The Skeptics Guide to Emergency Medicine

Date: July 22nd, 2022 Reference: Perry et al. Immobilisation of torus fractures of the wrist in children (FORCE): a randomised controlled equivalence trial in the UK. The Lancet 2022 Guest Skeptic: Dr. Tessa Davis is a Paediatric Emergency Consultant at the Royal London Hospital, Senior Lecturer at Queen Mary University of London, Co-founder of Don’t Forget The Bubbles (DFTB). Tessa also has a weekly newsletter with tips to help you level up your use of everyday technology and to optimise your writing and to reach the audience you want. Case: Jack is nine years old, and he presents to emergency department (ED) with an arm injury. Today he was running at school, and he fell over onto his outstretched arm. His right arm is neurovascularly intact, with no swelling or deformity. He has bony tenderness at the distal radius. The X-ray shows a buckle fracture of his right distal radius. Background: We covered buckle fractures way back in Season#1 of the SGEM on SGEM#19. In that episode from ten years ago we made the distinction between a buckle fracture and greenstick fractures. Buckle fractures (also called torus fractures) are defined as a compression of the bony cortex on one side with the opposite cortex remains intact. In contrast, a greenstick fractures the opposite cortex is not intact. Buckles of the distal radius are the most common fracture seen in children and very commonly present to the ED [1-2]. Despite being a common injury they are often managed differently. Some clinicians apply casts, some a splint, some have orthopedic follow up, some have no follow up [3]. This practice variation is not new. A survey done almost 20 years ago in Canada demonstrated the variability of managing buckle fractures by Pediatric orthopedic surgeons and pediatric emergency physicians [4]. An RCT published 12 years ago reported that a soft bandage wrapping treatment for four weeks was not statistically different for discomfort, function or fracture displacement compared a below elbow back slab cast for one week followed by circumferential cast for three weeks despite some more pain in the first week with the soft bandage [5]. Yet here we are ten years later doing an SGEM episode on whether it is ok to put a soft bandage on these pediatric patients with a distal radius buckle fracture. It is a great example of how knowledge translation can take years or even decades for clinically relevant information to reach the patients’ bedside due to leaks in the EM knowledge translation pipeline [6-7]. Clinical Question: What is the appropriate management of torus fractures in children? Reference: Perry et al. Immobilisation of torus fractures of the wrist in children (FORCE): a randomised controlled equivalence trial in the UK. The Lancet 2022 Population: Children between 4 and 15 years of age with a distal radius torus fracture that had been confirmed by x-ray. Exclusions: Other fractures, although a concomitant ulnar fracture did not lead to exclusion. Injury over 36 hours old, any cortical disruption seen on x-ray, and any reasons that meant follow-up would not be possible, such as a language barrier, lack of internet access or developmental delay. Intervention: Rigid immobiisation Comparison: Tensor (crepe) bandage Outcome: Primary Outcome: Pain on day three measured using the Wong-Baker FACES Pain Rating Scale [8]. Participants also recorded their pain score on day one, seven and weeks three and six. Secondary Outcomes: Measured a variety of other outcomes at the same time points, unless otherwise specified: Functional recovery using the PROMIS (Patient Report Outcomes Measurement System)Upper Extremity Score – a patient or parent-reported measure of physical function of the upper limbs. Health-related quality of life outcomes, using a EuroQol EQ-5DYa standardised questionnaire, suitable for children, which asks about quality of life, including activities of daily living and pain. Analgesia use and type taken (measured on days 1, 3 and 7) Days of school absence Health care resource use i.e. a new splint (measured at weeks 3 and 6), return to hospital Treatment satisfaction measured using a 7-item Likert scale determined on day 1 and week 6 Complications Trial: The FORCE study was a multi-centered, randomized, non-blinded, equivalence trial conducted at 23 Emergency Departments across the UK. Authors’ Conclusions: “This trial found equivalence in pain at 3 days in children with a torus fracture of the distal radius assigned to the offer of a bandage group or the rigid immobilisation group, with no between-group differences in pain or function during the 6 weeks of follow-up.” 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. 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 Financial conflicts of interest. This trial was funded by the UK National Institute for Health and Care Research. It is stated in the manuscript that “The funder of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report.” Results: They screened 1,513 patients between January 2019 and July 2020 for inclusion in this trial. The researchers randomized 965 children, 61% were boys, and a mean age of 10 years. More than half of those who declined to participate in the FORCE trial said they preferred rigid immobilisation, while only 1% indicated a preference for the soft bandage. Of the 458 (94%) participants in the “offer of a bandage” group chose for it to be applied in the ED. Of the 451 (95%) participants in the rigid immobilisation group were given a removable splint. The remaining 5% in this group were treated with either a plaster cast (back slab or circumferential) or a soft cast. We did mention crossover in the quality check list. A total of 57 children (11%) changed from bandage to rigid immobilisation while only 1 patient changed in the other direction. Key Result: A soft bandage was equivalent to rigid immobilization in children with a distal radius torus fracture. Primary Outcome: Pain on day three measured using the Wong-Baker FACES Pain Rating Scale. There was no statistically significant difference in pain scores with the mITT 3.21 (bandage) vs 3.13 (rigid) with effect size -10 (95% CI; -0.37 to 0.17) They dichotomized into aged 4-7 years and aged 8-15 years and the results were equivalent for the total population and the two subgroups with both the ITT analysis and the PP analysis Secondary Outcomes: There was no statistical difference between the two groups in terms of secondary outcomes either (including PROMIS scores and EQ-5DY-3L utility scores). Parents in the rigid immobilisation group were more satisfied on Day 1 but there was no difference by 6 weeks. Because the number of complications reported was very low no formal statistical comparison were made. There were no cases of worsening deformities. There was no difference in complication rate in either group. Both treatment options led to a similar number of missed school days – around one and a half. There was a (small) difference in analgesia use though. 83% of the bandage group had painkillers, compared to 78% in the rigid immobilisation group on the first day, though there was no significant difference down the track. 1. Something for Coming: Families did not like having no treatment provided. The trial was originally set up to compare rigid immobilisation with no treatment and discharge. A family focus group, carried out by the researchers, suggested that the offer of no treatment at all was unacceptable, and so the study was changed to compare rigid immobilisation with the offer of a soft bandage. 2. Equivalence Trials: We don’t often see trials designed to check for equivalence. The most common design is a superiority trial. The more conservative way to analyze superiority trials is with an ITT analysis. In contrast, non-inferiority trials it is better to conduct a PP analysis. Our friend Dr. Justin Morgenstern from First10EM has tweeted his thoughts about non-inferiority trials citing an article that says non-inferiority trials are unethical [9]. The FORCE trial did both types of analyses (ITT and PP) and demonstrated equivalence. 3. Clinician Variability: Not everyone diagnoses a torus fracture in the same way. We know the technical definition but what you would call a torus fracture might not be the same as me. Defining the line between a buckle of the cortex and a break is tricky. It's open to interpretation - some people have a broader net than others. 4. Don’t Just Do Something Stand There: This is a very important philosophy in medicine that I learned from Dr. Jerry Hoffman. It was explained very well in an article called “Don’t just do something, stand there! The value and art of deliberate clinical inertia” [10]. Clinicians have a desire to usually do something, and this is called intervention bias [11]. More care is not always better care. The use of a soft bandage to treat a distal radius buckle fracture in children is an excellent example.

Dr. Salim R. Rezaie, a community emergency physician and founder of REBEL EM, joins the discussion on the controversial role of Vitamin C in treating sepsis. They critically analyze a troubling case study involving a 59-year-old woman and delve into the study methodology, discussing the importance of evidence-based medicine. The conversation highlights the potential risks and mortality linked to Vitamin C therapy, urging caution in its use. Salim emphasizes the need for rigorous trials to ensure patient safety and effective treatment.

Date: July 1st, 2022 Guest Skeptic: Dr. Ravi Garg is a Neurologist in the Department of Neurology, Division of Neurocritical Care at Loyola University Chicago. Reference: Garg R, Mickenautsch S. Risk of selection bias assessment in the NINDS rt-PA stroke study. BMC Med Res Methodol. 2022 Jun 15;22(1):172. This is an SGEM Xtra episode. Dr. Garg saw some tweets about the NINDS trial and sent me his recent publication. I asked him to come on the SGEM and discuss the original NINDS trial, some of the reanalyses and share his analysis of the NINDS data. One of the criticisms of Emergency Medicine physicians who have done FOAMed post publication reviews of the stroke literature like Dr. Justin Morgenstern, Dr. Ryan Radecki, Dr. Anand Swaminathan and Dr. Salim Razaie, is that we are not neurologists and specifically not stroke neurologists. While this is true, we are part of the team that diagnose and treat acute stroke patients. The SGEM tries to include a wide variety of clinicians in this knowledge translation project. Great emergency care takes a team from the prehospital setting, emergency department, inpatient and outpatient all working together. That is why we have had paramedics, nurses, physiotherapists, pharmacists and a wide spectrum of physician specialists on the SGEM. However, until now have we not had a neurologist on the SGEM who has a specialized interest in stroke neurology and published on thrombolysis as a guest skeptic. Dr. Garg sent me his analysis of the NINDS trial that he wrote with his co-author Dr. Steffen Mickenautsch. This new peer reviewed publication is the basis of this SGEM Xtra episode. The NINDS trial was published back in 1995 and we did a structured critical appraisal of the classic paper with Dr. Anand Swaminathan on SGEM#70.  I was a resident at the time of publication and Dr. Garg was only eight years old. Dr. Garg was asked a series of questions. You can listen to his responses on the SGEM podcast. Thoughts on the NINDS Trial and Some of the Reanalyses Dr. Ravi Garg Any general thoughts about NINDS trial? One concern about the NINDS trial was the baseline differences in NIHSS score. This resulted in multiple reanalyzes attempting to control for these factors. NINDS commissioned an independent committee to investigate if any of these imbalances invalidated the entire trial. This committee’s findings supported the use of tPA in less than three hours (Ingall et al 2004). What are your thoughts on this commissioned report? Another reanalysis was done by Kwiatkowski et al 2005 that also confirmed that the baseline imbalance in the NINDS trial did not account for the better outcome of tPA-treated patients. Any brief comments on this reanalysis? Hoffman and Schrieger stirred things up a bit with their graphic reanalysis of the NINDS trial using the NIHSS score. They published their findings in Annals of EM 2009. The results questioned the effect of tPA for acute ischemic stroke in patients treated within three hours. The graphs created in the publication also failed to support the "time-is-brain" hypothesis. There are some criticisms of this graphic reanalysis. What are your thoughts on this contrarian view? Saver et al responded to Hoffman and Schrieger’s graphic reanalysis in Academic Emergency Medicine 2010. They pointed out number concerns with the publications. Did Saver and colleagues make some sound arguments? Ravi Garg and Steffen Mickenautsch BMC June 2022 The title of your paper is Risk of selection bias assessment in the NINDS rt-PA stroke study. It was published in BMC Medical Research Methodology, June 2022. With all the other reanalyses, what motivated you to do this another reanalysis of the NINDS trial? You were able to get patient level data for this review. Why is that important? What tool did you use to assess the NINDS trial for risk of selection bias? Can you walk us through the Cochrane Risk of Bias-2 (RoB-2) tool that address systematic error arising from the randomization process? You did four sensitivity analyses based on the randomization process using participant level data. Briefly what were the four analyses? What did you do to assess the potential effect of baseline imbalances on reported alteplase treatment effects? What were the results of your study on the NINDS trial? What did you discover with the four sensitivity analyses? You adjusted for the differences found in the sensitivity analyses. How did that impact the results? Why is unbiased randomization so important in RCTs? What points do you want to highlight from your discussion What do you think the limitations are to your study? Conclusions to this New Analysis of the NINDS Trial Data What conclusions did you draw from your assessment of the NINDS trial? What does this high risk of selection bias due to your certainty about this data? You conclude the imbalances seen in the NINDS trial were not noise (random error) in the data but rather an error in randomization. This can bias the results and move us away from the “truth” (the best point estimate of an observed effect size with a confidence interval around that effect size). So the results are fuzzier and less certain? This error in randomization would then be passed along into any systematic review and meta-analysis (SRMA) done on this topic. Could this bias a SRMA even if it used individual patient data which is considered the "gold standard" by Cochrane? Some of those convinced of the efficacy of tPA for acute ischemic stroke will say it is unethical to perform a placebo controlled RCT due to a lack of equipoise. How do you respond to that argument? How should we apply your paper clinically? Dr. Ravi Garg's Bottom Line: I’m very skeptical about the results in the NINDS study and thrombolytic studies for stroke in general. 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 Reading: Shinton R. Questions about authorisation of alteplase for ischaemic stroke. Lancet. 2014 Aug 23;384(9944):659-60. doi: 10.1016/S0140-6736(14)61385-4. PMID: 25152265. Appelros P, Terént A. Thrombolysis in acute stroke. Lancet. 2015 Apr 11;385(9976):1394. doi: 10.1016/S0140-6736(15)60714-0. PMID: 25890417. Mickenautsch S, Fu B, Gudehithlu S, Berger VW. Accuracy of the Berger-Exner test for detecting third-order selection bias in randomised controlled trials: a simulation-based investigation. BMC Med Res Methodol. 2014 Oct 6;14:114. doi: 10.1186/1471-2288-14-114. PMID: 25283963; PMCID: PMC4209086. Austin PC, Tu JV. Automated variable selection methods for logistic regression produced unstable models for predicting acute myocardial infarction mortality. J Clin Epidemiol. 2004 Nov;57(11):1138-46. doi: 10.1016/j.jclinepi.2004.04.003. PMID: 15567629. Goyal M, Menon BK, van Zwam WH, et al.  HERMES collaborators. Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials. Lancet. 2016 Apr 23;387(10029):1723-31. doi: 10.1016/S0140-6736(16)00163-X. Epub 2016 Feb 18. PMID: 26898852. Schulz KF, Chalmers I, Hayes RJ, Altman DG. Empirical evidence of bias. Dimensions of methodological quality associated with estimates of treatment effects in controlled trials. JAMA. 1995 Feb 1;273(5):408-12. doi: 10.1001/jama.273.5.408. PMID: 7823387. Johnstone C. Thrombolysis for acute ischemic stroke: does it work?--the con position. CJEM. 2015 Mar;17(2):180-3. doi: 10.1017/cem.2015.14. Erratum in: CJEM. 2015 Sep;17 (5):600. PMID: 26052969. Berger VW, Exner DV. Detecting selection bias in randomized clinical trials. Control Clin Trials. 1999 Aug;20(4):319-27. doi: 10.1016/s0197-2456(99)00014-8. PMID: 10440559. Estruch R, Ros E, Salas-Salvadó J, Covas MI, Corella D, Arós F, Gómez-Gracia E, Ruiz-Gutiérrez V, Fiol M, Lapetra J, Lamuela-Raventos RM, Serra-Majem L, Pintó X, Basora J, Muñoz MA, Sorlí JV, Martínez JA, Martínez-González MA; PREDIMED Study Investigators. Primary prevention of cardiovascular disease with a Mediterranean diet. N Engl J Med. 2013 Apr 4;368(14):1279-90. doi: 10.1056/NEJMoa1200303. Epub 2013 Feb 25. Retraction in: N Engl J Med. 2018 Jun 21;378(25):2441-2442. Erratum in: N Engl J Med. 2014 Feb 27;370(9):886. Corrected and republished in: N Engl J Med. 2018 Jun 21;378(25):e34. PMID: 23432189. Estruch R, Ros E, Salas-Salvadó J, Covas MI, Corella D, Arós F, Gómez-Gracia E, Ruiz-Gutiérrez V, Fiol M, Lapetra J, Lamuela-Raventos RM, Serra-Majem L, Pintó X, Basora J, Muñoz MA, Sorlí JV, Martínez JA, Fitó M, Gea A, Hernán MA, Martínez-González MA; PREDIMED Study Investigators. Primary Prevention of Cardiovascular Disease with a Mediterranean Diet Supplemented with Extra-Virgin Olive Oil or Nuts. N Engl J Med. 2018 Jun 21;378(25):e34. doi: 10.1056/NEJMoa1800389. Epub 2018 Jun 13. PMID: 29897866. Hicks A, Fairhurst C, Torgerson DJ. A simple technique investigating baseline heterogeneity helped to eliminate potential bias in meta-analyses. J Clin Epidemiol. 2018 Mar;95:55-62. doi: 10.1016/j.jclinepi.2017.10.001. Epub 2017 Oct 13. PMID: 29032245.

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.