Topics in this EM Quick Hits podcast
Justin Morgenstern & Eddy Lang on the problem of overdiagnosis in EM (0:37)
Anand Swaminathan on an approach to the indications and dosing of systemic thrombolytics for submassive pulmonary embolism (27:06)
Taraha Bhate’s QI corner on pericardial effusion (33:20)
Brit Long on emergency treatment of the bleeding hemophilia patient ( part 2 of 2 part series) (40:25)
Podcast production, editing and sound design by Anton Helman
Podcast content, written summary & blog post by Saly Halawa, Brit Long, edited by Anton Helman
Cite this podcast as: Helman, A. Swaminathan, A. Lang, E. Morgenstern J. Bhate, T. Long, B. EM Quick Hits 39 – Overdiagnosis, Lytics for Submassive PE, Pericardial Effusion, Hemophilia Treatment. Emergency Medicine Cases. June, 2022. https://emergencymedicinecases.com/em-quick-hits-june-2022/. Accessed [date].
Overdiagnosis in Emergency Medicine
- Definition of overdiagnosis: Labelling a person with a disease or abnormal condition that would not have caused the person harm if left undiscovered. Individuals derive no clinical benefit from overdiagnosis and can experience physical, psychological, and financial harm
- 5 main causes of overdiagnosis
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- Over reliance on medical tests. A societal belief in prevention and early diagnosis, despite the general lack of evidence to support cancer screening to decrease mortality
- Increasingly sensitive diagnostic tests, leading to findings of of questionable importance
- Risk averse medical culture
- Expanding disease definitions and thresholds/over-medicalization of disease
- Pervasive financial incentives from industry
- Common ED clinical scenarios
- Subsegmental PE – with higher resolution CTs pulmonary emboli are more prevalent than ever, yet PE mortality has not changed in decades
- CT angiogram for suspected subarachnoid hemorrhage – leads to detection of lesions that may not be causative but may result in follow-up burden without clinical benefit
- Exercise stress testing in low-risk chest pain has a high false positive rate with risk of needless downstream invasive testing (see Journal Jam 15 Cardiac Stress Testing for deep dive)
- Anaphylaxis – recent increase in the incidence of the diagnosis as many patients do not meet the disease threshold, leading to costly over-prescription of epinephrine auto-injectors.
- Solutions to the overdiagnosis problem in EM
- A collective understanding that in the pursuit of making a diagnosis in the ED diagnosis we should seek to balance our desire for a near zero miss rate with the downstream deleterious effects of overdiagnosis
- Use shared decision making so that patients understand the problems of overdiagnosis
- Aim to educate medical students, residents staff docs and each other about the downstream effects of overdiagnosis. The more we are collectively aware of the problems, the more likely we will be to address them.
- Vigna M, Vigna C, Lang ES. Overdiagnosis in the emergency department: a sharper focus. Intern Emerg Med. 2022 Apr;17(3):629-633. doi: 10.1007/s11739-022-02952-8. Epub 2022 Mar 5. PMID: 35249191.
Gilbert Welch’s landmark book Overdiagnosed: Making People Sick in the Pursuit of Health
Preventing Overdiagnosis Conference
An approach to the indications and dosing of systemic thrombolytics for patients with submassive pulmonary embolism
Despite murky evidence for IV thrombolytics in a wide spectrum of patients with submassive PE (more recently termed “intermediate risk” PE), we should risk stratify this group of PE patients and consider thrombolytics in those patients on the end of the submissive PE clinical spectrum that we anticipate might decompensate/develop shock (massive PE). For example, PE patients with soft BP, poor oxygen saturation, severe respiratory distress, very high elevated troponin, worrisome PoCUS findings for impending obstructive shock, large proximal clot burden on CTPA etc. The risk of death from PE needs to be weighed against the risk of death from bleeding.
Dr. Swaminathan’s approach to thrombolytics and interventional radiology in patients with submassive pulmonary embolism
- HIGH risk for decompensation and LOW risk bleeding – consider alteplase 50 mg infusion over 1 hr and repeat at the end of the infusion if no clinical improvement
- LOW risk for decompensation and HIGH risk for bleeding – consider holding off on thrombolytics and arranging for interventional radiology as catheter directed thrombolysis or embolectomy may be indicated
- HIGH risk for decompensation and unlikely to remain stable while waiting for interventional radiology – consider systemic thrombolytics
- HIGH risk for decompensation and HIGH risk for bleeding– in most cases thrombolytics are likely to portent more benefit than harm as these patients are more likely to die from PE than a bleed. Consider lower dose: alteplase 25mg over 1 hr, or a slower infusion over 2 or 6 hrs
- MODERATE risk for decompensation and LOW risk for bleed– arrange for interventional radiology, but if delay to interventional radiology consider low dose thrombolytics – alteplase 25mg infused over 1hr, repeat dose if no clinical improvement
Update 2022: An open label randomized clinical trial of 94 patients with intermediate-high risk pulmonary embolisms found that the proportion of patients with an RV/LV ratio >0.9 (suggestive of RV dysfunction) at 3 months was lower in patients who underwent catheter directed thrombolysis plus anticoagulation compared to those who received anticoagulation monotherapy, but was not a statistically significant difference (95% CI 0.06-1.69). One case of nonfatal major gastrointestinal bleeding occurred in the catheter-directed thrombolysis group. Note – this study was prematurely stopped due to the COVID-19 pandemic and underpowered. Abstract
- Igneri LA, Hammer JM. Systemic Thrombolytic Therapy for Massive and Submassive Pulmonary Embolism. J Pharm Pract. 2020 Feb;33(1):74-89. doi: 10.1177/0897190018767769. Epub 2018 Apr 19. PMID: 29673293.
- Nguyen PC, Stevens H, Peter K, McFadyen JD. Submassive Pulmonary Embolism: Current Perspectives and Future Directions. J Clin Med. 2021;10(15):3383. Published 2021 Jul 30. doi:10.3390/jcm10153383
- Murphy E, Lababidi A, Reddy R, Mendha T, Lebowitz D. The Role of Thrombolytic Therapy for Patients with a Submassive Pulmonary Embolism. Cureus. 2018;10(6):e2814. Published 2018 Jun 15. doi:10.7759/cureus.2814
- Chatterjee S, Chakraborty A, Weinberg I, Kadakia M, Wilensky RL, Sardar P, Kumbhani DJ, Mukherjee D, Jaff MR, Giri J. Thrombolysis for pulmonary embolism and risk of all-cause mortality, major bleeding, and intracranial hemorrhage: a meta-analysis. JAMA. 2014 Jun 18;311(23):2414-21.
- Konstantinides S, Geibel A, Heusel G, Heinrich F, Kasper W; Management Strategies and Prognosis of Pulmonary Embolism-3 Trial (MAPPET-3) Investigators. Heparin plus alteplase compared with heparin alone in patients with submassive pulmonary embolism. N Engl J Med. 2002 Oct 10;347(15):1143-50.
- Meyer G, et al; PEITHO Investigators. Fibrinolysis for patients with intermediate-risk pulmonary embolism. N Engl J Med. 2014 Apr 10;370(15):1402-11.
- Nakamura S, Takano H, Kubota Y, Asai K, Shimizu W. Impact of the efficacy of thrombolytic therapy on the mortality of patients with acute submassive pulmonary embolism: a meta-analysis. J Thromb Haemost. 2014 Jul;12(7):1086-95.
- Sharifi M, Bay C, Skrocki L, Rahimi F, Mehdipour M; “MOPETT” Investigators. Moderate pulmonary embolism treated with thrombolysis (from the “MOPETT” Trial). Am J Cardiol. 2013 Jan 15;111(2):273-7.
Internet book of critical care deep dive into management of submassive pulmonary embolism
QI Corner: Uremic pericardial effusion
- Consider pericardial effusion on the differential for patients with unexplained dyspnea, especially for those at high risk for pericardial effusion
- Check the nursing notes for repeat vital signs before discharge or have a system in place where repeat abnormal vitals are flagged
- Consider a quick cardiac PoCUS in patients with shortness of breath without an obvious cause – especially dialysis patients and cancer patients who are at high risk for pericardial effusions
Emergency treatment of bleeding in patients with hemophilia (part 2 of 2 part series)
Part 1: Hemophilia Recognition & Workup
Step 1: Identify immediate life-threatening emergencies
Step 2: Control bleed at local site if possible
Step 3: Replace coagulation factors – see treatment below
Step 4: Speak with a hematologist
- Treat based on history and suspected site/severity of bleeding. Do not wait for exam, imaging, or laboratory testing to administer factor replacement.
- Major bleeds: major trauma, the airway, CNS, GI hemorrhage, bleeding in the chest, the retroperitoneum, epistaxis, and the eyes or orbits.
- Raise factor to 100%
- Minor bleeds: muscles, joints, oral mucosa, and hematuria.
- Raise factor to 50%.
- May use patient’s own factor replacement.
- Each unit/kg of factor VIII replacement raises factor levels by 2%, and each unit/kg of factor IX replacement raises factor levels by 1%.
- Major bleeds in a hemophilia A patient, give 50 units/kg to reach 100%. In hemophilia B, give 100 units/kg to reach 100%.
- If concerned about bleeding and don’t know the patient’s baseline factor levels, assume the factor level is 0%. If there’s any doubt, give full factor replacement.
- Other indications for factor replacement: fracture, sprain, or dislocation, heavy menstrual bleeding with moderate to severe anemia or volume loss, need for an invasive procedure or surgery.
- If factor replacement not available, activated PCC or FEIBA can be used in hemophilia A (80-100 units/kg). Recombinant FVIIa can be used in both hemophilia A and B (90 mcg/kg IV), even if an inhibitor is present.
- Inhibitors cause multiple problems: interfere with the patient’s own circulating factors; interfere with infused factor concentrates.
- Difficult to diagnose in the ED unless the patient knows they have an inhibitor
- Consider in patient with recurrent or breakthrough bleeds
- Safest treatment for those with inhibitor in hemophilia A or B is recombinant factor VIIa at 90 mcg/kg
- Non-bleeding complications: HIV, hepatitis B, hepatitis C.
- If fever and long-term vascular access are present, consider line infection and infective endocarditis.
- Other considerations: avoid intramuscular (IM) administration of medications.
- Alblaihed L, Dubbs SB, Koyfman A, Long B. High risk and low prevalence diseases: Hemophilia emergencies. Am J Emerg Med. 2022 Feb 28;56:21-27.
- Tebo C, Gibson C, Mazer-Amirshahi M. Hemophilia and von Willebrand Disease: A Review of Emergency Department Management. J Emerg Med. 2020;58(5):756-766.
- Srivastava A, Brewer AK, Mauser-Bunschoten EP, et al. Guidelines for the management of hemophilia. Haemophilia. 2013;19(1):1-47.
- MASAC Document 257 – Guidelines for Emergency Department Management of Individuals with Hemophilia and Other Bleeding Disorders. Published 2019. Available at https://www.hemophilia.org/healthcare-professionals/guidelines-on-care/masac-documents/masac-document-257-guidelines-for-emergency-department-management-of-individuals-with-hemophilia-and-other-bleeding-disorders.
emDOCs Managing Hemophilia in the ED
None of the authors have any conflicts of interest to declare
Hi! I might have missed it, but is there a reference you have for the statement that no cancer screening test has demonstrated an all-cause mortality benefit? Was interested in checking it out.
Via Dr. Lang…See papers below and all-cause mortality data related to cancer screening. Mammography, PSA and colonoscopy…
Reanalysis of All-Cause Mortality in the U.S. Preventative Services Task Force 2016 Evidence Report on Colorectal Cancer Screening – PMC (nih.gov)
Reanalysis of All-Cause Mortality in the U.S. Preventative Services Task Force 2016 Evidence Report on Colorectal Cancer Screening
http://www.ncbi.nlm.nih.gov
The Impact of Cancer Screening on All-Cause Mortality – PMC (nih.gov)
The Impact of Cancer Screening on All-Cause Mortality – PMC
Material and methods. We extracted the most recent available mortality data (counts and population size) from Germany (2015) as provided by the Federal Statistical Office (www.gbe-bund.de, accessed January 24, 2018) and from the UK (England & Wales) (2015) provided by the Office for National Statistics (https://www.ons.gov.uk, accessed February 11, 2018) for screening-detectable cancers …
http://www.ncbi.nlm.nih.gov
Assessment of prostate-specific antigen screening: an evidence-based report by the German Institute for Quality and Efficiency in Health Care – PubMed (nih.gov)
Assessment of Prostate-Specific Antigen Screening: An evidence-based report by the German Institute for Quality and Efficiency in Health Care – PubMed
Context: Prostate-specific antigen (PSA) testing increases prostate cancer diagnoses and reduces long-term disease-specific mortality, but also results in overdiagnoses and treatment-related harms. Objective: To systematically assess the benefits and harms of population-based PSA screening and the potential net benefit to inform health policy decision-makers in Germany.
pubmed.ncbi.nlm.nih.gov
Screening for breast cancer with mammography – PubMed (nih.gov)
Screening for breast cancer with mammography – PubMed
Background: A variety of estimates of the benefits and harms of mammographic screening for breast cancer have been published and national policies vary. Objectives: To assess the effect of screening for breast cancer with mammography on mortality and morbidity. Search methods: We searched PubMed (22 November 2012) and the World Health Organization’s International Clinical Trials Registry …
pubmed.ncbi.nlm.nih.gov
As per Dr. Lang…just to clarify if all these screening tools reveal small decreases in cancer-specific mortality but no signal for improved all-cause mortality it seems to me that there are clearly harms in the screening approach as the fact that the reduction in cancer deaths doesn’t influence all cause, shows that there are harms to screening that contribute to all causes of death. Not surprising if you think that most who screen +ve get surgery chemo etc..
Of all jaw dropping, eye opening, curiosity sparking cases I’ve heard from you guys this episode 39 has me with goose bumps on how true over diagnosis affects healthcare. Awesome job. Thank you for all!!!
Thanks Audley. Not sure if it didn’t come up or was edited out but my BIG concern about overdiagnosis is how it is a major threat to the sustainability of healthcare system and a significant driver of inequity. When our wait times to see an MD are soaring and we are up to our gills in admitted patients I think about all the resources being hijacked by the downstream consequences of overdiagnosis and am furious. We can’t change our system but perhaps we can stem the tide by savvier MDs and patients (or more precisely citizens – not yet patients) who will bring some healthy critical thinking to diagnosis-focused encounters.
If interested this Vinay Prasad / Gil Welch podcast is enlightening. https://www.youtube.com/watch?v=cmoaJMq-DL8&t=37s