Emergency Medical Minute

Contributor: Aaron Lessen, MD Educational Pearls:    Agitated patients who are intoxicated with methamphetamine pose a unique challenge when selecting a sedative to counter their symptoms. Is there a superior medication? A recent study compared the efficacy of commonly used medications for methamphetamine-induced agitation in the emergency department. The study compared IM Droperidol 5mg, IM Olanzapine 10mg, IM Midazolam 5mg, and IM Lorazepam 2mg. The study concluded that Droperidol, Olanzapine, and Midazolam performed similarly, with a median time to adequate sedation of 15 minutes. Lorazepam took the longest, with a median time of 30 minutes to achieve adequate sedation. Patients who received Lorazepam also required rescue medication more frequently after the initial dose. Key takeaway: Droperidol, Olanzapine, and Midazolam may be more effective than Lorazepam for treating methamphetamine-induced agitation.   References: Martel M, Klein LR, Cole JB, et al. Intramuscular droperidol, olanzapine, midazolam, or lorazepam to treat methamphetamine intoxication in the emergency department. Am J Emerg Med. 2021;49:142-148. doi:10.1016/j.ajem.2021.05.045   Summarized by Ashley Lyons, OMS4 | Edited by Ashley Lyons & Ahmed Abdel-Hafiz, NREMT-P   Donate: https://emergencymedicalminute.org/donate/   Join our mailing list: http://eepurl.com/c9ouHf

Contributor: Meghan Hurley, MD Educational Pearls: What animal is the most lethal to humans?  Depending on how we define lethal, and animal, this answer is actually not straight forward.  Globally and in the U.S. the most lethal animal is humans, accounting for ~436,000 to ~20,000 deaths (homicides) per year on average respectively.  In the United States the most lethal animal is of the Hymenoptera order (bees, wasps, and hornets). It accounts for approximately ~60 deaths per year from anaphylaxis. Globally the number is harder to track, but is estimated between 250–3,800 deaths globally annually.  Globally the most lethal animal is venomous snakes, accounting for between 60,000-150,000 per year (whereas in the United States this number is closer to ~5).  Mosquitos, as a vector however for the pathogens they transmit, out rank all as the most lethal globally (excluding humans).   What are the key take-aways for each insect discussed in this episode? Mosquitos: In the United States, of lesser concern. Can potentially transmit West Nile Virus in the United States. Otherwise, treatment for general mosquito bites is topical antihistamines and over the counter steroid creams.  Hymenoptera order (bees, wasps, and hornets): Distributed throughout the US, and can also live in the ground.  Bees lose their stinger during a sting. Whereas wasps do not and can sting multiple times.  Typically stings are just localized for symptoms (pain and swelling) but can become anaphylactic.  Treat with IM Epinephrine as the first line. Consider bronchodilators from bronchospasms.  Multiple stings (around ~100), can cause end organ damage and rhabdomyolysis outside of just anaphylaxis alone. Require more aggressive management.  Fire Ants: Behave similar to bees (in swarm mentality), but have differing venoms. Can also cause global symptoms. Black Widow:  No deaths from Latrodectus hesperus (Western Black Widow) recorded in the United States. There are 3 deaths globally from widow species. Two from Madagascar, and one from a Mediterranean species of widow. Debate in the toxicology community about use of the antivenom, which may account for more deaths than the bite itself.  Black Widow bites are typically painful. Which is different from bites from recluse species.   Brown Recluse:  Rare in Colorado Typically painless bite, that creates a center necrotic eschar.  Tend to also not be lethal.  Bed Bugs Typically harmless and more of a nuisance to have. Can cause localized infections.  Bite presents in a "Breakfast, Lunch, and Dinner" formation (i.e. linear 2-3 or more bites as the bug tracks and feeds on skin).  Will feed primarily on exposed skin. The biggest concern is ensuring no cross contamination from patient to provider or facility.  Bed bug bite delivers a small amount of local anesthetic, which can make them hard to detect. References Haskell MG, Langley RL. Animal-Encounter Fatalities, United States, 1999-2016: Cause of Death and Misreporting. Public Health Rep. 2020;135(6):831-841. doi:10.1177/0033354920953211 Herness J, Snyder MJ, Newman RS. Arthropod Bites and Stings. AFP. 2022;106(2):137-147. GBD 2019 Snakebite Envenomation Collaborators. Global mortality of snakebite envenoming between 1990 and 2019. Nat Commun. 2022;13(1):6160. doi:10.1038/s41467-022-33627-9 Wei YL, Wu Z, Li RL, Tang F. Review of selected mosquito-borne diseases: arboviruses (dengue, chikungunya, Zika, West Nile, Japanese encephalitis, yellow fever) and parasitic diseases (malaria, lymphatic Filariasis). Front Public Health. 2025;13:1712094. doi:10.3389/fpubh.2025.1712094 Forsberg K, Sheats KJ, Blair JM, et al. Surveillance for Violent Deaths - National Violent Death Reporting System, 50 States, the District of Columbia, and Puerto Rico, 2022. MMWR Surveill Summ. 2025;74(5):1-42. doi:10.15585/mmwr.ss7405a1 Summarized by Dan Orbidan, OMS2 | Edited by Dan Orbidan & Ahmed Abdel-Hafiz, NREMT-P   Donate: https://emergencymedicalminute.org/donate/   Join our mailing list: http://eepurl.com/c9ouHf

Contributor: Travis Barlock, MD Educational Pearls:   First-pass success is critical to limit complications from apnea, hypoxia, and airway trauma.  Complication rate for patients intubated on the first pass is 14% Complication rates increase to 47% after two attempts, 64% after three, and 71% after the fourth attempt   How to improve likelihood of first-pass success: Use Video laryngoscopy (VL). VL increases chance of first-pass success to 85% from 71% Use a bougie, especially in patients with anatomically difficult or otherwise obstructed airways. The BEAM study cites a success rate in these patients of 96% with a bougie, compared to 82% without Use a Checklist mnemonic (SOAPME) Suction – On, ready, and within reach Oxygen – Patient is preoxygenated Adjuncts – Oral/nasal adjuncts and BVM ready Positioning - Patient positioned properly; consider obesity, using semi-Fowler/head-up positioning Medications – Rapid sequence intubation (RSI), sedation, vasopressor, and other medications prepared as necessary Equipment – Laryngoscope (blade), tube, bougie/stylet, syringe, scalpel/cric kit, others ready as necessary References Sakles, J.C., Chiu, S., Mosier, J., Walker, C. and Stolz, U. (2013), The Importance of First Pass Success When Performing Orotracheal Intubation in the Emergency Department. Acad Emerg Med, 20: 71-78. https://doi.org/10.1111/acem.12055 Prekker ME, Driver BE, Trent SA, et al. Video versus Direct Laryngoscopy for Tracheal Intubation of Critically Ill Adults. New England Journal of Medicine. 2023;389(5). doi:https://doi.org/10.1056/nejmoa2301601 Driver BE, Prekker ME, Klein LR, et al. Effect of Use of a Bougie vs Endotracheal Tube and Stylet on First-Attempt Intubation Success Among Patients With Difficult Airways Undergoing Emergency Intubation: A Randomized Clinical Trial. JAMA. 2018;319(21):2179–2189. doi:10.1001/jama.2018.6496 ‌Turner JS, Bucca AW, Propst SL, et al. Association of Checklist Use in Endotracheal Intubation With Clinically Important Outcomes: A Systematic Review and Meta-analysis. JAMA Netw Open. 2020;3(7):e209278. doi:10.1001/jamanetworkopen.2020.9278 Turner, Joseph S et al. "Feasibility of  upright patient positioning and intubation success rates At two academic EDs." The American journal of emergency medicine vol. 35,7 (2017): 986-992. doi:10.1016/j.ajem.2017.02.011   Summarized by Sam Pahl | Edited by Sam Pahl & Ahmed Abdel-Hafiz, NREMT-P   Donate: https://emergencymedicalminute.org/donate/   Join our mailing list: http://eepurl.com/c9ouHf  

Dan Orbidan, OMS-II and Dr. Travis Barlock, MD discuss a real out of hospital call. This episode covers the implications of a pharmacologically abnormal patient presentation and the pre and post hospital considerations for patient management and care.

Carepoint Journal Club is a quarterly series with discussions about a medical topic, brought to you by Carepoint's Emergency Physicians.

Contributor: Aaron Lessen, MD Educational Pearls:   UTIs are commonly seen in older women We often see them taking long-term prophylactic antibiotics because of common recurrence. Around 20-30% of older women who develop a UTI have a recurrence due to either diagnostic failure, treatment failure or non-compliance with treatment.  UTI signs and symptoms Burning sensation when urinating Strong urge to urinate Urinating often and passing small amounts of urine.  Pelvic pain    There are currently more guidelines and studies on treatments to prevent these recurrent UTIs in women that we can start in the Emergency Department. Vaginal estrogen has been shown to significantly reduce this issue of recurrence. Very simple prescriptions can be prescribed in the ED It has little systemic absorption and is generally very safe and effective.   References Wells BA, De EJB, Visingardi J, Feustel PJ. IP15-36 IMPACT OF VAGINAL ESTROGEN ON SERIOUS ADVERSE OUTCOMES IN POSTMENOPAUSAL WOMEN WITH RECURRENT URINARY TRACT INFECTIONS: A RETROSPECTIVE STUDY. Journal of Urology [Internet]. 2025 May 1;213(5S):e778. Available from: https://doi.org/10.1097/01.JU.0001109984.67114.74.36 Ackerman AL, Bradley M, D'Anci KE, Hickling D, Kim SK, Kirkby E. Updates to Recurrent Uncomplicated Urinary Tract Infections in Women: AUA/CUA/SUFU Guideline (2025). J Urol. 0(0). doi: 10.1097/JU.0000000000004723 Kaufman MR, Ackerman LA, Amin KA, et al. The AUA/SUFU/AUGS Guideline on Genitourinary Syndrome of Menopause. J Urol. 0(0). doi:10.1097/JU.0000000000004589 Meister MR, Wang C, Lowder JL, Mysorekar IU. Vaginal Estrogen Therapy Is Associated With Decreased Inflammatory Response in Postmenopausal Women With Recurrent Urinary Tract Infections. Female Pelvic Med Reconstr Surg. 2021 Jan 1;27(1):e39-e44. doi: 10.1097/SPV.0000000000000790. PMID: 31725016; PMCID: PMC7737516. Nazarko L. Recurrent lower urinary tract infection in older women [Internet]. Urology & Continence Care Today. Available from: https://www.ucc-today.com/journals/issue/launch-edition/article/recurrent-lower-urinary-tract-infection-in-older-women-ucct   Summarized by Aaryn David & Ahmed Abdel-Hafiz | Edited by Aaryn David & Ahmed Abdel-Hafiz, NREMT-P   Donate: https://emergencymedicalminute.org/donate/   Join our mailing list: http://eepurl.com/c9ouHf

Contributor: Aaron Lessen, MD Educational Pearls:  Back pain is a common presenting complaint in the emergency department. Challenges arise when tailoring care to elderly populations using standard medical therapy: Muscle relaxants carry the risk of CNS depression or anticholinergic effects such as urinary retention and confusion. Pain medications such as opiates have side effects including constipation, respiratory depression, and hypotension. NSAIDs carry a risk of GI bleeding and worsening kidney function with chronic use. A randomized clinical trial assessing the effects of acupuncture on low back pain took 800 adults aged 65 and older with chronic low back pain and placed them into one of three treatment arms: Usual medical care Standard acupuncture consisting of 8–15 treatment sessions over 12 weeks, plus usual medical care Standard acupuncture consisting of 8–15 treatment sessions over 12 weeks, plus 4-6 maintenance sessions during the next 12 weeks, plus usual medical care Using the Roland-Morris Disability Questionnaire (RMDQ) score, they assessed disability at 6 months and 12 months. The study found that those who had undergone treatment with acupuncture had significantly greater improvements in disability related to low back pain compared to the group that was only treated with usual medical care. Acupuncture is not used in the ER, but could represent a relatively safe adjunctive therapy for patients who are not responding to standard medical therapy alone.   References:  American College of Surgeons Committee on Trauma. Best practices guidelines: geriatric trauma management. American College of Surgeons; 2023. Accessed May 27, 2026. https://www.facs.org/media/ubyj2ubl/best-practices-guidelines-geriatric-trauma.pdf DeBar LL, Wellman RD, Justice M, et al. Acupuncture for chronic low back pain in older adults: a randomized clinical trial. JAMA Netw Open. 2025;8(9):e2531348. doi:10.1001/jamanetworkopen.2025.31348 Summarized by Ashley Lyons, OMS3 | Edited by Ashley Lyons & Ahmed Abdel-Hafiz, NREMT-P

Contributor: Travis Barlock, MD Educational Pearls:   Caffeine Geography and Types: Caffeine is found throughout the world and has evolved independently in various plants that are not evolutionarily related through direct lineage, but rather demonstrate convergent evolution (i.e. different species evolve the same traits).  These plants use caffeine as an insecticide.  Examples of caffeine sources include coffee, tea, yerba-mate, guaraná, cacao, and yaupon holly. Roughly 85% of Americans are estimated to consume caffeine daily.   Caffeine Pharmacology in Humans:  In humans, caffeine is a nonselective competitive antagonist (blocker) of adenosine receptors (A1 and A2A).  During waking hours, neuronal metabolic activity consumes ATP, and a byproduct of ATP hydrolysis is created: adenosine.  Adenosine proceeds to build a "sleep pressure".  Acting on A1 and A2A adenosine receptors to induce sleep (on A1, it suppresses neuronal "wakefulness" and on A2A it is believed to be an inducer of sleep).  Caffeine, by blocking those receptors, blunts sleep induction and feelings of being tired.  Caffeine has a half-life of around 6 hours, and a quarter life of approximately 12 hours, which is when the caffeine will off-load and adenosine can once again occupy those receptors, potentially causing a "crash".  Thus, for shift-workers, it is important to time caffeine intake roughly 10 hours before target bed time.  Caffeine exerts other effects on the body.  It is methylxanthine similar to theophylline, which works as a bronchodilator (via phosphodiesterase and adenosine pathways). Caffeine has clinical use to promote bronchodilation in pre-term infants.  Caffeine exerts diuretic effects as well (blocking proximal renal tubule reabsorption).  Recent ingestion of caffeine may blunt therapeutic use of adenosine in patients with SVT.  Key Takeaway? Caffeine exerts a wide variety of effects beyond making us feel more awake. It has cardiovascular, pulmonary, and renal implications in its pharmacodynamics.   References    Benarroch EE. Adenosine and its receptors: multiple modulatory functions and potential therapeutic targets for neurologic disease. Neurology. 2008;70(3):231-236. doi:10.1212/01.wnl.0000297939.18236.ec Mitchell DC, Knight CA, Hockenberry J, Teplansky R, Hartman TJ. Beverage caffeine intakes in the U.S. Food Chem Toxicol. 2014;63:136-142. doi:10.1016/j.fct.2013.10.042 Bruschettini M, Brattström P, Russo C, Onland W, Davis PG, Soll R. Caffeine dosing regimens in preterm infants with or at risk for apnea of prematurity - Bruschettini, M - 2023 | Cochrane Library. Accessed May 23, 2026. https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD013873.pub2/full?cookiesEnabled Huang R, O'Donnell AJ, Barboline JJ, Barkman TJ. Convergent evolution of caffeine in plants by co-option of exapted ancestral enzymes. Proc Natl Acad Sci U S A. 2016;113(38):10613-10618. doi:10.1073/pnas.1602575113 Cabalag MS, Taylor DM, Knott JC, Buntine P, Smit D, Meyer A. Recent caffeine ingestion reduces adenosine efficacy in the treatment of paroxysmal supraventricular tachycardia. Acad Emerg Med. 2010;17(1):44-49. doi:10.1111/j.1553-2712.2009.00616.x  Summarized by Dan Orbidan, OMS2 | Edited by Dan Orbidan & Ahmed Abdel-Hafiz, NREMT-P   Donate: https://emergencymedicalminute.org/donate/   Join our mailing list: http://eepurl.com/c9ouHf  

Contributor: Travis Barlock, MD Educational Pearls:   Endocannabinoid System: THC binds CB1 and CB2 receptors in neurons and immune cells Δ9-Tetrahydrocannabinol (THC) is the main psychoactive compound in cannabis CB1 and CB2 receptors typically bind endogenously-produced 2-arachidonoylglycerol (2-AG) and anandamide (AEA) to regulate pain, stress, and inflammation THC similarly binds CB1 and CB2, leading to the cannabinoid high: euphoria, paranoia, anxiety, analgesia, anti-inflammation, and appetite, among a variety of others Ingestion via edibles, vice inhalation via smoking, leads to chemical modification of Δ9-THC to 11-hydroxy-Δ9-THC, which more easily crosses the blood-brain barrier and binds CB1 with higher affinity, leading to increased psychoactivity   Cannabinoid Hyperemesis Syndrome (CHS): Chronic THC use leading to the classic presentation of persistent nausea and intense, frequent vomiting Chronic activation of CB1 receptors in brain builds a tolerance and dependence on THC, in addition to chronic activation of the capsaicin and vanilloid receptor TRPV1, which binds capsaicin or is activated by heat Treatment by warm showers works due to TRPV1 activation by heat Treated with benzodiazepines, fluids, and gastro-intestinal or central nervous system agents according to patient presentation   Over 200 synthetic cannabinoids have been created (K2, spice, black mamba, mojo, etc), which are more dangerous and can lead to a variety of etiologies   Acetaminophen binds CB1 receptors to reduce inflammatory pain   References Loganathan P, Gajendran M, Goyal H. A Comprehensive Review and Update on Cannabis Hyperemesis Syndrome. Pharmaceuticals (Basel). 2024;17(11):1549. Published 2024 Nov 18. doi:10.3390/ph17111549  Wall ME, Sadler BM, Brine D, Taylor H, Perez-Reyes M. Metabolism, disposition, and kinetics of delta-9-tetrahydrocannabinol in men and women. Clin Pharmacol Ther. 1983 Sep;34(3):352-63. doi: 10.1038/clpt.1983.179. PMID: 6309462.  Mills B, Yepes A, Nugent K. Synthetic Cannabinoids. Am J Med Sci. 2015 Jul;350(1):59-62. doi: 10.1097/MAJ.0000000000000466. PMID: 26132518. Klinger-Gratz PP, Ralvenius WT, Neumann E, et al. Acetaminophen Relieves Inflammatory Pain through CB1 Cannabinoid Receptors in the Rostral Ventromedial Medulla. J Neurosci. 2018;38(2):322-334. doi:10.1523/JNEUROSCI.1945-17.2017   Summarized by Sam Pahl | Edited by Sam Pahl & Ahmed Abdel-Hafiz, NREMT-P   Donate: https://emergencymedicalminute.org/donate/ Join our mailing list: http://eepurl.com/c9ouHf

Contributor: Aaron Lessen, MD Educational Pearls: There has long been many questions about which IV fluid is best for ED resuscitation Multiple adult studies have shown no clear benefit of balanced fluid vs normal saline A large pediatric randomized clinical trial published in April compared balanced fluid vs normal saline in children with septic shock  The study included about 9,000 patients from 47 emergency departments in five countries Patients with septic shock were randomized to receive either balanced fluid or normal saline The primary outcome was adverse kidney event (death, dialysis, or persistent kidney dysfunction) at 30 days or hospital discharge Results showed no difference in any safety outcomes and no adverse events occurred The key takeaway is that early fluid resuscitation matters more than which crystalloid you choose   References Balamuth F, Weiss SL, Long E, et al. Balanced Fluid or 0.9% Saline in Children Treated for Septic Shock. New England Journal of Medicine. Published online April 23, 2026. doi:https://doi.org/10.1056/nejmoa2601969   Summarized by Meg Joyce, MS3 | Edited by Meg Joyce & Ahmed Abdel-Hafiz, NREMT-P Donate: https://emergencymedicalminute.org/donate/  

Carepoint Journal Club is a quarterly series with discussions about a medical topic, brought to you by Carepoint's Emergency Physicians.

Contributor: Taylor Lynch, MD Educational Pearls:    Conduction abnormalities are a common and clinically significant complication in patients who undergo transcatheter aortic valve replacement (TAVR)   Clinical Features The most common abnormalities include high grade AV block and new onset LBBB  Due to the close proximity of the aortic annulus to the AV node and His-Purkinje system More common in males, the elderly, and those with pre-existing conduction disease (RBBB or LBBB) Sinus pauses and sinus arrest are a rare post-TAVR rhythm disturbances Temporary failure of sinus node firing with absent P waves, followed by return of sinus rhythm Sinus Pauses: Typically last Sinus Arrest: Typically last > 3 seconds Not due to direct mechanical injury from the valve, but may occur in patients as a result of pre-existing disease or other external factors: Medications Beta blockers, calcium channel blockers, digoxin Pre-existing damage to the SA node Fibrosis from a previous MI   Treatment If the patient is asymptomatic, provide ongoing surveillance If the patient is symptomatic, treatment should be aimed at the underlying cause: For medication-induced abnormalities, stop the offending medication For acute, unstable bradycardia: Medications: Atropine, Dopamine Infusion, Epinephrine Infusion If cardiology is not immediately available, initiate transcutaneous pacing or insert a temporary transvenous pacemaker Definitive treatment: Pacemaker ~10–15% of patients may develop a bradyarrhythmia post TAVR, with ~8-15% later requiring a pacemaker   Due to the risk of conduction abnormalities post TAVR, many patients are discharged with ambulatory rhythm monitoring such as a ZioPatch or Holter monitor, and may present to the emergency department for evaluation of rhythm disturbances.   References: Kusumoto FM, Schoenfeld MH, Barrett C, et al. 2018 ACC/AHA/HRS guideline on the evaluation and management of patients with bradycardia and cardiac conduction delay. Heart Rhythm. 2019;16(9):e128-e226. Lilly, S, Deshmukh, A, Epstein, A. et al. 2020 ACC Expert Consensus Decision Pathway on Management of Conduction Disturbances in Patients Undergoing Transcatheter Aortic Valve Replacement: A Report of the American College of Cardiology Solution Set Oversight Committee. JACC. 2020 Nov, 76 (20) 2391–2411. https://doi.org/10.1016/j.jacc.2020.08.050 Sammour, Y, Krishnaswamy, A, Kumar, A. et al. Incidence, Predictors, and Implications of Permanent Pacemaker Requirement After Transcatheter Aortic Valve Replacement. J Am Coll Cardiol Intv. 2021 Jan, 14 (2) 115–134. https://doi.org/10.1016/j.jcin.2020.09.063 Tarakji KG, Patel D, Krishnaswamy A, et al. Bradyarrhythmias detected by extended rhythm recording in patients undergoing transcatheter aortic valve replacement (Brady-TAVR Study). Heart Rhythm. 2022;19(3):381-388.   Summarized by Ashley Lyons, OMS3 | Edited by Ashley Lyons & Ahmed Abdel-Hafiz, NREMT-P   Donate: https://emergencymedicalminute.org/donate/   Join our mailing list: http://eepurl.com/c9ouHf

Contributor: Aaron Lessen, MD Educational Pearls: Supplemental oxygen is not a completely benign intervention.  A recent meta-analysis found that O2 saturations above 96% while on supplemental O2 were associated with worse outcomes. Only start a patient on supplemental oxygen if absolutely necessary and aim for a goal of no higher than 96% References Derek K Chu, Lisa H-Y Kim, Paul J Young, Nima Zamiri, Saleh A Almenawer, Roman Jaeschke, Wojciech Szczeklik, Holger J Schünemann, John D Neary, Waleed Alhazzani. Mortality and morbidity in acutely ill adults treated with liberal versus conservative oxygen therapy (IOTA): a systematic review and meta-analysis. The Lancet. Volume 391, Issue 10131. 2018. Pages 1693-1705,   Summarized by Will Dewispelaere, MD | Edited by Erik Verzemnieks, MD

Contributor: Aaron Lessen, MD Educational Pearls:.   Focused assessment with Sonography for Trauma (FAST) exam and the extended-FAST (eFAST) are essential components of current trauma care and evaluation There has been an accumulation of research to provide an estimate of effectiveness of identifying certain injuries with ultrasound: For identifying a pneumothorax, the sensitivity ~70% and specificity ~99%. For pericardial effusions, sensitivity 90% and specificity ~ 94%. For hemoperitoneum, sensitivity ~74% and the specificity ~98%. While ultrasound is excellent for identifying many injuries, it may not be adequate alone to rule out serious injuries if the clinical suspicion is high based on these pooled studies References Netherton S, Milenkovic V, Taylor M, Davis PJ. Diagnostic accuracy of eFAST in the trauma patient: a systematic review and meta-analysis. CJEM. 2019;21(6):727‐738. doi:10.1017/cem.2019.381 Summarized by Jackson Roos, MS4 | Edited by Erik Verzemnieks, MD