The Skeptics Guide to Emergency Medicine

Date: December 21st, 2021 Guest Skeptic: Dr. Spencer Greaves is an Emergency Medicine resident at Florida Atlantic University. He received his Bachelors in Biomedical Engineering from Marquette University and his Masters in Public Health from Dartmouth College.  Spencer completed his medical doctorate at the Medical College of Wisconsin. He and his wife live in Boynton Beach, FL where they recently celebrated the birth of their first child. Disclaimer: "While I am proud to be attending this institution, my opinions expressed here are mine alone and do not represent my residency program, hospitals I work at, or any other affiliated organizations." Reference: Vallentin et al. Effect of Intravenous or Intraosseous Calcium vs Saline on Return of Spontaneous Circulation in Adults With Out-of-Hospital Cardiac Arrest - A Randomized Clinical Trial. JAMA 2021 This was an SGEM Journal Club and all the slides from the presentation can be downloaded using this LINK. As a reminder, here are the five rules for SGEM JC. Case: An EMS crew arrives at the home of a 68-year-old suffering from a witnessed out-of-hospital cardiac arrest (OHCA). They have a history of hypertension, elevated cholesterol, and smoked cigarettes for 50+ years. Bystander CPR is being performed. The monitor is hooked up. The paramedics performed high-quality CPR and follow their ACLS protocol. Intraosseous access is quickly obtained, and a dose of epinephrine is provided. CPR is continued while a supraglottic airway is placed successfully. The patient is transported to the emergency department with vital signs absent (VSA). Background: We have covered adult OHCA multiple times on the SGEM. This has included the following issues: Calcium has a theoretical benefit on patients with cardiac arrest as it has inotropic and vasopressor effects. Previous small, randomized control trials (RCTs) have shown no superiority to calcium for return of spontaneous circulation (ROSC). However, the point estimated did favor calcium. Clinical Question: Does administration of calcium during out-of-hospital cardiac arrest improve sustained return of spontaneous circulation? Reference: Vallentin et al. Effect of Intravenous or Intraosseous Calcium vs Saline on Return of Spontaneous Circulation in Adults With Out-of-Hospital Cardiac Arrest - A Randomized Clinical Trial. JAMA 2021 Population: Adults 18 years of age and older with OHCA in the central Denmark region from January 2020 to April 2021 who received at least one dose of epinephrine Exclusions: Traumatic cardiac arrest, known or strongly suspected pregnancy, prior enrollment in the trial, receipt of epinephrine outside the trial, or a clinical indication for calcium administration during the cardiac arrest. Intervention: Calcium chloride 5 mmol given IV or IO immediately after first dose of ACLS epinephrine up to two doses Comparison: Saline placebo given IV or IO immediately after first dose of ACLS epinephrine up to two doses Outcome: Primary Outcome: Sustained ROSC defined as no further need for chest compressions for at least 20 minutes Secondary Outcomes: Survival, favorable neurological outcome, and quality of life assessment at 30 and 90 days Trial: Double-blind, placebo-controlled, parallel group, superiority, randomized clinical trial Authors’ Conclusions: “Among adults with out-of-hospital cardiac arrest, treatment with intravenous or intraosseous calcium compared with saline did not significantly improve sustained return of spontaneous circulation. These results do not support the administration of calcium during out-of-hospital cardiac arrest in adults.” 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). Yes The patients in both groups were similar with respect to prognostic factors. Yes All participants (patients, clinicians, outcome assessors) were unaware of group allocation. Yes All groups were treated equally except for the intervention. Yes Follow-up was complete (i.e. at least 80% for both groups). Yes All patient-important outcomes were considered. Yes The treatment effect was large enough and precise enough to be clinically significant. No Financial Conflicts of Interest. Yes Results: There were 1,221 OHCAs during the trial period. They excluded 824 for a variety of reasons with the most common reason (69%) because they did not receive any epinephrine. The mean age was 68 years, 71% male, more than 80% arrested at home, 85% received bystander CPR and half were in asystole. Key Result: No statistical difference in ROSC Primary Outcome: ROSC 19% in the calcium group vs 27% in the saline group Risk ratio (RR) 0.72 (95% CI; 0.49 to 1.03) Risk Difference, −7.6% (95% CI; −16% to 0.8%); P = 0.09) Secondary Outcomes:  No statistically significant differences in 30-day survival, 30-day survival with a favorable neurological outcome or 90-day survival Survival at 90-days with favorable neurological outcome was statistical better in the placebo group. Quality of life assessment assessed by the patient was not statistically different at 30-days but was at 90-days favoring calcium 1. Outcomes: It would be great if there was consistency in reporting outcomes. The trial was registered with ClinicalTrials.gov. Primary outcome was the same in the registration, protocol, and published manuscript. However, there was no quality-of-life assessment registered as an outcome, it was called a tertiary outcome in the protocol, categorized as a secondary outcome on the Table 2 of the manuscript and a tertiary outcome in the text of the manuscript. Same thing for the 90-day outcome which was not mentioned in the trial registry, was considered a tertiary outcome in the protocol but elevated to a secondary outcome in Table 2 and tertiary outcome in the body of the text. 2. External Validity: This trial was conducted in Denmark. They have a two-tiered EMS service that has an ambulance and a mobile emergency care unit with a physician. This is different from most places in north America that do not have physicians in the pre-hospital setting. In addition, the latest statistics from the American Heart Association on cardiac arrests in the USA are different than the cohort included in this trial. The biggest difference was bystander CPR was 39% in the USA vs 85% in this Danish trial. These and other differences could limit the external validity to your own community. 3. Dose of Calcium: It is possible but not likely that a different dose of calcium may have made a difference. Proving a negative is harder than proving a positive. We start with a null hypothesis of no superiority. In this case, the null hypothesis is that calcium is not superior to placebo. The results did not support the alternative hypothesis of superiority, so we accept the null hypothesis. It would be a separate claim to say that calcium does not work for OHCAs. The more accurate statement would be there is no high-quality evidence to support the routine use of calcium in OHCAs. 4. OHCA: This data directly applies to OHCAs and not necessarily IHCA. There are longer times to drug administration in the pre-hospital setting. Time to drug administration was a median of 17 minutes. It could be hypothesized that early time to treatment could provide a patient-oriented outcome of benefit. However, that would need to be demonstrated. 5. Stopping Early: We have discussed the problem of stopping trials early before on the SGEM. It can introduce bias and increase uncertainty of the results. Stopping trials early over-estimates the effect size if there is a regression to the mean. Also, including trials that are stopped early can introduce bias into SRMA making them more difficult to interpret (Bassler et al JAMA 2010). Comment on Authors’ Conclusion Compared to SGEM Conclusion: We agree with the authors’ conclusions. SGEM Bottom Line: The routine use of calcium in an OHCA is not supported by the available evidence. Case Resolution: Three rounds of epinephrine are eventually provided without ever achieving ROSC. ECG shows no electrical activity, pupils are fixed and dilated, and POCUS shows no cardiac activity. The patient is pronounced deceased in the ED. Dr. Spencer Greaves Clinical Application: We have not and will continue to not routinely give calcium to adult patients with OHCAs. What Do I Tell the Patient?  You tell the patients family that they had a cardiac arrest. The paramedics did great CPR, put in an airway to help breathing and gave epinephrine to try and restart the heart. Despite everyone’s efforts we were not able to get their heart going again and they have died. Keener Kontest: Last weeks’ winner was Josh McGough at third year medical student from Stony Brook University. He knew Dr. Pam Bensen was the first EM resident in North America in 1971. 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. Other FOAMed: First10EM: Calcium for OHCA - The COCA Trial The Bottom Line: COCA Remember to be skeptical of anything you learn, even if you heard it on the Skeptics’ Guide to Emergency Medicine.

Date: December 13th, 2021 Reference: Lee et al. Addressing gender inequities: Creation of a multi-institutional consortium of women physicians in academic emergency medicine. AEM December 2021 Guest Skeptic: Dr. Justin Morgenstern is an emergency physician and the creator of the #FOAMed project called First10EM.com Case: At the completion of her 1-month elective in your rural emergency department (ED), you are discussing career plans with a medical student. She says that she is very interested in emergency medicine, but she isn’t sure if it is the right choice for her. She has worked in five EDs so far, and a man has filled almost every leadership position. She also just got back from an emergency medicine conference, and more than 90% of the speakers were white males. She loves the clinical work in emergency medicine, but she is worried that these apparent gender inequities will limit her career opportunities. Background: Gender equity is something we have spoken about often on the SGEM. Some listeners are happy we cover this topic while others have expressed concern. We recognize this can be an emotional issue. Our position is gender inequity exists in the house of medicine and it should be an issue everyone is interested in addressing. Here are some of the previous SGEM episodes that discussed gender equity: SGEM Xtra: From EBM to FBM – Gender Equity in the House of Medicine SGEM Xtra: Unbreak My Heart – Women and Cardiovascular Disease SGEM#248: She Works Hard for the Money – Time’s Up in Healthcare SGEM Xtra: Money, Money, Money It’s A Rich Man’s World – In the House of Medicine SGEM Xtra: I’m in a FIX State of Mind It is hard to believe some people deny the significant gender inequities that currently exist in medicine. Women are under-represented in leadership positions [1-3]. Women are less likely to be given senior academic promotions [4]. There are fewer women in editor positions in our academic journals [5]. Women receive less grant funding [6-7]. Women are paid less than men, even after accounting for potential confounders [2, 8-10]. Yet a recent twitter poll had more than 1/3 of respondents saying they did not think a physician gender pay gap existed in their emergency department. It is hard to move forward and address a problem when a significant portion of physicians do not even recognize that there is a problem. The literature describes many factors that contribute to gender inequity. Institutional policies related to promotion or advancement may inherently disadvantage women and are likely exacerbated by implicit bias and stereotyping. There are an insufficient number of women in current leadership positions, resulting in fewer mentors and role models for women earlier in their career. Policies around parental leave, emergency child-care, and breast-feeding support affect women disproportionately. Unfortunately, sexual harassment is also still widely documented in emergency medicine and has a major impact on career advancement and attrition [11-13]. The reasons for the gender gap are complex, and likely not completely understood. Existing gender balance within specialties, among other aspects of the "hidden curriculum", likely influence career decisions, with women trainees more likely to enter lower paying specialties. Current leadership positions are dominated by males, who may consciously or not be more supportive of other males for future promotions. Furthermore, there are numerous gender differences, both internal and external, that influence salary expectations and negotiations [14]. Female physicians are more likely to have female patients, and medical pay structures are often inherently biased. For example, in Ontario, where we both work, a biopsy of the penis pays almost 50% more than a biopsy of the vulva. Similarly, incision and drainage of a scrotal abscess pays twice as much as incision and drainage of a vulvar abscess [14]. There is data that suggests that practice patterns vary between women and men. Women in primary care are more likely to address multiple issues during a single appointment. They are more likely to provide emotional support and address psychosocial issues, and less likely to perform procedures. Although these are features most of us would want in a physician, unfortunately they result in lower remuneration in more medical payment models [14]. And of course, all of this occurs in the larger societal context in which women perform far more unpaid labour outside of medicine, resulting in much larger overall workloads, most of which is often overlooked. For a wonderful book on the topic, considering reading Invisible Women by Caroline Criado Perez. Too often, women are blamed for the gender pay gap. It is true that women, on average, work fewer hours, and are more likely to work part time. However, this difference in work is not enough alone to explain the pay gap. For example, one study found that women earned 36% less than their male colleagues, despite only working three hours less per week [14]. It is also not true that women earn less because they are less efficient. Data from Ontario revealed that female surgeons earn 24% less per hour spent operating, despite completing procedures in the same amount of time as men. The difference seems to derive from women performing less lucrative procedures [15]. We clearly have a problem in medicine. There is no denying the current state of gender inequity. Solutions, while in some cases glaringly obvious, are probably rather complex. Solutions are unlikely to be "one size fits all". The needs and desires of individual women will obviously be far more varied and far more complex than the "average woman", and we should always be wary of unintended consequences when implementing social policy. However, those are not excuses. The data speaks for itself. More action is needed, and it is needed now. The first step is to acknowledge the current problem widely and openly. This would be aided with transparent reporting on physicians’ payment, stratified by gender. It is worth noting that gender is not the only source of inequality in medicine, and this same data should be used to examine other factors such as race or disability. We need better training about bias in medicine, especially for those in leadership positions. We need to consider more egalitarian interview processes, where leadership are blinded to characteristics like gender or race. We need to consider the impacts of systemic discrimination and recognize that simply being fair in a single hiring decision is unlikely to be good enough, as it doesn’t account for the incredibly different paths that candidates took to reach the same point. We need to fix the biased billing codes and referral patterns. We need better parental benefits, and systems to ensure career advancement can continue even when one is taking time to raise children. So clearly there is a lot that needs to be done on this topic. But neither of us are experts on the topic, so I think we had better get into the meat of the episode and start talking to our guest who is an expert. Clinical Question: What can be done about gender inequity in emergency medicine? Reference: Lee et al. Addressing gender inequities: Creation of a multi-institutional consortium of women physicians in academic emergency medicine. AEM December 2021 There is no real PICO statement for this publication. We also normally do a quality check list to probe the publication for its validity. No such check list exists for this type of study seems to exist. it is still worth thinking critically about their methodology to consider the intrinsic and extrinsic validity of their discussion. When considering whether to develop a similar program, there are three major questions to consider: Does this program accomplish its intended goals? Will the results here extrapolate to other settings? What are the costs and alternative options? Methods: This article describes the creation of a multi-institutional consortium of women faculty in emergency medicine to promote career advancement and address issues of gender inequity. The consortium brought together female faculty from four hospitals associated with Harvard Medical School. Dr. Lois Lee This is an SGEMHOP episode which means we have the lead author on the show, and we can hear about this program directly from the author. Dr. Lois Lee is a pediatric emergency medicine physician at Boston Children’s Hospital and an Associate Professor of Pediatrics and Emergency Medicine at Harvard Medical School. Neither Ken nor I have experienced these issues firsthand. Is there anything else you think is important to add to the background material we provided? Thank you for continuing to highlight gender inequities in medicine and also for working to figure out some solutions to this complex problem. Although there are some things as an individual that can be done, many—if not most—of the solutions really need to be at the departmental leadership, institutional, and systemic level. What is the history behind this project and why did you think there was a need for this program? Under our medical school there are five different institutions with separate emergency departments—four adult or general EDs and one pediatric specific. And it turns out over the last 5-10 years four of them had either formally or informally developed women faculty groups for career support. Then in 2018 several women from the different institutions came together and they formed the Harvard Medical School Women in EM Consortium.  Although we all have academic affiliations under the same medical school, we otherwise had no formal connections through our EDs. Can you briefly describe the consortium and curriculum you developed? Site champions—at least two from each site

Date: December 10th, 2021 Guest Skeptic: Dr. Carly Eastin is an Associate Professor, Division of Research and Evidence Based Medicine, Department of Emergency Medicine, University of Arkansas for Medical Sciences. She is also the Chair of the SAEM Evidence Based Healthcare and Implementation (EBHI) Interest Group. Carly was a guest skeptic on the SGEM two years ago. That was in the BC Times- (Before Covid). We had the pleasure of recording a live episode of the SGEM at the University of Arkansas.  Back in 2019 we were talking about Vitamin C for sepsis (SGEM#268). SGEM Bottom Line: “There is not enough evidence to support the routine use of vitamin C in critically ill patients.” Not much has changed over the last two years. There have been at least two randomized control trials published that do not support the use of Vitamin C in sepsis. Fujii et al (VITAMINS RCT) JAMA 2020: n=216 patients with septic shock. No statistical difference in their primary outcome for duration of time alive and free of vasopressor administration up to day 7 or the secondary outcome of 90-day mortality. Moskowits et al (ACTS RCT) JAMA 2020: n=205 patients with septic shock. no statistical difference in primary outcome of SOFA scores at 72 hours or the secondary outcome of 30-day mortality. It was Dr. Paul Marik who has been a big advocate for Vitamin C sepsis. We did an SGEM episode on his before-after study (SGEM#174: Don’t Believe the Hype) with a dozen skeptics expressing their concern the results were too good to be true. Dr. Marik has also been promoting the use of Vitamin C for COVID19. However, there is insufficient evidence to support the routine use of Vitamin C in the treatment of critically ill or non-critically ill COVID19 patients (NIH COVID19 Treatment Guidelines and Thomas et al JAMA 2021). There is also no high-quality evidence that Vitamin C can prevent COVID19. There is a Phase II interventional randomized placebo-controlled trial testing whether treatment with Vitamin C can prevent symptoms of COVID19 (ClinicalTrials.gov). This SGEM Xtra episode is not to talk about Vitamin C, COVID19 or even do a structured critical appraisal of a recent publication. This is an SGEM Xtra episode to pay tribute to a friend and champion of the EBM community, Dr. Rakesh Engineer. Dr. Rakesh Engineer Rakesh died suddenly in 2019 and the Society of Academic Emergency Medicine (SAEM) reflected upon how best to honour him. SAEM decided to name an award after Rakesh, focusing on his passion for implementation science. Dr. Chris Carpenter knew Rakesh well and was asked to give a brief introduction to those who did not know him. You can listen to his introduction at this LINK. Chris Carpenter: "[Rakesh] was a devoted husband and dedicated father to three sons.  He was born in Cleveland, Ohio and attended Ohio State University where he earned both his Bachelors and MD. After his internship at Barnes Jewish Hospital at Washington University St. Louis. He trained in Emergency Medicine at Spectrum Health in Grand Rapid Michigan. After that, he joined the Cleveland Clinic to be with his family, to educate the next generation of emergency physicians and launch his own clinical research career. Rakesh's vision epitomized implementation science, in which knowing is not enough: we must apply. As an emergency medicine clnical researcher, Rakesh thrived at the interface between published evidence and pragmatic application at the bedside.  He was a friend and I miss him dearly." Carly: "I did not have the privilege of knowing Rakesh personally very well, but was following him because I was a member of the SAEM Evidence-Based Healthcare and Implementation group when he was active and I was still trying to find my way in the EBM world. He was such a good speaker and was really funny. I also remember that it was Rakesh that gave me my first real understanding of implementation science, and I’ve been hooked ever since." Ken: "I remember running into Rakesh at an SAEM meeting in Indiana. To be more accurate, he almost ran into Chris and me outside the hotel. We were heading out to get something to eat or something and Rakesh pulled up in a big sedan. I want to remember that it was a convertible. We pretended to be almost run over by him. Rakesh quickly jumped out of the car, usual big smile on his face and we had a quick nerdy chat. That is the last memory I have of Rakesh. Chris sent me a goofy picture of Rakesh". Carly: "It’s hard to look at that picture without smiling. I can’t tell you how many stories just like yours I’ve heard about his laughter and fun personality. He was clearly highly respected and loved by many." Rakesh published a lot of peer reviewed articles during his career. This included biomarkers, gun safety and diagnostic imaging studies. Rakesh had just been elected Chair of the Evidence Based Healthcare and Implementation (EBHI) Interest Group for SAEM. He had been an active member of the interest group for many years. The mission of the EBHI Interest Group is the applied concept of merging healthcare professional expertise, research, and patient priorities and circumstances through a defined process of finding, appraising, and employing clinical science at the bedside. This mission aligns with the three pillars of EBM. There is the literature which informs our care, our clinical judgment and the patients’ preferences and values. This is what Dr. Davide Sackett said EBM is and what it isn't (BMJ 1996). Rakesh believed in integrating these three important aspects of EBM into practice. The EBHI Interest Group provides a network of expertise from the emergency medicine resident to the seasoned investigator, which serves as a forum for research, education, and clinical practice. Objectives of the EBHI Interest Group Engage the membership regularly and broaden the active core group through mentorship and collaboration for junior members. Increase use of social media and internet platforms to improve the visibility of the interest group and its members as well as to disseminate best practices. Continue focus on inter-institutional collaboration on journal clubs and scholarly projects, including original research or systematic reviews. Sponsor high-quality didactic submissions to the SAEM annual meeting. The Rakesh Engineer Award The Dr. Rakesh Engineer award will be given to an outstanding presentation related to Implementation Science at the SAEM annual meeting. Quality improvement projects can be considered if the implementation methods, effectiveness, and outcomes are reported. De-implementation studies are also eligible. More information on the Rakesh Engineer Award can be found at this LINK. If you are interested in nominating someone or yourself for this award you can click on this LINK. You can also click on the QR Code. The award will be given out for the first time at the conclusion of SAEM 2022 which will be held in New Orleans, May 10-13. The award committee will consider abstracts accepted to SAEM’s annual meeting and grade them based a list of criteria related to knowledge translation. The top three abstracts will be judged live at the meeting,  a winner chosen and the Rakesh Engineer Award presented. Implementation Science The journal Implementation Science defines this as “the scientific study of methods to promote the uptake of research findings into routine healthcare in clinical, organizational, and policy contexts.” In other words, implementation science programs use the available evidence to achieve measurable improvements in the quality of clinical care. It is easy to think that once something is determined to be the standard of care, people will just start doing it. But there are a lot of factors that influence the success of implementing a new practice to improve care or removing an old, outdated practice that might be harmful. Implementation science methods allow you to move through this process in a way that will be effective, sustainable over time, and lead to your desired outcomes. For those who would like to learn more, we suggest you read the manuscript titled, “Fostering implementation of health services research findings into practice: a consolidated framework for advancing implementation science,” by Laura Damschroder and her colleagues published in Implementation Science 2009. You can also find a wealth of information at the NIH’s Implementation Science website. For those in academic or university settings, you may have an implementation science group locally who can provide additional resources. We would suggest exploring your institution’s website for implementation science experts. The SGEM will be back next episode doing a structured critical appraisal of a recent publication. Trying to cut the KT window down from over ten years to less than one year using the power of social media. So, patients get the best care, based on the best evidence. Remember to be skeptical of anything you learn, even if you heard it on the Skeptics’ Guide to Emergency Medicine.

Date: November 16th, 2021 Reference:  Hammouda et al. Moving the Needle on Fall Prevention: A Geriatric Emergency Care Applied Research (GEAR) Network Scoping Review and Consensus Statement. AEM November 2021 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: Mid-shift, you realise that the next patient you are about to see is the third in a row aged over 70 who has fallen at home, and that this is her third attendance for a fall in the last two months. You wonder if any emergency department (ED)-based interventions would help her and people like her be safe. Background: We looked at geriatric falls on an SGEM Xtra in 2015. Back then we found that at one academic site older adults attending ED with falls didn't receive guideline-based assessment, risk stratification or management. Dr. Chris Carpenter In 2014 the SGEM looked at a systematic review by Dr. Chris Carpenter, which concluded that there wasn't a good tool to help us predict which ED patients are at risk of recurrent falls (SGEM #89). Close to three million adults aged 65 and over visit American EDs annually after a fall [1]. Falling is the most common cause of traumatic injury resulting in older adults presenting to the ED [2]. Approximately 20% of falls result in injuries, and falls are the leading cause of traumatic mortality in this age group [3-5]. The SAEM Geriatric Emergency Medicine Task Force recognized fall prevention as a priority over 10 years ago. There is the Geriatric Emergency care Applied Research (GEAR) network, which is trying to improve the emergency care of older adults and those with dementia and other cognitive impairments. GEAR looks to identify research gaps in geriatric emergency care support research and evaluation of these areas. GEAR 2.0 has recently been launched with funding opportunity in conjunction with EMF. There are three other GEAR 1.0 manuscripts which have been published: Delirium Prevention, Detection, and Treatment in Emergency Medicine Settings AEM 2020 Care Transitions and Social Needs AEM 2021 Research Priorities for Elder Abuse Screening and Intervention J Elder Abuse Negl 2021 Clinical Question: In older patients presenting to ED with falls do risk stratification or fall prevention interventions influence patient-centered or operational outcomes? Reference:  Hammouda et al. Moving the Needle on Fall Prevention: A Geriatric Emergency Care Applied Research (GEAR) Network Scoping Review and Consensus Statement. AEM November 2021 This publication presents two related but different scoping reviews so there are  two PICOs. PICO #1 Population: Systematic search that found 32 studies of fall prevention interventions for patients aged 60 or over who presented to ED with a fall. Exclusions: Abstracts repeating data already included in full, not original research. Intervention: Fall prevention interventions including multifactorial risk reduction, medication review, exercise training, models of care like Hospital-at-Home. Comparison: Standard of Care. Outcomes: Quality of care ED metrics, ED operational outcomes like length of stay, patient-centered outcomes like ED returns, further falls, fear of falling, functional decline, institutionalization. PICO #2 Population: Systematic search that found 17 studies of risk stratification and falls care plans in patients aged 60 or over in ED or pre-ED settings. Exclusions: As review 1. Intervention: Risk stratification and falls care plan. Comparison: No risk stratification and falls care plan. Outcomes: ED referral (from pre-ED setting), quality of care ED metrics, ED operational outcomes, patient-centered outcomes. This is an SGEMHOP episode which means we have the honour of having the lead author, Dr. Elizabeth (Liz) Goldberg, on the show. She is an Associate Professor of Emergency Medicine and Health Services, Policy and Practice at Brown University. Her specific areas of interest include improving care for older adults and public health interventions to enhance longevity and healthy aging. Dr. Elizabeth Goldberg Authors’ Conclusions: “Harmonizing definitions, research methods, and outcomes is needed for direct comparison of studies. The need to identify ED-appropriate fall risk assessment tools and role of emergency medical services (EMS) personnel persists. Multifactorial interventions, especially involving exercise, are more efficacious in reducing recurrent falls, but more studies are needed to compare appropriate bundle combinations. GEAR prioritizes five research priorities: (1) EMS role in improving fall-related outcomes, (2) identifying optimal ED fall assessment tools, (3) clarifying patient-prioritized fall interventions and outcomes, (4) standardizing uniform fall ascertainment and measured outcomes, and (5) exploring ideal intervention components.” Quality Checklist for Scoping Systematic Reviews: Did they provide a structured summary that includes (as applicable): background, objectives, eligibility criteria, sources of evidence, charting methods, results, and conclusions that relate to the review questions and objectives? Yes Was a rationale for the review in the context of what is already known provided? Yes Was there an explicit statement of the questions and objectives being addressed with reference to their key elements? Yes Was their protocol pre-published and the study registered? No Characteristics of the sources of evidence used as eligibility criteria was specified? Yes All information sources in the search were described? Yes The presented the full electronic search strategy for at least one database, including any limits used, such that it could be repeated. Yes The process for selecting sources of evidence (i.e., screening and eligibility) was included in the scoping review. Yes Methods of charting data from the included sources of evidence was described. Yes There was a list of all variables and definitions for which data were sought and any assumptions and simplifications made. Yes If done, a rationale for conducting a critical appraisal of included sources of evidence; describe the methods used and how this information was used in any data synthesis (if appropriate) was provided. No The methods of handling and summarizing the data that were charted was described. Yes Give numbers of sources of evidence screened, assessed for eligibility, and included in the review, with reasons for exclusions at each stage, ideally using a flow diagram. Yes For each source of evidence, present characteristics for which data were charted and provide the citations. Yes If done, present data on critical appraisal of included sources of evidence (see item 12). No For each included source of evidence, present the relevant data that were charted that relate to the review questions and objectives. Yes The authors summarized and/or present the charting results as they relate to the review questions and objectives. Yes The authors summarized the main results (including an overview of concepts, themes, and types of evidence available), link to the review questions and objectives, and consider the relevance to key groups. Yes They discuseds the limitations of the scoping review process. Yes The provided a general interpretation of the results with respect to the review questions and objectives, as well as potential implications and/or next steps. Yes The described sources of funding for the included sources of evidence, as well as sources of funding for the scoping review. Describe the role of the funders of the scoping review. Yes Results: 32 studies were included (3 meta-analyses and 23 RCTs) with a total of 571,071 patients to try to answer the first PICO question about falls prevention. Studies were from 11 countries, 1999-2019, with follow-up from 1 to 18 months. Interventions included falls risk assessment, physical rehabilitation sessions, preventive education, educational guidelines, follow-up with NP or PT, and alert devices. Most used recurrent falls as the outcome although anxiety over falls, functional ability and QALYs also featured. 17 studies were included (4 meta-analyses and 8 RCTs) with a total of at least 17,232 patients to address the second PICO question about risk stratification. Studies were from 9 countries, 2011-18, with follow-up from 6 to 12 months. 11 screening instruments were identified with interventions including educational, physical therapy, follow-up calls, discharge planning and home visits. Most used recurrent falls as the outcome. Key Result: The GEAR-Falls group identified five research priorities. EMS role in improving fall-related outcomes Identifying optimal ED fall assessment tools Clarifying patient-prioritized fall interventions and outcomes Standardizing uniform fall ascertainment and measured outcomes Exploring ideal intervention components We asked Liz five nerdy questions about her study.  Listen to the SGEM podcast to hear her responses. 1. Question Selection: Your group original had three PICO questions (the third was about specific risk factors for falls e.g. polypharmacy). How and why did you decide to address the two that you did? 2. Consensus Conference: You held a consensus conference of your multidisciplinary group with the initial findings of the scoping review to generate and vote on research priorities.

Date: November 10th, 2021 Reference: Andersen, et al: Effect of Vasopressin and Methylprednisolone vs Placebo on Return of Spontaneous Circulation in Patients With In-Hospital Cardiac Arrest. JAMA Sept 2021. Guest Skeptic: Dr. Neil Dasgupta is an emergency physician and ED intensivist from Long Island, NY, and currently an assistant clinical professor and Director of Emergency Critical Care at Nassau University Medical Center. Case: A code blue is called for a 71-year-old male in-patient that is boarding in the emergency department (ED). He had been admitted the night before for a new diagnosis of rapid atrial fibrillation. He has a history of hypertension, dyslipidemia, and type-2 diabetes. His medications include a beta-blocker, statin, angiotensin converting enzyme inhibitor (ACE-I), metformin, ASA and direct oral anticoagulant (DOAC). You arrive and see that the Advanced Cardiac Life Support (ACLS) algorithm is being followed for adult cardiac arrest patients with pulseless electrical activity (PEA). Cardiopulmonary resuscitation (CPR) is in progress. The monitor shows a non-shockable rhythm. Epinephrine is provided and you quickly place an advanced airway. A second dose of epinephrine is given, and you start to think about reversible causes and your next steps for in-hospital cardiac arrests (IHCA). SGEM#50: Under Pressure Background: We have looked an IHCA a couple of times on the SGEM. The first time we looked at this issue on (SGEM#50). This was also the first SGEM JC done where Dr. William Osler started the Journal Club initiative at McGill University. We reviewed a randomized, double-blind, placebo-controlled, parallel-group trial done in three Greek tertiary hospitals. This trial (n=268) reported increased return of spontaneous circulation (ROSC) and increased survival to hospital discharge with good neurologic function with a vasopressin, steroids, and epinephrine (VSE) protocol compared to epinephrine alone. We felt this was interesting but would need to be validated/replicated before changing our IHCA protocols. Corticosteroids have been suggested as a possible therapy in these cardiac arrest situations. A SRMA published in 2020 on the use of steroids after cardiac arrest reported an increase in ROSC and survival to discharge but was limited by the availability of adequately powered high-quality RCTs (Liu et al JIMR 2020). We covered another SRMA that was published in 2021 looking at the same issue of whether the use of corticosteroids impact neurologic outcomes and mortality in patients with a cardiac arrest (SGEM#329)? These authors reported a statistical increase in good neurologic outcome and survival to hospital discharge with steroids but not survival at one year or longer. This study provided weak evidence in support of using corticosteroids for IHCA as part of a VSE protocol. Answering clinical questions about cardiac arrest with clinical trials has always been fraught with difficulty. However, cardiac arrest is something we regularly treat in the emergency department, and we need more high-quality data to inform our care. Vasopressin had been included as a part of the American Heart Association (AHA) ACLS protocol for quite a while but was removed in favor of a vasopressor monotherapy strategy with epinephrine.  The tide now is shifting in resuscitation research to shift our focus from obtaining ROSC to measuring functionality and good neurologic outcomes.  In the context of questioning epinephrine’s role in ACLS after Paramedic2, we look at using the VSE protocol in cardiac arrest. Clinical Question: Does adding a combination of vasopressin and methylprednisolone increase the chance of achieving ROSC in cardiac arrest? Reference: Andersen, et al: Effect of Vasopressin and Methylprednisolone vs Placebo on Return of Spontaneous Circulation in Patients With In-Hospital Cardiac Arrest. JAMA Sept 2021. Population: Adult patients 18 years of age and older with an in-hospital cardiac arrest. Excluded: Out-of-hospital cardiac arrest (OHCA), valid do-not-resuscitate order, invasive mechanical circulatory support and known or suspected pregnancy at the time of the cardiac arrest. Intervention: Vasopressin 20 IU and methylprednisolone 40 mg given as soon as possible after first dose of epinephrine, followed by vasopressin 20 IU after each epinephrine up to four doses. Comparison: Placebo of normal saline Outcome: Primary Outcome: ROSC defined as no further need of chest compressions for at least 20 minutes Secondary Outcomes: 30-day survival and 30-day survival with favorable neurologic outcome (defined as a Cerebral Performance Category of 1 or 2) Trial Design: Multicenter, single nation, multicenter, randomized, placebo-controlled, parallel group, double-blind, superiority trial Authors’ Conclusions: “Among patients with in-hospital cardiac arrest, administration of vasopressin and methylprednisolone, compared with placebo, significantly increased the likelihood of return of spontaneous circulation. However, there is uncertainty whether this treatment results in benefit or harm for long-term survival.” 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). Yes The patients in both groups were similar with respect to prognostic factors. Yes All participants (patients, clinicians, outcome assessors) were unaware of group allocation. Yes All groups were treated equally except for the intervention. Yes Follow-up was complete (i.e. at least 80% for both groups). Yes All patient-important outcomes were considered. Yes The treatment effect was large enough and precise enough to be clinically significant. No Was the study without any financial conflicts of interest. No Results: They recruited and analyzed 501 patients with a mean age of 71 years, 64% were male and 2/3 were on a medical ward. Key Result: More ROSC was achieved with VSE compared to epinephrine alone, but this did not translate into better long term-survival or with favorable neurologic outcome. Primary Outcome: ROSC 42% intervention group vs 33% in control group. Absolute difference of 9.6% (95% CI, 1.1% to 18.0%). Risk ratio of 1.30 (95% CI, 1.03 to 1.63) p=0.03. Secondary Outcomes:No statistical difference between groups for both key secondary outcomes. Survival at 30 days: 9.7% vs 12%. Absolute difference −2.0% (95% CI, −7.5% to 3.5%) with risk ratio, 0.83 (95% CI, 0.50-1.37); P = 0.48). A favorable neurologic outcome at 30 days: 7.6% vs 7.6% with a risk ratio, 1.00 (95% CI, 0.55 to 1.83); P >0.99 1. ED Patients: These are not ED patients, but they are often emergency physicians’ responsibility. In many hospitals the only in-house physician at certain times is in the ED and will be responding to Code Blues. We need to be cautious not to over-interpret the data and directly apply it to patients who arrive in the ED and have an arrest. This data can help inform and guide our care, but it should not dictate our care. These might be more like our patients than we think. Digging into the demographics of the included patients they seem like a surprisingly healthy cohort for IHCA. RRT (11% vs 8%), mechanical ventilation (8% vs 11%) and on pressor support (5% vs 9). Only 10% vs 7% of patients in the ICU, and 8% vs 14% in the ED.  This may actually help us to better extract its applicability to the ED population and what gets brought in via EMS.  It also may be a result of the inclusion/exclusion criteria set up. 2. Enrollment: This was surprisingly low. From 2,362 screened patients to 512 randomized, and 501 ultimately included for analysis. There were a lot of exclusions despite a liberal inclusion criteria and limited exclusion criteria. Large numbers of patients were excluded for not receiving epinephrine, ROSC prior to getting the drug, and a whole series of clinical team dependent factors (forgot about the study/early termination/physician preference/logistics). While the authors claim this did not have an impact on the outcome, it’s hard to imagine it didn’t have any impact on the included cohort or introduced some selection bias. 3. Patient-Oriented Outcome: The endpoint of ROSC is patient-centered, and a prerequisite for a good neurologic function. However, it is not a net benefit to save more people who have a poor quality of life. This is what was demonstrated in the PARAMEDIC2 trial (SGEM#238). There was an increase in survivors with epinephrine for OHCA. Unfortunately, the increase was mainly for patients having severe neurologic impairment was more common among survivors in the epinephrine groups compared to the placebo group (31.0% vs. 17.8%). 4. Cerebral Performance Category (CPC) Score: Speaking of POO. The outcome measure for favorable neurologic outcome was the CPC score. Legend of EM, Dr. Ian Stiell from Ottawa published some data from the classic OPALS trail. They said that while the CPC can be an important outcome tool, it should not be considered a substitute for the Health Utilities Index (Annals EM 2009). The inter and intra-rater reliability of the CPC score has also been questioned. A cohort study of patients with OHCA reported poor kappa values for classifying favorable vs unfavorable neurologic status at hospital discharge (Ajam et al Scan J Trauma Resusc Emerg Med 2001) Another study looked about both OHCA and IHCA patients and the interrater reliability of the CPC score. They too found poor kappa values suggesting substantial variability in determining neurologic outcomes (Grossestreuer et al Resuscitation 2016).

Date: November 1st, 2021 Reference: Katsanos et al. Utility of Intravenous Alteplase Prior to Endovascular Stroke Treatment: A Systematic Review and Meta-analysis of RCTs. Neurology 2021 Guest Skeptic: Dr. Michal Krawczyk is in his fifth year of neurology residency at Western University in London, Ontario, Canada. He is interested in acute neurological illness, including cerebrovascular disease and epilepsy. Next year he will be beginning a Neurohospitalist fellowship at the University of Texas at Houston. Case: A 70-year-old male with a past medical history of hypertension and peripheral artery disease, last seen normal 1.5 hours ago, presenting with acute onset of aphasia and right sided face and arm weakness. He has a National Institute of Health Stroke Scale (NIHSS) score of 7. At 1am a CT angiogram is obtained that demonstrated a left M2 occlusion, and an Alberta Stroke Program Early CT Score (ASPECTS) of 10. Given the recent publications of trials assessing if mechanical thrombectomy alone is non-inferior to a bridging approach with tPA in addition to mechanical thrombectomy, you wonder whether these trials apply to your patient and what is the best course of action. Background: There are two treatments for acute ischemic stroke, systemic tPA and mechanical thrombectomy (MT). We have covered some studies looking at both treatment modalities on the SGEM. SGEM#29: Stroke Me, Stroke Me SGEM#70: The Secret of NINDS (Thrombolysis for Acute Stroke) SGEM#85: Won’t Get Fooled Again (tPA for AIS) SGEM#137: A Foggy Day – Endovascular Treatment for Acute Ischemic Stroke SGEM#292: With or Without You – Endovascular Treatment with or without tPA for Large Vessel Occlusions SGEM#297: tPA Advocates Be Like – Never Gonna Give You Up SGEM#333: Do you Gotta Be Starting Something – Like tPA before EVT? Mechanical thrombectomy is indicated only for patients with large vessel occlusions (LVOs) on imaging. There were a few earlier studies on MT that failed to demonstrate superiority, but it was the study MR CLEAN published in NEJM 2015 that really changed practice. It was a multicenter, randomized, unblinded trial treating 500 patients with an anterior circulation LVO within six hours of symptom onset. The primary outcome was mRS 0-2 at 90 days and it showed an absolute difference of 14% favoring MT. This gives a NNT of 7. Six RCTs have been published since MR CLEAN.  All supported MT and all were stopped early (SWIFT PRIME, EXTEND-IA, REVASCAT, ESCAPE, DAWN, and DEFUSE). For patients with LVOs it is unclear whether there is any additional benefit with administering tPA before thrombectomy, also known as a bridging approach, in contrast to skipping tPA and directly proceeding with MT. There are several theoretical advantages of a bridging approach. These potential advantages include thrombus debulking allowing easier clot retrieval, distal emboli lysis, recanalization prior to MT, and it may be beneficial in cases of unsuccessful MT. Conversely, a direct to MT approach may lead to fewer intracerebral hemorrhages (ICH) and quicker initiation of endovascular thrombectomy. Recently, three randomized control non-inferior trials on this topic have been published, two from China (DIRECT-MT, and DEVT) and one from Japan (SKIP). Two trials demonstrated non-inferiority while one trial failed to show that direct MT was non-inferior. Clinical Question: What is the best strategy for treating patients with an acute large vessel occlusion stroke, direct to mechanical thrombectomy or a bridging approach with tPa followed by mechanical thrombectomy? Reference: Katsanos et al. Utility of Intravenous Alteplase Prior to Endovascular Stroke Treatment: A Systematic Review and Meta-analysis of RCTs. Neurology 2021 Population: Randomized controlled trials of patients with acute large vessel occlusion stroke qualifying for MT Exclusions: Observational studies and non-randomized trials Intervention: MT alone Comparison: MT bridged with tPA Outcome: Primary Outcome: mRS score 0-2 at three months Secondary Outcomes: mRS 0-1 and ordinal shift at three months, successful recanalization before MT, successful recanalization after MT, randomization to puncture time, symptomatic intracranial hemorrhage (sICH), any ICH and all-cause mortality Authors’ Conclusions: “We detected no differences in functional outcomes of IV thrombolysis–eligible patients with an acute LVO receiving dEVT compared to BT. Because uncertainty for most endpoints remainslarge and the available data are not able to exclude the possibility of overall benefit or harm, further RCTs are needed.” 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. Yes The treatment effect was large enough and precise enough to be clinically significant. No Results: The three RCTs included a total of 1,092 patients. Median age was in the early 70’s and 42% were female. Key Results: No statistical difference in good neurologic outcome Primary Outcome: mRS score 0-2 at three months OR 1.08 (95% CI 0.85 to 1.38) and adjusted OR 1.11 (95% CI 0.76 to 1.63) Secondary Outcomes: mRS score 0-1 at three months OR 1.10 (95% CI 0.84 to 1.43) and adjusted OR 1.16 (95% CI 0.84 to 1.61) Successful recanalization before EVT: OR 0.37 (0.18-0.77) Moderate certainty Successful recanalization after EVT: OR 0.77 (0.54-1.08) Low certainty sICH: OR 0.75 (0.45-1.25) Low certainty Any ICH: OR 0.67 (0.49-0.92) Moderate certainty All-cause mortality: OR 0.93 (0.68-1.29) Low certainty 1. External Validity: All three trials were from Asia and as such may not be directly applicable to North American populations and healthcare systems. In one of the trials, they used 0.6mg/kg of tPA (SKIP) instead of the standard 0.9mg/kg. This could bias the trial to finding non-inferiority. In addition, these studies were all conducted at stroke centres with MT availability and do not address a drip and ship model of care. 2. Non-Inferiority Margins: All three studies included in the SRMA were non-inferiority trial designs. They were asking if direct to MT was non-inferior to the standard bridging with tPA before MT. Two out of three trials (DIRECT-MT and DEVT) the non-inferiority was met, but the non-inferiority margin was set at ≤10% absolute clinical effect in DEVT, and 20% effect size in odds ratio in DIRECT-MT. Even if non-inferiority is demonstrated, it does not mean there is no clinical benefit from a bridging approach if the non-inferiority margin is too large, which may represent a clinically important difference. Many argue that the non-inferiority claim should only be reserved when a less conservative margin of 5% is utilized. None of the trials met this less conservative margin. 3. Performance Bias: We have discussed different forms of bias many times on the SGEM. This is the first time we have mentioned performance bias. This type of bias is defined by Cochrane Risk of Bias (RoB) Tool as the result of “systematic differences between groups in the care that is provided, or in exposure to factors other than the interventions of interest.” As highlighted in this SRMA, there was a performance bias in the DIRECT-MT trial with 9.4% of patients in the bridging group not receiving MT, while only 5.2% in the direct group did not receive MT. This 4.2% difference may have resulted in worse outcomes in the bridging group, favoring direct MT and a finding of non-inferiority. 3. Selection Bias: This is a type of bias we have discussed many times on the SGEM. The Cochrane RoB Tool defines selection bias as the result of “systematic differences between baseline characteristics of the groups that are compared.” Selection bias may affect the estimate of the per-protocol effect and/or the intention-to-treat effect. It depends on the definition that is used for the groups that are being compared. In the DEVT trial, an exclusion criterion was “arterial tortuosity and/or other arterial disease that would prevent the device from reaching the target vessel.”  This exclusion criterion may effectively ‘cherry-pick’ patients, excluding those where thrombectomy would have been difficult, potentially resulting in less favorable outcome in the direct MT group. It is unclear how many patients were excluded from the DEVT trial for this reason. In the DIRECT-MT trial approximately 5.8% (38/654) of patients intended to undergo thrombectomy did not due to technical reasons, highlighting that even in specialized academic centers thrombectomy remains technically challenging. 4. Timing of tPA: In the SKIP trial, 21% of patients in the bridging group had tPA started after groin puncture for MT. It is likely that in a significant proportion of these patients MT was completed even before the tPA infusion was finished. In the DIRECT-MT trial 87% of patients had a tPA infusion ongoing during MT, and 9% of patients in the bridging group did not receive the full dose of tPA. This could have biased the study towards finding non-inferiority for MT alone. 5. Subgroups: Certain subgroups that may benefit more from a bridging approach were underrepresented in the three trials. In the study design of the DEVT and SKIP trials they did not include patients with M2 occlusions. After final adjudication the percentage of M2 occlusions in the DEVT trail was 1.7%, SKIP 19%, and DIRECT-MT 10.1%. It is known that compared to M1/ICA occlusions, tPA is much more effective at lysing M2 clots. In the INTERRSeCT study,

Date: October 20th, 2021 Reference: Talan et al. Pathway with single-dose long-acting intravenous antibiotic reduces emergency department hospitalizations of patients with skin infections. AEM October 2021 Guest Skeptic: Dr. Lauren Westafer an Assistant Professor in the Department of Emergency Medicine at the University of Massachusetts Medical School – Baystate. She is the cofounder of FOAMcast and a pulmonary embolism and implementation science researcher. Dr. Westafer serves as the Social Media Editor and research methodology editor for Annals of Emergency Medicine. Lauren also recently won the SAEM FOAMed Excellence in Education Award. Case: A 46-year-old male with a history of diabetes controlled on metformin presents with erythema and warmth to his right lower leg measuring 27 cm by 10 cm for the past four days. The patient is neurovascularly intact and there is no evidence of deep vein thrombosis (DVT) on ultrasound. He has no fever, and his white blood cell count is 12,500. Background: Emergency department visits for skin and soft tissue infections (SSTI) are common and increasing [1]. These types of infections include cellulitis and abscesses. The SGEM has a couple of episodes on the treatment of cellulitis with antibiotics (SGEM#131 and SGEM#209). The treatment of abscesses has been covered a few more 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. The result was no statistical difference in failure rates between the loop and standard packing. Our conclusion was to consider using the loop technique on your next uncomplicated abscess. Most patients can be managed as outpatients. However, the average length of stay for inpatient care is one week and costs close to $5 billion dollars a year in the USA [2]. The mortality rate for hospitalized patients with SSTI is <0.05% [3, 4]. The only reason for in-patient management in 40% of patients was to provide parenteral antibiotics [5]. This has led to greater interest in long-acting parenteral antibiotics as a possible alternative to admission.  Clinical Question: Does the use of a clinical pathway, including a dose of intravenous dalbavancin, in emergency department patients with skin and soft tissue infections reduce hospitalizations? Reference: Talan et al. Pathway with single-dose long-acting intravenous antibiotic reduces emergency department hospitalizations of patients with skin infections. AEM October 2021 Population: Patients ≥18 years old with abscess, cellulitis, or wound infection believed or confirmed to be due to gram-positive bacteria and an area of infection of at least 75 cm2. Excluded: Unstable comorbidity (e.g. severe sepsis), immunosuppression, injection drug use and fever, pregnancy, breastfeeding, bilateral lower extremity involvement, severe neurologic disorder, allergy to glycopeptide antibiotics, suspected gram negative infection or infection likely to need more intensive care or broad spectrum antibiotics, suspected osteomyelitis, septic arthritis, or endocarditis. Intervention: Clinical pathway included a single dose of intravenous (IV) dalbavancin 1500 mg (creatinine clearance ≥30 mL/min) or 1,125 mg for creatinine clearance <30 mL/min not on dialysis Telephone follow up call 24 hours after the visit and a follow up appointment 48-72 hours after discharge Comparison: Usual care pre-implementation of the new clinical pathway Outcome: Primary Outcome: Hospitalization rate at the time of initial care in the population that received at least one antibiotic dose Secondary Outcomes: Hospitalizations through 44 days, health resource utilization (length of stay, level of care, major surgical interventions, ICU admissions), adverse events, and patient-related outcomes (satisfaction, work productivity, and quality of life surveys at 14 days) Trial Design: Before-and-after observational study at eleven US academic affiliated emergency departments (EDs). Dr. David Talan This is an SGEMHOP episode which means we have the lead author on the show. Dr. Talan is considered an authority in acute infections that result in severe morbidity and death. He is currently on the faculty of the Department of Emergency Medicine, and Department of Medicine, Division of Infectious Diseases at UCLA Medical Center. Dr. Talan also serves on the editorial board of the Annals of Emergency Medicine. Authors’ Conclusions: “Implementation of an ED SSTI clinical pathway for patient selection and follow-up that included use of a single-dose, long-acting IV antibiotic was associated with a significant reduction in hospitalization rate for stable patients with moderately severe infections.” 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 precise 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 Results: Over 3,000 patients were screen in the before and in the after phase of this study. Only 5% were eligible for inclusion. The median age of participants was in the late 40’s, two-thirds were male, and over 80% had cellulitis. Key Result: Less patients were hospitalized after the implementation of the new clinical pathway that included a single-dose, long-acting IV antibiotic. Primary Outcome: Hospitalization rate at the time of initial care 38.5% usual care vs 17.6% new pathway Absolute Difference 20.8% (95% CI; 10.4% to 31.2%) Secondary Outcome: Hospitalizations through 44 days: Absolute Difference 16.1% (95% CI; 4.9% to 27.4%) Length of Stay: 3.0 days (IQR 2.0 to 5.0) vs 2.0 days (IQR 1.0 to 4.0) Infection-Related Surgery: 0.6% vs. 3.3% ICU Admissions: 1.9% vs 0.7% Mild, Moderate and Severe AE: Were all more common in the new pathway group Deaths: None Patient-Related Outcomes; These were detailed in the supplemental material We asked David five nerdy questions about his study.  Listen to the SGEM podcast to hear his responses. 1. Inclusion/Exclusion - The patient flow diagram, Figure 1, does not list reasons for exclusion, so it’s difficult to know why patients weren’t included and if they are different than those who were excluded. Do you have any data on the characteristics of the excluded patients, and could this have led to some selection bias? 2. Study Design – Your team used a before/after study design to investigate the association between a new clinical pathway and hospitalization for patients with SSTI. One drawback to this type of design is the possible contamination of treatment effect by confounders such as other system or local factors. For example, it’s not clear how much the protocol to ensure close outpatient follow up or education contributed to the lower hospitalization rates. 3. Hawthorne Effect – In this study, clinicians in the intervention period knew they were being studied. It is possible that some portion of the treatment effect was the result of the clinicians being aware that their management of skin and soft tissue infections was being evaluated and that discharge was encouraged. 4. Impact – The pathway demonstrated an absolute difference of 21% for the primary outcome of hospitalizations. As mentioned earlier, only 5% of those screened for eligibility were enrolled. That means most patients who present with SSTI the data does not directly apply to their management. Does this not limit the impact of this intervention significantly? 5. External validity – This study was conducted in 11 academic affiliated EDs in the US. The US has a much different healthcare system than other countries like Canada, UK and Australia. Do you think this data can be applied outside the US? The academic world is also different than community EDs. The clinical pathway included telephone follow up and an outpatient follow up visit within 48-72 hours. This may not be feasible in many community practice environments or certain patient populations. Comment on Authors’ Conclusion Compared to SGEM Conclusion: We generally agree with the authors’ conclusions. SGEM Bottom Line: 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. Case Resolution: You offer the man the new long-acting single-dose IV antibiotic and outpatient management. He is happy to not need to be admitted to hospital and is discharged home with follow-up instructions. Clinical Application: It all depends. This medication costs ~$5,000 for 1,500mg. It is unclear if this would be a cost effective strategy. There could also be a concern with indication creep leading to increased antibiotic resistance. Dr. Lauren Westafer What Do I Tell My Patient? You have a skin infection. Traditionally, people are often admitted to hospital for about one week to get IV antibiotics. We have a new medication that only requires one dose here in the ED. It is a long-acting antibiotic. You can go home today after the treatment. We will give you a call to make sure you are doing ok. You will also get an in-person follow-up in the next couple of days. Would you like to be admitted to hospital or be treated and sent home today?

Date: October 7th, 2021 This is an SGEM Xtra episode. I had the honour of co-presenting at the Renaissance School of Medicine, Stony Brook University, Department of Emergency Medicine Grand Rounds. The title of the talk "From EBM to FBM - Gender Equity in the House of Medicine. You may be wondering: why is a middle aged, white, heterosexual, cis gender, male, atheist, nerd co-presenting on gender equity in the house of medicine? "And isn’t it ironic, don't you think? A little too ironic. And, yeah, I really do think".  According to Sir Patrick Steward (Captain Jean-Luc Picard from Star Trek), “People won’t listen to you or take you seriously unless you’re an old white man, and since I’m an old white man I’m going to use that to help the people who need it” My co-presenter was Dr. Suchismita Datta. She is an Assistant Professor in the Department of Emergency Medicine and GME Diversity Leader for the NYU Long Island School of Medicine. The presentation is available to listen to on iTunes and GooglePlay and all the slides can be downloaded using this LINK. Three Objectives Recognize gender inequity in medicine Identify gender inequities in each of the three pillars of of evidence-based medicine (EBM) Understand how gender inequities can impact the cardiovascular care of women Dr. Datta's Journey Dr. Datta Dr. Datta shares her personal journey from medical school to attending physician and discusses the challenges she faced along the way. She and her husband Neil met at medical school. They both matched to the same emergency medicine (EM) program. After graduation they began working at a high-volume, high-acuity critical access hospital.  After a few years they moved back to New York. Dr. Datta describes her unpaid and paid maternity leave, difficulties in pumping breast milk while on shift and the pay gap she experienced. Gender Inequities Using the EBM Model There are three pillars of EBM. The literature should inform care, guide care but it should not dictate care.  Clinicians must also use their good clinical judgment in applying the literature. We also need to ask patients about what they value and prefer. This can be summarized into a Venn diagram capturing the Dr. Sackett's definition of EBM. The Medical Literature: Who gets most of the grant money in medicine? Men Who rises to the top academic positions at universities? Men Who rises to the top academic positions in medicine? Men Who rises to the top academic positions in Emergency Medicine? Men Who is most likely to be the first author on a medical publication? Men Who is most likely the first author on a emergency medicine publication? Men Who is most likely to be the first author on a Pediatric Emergency Medicine (PEM) Paper? Men Who are often excluded from being subjects in medical research? Women The Clinicians: Who historically has been the clinician in the room? Men Who is most likely to rises to top leadership positions within the hospital structure? Men Who gets paid more in medicine? Men Who gets paid more in academic medicine? Men Who gets paid more in academic Emergency medicine? Men Who is more likely to be introduced with their professional title at grand rounds? Men Who get's paid more in Ontario, Canada? Men What can be done about the gender pay gap? CMAJ 2020 The Patients: Who traditionally was more likely to access health care? Women Who is typically responsible for most family health care needs? Women Who has been systemically under-treated when it comes to painful conditions? Women Who are provided less care for life threatening illnesses like STEMIs? Women   Cardiovascular Disease in Women Gender biases and inequities can seriously impact our clinical management. Cardiovascular disease in women is understudied, women are underrepresented in clinical trials, CVD is under recognized in women, they are being under diagnosed and under treated. This is associated with women having worse outcomes compared to men for this clinical situation. Women presenting with without the classic chest pain during coronary syndrome were less likely to receive timely therapies. This included less fibrinolytics and less primary percutaneous intervention (Canto et al JAMA 2012 and Rogers et al Circulation 2012) Women get the same benefit from PCI but have been shown to have more experience periprocedural complications (Alexander et al Circulation 2006, Regitz-Zagrosek et al Our Heart J 2011 and Dey et al Heart 2009) Women with atypical presentations were also less likely to receive aspirin, other antiplatelet agents, heparin, and beta-blocker therapies during their hospitalization (Canto et al JAMA 2012 and Rogers et al Circulation 2012) Women had a 4% absolute higher in-hospital mortality after presentation with ACS when compared to men (Canto et al JAMA 2012) Women and cardiovascular disease Commission: reducing the global burden by 2030 (Vogel et al Lancet 2021) Conclusion We hope that Dr. Datta's personal journey helps you recognize that gender inequity does exist in the house of medicine. You can appreciate that there are systemic gender inequities in each of the three pillars of EBM and we should be working towards a Humanist-Based Medicine (HBM) model that is inclusive of everyone.  Understand how these gender inequities can have serious impact our clinical management. The example we used was that women with cardiovascular disease were under-diagnosed, under-treated and had worse outcomes compared to men. 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. The ultimate goal of the SGEM is for patients get the best care, based on the best evidence. REMEMBER TO BE SKEPTICAL OF ANYTHING YOU LEARN, EVEN IF YOU HEARD IT ON THE SKEPTICS’ GUIDE TO EMERGENCY MEDICINE. Additional Reading: Davies RE, Rier JD. Gender Disparities in CAD: Women and Ischemic Heart Disease. Curr Atheroscler Rep. 2018 Sep 4;20(10):51. doi: 10.1007/s11883-018-0753-7. PMID: 30178384 Mehilli J, Presbitero P. Coronary artery disease and acute coronary syndrome in women. Heart 2020;106:487-492. Greenwood BN, Carnahan S, Huang L. Patient-physician gender concordance and increased mortality among female heart attack patients. Proc Natl Acad Sci U S A. 2018 Aug 21;115(34):8569-8574. doi: 10.1073/pnas.1800097115. Epub 2018 Aug 6. PMID: 30082406; PMCID: PMC6112736 Nguyen PK, Nag D, Wu JC. Sex differences in the diagnostic evaluation of coronary artery disease. J Nucl Cardiol. 2011;18(1):144-152. doi:10.1007/s12350-010-9315-2 Lichtman JH, Leifheit EC, Safdar B, Bao H, Krumholz HM, Lorenze NP, Daneshvar M, Spertus JA, D’Onofrio G. Sex Differences in the Presentation and Perception of Symptoms Among Young Patients With Myocardial Infarction: Evidence from the VIRGO Study (Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients). Circulation. 2018 Feb 20;137(8):781-790. doi: 10.1161/CIRCULATIONAHA.117.031650. PMID: 29459463; PMCID: PMC5822747 Mosca L, Benjamin EJ, Berra K, Bezanson JL, Dolor RJ, Lloyd- Jones DM, et al. Effectiveness-based guidelines for the prevention of cardiovascular disease in women–2011 update: a guideline from the American Heart Association. Circulation. 2011;123:1243–62 Bank IEM, de Hoog VC, de Kleijn DPV, et al. Sex-Based Differences in the Performance of the HEART Score in Patients Presenting to the Emergency Department With Acute Chest Pain. J Am Heart Assoc. 2017;6(6):e005373. Published 2017 Jun 21. doi:10.1161/JAHA.116.005373

Date: September 28th, 2021 Reference: Zampieri et al. Effect of Intravenous Fluid Treatment With a Balanced Solution vs 0.9% Saline Solution on Mortality in Critically Ill Patients: The BaSICS Randomized Clinical Trial. JAMA 2021 Guest Skeptic: Dr. Aaron Skolnik is an Assistant Professor of Emergency Medicine at the Mayo Clinic Alix School of Medicine and Consultant in the Department of Critical Care Medicine at Mayo Clinic Arizona. Board certified in Emergency Medicine, Medical Toxicology, Addiction Medicine, Internal Medicine-Critical Care, and Neurocritical Care, Aaron practices full time as a multidisciplinary intensivist. He is the Medical Director of Respiratory Care for Mayo Clinic Arizona and serves proudly as the medical student clerkship director for critical care medicine. Case:  A 66-year-old woman is brought in by EMS from home with lethargy and hypotension.  Chest x-ray is clear, labs are remarkable for a leukocytosis of 16,000 with left shift; exam is notable for left flank pain and costovertebral tenderness.  Straight catheter urinalysis is grossly cloudy, and pyuria is present on microscopy. Blood pressure is 85/50 mm Hg.  You wonder which intravenous (IV) fluid should you order? Background: In ten seasons of the SGEM we have not covered the issue of which IV solution is the best in critical ill patients. That includes both trauma patients and septic patients. The controversy has been long standing with the standard joke being that there is nothing “normal” about normal saline. Saline is a hypertonic acidotic fluid. Many critically ill patients receive intravenous crystalloids for volume expansion as part of their resuscitation.  Some bench work, observational studies, and now two large, unblinded, cluster-randomized single-center trials (SMART and SALT-ED) suggested a benefit to using balanced crystalloids (i.e. Lactated Ringer’s or Plasmalyte 148) over 0.9% saline. In the two large trials, this benefit was seen as a reduction in a composite outcome of major adverse kidney events within 30 days (MAKE-30). In the non-blinded SMART trial, there was no statistical difference in the individual components of the composite outcome (in-hospital death before 30 days, new renal replacement therapy or in creatinine >200% of baseline). The SALT-ED trial was also a single-centre unblinded trial, but the primary outcome was hospital free days. They reported no statistical difference between the two groups. Their secondary composite outcome of death, new renal-replacement therapy, or final serum creatinine >200% of baseline, was statistically better with balanced crystalloid vs saline. However, there was not a statistical difference in any of the individual components of the composite outcome. The BaSICS trial attempts to answer whether balanced solutions are superior to saline using a large, double-blind, factorial, multi-center randomized trial. Clinical Question: Does administration of a balanced solution (Plasma-Lyte 148) during intensive care unit (ICU) stay, compared with saline solution, result in improved 90-day survival in critically ill patients? Reference:  Zampieri et al. Effect of Intravenous Fluid Treatment With a Balanced Solution vs 0.9% Saline Solution on Mortality in Critically Ill Patients: The BaSICS Randomized Clinical Trial. JAMA 2021 Population: Adult patients admitted the ICU for more than 24 hours, needing at least one fluid expansion and with at least one risk factor for acute kidney injury (age over 65, hypotension, sepsis, required mechanical ventilation or non-invasive ventilation, oliguria or increased serum creatinine level, cirrhosis or acute liver failure) Exclusions: Required or expected to require renal replacement therapy within 6 hours of admission, severe electrolyte disturbances (sodium < 120 mmol/L or > 160 mmol/L), death considered imminent within 24 hours, suspected or confirmed brain death, palliative or comfort care only or patients previously enrolled in the trial. During the study, hyperkalemia (K+ > 5.5 mEq/L) was removed as an exclusion criteria, after the second interim analysis. Intervention: Plasmalyte 148 solution at either slow (333 mL/hr) or fast (999 mL/hr) infusion rate. Comparison: 0.9% sodium chloride solution at either slow (333 mL/hr) or fast (999 mL/hr) infusion rate. Outcomes: Primary Outcome: 90-day survival Secondary Outcomes: Need for renal replacement therapy up to 90 days after enrollment, occurrence of acute kidney injury, for patients without acute kidney injury at enrollment, SOFA score and, number of days not requiring mechanical ventilation within 28 days Trial Design: Double-blind, factorial, randomized clinical trial conducted at 75 ICUs in Brazil. Authors’ Conclusions: “Among critically ill patients requiring fluid challenges, use of a balanced solution compared with 0.9% saline solution did not significantly reduce 90-day mortality. The findings do not support the use of this balanced solution.” 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. No Follow-up was complete (i.e. at least 80% for both groups). Yes All patient-important outcomes were considered. Yes The treatment effect was large enough and precise enough to be clinically significant. Unsure Results: A total of 10,520 patients were randomized and available for analysis. The mean age was 62 years, 44% were female, 48% admitted after elective surgery, 68% had received crystalloid bolus before ICU admission (45% getting > 1 litre), 60% were hypotensive or getting vasopressors, 44% required mechanical ventilation and median volume of fluid was 1.5 litres during the first day of enrollment. Key Results: No significant interaction between fluid type or infusion rate for the primary outcome of death at 90 days. Secondary Outcomes: There were 19 secondary outcomes evaluated. Of those, two met the threshold for statistical significance with both reporting harm with the balanced solution. Specifically, SOFA score at day 7 (absolute difference 0.27 [0.08-0.45]) and neurological SOFA score > 2 at day 7 (32.1% vs 26.0% for the saline solution group; odds ratio, 1.40 [95% CI, 1.18-1.66]). 1) External Validity: This study was conducted in 75 ICUs in Brazil. Half of the patients were admitted after elective surgery and 44% were on mechanical ventilation. The median APACHE II score was 12 and the median SOFA score was 4. Are these the same patients you see in your ICU? 2) Fluids: Almost half of patients had received more than 1 litre of IV fluids prior to enrollment. More of the patients received balanced solution compared to saline solution. This could have impacted the results. The total volume of crystalloids received by patients in the trial was small. The median volume of fluid was 1.5 litres during the first day of enrollment. During the first three days after enrollment the accumulated median fluid administered (including study fluid and non-study fluid) was 4.1 L (SD, 2.9 L) and the median study fluid administered during the same period was 2.9 L (SD, 2.4 L). 3) Power Calculation. The sample size was calculated based on an estimated 90-day mortality of 35% in the saline group. Actual mortality was lower (around 27%) in both groups.  The authors say that this may have resulted in a lower power to observe a clinically important difference. Power calculation is mainly dependent on two things: the effect size, and the sample size. The effect size is the delta, the difference between intervention and the control or comparison group. The sample size is the number of participants in the cohort. You will read papers that say the study was underpowered to find a difference. I’ve probably said this before and been in error. Once you have run the experiment the results are as reported. An assumption was made a priori as to effect size. You no longer have an assumption for the magnitude of effect. Now you have a data set with the “actual” effect size in that population. This is probed for analyzed for statistical significance with the appropriate tools. No more assumptions on effect size needs to be made and what you see is what you get. 4) Secondary Outcomes or Subgroup Analyses: They found two of 19 secondary outcomes that were statistically significant. Both showed increased harm with balanced solution compared to saline The authors say: “all of the subgroup and secondary outcome analyses should be considered as only hypothesis-generating”. The authors are correct that it is hypothesis generating. We should not over-interpret secondary outcomes or subgroups. We have seen in other trials where these statistical differences are highlighted (CRASH-3) because of the potential positive patient impact. I think this could be an example of intervention bias (Foy and Filippone 2013). I doubt we will see people advocating for “normal” saline in the ICU for these secondary outcomes 5) Industry Involvement: Baxter supported this large trial by providing the fluids. There were some financial conflicts of interest declared with some of the authors. However, Baxter did not have a role in the design and conduct of the study. Funding and fCOIs are just additional data points that need to be considered. They occur on a spectrum from no industry involvement to being designed,

Date: September 20th, 2021 Reference: Litell et al. Most emergency department patients meeting sepsis criteria are not diagnosed with sepsis at discharge. AEM 2021. Guest Skeptic: Dr. Jess Monas is a Consultant in the Department of Emergency Medicine at the Mayo Clinic Hospital, Phoenix, Arizona. She is also an Assistant Professor, Department of Emergency Medicine Mayo Clinic Alix School of Medicine in Scottsdale, Arizona. Jess also does the ultra summaries for EMRAP. Case: A 60-year-old man presents to the emergency department with a non-productive cough and increasing shortness of breath.  He has a history of chronic obstructive pulmonary disease (COPD), hypertension (HTN), congestive heart failure (CHF), and benign prostatic hypertrophy (BPH).  He’s afebrile.  He has a heart rate of 93 beats per minute, a blood pressure of 145/90 mm Hg, respiratory rate of 24 breaths per minute, and an oxygen saturation of 92% on room air. Initial labs come back with a slightly decreased platelet count (149) and a minimally elevated creatinine (1.21 mg/dl or 107 umol/L).  He triggers a sepsis alert, and you get a pop-up suggesting IV antibiotics and 30cc/kg of IV fluids.  So, you ask yourself, is this guy really septic and should we bypass those fluids? Background: We have covered sepsis many times on the SGEM since 2012.  This has included the three large RCTs published in 2014-15 comparing early goal-directed therapy (EGDT) to usual care. All three showed no statistical difference between the two treatments for their primary outcome (SGEM#69, SGEM#92 and SGEM#113). There was also SGEM#174 which said don’t believe the hype around a Vitamin C Cocktail that was being promoted as a cure for sepsis and SGEM#207 which showed prehospital administration of IV antibiotics did improve time to get them in patients with suspected sepsis, but did not improve all-cause mortality.  The SGEM was part of a group of clinicians who were concerned about the updated 2018 Surviving Sepsis Campaign (SSC) guidelines. Specifically, the fluid, antibiotics, and pressor requirements within the first hour of being triaged in the emergency department. Despite the lack of high-quality evidence to support these sepsis bundles, many hospitals incorporated them into their electronic medical record (EMR).  They created these sepsis alerts with the intention of identifying septic patients, so they can be treated accordingly.  Most physicians agree that antibiotics should be given early in septic patients.  However, the jury is still out for other interventions with potential for harm, particularly, the infusion of 30cc/kg of IV fluids. Worldwide sepsis contributes to the death of 5.3 million hospitalized people annually.  It is the leading cause of death in the intensive care unit (ICU) in the US and the most expensive diagnosis.  Since 2015, the Centers for Medicare & Medicaid Services (CMS) have indexed the quality of hospital care for sepsis to the SEP-1 core measure.  Interventions, particularly early antibiotics, have been associated with improved mortality. Diagnosing sepsis can be challenging.  To adequately capture patients, specificity has been sacrificed for better sensitivity.  We care more about catching all the true positives and worry less if a few true negatives get mixed up in there.  Using vital signs and lab abnormalities certainly captures more patients, but it also identifies those without an infection.  Patients with cirrhosis, toxicities, those on dialysis.  It is possible that some of these patients can be at risk for harm from one of these interventions. Clinical Question: What proportions of patients meeting sepsis criteria were actually diagnosed with sepsis, and how many non-septic patients had risk factors for harm from aggressive fluid resuscitation? Reference: Litell et al. Most emergency department patients meeting sepsis criteria are not diagnosed with sepsis at discharge. AEM 2021. Population: These were adult ED patients presenting to a tertiary academic medical center who met criteria for Sepsis-3 or Sepsis-3 plus shock. Sepsis-3 was defined as patients with a SOFA score ≥ 2 (Sequential Organ Failure Assessment score) and a suspected infection (which they counted if patients were given IV antibiotics within 24 hours of admission).  Sepsis-3 plus shock was defined as Sepsis-3 with an initial lactate level > 2 and any systolic blood pressure < 90. Excluded: Trauma patients and those with missing ICD-9 codes. This is because prophylactic antibiotics often administered in traumatic or orthopaedic injuries. Intervention: N/A Comparison: They compared those with a sepsis diagnosis at discharge to those without a sepsis diagnosis at discharge. Outcome: Primary Outcome: The primary outcome was proportion of ED patients with suspected sepsis based on consensus criteria who were not diagnosed with sepsis at discharge. Basically, they were initially flagged as potentially septic, but didn’t turn out to be. Secondary Outcomes: Proportion of non-septic patients at risk of harm from the administration of a rapid weight based IV fluid bolus. The risk factors included congestive heart failure, cirrhosis, dialysis-dependent renal failure, and morbid obesity. They also looked at mortality for Sepsis-3 and Sepsis-3 plus patients. Type of Study: Retrospective observational cohort design. Authors’ Conclusions: “Most patients meeting sepsis criteria in the ED were not diagnosed with sepsis at discharge.  This may result in many patients receiving sepsis treatment bundles that has the potential for harm.” 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? No 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? No Have the authors identified all-important confounding factors? No Was the follow-up of subjects complete enough? Yes How precise are the results? Not very 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 Results: They identified 4,060 patients who received IV antibiotics and had a SOFA ≥ 2. There were 935 patients excluded because of a primary trauma diagnosis and four with missing ICD-9 codes. There were 3,121 patients meeting Sepsis-3 criteria and 1,032 meeting Sepsis-3 plus shock criteria. The mean age was 60 years and 37% were female. Key Results: Most patients meeting sepsis criteria were not diagnosed with sepsis at discharge. Primary Outcome: The proportion of ED patients with suspected sepsis based on consensus criteria who were not diagnosed with sepsis at discharge 75% of patients meeting Sepsis-3 criteria did not receive an explicit diagnosis of sepsis at discharge and about half (52%) did not receive an implicit diagnosis. 52% of patients meeting Sepsis-3 plus shock criteria did not receive an explicit diagnosis of sepsis at discharge and 38% did not receive an implicit diagnosis Secondary Outcome: Proportion of non-septic patients at risk of harm from the protocolized administration of a rapid weight-based crystalloid bolus. About 40% of patients meeting Sepsis-3 criteria and 30% of patients meeting Sepsis-3 plus shock, were not diagnosed with sepsis at discharge, but did have at least one risk factor for harm from large-volume fluid resuscitation. About 30% treated for suspected sepsis, had no infectious etiology found. The most common non-infectious diagnoses were overdose, inhalation pneumonitis, acute respiratory failure (asthma, COPD, CHF), DKA and acute renal failure 9% mortality in Sepsis-3 patients and 16% in Sepsis-3 plus shock patients 1) Retrospective Study Design: The authors used a retrospective method to collect data. The study was not originally designed to answer the question being asked. This retrospective methodology may have both overestimated the patients that would have been considered septic by assuming a normal baseline and underestimated the patients by assuming normal values when data was missing. Sepsis-3 states that the SOFA score should be an increase in organ dysfunction, meaning a change ≥ 2 from baseline.  It appears that the study assumed a normal baseline and assigned sepsis label if SOFA ≥ 2. This leads to uncertainty and greater difficulty in interpreting the data. 2) Diagnosis of Sepsis: How accurate was the diagnosis of sepsis? ICD-10 codes are used for SEP-1 core measures in reporting to CMS.  However, this hospital used ICD-9 codes as the reference standard for the final diagnosis.  This could have led to misattribution bias.  It would have been less likely to occur using explicit codes rather than implicit codes which are comparatively more ambiguous. 3) SOFA Score: The SOFA score has good but not great ability to predict outcomes from sepsis in various populations. (Ferreira 2001, Arts 2005, Jones 2009, Cárdenas-Turanzas 2012, and Miller 2021). Sepsis-3 states that the SOFA score should be an increase in organ dysfunction, meaning a change ≥ 2 from baseline. They assumed a normal baseline which could overestimate the prevalence of sepsis. If data was missing, they assumed normal values and that would underestimate the number of patients with sepsis.  4) Single Center: This was a single center study which can limit the external validity of their findings.  It would depend on how sick the patients were in this study at baseline compared to local populations.  In order to generalize to your demographic, it would be helpful to know what the baseline SOFA score is of this population.  This paper assumed that patients had no organ dysfunction at baseline,