The Skeptics Guide to Emergency Medicine

Date: September 16th, 2022 Reference: Gerlier C, et al.  Differentiating central from peripheral causes of acute vertigo in an emergency setting with the HINTS, STANDING and ABCD2 tests: A diagnostic cohort study. AEM 2021 Guest Skeptic: Dr. Peter Johns has been practicing emergency medicine since 1985 and has been passionate about vertigo education for the last two decades.  He co-authored the Vertigo chapter in the current edition of Tintinalli’s emergency medicine textbook and has a YouTube channel about vertigo with over 16,000 subscribers and five million views. Case: This is a real case seen by Peter and you can see the actual exam findings in a video on his YouTube channel. A 70-year-old woman wakes up with dizziness and presents to the emergency department (ED) later that day.  She’s vomited twice, and describes her dizziness as a constant spinning sensation, which gets worse when she moves her head.  She has some unsteadiness but can walk unaided.  She has no other neurologic symptoms.  In particular, she denies any new significant headache or neck pain, or focal weakness or paresthesia, dysarthria, diplopia, dysmetria, dysphagia or dysphonia, (the so-called Dangerous D’s).  When you examine her, and she is looking straight ahead, you observe that she has horizontal and slight torsional nystagmus beating towards her left ear. That means that the fast component of the nystagmus is horizontal, to the left, and there is a slight rotation with the upper pole of the eyes beating towards the left as well. Background: We have looked at acute vestibular syndrome (AVS) on the SGEM with Dr. Mary McLean who was the guest skeptic on SGEM #310. The bottom line from that episode was that: Dr. Mary McLean "the available evidence does not support the use of the HINTS examination alone by emergency physicians in patients with isolated vertigo or AVS to rule out a posterior stroke." In that episode, the case patient was told they would be admitted to the hospital to have a neurologist do the HINTS exam and decide if an MRI was necessary. But the question remains: can emergency physicians be taught how to use the HINTS exam to make clinical decisions? This is a difficult task, in part because vertigo education for emergency physicians has historically contained lots of  misinformation.  If there’s one thing we learned from the current pandemic, it is that misinformation is easier to spread than to correct. The tsunami of misinformation around COVID-19 has been coined the “infodemic”. We talked about this with Simon Carley on an SGEM Xtra and he emphasized “principles EBM are even more important now than in any time in our career”. There is a great quote by Thomas Francklin in 1787 about misinformation that rings true over two-hundred years later in the age of social media. He said: “Falsehoods will fly, as it were, on the wings of the wind, and carry its tale to every corner of the earth; whilst truth lags behind; her steps, though sure, are slow and solemn.” There is quote from another famous Franklin, Ben, which is apropos to the HINTS exam. "You will observe with concern how long a useful truth may be known, and exist, before it is generally received and practiced on." Myths & Misinformation about Dizziness: Myth: Asking what they mean by dizzy is the most important question to ask a dizzy patient. In fact, the patient's description of the sensation of their dizziness cannot be used to generate a reliable differential diagnosis. Myth: Tables of central vs peripheral characteristics of vertigo are helpful. Let us just say they are not.  You can watch my YouTube video about this for more info. Myth: If it gets worse when you move your head, that means it’s a peripheral cause. All vertigo gets worse when you move your head. If it does not, it probably is not vertigo. Myth: A CT or CTA will prevent you from sending home a stroke presenting with dizziness. Nope. CT has very poor sensitivity for stroke. Myth: Hearing loss only happens in peripheral causes. In fact, an AICA stroke, (anterior, inferior cerebellar artery) can cause hearing loss. Myth: If you see any vertical nystagmus, it must be a central cause. In fact, the most common cause of nystagmus is BPPV, and vertical upward nystagmus is an expected finding. Spontaneous vertical nystagmus, (nystagmus you see when the patient is just sitting or lying there) is central. There are a lot of dogmas and myths in medicine. We have discussed some of them on the SGEM including SGEM#9, SGEM#63, and SGEM Xtra: Dogmalysis 2021.  It is no wonder emergency physicians struggle with dizzy patients when what we were taught for decades is often not very helpful. Added to these myths is the fact that some cerebellar strokes appear very similar to vestibular neuritis.  Poor understanding of vertigo leads to fear and avoidance of seeing these kinds of patients, which leads to continued poor knowledge, more avoidance and so on.  I call this the Vertigo Vicious Cycle of Vexation.  And most emergency physicians are caught in that cycle. The problem, as illustrated by the case, is that most of the patients with AVS (constant vertigo, which is worse with head movement, nausea/vomiting, difficulty walking, AND nystagmus) have vestibular neuritis (VN).  But some will be have a posterior circulation stroke (PCS). There are other rarer causes of AVS but, functionally, the differential diagnosis in AVS is VN vs stroke.  Many, but not all, patients with PCS will have other central features. It would be unusual for a patient with VN to have a new significant headache or neck pain, which are red flags for a cerebellar hemorrhage or vertebral artery dissection. Other concerning features would include focal weakness or paresthesia, or diplopia, dysarthria, dysmetria, dysphagia, dysphonia, or spontaneous vertical nystagmus or the inability to walk unaided. Any of those features in a patient with vertigo and nystagmus at rest should make you very concerned that your patient is having a stroke.  The first line of defence against missing a PCS should therefore be screening for thee central features, and NOT the HINTS exam.  If you find any of those central features, work them up for stroke. What do we do with the majority of patients who have AVS but, none of those central features, like in the case scenario? Do we just say: “no neuro findings, must be VN, and send them home” or do we get an MRI in them all? Since most patient with AVS (again with nystagmus) have VN, the cost and availability of MRI for this indication becomes a real practical issue.   In addition, MRIs done within the first 24 hours of onset can miss approximately 20% of PCS. (Shah et al AEM 2022). Should we admit all of these dizzy patients for two or three days and get an MRI? Some well-funded systems do that, but most systems are simply unable to afford such practices. Therefore, there is a great need for a clinical test with excellent negative predictive value to rule out stroke in these low risk AVS patients with no central features. The HINTS plus exam has been shown in expert hands to have a -LR of 0.01, that’s pretty darn low. (Newman-Toker et al AEM 2013) The key phrase is in “expert hands”. David Newman-Toker is an MD, PhD and Professor of Neurology, Ophthalmology, & Otolaryngology. This leads back to the question of can the HINTS exam be correctly applied and interpreted in the hands of an emergency physician? The SRMA by Ohle et al AEM 2020 suggested they cannot. In the one study that included a specially trained emergency physician, the diagnostic accuracy of the HINTS exam was not impressive: sensitivity was 83% and specificity was 44%. In Kerber’s 2015 study, there was only one emergency physician amongst the three physicians using the HINTS exam.  The HINTS should be seen as an extra safety measure to ensure we aren’t missing a stroke in patients suffering with what is most likely vestibular neuritis. It is very important to stress that the HINTS exam should not be viewed as a stand-alone test on all patients presenting with vertigo. The HINTS exam must also be applied in the correct clinical situation. In a retrospective chart review of 2,309 patients presenting with dizziness, the HINTS exam was misapplied 97% of the time. (Dmitriew et al AEM 2021). This study showed the drawbacks of applying a new, somewhat sophisticated bedside examination technique without training.  If you just handed out ultrasound machines in the 1990’s without training, you'd be getting similar bad results. Again, HINTS should only be used in patients with significant, constant vertigo AND spontaneous nystagmus who don’t have the central features we already described. The HINTS exam consists of three bedside tests: assessment of nystagmus, test of skew, and the head impulse test. The HINTS “plus” exam is HINTS with the addition of a bedside test of hearing (the finger rub test) to help pick up an AICA stroke. An anterior inferior cerebellar artery stroke can present with the other HINTS exam findings identical to vestibular neuritis, as the AICA stroke produces an infarct of the organs of balance and hearing as well as part of the cerebellum.  So, a new hearing loss in a patient who presents with vertigo and findings consistent with a vestibular neuritis in that same ear signals a potential AICA stroke.  The bedside test of hearing can pick up these AICA strokes and make the negative predictive value for HINTS even higher. The questions remain: how much training is required to use the HINTS exam in clinical decisions, and how should it be taught? And, if you decide to not use the HINTS exam, what are you using to evaluate these patients in its place? The paper we will discuss compares the HINTS exam to the STANDING protocol.  STANDING is an algorithm by Dr. Vanni et al.

Date: August 25th, 2022 Reference: Martin et al. Single-dose dexamethasone is not inferior to 2 doses in mild to moderate pediatric asthma exacerbations in the emergency department. Pediatr Emerg Care. 2022 Dr. Harrison Hayward Guest Skeptic: Dr. Harrison Hayward is a Pediatric Emergency Medicine fellow at Children’s National Hospital. He finished his General Pediatrics residency at Yale-New Haven Hospital. As an editor and writer of continuing medical education material for the clinical case-sharing app, Figure 1, he enjoys interprofessional learning and is passionate about improving health care delivery to children with complex medical needs. Case: A 7-year-old female with asthma presents to the emergency department (ED) with difficulty breathing in the setting of 1-2 days of cough and runny nose. She reports that her albuterol helped her feel better yesterday, but it is providing no relief today. On exam, she has diffuse expiratory wheezing but good aeration to bilateral lung bases with a respiratory rate of 22. She has some intercostal retractions. SpO2 97% on room air. She can speak in full sentences. You diagnose her with a mild asthma exacerbation and begin treating her with albuterol/ipratropium and a dose of dexamethasone. After you explain the plan to the family, her mother says to you, “last time she was here, we got another dose of that steroid medication to take the next day. Do you think she needs it? She doesn’t like taking it, and it makes it hard for her to get to sleep.” Background: Asthma affects around 9% of children in the United States and asthma exacerbations are a common cause for ED visits. Corticosteroids are commonly use for treatment of acute asthma exacerbations. Previous research has compared the efficacy of a multi-day course of prednisone/prednisolone to single dose or two doses of dexamethasone [1-4]. We covered one of these studies on the SGEM: Highway to the Dexamethasone (SGEM #194) “A single dose of dexamethasone is non-inferior to a three-day course of oral prednisolone in the treatment of children with acute asthma exacerbation presenting to the emergency department.” So why are we back here talking about corticosteroids and asthma again? Studies had compared prednisone/prednisolone with one or two-dose dexamethasone. However, no prospective clinical trial has directly compared single dose dexamethasone to two doses. Clinical Question: Is a single dose of dexamethasone non-inferior to two doses of dexamethasone in the treatment of mild to moderate pediatric asthma exacerbations? Reference: Martin et al. Single-dose dexamethasone is not inferior to 2 doses in mild to moderate pediatric asthma exacerbations in the emergency department. Pediatr Emerg Care. 2022 Population: Children aged 2 to 20 years with known history of asthma who presented to the ED between April 2015 and March 2018 with an acute mild (PAS 5-7) or moderate (PAS 8-11) asthma exacerbation. “History of asthma” defined as at least one prior episode of wheezing responsive to beta agonists. Pediatric Asthma Score (PAS) Exclusion: Severe exacerbation (PAS >=12), systemic steroid use in the last two weeks, chronic lung disease (ie cystic fibrosis), or vomiting of two doses oral steroids in the ED Intervention: Two-dose dexamethasone Comparison: Single-dose dexamethasone Outcome: Primary Outcome: Return visits to either the primary care physician/ED/urgent care for persistent asthma symptoms Secondary Outcomes: Length of time symptoms persisted, missed school days, vomiting, adverse events (appetite changes, insomnia, mood swings) Trial: Prospective, randomized, single-center, unblinded, parallel-group randomized clinical trial Authors’ Conclusions: “In this single-center, unblinded randomized trial of children and adolescents with mild to moderate acute exacerbations of asthma, there was no difference in the rate of return visits for continued or worsened symptoms between patients randomized to 1 or 2 doses of dexamethasone.” 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 treated. 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. Yes The treatment effect was large enough and precise enough to be clinically significant. Unsure Financial conflicts of interest. No Results: 308 children were randomized into two groups of 154. Ultimately, 141 were enrolled in group 1 (single dose), 143 were enrolled and in group 2 (two doses). The mean age was 7.5 years and 60% male. Key Result: There were no statistical differences between groups with regards to return visits, days to symptom resolution, missed school days, or vomiting. Primary Outcome: No statistically significant difference in return visits for persistent asthma symptoms between groups. Secondary Outcomes: No statistically different difference in days to symptom resolution, missed school, vomiting, or adverse effects. Note that the two groups had a different breakdown of asthma severity with a larger proportion of patients with mild exacerbations included in the group receiving 2 doses of dexamethasone (77% compared to 62%). 1) Outcomes: Authors chose their primary outcome to be a return visit to primary care physician, urgent care, or emergency department for persistent asthma symptoms. The authors report that 26 (11%) of all patients had a return visit for asthma. Of the 26, 11 returned to the ED. One patient was admitted, who was in the single-dose group. Are those all equivalent? A return visit to the emergency department could mean that this child’s symptoms were more severe compared to the child that presented to their primary care physician? Or maybe the symptoms were mild but the primary care physician’s office was closed. We do not know that information. The authors initially report that there was no difference in the number of school days missed per group. However, they report a binary “school missed or not” result in their tables. But what about the actual number of missed school days? Is missing one day of school vs. two or three or even longer a significant outcome. It might be for a parent or caregiver who may have to miss work or find alternative childcare. It is unclear how resolution of symptoms is defined. Does the family consider “resolution” to be the day of no albuterol requirement? when they are able to resume regular activity on q4-6 albuterol? When cough ends or when wheeze ends? 2) Unblinded: In this study, families and research assistants were not blinded to the intervention. They both knew at some point in the study whether the patient received one or two doses of dexamethasone. The authors acknowledge this and state it was due to lack of funding. We hope future studies will be blinded and use a placebo. 3) Missing Data: Out of the 284 patients randomized and included in the trial 52 were lost to follow-up (25 in single dose and 27 in two dose). That represents over 18% of the total cohort. When loss to follow-up (18%) exceeds the a priori established non-inferiority margin (11%) we get more uncertain of the results. 4) Did They Really Get Two Doses? Adherence to the prescribed regimen was reported by the families. The researchers worked with pharmacy to dispense a second dose of dexamethasone but did not confirm with the pharmacy whether the family picked up the second dose. Of the patients in the 2-dose group, only 81% reported that they took the prescribed second dose. Could this number possibly be lower due to reporting bias? We know that generally, reported adherence is higher than actual adherence. As such, we need to weigh any possible benefit of an additional dose with the suboptimal adherence of 81% - at what point does it become not worth it? 5) Generalizability: Asthma is a heterogenous disease process that can be impacted by hereditary, environmental, geographical, and socioeconomic factors [5-6]. This was a single site study and majority of patients (64%) were scored as having a mild asthma exacerbation based on PAS and there were more mild exacerbations in the group receiving two doses of dexamethasone. These findings may not be generalizable to your population or to patients with more moderate to severe exacerbations. We hope there are multi-center, blinded trials conducted in the future. Comment on Authors’ Conclusion Compared to SGEM Conclusion: This study suggests that a single dose of dexamethasone may be non-inferior to two-doses of dexamethasone in treating mild to moderate asthma exacerbations, but there are many limitations to consider. SGEM Bottom Line:  For pediatric patients presenting to the ED for mild to moderate asthma exacerbations, you may consider a single dose or two doses of dexamethasone. Case Resolution: You discuss with the risks and benefits of single versus two-dose dexamethasone treatment with the family and acknowledge that there is still some uncertainty surrounding if any regimen is better compared to the other. After some shared decision-making, you and the family feel comfortable having the patient take just one dose of dexamethasone given that this is a mild asthma exacerbation and with the goal of limiting any side effects of the corticosteroid.

Date: September 3rd, 2022 Reference: Milne WK, Carpenter CR and Young T. A Hero Is Rising – Season#8 Book Dr. Tayler Young Guest Skeptic: Dr. Tayler Young is a first year Family Medicine resident at Queen’s University. Her interests are quality improvement and Free Open Access to Medical Education (FOAMed). This is an SGEM Xtra to announce Season#8 has now been summarized into a free PDF book. The SGEM provided the content, and Tayler designed the book. She has experience designing infographics for the Emergency Medicine Ottawa Blog and Emergency Medicine Cases. Tayler also one of the authors of the fourth version of the Emergency Medicine Ottawa Handbook which is now live. Seven seasons of the SGEM have been summarized into books, each with a different theme. Season#7 was designed by my daughter Sage and was inspired by the classic 1982 movie Tron. You can click on the cover page below and get access to all seven previous SGEM books. Tayler chose a Marvel theme for Season#8. This is because she is a huge fan of the Marvel Cinematic Universe (MCU). Her favourite Marvel movie is Avengers: Endgame and her favourite Marvel character is Steve Rogers or Captain America. I’m more of a DC fan myself and my favourite character is obviously Batman. I like him because he did not possess any superpower. He did not get bitten by a radioactive spider, exposed to gamma radiation like the Hulk or get his strength from our yellow sun like Superman. Bruce Wayne had to train very hard physically and study very hard to become Batman. Reminds me of the physical and mental training of residency. SGEM Season#8 Each chapter starts with the title of the SGEM episode, the clinical question and the bottom line on the first page. It also tells you who the guest skeptic is for the episode with a superhero cartoon picture of that individual. Then the format continues with the following sections: Case presentation using Spiderman and some background information on the topic. PICO question is represented by Thanos’ gauntlet with each infinity stone representing the population, intervention, comparison/control and outcome. Authors’ conclusions from the abstract Appropriate quality check list to probe the study for its validity Ironman shows up to give the key results. Talk nerdy to me section has Dr. Strange’s medallion, the eye of Agamotto. Clinical application, what do I tell the patients and a case resolution End notes with other FOAMed resources, twitter poll results and the Paper in a Picture infographic by Dr. Kirsty Challen summarizing the episode Part of the SGEM knowledge translation project is the theme music. Most of the music comes from the best musical era the 1980’s and that is a hill I'm willing to die upon. At the end of the book there are a few pages dedicated to listing all the songs that correspond to each chapter of the book. There is also a QR code that takes you directly to the SGEM Spotify Season#8 play list.  2021-2022 has been a long hard year as COVID continues. People are exhausted, burned out and suffering from moral injury. Remember, it is ok not to be ok. Asking for help is a sign of strength not weakness. As my friend Simon McCormack says, you cannot keep others warm by lighting yourself on fire. To provide great patient care you need to take care of yourself. The SGEM will be back next episode to start Season#11. It will be a structured critical appraisal of a recent publication. Trying to cut the knowledge translation window down from over ten years to less than one year using the power of social media. So, patients get the best care, based on the best evidence. Remember to be skeptical of anything you learn, even if you heard it on the Skeptics’ Guide to Emergency Medicine.

Date: August 23rd, 2022 Reference: Schoenfeld et al. “Just give them a choice”: Patients’ perspectives regarding starting medications for opioid use disorder in the ED. AEM August 2022 Guest Skeptic: Dr. Chris Bond is an emergency medicine physician and assistant Professor at the University of Calgary. He is also an avid FOAM supporter/producer through various online outlets including TheSGEM. Case: A 24-year-old male presents to the emergency department (ED) after a fentanyl overdose. He is successfully resuscitated using naloxone and is stable after an observation period. You are interested in seizing this opportunity to offer some type of help to this patient to prevent another opioid overdose in his future. Background: We have done a few shows on opioids over the past decade: Incidence of opioid use disorder (SGEM#264) Observing patients after giving naloxone (SGEM#241) Department guideline to prevent opioid use disorder (SGEM#55) Drug overdose deaths continue to rise in the United States with opioids being the number one cause (1). There are several medications available to treat Opioid Use Disorder, including methadone and buprenorphine, which are the most effective means to decrease future illicit opioid use and death (2-5). The ED has been identified as a low barrier environment where medications for OUD (MOUD) can be initiated, even in resource-constrained settings (3,6,7). Despite the relatively easy availability of buprenorphine, less than 5% of patients discharged from the ED after a non-fatal opioid overdose fill a prescription for buprenorphine in the next 90 days (8-11). Past studies have focused on clinician-reported barriers to administering or prescribing buprenorphine in the ED (11-19). However, the perspectives and preferences of patients have not been so thoroughly explored. Shared decision making (SDM) puts patients at the center of clinical decisions and has been shown to increase knowledge, trust, and adherence in other clinical decisions (20-23). An SDM framework that fosters conversations and addresses common misconceptions around MOUD initiation may improve the patient-provider interaction and ultimately increased ED-based MOUD administration. Clinical Question: What are patient’s perspectives regarding the initiation of medications for opioid use disorder in the ED? Reference: Schoenfeld et al. “Just give them a choice”: Patients’ perspectives regarding starting medications for opioid use disorder in the ED. AEM August 2022 As this is a qualitative study, we will use a modified PICO question Population: Patients with opioid use disorder Interest: Exploring patient perspectives and experiences with OUD and using medications for OUD Context: Improving the initiation and adherence to treatment with medications for OUD from the ED Dr. Elizabeth Schoenfeld This is an SGEMHOP episode and it is my pleasure to introduce Dr. Elizabeth Schoenfeld. She is an Emergency Physician and researcher, and the Vice Chair for research in the Department of Emergency Medicine at UMass - Baystate. Her research focuses on Shared Decision-Making (SDM) in the setting of Emergency Department care. Dr. Schoenfeld and her co-authors used the Ottawa Decision Support Framework for their study. Listen to the podcast to hear her describe this tool in more detail. Authors’ Conclusions: “Although participants were supportive of offering buprenorphine in the ED, many felt methadone should also be offered. They felt that treatment should be tailored to an individual’s needs and circumstances, and clarified what factors might be important considerations for people with OUD.”  CASP Checklist for Qualitative Research Was there a clear statement of the aims of the research? Yes Is a qualitative methodology appropriate? Yes Was the research design appropriate to address the aims of the research? Yes Was the recruitment strategy appropriate to the aims of the research? Yes Was the data collected in a way that addressed the research issue? Yes Has the relationship between researcher and participants been adequately considered? Yes Have ethical issues been taken into consideration? Yes Was the data analysis sufficiently rigorous? Yes Is there a clear statement of findings? Yes How valuable is the research? Valuable Results: There were 26 participants interviewed, seven of whom were recruited and interviewed in the ED and 19 who were recruited and interviewed via video conferencing. The mean age of study participants was 36 and the majority had used an unprescribed opioid within the past two years. The majority had also tried both buprenorphine and methadone. Nearly all participants had ED visits related to opioid use and the goals for participant heterogeneity outlined in the methods were met. There are three themes we pulled out of the results section. Elizabeth added her own comments on the podcast after each theme was discussed. 1. Decisional Needs and Factors Relevant for Decision-Making Factors for decision making generally fell into either social, pharmacological, or emotional categories. Focusing on pharmacological factors, participants noted the logistical ease of using buprenorphine (at home dosing vs. methadone’s observed dosing at a pharmacy) and that it was effective in helping with withdrawal and avoiding street drugs. Disadvantages of buprenorphine were the ability to sell it and buy illicit opioids, the need to be in severe withdrawal to initiate it and that it could trigger precipitated withdrawal. It was also noted that with methadone you could continue using opioids as needed whereas this wasn’t an option with buprenorphine. Nearly all patients were unaware that buprenorphine could be initiated in the ED and thought it should be offered. Whether it was initiated on that ED visit or not, even offering it helped to “open the door” for future use and lessen stigma surrounding MOUD. Many patients also thought that any conversation surrounding MOUD should include both buprenorphine and methadone. 2. Informing Decisional Support Participants identified that it was important for clinicians to avoid appearing judgmental and hoped clinicians had additional training in discussing the pros and cons of MOUD. They also recognized that clinicians were not experts in MOUD and should be honest about their knowledge of MOUD. Several noted a “peer recovery” coach in the ED with lived experience would be more beneficial than a physician. “Readiness” was also described as an important factor and patients noted that they would often be at different stages of readiness to change on each visit to the ED. They further identified it was important to offer MOUD at each visit because of this. Coordination with outpatient care was also identified as important, eg. OUD clinic and outpatient resource list, psychiatric care, naloxone kit training, peer recovery coach contacts and comfort medications such as clonidine or acetaminophen would all be useful. 3. Additional relevant themes identified by researchers “Recovery” has a different meaning to different people. For example, it can mean complete abstinence from opioids and MOUD to one person, use of MOUD and no illicit opioids to another person, and even use of MOUD with reduced use of illicit opioids to a third. Relapse was a part of every single story and getting to the point of non-use always took multiple attempts and different methods. Participants felt psychiatric care should be integrated into OUD care as opioid use was frequently in response to their mental health problems such as depression or PTSD. Listen to the podcast to hear Elizabeth answer our five nerdy questions. 1. External Validity: Two thirds of your patients were recruited from urban MOUD clinics. How do you think this may have affected your results and do you think they have external validity to rural or resource low environments? 2. Shared Decision Making: You mention that you did not specifically ask patients about shared decision making but that it was brought up by many of them. Why wasn’t this asked specifically? 3. Participant Heterogeneity: How did you determine the seven groups that you used as goals for establishing participant heterogeneity and what were the seven groups? 4. Non-English: One of the inclusion criteria was the ability to speak conversational English. How do you address this significant limitation for discussing cultural barriers to MOUD in non-English speaking populations? 5. Contextual Factors: You had a figure in your manuscript to help understand decisional needs in the context of the whole patient, salient themes of participants' recovery stories, organized via the socioecological model of addiction. Can you briefly explain this and we will put Figure 3 in the show notes? Comment on Authors’ Conclusion Compared to SGEM Conclusion: We generally agree with the authors’ conclusions.  SGEM Bottom Line: Consider offering MOUD to patients in the ED and tailor treatment to the individual needs and circumstances of each patient. Dr. Chris Bond Case Resolution: You discuss the availability of buprenorphine which can be prescribed from the ED and methadone from clinics within your city. You discuss the pros and cons of each treatment as best you understand them, and he is interested in trying buprenorphine at home. You also provide him with a list of outpatient clinics that can help with the multifactorial interventions needed to address his OUD. Clinical Application: The patient agrees to take home four doses of buprenorphine-naloxone as well as instructions on when to take the first dose with respect to the development of significant withdrawal symptoms. He will try to follow up at a local clinic tomorrow. What Do I Tell the Patient?

Date: August 18th, 2022 Reference: Munn et al. Fragility Index Meta-Analysis of Randomized Controlled Trials Shows Highly Robust Evidential Strength for Benefit of <3 Hour Intravenous Alteplase. Stroke 2022 Dr. Jeff Saver Guest: Dr. Jeff Saver is a Professor and SA Vice Chair for Clinical Research, Carol and James Collins Chair, Department of Neurology, Director of the UCLA Comprehensive Stroke and Vascular Neurology Program at the David Geffen School of Medicine at UCLA. This is an SGEM Xtra. Jeff and I have an interesting back story to how we met. I knew about Jeff from his multiple publications in the stroke literature. I did not know he knew about me until an EM physician sent me a video of a presentation that was given at an international stroke meeting. On one of the slides, Professor Daniel Fantovich and I were referred to as "Non-Expert EM Contrarians". I reached out to Jeff and we had a very good conversation. He clarified what he meant by “non-experts”: that we were not stroke neurologists or emergency physicians with subspecialty neuro expertise, such as having completed fellowship training in neurologic critical care. He did acknowledge that both Dr. Fatovich and I had expertise on critical appraisal of the medical literature. The conversation ended well with Jeff requesting one of the t-shirts I planned to make with the title of non-expert ER contrarian on the chest. Jeff recently reached out to me with his new publication called Fragility Index Meta-Analysis of Randomized Controlled Trials Shows Highly Robust Evidential Strength for Benefit of <3 Hour Intravenous Alteplase asking about my thoughts.  I thought this would be a great opportunity to dig deeper into the fragility index and have another expert in stroke neurology on the SGEM. Dr. Eddy Lang We have had a couple of individuals previously on the SGEM who strongly support the use of tPA in acute ischemic stroke (AIS). One was Dr. Eddy Lang who is a well-known Canadian researcher and emergency physician in Calgary, Alberta. Eddy appeared on the SGEM Xtra episode called the Walk of Life discussing AIS.  We had a debate on the issue of tPA for stroke published in CJEM 2020 as part of their debate series. Eddy is also the senior author on the CJEM article summarizing the Canadian Stroke Best Practice (CSBP) 2018 Guidelines. This Canadian guideline gives a level “A” recommendation for the use of tPA in AIS in patients last seen normal within 4.5 hours. “All eligible patients with disabling ischemic stroke should be offered intravenous alteplase (tPA). Eligible patients are those who can receive intravenous alteplase (tPA) within 4.5 hours” of symptom onset time or last seen normal (Evidence Level A; Section 5.3.i). We also had a neurology resident on to critically appraise a systematic review and meta-analysis of endovascular therapy plus/minus tPA as a bridging therapy (SGEM#349). A few more publications have come out since that podcast and the European Stroke Organization (ESO) recommends intravenous thrombolysis before mechanical thrombectomy in patients with acute ischemic stroke and anterior circulation large vessel occlusion. There have been several tPA skeptics on the SGEM including Dr. Hoffman, Dr. Fatovich, and Dr. Morgenstern. However, not until now have we had a stroke neurologist who is very much in support of using tPA in AIS. I think it is very important to try and mitigate against echo chambers, our own biases and listen carefully to other points views. Fragility Index Meta-Analysis of Randomized Controlled Trials Shows Highly Robust Evidential Strength for Benefit of <3 Hour Intravenous Alteplase. Jeff was asked a number of questions about his new publication. Some of the answers are listed as bullet points, but most of his responses can be heard in full by listening to the SGEM podcast: Who were your co-authors on this publication? Why did you decide to write this article? What is the fragility index (FI)? The FI is the minimum number of nonevents that when changed to events in one arm of an interventional trial or meta-analysis of trials converts the result to statistical nonsignificance. Lower FIs indicate greater fragility, higher FIs more robust results. This definition of the FI is slightly different than the one provided by Walsh et al JClinEpi 2014 because it did not mention SRMA and was only looking at RCTs. There are critics of the FI who say, among other things, it could be viewed as just restating the p-value in a different way (Dr. Ed Palmer). Medicine has this very low bar of p-value of 0.05 (95%) or two sigmas to get over to consider something “statistically significant”. In contrast, particle physics uses five sigma or 99.9999%, this is a p-value of 3×10-7, or about 1 in 3.5 million chance the data is at least as extreme as what they observed. A lot of ink has been spilled about the problems with p-values. Over 800 scientists call for the abandonment of “statistical significance”. What are your thoughts on the use/misuse of the p-value? Others have said let’s raise the bar by lowering the number we would consider statistically significant from 0.05 to 0.005 to be more certain and mitigate against things like p-hacking. Do you think we should change what is considered statistically significant by an order of magnitude to 0.005? Does the fragility index convey different information than the p-value of the test statistic? If not, how would your analysis using the cumulative FI change our confidence in the tPA evidence for acute ischemic stroke that we could not obtain from the gold standard SRMA of individual patient data like the 2014 Emberson et al publication? The FI is a summary statistic not unlike the Number Needed to Treat (NNT) with both strengths and weaknesses. A major strength of the FI is its simplicity, making complex research easier to understand. A weakness, however, is also simplicity, hiding the complexity of research, ignoring confidence intervals, and obscuring potential biases. Do you think the FI is a useful metric? Often people will criticize a trial because the FI is low. However, studies are generally powered for their primary outcome of efficacy. To be efficient, researchers estimate how many participants would be needed to observe the magnitude of effect to be statistically significant. This power calculation should be done a priori based upon the “delta” or difference between treatment and control cohorts. If a study is done correctly, most should give a result that clusters around a p-value of 0.05. Therefore, the study would be designed to have a low FI. It could be considered a circular argument to then criticize the study as being “fragile”. Another way to interpret a low FI is that the researchers did a great job estimating the number of participants necessary to answer their hypothesis. They could be congratulated for conducting a very efficient trial that was not overpowered which wastes time, resources and patients. The introduction of the fragility index paper starts by saying the era of performing randomized placebo control trials comparing tPA for AIS in < 3 hours for patients with small to medium level occlusions is over. This is because it’s the standard of care making it unethical to randomize patients to placebo. What evidence do you provide to support your position? ACEP updated their policy on stroke in 2015 with lead author Dr. Michael Brown and gave no Level “A” recommendations in their policy statement. < 3 hours: Level B recommendations. With a goal to improve functional outcomes, IV tPA should be offered and may be given to selected patients with acute ischemic stroke within 3 hours after symptom onset at institutions where systems are in place to safely administer the medication. The increased risk of symptomatic intracerebral hemorrhage (sICH) should be considered when deciding whether to administer IV tPA to patients with acute ischemic stroke. Do you have any ideas why the ACEP policy statement seems to differ from AHA, ESO and CBSP? The ethics of conducting a placebo-controlled tPA trial is an interesting question. Stroke neurologist Dr. Peter Appelros and colleagues wrote an editorial called: Ethical issues in stroke thrombolysis revisited. It was a follow-up to a bioethics paper written in 1997 by Furland and Kanoti. The original article identified five areas of concern. Appelros’ position is that the ethical issues raised over two decades ago have not been satisfactorily answered. Have you read that editorial and what are your thoughts? Standard of care is also an interesting topic. It is a legal term that has a specific definition. the reasonable degree of care a person should provide to another person, typically in a professional or medical setting.  SGEM#200 Standard of care is often discussed by  emergency physicians (Moffett and Moore WestJEM 2011). Standard of care does not necessarily mean the best care. There are many examples in the medical literature where the standard of care was not the best care. The classic story I’ve often told is about bloodletting (SGEM#200). Standard of care could be considered an argument from popularity, and I think it is better for us as scientists to look at the evidence.  Do you agree? Can you briefly describe the methods used for your fragility index study? How many studies did you find and how big was the included cohort? Using your definition of FI: The minimum number of nonevents that when changed to events in one arm of an interventional trial or meta-analysis of trials converts the result to statistical nonsignificance. In other words, the FI is the minimum number of patients who would need to have a different outcome to change the p value from <0.05 to >0.05. How many would be required to flip statistically significant to insignificant (or “positive” result to a “negative” result).

Date: August 7th, 2022 Dr. Dennis Ren Host Skeptic: Dr. Dennis Ren is a pediatric emergency medicine attending at Children’s National Hospital in Washington, DC. You might remember him from the SGEM episodes on febrile infants, aseptic meningitis, and community acquired pneumonia. This is an SGEM Xtra episode. Season 10 is coming to an end. We want to thank all our listeners and skeptics who have tuned in for ten years. We have ~67,000 subscribers and the SGEM has been translated into four other languages. We have tried different initiatives over the years to improve the quality of the SGEM. Sometimes this has worked (Keener contest, Meme Monday, Twitter Poll Tuesday and Paper in a Pic Thursday) and sometimes it has not worked (Hot or Not and Continuing Medical Education Credits). For Season 11, we knew we had to do something special and turn it up to eleven.  To accomplish this we have invited Dennis to join the SGEM faculty and provide his pediatric expertise on a regular basis. Each month he will be leading an SGEM episode. Don't Panic! Dennis will use the same critical appraisal tools to probe the literature for its validity. The theme music may be more contemporary, but the content will still be fantastic FOAMed. We recognize that Dennis' clinical experience working in a tertiary centre may be different than the clinicians who provide care to the vast majority of pediatric patients that are seen in community EDs. The evidence-based medicine principles will still apply. The evidence discussed on the SGEM should inform your care but it should not dictate your care. You will still need to use your good clinical judgment and ask your patients about their values and preferences. The ultimate goal of the SGEM remains the same, to provide patients with the best care, based upon the best evidence. And we want to hear from you. Are you a passionate researcher who just published an amazing article? Or do you have an article or topic you want us to cover? Please send Dennis an email SGEMpeds@gmail.com to suggest an article or topic to cover. The SGEM will be back next episode doing a structured critical appraisal of a recent publication. Trying to cut the knowledge translation window down from over ten years to less than one year using the power of social media. So patients get the best care, based on the best evidence. REMEMBER TO BE SKEPTICAL OF ANYTHING YOU LEARN, EVEN IF YOU HEARD IT ON THE SKEPTICS’ GUIDE TO EMERGENCY MEDICINE

Date: July 28th, 2022 Reference: Brower et al. Point-of-Care Ultrasound-First for the Evaluation of Small Bowel Obstruction: National Cost Savings, Length of Stay Reduction, and Preventable Radiation Exposure. AEM July 2022 Guest Skeptic: Dr. Kirsty Challen is a Consultant in Emergency Medicine at Lancashire Teaching Hospitals. She is also the creator of all those wonderful Paper in a Pictures. Case: A 63-year-old woman presents to your emergency department (ED) with two-day history of nausea, vomiting and constipation. She tells you that she had appendicitis complicated by perforation and peritonitis ten years ago and you suspect she has adhesional small bowel obstruction. You call your surgical colleague who, predictably, asks you to order a CT. The patient asks if there is an alternative as she had several CTs on her last admission and is worried about her radiation exposure and her co-pay. Background: Somewhere between two and four percent of patients presenting to US EDs with abdominal pain have a small bowel obstruction (SBO) – those who are managed operatively (who are only 20-30%) account for 60,000 hospitalizations and 565,000 inpatient care days per year. We know that clinical examination has poor sensitivity and specificity for diagnosing SBO and that imaging is therefore necessary. CT is generally the first choice of imaging, the “abdominal series” of plain X-rays have been demonstrated to have poor predictive value, but a 2018 meta-analysis found 92.4% sensitivity and 96.6% specificity with ultrasound [1]. A 2020 national UK report into patients treated for bowel obstruction found delays in imaging and diagnosis and recommended CT with IV contrast as the first-line investigation [2]. Somewhat surprisingly, we’ve never covered SBO on the SGEM, although Ped EM Superhero, Dr Anthony Crocco shared his views on the (lack of) utility of abdominal X-rays in paediatric constipation back in 2016 (SGEM Xtra: RANThony#4). CLINICAL QUESTION: DOES USING POINT OF CARE ULTRASOUND FIRST LINE IN SUSPECTED SMALL BOWEL OBSTRUCTION REDUCE COST, LENGTH OF STAY AND RADIATION EXPOSURE? Reference: Brower et al. Point-of-Care Ultrasound-First for the Evaluation of Small Bowel Obstruction: National Cost Savings, Length of Stay Reduction, and Preventable Radiation Exposure. AEM July 2022 Population: Patients with ICD-10 coding “intestinal obstruction” from 2018 National Hospital Ambulatory Medical Care Survey. Intervention: POCUS-first approach Comparison: CT imaging as baseline Outcomes: Primary Outcome: Cost savings Secondary Outcomes: Reduction in ED length of stay, reduction in radiation exposure and preventable cancer Type: Monte Carlo Modelling This is an SGEM HOP episode, so we are pleased to have two of the authors on the show. Dr. Charles Brower is a second-year resident training in Emergency Medicine at the University of Cincinnati. His primary research interest is the intersection between clinical operations and ultrasound to improve patient outcomes in an efficient and cost-effective way. Also joining us is Dr. Andrew Goldsmith. He is the director of Emergency Ultrasound in the Department of Emergency Medicine at Brigham and Women’s Hospital at Harvard Medical School Authors’ Conclusions: “If adopted widely and used consistently, a POCUS-first algorithm for SBO could yield substantial national cost savings by averting advanced imaging, decreasing ED LOS, and reducing unnecessary radiation exposure in patients. Clinical decision tools are needed to better identify which patients would most benefit from CT imaging for SBO in the ED.” Quality Checklist for Cost Analysis Studies: Part 1: Are the recommendations valid? Did the investigators adopt a sufficiently broad viewpoint? Yes Are the results reported separately for patients whose baseline risk differs? No Were costs measured accurately? Yes Did investigators consider the timing of costs & outcomes? No Part 2: How can I apply the results to patient care? Are the treatment benefits worth the harms and costs? Yes Could my patients expect similar health outcomes? Unsure Can I expect similar costs at my setting? Unsure Are the criteria relevant to my practice setting? Yes Have the criteria been field-tested for feasibility of use in diverse settings, including settings similar to mine? No Results: In the US, a POCUS-first approach for imaging of SBO would avert a mean of 143,000 (+/- 31,000) CT scans annually, saving $30.1million (+/- $8.9million). 507,000 bed hours (+/- 268,000) could be saved, and 98 (+/-28) excess cancer deaths prevented. KEY RESULT: USING POCUS AS FIRST-LINE IMAGING IN SUSPECTED SBO COULD AVOID 143,000 CT SCANS ANNUALLY IN THE US POTENTIALLY SAVING MILLIONS OF DOLLARS Listen to the SGEM podcast to hear Charles and Andrew answer our five nerdy questions. Dr. Chalres Brower 1. Monte Carlo Simulation: Can you describe this for us in clinician-friendly language? And why is it the right method for your question? 2. Modelling Assumptions: Models are only as good as the information fed into them (garbage in, garbage out!). How reliable was the information you were able to get for your assumptions (eg numbers of patients needing confirmatory CT)? Dr. Andrew Goldsmith 3. Sensitivity Analyses: Can you explain the importance of sensitivity analyses? Why did you do the ones you did? 4. Subgroups: It’s likely that the effects of a change in practice would vary across different patient groups (especially cancer incidence dependent on patient age) but you have presented population-wide results. Did you consider modelling different subgroups? 5. Supporting Evidence: You have commented that the simulation nature of your study is a limitation. Do you have any plans for further research to address this? Comment on Authors’ Conclusion Compared to SGEM Conclusion: We generally agree with the authors’ conclusions for the US, but don’t consider that they can be extrapolated to Canada, UK, Australia or elsewhere without further study. SGEM BOTTOM LINE: POCUS AS FIRST-LINE IMAGING IN SUSPECTED SBO COULD AVOID SIGNIFICANT NUMBERS OF CT SCANS IN US. Case Resolution: You meet your surgical colleague at the bedside and perform POCUS, which shows SBO. After discussion with the patient, she is admitted for conservative management and a CT is avoided. Dr. Kirsty Challen Clinical Application: We may be able to avoid significant numbers of CTs for suspected SBO by using POCUS as first-line imaging. What Do I Tell the Patient? We can perform bedside ultrasound which can demonstrate SBO – it is likely though that if operative intervention is needed the surgeon will still want you to have a CT scan performed. Keener Kontest: Last weeks’ winner was Mario Pinoli. He knew torus is a geometric shape made by rotating a circle around an axis, making a donut shape, a torus. 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 POCUS for SBO? Tweet your comments using #SGEMHOP.  What questions do you have for Charles, Andrew and their team? Ask them on the SGEM blog. The best social media feedback will be published in AEM. REMEMBER TO BE SKEPTICAL OF ANYTHING YOU LEARN, EVEN IF YOU HEARD IT ON THE SKEPTICS’ GUIDE TO EMERGENCY MEDICINE. References:  Gottlieb M, Peksa GD, Pandurangadu AV, Nakitende D, Takhar S, Seethala RR. Utilization of ultrasound for the evaluation of small bowel obstruction: A systematic review and meta-analysis. Am J Emerg Med. 2018 Feb;36(2):234-242. doi: 10.1016/j.ajem.2017.07.085. Epub 2017 Jul 29. PMID: 28797559. Shotton H, Kelly K, Sinclair M, Michalski A. Delay in transit: the NCEPOD review of care provided to patients with acute bowel obstruction. Br J Hosp Med (Lond). 2021 Jan 2;82(1):1. doi: 10.12968/hmed.2020.0399. Epub 2021 Jan 4. PMID: 33512283.

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.