The Skeptics Guide to Emergency Medicine

Date: March 3rd, 2022 Reference: Macnow et al. Effect of Screen Time on Recovery From Concussion: A Randomized Clinical Trial. JAMA Pediatrics 2021 Guest Skeptic: Dr. Catherine Varner is an Assistant Professor and Clinician Investigator in the Department of Family and Community Medicine at the University of Toronto. She is an emergency physician at Mount Sinai Hospital and a Clinician Scientist and the Deputy Director of the Schwartz-Reisman Emergency Medicine Institute. Dr. Varner's research interests are in concussion and pregnancy care in the ED. Case: An 18-year-old female presents to the emergency department (ED) after falling off a moving snowmobile and hitting her head on the ground. It was a witnessed fall; she was wearing a helmet at the time and there was no loss of consciousness. There were no other injuries reported and she is found to have a GCS score of 15 after the injury. The Acute Concussion Evaluation–Emergency Department (ACE-ED) Tool is used, and she scores a 2 for headache and feeling foggy. She knows about taking it easy physically for the next couple of days but wonders if she must stay off her computer as well? Background: Concussions or mild traumatic brain injury (mTBI) are commonly diagnosed in the Emergency Department (ED). Most patients recover within the first week; however, 15-30% of patients develop persistent post-concussive symptoms. An issue that often comes up with minor head injuries is do we need to get advanced imaging. A paper by Dr. Ian Stiell and his group gave us a tool to help us decide who to scan with the now infamous clinical decision instrument called the Canadian CT Head Rule [1]. This classic paper was published in Lancet 2001 and reviewed on SGEM#106. Another issue that comes up is whether children need strict rest after a concussion. SGEM#112 reviewed a small study by Thomas et al published in Pediatrics 2015 asking if there was a benefit to recommending strict rest after a child has a concussion [2]. The bottom line from that episode was that in children with concussion, two days of rest followed by a gradual return to activity is preferred over five days of rest followed by a gradual return to activity. The longer strict rest period appears to cause more post-concussive symptoms. Our episode together looked at the impact of light exercise in adults with mild concussions on the likelihood of developing persistent symptoms up to 30 days following their injury (SGEM#331). We found there was not a statistical difference between light activities like walking and 48 hours of rest with gradual return to activity as tolerated. Our conclusions were that early light exercise may be encouraged as tolerated at ED discharge following mTBI, but this guidance is not sufficient to prevent persistent concussion symptoms [3]. The Acute Concussion Evaluation–Emergency Department (ACE-ED) tool is an instrument used by ED clinicians to diagnose a concussion and identify risk factors for prolonged recovery. It is both helpful for diagnosis and future management of symptoms. When a patient is recovering from a concussion, whether you are using ACE or another symptom scoring tool like the Postconcussion Symptom Scale or the Rivermead Post-concussion Symptom Questionnaire, future health care providers caring for the concussion patient may refer to the quantitative assessment of the patient’s symptoms in the acute phase of the injury. Clinical Question: Does screen time in the first 48 hours after concussion have an impact on the duration of concussive symptoms? Reference: Macnow et al. Effect of Screen Time on Recovery From Concussion: A Randomized Clinical Trial. JAMA Pediatrics 2021 Population: Patients aged 12 to 25 years presenting to the emergency department within 24 hours of sustaining a concussion according to the Acute Concussion Evaluation–Emergency Department (ACE-ED) tool (Giola et al 2008) Exclusions: Attending physician declined participation; their guardian was not present; the patient was younger than 18 years, or they (or their parent or guardian) were not fluent in English; intoxication; had a GCS score < 15; had intracranial abnormalities identified on imaging; had pre-existing intellectual disability, severe psychiatric illness, severe neurological conditions, or substantial previous neurological surgery; or required neurosurgical intervention, intubation, or hospital admission. Intervention: Patients were asked to abstain from screen time for 48 hours after injury. This was the screen time abstinent group. Comparison: Patients were permitted to engage in screen time in the first 48 hours after injury. This was the screen time permitted group. Outcome: Primary Outcome: Number of days until functional resolution of concussive symptoms, which was defined as the first day with a total score of three points or lower on the Post-Concussive Symptom Scale (PCSS) Secondary Outcomes: Amount of screen and sleep time during the intervention period, the day of return to school or work after the intervention period, the day of return to exercise after the intervention period, and daily PCSS scores. Trial: Single-centre, unblinded, randomized clinical trial Authors’ Conclusions: “The findings of this study indicated that avoiding screen time during acute concussion recovery may shorten the duration of symptoms. A multicenter study would help to further assess the effect of screen time exposure.” Quality Checklist for Randomized Clinical Trials: The study population included or focused on those in the emergency department. Yes The patients were adequately randomized. Yes The randomization process was concealed. Yes The patients were analyzed in the groups to which they were randomized. Yes The study patients were recruited consecutively (i.e. no selection bias). No The patients in both groups were similar with respect to prognostic factors. 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). No All patient-important outcomes were considered. Unsure The treatment effect was large enough and precise enough to be clinically significant. No Funding. The stated conflicts of interests by the authors would not likely influence the conclusions of this trial. Results: They enrolled 125 patients into the study. The mean age was 17 years and 49% were female. Key Results: Patients with concussions who abstained from screen time recovered quicker than those permitted screen time. Primary Outcome: Median number of days until functional resolution of concussive symptoms, which was defined as the first day with a total score of 3 points or lower on the Post-Concussive Symptom Scale (PCSS) Abstained 3.5 days vs permitted 8.0 days Hazard ratio [HR], 0.51 (95% CI; 0.29-0.90) Secondary Outcomes:  Sensitivity analysis using different PCSS thresholds for recovery 1. Recruitment of Patients – This was a convenience sample when study staff was available. It is very difficult to enroll consecutive patients in the ED 24/7/365. However, we would have liked to know how many people were not approached, why and their characteristics. This would help us know if the patient population included is similar to those being seen at our own centres (tertiary, community or rural). Patients could also be excluded if the physician did not wish to participate. These factors could have introduced an element of selection bias. 2. Who Were These Patients - Let’s talk about generalizability? This study took place in a large volume, tertiary care level 1 trauma centre. They enrolled patients ages 12 to 25 years old, so a population in whom concussions are common. In that regard, this study can be generalized to many of the centres where we work and many of the patients whom we commonly see. However, just like in nerdy point #1, I want to know more about the clinical characteristics of the included patients. What happened to them in the ED? Did they undergo head CT? Did they need analgesics or antiemetics? Were they at risk of prolonged symptoms based on their pre-injury risk factors such as having anxiety or depression? These are some aspects of generalizability that I can’t answer when I read this trial. Our group completed a randomized trial in 241 patients with mild traumatic brain injury, published in Academic Emergency Medicine last year, and when we did a secondary analysis to identify risk factors associated with prolonged symptoms, we found, having a history of anxiety or depression increased the risk of persistent symptoms. Consistently studies looking at predictors of persistent symptoms have identified pre-injury depression or anxiety as risk factors. It would have been helpful to know what proportion of participants in this trial previously identified pre-injury risk factors for prolonged symptoms. 3. Blinding – This is an important aspect of RCTs but not always possible. Patients knew what group they were assigned. Were they aware of the hypothesis and did they have pre-conceived notion of the impact of screen time on concussions? This is important because they self-reported their amount of screen. This reporting could have been biased in the intervention control group. It is unclear if this would have biased the results towards or away from the null hypothesis. 4, Primary Outcome - Ensuring the primary outcome and a priori sample size calculation reflect what has already been published in the preceding literature is, in my opinion, the most important aspect to designing a randomized trial. I found this undertaking a bit confusing.

Date: February 24th, 2022 Reference: Parish et al. An umbrella review of effect size, bias, and power across meta-analyses in emergency medicine. AEM 2021 Guest Skeptic: Professor Daniel Fatovich is an emergency physician and clinical researcher based at Royal Perth Hospital, Western Australia. He is Head of the Centre for Clinical Research in Emergency Medicine, Harry Perkins Institute of Medical Research; Professor of Emergency Medicine, University of Western Australia; and Director of Research for East Metropolitan Health Service. Case: A resident has been following the literature over their four years of training. They have already seen several things come into fashion and go out of fashion during this short time. This includes therapeutic hypothermia for out-of-hospital cardiac arrest (OHCA), tranexamic acid (TXA) for epistaxis and electrolyte solutions for mild pediatric gastroenteritis. They wonder how strong the evidence is for much of what we do in emergency medicine. Background: There are many things in medicine that could be considered myth or dogma. We have covered some of these over the 10 years. Topical anesthetic uses of 24-48 hours for mild cornea abrasions will cause blindness- No (SGEM# 315) Epinephrine for adult out-of-hospital cardiac arrests (OHCAs) results in better neurologic outcomes – No (SGEM#238) TXA for intracranial hemorrhage, isolated traumatic brain injury, post-partum hemorrhage or gastrointestinal bleed results in better primary outcomes - No (SGEM#236, SGEM#270, SGEM#214, and SGEM#301) Therapeutic hypothermia in adult OHCA saves lives – No (SGEM#336) Electrolyte solutions are needed in mild pediatric gastroenteritis - No (SGEM#158) A lot of medical practice is based on low quality research. Tricoci et al. JAMA Feb 2009 looked at the ACC/AHA guidelines from 1984 to 2008. They found 53 guidelines with 7,196 recommendations. The results were only 11% of recommendations were considered Level A, 39% were Level B and 50% were Level C. The definitions used for each level of evidence are as follows: 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%. This lack of evidence is not isolated to cardiology. A recent study looked at the top ten elective orthopaedic procedures. It was an umbrella review of meta-analyses of randomized control trials (RTCs) or other study designs if no RCTs existed (Blom et al BMJ 2021). The comparison was the clinical efficacy of the most common orthopaedic procedures with no treatment, placebo, or non-operative care. The primary outcome was the quality of the evidence for each procedure. Only two out of ten common procedures, carpal tunnel decompression and total knee replacement, showed superiority over non-operative care. Clinical Question: What is the effect of faults such as underpowered studies, flawed studies (i.e. methodologic and statistical errors, poorly designed studies) and biases in the field of therapeutic interventions in the emergency medicine literature? Reference: Parish et al. An umbrella review of effect size, bias, and power across meta-analyses in emergency medicine. AEM 2021 Population: SRMAs 1990-2020 in the top 20 journals under the google scholar subcategory: emergency medicine; emergency medicine meta-analyses from JAMA, NEJM, BMJ, The Lancet, and the Cochrane Database of Systematic Reviews; emergency medicine topics across all PubMed journals; and an extraction of all studies from the Annals of Emergency Medicine Systematic Review Snapshots (SRS) series. Exclusions: Articles were excluded if they did not include a quantitative synthesis (meta-analysis); did not contain at least two summarized studies; did not make a comparison between two groups to assess an effect size; did not report an effect size as at least one of mean difference or standardized mean difference (SMD; Cohen's d), odds ratio (OR), risk ratio (RR), hazard ratio (HR), or transformations of these effect sizes; were meta-analyses of diagnostic accuracy studies; or were not related to the practice of emergency medicine. Intervention: Data supplement 1 lists all 431 MAs derived from 332 published SRMAs. Comparison: Includes placebo, usual care, nothing. Outcomes: Identify broad patterns in study parameters (effect size, power, mortality benefit and potential bias). Dr. Austin Parish We are fortunate to have the lead author on this episode even though it is not an SGEMHOP. Dr. Austin Parish is the Chief Resident in Emergency Medicine at the Lincoln Medical Center, Bronx NY. He is also a researcher for the Meta Research Innovation Center at Stanford (METRICS) Authors’ Conclusions: “Few interventions studied within SRMAs relevant to emergency medicine seem to have strong and unbiased evidence for improving outcomes. The field would benefit from more optimally powered trials.” Quality Checklist for Therapeutic Systematic Reviews: The clinical question is sensible and answerable. Yes The search for studies was detailed and exhaustive. Yes The primary studies were of high methodological quality. No The assessment of studies were reproducible. Yes The outcomes were clinically relevant. Yes There was low statistical heterogeneity for the primary outcomes. No The treatment effect was large enough and precise enough to be clinically significant. Sometimes Results: The systematic review identified 431 eligible meta-analyses (MAs) relevant to emergency medicine. The MAs included a total of 3,129 individual study outcomes of which 2,593 (83%) were from randomized controlled trials. Key Result: A minority of interventions published in SRMA and relevant to emergency medicine have unbiased and strong evidence for improved outcomes. Primary Outcome: Broad patterns in study parameters Effect Size: The median Odds Ratio (OR) across all studies was 0.70. Within each MA, the earliest study effect on average demonstrated larger benefit compared to the overall summary effect. Only 57 of 431 meta-analyses (13%) both favored the experimental intervention and did not show any signal of small study effects or excess significance. Power: Only 12 of 431 MAs had at least one study with 80% or higher power to detect an OR of 0.70 Mortality: Zero out of 431 MAs reported the interventions significantly decreased mortality in well-powered trials. Although the power of studies increased somewhat over time, most studies were underpowered. Biases: 92 of the SRMAs included 10 or more studies that could be analyzed with a funnel plot for asymmetry. 25% (23/92) showed evidence of asymmetry suggesting excess significance. 85 (20%) of the SRMAs reported statistical significance in favor of the intervention. Of these, 1/3 showed a signal of small study effect and/or excess significance while 2/3 (57/85) did not. Of the 57, only 36 (63%) had a GRADE assessment reported. Half were rated as low-quality evidence and only 11% rated as high-quality evidence. 1. How Good is the Evidence? I’ve often posed the question: what proportion of our EM clinical practice is backed up by high level evidence? After speaking with thought leaders the answer I got to was less than 10%. This umbrella review quantifies the answer in more detail: 12/431 = 2.8%. There is not a large amount of high-level evidence supporting most EM practices. The results demonstrate that very few interventions meet the highest evidence standards, and most of the SRMAs are significantly flawed and may overstate true treatment effects. So, we need to advance our knowledge and practice through never ending questioning of it, via a research culture, whereby clinical trials and clinical research are a routine part of everyday EM work, research that engages clinicians and patients with clinically useful questions – to be a learning health system. What is the proportion of our EM clinical practice is backed up by high level evidence? 2. The Best Evidence: Table 1 in the paper lists the 12 MAs in EM that have statistically significant results (p < 0.05 by random effects), based on data with no signal for small study effects or excess significance and at least one RCT and at least one study with 80% power to detect a small effect (d = 0.2). The biggest effect of an intervention was the rate of haemolysis using straight needle venepuncture vs an IV; OR 0.11(95%CI; 0.05-0.23). Of the 12 MAs, only another three had a 95% confidence intervals that did not cross 1 (the line of no statistical difference), for well powered studies (fixed effect): senior doctor vs no senior doctor in triage for preventing patient left without being seen (OR 0.74, 95% CI; 0.70-0.77); clopidogrel pre-treatment vs no clopidogrel pre-treatment in acute coronary syndrome patients to receive percutaneous intervention (OR 0.79, 95% CI; 0.73-0.85) for a major coronary event; glucocorticoids and usual care vs usual care for croup (OR 0.44, 95% CI; 0.27-0.72) on rate of return visits. While there were no mortality benefits listed under fixed effect, well powered studies, under the heading of random effects, all studies – there were some mortality benefits for mechanical CPR, transfer for angioplasty, thrombolysis for PE and vasopressin + catecholamines. The details will be listed in the blog. Mechanical CPR vs manual CPR for OHCA on mortality by arrival to hospital (OR 0.80, 95% CI; 0.68-0.94); Transfer for angioplasty vs on site thrombolysis for ST elevated myocardial infarction on 30-day mortality (OR 0.78, 95% CI; 0.61-0.99); Thrombolysis vs conventional anticoagulation for pulmonary embolism (OR 0.42, 95% CI; 0.19-0.93);

Date: February 21st 2022 Reference: Kim et al. Emergency psychiatric assessment, treatment, and healing (EmPATH) unit decreases hospital admission for patients presenting with suicidal ideation in rural America. AEM February 2022. Guest Skeptic: Dr. Kirsty Challen (@KirstyChallen) is a Consultant in Emergency Medicine and Emergency Medicine Research Lead at Lancashire Teaching Hospitals Trust (North West England). She is Chair of the Royal College of Emergency Medicine Women in Emergency Medicine group and involved with the RCEM Public Health and Informatics groups. Kirsty is also the creator of the wonderful infographics called #PaperinaPic. Case: You are in discussion with your emergency department (ED) manager about the number of patients boarding for hours to days and you are both aware that many of these patients are attending with mental health crises. You wonder whether a model of care involving a specifically designed unit would improve their patient experience and ED boarding times. Background: We have covered mental health issues only a few times on the SGEM. The latest SGEM Xtra was a very powerful episode with Dr. Tim Graham sharing his story of burnout, anxiety, and depression. This was based upon his article published in the Canadian Medical Association Journal (CMAJ). We also had Dr. Tyler Black on that episode to provide his expertise as a suicidologist.  ED visits in the US for mental health conditions has increased by 44% from 2006 to 2014. Inadequately resourced provision for emergency mental health care is familiar to health care professionals in multiple jurisdictions and patients can spend days in the ED waiting for inpatient admission. We've talked about mental health issues in SGEM #252 in 2019. In that episode we concluded that clinician gestalt was likely to be as accurate and efficient in screening for suicidality as a specific tool (Convergent Functional Information for Suicidality screening tool). Also, in SGEM #313 we recognised that three or more ED attendances for alcohol-related issues was associated with a 1-year mortality risk of over 6%. Clinical Question: Does the implementation of a dedicated interdisciplinary unit for mental health patients presenting to an ED with suicidal ideation or a suicide attempt reduce inpatient admissions and ED boarding time? Reference: Kim et al. Emergency psychiatric assessment, treatment, and healing (EmPATH) unit decreases hospital admission for patients presenting with suicidal ideation in rural America. AEM February 2022. Population: Adults presenting to a single academic tertiary referral ED in Iowa with suicidal ideation or after a suicide attempt – determined using administrative data.. Excluded: Patients that were medically unstable, needed co-management of a medical condition, were incarcerated, actively violent or judged by the provider to be intoxicated. Also, patients with mental health conditions other than suicidal ideation or attempt. Intervention: Post-establishment of EmPATH unit Nov 2018 – May 2019. Comparison: Pre-establishment of EmPATH unit Nov 2017 – May 2018. Outcome: Primary Outcome: Proportion of patients admitted to inpatient psychiatric unit (direct from ED, via EmPATH Unit or by transfer). Secondary Outcomes: Any admission including psychiatry, intensive care, or medicine; complete vs incomplete psychiatric admission; hospital length of stay in those with a bed requested; ED length of stay; use of restraints in ED, scheduled follow-up, 30-day ED return; restraint use; code green Dr. Allie Kim This is an SGEMHOP episode which means we have the lead author on the show (Dr. Kim). And as a special treat we also have the senior author (Dr. Lee). Dr. Allie Kim graduated from emergency medicine residency at the University of Iowa last July and now works as an attending physician at Unity Point Health hospitals in Des Moines, Iowa. We also have senior author Dr. Sangil Lee who is a Clinical Associate Professor of Emergency Medicine at the University of Iowa. The state of Iowa has only a handful of inpatient psychiatric units. The University of Iowa, where the EmPATH unit was implemented, is one of them. We see patients from all over the state, plus even out of state, and with the increase in numbers of mental health presenting to our emergency department, the sheer percentage of our patients needing inpatient psychiatric care was high. And, as many of us have seen, patients may wait in their ER bed for days until an inpatient bed became available. This “boarding” of patients delayed their psychiatric care and left less room for us to see other patients. Dr. Sangil Lee The EmPATH program we created, in conjunction with the Department of Psychiatry, is an open concept unit with the capacity to treat 12 adults. Patients must be medically cleared first in the ED, and also be behaviorally appropriate, to enter the EmPATH unit. Once in the unit, there are psychiatrists, nurses, and social workers to help patients. Average stay is about two days and most patients go home after stabilization there; however, if they need additional time, they can be transferred to the inpatient psychiatry unit. Authors’ Conclusions: “The introduction of the EmPATH unit has improved management of patients presenting to the ED with suicidal attempts/ideation by reducing ED boarding and unnecessary admissions and establishing post-ED follow-up care.” Quality Checklist for Observational Study: Did the study address a clearly focused issue? Yes Did the authors use an appropriate method to answer their question? Yes Was the cohort recruited in an acceptable way? Yes Was the exposure accurately measured to minimize bias? Yes Was the outcome accurately measured to minimize bias? Yes Have the authors identified all-important confounding factors? No Was the follow up of subjects complete enough? Yes How precise are the results? Fairly precise for the primary outcome Do you believe the results? Yes Can the results be applied to the local population? Unsure Do the results of this study fit with other available evidence? Yes Funding of the Study: Department seed grant Results: There were 435 patients included in the pre-EmPATH stage and 527 patients included in the post-EmPATH stage. This gives a total cohort size of 962 patients presenting to the ED with suicidality. The median age was 32 years, it was close to a 50/50 male/female split, almost two-thirds arrived as walk-ins with the rest being by EMS or police, and 13% were identified as homeless. Key Result: Psychiatric admissions were reduced significantly after the introduction of the EmPATH Primary Outcome: Proportion of patients admitted to inpatient psychiatric unit (direct from ED, via EmPath Unit or by transfer). 57.1% in the pre-EmPATH stage vs 27.3% in the post-EmPATH stage Absolute difference of 29.8% and RR = 0.48 (95% CI = 0.40 to 0.56) Secondary Outcomes: ED boarding time was reduced from a mean of 16 hours to a mean of 5 hours We asked Allie and Sangil 10 nerdy questions to better understand their research. Listen to the SGEM podcast to hear their responses. Retrospective Observational Study – You acknowledge this as your first limitation. Why do you think it is important to caution readers about this type of study design? Administrative Data – You used administrative data (admitting diagnosis) to identify the patients to include in this study. Particularly with patients presenting after suicide attempt, who may have a diagnosis involving injury or poisoning, how sure are you that you can capture all these? Before and After Study – This was an uncontrolled before and after observational study. An editorial in the EBM_BMJ by Goodacre cautions against these types of studies. Stepped Wedge Design – One way to address this limitation of uncontrolled before and after study design would be to perform a stepped wedge design. A multi-centred cluster RCT would provide more robust information. Have you considered this as a future project? Single Centre – That is a great Segway into another nerdy point. This was a single center study. How representative is your center of US EDs in general and academic EDs in particular? Confounders - We mentioned in the quality checklist that you haven't presented rates of substance misuse or previous psychiatric diagnosis in the paper. Do you think they have changed or might have had an effect on the EmPATH unit? Washout - You had a washout period from May – Nov 2018. Can you explain to listeners why this was important for your study design and what was happening in the ED and EmPATH units during that time? Length of Stay – In the United Kingdom they have a goal to try to disposition emergency department patients within 4 hours. The decrease ED length of stay (LOS) decreased from 16 hours down to 5 hours. If confirmed, this could make a significant impact on ED flow. However, the total hospital LOS for patients who had a psychiatric bed request placed did not change with the implementation of EmPATH. Might you just be shifting the boarding problem from the ED to EmPATH, or do you think patients still benefit from the wider scope of care provided in the EmPATH unit? Long-Term Data – Why did you not follow-up on the long-term patient outcome such as suicide related using national data as you had done in previous studies? Anything Else – Is there anything else you would want the SGEM listeners to know about your research that we have not asked or was not published in the manuscript? Comment on Authors’ Conclusion Compared to SGEM Conclusion: We agree that in this case the EmPATH unit has been associated with a reduction in psychiatric admissions and ED boarding times.

Date: February 15th, 2022 Guest Skeptic: Dr. Tim Graham is a Clinical Professor of emergency medicine at the University of Alberta, and Associate Chief Medical Information Officer, Edmonton Zone, of Alberta Health Services from Edmonton, Alberta. Reference: Graham T. Physician heal thyself. CMAJ 2021 TRIGGER WARNING: As a warning to those listening to the podcast or reading this blog post, there may be some things discussed that could be upsetting. The SGEM is a free open access project trying to cut the knowledge translation down to less than one year. It is intended for clinicians providing care to emergency patients, so they get the best care, based on the best evidence. Some of the material we are going to be talking about on this episode could trigger some strong emotions. If you are feeling upset by the content, then please stop listening to the podcast or reading the blog. There will be resources listed at the end of the blog for those looking for assistance. Dr. Tim Graham This is an SGEM Xtra episode. Tim approached me about an article he wrote and published in the Canadian Medical Association Journal (CMAJ). The title of the article was "Physician, heal thyself" and was in the humanities section of the October 2021 issue. This article resonated with many people and was the 6th most read CMAJ article of 2021. Tim thanked his wife, Dr. Samina Ali, in the CMAJ article and on the podcast. Samina has been a guest skeptic on the SGEM. She is the one who suggested Tim share his story to reach an even wider audience. In this SGEM Xtra episode, Tim tells his experience with burnout. This is a topic we have discussed many times on the SGEM and I have shared my personal experience with burnout. SGEM Xtra: The Water is Wide SGEM#289: I Want a Dog to Relieve My Stress in the Emergency Department SGEM Xtra: CAEP Wellness Week 2019 SGEM Xtra: On the Edge of Burnout SGEM Xtra: Don’t Give Up – The Power of Kindness SGEM#178: Mindfulness – It’s not Better to Burnout than it is to Rust SGEM Xtra: Five Tips to Avoid Emergency Medicine Burnout A 2015 study by Shanafelt et al of US physicians showed that more 50% had at least one symptom of burnout. The highest prevalence of burnout was reported by emergency physicians. COVID19 has been hard on the health care system. Medscape just published a 2021 survey of 13,000 physician from 29 specialties and emergency physicians were still #1 reporting the highest level of burnout.  People have made a distinction between burnout and moral injury. Journalist Diane Silver describes moral Injury as “a deep soul wound that pierces a person’s identity, sense of morality, and relationship to society.” It is something that tears us apart at the fabric of what it is to be a physician. Tim discusses how he started getting suicidal ideations and what he did to try and address these thoughts. This included seeking professional help, medication, and lifestyle changes. Some interventions helped more than others. Tim reports he is now in the best place mentally and physically than he has been in many years. Tim also gives some advice to prevent others from going through a similar experience. This includes a wellness tool kit that starts with a healthy diet, regular exercise and good sleep. Two things he found really helpful were meditation and yoga. Suicidologist: Dr. Tyler Black When preparing this SGEM Xtra episode, I suggested to Tim we get an expert in mental health to give us some more information on the topic. I'm not an expert in this area and reached out to Dr. Tyler Black. Tyler is a suicidologist, emergency psychiatrist and pharmacologist from Vancouver. Dr. Tyler Black Tyler provided a definition for suicidologist. He discussed burnout and the association with suicidal ideation in physicians (Menon et al JAMA 2020. Tyler gave some potential reasons why physicians do not seek mental health care (stigma, colleges/regulatory bodies, access to care, etc).  He  also described how we can help each other and ourselves stay mentally healthy. Tyler was also asked what he would do if given a blank cheque to address this problem of physician burnout. He would spend the money on research and getting scribes to interact with the EMR and not buy muffins for the break room. Tim was asked at the end of the podcast what he would tell his younger self. I challenge the SGEM audience to think about what you would say to your younger self. Here is what Tim would say: "I would tell young me that no matter how important I think work is, I am really just another cog in the never-ending gears of the health care system. Once internalized, this knowledge was liberating, and it gave me permission to prioritize myself and my well-being. In the end, if you die tomorrow, your employer will replace you, but your loved ones cannot." 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. Resources: Physician Wellness Resources Physician Health Program ACEM Member Wellbeing ACEP Wellness Section CAEP Resident Wellness EMRA Wellness Committee Meditation Apps Waking Up with Sam Harris Headspace Suicide Telephone and Websites Prevention Hotline 1-800-273-8255 (SAFE) USA Text HOME to 741741 Canada Text 686868 Suicide Prevention Life Line American Foundation for Suicide Preventio (AFSP) Suicide Prevention Resource Center AFSP for Professionals Podcasts Peter Attia Drive

Date: February 7th, 2022 Reference: Williams et al. Short- vs standard-course outpatient antibiotic therapy for community-acquired pneumonia in children: the scout-cap randomized clinical trial. JAMA Pediatrics 2022 Guest Skeptic: Dr. Dennis Ren is a pediatric emergency medicine fellow at Children’s National Hospital in Washington, DC. Case: A three-year-old boy presents to the emergency department (ED) with fever and cough. On exam, he is breathing a little fast and his oxygen saturation is 94% on room air but otherwise appears comfortable. You appreciate some decreased breath sounds and crackles on your lung exam. You make a clinical diagnosis of community-acquired pneumonia (CAP) and plan to send him home with a 10-day course of amoxicillin. His mother asks you, “Last time he took antibiotics for that long, he had terrible diarrhea. Do you think we can do fewer days of antibiotics and still treat the pneumonia?” Background: We have covered the topic of pediatric community-acquired pneumonia before on the SGEM #338 (Are Children with CAP Safe and Sound if Treated for 5 days rather than 10 days of antibiotics?) with Dr. Andrew Tagg on the Canadian SAFER Trial [1]. This trial suggested that a 5-day course of antibiotics was not non-inferior to the traditional 10-day course of antibiotics for children with CAP treated as outpatients. Things were much simpler when I started my pediatric training. I learned that a well-appearing child presenting to clinic with fever, slight tachypnea, and focal lung exam findings could be diagnosed with pneumonia by history and physical exam alone and go home with 10 days of amoxicillin BID. But now for some reason, this topic feels more complicated…maybe because there are so many different ways people go about diagnosing pneumonia and such variability in the reliability of physical exam findings [2,3]. Since we covered the SAFER trial, we have also had the CAP-IT [4] trial from the United Kingdom and Ireland which evaluated both high and low-dose amoxicillin for the treatment of CAP over three or seven days. They found that both a lower dose and a shorter duration of antibiotic therapy was non-inferior to higher dose, longer duration antibiotic therapy. They did find that cough persisted longer with the group that received a shorter duration of antibiotic therapy but overall adherence to medication was better in the group receiving a shorter duration of antibiotics. Why so many pneumonia studies? Ultimately, we want to find that balance of treating an infection but avoiding antibiotic-associated adverse effects and antibiotic resistance. So where is that sweet spot?  Clinical Question: Is a 5-day course of antibiotics superior to a 10-day course for the treatment of non-severe community-acquired pneumonia in children with respect to clinical outcomes, adverse effects, and antimicrobial resistance? Reference: Williams et al. Short- vs standard-course outpatient antibiotic therapy for community-acquired pneumonia in children: the scout-cap randomized clinical trial. JAMA Pediatrics 2022 Population: Children 6 to 71 months of age from 8 US cities diagnosed with uncomplicated CAP demonstrating early clinical improvement (no fever, tachypnea, severe cough) on day 3 to 6 of their initially prescribed oral beta-lactam therapy. Excluded: Severe pneumonia (Hospitalization, radiographic evidence of parapneumonic effusion, empyema, lung abscess, pneumatocele or Microbiologically confirmed Staph aureus or Strep pyogenes pneumonia. Parenteral or combination antibiotic therapy. Undergoing surgery or invasive airway procedures 7 days prior to diagnosis of CAP. Beta-lactam allergy. Concurrent bacterial infection necessitating >5 days of antibiotics. Aspiration pneumonia, bronchiolitis, bronchitis, acute asthma exacerbation. Chronic medical conditions. History of pneumonia within prior 6 months Intervention: Short 5 days course of previously prescribed antibiotic therapy (amoxicillin, amoxicillin with clavulanate, cefdinir) with 5 days of placebo Comparison: Standard course of 10 days of previously prescribed antibiotic therapy Outcomes: Primary Outcome: End of treatment response adjusted for duration of antibiotic risk (RADAR) at the first outcome assessment visit (OAV1) which occurred on study days 6 to 10. This was a 2-step process: Desirability of outcome ranking (DOOR) based on adequate clinical response, resolution of symptoms, presence, and severity of antibiotic-associated adverse effects. Ranked overall experience based on actual reported treatment duration Secondary Outcomes: RADAR at the second outcome assessment visit (OAV2) on study days 19 to 25. A portion of participants also consented to throat swab collection at the second outcome assessment visit to evaluate antibiotic resistance genes in oropharyngeal flora. Trial: Prospective, multicenter randomized double-blind placebo-controlled superiority clinical trial. Authors’ Conclusions: “In this study, among children responding to initial treatment for outpatient CAP, a 5-day antibiotic strategy was superior to a 10-day strategy. The shortened approach resulted in similar clinical response and antibiotic-associated adverse effects, while reducing antibiotic exposure and resistance.” 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. Yes All groups were treated equally except for the intervention. Yes Follow-up was complete (i.e. at least 80% for both groups). Yes All patient-important outcomes were considered. Yes The treatment effect was large enough and precise enough to be clinically significant. Unsure Lack of conflicts of interest. No Results: They included 380 children (189 randomized to short course and 191 randomized to standard course). Mean age was 36 months, 51% male and 91% were treated with amoxicillin. Key Result: 5-day course of antibiotics for the treatment of outpatient CAP was superior to a 10-day course (similar efficacy, similar adverse events, while reducing antibiotic exposure and resistance). Primary Outcome: No significant difference in proportions of inadequate clinical response, persistent symptoms, or antibiotic-associated adverse effects between short-course vs standard-course groups. Short course therapy had 69% (95% CI, 63% to 75%) probability of more desirable RADAR outcome compared to standard course. This reflects the probability of a better DOOR (clinical response, resolution of symptoms, and antibiotic-associated adverse effects) for a randomly selected participant from the short course vs the standard course strategy. Secondary Outcomes: 1. Potential Selection Bias: They included 380 patients over a three-year study period. They do not remark on whether patients were enrolled consecutively, but I would assume there were probably quite a few more cases of pneumonia diagnosed across multiple institutions in that study period than were included in the final analysis. There was also some subjectivity in the enrollment. Patients could not have been included if they had a severe cough. Who decided whether the cough was severe and did they have some objective measure? They also used tachypnea to exclude patients. Measuring tachypnea is well known to be inaccurate and lack inter-rater reliability [5-7]. These factors may lead to some selection bias. 2. Included Patients: Patients included in this study were relatively healthy from 6 months to 71 months of age. We need to be cautious when extrapolating the results to children with underlying conditions or outside those age ranges. 3. Outcomes: We need to say a few things about the outcomes in this trial Complicated: Their primary outcome was a composite outcome which can make a fuzzier target. It was also a little hard to interpret. ClinicalTrials.gov Data - We should applaud the authors of this study for reporting the primary and secondary outcomes that they originally proposed. It is still surprising the number of published research trials in which the reported outcomes differ from the proposed outcomes. DOOR Score: The DOOR score evaluated patient-oriented outcomes, specifically clinical response, persistence of symptoms, and adverse effects from antibiotic therapy. We acknowledge that these have a degree of subjectivity including grading of cough severity and adverse effects of antibiotic therapy. Resistomes: A subgroup of the patients had throat swabs to assess for antibiotic resistance genes (ARGs) expressed as resistance genes per prokaryotic cell (RGPC). The authors reported that there were significantly lower RGPCs in the group that had short-course therapy in comparison to standard therapy. This is a lab-oriented outcome that brings up a few questions: Does this assessment of respiratory flora from a throat swab really correlate with what is happening in the lungs? What does a difference of 1.17 vs 1.33 mean clinically if anything? Is this going to be a persistent change? 4. Diagnosis of Pneumonia: All the patients included in this study were previously diagnosed with CAP in an outpatient clinic, urgent care centre, or emergency department. Unfortunately, we do not know how the diagnosis of pneumonia was made. Was it by clinical exam findings? Chest radiograph? Respiratory cultures? How accurate were these diagnoses? However,

Date: January 25th, 2022 Reference: Beyde et al. Efficacy of empiric antibiotic management of septic olecranon bursitis without bursal aspiration in emergency department patients. AEM January 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’re working in your busy freestanding emergency department (ED) getting absolutely crushed handing out COVID19 tests like candy and are relieved to see a patient with something different. A 27-year-old male construction worker building a local house presents with a tender, warm, erythematous olecranon and you diagnose him with septic olecranon bursitis. You offer to drain the bursa and get him back to work ASAP, and the patient looks very anxious and asks if you really must. Background: We have covered skin and soft tissue infections multiple times on the SGEM. The most recent time was with guest skeptic and SAEM FOAMed Excellence in Education Award winner Dr. Lauren Westafer (SGEM#348). We reviewed Dr. David Talan and colleagues’ study that was the October 2021 SGEM Hot Off the Press. That study investigated if a single-dose long-acting intravenous antibiotic could reduce hospitalization in patients with skin infections. The SGEM bottom line from that episode was in hospital systems with access to IV dalbavancin and the ability to establish expedited telephone and in-person follow up, this clinical pathway is associated with a decrease in hospitalizations for patients with moderately severe cellulitis. A couple of other SGEM episodes have looked at the management of cellulitis including SGEM#131 and SGEM#209. The treatment of abscesses has been covered four times on the SGEM (SGEM#13, SGEM#156, SGEM#164 and SGEM#311). The latest episode looked at the loop technique to drain uncomplicated abscesses. One topic we have not looked at is infected bursa. It’s estimated that about half of olecranon bursitis cases are septic[1]. Often, diagnostic aspiration is performed, but complications include fistula formation, further infection, and need for bursectomy [2-6]. Often the workup of septic bursitis is based upon anecdotal evidence [7]. This is likely due to the lack of high-quality evidence to direct our care. One area with limited information is the efficacy of empiric antibiotics without bursal aspiration. Clinical Question: What is the efficacy and outcomes associated with empiric antibiotic therapy, without aspiration, for septic olecranon bursitis? Reference: Beyde et al. Efficacy of empiric antibiotic management of septic olecranon bursitis without bursal aspiration in emergency department patients. AEM January 2022 Population: Adults >18 years old with olecranon bursitis Excluded: Declined authorization, underlying fracture, or surgery on the joint within 3 months Exposures: Antibiotics, aspiration, surgery or admission to hospital Comparison: None Outcome: Primary Outcome: Complicated versus uncomplicated bursitis resolution (Uncomplicated was defined as bursitis resolution without the need for bursal aspiration, surgery, or hospitalization) Secondary Outcome: Descriptive statistics of the cohort Study Design: Retrospective observational cohort study Dr. Ronna Campbell This is an SGEMHOP episode which means we have the senior author on the show. Dr. Ronna Campbell is an emergency physician practicing since 2007 in Rochester, MN. She enjoys mentoring medical students, residents and others in research. Authors’ Conclusions: “Eighty-eight percent of ED patients with suspected septic olecranon bursitis treated with empiric antibiotics without aspiration had resolution without need for subsequent bursal aspiration, hospitalization, or surgery. Our findings suggest that empiric antibiotics without bursal aspiration may be a reasonable initial approach to ED management of select patients with suspected septic olecranon bursitis.” Quality Checklist for Observational Study: Did the study address a clearly focused issue? Yes Did the authors use an appropriate method to answer their question? Yes Was the cohort recruited in an acceptable way? Yes Was the exposure accurately measured to minimize bias? Yes Was the outcome accurately measured to minimize bias? Yes Have the authors identified all-important confounding factors? Unsure Was the follow up of subjects complete enough? Yes How precise are the results? Fairly wide 95% CI around some of the point estimates Do you believe the results? Yes Can the results be applied to the local population? Unsure Do the results of this study fit with other available evidence? Yes Funding of the Study? NCATS/NIH grant Results: 264 patients included in the study, 229 with three months of follow up, 220 with six months. The age ranged from 42-69 years with 85% male. The most common presenting symptoms were swelling (94%), erythema (77%), and pain (85%). Key Results: Most patients with suspected septic olecranon bursitis had an uncomplicated resolution of their bursitis. Primary Outcome: Complicated vs uncomplicated resolution 88.1% were uncomplicated (95% CI: 81.1%–92.8%) 6.0% had subsequent bursal aspiration (95% CI: 2.8%–11.8%) 6.7% were subsequently admitted to hospital for antibiotics (95% CI: 3.3%–12.7%) Secondary Outcomes: 1.5% (4) had ED aspiration with no known complications (one lost to follow-up) 15% (39) were admitted to hospital on the initial visit 56% (147) were discharged from the ED with antibiotics 8.8% (13) lost to follow up, 17.2% (27) 95% CI 11.4%-25.9% had subsequent bursitis-related visit, 88.1% (118) 95% CI 81.1-92.8% uncomplicated resolution and 8 (6.0%, 95% CI 2.8%-11.8%) underwent subsequent bursal aspiration 29% (76) were discharged from the ED without Antibiotics 12% (9) lost to follow up, 97% (65) 95% CI 89-99% resolved without antibiotics, 91% (61) 95% CI 81.96% had an uncomplicated resolution and 3% (2) 95% CI 1-11% received inpatient antibiotics in a subsequent hospitalization Listen to the SGEM podcast to hear Ronna answer our five nerdy questions about her study. 1. Study Design: You decided to perform a retrospective observational study. This really limits the strength of conclusions that can be made from the data. Can you comment on the decision not to perform a prospective observational study or a randomized control trial (CEBM)? 2. STROBE – You mentioned the STROBE guidelines (Strengthening the Reporting of Observational Studies in Epidemiology). Some of the SGEM listeners may not be familiar with these guidelines. Can you tell us a little about these guidelines and why it is important to follow them? 3. Lack of Blinding – The abstractors were not blinded to the study objectives. Do you think that could have impacted the results and what did you do to mitigate this potential bias? 4. Gold Standard - Was there any gold standard for the diagnosis of septic olecranon bursitis other than provider impression? 5. External Validity – This study was conducted at a single centre. In addition, it was the Mayo Clinic which is a quaternary care ED. Practice patterns of clinical staff (MD/DO/NP/PA) and management may be different here than at other quaternary EDs or community and rural EDs. Do you think your study has external validity to other practice environments? Comment on Authors’ Conclusion Compared to SGEM Conclusion: We generally agree with their conclusions SGEM Bottom Line: Antibiotics without aspiration seems safe and may be an effective method of treatment for suspected septic olecranon bursitis. Case Resolution: You discuss the options with the patient and using shared decision making, decide on an empiric antibiotic approach, without aspiration. The patient has a full and uncomplicated resolution. Clinical Application: The evidence base is weak and does not provide a clear answer. When deciding on a treatment plan, it is reasonable to not perform an aspiration for suspected septic olecranon bursitis. Dr. Corey Heitz What Do I Tell My Patient? You have what appears to be an infected elbow bursa. A bursa is a fluid-filled pad around our joints. We can either stick a needle in the bursa (aspirate) and try to get some fluid. This fluid can be tested for infection. Aspiration of a bursa can have complications such as bleeding, causing an infection or hitting a nerve. Another option is to not do the aspiration and treat you with antibiotics. If this does not work or you are getting worse, you can always return to the ED. Would you prefer aspiration plus antibiotics or no aspiration plus antibiotics? Keener Kontest: Last weeks’ winner was Ravin Debie. They knew budesonide was patented in 1973. 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 septic olecranon bursitis? Tweet your comments using #SGEMHOP.  What questions do you have for Ronna and her team? Ask them on the SGEM blog. The best social media feedback will be published in AEM. Don’t forget those of you who are subscribers to Academic Emergency Medicine can head over to the AEM home page to get CME credit for this podcast and article. Remember to be skeptical of anything you learn, even if you heard it on the Skeptics’ Guide to Emergency Medicine. References: Stell IM. Management of acute bursitis: outcome study of a structured approach. J R Soc Med. 1999;92:516-521. Lormeau C, Cormier G, Sigaux J, Arvieux C, Semerano L. Management of septic bursitis. Joint Bone Spine. 2019;86:583-588. Deal JB Jr, Vaslow AS, Bickley RJ, Verwiebe EG,

Date: January 22nd, 2022 Reference: Yu et al. Inhaled budesonide for COVID-19 in people at high risk of complications in the community in the UK (PRINCIPLE): a randomised, controlled, open-label, adaptive platform trial. Lancet 2021 Guest Skeptic: Dr. Justin Morgenstern is an emergency physician and the creator of the #FOAMed project called First10EM.com. Case: A 65-year-old woman with a history of diabetes, hypertension, and gastroesophageal reflux disease (GERD) presents with three days of fever, cough, and myalgias. She is fully vaccinated against COVID-19. Her husband tested positive for COVID-19 yesterday, and she used a home rapid test this morning that is also positive. Her vitals signs are all normal and she feels well enough to isolate at home. As you are preparing to discharge her, she asks if there is anything you can prescribe her to help. She thinks her friend might have been prescribed a puffer of some sort. Background: I’ve tried not to focus too much on COVID-19. There are many great FOAMed resources that have done a good job of covering the topic. The SGEM has only done a few shows over the two years including: Debate regarding a universal mandate for masks early in the pandemic with Dr. Joe Vipond (SGEM Xtra: Masks4All in Canada Debate) Skeptical review of the early therapeutics with Dr. Sean Moore for the Canadian Association of Emergency Physicians (CAEP) Town Hall (SGEM Xtra: COVID19 Treatments – Be Skeptical) Diagnostic accuracy of various tests for COVID19 with Dr. Chris Carpenter (SGEM#299: Learning to Test for COVID19) Structured critical appraisal of the DANMASK trial with Dr. Joe Vipond (SGEM#309: That’s All Joe Asks of You – Wear a Mask) The First10EM has done more than 30 blog posts about COVID-19 at this point, with a lot more to come. I know we all wish COVID-19 would just go away. But unfortunately, wishful thinking won’t help us, but hopefully science will. There is strong evidence that systemic steroids improve outcomes in patients with severe COVID-19 (First10EM: Steroids for COVID). This has raised the question of whether inhaled steroids might be helpful. After all, the infection is primarily in the lungs. Early in the pandemic, there was some observational data that concluded that inhaled steroids were associated with an increased mortality from COVID-19 in patients with asthma and COPD (Schultze Lancet Resp Med 2020). However, the most likely explanation was not causal. Sicker patients are prescribed steroids more often, and so the association is not surprising. The STOIC trial was an initial phase 2 open-label randomized control trial of inhaled budesonide for patients with mild symptoms of COVID-19 (Ramakrishnan et al Lancet Resp Med 2021). It did report positive results. Their primary outcome was a ‘COVID-19 related’ urgent care visit, emergency department assessment, or hospitalization, and was significantly reduced in the budesonide arm (15% vs 3%, p=0.009). However, the unblinded trial design, less relevant composite outcome, and fact that the trial was stopped early limit confidence in the results. That bring us to the PRINCIPLE trial. Clinical Question: Does inhaled budesonide improve clinical outcomes in high-risk outpatients with COVID-19? Reference: Yu et al. Inhaled budesonide for COVID-19 in people at high risk of complications in the community in the UK (PRINCIPLE): a randomised, controlled, open-label, adaptive platform trial. Lancet 2021 Population: Outpatients with symptomatic COVID-19 within 14 days of symptom onset who were considered high risk for adverse events. This included adults over 65 years of age, or over 50 years of age with co-morbidities. Exclusions: Known allergy or contraindication to inhaled budesonide, were unable to use an inhaler, or already using inhaled or systemic glucocorticoids. Intervention: Inhaled budesonide 800 ug BID for 14 days Comparison: Usual care (there was no placebo) Outcome: Primary Outcome: Composite outcome of COVID-19-related hospital admission or death within 28 days. However, partway through the trial they realized hospitalization was lower than normal, and so they added a second primary outcome: illness duration. Secondary Outcomes: Recovery by 14 days, daily symptoms rating, time to sustained alleviation of symptoms, time to initial reduction of symptoms, contact with health services, oxygen administration, ICU admission, mechanical ventilation and adherence to study medication Trial Design: Multicentre, open-label, multi-arm, randomised, controlled, adaptive platform trial Authors’ Conclusions: “Inhaled budesonide improves time to recovery, with a chance of also reducing hospital admissions or deaths (although our results did not meet the superiority threshold), in people with COVID-19 in the community who are at higher risk of complications.”  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. Unsure The study patients were recruited consecutively (i.e. no selection bias). No The patients in both groups were similar with respect to prognostic factors. Yes All participants (patients, clinicians, outcome assessors) were unaware of group allocation. No All groups were treated equally except for the intervention. No Follow-up was complete (i.e. at least 80% for both groups). Yes All patient-important outcomes were considered. No The treatment effect was large enough and precise enough to be clinically significant. Unsure Funding and Conflicts of Interest: This is primarily government funded. However, multiple authors declared COIs associated with AstraZeneca. Results: They recruited 1,959 into the trial for the primary analysis (833 budesonide and 1,126 usual care). Mean age was 64 years, 81% had comorbidities, 52% female, 11% had been vaccinated (1 or 2 shots), 5% were current smokers and median duration of illness was 6 days. Key Result: No statistical difference in hospitalization or death but quicker recovery reported in budesonide group. Primary Outcome: There was no statistical difference for the original primary outcome of hospital admission or death due to COVID-19: 6.8% with budesonide versus 8.8% with usual care (ARR 2.0%, 95% CI -0.2 to 4.5%) For the added primary outcome of time to first reported recovery, budesonide was better at 11.8 vs 14.7 days, absolute benefit 2.9 days (95% CI: 1.2-5.1 days) Secondary Outcomes:  No statistical difference in mortality (1% v 1%), mechanical ventilation (2% v 2%), need for supplemental oxygen (7% v 9%) or need for ICU (1% v 3%) There are a large number of symptom-based outcomes. In general, they demonstrate statistically less symptoms with budesonide, although the actual clinical difference seems small, and this is an unblinded study. We will discuss this further in the Talk Nerdy section. 1) Unblinded Trial: The biggest limitation in this study is its lack of blinding, especially considering they added a second primary outcome that was entirely symptom based. In any unblinded trial, we should expect that the treatment group will have fewer symptoms, so those results are unreliable here. However, even seemingly objective outcomes like hospitalizations can end up biased in unblinded trials. Imagine a patient who feels like ‘nothing is being done for them’, struggling with the cough and fatigue of COVID-19. They may not meet any formal admission criteria for COVID-19, but if it is there third ED visit, they might end up admitted anyway. (I have seen this happen many times.) Therefore, symptoms translate into hospitalizations, and so the unblinded nature of the trial even biases their original primary outcome. 2) Disease Specific Outcomes: For their original primary outcome, they looked at “COVID-19-related hospital admission or death” rather than just hospital admission or all death. This is an issue and can bias a trial from the outset. These outcomes fundamentally ignore harms of medications. If a patient is admitted to hospital because of a medication-related adverse event, then don’t get counted in this primary outcome. Luckily, adverse events are rare from inhaled budesonide, so this bias probably did not have a huge impact on these results. 3) Adding a Second Primary Outcome: The original primary outcome was a composite of COVID-19-related hospital admission or death within 28 days. This was changed to add a co-primary outcome of illness duration. The rationale was that the hospital admission rates in the UK were lower than the authors initially expected. Ethics approval was provided for this amendment and implemented before performing any interim analyses. The more objective primary outcome of hospitalization and death were not statistically different, but the subjective outcome of illness duration was better with budesonide. As mentioned in nerdy point #1 the lack of blinding likely impacted the additional primary outcome and may have impacted hospitalizations. 4) Extrapolation: Most of these patients were unvaccinated. Vaccinated patients have better outcomes after COVID-19 infection, and therefore are much less likely to benefit from treatment. Therefore, we shouldn’t expect to see the same degree of benefit in vaccinated populations. The same concern may apply to the shifting severity we see from new COVID-19 variants. 5) Threshold for Evidence During a Pandemic: This is a longer and more philosophical discussion. For any study, we will see a range of possible interpretations. During COVID-19, in particular, I have found myself disagreeing with some very smart evidence-based doctors who I usually agree with,

Date: January 16th, 2022 Reference: Matchett, G. et al. Etomidate versus ketamine for emergency endotracheal intubation: a randomized clinical trial. Intensive Care Med 2021 Guest Skeptic: Missy Carter, former City of Bremerton Firefighter/Paramedic, currently a professor of Emergency Medical Services at Tacoma Community College’s paramedic program. Missy is currently working in a community emergency department as a physician assistant and recently accepted a critical care position in Tacoma Washington. Case: You respond to a rapid response on the floor for a 58-year-old woman in septic shock who is requiring emergent rapid sequence intubation (RSI). As you prepare to intubate the pharmacist asks if you would prefer ketamine or etomidate for induction in this patient. Background: We have covered the issue of intubation multiple times on the SGEM. This has included looking at supraglottic airways for out-of-hospital cardiac arrests (SGEM#247), video vs. direct laryngoscopy (SGEM#95), tracheal intubation for in-hospital cardiac arrests (SGEM#197), apneic oxygenation (SGEM#186) and confirming intubation with POCUS (SGEM#249). One thing we have not covered is the choice of induction agent for intubation. There has been much debate regarding the use of etomidate verses ketamine for induction in the critically ill [1-4]. A 2009 randomized control trial conducted in French ICUs supported the use of ketamine in this patient population [5]. Both agents are considered hemodynamically stable, but any induction agent may precipitate shock in the critically ill. There is some conflicting evidence as to which agent is preferred for patients who are at high risk of peri intubation complications. Historically there has been concern about adrenal insufficiency caused by etomidate being harmful for patients with sepsis but this has not been shown to cause increased mortality in the literature [6, 7]. Ketamine has emerged as a reasonable alternative but in recent years there has been concern about increased cardiovascular collapse with ketamine especially in those with sepsis or a high shock index [1, 8].    Clinical Question: Which induction agent has a better day 7 survival for critically ill patients requiring emergency endotracheal intubation, ketamine or etomidate? Reference: Matchett, G. et al. Etomidate versus ketamine for emergency endotracheal intubation: a randomized clinical trial. Intensive Care Med 2021 Population: Adults 18 years of age and older in need of emergency endotracheal (ET) intubation Exclusions: Children, pregnant patients, patients needing ET intubation without sedation or allergic to one of the agents being used Intervention: Ketamine 1-2mg/kg IV Comparison: Etomidate 0.2-0.3mg/kg IV Outcome: Primary Outcome: 7-day survival Secondary Outcomes: 28-day survival, duration of mechanical ventilation, ICU length of stay, need for vasopressor use, SOFA scores and an assessment of a new diagnosis of adrenal insufficiency by the treating critical care teams. Trial: Prospective, randomized, parallel-assignment, open-label, single-center trial (NCT02643381) Authors’ Conclusions: While the primary outcome of Day 7 survival was greater in patients randomized to ketamine, there was no significant difference in survival by Day 28.” 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. Unsure Lack of conflicts of interest. No Results: The cohort consisted of 801 critically ill patients that required ET. The mean age was 55 years, 38% female, 69% were in the MICU, and 51% had diagnosis of sepsis. Key Result: Day 7 survival was statistically higher in the ketamine arm compared to the etomidate arm Primary Outcome: 7-day survival favored Ketamine (85.1%) vs etomidate (77.3%), difference − 7.8, (95% CI; − 13 to − 2.4) p = 0.005 Secondary Outcomes: There was no statistical difference in 28-day survival between groups (ketamine 66.8% vs etomidate 64.1%) 1. Selection Bias: These were not consecutive patients. The manuscript says physicians were “encouraged to consider screening and enrolling patients whenever clinical circumstances reasonably permitted but were under no obligation to do so.” When you look at the number of patients excluded due to “clinical circumstances, clinician preference for usual care” in each arm of trial they were similar (n =396 for etomidate, and n = 398 for Ketamine). The reasons for these exclusions are unclear and may have biased the results towards whichever medication the physician favored. How these exclusions would ultimately impact the over-all results is also unclear. 2. Blinding: This was an open label trial. The authors said: “After extensive discussions with hospital and community stakeholders, we were unable to arrive at a satisfactory plan for masking.” This lack of blinding could have been responsible for the reported higher level of adrenal insufficiency was found in the etomidate arm. Having knowledge of group allocation may have led clinicians to more testing for adrenal insufficiency in the etomidate arm verses the ketamine arm. 3. Outcome Measure: The authors recognize that selecting 7 day survival is an unconventional outcome measure in an RCT of critically ill patients. They chose one Constantine unit (7 days) as the outcome because of their quality improvement data and to have the endpoint close to randomization. While the 7 day mortality was statistically better in the ketamine group compared to the etomidate group, there was not statistical difference reported at 28 days. Also, a more patient oriented outcome would be survival with good neurologic status. 4. External Validity: This trial was a single center trial including largely ICU patients who were intubated by an anesthesia lead airway team. This airway team uses the Montpellier Intubation protocol which includes the presence of two skilled operators, head-up positioning, deliberate preoxygenation, routine use of neuromuscular blocking agents and intubating stylets and frequent use of VL. They use EtCO2 detection for tube confirmation and are focused on prompt treatment of post intubation hypotension with vasopressors and IVF. This practice produced a 91% first pass success rate and likely contributed to standardized care in each group. The practice may not be generalizable to other centers who do not use such standardized protocols. 5. Hypothesis Generating: There were some interesting secondary outcomes regarding hemodynamics and cardiovascular collapse that are thought provoking and hypothesis generating. Ketamine had higher rates of vasopressors use, more frequent post intubation CPR, and higher incidence of post induction cardiovascular collapse compared to etomidate. This is very interesting given the 7-day mortality was better with ketamine. It may be that the airway team was so aggressive about post intubation management that they were able to overcome these complications. This circles back to nerdy point #4 and raises another question about generalizability. If these complications are encountered in other practice settings, such as the pre-hospital setting where there are less resources, would the patient receive the same aggressive post intubation management for these complications and might that change the outcomes. Comment on Authors’ Conclusion Compared to SGEM Conclusion: We agree with the authors conclusion. SGEM Bottom Line: It likely does not make a patient-oriented difference whether you use ketamine or etomidate for emergency endotracheal induction in most critically ill patients. Case Resolution: You tell your pharmacist you would like to use etomidate at a half dose but prior to intubation. First you would like to optimize hemodynamics and oxygenation and have a vasopressor ready in case you encounter post intubation hypotension. Missy Carter Clinical Application: Both ketamine and etomidate have similar hemodynamic stability, but both should be used with caution in the critically ill patient. There may be certain patient populations who might benefit from one medication over the other, but more research is needed on this topic. Regardless of which agent used there should be a focus on optimizing patient physiology by aggressively resuscitating before you intubate. Considering lower dosing for either induction agent in the critically ill may be further protective. What Do I Tell the Patient? You tell the patients family she is requiring a breathing tube to keep her safe while we manage her illness. She will be given medications to make them comfortable during and after the procedure. Although complications are possible, we will be doing everything we can to reduce her risk and keep her safe and comfortable. Keener Kontest: Last weeks’ winner was Dr. Paul Ehlers a PGY4 from UCSF. He knew the Rak Su singer who suffered a hemothorax was Myles Stephenson. Listen to the SGEM podcast for this weeks’ question.  If you know, then send an email to thesgem@gmail.com with “keener” in the subject line.

Date: December 28th, 2021 Reference: Kulvatunyou et al. The small (14 Fr) percutaneous catheter (P-CAT) versus large (28–32 Fr) open chest tube for traumatic hemothorax: A multicenter randomized clinical trial. J Trauma and Acute Care Surgery. November 2021. Guest Skeptic: Dr. Chris Root is a second-year resident physician in the Department of Emergency Medicine at the University of New Mexico Health Sciences Center in Albuquerque, NM. He is also a resident flight physician with UNM’s aeromedical service, UNM Lifeguard. Prior to earning his MD, he worked as a paramedic in the New York City 911 system. Case: A 43-year-old male presents to your emergency department (ED) the day after being involved in an all-terrain vehicle (ATV) accident. He reports he was riding his ATV along an embankment when it rolled, landing on top of him briefly. He did not seek medical attention at the time of the incident, but he has had persistent chest wall pain and worsening shortness of breath since yesterday evening. He is hemodynamically stable, oxygen saturation is 91% on room air, physical exam reveals ecchymosis and tenderness over the right chest wall with diminished right sided lung sounds. CT scans reveal multiple right sided rib fractures and a hemothorax estimated to measure 500cc with no additional injuries. Background:  We have discussed chest tubes a couple of times on the SGEM. This is usually with the master himself, Dr. Richard (Thoracic Rick) Malthaner. The first time was looking at a study about where to put the chest tube in a trauma patient. It turns out location (high or low) does not matter. The most important thing is placing the chest tube in the triangle of safety in the plural space (SGEM#129). The other episode on chest tubes looked at conservative vs interventional treatment for spontaneous pneumothorax (SGEM#300). This randomized controlled trial demonstrated that conservative management was non-inferior to placing a chest tube in a patient with a large first-time spontaneous pneumothorax. Another SGEM episode we did looked at the location of needle decompression for tension pneumothorax (SGEM#339). This was done with our good friend and frequent guest skeptic Dr. Robert Edmonds. This observational study did not support the claim that the second intercostal space-midclavicular line is thicker than the fourth/fifth intercostal space-anterior axillary line. This new SGEM episode looks at the size of chest tubes needed to successfully treat a traumatic hemothorax. Traditionally, these are treated by inserting a large bore chest tube (LBCT). There is increasing evidence supporting the use of smaller, percutaneously inserted chest tubes or pigtail catheter (PC) for the drainage of pleural effusions and pneumothoraces as well as some evidence of their efficacy for hemothorax. Clinical Question: Are small (14fr) pigtail catheters as effective as large (28-32 fr) chest tubes for the treatment of hemodynamcially stable patients with traumatic hemothorax? Reference: Kulvatunyou et al. The small (14 Fr) percutaneous catheter (P-CAT) versus large (28–32 Fr) open chest tube for traumatic hemothorax: A multicenter randomized clinical trial. J Trauma and Acute Care Surgery. November 2021. Population: Hemodynamically stable adult patients 18 years or older suffering traumatic hemothorax or hemopneumothorax requiring drainage at the discretion of the treating physician. Exclusions: Emergent indication, hemodynamic instability, patient refuses to participate, prisoner or pregnancy Intervention: Placement of small (14 fr PC) chest tube using a percutaneous seldinger technique Comparison: Placement of a large (28-32 fr LBCT) chest tube using a traditional surgical thoracostomy Outcome: Primary Outcome: Failure rate defined as radiographically apparent hemothorax after tube placement requiring an additional intervention such as second tube placement, thrombolysis or video-assisted thorascopic surgery Secondary Outcomes: Insertion complication rate; drainage output (30 minutes, 24-hour, 48-hour, and 72-hour); hospital course outcome up to 30 days (total tube days, ICU LOS, hospital LOS, and ventilator days); and insertion perception experience (IPE) score (1-5 score subjective score,1 - it was okay to 5 - it was the worst experience of my life). Trial: Multicenter, non-inferior, unblinded, randomized, parallel assignment comparison trial Authors’ Conclusions: “Small caliber 14-Fr PCs are equally as effective as 28- to 32-Fr chest tubes in their ability to drain traumatic HTX with no difference in complications. Patients reported better IPE scores with PCs over chest tubes, suggesting that PCs are better tolerated.” Quality Checklist for Randomized Clinical Trials: The study population included or focused on those in the emergency department. Yes The patients were adequately randomized. Yes The randomization process was concealed. Yes The patients were analyzed in the groups to which they were randomized. Yes The study patients were recruited consecutively (i.e. no selection bias). Unsure The patients in both groups were similar with respect to prognostic factors. Yes All participants (patients, clinicians, outcome assessors) were unaware of group allocation. No All groups were treated equally except for the intervention. Unsure Follow-up was complete (i.e. at least 80% for both groups). Yes All patient-important outcomes were considered. Yes The treatment effect was precise enough to be clinically significant. Yes Financial conflicts of interest. Yes Results: There were 222 eligible patients identified over five years. The final cohort consisted of 119 patients (56 PC and 63 LBCT). The mean age was 55 years, 82% were male, 81% blunt trauma and median time to tube placement was 1 to 2 days from injury. Key Result: Small percutaneous catheters were non-inferior to large open chest tube for traumatic hemothorax Primary Outcome: Failure rate between PC and LBCT for the drainage of traumatic hemothorax 11% vs 13% (p=0.74). Secondary Outcomes: There were two insertion-related complications one from each group (bleeding from PC necessitated a thoracotomy and extra pleural position from chest tube placement required another tube placement). There were two deaths, one from each group (PC group had a PE on postinjury day 10 and the tube had already been removed and chest tube group had a nontrauma-related death at an outside institution). No statistical difference between PC and LBCT in terms of drainage tube output except at 30 minutes. No statistical difference in hospital course (tube days, ICU LOS, total hospital LOS or ventilatory days). Patients reported better IPE scores in the PC group compared to the LBCT group. 1. Selection Bias: There was no explicit statement that patients were consecutively recruited into the trial. They identified 222 eligible patients over five years. There were 102 excluded with 27 for “MD preference”.This means 27/102 (26%) of exclusions were for a subjective reason. This could have introduced some selection bias into the trial. 2. Exclusion of Hemodynamically Unstable Patients: Hemodynamically unstable trauma patients were excluded from study enrollment. Open thoracostomy and the placement of a LBCT is still considered by many to be the primary treatment for the evacuation of hemothorax in the hemodynamcailly unstable trauma patient. The authors did not seek to deviate from that idea in this study. However, they do allude to anecdotal experience placing PCs in hemodynamically unstable patients, and the output from PCs in the first hour was greater than that from LBCT in their trial, but further studies are needed to investigate the utility of PCs in hemodynamically unstable trauma patients. The exclusion of hemodynamically unstable patients could also explain the lower than anticipated failure rate which will be discussed later. 3. Patient Oriented Outcome: Tube failure rate is a simple, dichotomous, and clinically important primary outcome. However, the IPE score is a critical patient-oriented outcome (POO) that should be considered when managing these patients. The lead author, Dr. Kulvatanyou, alludes to having had friends and family members who have undergone LBCT placement express how horrible it was. Although the IPE scale developed by the investigators was not externally validated it is a straightforward and effective means of comparing the subjective experience of patients receiving either intervention. If you had a traumatic hemothorax, would you like the big tube or the small tube? 4. Low Overall Failure Rates: This study reports failure rates of 11% and 13% for PCs and LBCT respectively. These figures are significantly lower than a rate of 28.7% reported in a recent multi-institutional study from the Eastern Association for the Surgery of Trauma (EAST). The authors comment that this may be because their study excluded patients in extremis who may have additional injuries or require a level of procedural urgency that predisposes them to complications, however it is interesting to note that the study population in this trail had a mean hemothorax volume of 612mL vs 191 mL is the EAST study indicating that volume of blood did not appear to influence rate of failure compared to what has been published elsewhere (Prakash et al 2020). 5. Stopped Early: This is a multi-center RCT building on this groups previously published single center experience using PCs for the treatment of traumatic hemothorax (Kulvatunyou JTACS 2012). Despite enrolling at four sites for five years, they only enrolled 119 total patients. The authors initially estimated that they would have had to enroll 95 patients in each arm to have adequate power to detect a 15% absolute difference in efficacy between PCs and LBCTs.

Date: December 21st, 2021 Guest Skeptic: Dr. Howard “Howie” Mell began his career as a firefighter / paramedic in Chicago. He became double board certified in Emergency Medicine (EM) and Emergency Medical Services (EMS). Howie also has a Master of Public Health. Reference: Grotta JC et al. Prospective, multicenter, controlled trial of mobile stroke units. NEJM 2021 Case: The Mayor of your community consults you as an expert in public health, EMS and as an EM physician on whether they should purchase a mobile stroke unit (MSU) ambulance. Background: No one who has listened to the SGEM will be surprised we are covering another paper looking at stroke. We have often discussed the use of thrombolysis for acute ischemic stroke (AIS) with or without endovascular therapy (EVT). However, the SGEM has also looked at secondary stroke prevention on previous episodes (SGEM#24, SGEM#303). The SGEM has looked at pre-hospital stroke care using early administration of nitroglycerin by paramedics to see if it would improve neurologic outcome in patients with a presumed acute stroke (SGEM#269). The results from the RIGHT-2 trial reported no statistical difference in functional outcome as measured by the modified Rankin Scale (mRS) score at 90 days. The SGEM bottom line was that very early application of transdermal nitroglycerin by paramedics in the pre-hospital setting cannot be recommended at this time in patients with a suspected stroke. Mobile Stroke Unit The issue of having a MSU has also been discussed on  SGEM#330. A systematic review and meta-analysis which included seven randomized controlled trials and four observational studies including 21,297 patients was critically appraised.  The primary outcomes reported better neurologic outcome at seven days but not at one day post treatment by a MSU compared to conventional care (Fatima et al Int J Stroke 2020). The SGEM bottom line from that episode was we cannot recommend the use of MSU based on the available evidence. Clinical Question: Should mobile stroke units be purchased and deployed in your community? Reference: Grotta JC et al. Prospective, multicenter, controlled trial of mobile stroke units. NEJM 2021 Population: Patients calling EMS with a history and physical/neurological examination consistent with acute stroke who is last seen normal (LSN) possibly within 4 hours and 30 minutes and who had no definite tPA exclusions per guidelines, prior to CT scan or baseline labs. Daytime hours and mostly weekdays. Intervention: Care by a mobile stroke unit (MSU) Comparison: Care by traditional EMS referred to as standard management (SM) Outcome: Primary Outcome: Score on the utility-weighted modified Rankin scale (uw-mRS) at 90 days in patients who were adjudicated to be eligible to receive tPA on the basis of subsequent blinded review Secondary Outcomes: There were twelve secondary endpoints in their final protocol listed in hierarchical sequence of importance Agreement between on-board vascular neurologists (VN) and the remote VN Exploratory cost-effectiveness analysis (CEA) Outcomes comparing patients found eligible for tPA on MSU weeks compared to patients on SM weeks Ordinal (shift) analysis of mRS at 90 days, and Proportion of patients achieving 90 day mRS 0,1 vs 2-6 30% improvement from baseline to 24hr NIHSS Outcomes comparing all patients treated with tPA (whether or not adjudicated as tPA eligible) on MSU weeks compared to patients on SM weeks. Uw-mRS at 90 days Ordinal (shift) analysis of mRS at 90 days, and Proportion of patients achieving 90 day mRS 0,1 vs 2-630% Improvement from baseline to 24hr NIHSS Outcomes of those treated within 60 min LSN compared to those treated from 61 to 270 minutes Change in uw-mRS from baseline at 90 days Ordinal shift analysis of MRS at 90 days Proportion of patients achieving 90 day mRS 0,1 vs 2-6 30% improvement from baseline to 24hr NIHSS Outcomes all patients treated with IAT (separate analyses for those adjudicated as tPA eligible, all tPA treated, or all IAT with or without tPA) on MSU weeks compared to patients on SM weeks. Uw-mRS at 90 days Ordinal (shift) analysis of mRS at 90 days, and Proportion of patients achieving 90 day mRS 0,1 vs 2-6 30% improvement from baseline to 24hr NIHSS The time from LSN to tPA treatment on all patients treated within 4.5 hours of LSN on MSU weeks compared to similarly eligible patients on SM weeks Proportion of patients treated within 60 minutes of LSN on MSU weeks vs SM weeks. The time from LSN and from ED arrival to start of endovascular procedure on MSU vs SM weeks Proportion of all tPA-eligible patients having EVT on MSU vs SM weeks The median/mean time from LSN to tPA therapy decision on all patients considered for treatment within 4.5 hours of LSN on MSU weeks compared to SM weeks Time between 911 call and onset of etiology-specific BP management on MSU vs SM weeks. Safety Endpoints: Incidence of symptomatic intracranial hemorrhage (sICH) in enrolled tPA treated patients on MSU weeks compared to SM weeks. sICH was defined as any intracranial blood accumulation associated with a clinical deterioration of 4 points of the NIHSS for which the hemorrhage has been identified as the dominating cause of the neurologic deterioration) Mortality up to one year Incidence of stroke mimics and transient ischemic attacks (TIAs) in tPA treated patients on MSU weeks compared to SM weeks. Trial: Prospective cohort study with cluster randomized deployment weeks and blinded assessment of both trial entry and clinical outcomes. Cluster randomization can have both strengths and weaknesses just like any study design. For those less familiar with this methodology Taljaard and Grimshaw wrote a good article the topic in 2014. Authors’ Conclusions: "In patients with acute stroke who were eligible for t-PA, utility-weighted disability outcomes at 90 days were better with MSUs than with EMS." Quality Checklist for Observational Studies: Did the study address a clearly focused issue? Yes Did the authors use an appropriate method to answer their question? No Was the cohort recruited in an acceptable way? No Was the exposure accurately measured to minimize bias? Yes Was the outcome accurately measured to minimize bias? No Have the authors identified all-important confounding factors? No Was the follow up of subjects complete enough? Yes How precise are the results? Unsure Do you believe the results? No Can the results be applied to the local population? No Do the results of this study fit with other available evidence? Yes Did the study have no conflicts of interest. No Key Results: This prospective observational study screened 10,443 patients and enrolled 1,515 patients (58.5% MSU vs 41.5% SM). Fourteen percent overall were not eligible for tPA due to intracranial blood seen on CT scan. Two-thirds in both groups (1,047 total) were decided post-hoc to be eligible for tPA. Of the tPA eligible patients, 97% in the MSU group received tPA compared to 79.5% in the SM group. This results section was a real struggle. It was unclear which primary and secondary outcomes we should highlight in the review. Should it be those published in the NEJM or do we discuss the original ClinicalTrials.gov outcomes, the current ClinicalTrials.gov outcomes or pre-specified published protocol outcomes (Yamal et al Int J Stroke 2018)? At the end of the day, we decided to provide the published primary outcome, mention the secondary outcomes and give a few of the safety outcomes. Key Result: Patients treated with a mobile stroke unit had better 90 day outcomes. Primary Outcome (NEJM): Score on the uw-mRS at 90 days in patients who were adjudicated to be eligible to receive tPA on the basis of subsequent (post-hoc) blinded review 0.72 in the MSU group and 0.66 in the SM group Adjusted Odds Ratio (aOR) ≥0.91, 2.43 (95% CI, 1.75 to 3.36; P<0.001). Secondary Outcomes: Among the patients eligible for tPA, 55.0% in the MSU group and 44.4% in the SM group had a score of 0 or 1 on the mRS at 90 days. Among all enrolled patients, the mean score on the uw-mRS at discharge was 0.57 in the MSU group and 0.51 in the SM group (aOR for a score of ≥0.91, 1.82; 95% CI, 1.39 to 2.37; P<0.001). For more secondary outcomes see the NEJM publication. Safety Endpoints: sICH in ~2% of patients who received tPA in each group and none of the patients considered to be stroke mimics. Mortality at 90 days was 8.9% in the MSU group vs 11.9% SM group. 1. Houston, We Have a Problem: They changed their protocol at least four times over the course of the study. These changes were described in the PDF of their protocol. Sometimes the changes were minor and other times they were major. You can also see how their primary outcomes changed on ClinicalTrials.gov, in their pre-published protocol and through to their published manuscript in the NEJM. We were unable to find the any data in the manuscript or supplemental material on the other three “original” or “current” primary outcomes. This included the kappa value for the agreement between on scene vascular neurologist and remote vascular neurologist, cost effectiveness or the change in uw-mRS from baseline at 90 days. We have reached out to the lead author Dr. Grotta and will update the blog if this information becomes available. UPDATE: The Cohen kappa was published by Wu et al in 2017 with a value of 0.73 which is considered moderate inter rater reliability according to McHugh 2012.