigorous research methodology to inform future clinical guidelines.” Quality Checklist for a Guideline: The study population included or focused on those in the emergency department? Yes An explicit and sensible process was used to identify, select and combine evidence? Yes The quality of the evidence was explicitly assessed using a validated instrument? Yes An explicit and sensible process was used to the relative value of different outcomes? Yes The guideline thoughtfully balances desirable and undesirable effects? Yes The guideline accounts for important recent developments? Yes The guidelines has been peer-reviewed and tested? Yes/No Practical, actionable and clinically important recommendations are made? Yes The guideline authors’ conflicts of interest are fully reported, transparent and unlikely to sway the recommendations of the guidelines? Yes Key Recommendations: We don't have a key result section but what we do have is the key recommendations. It is important to understand the definitions created by the guideline committee for terms "low-risk, undifferentiated and recurrent".  Listen to the SGEM podcast to hear Josh comment on each of these four recommendations. Recommendation #1 In adult ED patients with low-risk, recurrent, undifferentiated abdominal pain and prior negative CTAP within 12-months, there is insufficient evidence to accurately identify populations in whom repeat imaging can be safely avoided or routinely recommended in the ED. (No recommendation) [No evidence] Recommendation #2 In adult ED patients with low-risk, recurrent, undifferentiated abdominal pain and a negative CTAP with IV contrast in the ED, we suggest against ultrasound unless there is concern for pelvic or biliary pathology. (Conditional recommendation, against) [Very low certainty of evidence] Recommendation #3 In adult ED patients with low-risk, recurrent, undifferentiated abdominal pain, we suggest screening for depression and/or anxiety may be performed during the ED evaluation. (Conditional recommendation, either) [Very low certainty of evidence] Recommendation #4 In adult ED patients with low-risk, recurrent, undifferentiated abdominal pain, we suggest an opioid-minimizing strategy for pain control. (Conditional recommendation. [Consensus, no evidence] Listen to the podcast to hear Josh answer our five nerdy questions. 1. Scope of the Review: There are thousands of questions I could imagine asking for this guideline. What is the role of observation and repeat exams instead of imaging? When is blood work required? What chronic therapeutic options should the emergency physician consider? Obviously, this guideline was a massive undertaking as it stands. How did you decide which questions were the most important to ask? 2. Pediatric Patients: This guideline only applies to adult patients. Those of us who work community ED or as Pediatric Emergency Medicine know many children present with abdominal pain. Are there any plans for the GRACE group to look at this issue? 3. Patient Representative: In the recommendation to screen for depression, you lean heavily of the comments of a patient representative in your group. For a scientific guideline, I think that might surprise people. Can you explain the role of the patient representative in the creation of these guidelines? Patients are all unique. I wonder how representative this one patient’s views are for the average patient. 4. Gaps in Knowledge: Clearly there are huge gaps in knowledge in this area. That could be looked at as a negative or a positive. It is an opportunity for those listening to design a study with a clinically relevant question and proper methods to answer the question. If could give future researchers one area that you think would have the biggest impact for patients, what would it be? 5. Making Guidelines without Evidence: Personally, I find it very frustrating when guidelines make strong recommendations in the absence of evidence. This guideline does a very good job discussing the absence of evidence, and explaining why recommendations were made, but it is still a difficult task without evidence. I wonder if you could comment on what you think is the best approach to writing a guideline when no evidence exists, and the clinical value of such guidelines. Comment on Authors’ Conclusion Compared to SGEM Conclusion: We agree with the authors’ conclusion that there is no direct evidence to guide our management of patients with low risk, recurrent, undifferentiated abdominal pain. SGEM Bottom Line: Given the lack of evidence available to guide is, there is tremendous uncertainty in the most appropriate management plan for these patients. We should be open about that uncertainty without our patients and involve them in shared decision-making to ensure that the chosen management plan matches their personal values. Case Resolution: You discuss the potential harms and the potential benefits of repeat imaging with your patient and opt for repeat exams over a brief period of observation with rapid follow-up with his primary care provider. You treat his pain effectively with non-opioid analgesia. You discuss depression and anxiety with him, and he admits that the recurrent abdominal pain has been causing significant anxiety, but he is already addressing that with his family doctor. Clinical Application: Although the current lack of evidence is somewhat disappointing, managing uncertainty is a core skill of emergency physicians. In some ways, the lack of clear science frees us up to use our clinical judgement and talk to our patients to develop individualized treatment plans that suit their values best. Dr. Justin Morgenstern What Do I Tell the Patient? Unfortunately, despite recurrent abdominal pain being a very common presentation, there is very little good science to guide us. You have been through these symptoms many times before, so you know that it is unlikely that a repeat CT scan will provide us with an answer today. However,

Date: May 13th, 2022 Reference: Abril et al. The Relative Efficacy of Seven Skeletal Muscle Relaxants. An Analysis of Data From Randomized Studies. J Emerg Med 2022 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 and specifically the use of ketamine. His twitter handle is @PainFreeED. Case: A 45-year-old man without a significant past medical history presents to your emergency department (ED) with two days of severe lower back pain after shoveling some dirt. The pain is 10/10 in intensity, gets worse with bending, turning, and prolonged walking. He denies numbness or paresthesia in both lower extremities, as well as bowel or bladder dysfunctions. A heating pad and acetaminophen has not helped with the pain. On examination, he is in moderate distress and has prominent tenderness to palpation at the bilateral paralumbar region and intact neurovascular examination. You diagnose him with a lumbar muscle strain and plan to prescribe him a non-steroidal anti-inflammatory (NSAID) while setting expectations. However, the patient wonders if you can give him something that can relax his back muscles and take his pain away. Background: Low back pain (LBP) is one of the most encountered ailments in clinical practice and is responsible for 2.6 million visits to U.S. EDs annually (1). Many patients with acute LBP experience substantial improvement in the first month, but up to one third report persistent back pain, and 1 in 5 report some limitations in activity. These persistent symptoms are associated with high costs, including those related to health care, and indirect costs from missed work or reduced productivity (2). Many pharmaceutical treatments besides opioids have been tried to address acute LBP pain with limited success (SGEM#87 and SGEM#173). These include: acetaminophen (Williams et al Lancet 2014), steroids (Balakrishnamoorthy et al Emerg Med J 2014) and benzodiazepines (Friedman et al Ann Emerg Med 2017). Nonsteroidal anti-inflammatory drugs (NSAIDs) are recommended as first-line medication therapy for patients with LBP despite a lack of evidence of efficacy (Machado et al Ann Rheum Dis 2017), There are several non-pharmaceutical treatments that have also been tried to treat LBP. 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). Unfortunately, none of these other treatment modalities has high-quality evidence supporting their use. Skeletal muscle relaxants (SMRs) are a frequently used in the ED and at discharge for acute back pain management and include methocarbamol, cyclobenzaprine, orphenadrine, carisoprodol, tizanidine, metaxalone, and baclofen. Estimates suggest up to 35% of patients with nonspecific low back pain are prescribed SMRs, with orphenadrine, and methocarbamol being used in more than 250,000 U.S. ED visits for low back pain annually (3-5). Despite their branding as muscle relaxants, the anti-spasmodic and analgesic effects of SMRs are predominantly due to unknown mechanism of action. Clinical Question: What is the efficacy of skeletal muscle relaxant administration in addition to an NSAID in treating acute low back pain? Reference: Abril et al. The Relative Efficacy of Seven Skeletal Muscle Relaxants. An Analysis of Data From Randomized Studies. J Emerg Med 2022 Population: Patients were considered for inclusion if they were 18– 69 years of age and presented to the ED primarily for management of acute LBP. This was defined as pain of two weeks’ duration or less originating between the lower border of the scapulae and the upper gluteal folds, and received a diagnosis consistent with nontraumatic, non-radicular, musculoskeletal LBP, as determined by the attending emergency physician. All patients had already received a dose of an NSAID. Exclusions: Radicular pain, pain duration for greater than two weeks, direct trauma to the back within the previous month, or a history of experiencing LBP on average more than several times per year, pregnancy, breastfeeding, allergy to study medications. Intervention: One of seven skeletal muscle relaxants (metaxalone, tizanidine, baclofen, diazepam, orphenadrine, methocarbamol, or cyclobenzaprine) Comparison: Placebo Outcome: Primary Outcome: Improvement in the Roland-Morris Disability Questionnaire (RMDQ) between ED discharge and the 1-week follow-up. The RMDQ goes from 0 to 24 with a 5-point improvement on this scale generally considered clinically significant. Secondary Outcomes: Moderate or severe LBP 1 week after the ED visit and medication adverse effects, assessed by asking patients to report any symptoms from the medications and dichotomizing their responses (yes/no). Authors’ Conclusions: “Among patients in the ED with acute LBP treated with a nonsteroidal anti-inflammatory drug, SMRs do not improve outcomes more than placebo. Neither age, sex, nor baseline impairment impacts these results.” Quality Checklist for Non-Systematic Review: The clinical question is sensible and answerable. Yes The primary studies were of high methodological quality. Yes The assessment of studies were reproducible. Yes The outcomes were clinically relevant. Yes There was low statistical heterogeneity for the primary outcomes. Yes 6.The treatment effect was large enough and precise enough to be clinically significant. No  Results: There were four RCTs conducted between 2012 and 2018 by the same research group with a combined total of 887 patients. The mean age was 39 years, 56% were male, median RMDQ score was 18 and 67% had a history of LBP. Key Result: All treatments including placebo had a clinically significant decrease in their RMDQ score without a statistical difference between groups. Primary Outcome: The seven SMRs and placebo group reported a decrease in their RMDQ score by about 10 points. The between-group differences were not statistically significantly different. We will put a table in the show notes with the point estimates and the 95% confidence intervals. Results were similar regardless of age, sex, and baseline severity. Higher baseline RMDQ was associated with greater clinical improvement (B coefficient 5.7 < 0.01). Secondary Outcomes: Regarding pain intensity at 1 week, there was also no statistically significant differences among the groups (p = 0.93). Adverse medication effects were more common with cyclobenzaprine than with placebo (p < 0.01). 1. Not a SRMA – This publication was a planned analysis of four RCTs looking at seven different SMRs with a total of 887 patients. All four of the RCTs had the same principal investigator, Dr. Friedman, and he was the senior author on this manuscript. Dr. Friedman has contributed greatly to the area of pain management. The analysis was not a SRMA nor was it claimed to be one. The team presented the results of their four RCTs. A more comprehensive study would been to conduct a systematic review using the PRISMA guidelines. This would have included an exhaustive search of the world’s literature without language restrictions and of the grey literature. Some of these RCTs may have been captured in the search depending on the inclusion and exclusion criteria. 2. Statistical Analysis – They performed a reasonably robust statistical analysis of their data. This was beyond the baseline characteristics of age, sex, RMDQ score and type of SMR recorded as a mean with a standard deviation, median with interquartile range or frequency with a precent when appropriate. Their analysis included an ANOVA to determine if the between group differences measured on the RMDQ were statistically significant. There was no statistical or clinical (5-point change) difference between the seven SMR or placebo. They conducted a linear regression model to determine if there was an association of age, sex, baseline RMDQ severity, and history of back pain with the primary outcome. They also performed two logistic regression models with detailed explanation of variables. 3. Age Restriction – None of the four RCTs included patients over the age of 69 years. This is important to remember because this older cohort of patients is generally at greater risk of adverse events from medications with sedative side effects. Any potential benefit from the treatment, which was not demonstrated in this publication, would need to be weighed against the potential harms. The harms in a geriatric age group could be more serious. As an example, SMR could lead to more falls. Falls are the most common cause of traumatic injury resulting in older adults presenting to the ED [6]. Approximately 20% of falls result in injuries, and falls are the leading cause of traumatic mortality in this age group [7-9]. 4. Placebo Effect – This study provides more evidence that the placebo effect is real and can be clinically significant. The mean improvement on the RMDQ score was 10.5 which is more than double what is considered clinically important. It demonstrates how easily it could patients can be fooled and how we can fool ourselves thinking the treatment provided “works”. SMR were just as effective in lowing RMDQ scores as a placebo. We also need to consider the ethical considerations of knowingly prescribing a placebo in clinical practice (10). 5. Nihilism – It is hard not to become nihilistic when reviewing the evidence for LBP. There is a serious lack of high-quality evidence demonstrating clinical improvement to inform our care. This includes both pharmacologic (steroids, NSAIDS, and acetaminophen), and non-pharmacologic therapies (chiropractic, acupuncture,

Date: April 19th, 2022 Guest Skeptic: Sarah Mojarad is a Lecturer in Advanced Writing, #SciComm, & Mis/disinfo topics • Kavli Fellow • Reed Awardee. Sarah Mojarad This is an SGEM Xtra episode. When planning a brief trip to Los Angeles for the EMRAP One Conference, I remembered that Sarah is from LA. I thought to myself, perhaps she would come on the SGEM as a special guest. I'm happy to say Sarah graciously accepted the invitation. We recorded the episode sitting outside on the patio at the Luskin Conference Centre. It is an example of how twitter can be a great way for making new friends. When I reached out to Sarah for a topic for the podcast she suggested five tips for science communication (SciComm) using social media. She shared with me a short YouTube video she had made for students interested in SciComm. We based our discussion on that video. It is clearly not an exhaustive list of tips but it did serve as the basis of our discussion. You can hear our conversation on the SGEM Xtra Podcast. Five Tips for Science Communication Tip #1: Be Yourself I think this is such an important piece of advice. Authenticity really resonates with people. One of the best compliments I received recently was from a wonderful dental student named Ellie from Schulich School of Medicine and Dentistry. We met at an Interprofessional Educational event, and she said it was so great to meet someone IRL who is so much like their twitter feed. Follow me and you will find out I am a huge advocate for evidence-based medicine (EBM), love Star Trek TOS, have a dog named Loki the Dog of Mischief, upset other physicians like neurologists when discussing the evidence for tPA in acute ischemic stroke, I think the 80’s is the best era for music/movies, and have been known to play BatDoc at times. Tip #2: Don't’ Be Afraid of Failing Another great tip. One of the best presentations I gave was about my many failures. The joke was that first grade was the longest two years of my life because I needed to repeat grade one. I failed to get into medical school the first time. I felt guilty and inadequate when I could not complete my orthopaedic residency. These and so many other “failures” that cause a lot of pain over the years. However, as Maya Angelou said: “Without defeats, how do you really know who the hell you are? If you never had to stand up to something - to get up, to be knocked down, and to get up again - life can walk over you wearing football cleats. But each time you do get up, you're bigger, taller, finer, more beautiful, more kind, more understanding, more loving. Each time you get up, you're more inclusive. More people can stand under your umbrella.” Tip #3: Find A Mentor I have had many mentors over the years. These include amazing people like: Dr. Kirsty Challen, Dr. Andrew Worster, Dr. Dara Kass, Dr. Michelle Johnson, Dr. Rick Bukata, Dr. Chris Carpenter and many, many more people who have helped me get where I am today. Sir Isaac Newton Tip #4: What Do You Want to Say? What is your message? Do you have a story, a narrative or goal in mind? My goal for the SGEM is to provide structured critical appraisals of the recent literature and probe it for its validity. We are trying to cut the knowledge translation window down from over ten years to less than one year using the power of social media. Ultimately, the goal is for patients to get the best care, based on the best evidence. Tip #5 How Do You Want to Say It? I want to make critical appraisal, clinical epidemiology, and biostatistics fun, engaging and exciting. I try to do this with 80’s music, memes, twitter polls, the keener contest, and other things. I learned a lot from Ross Fisher and his P Cubed Presentation initiative on how to create better presentations. I really like the way Melanie Trecek-King from Thinking is Power does her SciComm. She has a great educational approach and posts some useful tools for critical thinking like the FLOATER acronym. I’ve also learned from Dr. Brian Goldman to be more kind online. It follows the Spinoza philosophy of not ridiculing or bewailing or scorning people on twitter but rather trying to understand them. Some Dangers of SciComm Mansplaining I’ve seen a lot of women mansplained on twitter. For those who do not know mansplaining is a pejorative term meaning "to comment on or explain something to a woman in a condescending, overconfident, and often inaccurate or oversimplified manner". It is often done by a male  layperson to a woman who is an expert in the field he is mansplaining to her. Examples include experts like Dr. Jennifer Gunter on gynecology, Dr. Megan Ranney on the science of gun safety, and Dr. Michelle Cohen on gender equity in the house of medicine. Harassment There was a recent disturbing article published in Science about scientists who have spoken out during this current global pandemic and have been threatened. The title of the article was In the Line of Fire. It talks about how COVID has increased the harassment of scientists who speak publicly. Their survey reported that more than one-third of COVID researchers experienced harassment. Final Thoughts from Sarah Social media based SciComm is a worthwhile endeavor. Understanding the landscape can help you minimize distractions. And maximize the benefits. The SGEM will be back next episode doing a structured critical appraisal of a recent publication. Trying to cut the knowledge 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: April 16th, 2022 Reference: Blom et al. Common elective orthopaedic procedures and their clinical effectiveness: umbrella review of level 1 evidence. BMJ 2021 Guest Skeptic: Dr. Matt Schmitz, Pediatric Orthopedics, Adolescent Sports Medicine and Young Adult Hip Preservation Surgeon at San Antonio Military Medical Center in Texas. Disclaimer: The views and opinions of this blog and podcast do not represent the United States Government or the US Military. Case: A 55-year-old man comes into the emergency department (ED) for increasing knee pain and decrease in function. He’s had an anterior cruciate ligament (ACL) repair and used to run marathons. However, he is finding it more difficult to even put his socks on. Physical exam shows varus deformity at the knee, decreased range of motion, crepitus, no locking and neurovascularly intact distal. X-rays show severe, tri-compartment arthritis. Background: Musculoskeletal complaints are one of the most common presentations to emergency departments. Often emergency physicians are assessing, treating, and answering patients question about orthopedic surgical procedures. How good is the evidence for the most common elective procedures? Before we answer that question, let’s remind everyone that only a small number (2.8%) of interventions published in SRMA and relevant to emergency medicine have unbiased and strong evidence for improved outcomes (SGEM#361). This is a broader problem in medicine. Tricoci et al. JAMA Feb 2009 looked at the ACC/AHA guidelines from 1984 to 2008. They found 53 guidelines with 7,196 recommendations. Only 11% of recommendations were considered Level A, 39% were Level B and 50% were Level C. An update was published by Fanaroff et al in JAMA 2019. The level of high-quality evidence had not changed much when looking at the ACC/AHA guidelines from 2008-2018. There were 26 guidelines with 2,930 recommendations. Now Level A recommendations were down to 9%, Level B 50% and Level C 41%. Time to turn our skeptical eye to the evidence for elective orthopaedic procedures. Clinical Question: What is the effectiveness of common elective orthopaedic procedures compared with no treatment, placebo, or non-operative care? Reference: Blom et al. Common elective orthopaedic procedures and their clinical effectiveness: umbrella review of level 1 evidence. BMJ 2021 Population: Meta-analyses of randomised controlled trials Exclusions: Network meta-analyses (when pairwise meta-analyses were available), narrative reviews, systematic reviews that did not pool data or do a meta-analysis, and meeting abstracts Intervention: Surgery Comparison: No treatment, placebo, or non-operative care Outcome: Quality and quantity of evidence behind the ten most common elective orthopaedic surgeries and comparisons with the strength of recommendations in relevant national clinical guidelines. Authors’ Conclusions: “Although they may be effective overall or in certain subgroups, no strong, high quality evidence base shows that many commonly performed elective orthopaedic procedures are more effective than non-operative alternatives. Despite the lack of strong evidence, some of these procedures are still recommended by national guidelines in certain situations.” Quality Checklist for Therapeutic Systematic Reviews: The clinical question is sensible and answerable.  Yes/Unsure The search for studies was detailed and exhaustive. Yes The primary studies were of high methodological quality. Yes The assessment of studies were reproducible. Yes The outcomes were clinically relevant. Yes There was low statistical heterogeneity for the primary outcomes. Unsure The treatment effect was large enough and precise enough to be clinically significant. Yes, No and Unsure Results: The ten most common elective orthopaedic procedures were identified using a literature search, an assessment of Hospital Episode Statistics procedure frequency counts, and discussions with expert orthopaedic surgeons. Ten Most Common Elective Orthopaedic Procedures arthroscopic anterior cruciate ligament reconstruction arthroscopic meniscal repair of the knee arthroscopic partial meniscectomy of the knee arthroscopic rotator cuff repair arthroscopic subacromial decompression carpal tunnel decompression lumbar spine decompression lumbar spine fusion total hip replacement total knee replacement Key Result: Only two out of ten common procedures, carpal tunnel decompression and total knee replacement, showed superiority over non-operative care. They identified no RCTs that specifically compared total hip replacement or meniscal repair with non-operative care. The six other common orthopaedic procedures showed no benefit over non-operative care. 1. Jadad Decision Algorithm: This is probably an unfamiliar process to most SGEM listeners. It is a process proposed in the late 1990’s to help decision-makers select from among discordant reviews [1]. Since its publication, the Jadad decisions algorithm is now commonly used to interpret between SRMA with discordant results [2,3]. 2) Absence of Evidence: Just because we do not have high-quality RCTs does not mean we can conclude the procedures do not work. Total hip arthroplasty is one of the most successful surgical procedures in all of orthopedics. 3) Arthroscopic ACL Repair: The overall evidence does not support the routine reconstruction of a patients ACL. That does not mean a certain individual does not need their ACL repaired. There as a landmark study called KANON (Knee Anterior cruciate ligament NON operative vs operative treatment) published over a decade ago (NEJM 2010).  KANON was an RCT of 121 young active adults with an acute ACL injury. The primary outcome was the change from baseline to two years in the average score on four subscales of the Knee Injury and Osteoarthritis Outcome Score (KOOS) and knee-related quality of life. They found that rehabilitation plus early ACL reconstruction was not superior to rehabilitation plus optional delayed ACL reconstruction. A secondary analysis was just published that looked at the incidence of spontaneous healing of the ruptured ACL in the KANON trial (BMJ Sport and Ex Med 2022). They found there was a high rate of ACL healing in patients managed without surgery and only rehabilitation (56% at two years and 58% at five years). In addition, these individuals reported better patient-reported outcomes compared to the non-healed and reconstructed groups. So, like most things in medicine the answer is it all depends. Decision to perform surgery depends on many factors including the patients’ values and preferences. What are their current activities, and do they want to continue those activities? I had both my ACLs repaired well before the KANON trial. One repair went well while the other injured my common peroneal nerve, leaving me with foot drop for months and permanent decrease in sensation. 4) Possible Parachute: One of the other 10 common procedures lacking RCTs was arthroscopic meniscus repair. I don’t need an RCT to verify that it is not safe to jump out of an airplane without a parachute and I don’t need an RCT to inform my decision to repair a meniscus. I would caution you that most medical procedures are not parachutes and an RCT could be conducted [4].  In fact, even parachutes were tested in a RCT, but the plane was on the ground and not moving (SGEM#284). 5) Potential Harms: We have been discussing the lack of superiority for efficacy in six out of ten common orthopedic procedures. It is important to also consider the potential harms. While modern surgery is very safe, there is increased morbidity and mortality with surgical interventions. There is always a risk with surgical intervention.  Higher risks with things like joint arthroplasty or spine surgery so it is important to exhaust conservative measures.  However, when there is nerve impingement causing weakness (carpal tunnel, herniated disk, etc) delaying surgical decompression can lead to permanent weakness (different then neurogenic pain). Comment on Authors’ Conclusion Compared to SGEM Conclusion: We generally agree with the authors’ conclusions. SGEM Bottom Line: There is a lack of high-quality evidence to support all but two out of the ten most common elective orthopedic procedures. Case Resolution: The patient with his progressively worse knee is referred to an orthopedic surgeon to discuss his options. Clinical Application: This information can help patients and physicians in their decision-making process. In their supplemental material they compare their results to the American Academy of Orthopaedic Surgeons (AAOS) guidelines in Appendix 11. AAOS clinical practice guidelines (CPGs) use similar methodology with work groups analyzing the best available evidence and grading it.  They look at not only surgical options but also non-surgical options (orthobiologics, steroids, physiotherapy for knee osteoarthritis, etc).  As is highlighted in this review, there is frequently a lack of high-level studies to support any intervention (operative or nonoperative) and that is reflected in the grading of CPG. Dr. Matt Schmitz What Does the Orthopedist Tell the Patient? I recommend exhausting all conservative measures before considering joint replacement surgery.  Although the technology is getting better (implants lasting longer), you will want to delay as long as possible because we know primary joint replacements have better outcomes than originals.  So, if you have it replaced, you only want it replaced once.  There is little downside to trying conservative management (therapy, injections, etc). Keener Kontest:  Last weeks’ winner was Dr. Paeta Lehn from Vancouver Island.

Date: April 7th, 2022 Reference: Wong et al. Sensitivity of diffusion-weighted magnetic resonance imaging in transient global amnesia as a function of time from symptom onset. AEM April 2022 Guest Skeptic: Dr. Chris Bond is an emergency medicine physician and assistant Professor at the University of Calgary. Case: A 65-year-old man presents to your emergency department with his wife. She tells you that he woke up normally this morning, but after breakfast he began asking the same questions repetitively and was amnestic to the answer, seemingly unable to form new memories. He remained completely awake and alert and otherwise appeared well.  There was no history of recent trauma, infectious symptoms, or any other illness.  Background: Transient global amnesia (TGA) is an idiopathic acute neurological disorder that presents with sudden onset anterograde memory loss. It was first described as a syndrome in 1956 by Courjon and Guyotat and also by Bender [1,2].  Fisher and Adams formally described as TGA in 1964 [3]. The usual presentation is a patient between 50 and 70 years of age who are cognitively and neurologically intact but asking repetitive questions, unable to form new memory. Symptoms do not last very long and resolve within 24 hours. The incidence has been reported as 23.5 per 100,000 people per year [4] and is more common in people who get migraine headaches [5]. TGA is often precipitated by physical or emotional stressors, pain, the Valsalva maneuver, hot or cold-water immersion or sexual intercourse [6] Diagnosing TGA combines items put forward by Hodges and Warlow and Caplan [7-9]. This results in seven diagnostic criteria for TGA. Diagnostic Criteria for Transient Global Amnesia Attack is witnessed Clear-cut anterograde amnesia during the attack No neurologic symptoms or signs during the attack other than amnesia (no clouding of consciousness or loss of personal identity) No neurologic physical examination findings others than anterograde amnesia Memory loss is transient (resolution within 24 h) No epileptic features and no active epilepsy (defined as no seizure within 2 years or on antiepileptic medication) No recent head injury A diagnostic algorithm has been published for patients with sudden onset of anterograde amnesia [6]. Included in this differential is transient epileptic amnesia, transient ischemic attack, stroke, metabolic disorders, psychogenic disorders, and post traumatic amnesia. The workup can include laboratory testing, EEGs, ECGs, echocardiogram and advanced neuroimaging. Clinical Question: What is the sensitivity of diffusion-weighted magnetic resonance imaging (DW-MRI) as a function of time from symptom onset compared to clinical diagnosis of TGA? Reference: Wong et al. Sensitivity of diffusion-weighted magnetic resonance imaging in transient global amnesia as a function of time from symptom onset. AEM April 2022 Population: Adult patients 16 years of age and older with a diagnosis of TGA based on the existing clinical criteria Intervention: Evaluation with DW-MRI at varying time intervals post symptom onset Comparison: No comparison as no studies of patients without DW-MRI were included Outcome: Sensitivity of DW-MRI in diagnosis of TGA Dr. Matt Wong This is a back-to-back SGEMHOP episode. We did the March episode at the end of last month and the April episode is the first week of this month. We are pleased to have the lead author on the show. Dr. Matthew Wong is an emergency physician and educator at Beth Israel Deaconess Medical Center, and an Assistant Professor at Harvard Medical School. Authors’ Conclusions: “DW-MRI lesions are uncommon in patients with TGA early after symptom onset, but the sensitivity (i.e., positivity rate) of DW-MRI increases with time. Despite the limited quality of existing evidence, obtaining an early DW-MRI in patients with clinical diagnosis of TGA in the acute setting is likely a low-yield test.” Quality Checklist for Systematic Review Diagnostic Studies: The diagnostic question is clinically relevant with an established criterion standard. Yes 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. No The summary diagnostic accuracy is sufficiently precise to improve upon existing clinical decision-making models. No Results: They identified 23 studies in their search with a total of 1,688 patients who met inclusion criteria. All studies were case series of adult patients clinically diagnosed with TGA who underwent DW-MRI. Key Result: The sensitivity of DW-MRI in diagnosing TGA increases with time. In the first 12 hours from symptom onset, sensitivity of DW-MRI is 15.6%. It improves thereafter to sensitivities between 66 and 83%, with very wide confidence intervals for all point estimates. There is also significant heterogeneity between studies. Listen to the SGEM podcast to hear Matt answer our ten nerdy questions. 1. Number of Studies: It’s unfortunate that there was a paucity of data to inform our care on TGA. While you identified 23 studies with almost 1,700 patients there were only 2 studies for some time frames with a few dozen patients. The largest time frame only had 10 studies containing 539 patients. 2. Observational Studies: All the studies were observational in nature. There were no randomized trials allocating patients to any time frame (early or late). This limits conclusions to time being associated with better sensitivity for diagnosis TGA with DW-MRI. There could have been reasons why some patients go an MRI sooner while others receive an MRI later. 3. Heterogeneity: The heterogeneity measured by the I2 test was very high (72%-96%) for all time points besides 36-48 hours and 60-72 hours. Why did you decide to meta-analyze the data rather than just providing a narrative report? 4. Table 3: This has 0-12, 0-24 and 12-24 hour groups for time interval from onset. Why did you use three-time groupings here? 5. Partial Verification Bias (Referral Bias, Work-up Bias) – This happens when only a certain set of patients who underwent the index test is verified by the reference standard. Only those who met the clinical criteria for TGA got a DW-MRI. What about all those patients who did not meet clinical criteria and therefore did not get an MRI? This could increase sensitivity. Spectrum Bias 6. Spectrum Bias – Sensitivity depends on the spectrum of disease, while specificity depends on the spectrum of non-disease. So, you can falsely raise sensitivity if the clinical practice has lots of people with TGA. Do you know what the prevalence of TGA was in the included studies? Responds 7. Imperfect Gold Standard Bias (Copper Standard Bias): This is what can happen if the “gold’ standard is not that good of a test. False positives and false negatives can really mess up results. What is the diagnostic accuracy of the clinical criteria for diagnosing TGA? Responds 8. Serial MRIs: Some of the studies included in the SRMA used serial MRIs. Can you comment if the results were aligned with the entire group within the meta-analysis? 9. Future Studies: You know this area well after having looked at all these studies. How would you design a study using DW-MRI to evaluate for TGA based upon what you know now? 10. Open Question: Is there anything else you would like the SGEMer to know about TGA in general or your study specifically? Comment on Authors’ Conclusion Compared to SGEM Conclusion: We generally agree with the authors conclusions. SGEM Bottom Line: Urgent DW-MRI for patients meeting standard diagnostic criteria for TGA is a low yield intervention. Case Resolution: You perform a good history, followed by a directed physical examination. You then observe him over a period of hours in the emergency department and he slowly begins to form new memories. You perform an unenhanced CT head and basic bloodwork which is normal. He is discharged home with his wife and will follow up with a neurologist as an outpatient. Dr. Chris Bond Clinical Application: We do not need to request an urgent DW-MRIs in patients who meet clinical diagnostic criteria for TGA. What Do I Tell the Patient? You have something called transient global amnesia or TGA. This condition is not a stroke or seizure or other dangerous disease and will mostly likely resolve over 24 hours. You should have no long-lasting effects from this. You also explain this to the patient’s caregiver and provide a written handout from the Mayo Clinic explaining the same. Should you develop any other neurologic symptoms such as weakness, sensory changes, speech abnormalities or confusion, or are worried you should return to the emergency department immediately. Keener Kontest: Last weeks’ winner was Dr. Steven Stelts from NZ. Man is he quick with the answers. He knew Morton Heilig submitted a patent for the first head-mounted virtual reality display in 1957 . Listen to the SGEM podcast for this weeks’ question.  If you know, then send an email to thesgem@gmail.com with “keener” in the subject line. The first correct answer will receive a cool skeptical prize. SGEMHOP: Now it is your turn SGEMers. What do you think of this episode on the DW-MRI in diagnosing TGA? Tweet your comments using #SGEMHOP.  What questions do you have Matt and his team Ask them on the SGEM blog? The best social media feedback will be published in AEM. Don’t forget (unless you have TGA) those of you who are subscribers to Academic Emergency Medicine can head over to the AEM home page to get CME credit for this podcast and article. Remember to be skeptical of anything you learn,

Date: March 31st, 2022 Reference: Butt et al. Take-Pause: Efficacy of mindfulness-based virtual reality as an intervention in the pediatric emergency department. AEM March 2022 Guest Skeptic: Dr. Lauren Westafer is an Assistant Professor in the Department of Emergency Medicine at the University of Massachusetts Medical School – Baystate. She is the cofounder of FOAMcast and is a pulmonary embolism and implementation science researcher. Lauren won the 2021 SAEM FOAMed Excellence in Education Award. Case: A 15-year-old male presents to the pediatric emergency department (ED) with right ankle pain sustained while twisting his ankle during dance practice. The right ankle is swollen and tender. He rates his pain a 5 on the FACES scale and is awaiting examination by the treating clinician. Background: Pediatric emergency department (ED) visits and related procedures can invoke pain and anxiety among children. Patients who experience adequate pain relief during their ED stay have significant reductions in distress, improved rapport with their physician, improved intent to comply with discharge instructions and higher levels of personal and caregiver satisfaction. Children represent one group of patients that are less likely to receive adequate analgesia (Brown et al, Selbst and Clark). This phenomenon is known as oligoanalgesia or poor pain management through the underuse of analgesia. Dr. Anthony Crocco We have covered pediatric pain with PEM super hero Dr. Anthony Crocco on SGEM#78 who did a RANThony on this issue. Dr. Samina Ali is a PEM super (s)hero who was on SGEM#242 looking at intranasal (IN) ketamine vs fentanyl on pain reduction for extremity injuries in children. The bottom line from that trial was IN ketamine appears to be non-inferior to IN fentanyl for efficacy, but with more adverse events. Many clinicians utilize distraction techniques to reduce pain and anxiety in children during their ED visits [4]. However, there are no prospective randomized trials using virtual reality (VR) as a distraction technique while awaiting physician evaluation. Clinical Question: Does a 5-minute virtual reality program reduce situational anxiety in the pediatric ED? Reference: Butt et al. Take-Pause: Efficacy of mindfulness-based virtual reality as an intervention in the pediatric emergency department. AEM March 2022 Population: Patients ages 13-17 years who presented to the pediatric ED with mild to moderate acute pain (pain score 2-6 on FACES pain scale) Exclusions: Patients with developmental delays, inability to speak English, prone to motion sickness, significant visual/hearing impairment, pregnancy, parental refusal, received analgesic ≤4 hours prior to ED arrival, or inability to use the pain scale. Intervention: Virtual reality “Take Pause” program for 5 minutes Comparison: Passive distraction technique with hospital-owned iPad with pre-downloaded age-appropriate games for 5 minutes Outcome: Primary Outcome: Difference in the change in situational anxiety level between groups 15 minutes after intervention using the Spielberger State – Trait Anxiety Inventory (STAI: Y-6 item) Secondary Outcomes: Mean difference in pain score on the FACES scale, heart rate, respiration rate from baseline to 15 minutes after intervention Trial: Prospective, randomized, single-blind trial Mahlaqa Butt This is an SGEMHOP episode which means we have the lead author on the show. Mahlaqa Butt, MPH is a third-year medical student at New York Institute of Technology-College of Osteopathic Medicine and a clinical research associate at the Department of Emergency Medicine at Maimonides Medical Center, Brooklyn NY. She has co-authored 11 peer-reviewed emergency medicine research publications primarily focused on opioid-free pain management in the ED. She will be pursuing a residency in emergency medicine this fall. Authors’ Conclusions: “Take-Pause, offering an active and immersive distraction technique, is more effective than a passive distraction approach to lower anxiety levels in adolescent ED patients.” Quality Checklist for Randomized Clinical Trials: The study population included or focused on those in the emergency department. Yes The patients were adequately randomized. Yes The randomization process was concealed. Yes The patients were analyzed in the groups to which they were randomized. Yes The study patients were recruited consecutively (i.e. no selection bias). No The patients in both groups were similar with respect to prognostic factors. Unsure All participants (patients, clinicians, outcome assessors) were unaware of group allocation. No All groups were treated equally except for the intervention. Yes Follow-up was complete (i.e. at least 80% for both groups). Yes All patient-important outcomes were considered. No The treatment effect was large enough and precise enough to be clinically significant. Unsure Financial conflicts of interest. The authors stated they had no potential conflicts to disclose. Results: They enrolled 110 teenagers into the trial with 55 participants in each group. The mean age was 15 years, 60% were male and the mean pain score was 4.1/10. Key Result: Anxiety levels were reported lower in the intervention group compared to the comparison group. Primary Outcome: Mean anxiety score on the Spielberger State – Trait Anxiety Inventory (STAI: Y-6 item) VR group improved by 10 points vs. 6 points in the iPad group (95% CI: 0.44 to 7.6) p < 0.001 Secondary Outcomes: At 15 minutes, there was no difference in mean pain scores (3.6 vs 3.6), heart rate (intervention 81 bpm vs control 83 bpm), or respiratory rate (intervention 18 vs control 20) Listen to the SGEM podcast to hear Mahlaqa answer our five nerdy questions. 1. Patient Characteristics – Very little information is given regarding patient characteristics. For example, we have no information on traumatic vs nontraumatic pain, location of pain, race/ethnicity, or other potentially important variables. Although randomization should theoretically balance out any differences, it is helpful to have patient characteristics reported so we can gauge – are these patients like my patients? 2. Virtual Reality (VR) for Mindfulness – We have looked at mindfulness to help relieve the stress of interns on their EM rotation on SGEM#178. In this other small study, it seemed to be effective. However, that study had 10 weeks of mindfulness training sessions as the intervention. Can you describe this Take Pause VR immersion tool in more detail? 3. Effect Size - Effect size is a quantitative measurement of the magnitude of the difference between groups. In this study, the authors set out to find a difference of ≥3 on the STAI Y-6 from baseline to post-intervention. They felt this would be statistically significant as a 1999 study that looked at music before bronchoscopy had a 3.6 reduction on the anxiety score (but did not meet the arbitrary 5 points set out by those authors). It often takes more participants to detect a smaller effect size. 4. Comparison Group – You compared the VR Take Pause immersion tool to standard distraction techniques using an iPad. This could have introduced a bias towards lower anxiety because some teenagers desire to use some cool new technology. Why not use another VR headset intervention? Patients knew they were going to be randomized into the VR or iPad group. You mentioned in your publication this could have led to optimism bias. Could you explain that type of bias further? Did you consider other techniques not involving technology like animal therapy? On SGEM#289 we looked at having a dog to play with to relieve stress on the staff. The intervention looked promising, and I wonder how it would have compared to using a VR device. 5. Statistical Significance vs Clinical Significance - The mean baseline anxiety score (STAI Y-6 score) placed nearly the same proportion of patients in the mild anxiety group (score 20-40) ~82-94% and in the moderate anxiety group (score 41-60) – 16% of patients in both groups. The virtual reality arm had a 10-point reduction from baseline while the iPad group had a 6-point reduction. However, the post-intervention score was only 2.9 points different between groups. Overall, it’s not clear that the statistically significant difference between groups is clinically significant. Comment on Authors’ Conclusion Compared to SGEM Conclusion: We disagree with the authors conclusion and believe that this trial shows both Take-Pause and passive distraction with an iPad reduce self-reported anxiety levels in adolescent ED patients. SGEM Bottom Line: The virtual reality "Take Pause" immersion tool is another possible non-pharmaceutical intervention to reduce anxiety of paediatric patients in the ED. Case Resolution: The patient is offered either a mindfulness-based virtual reality program or an iPad with preprogrammed games while awaiting clinician evaluation. Dr. Lauren Westafer Clinical Application: Reducing anxiety is important in the emergency department. There are several non-pharmacologic techniques that can be used. This small study suggests the VR Take Pause immersion tool can be one of those techniques. What Do I Tell My Patient?  There are several ways to reduce anxiety in the pediatric emergency department. Both a mindfulness based virtual reality program and playing games on an iPad may help reduce your anxiety. Keener Kontest: Last weeks’ winner was Danny Driskill from the Kentucky College of Osteopathic Medicine. He knew IBM Simon Personal Communicator was the first “smart phone”.  It was released August 16, 1994. Listen to the SGEM podcast for this weeks’ question.  If you know, then send an email to thesgem@gmail.com with “keener” in the subject line.

Date: March 26th, 2022 Guest Skeptic: Professor Melanie Trecek-King Associate professor of biology at Massasoit Community College in Massachusetts. Founder and creator of Thinking Is Power. Reference: Trecek-King M.A Life Preserver for Staying Afloat in a Sea of Misinformation.  Skeptical Inquirer March/April 2022 Prof Trecek-King This is an SGEM Xtra episode. I met Melanie through our online interactions on Twitter. She posts excellent tweets about critical thinking. I then discovered her amazing website called Thinking is Power. We also discovered through our social media interactions that were were both Feynman fans. I asked Melanie to come on the show and discuss her recent article in Skeptical Inquirer and explain the acronym she created called FLOATER. Melanie explains that FLOATER grew out of James Lett’s “A Field Guide to Critical Thinking” (Lett J. Skeptical Inquirer 1990), in which he summarized the scientific method with the acronym FiLCHeRS (Falsifiability, Logic, Comprehensiveness of evidence, Honesty, Replicability, and Sufficiency of evidence). The FLOATER acronym stands for Falsifiability, Logic, Objectivity Alternative explanation, Tentative conclusion, Evidence, and Replicability. This was the basis for her article in Skeptical Inquirer. Melanie published her first article in the January/February edition called "Teach Skills, Not Facts". Listen to the SGEM Xtra podcast to hear Melanie explains each of the seven tools/rules that make up the FLOATER acronym. Tool 1: Falsifiability It must be possible to think of evidence that would prove the claim false. It seems counterintuitive, but the first step in determining if a claim is true is to determine if you can prove it wrong. Tool 2: Logic Arguments for the claim must be logical. They can be deductive or  inductive arguments. We should try and not commit logical fallacies when arguing positions. Tool 3: Objectivity The evidence for a claim must be evaluated honestly. Tool 4: Alternative Explanations Other ways of explaining the observation must be considered.  Tool 5: Tentative Conclusions In science, any conclusion can change based on new evidence. Tool 6: Evidence The evidence for a claim must be reliable, comprehensive, and sufficient. Tool 7: Replicability Evidence for a claim should be able to be repeated. We have a reproducibility crisis in science.  We ended this SGEM Xtra show with a quote from Marie Curie. I think Melanie is an amazing skeptic and educator. It was an absolute pleasure to have her on the show as the guest skeptic. 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 Additional Readings: Kahan et al. Science Curiosity and Political Information Processing. Political Psychology. January 2017 Kahan DM. Why Smart People Are Vulnerable to Putting Tribe Before Truth. Scientific America. December 2018 Trecek-King M. Teach Skills, Not Facts. Skeptical Inquirer. January/February 2022