Podcasts about Furosemide

In this episode of the Real Life Pharmacology podcast, I cover drugs 16-20 of the top 200 drugs. This podcast includes information about clozapine, furosemide, heparin, tetracycline, and vardenafil. Clozapine has five boxed warnings and these are all items that you may see on your pharmacology and board exams! I've also blogged about these in the past at meded101. Furosemide is a loop diuretic and a common indicator of the prescribing cascade. I discuss this in this podcast episode. Heparin can cause thrombocytopenia. I discuss what HIT (heparin-induced thrombocytopenia) may look like.

In this episode, we discuss the differences between two diuretic medications - Furosemide and Acetazolamide.

Most doctors don't use loop diuretics like lasix, bumex correctly. Here is why. And here is how to use them correctly. https://dralo.net/links

In the first of our special guest episodes, Professor Virginia Luis Fuentes from the Royal Veterinary College, London, joins Kieran and Jose to talk about treating cardiomyopathy in cats - beyond furosemide and clopidogrel. Listen in as Prof Luis Fuentes, a world-renowned expert and thought leader in feline heart disease, describes how she approaches a variety of treatment situations in cats, and the current thinking in human and feline medicine.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.11.548438v1?rss=1 Authors: Peerboom, C. N. E., Wijne, T. B., Wierenga, C. J. Abstract: During the first two postnatal weeks intraneuronal chloride concentrations in rodents gradually decrease, causing a shift from depolarizing to hyperpolarizing {gamma}-aminobutyric acid (GABA) responses. GABAergic depolarization in the immature brain is crucial for the formation and maturation of excitatory synapses, but when GABAergic signaling becomes inhibitory it no longer promotes synapse formation. Here we examined the role of chloride transporters in developing postnatal hippocampal neurons using furosemide, an inhibitor of the chloride importer NKCC1 and chloride exporter KCC2 with reported anticonvulsant effects. We treated organotypic hippocampal cultures made from 6 to 7-day old mice with 200 M furosemide from DIV1 to DIV8. Using perforated patch clamp recordings we observed that the GABA reversal potential was depolarized after acute furosemide application, but after a week of furosemide treatment the GABA reversal potential but was more hyperpolarized compared to control. Expression levels of the chloride cotransporters were unaffected after one week furosemide treatment. This suggests that furosemide inhibited KCC2 acutely, while prolonged treatment resulted in (additional) inhibition of NKCC1, but we cannot exclude changes in HCO3-. We assessed the effects of accelerating the GABA shift by furosemide treatment on inhibitory synapses onto CA1 pyramidal cells. Directly after cessation of furosemide treatment at DIV9, inhibitory synapses were not affected. However at DIV21, two weeks after ending the treatment, we found that the frequency of inhibitory currents was increased, and VGAT puncta density in stratum Radiatum was increased. In addition, cell capacitance of CA1 pyramidal neurons was reduced in furosemide-treated slices at DIV21 in an activity-dependent manner. Our results suggest that furosemide indirectly promotes inhibitory transmission, but the underlying mechanism remains unresolved. The furosemide-induced increase in inhibitory transmission might constitute an additional mechanism via which furosemide reduces seizure susceptibility in the epileptic brain. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Visit: https://nursing.com/140meds to request your free copy of "140 Must Know Meds" Generic Name Furosemide Trade Name Lasix Indication Edema, hypertension Action Prevents reabsorption of sodium and chloride in the kidneys, increase excretion of water, sodium, chloride, magnesium, potassium Therapeutic Class Diuretics Pharmacologic Class Loop diuretics Nursing Considerations • Use caution with liver disease • May cause hypotension, dry mouth, excessive urination, dehydration, electrolyte abnormalities, metabolic alkalosis • Hypokalemia may lead to increase risk of digoxin toxicity • Monitor renal panel • Use caution with other antihypertensives • Causes arthritic symptoms/do not administer with aminoglycosides due to ototoxicity

The Filtrate:Joel TopfNayan AroraSophia AmbrusoWith Special Guest:Boback Ziaeian @boback Assistant Professor of Medicine David Geffen School of Medicine at UCLA. His Google Schoolar page is better than yours. And returning for her fourth time (why do we keep inviting her back?)Sadiya Khan @heartDocSadiya Assistant Professor of Medicine (Cardiology) and Preventative Medicine at Northwestern Feinberg School of Medicine. LinkEditor:Priya YenebereShow Notes:Diuretic Therapy review by. Craig Brater NEJMThe manuscript in JAMA | NephJCMetoprolol vs Carvedilol: Comparison of carvedilol and metoprolol on clinical outcomes in patients with chronic heart failure in the Carvedilol Or Metoprolol European Trial (COMET): randomised controlled trial (Lancet)EMPULSE: The SGLT2 inhibitor empagliflozin in patients hospitalized for acute heart failure: a multinational randomized trial (Nature Medicine)Effect of Aliskiren on Postdischarge Mortality and Heart Failure Readmissions Among Patients Hospitalized for Heart Failure The ASTRONAUT Randomized TrialEffects of Oral Tolvaptan in Patients Hospitalized for Worsening Heart Failure The EVEREST Outcome TrialSophia ended up placing fifth in NephMadness 2023. (Link)Joel finished 697thAfter winning in the opening round, Northwestern lost to UCLA, in the second round of the March Madness tournament, 68-63.Torsemide to furosemide equivalents CardioMems positive trial: Sustained efficacy of pulmonary artery pressure to guide adjustment of chronic heart failure therapy: complete follow-up results from the CHAMPION randomised trial (The Lancet)CardioMems negative trial: Haemodynamic-guided management of heart failure (GUIDE-HF): a randomised controlled trial (The Lancet)Estimation of the Absolute Risk of Cardiovascular Disease and Other Events: Issues With the Use of Multiple Fine-Gray Subdistribution Hazard Models (Circulation)Torasemide in chronic heart failure: results of the TORIC study (PubMed)Tubular SecretionsNayan: Louise Penny A World of Curiosities: A Novel (Amazon)Sadiya: Ted Lasso season threeSophia:The Last of Us on HBO and SNL skit Mario Cart as Prestige DramaBoback: Duolingo for Japanese

The following question refers to Section 9.3 of the 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure.The question is asked by Keck School of Medicine USC medical student & CardioNerds Intern Hirsh Elhence, answered first by Cedars Sinai medicine resident, soon to be Vanderbilt Cardiology Fellow, and CardioNerds Academy Faculty Dr. Breanna Hansen, and then by expert faculty Dr. Anu Lala.Dr. Lala is an advanced heart failure and transplant cardiologist, associate professor of medicine and population health science and policy, Director of Heart Failure Research, and Program Director for the Advanced Heart Failure and Transplant fellowship training program at Mount Sinai. Dr. Lala is Deputy Editor for the Journal of Cardiac Failure. Dr. Lala has been a champion and role model for CardioNerds. She has been a PI mentor for the CardioNerds Clinical Trials Network and continues to serve in the program's leadership. She is also a faculty mentor for this very 2022 heart failure decipher the guidelines series.The Decipher the Guidelines: 2022 AHA / ACC / HFSA Guideline for The Management of Heart Failure series was developed by the CardioNerds and created in collaboration with the American Heart Association and the Heart Failure Society of America. It was created by 30 trainees spanning college through advanced fellowship under the leadership of CardioNerds Cofounders Dr. Amit Goyal and Dr. Dan Ambinder, with mentorship from Dr. Anu Lala, Dr. Robert Mentz, and Dr. Nancy Sweitzer. We thank Dr. Judy Bezanson and Dr. Elliott Antman for tremendous guidance.Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values. Question #23 Mrs. Hart is a 63-year-old woman with a history of non-ischemic cardiomyopathy and heart failure with reduced ejection fraction (LVEF 20-25%) presenting with 5 days of worsening dyspnea and orthopnea.   At home, she takes carvedilol 12.5mg BID, sacubitril-valsartan 24-46mg BID, empagliflozin 10mg daily, and furosemide 40mg daily.   On admission, her exam revealed a blood pressure of 111/79 mmHg, HR 80 bpm, and SpO2 94%. Her cardiovascular exam was significant for a regular rate and rhythm with an audible S3, JVD to 13 cm H2O, bilateral lower extremity pitting edema with warm extremities and 2+ pulses throughout.  What initial dose of diuretics would you give her? A Continue home Furosemide 40 mg PO B Start Metolazone 5 mg PO C Start Lasix 100 mg IV D Start Spironolactone Answer #23 Explanation The correct answer is C – start Furosemide 100 mg IV. This is the most appropriate choice because patients with HF admitted with evidence of significant fluid overload should be promptly treated with intravenous loop diuretics to improve symptoms and reduce morbidity (Class 1, LOE B-NR). Intravenous loop diuretic therapy provides the most rapid and effective treatment for signs and symptoms of congestion. Titration of diuretics has been described in multiple recent trials of patients hospitalized with HF, often initiated with at least 2 times the daily home diuretic dose (mg to mg) administered intravenously. Titration to achieve effective diuresis may require doubling of initial doses, adding a thiazide diuretic, or adding an MRA that has diuretic effects in addition to its cardiovascular benefits. Choice A is incorrect as continuing oral loop diuretics is not recommended for acute decongestion. Moreover, Ms. Hart has become congested despite her home, oral diuretic regimen. Choice B and D are incorrect as starting a thiazide diuretic or a mineralocorticoid receptor antagonist are not first-line therapy for acute HF. Rather, in patients hospitalized with HF when diuresis is inadequate to relieve symptoms and signs of congestion, it is reasonable to intensify the diuretic regimen using either: a.

Show notes at pharmacyjoe.com/episode824. In this episode, I'll discuss torsemide vs furosemide for symptoms and quality of life among patients hospitalized for heart failure. The post 824: Torsemide vs Furosemide – Which Is Better For Symptoms and Quality of Life Among Patients Hospitalized for Heart Failure? appeared first on Pharmacy Joe.

Show notes at pharmacyjoe.com/episode824. In this episode, I ll discuss torsemide vs furosemide for symptoms and quality of life among patients hospitalized for heart failure. The post 824: Torsemide vs Furosemide – Which Is Better For Symptoms and Quality of Life Among Patients Hospitalized for Heart Failure? appeared first on Pharmacy Joe.

In this VETgirl online veterinary CE podcast, Dr. Jessica Ward, DACVIM discusses whether kidney injury can occur after furosemide use when treating dogs with congestive heart failure (CHF). When we treat dogs dogs with CHF in the emergency or critical care setting, can we potentially cause more harm and cause acute kidney injury (AKI)?

Furosemide is the most prescribed loop diuretic for heart failure; however, furosemide's pharmacokinetic parameters are less than ideal compared to other loop diuretics. Join host, Geoff Wall, as he evaluates the first randomized controlled trial comparing loop diuretics in heart failure.The GameChangerTorsemide has potential pharmacokinetic advantages compared to furosemide in the treatment of heart failure. However, a recent study did not find meaningful differences in clinical outcomes when comparing loop diuretics for the treatment of heart failure.Show Segments00:00 - Introduction01:00 - Current Loop Diuretic Use02:21 - Furosemide vs Torsemide Pharmacokinetics04:58 - Looking at the TRANSFORM-HF Study14:54 - The GameChanger: TRANSFORM-HF Outcomes19:16 - Connecting to Practice: Picking Between the Two21:52 - Closing RemarksHostGeoff Wall, PharmD, BCPS, FCCP, CGPProfessor of Pharmacy Practice, Drake UniversityInternal Medicine/Critical Care, UnityPoint HealthReferences and ResourcesEffect of Torsemide vs Furosemide After Discharge on All-Cause Mortality in Patients Hospitalized With Heart Failure: The TRANSFORM-HF Randomized Clinical Trial. Redeem your CPE hereCPE (Pharmacist)Get a membership & earn CE for GameChangers Podcast episodes (30 mins/episode)Pharmacists: Get a membershipCE InformationLearning ObjectivesUpon successful completion of this knowledge-based activity, participants should be able to:1. List the pharmacokinetic differences between furosemide and torsemide2. Discuss the findings of the Mentz et al study evaluating loop diuretics0.05 CEU/0.5 HrUAN: 0107-0000-23-101-H01-PInitial release date: 02/27/2023Expiration date: 02/27/2024Additional CPE and CME details can be found here.Follow CEimpact on Social Media:LinkedInInstagramDownload the CEimpact App for Free Continuing Education + so much more!

Dr. Ebell and Dr. Wilkes discuss the POEM titled ' No benefit with torsemide over furosemide for posthospitalization treatment of heart failure (TRANSFORM-HF) '

We're back with Season 4! Sorry for the unplanned hiatus. Today we talk about the CLOVERS trial, which tested the hypothesis that early vasopressors and restrictive fluid would be superior to liberal fluids plus rescue vasopressors. We also looked at the TRANSFORM-HF study, which compared torsemide and furosemide in congestive heart failure, the PREVENT CLOT study, which compared aspirin to enoxaparin for VTE prophylaxis after a traumatic fracture, and the AID-ICU study, which compared haloperidol to placebo in the treatment of ICU delirium. CLOVERS trialTorsemide vs Furosemide in CHFAspirin vs Enoxaparin for VTE ppx after FractureIV Haloperidol in ICU DeliriumWe also quickly review some papers we missed in 2022:Apixaban for VTE in ESRD Acetazolamide for Congestive Heart FailureModerate or Aggressive IV Fluids for PancreatitisPerioperative Management of AnticoagulationCRISTAL study (aspirin vs enoxaparin after TKA/THA)Music from Uppbeat (free for Creators!):https://uppbeat.io/t/soundroll/dopeLicense code: NP8HLP5WKGKXFW2R

The loop diuretic duels, adverse events during hospital admissions, BP accuracy, and, again, left main revascularization strategies (again) are the topics John Mandrola discusses in this week's podcast. This podcast is intended for healthcare professionals only. To read a partial transcript or to comment, visit: https://www.medscape.com/twic I. TRANSFORM HF Clarity on Torsemide vs Furosemide in HF: TRANSFORM-HF Published https://www.medscape.com/viewarticle/987128 • Effect of Torsemide vs Furosemide After Discharge on All-Cause Mortality in Patients Hospitalized With Heart Failure https://jamanetwork.com/journals/jama/fullarticle/2800428 • RANSFORM-HF—Can We Close the Loop on Diuretics in Heart Failure? https://jamanetwork.com/journals/jama/fullarticle/2800445 II. Adverse Events in the Hospital Adverse Events Reported in One Quarter of Inpatient Admissions https://www.medscape.com/viewarticle/987091 • The Safety of Inpatient Health Care https://www.nejm.org/doi/full/10.1056/NEJMsa2206117 III. BP Accuracy Experts Demand Validation of Automatic Blood Pressure Devices https://www.medscape.com/viewarticle/987032 IV. Left Main Coronary Artery Disease Real-World Examination of Revascularization Strategies for Left Main Coronary Disease in Ontario, Canada https://doi.org/10.1016/j.jcin.2022.10.016 Management of Left Main Coronary Artery Disease in Nonemergent Settings: The Heart of Multidisciplinary Teamwork https://doi.org/10.1016/j.jcin.2022.11.024 You may also like: Medscape editor-in-chief Eric Topol, MD, and master storyteller and clinician Abraham Verghese, MD, on Medicine and the Machine https://www.medscape.com/features/public/machine The Bob Harrington Show with Stanford University Chair of Medicine, Robert A. Harrington, MD. https://www.medscape.com/author/bob-harrington Questions or feedback, please contact news@medscape.net

Trials on heart failure, hypertension and lipid-lowering drugs, and the evolution of antithrombin and antiplatelet therapy are discussed in part 2 of cardiologists Bob Harrington and Mike Gibson's annual review. This podcast is intended for healthcare professionals only. To read a transcript or to comment, visit https://www.medscape.com/author/bob-harrington Lipid Lowering Safety, Tolerability and Efficacy of Up-Titration of Guideline-Directed Medical Therapies for Acute Heart Failure (STRONG-HF): A Multinational, Open-Label, Randomised, Trial https://doi.org/10.1016/S0140-6736(22)02076-1 Why Combination Lipid-Lowering Therapy Should Be Considered Early in the Treatment of Elevated LDL-C for CV Risk Reduction https://www.acc.org/latest-in-cardiology/articles/2022/06/01/12/11/why-combination-lipid-lowering-therapy-should-be-considered Incidental Coronary Artery Calcium: Opportunistic Screening of Prior Non-gated Chest CTs to Improve Statin Rates (NOTIFY-1 Project) https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.122.062746 Equivalent Impact of Elevated Lipoprotein(a) and Familial Hypercholesterolemia in Patients With Atherosclerotic Cardiovascular Disease https://doi.org/10.1016/j.jacc.2022.09.021 Comparative Effects of Low-Dose Rosuvastatin, Placebo and Dietary Supplements on Lipids and Inflammatory Biomarkers https://doi.org/10.1016/j.jacc.2022.10.013 Antihypertensive Drugs No Survival Advantage for Either Torsemide or Furosemide in HF: TRANSFORM-HF https://www.medscape.com/viewarticle/983611 Chlorthalidone vs. Hydrochlorothiazide for Hypertension–Cardiovascular Events www.nejm.org/doi/full/10.1056/NEJMoa2212270 Antiplatelets Duration of Antiplatelet Therapy After Complex Percutaneous Coronary Intervention in Patients at High Bleeding Risk: A MASTER DAPT Trial Sub-analysis https://doi.org/10.1093/eurheartj/ehac284 PANTHER: Should Clopidogrel Become the 'New Aspirin' in CAD? https://www.medscape.com/viewarticle/980117 P2Y12 Inhibitor Versus Aspirin Monotherapy for Secondary Prevention of Cardiovascular Events: Meta-analysis of Randomized Trials https://doi.org/10.1093/ehjopen/oeac019 Ticagrelor Versus Clopidogrel in Patients With Acute Coronary Syndromes https://doi.org/10.1056/nejmoa0904327 TCT-320 Pharmacokinetic and Pharmacodynamic Profile of PL-ASA, a Novel Phospholipid-Aspirin Complex Liquid Formulation, Compared to Enteric-Coated Aspirin at an 81-mg Dose – Results From a Prospective, Randomized, Crossover Study https://www.jacc.org/doi/10.1016/j.jacc.2021.09.1173 Pharmacokinetic and Pharmacodynamic Profile of a Novel Phospholipid Aspirin Formulation https://europepmc.org/article/pmc/pmc8773391 Antithrombins/Factor XI Rivaroxaban in Patients With a Recent Acute Coronary Syndrome https://www.nejm.org/doi/full/10.1056/nejmoa1112277 Genetically Determined FXI (Factor XI) Levels and Risk of Stroke https://doi.org/10.1161/strokeaha.118.022792 Factor XIa Inhibition With Asundexian After Acute Non-cardioembolic Ischaemic Stroke (PACIFIC-Stroke): an International, Randomised, Double-Blind, Placebo-Controlled, Phase 2b Trial https://doi.org/10.1016/s0140-6736(22)01588-4 Safety of the Oral Factor Xia Inhibitor Asundexian Compared With Apixaban in Patients With Atrial Fibrillation (PACIFIC-AF): a Multicentre, Randomised, Double-Blind, Double-Dummy, Dose-Finding Phase 2 Study https://doi.org/10.1016/S0140-6736(22)00456-1 A Multicenter, Phase 2, Randomized, Placebo-Controlled, Double-Blind, Parallel-Group, Dose-Finding Trial of the Oral Factor XIa Inhibitor Asundexian to Prevent Adverse Cardiovascular Outcomes After Acute Myocardial Infarction https://doi.org/10.1161/circulationaha.122.061612 You may also like: Medscape editor-in-chief Eric Topol, MD, and master storyteller and clinician Abraham Verghese, MD, on Medicine and the Machine https://www.medscape.com/features/public/machine Hear John Mandrola, MD's summary and perspective on the top cardiology news each week, on This Week in Cardiology https://www.medscape.com/twic Questions or feedback? Please contact news@medscape.net

The Filtrate:Joel TopfSwapnil HiremathNayan AroraSophia AmbrusoEditor: Nayan AroraShow Notes:Joel's Conflict of Interest StatementThe Draft Board EMPA-Kidney is “off the board”Lunch Symposium on Current and Future Approaches to the Diagnostic Assessment and Management of AKI in Patients with Cirrhosis provided by an educational grant from Mallinckrodt PharmaceuticalsThe CONFIRM Trial Terlipressin plus Albumin for the Treatment of Type 1 Hepatorenal Syndrome in NephJCClinical Practice Session Leveraging Social Media to Create, Learn, Teach, Advocate, and Dispel MisinformationThe BEST-Fluids Trial: A Randomized Controlled Trial of Balanced Crystalloid Solution vs. Saline to Prevent Delayed Graft Function in Deceased Donor Kidney Transplantation - Michael G. Collins, Magid Fahim, Elaine Pascoe, Carmel Hawley, David W. Johnson, Philip A. Clayton, Steven J. Chadban (ClinicalTrials.gov)The Late Breaking and High Impact Trials Session line upStop ACEiCLARITY Angiotensin receptor blockers for the treatment of covid-19: pragmatic, adaptive, multicentre, phase 3, randomised controlled trialEffects of Pantoprazole on Kidney Outcomes: Post Hoc Analyses From the COMPASS Randomized Controlled Trial by Lonnie Pyne, et alNo Stone: Hydrochlorothiazide for the Prevention of Kidney Stone Recurrence by Daniel Foster, et alMyTEMP: Personalised cooler dialysate for patients receiving maintenance haemodialysis (MyTEMP): a pragmatic, cluster-randomised trialClinical Practice Session Best of NephJC“We'd Now Like To Open The Floor To Shorter speeches disguised as questions.”ASN Task Force on the Future of NephrologyAttracting Osteopathic Medical Students Into NephrologyHasan Minhaj's joke at the expense of DOsTRANSFORM-HF: Torsemide vs. Furosemide in Treating Patients With HFPoint-of-Care Ultrasound in Nephrology specifically VExUS

CME credits: 1.25 Valid until: 23-11-2023 Claim your CME credit at https://reachmd.com/programs/cme/torsemide-comparison-with-furosemide-for-management-of-heart-failure/14367/ In this program, expert faculty review and discuss real-world applications of the latest, practice-changing data across different therapeutic areas within cardiovascular medicine presented at the American Heart Association Scientific Session 2022.

AHA 2022 Part 1: ISCHEMIA-EXTEND, STRONG-HF, chlorthalidone vs HCTZ, experts vs practitioners; torsemide vs furosemide; and TG lowering are discussed by John Mandrola, MD, in this week's podcast. This podcast is intended for healthcare professionals only. To read a partial transcript or to comment, visit: https://www.medscape.com/twic I. AHA Meta-comments II. ISCHEMIA-Extended - ISCHEMIA-EXTEND: Conservative Stable CAD Management Holds Up https://www.medscape.com/viewarticle/983657 - Survival After Invasive or Conservative Management of Stable Coronary Disease https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.122.062714 III. STRONG-HF - Rapidly, Fully Optimize HF Meds After Hospital Discharge: STRONG-HF https://www.medscape.com/viewarticle/983870 - STRONG HF: More Beats Less After Discharge for Heart Failure https://www.medscape.com/viewarticle/983698 - Safety, tolerability and efficacy of up-titration of guideline-directed medical therapies for acute heart failure (STRONG-HF): a multinational, open-label, randomised, trial https://doi.org/10.1016/S0140-6736(22)02076-1 IV. DCP - Diuretic Agents Equal to Prevent CV Events in Hypertension: DCP https://www.medscape.com/viewarticle/983608 - HCTZ vs Chlorthalidone -- A Win for Practicing Doctors and Science https://www.medscape.com/viewarticle/983614 V. TRANSFORM HF - No Survival Advantage for Either Torsemide or Furosemide in HF: TRANSFORM-HF https://www.medscape.com/viewarticle/983611 VI. PROMINENT - Triglyceride Lowering Fails to Show CV Benefit in Large Fibrate Trial https://www.medscape.com/viewarticle/983610 - Triglyceride Lowering with Pemafibrate to Reduce Cardiovascular Risk https://www.nejm.org/doi/full/10.1056/NEJMoa2210645 You may also like: Medscape editor-in-chief Eric Topol, MD, and master storyteller and clinician Abraham Verghese, MD, on Medicine and the Machine https://www.medscape.com/features/public/machine The Bob Harrington Show with Stanford University Chair of Medicine, Robert A. Harrington, MD. https://www.medscape.com/author/bob-harrington Questions or feedback, please contact news@medscape.net

Bivalent COVID-19 booster vaccines for children; wearable device to help treat fluid overload in adults with chronic heart failure; real-world data insights into molnupiravir efficacy; vaccine for the third trimester of pregnancy to prevent pertussis; and an FDA update on apomorphine infusion in Parkinson disease. 

Download the cheat: https://bit.ly/50-meds  View the lesson: https://bit.ly/FurosemideLasixNursingConsiderations    Generic Name Furosemide Trade Name Lasix Indication Edema, hypertension Action Prevents reabsorption of sodium and chloride in the kidneys, increase excretion of water, sodium, chloride, magnesium, potassium Therapeutic Class Diuretics Pharmacologic Class Loop diuretics Nursing Considerations • Use caution with liver disease • May cause hypotension, dry mouth, excessive urination, dehydration, electrolyte abnormalities, metabolic alkalosis • Hypokalemia may lead to increase risk of digoxin toxicity • Monitor renal panel • Use caution with other antihypertensives • Causes arthritic symptoms/do not administer with aminoglycosides due to ototoxicity

In Episode 3.9, Lauren and JJ investigate a case of dyspnea in a cat patient. This episode includes a complete review of hypertrophic cardiomyopathy in the cat. References: (1) Lake-Bakaar, G. & Kittleson, M. D. (2017). Cardiomyopathy, hypertrophic (feline). VINcyclopedia. www.vin.com (2) Stern, J. (2019). Hypertrophic cardiomyopathy and co-managing hypertension or hyperthyroidism. American Association of Feline Practitioners Conference Proceedings. (3) Kittleson, M. D. (2021). The feline cardiomyopathies: 2. Hypertrophic cardiomyopathy. Journal of Feline Medicine and Surgery, 23(11), pp 1028-1051. (4) Pereira, Y. M. (2018). Approach to the dyspnoeic cat. British Small Animal Veterinary Conference Proceedings. (5) Rothrock, K. & Shell, L. (2021). Pulmonary edema (feline). VINcyclopedia. www.vin.com (6) Rishniw, M. (2017). Feline heart size and hypertrophy. VIN Medical FAQs. www.vin.com (7) Lisciandro, G. R. (2015). Lung ultrasound in small animals: The vet blue. American College of Veterinary Internal Medicine Conference Proceedings. (8) Brister, J. (2018). Heart failure, left-sided (feline). VINcyclopedia. www.vin.com (9) Rishniw, M. (2017). Furosemide trial. VIN Medical FAQs. www.vin.com (10) Rishniw, M. (2017). Feline murmurs and gallop sounds: A quick primer. VIN Medical FAQs. www.vin.com (11) Campbell, F. E. (2013). Cardiac disease and examination. World Small Animal Veterinary Association World Congress Proceedings.

The FDA decide to decline COVID-19 treatment; Booster doses authorized for children; A direct to consumer test to detect COVID-19, influenza, and RSV; And a wearable furosemide delivery system accepted for review.

Trade – LasixClass – Loop Diuretic MOA – Inhibits the absorption of the sodium and chloride ions and water in the loop of Henle, as well as the convoluted tubule of the nephron. This results in decreased absorption of water and increased urination Indication – Pulmonary edema, CHF, HTN emergencyContraindications – Known Sensitivity to sulfonamides or furosemideSide Effects - Vertigo, dizziness, weakness, orthostatic hypotension, hypokalemia, thrombophlebitisDosage:Congestive Heart Failure and Pulmonary EdemaAdult: 20 – 40mg IV,IO slow push over 1-2 minsPedi: 1mg/kg IV, IO, IMPedi 2nd Dose: 2mg/kg IV, IO, IMHypertensive Emergency Adult: 40mg IV, IOPedi:  1mg/kg IV,IM

SUMMARY--What diuretic do you usually write for during CHF hospitalizations??   If you said furosemide you are not alone  One in a study in JACC 2013 looked at HF hospitalizations in 2009 and 2010 – In total 251,472 patients got a loop diuretic during their hospitalization and almost 87% got just furosemide, about 3% only got bumex, while only 0.4 received only torsemide.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4038646/#R11  What is the difference between bumetanide and furosemide? Nothing—or at least nothing we care about. No hard outcomes, no patient oriented outcomes.  Bumetanide is stronger—An article from 2015 in American Heart Journal states bumetanide is about 40 times stronger than furosemide- thus at times you might have your sphincter tighten when you go to write for 120-160mg of furosemide but feel comfortable writing for 3-4mg of bumex. They also discuss how bumetanide also appears to have a higher more consistent bioavailability at around 80-100% while furosemide seems to range from 10-100% depending on the study. Conclusion: the benefits for bumetanide are there in theory but no hard outcomes that I could find. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4346710/  What about torsemide??The bioavailability of torsemide is 76% to 96% and as I mentioned before furosemide hangs out around 10% to 100%. In addition, furosemide bioavailability can decrease by up to 30% with food while torsemide is not affected by food consumption.https://oce.ovid.com/article/00006562-199701000-00009https://pubmed.ncbi.nlm.nih.gov/3709617/  HOWEVER, no patient cares about bioavailability they want to know if they will live longer or live better (patient oriented outcomes)??  First paper- 2001 Nov;111(7):513-20.American Journal of Medicine we have a paper titled“Open-label randomized trial of torsemide compared with furosemide therapy for patients with heart failure” This was open-label trial of 234 patients who were randomized to torsemide or furosemide and followed for 1 yr. The outcome was heart failure readmissions and it occurred significantly less in the torsemide group, only 17% of the time compared to 32% in the furosemide group. https://pubmed.ncbi.nlm.nih.gov/11705426/ That is almost a 50% relative reduction for heart failure hospitalization at one year! This is an outcome both patients and hospitalist would love to see! Second paper-In 2002- a year later-European Journal of Heart Failure a paper titledTorasemide in chronic heart failure: results of the TORIC studyThis was the published results of the ‘TOrasemide In Congestive Heart Failure (TORIC)' study- It was an open-label, non-randomised, post-marketing surveillance trial. The individuals who were prescribed torsemide on top of their other CHF medications for 12 months had almost a 50% relative reduction in mortality!! That may not seem like a lot but remember this is only 12 months and the outcome was DEATH! In absolute terms roughly 2% of participants died in the torsemide group and 4% died in the furosemide/other diuretic group. PLUS, those in the torsemide group also had an improvement in their NYHA functional heart class.https://pubmed.ncbi.nlm.nih.gov/12167392/  Finally, there is a meta-analysis from 2019 in Journal of Cardiovascular Medicine titledTorsemide versus furosemide and intermediate-term outcomes in patients with heart failure: an updated meta-analysis  Which looked at a total of 14 randomized trials and just over 8000 pts and found torsemide to have both fewer heart failure hospitalizations and those individuals taking torsemide were more likely to have an improvement in their new york heart association class but they didnt find a difference in mortality.https://pubmed.ncbi.nlm.nih.gov/30950982/ Currently there is 6000 pt randomized trial that is underway and will be done in august 2023. https://clinicaltrials.gov/ct2/show/NCT03296813  That is it, that is all that I could find!!!! However, with the evidence clearly in favor of torsemide, why have I never even considered it before doing this lecture?? Likely 2 problems 1) It is what we have always done and it is hard to change practice! Furosemide was approved for medical use in 1964.Torsemide was approved in 1993. We as providers get into a rut, the next drug we prescribe is likely to be one of the most recent drugs we prescribed. If you show me the last 10 hypertension medications you prescribed then with almost 90-100% certainty I can guess the next one that you are going to prescribe.  2) There use to be a cost issue when furosemide was generic and torsemide was not. However, now these are both old drugs and per goodrx down here in Florida they only differ by about 1.50$ per month, but we are saving hospitalizations which cost 1000$.  A paper from 2000 in Pharmacoeconomics titled “Healthcare costs of patients with heart failure treated with torasemide or furosemide” found torsemide average hospitalization cost per patient each year was $1000 while those in the furosemide group had an average cost of $1500 dollars, and this was back when torsemide wasn't nearly as cheap as it is now.  I know I have given you a lot of numbers but a good take away is- Torsemide compared to furosemide has a NNT at 10.5 months to prevent a heart failure hospitalization around 6!!! https://pubmed.ncbi.nlm.nih.gov/10977385/ https://www.medscape.com/viewarticle/771976_8  Even if the number is off a little because of study design flaws like blinding and sample size the evidence does appear to continually point the direction of benefit towards torsemide. Even if you doubled it, a NNT of 12, it is still really good.

Gabapentin Trade - Neurontin Use – Epilepsy Furosemide Trade – LasixUse – CHF/HTN/EdemaSertraline HCL Trade – Zoloft Use - Antidepressant

Patrick has a problem, but he doesn't know how to address it. Fitting in was something Patrick sought after. Whether it be smoking cigarettes or drinking alcohol excessively at parties, Patrick found a way to make it happen. Years of smoking, drinking, and eating excessively lead to health issues. Patrick had amassed a weight of 302 pounds and was suffering from high blood pressure, migraines, sleep apnea, as well as anxiety and depression. Patrick's physician instructed he take 5 medications (Alprazolam, Sertraline, Valsartan, Furosemide, and Provigil) to address his health issues. But Patrick thought otherwise.  Against the doctor's instructions, Patrick sought after a more natural solution. First he began a vegetarian lifestyle and removed alcohol completely from his diet. He also began minding the composition of his foods to avoid artificial ingredients. After doing his own research about health, food, and wellness, Patrick concluded that veganism was the next logical step.  Three months later, Patrick is excited to share the news of his improved mood and weight loss with his physician. On this visit, Patrick was revealed to have lost 122 pounds and lowered his blood pressure from 150/110 to 110/74. Patrick realized these changes were only possible through the support of his family and friends. Knowing how critical a strong support system is to health and wellness, he now strives to BE that support for others. One of his efforts is a weekly podcast show where he opens up about his life to provide transparency to others who may be going through life issues or need to hear positivity for a change. #WeAllCanWin Instagram  www.Instagram.com/thepodotshow  https://instagram.com/clearmind_fitnesspodcast?utm_medium=copy_link Facebook  https://www.facebook.com/ClearMindPat www.Instagram.com/ELT.thepodcast  Dee    Facebook:  www.Facebook.com/deemariehair    Instagram:  www.Instagram.com/deemariehair    YouTube:  www.YouTube.com/deemariehair    Crystal    Instagram  www.Instagram.com/crystalbaldazo    Abby    Instagram:  www.Instagram.com/theabigailmarie    Facebook:  www.facebook.com/abigailmarieartistry                   

Furosemide is an antihypertensive loop diuretic drug. The main indications are for edema and hypertension with an off-label use for hypercalcemia. The general dosing range is between 40-120 mg per day with a max of 600 mg per day. The mechanism of action is it interferes with the chloride-binding co-transport system causing a natriuretic effect. It inhibits sodium and chloride resorption in the ascending Loop of Henle and the proximal and distal renal tubules. The onset of action for diuresis is around 30-60 minutes with symptomatic improvement of acute pulmonary edema occurs within 15-20 minutes. Caution should be observed in patients with electrolyte imbalances, the elderly, premature neonates, patients with gout, lupus, and diabetes. There is a black box warning for fluid and electrolyte loss if excessive amounts are used. When considering the drug interactions one should consider that furosemide is an OAT1 and OAT3 substrate, it may cause hypocalcemia, hypokalemia, hyponatremia, ototoxicity, and others. Go to DrugCardsDaily.com for episode show notes which consist of the drug summary, quiz, and link to the drug card for FREE! Please SUBSCRIBE, FOLLOW, and RATE on Spotify, Apple Podcasts, or wherever your favorite place to listen to podcasts are. The main goal is to go over the Top 200 Drugs with the occasional drug of interest. Also, if you'd like to say hello, suggest a drug, or leave some feedback I'd really appreciate hearing from you! Leave a voice message at anchor.fm/drugcardsdaily or find me on twitter @drugcardsdaily --- Send in a voice message: https://anchor.fm/drugcardsdaily/message

This week we replay an episode that reviews a critically important neurodevelopmental issue affecting infants who have single ventricle palliation - namely hearing loss. How common is hearing loss seen and what role does IV furosemide play in this finding amongst single ventricle patients? Are there techniques to avoid this complication and yet still use this commonly used diuretic agent? We discuss this important issue and study with Dr. Ari Joffe, Professor of Pediatrics University of Alberta - Stollery Children's Hospital who is the senior author of this week's work. doi: 10.1097/PCC.0000000000001807

The Filtrate:Joel TopfSwapnil HiremathNayan AroraSophie AmbrusoAnd special guests:Jay L Koyner, Professor of Medicine, University of ChicagoSarah Faubel, Professor of Medicine, University of Colorado EditorNayan AroraShow Notes:It was Kidney 360, not Kidney Medicine. Here is the study I was thinking of: https://kidney360.asnjournals.org/content/2/1/33 SNL Five-Timers Club: https://www.youtube.com/watch?v=6bWGoWFMwKE The Fluid and Electrolyte Companion. Download The Whole EnchiladaAbout the Authors from Topf and Faubel's first book, The Microbiology Companion.Ted Post: The Sarah Faubel of The Clinical Physiology of Acid Base and Electrolyte Disorders.Meta analysis of early dialysis in AKI by Victor Seabra: https://pubmed.ncbi.nlm.nih.gov/18562058/ Meta analysis of early dialysis in AKI by Morgan Grimes: https://www.ajkd.org/article/S0272-6386(15)00530-2/abstract H-index: https://en.wikipedia.org/wiki/H-index Mortality in ARDS: ACURASYS study. The hazard ratio for death at 90 days in the cisatracurium group, as compared with the placebo group, was 0.68 https://www.nejm.org/doi/full/10.1056/nejmoa1005372 Has Mortality from Acute Respiratory Distress Syndrome Decreased over Time? A Systematic Review It is commonly stated and assumed that mortality from acute respiratory distress syndrome (ARDS) is decreasing.We found that mortality from ARDS has not decreased substantially since the publication of a consensus definition in 1994. Based on our findings, a baseline mortality risk from ARDS of 40 to 45% for observational studies and 35 to 40% for randomized control trials should be expected. These results highlight the need for future effective therapeutic interventions for this highly lethal syndrome.https://www.atsjournals.org/doi/full/10.1164/rccm.200805-722oc From Up To Date:Numerous studies suggest that survival has improved over time [2,9,10,11]. As an example, an observational study of 2451 patients who had enrolled in ARDSNet randomized trials found a fall in mortality from 35 to 26 percent between 1996 and 2005 [10]. To the extent that mortality may be decreasing with time, several issues should be considered:● It is not known if mortality has decreased among patients who received their care outside of a specialized center or a clinical trial.● The improved mortality may be attributable to patients who have ARDS related to risk factors other than sepsis, such as trauma [9].● To the extent that mortality has decreased, the reasons are uncertain. Likely causes include better supportive care and improved ventilatory strategies, such as low tidal volume ventilation [10,12,13]Early Goal-Directed Therapy in the Treatment of Severe Sepsis and Septic Shock by Emanuel Rivers https://www.nejm.org/doi/full/10.1056/nejmoa010307 Early Goal Directed Therapy from NephMadness 2015 https://ajkdblog.org/2015/03/01/nephmadness-2015-critical-care-nephrology-region/#Early Counter point by NSMC graduate Kamran Boka https://ajkdblog.org/2015/03/18/nephmadness-2015-process-arise-promise-and-the-promise-of-early-goal-directed-therapy/ Furosemide stress test https://jasn.asnjournals.org/content/26/8/2023 EM Crit looks at the furosemide stress test: https://emcrit.org/pulmcrit/furosemide-stress-test/ ASN Kidney Week Biomarker debate between Faubel and Koyner. https://www.asn-online.org/education/kidneyweek/2020/program-session-details.aspx?sessId=371699&sessPar=371678 NAD therapy Samir Parikh Don Seldin Young Investigator Award winner 2019.Sarah Faubel's Dream RCT https://ukidney.com/nephrology-resources/dream-rct-initiative/dream-rct-entries/item/nephrologist-driven-rrt-usual-late-or-early-start-for-acute-kidney-injury Perry Wilson's DreamRCT https://www.medpagetoday.com/Nephrology/DreamRCT/53876 Steve Coca on “Permissive AKI” with treatment of heart failure https://www.kidney-international.org/article/S0085-2538(19)30708-2/pdf Edward Clark on HIRRT: Mechanisms for hemodynamic instability related to renal replacement therapy: a narrative review https://pubmed.ncbi.nlm.nih.gov/31407042/ Cytokine adsorption in patients with severe COVID-19 pneumonia requiring extracorporeal membrane oxygenation (CYCOV): a single centre, open-label, randomised, controlled trial https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(21)00177-6/fulltext The Handbook of Critical Care Nephrology Amazon | Target (actually not available

On this episode, I discuss furosemide pharmacology and its ability to promote fluid loss. I discuss conversion to other diuretics and between IV and oral furosemide. Drug interactions are possible with furosemide and the most common interaction is an increased risk of renal impairment with drugs like NSAIDs. Hypokalemia can be dramatic with furosemide and potassium supplementation is often necessary.

In this episode The Curious Clinicians investigate why furosemide can improve dyspnea in acute heart failure almost immediately, long before any diuresis occurs.  Check out the show notes on our website. Don't forget to pick up your CME/MOC credits, courtesy of VCU Health! Sound editing by Nodderly. 

Episode 373 is another conversation with Andy where we covered My Boxing Programming, Females & Insulin Usage, Protein as the BEST Food Altering Drug, aThiazide/Furosemide Blended Diuretic product, How the World Has Gotten Most Biology WRONG, and a lot more! Enjoy the episode and be sure to take notes! Always support Andy at: www.theperformancevibe.com    •••SPONSOR•••   (BEEF) www.skinnybeef.com___use discount code “alex10” to save off your order!   (SUPPLEMENTS) www.tigerfitness.com___use discount code “alex10” to save off your order for MTS Products!   (PEPTIDES) www.real-peptides.com___use discount code “alex10” to save off your order!   •••FIND THE EPISODES•••   ITUNES:https://itunes.apple.com/us/podcast/beastfitness-radios-podcast/id1065532968   LIBSYN:http://beastfitnessradio.libsyn.com   VIMEO: www.vimeo.com/theprepcoach        •••PREP COACH APPAREL•••   https://teespring.com/stores/the-prep-coach-apparel    

In today's VETgirl online veterinary CE podcast, we discuss the DELAY study, which stands for the "DELay of Appearance of sYmptoms of Canine Degenerative Mitral Valve Disease treated with spironolactone and benazepril." If you see small dogs diagnosed with heart murmurs, then keep on listening, as this one is important. Now, most of us feel comfortable grading heart murmurs, taking chest radiographs, and starting dogs on pimobendan, right? But does it work? When should we add in a diuretic - and if we do, which type should we reach for? Furosemide, the common loop diuretic, or spironolactone, the potassium-sparing one? Does it make a difference? When do we reach for an angiotensin converting enzyme (ACE) inhibitor? Over the years, I've noticed more cardiologists switching from furosemide to spironolactone, but what's the evidence?

What dose of diuretics did the "DOSE" trial use in heart failure exacerbations? Was oral bioavailability taken into account?References:Felker, GM, Lee, KL, Bull DA, et al. Diuretic strategies in patients with acute decompensated heart failure. NEJM. 2011; 364(9): 797- 805

Þórir Einarsson Long sérnámslæknir í almennum lyflæknir ræðir hýpónatremíu í eitt skipti fyrir öll. Hvað er hýpónatremía og hvað eigum við að lesa í það að ef sjúklingur mælist með of lágt natríum? Þórir ræðir hvaða stýrikerfi í líkamanum koma hér við sögu og fer í kerfisbundið í gegnum uppvinnslu og meðferð. Hvað ber að varast og hvernig forðum við sjúklingnum frá natríumbjargbrúninni? Stjórnendur Dagáls læknanemans eru Sólveig Bjarnadóttir læknanemi á 6. ári og Teitur Ari Theodórsson læknanemi á 5. ári. Dagáll læknanemans er sjálfstæð þáttasyrpa innan Hlaðvarps Landspítala.

Have you been trying to keep up with the medical literature, but its eat out to help out, and nothing is getting in the way of 50% your favourite pizza joint?In this months episode:..How to use D-dimers to diagnose cerebral venous thrombosis...(04:17)Heldner, Mirjam R et al. “Prediction of cerebral venous thrombosis with a new clinical score and D-dimer levels.” Neurology vol. 95,7 (2020): e898-e909. doi:10.1212/WNL.0000000000009998...Do we still need metronidazole for pneumonia?...(07:13) Marin-Corral, Judith et al. “Aspiration risk factors, microbiology and empiric antibiotics for patients hospitalized with community-acquired pneumonia.” Chest, S0012-3692(20)31905-X. 17 Jul. 2020, doi:10.1016/j.chest.2020.06.079...Ambulatory pneumothorax management...(09:45) Hallifax, Rob J et al. “Ambulatory management of primary spontaneous pneumothorax: an open-label, randomised controlled trial.” Lancet (London, England) vol. 396,10243 (2020): 39-49. doi:10.1016/S0140-6736(20)31043-6...SIADH management: more to it than just fluid restriction?... (16:37)Krisanapan, Pajaree et al. “Efficacy of Furosemide, Oral Sodium Chloride, and Fluid Restriction for Treatment of Syndrome of Inappropriate Antidiuresis (SIAD): An Open-label Randomized Controlled Study (The EFFUSE-FLUID Trial).” American journal of kidney diseases : the official journal of the National Kidney Foundation vol. 76,2 (2020): 203-212. doi:10.1053/j.ajkd.2019.11.012...How harmful are steroid bursts?... (22:15)Yao, Tsung-Chieh et al. “Association Between Oral Corticosteroid Bursts and Severe Adverse Events : A Nationwide Population-Based Cohort Study.” Annals of internal medicine vol. 173,5 (2020): 325-330. doi:10.7326/M20-0432...Candesartan's role in cognitive decline... (25:11)Hajjar, Ihab et al. “Effects of Candesartan vs Lisinopril on Neurocognitive Function in Older Adults With Executive Mild Cognitive Impairment: A Randomized Clinical Trial.” JAMA network open vol. 3,8 e2012252. 3 Aug. 2020, doi:10.1001/jamanetworkopen.2020.12252...Weight loss: when do you go hunting for cancer?... (29:16)Nicholson, Brian D et al. “Prioritising primary care patients with unexpected weight loss for cancer investigation: diagnostic accuracy study.” BMJ (Clinical research ed.) vol. 370 m2651. 13 Aug. 2020, doi:10.1136/bmj.m2651...Baloxavir: the antiviral no ones talking about...yet...(33:15)Ikematsu, Hideyuki et al. “Baloxavir Marboxil for Prophylaxis against Influenza in Household Contacts.” The New England journal of medicine vol. 383,4 (2020): 309-320. doi:10.1056/NEJMoa1915341...Is race/ethnicity a factor in physician burnout?... (29:16)Garcia, Luis C et al. “Burnout, Depression, Career Satisfaction, and Work-Life Integration by Physician Race/Ethnicity.” JAMA network open vol. 3,8 e2012762. 3 Aug. 2020, doi:10.1001/jamanetworkopen.2020.12762

Cardiovascular antihypertensive meds. Hydrochlorothiazide, loop diuretics, thiazide diuretics, potassium wasting diuretics, potassium sparing diuretics, Furosemide, torsemide, bumetanide, chlorthalidone, Cardiac Pharmacology, Antihypertensive drugs, blood pressure medications, heart failure pharmacology, HF drugs, CHF drugs, hypertensive drugs, high blood pressure drugs. Free quiz & full course at https://Simplenursing.com/nursing-school  Pharmacology Master Class - 100 videos not on YouTube - Try it for Free!    Pharmacology Master Class - Try it for Free: https://Simplenursing.com/nursing-school  100 videos not on YouTube    FREE Access to new app + 1,000 videos not on youtube!  https://Simplenursing.com/nursing-school   NCLEX FREE TRIAL:  https://simplenursing.com/NCLEX   STAY IN TOUCH

The Filtrate:Joel TopfSwapnil HiremathSamira FaroukMatt SparksAnd special guests:Sadiya Kahn a heart failure specialist at Northwestern University. @HeartDocSadiyaandPaul Welling a professor of medicine and nephrology at Johns Hopkins. @PAWellingMDShow Notes:The Study: https://www.ahajournals.org/doi/abs/10.1161/CIRCULATIONAHA.120.045691Coverage at NephJC: http://www.nephjc.com/news/sglt2mechanismDiuretics for heart failure NEJM Review article: https://www.nejm.org/doi/full/10.1056/nejmra1703100Don’t say renal: https://www.kidney-international.org/article/S0085-2538(20)30233-7/fulltext?mobileUi=0Sanjiv “We pronounce HFpEF huff-puff” Shah, MD https://www.feinberg.northwestern.edu/faculty-profiles/az/profile.html?xid=16814 and https://asecho.org/wp-content/uploads/2016/02/Shah-HFpEF.pdfHuff Puff is like fetch. It is not going to happen. https://www.youtube.com/watch?v=Pubd-spHN-0Did he have buttons? https://ajkdblog.org/2019/06/17/muscle-relaxant-use-in-dialysis/Rate My Room: https://twitter.com/ratemyskyperoom?lang=enReview on Renal Glucosuria from CJASN: https://cjasn.asnjournals.org/content/5/1/133 and another from the National Organizations of Rare Disorders: https://rarediseases.org/rare-diseases/renal-glycosuria/Mechanism of Impaired Natriuretic Response to Furosemide during Prolonged Therapy: https://pubmed.ncbi.nlm.nih.gov/2811065/Two studies that showed drops in BNP with SGLT2iDAPA HF: https://www.nejm.org/doi/full/10.1056/NEJMoa1911303DEFINE HF showing nice reduction BNP with dapagliflozen: https://pubmed.ncbi.nlm.nih.gov/31524498/?dopt=AbstractCopeptin, what is it? https://pubmed.ncbi.nlm.nih.gov/18291667/?dopt=AbstractSIADH treatment with empagliflozen: https://jasn.asnjournals.org/content/31/3/615.abstract and it is JASN not CJASN. My bad.EVEREST. Tolvaptan for heart failure: https://jamanetwork.com/journals/jama/fullarticle/206251Remdesivir placebo controlled RCT: https://www.nejm.org/doi/full/10.1056/NEJMoa2007764Joel’s Remdesivir study: https://www.nejm.org/doi/full/10.1056/NEJMoa2007016Remdesivir for 5 or 10 Days in Patients with Severe Covid-19: https://www.nejm.org/doi/full/10.1056/NEJMoa2015301Swap showing a lot of skepticism to the Lancet HCQ data even before the retraction (which happened after this recording) https://www.the-scientist.com/news-opinion/lancet-retracts-surgispheres-study-on-hydroxychloroquine-67613Baclofen is dangerous https://www.kidney-international.org/article/S0085-2538(20)30552-4/abstract

Credits: 0.25 AMA PRA Category 1 Credits™ Claim CME/CE credit: https://www.pri-med.com/online-education/podcast/frankly-speaking-cme-174  Overview: In this episodes, we will discuss a systematic review and meta-analysis that examines outcomes from the use of furosemide compared to torsemide in patients with congestive heart failure. Guest: Guest: Jill Terrien PhD, ANP-BC Music Credit: Richard Onorato

Credits: 0.25 AMA PRA Category 1 Credits™ Claim CME/CE credit: https://www.pri-med.com/online-education/podcast/frankly-speaking-cme-174 Overview: In this episodes, we will discuss a systematic review and meta-analysis that examines outcomes from the use of furosemide compared to torsemide in patients with congestive heart failure. Guest: Guest: Jill Terrien PhD, ANP-BC Music Credit: Richard Onorato

Brian, Katie, and I sit down with Vince Fuoco, a pharmacist from the greater Seattle area. We discuss a wide range of medication-related issues, including Coronavirus, dieting and nutrition, the placebo effect, the opioid crisis, and mental health. We also delve into a few less-scientific topics, drink fantastic beer from Geaux Brewing in Auburn, and much more! Recorded March 7th, 2020 at the TPDM studio in Wenatchee, Washington. Check out Vince Fuoco's podcast: Pick A Topic https://anchor.fm/vincent-fuoco/ Geaux Brewing -- Auburn, WA http://www.geauxbrewing.com/   EPISODE NOTES: Peramivir — an antiviral injection for treating influenza https://www.fda.gov/drugs/information-drug-class/rapivab-peramivir-information The Game Changers (documentary) https://en.wikipedia.org/wiki/The_Game_Changers The Complete Guide to Fasting: Heal Your Body Through Intermittent, Alternate-Day, and Extended Fasting (book by Jason Fung and Jimmy Moore) https://www.amazon.com/Complete-Guide-Fasting-Intermittent-Alternate-Day/dp/1628600012 https://www.dietdoctor.com/intermittent-fasting/guides Angus Barbieri's record-breaking fast https://en.wikipedia.org/wiki/Angus_Barbieri%27s_fast The Placebo Effect https://www.webmd.com/pain-management/what-is-the-placebo-effect Eddy Merckx — Belgian cycling legend https://en.wikipedia.org/wiki/Eddy_Merckx Magic Bullet Effect (medicine) http://broughttolife.sciencemuseum.org.uk/broughttolife/techniques/magicbullet Cure for Hepatitis C https://www.mayoclinic.org/medical-professionals/digestive-diseases/news/most-patients-with-hcv-cured-with-new-drugs-but-at-what-price/mac-20430491 Avandia (rosiglitizone) https://en.wikipedia.org/wiki/Rosiglitazone https://blogs.scientificamerican.com/observations/avandia-restricted-in-u-s-banned-in-europe/ Heroin marketed for children in the early 1900's https://www.narconon.org/drug-information/heroin-history-1900s.html The Pharmacist (documentary) https://www.netflix.com/title/81002576 Cigarette advertisements featuring physicians https://www.healio.com/hematology-oncology/news/print/hemonc-today/%7B241d62a7-fe6e-4c5b-9fed-a33cc6e4bd7c%7D/cigarettes-were-once-physician-tested-approved Washington State prescriptive authority for Narcan https://www.wsparx.org/page/NaloxoneOpioid https://stopoverdose.org/naloxone-law-in-washington/ Supervised consumption services in Switzerland JRE #1250 — Johann Hari https://www.youtube.com/watch?v=CDpjvFn4wgM&t=1722s Medical Heroin program in Norway https://www.theguardian.com/world/2018/aug/10/norway-trials-free-heroin-prescriptions-for-most-serious-addicts Ibogaine Therapy for drug addiction https://maps.org/research/ibogaine-therapy Ibogaine for treatment of alcoholism — clinical trial in Brazil https://www.clinicaltrials.gov/ct2/show/NCT03380728 Jay Greenberg — prolific composer and cello prodigy twice featured on 60 minutes https://en.wikipedia.org/wiki/Jay_Greenberg_(composer) Daniel Tammet — British man who memorized over 22,000 digits of Pi (π) https://www.sciencemag.org/news/2005/04/man-who-memorized-pi Medical Cannabinoids for Cancer Cachexia https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6360413/ Marinol — brand name for dronabinol, a specific type of THC used for chemotherapy-induced nausea/vomitting https://en.wikipedia.org/wiki/Dronabinol https://medlineplus.gov/druginfo/meds/a607054.html Notes from Brian: Lisinopril is not a duretic. It's an angiotensin-converting enzyme (ACE) inhibitor. Furosemide is an example of a duretic which would have a fluid-reducing effect. The New England Patriots started four different quarterbacks in 1992. Hugh Millen, who played for the University of Washington in 1985, led the '92 Patriots in passing yards. Drew Bledsoe played high school football for the Walla Walla Blue Devils, not the Prosser Mustangs. https://www.thisprobablydoesntmatter.com/

Does that work? Is it a good idea?

Does Lasix work to control your ICP? Is it synergistic with mannitol? No. Oh, you want evidence? Fine... ech... Todd, M., Cutkomp, J., Brian, J. (2006). Influence of Mannitol and Furosemide, Alone and in Combination, on Brain Water Content after Fluid Percussion Injury Anesthesiology 105(6), 1176-1181. https://dx.doi.org/10.1097/00000542-200612000-00017

NKCC2| Furosemide induced urinary acidification | Diuretics --- Support this podcast: https://anchor.fm/kamesa-anota/support

How Furosemide causes Alkalosis and urinary acidification --- Support this podcast: https://anchor.fm/kamesa-anota/support

In this podcast, Dr. Carl Dean, a Nephrologist with Kidney Specialists of Minnesota, presented at Ridgeview Medical Center's Live Friday CME Series on September 27th, 2019. At this event, Dr. Dean provided information on acute kidney injury (AKI)- its frequency, management, and treatment modalities available for AKI. Enjoy the podcast! Objectives:    Upon completion of this podcast, participants should be able to: Evaluate for the cause of acute kidney injury. Describe when a referral to a nephrologist is warranted. Identify treatment options available for acute kidney injury. CME credit is only offered to Ridgeview Providers for this podcast activity. Complete and submit the online evaluation form, after viewing the activity.  Upon successful completion of the evaluation, you will be e-mailed a certificate of completion within 2 weeks.  You may contact the accredited provider with questions regarding this program at  rmccredentialing@ridgeviewmedical.org. Click on the following link for your CME credit: CME Evaluation: "Approach to Acute Kidney Injury" (**If you are listening to the podcasts through iTunes on your laptop or desktop, it is not possible to link directly with the CME Evaluation for unclear reasons. We are trying to remedy this. You can, however, link to the survey through the Podcasts app on your Apple and other smart devices, as well as through Spotify, Stitcher and other podcast directory apps and on your computer browser at these websites. We apologize for the inconvenience.)  The information provided through this and all Ridgeview podcasts as well as any and all accompanying files, images, videos and documents is/are for CME/CE and other institutional learning and communication purposes only and is/are not meant to substitute for the independent medical judgment of a physician, healthcare provider or other healthcare personnel relative to diagnostic and treatment options of a specific patient's medical condition.”   FACULTY DISCLOSURE ANNOUNCEMENT  It is our intent that any potential conflict should be identified openly so that the listeners may form their own judgments about the presentation with the full disclosure of the facts. It is not assumed any potential conflicts will have an adverse impact on these presentations. It remains for the audience to determine whether the speaker’s outside interest may reflect a possible bias, either the exposition or the conclusions presented. Planning committee members and presenter(s) have disclosed they have no significant financial relationship with a pharmaceutical company and have disclosed that no conflict of interest exists with the presentation/educational event. SHOW NOTES: Nephrons are the functional unit of the kidneys. The nephrons have specialized capillary beds that have low partial pressures of oxygen which make kidneys susceptible to AKI. The afferent/efferent capillary bed have a unique ability to constrict and dilate to maintain GFR during times of physiologic stress, this is called autoregulation. The thickness of the renal cortex (or essentially where all the glomeruli are located) is important for detecting or estimating the chronicity of kidney disease. A thick cortex tells us that you have decreased renal function. The proximal tubule is the workhorse of the nephron where the electrolytes, proteins and glucose are reabsorbed. Podocytes are specialized epithelial cells that surround the capillary within the glomeruli assisting with the filtration system of the kidney. A strong electronegative charge. A classic disruption of this system leads to nephritic syndrome. The kidney gets about 20% of blood flow from the heart. Prostaglandins and Angiotensin 2 maintain GFR by driving constriction and dilation of the afferent and efferent capillary beds. NSAIDS (diminish the ability to generate prostaglandins through arachidonic acid pathway), ARBs and ACE inhibitors inhibit -- Angiotensin 2 which generates constriction on the afferent and efferent cap beds (preferential on efferent). Patients susceptible to AKI generally have preexisting chronic kidney disease. We detect AKI through creatinine and urine output. Factors that affect creatinine function include: age, gender, lean muscle mass, drugs (bacterium, cimetidine, tyrosine kinase inhibitors), ethnicity, diet. NGAL, KIM-1 and IL-18 are true markers of structural injury to the kidney. They can be found in the serum as well as urine. NGAL and KIM-1 tend to go up rather fast with AKI in comparison to say creatinine.  NGAL (neutrophil gelatinase-associated lipocalin) is one of the earliest and most robustly induced proteins in the kidney after ischemic or nephrotoxic AKI in animal models and KIM-1 (kidney injury molecule-1) is a type 1 transmembrane protein, with immunoglobulin and mucin domain, whose expression is markedly up-regulated in the proximal tubule in the post-ischemic rat kidney. Pre-renal causes of CHF, hypovolemia, V/D, MI, PE, antihypertensives, anaphylaxis, cirrhosis, sepsis, hemorrhage, etc. Essentially: "The kidneys are not getting enough blood flow". Post-renal causes include: obstruction can occur anywhere from renal tubule to the urethra. Generally, bilateral etiology to cause AKI. 1st step in evaluation for AKI is comparing present creatinine with previous and how rapidly the creatinine is rising. Next, how is the patient feeling? Med review, screen of oral intake, loss, infection, etc. Recent procedures. Labs to consider: UA, CBC, US, protein/CR ratio, CBC for TTP and micro-angiopathy.  Additional testing include: Renal U/S, PTH, and anemia may give clues to the duration of decreased renal function/ Active Urine Sediment - concerning for acute glomerulonephritis, hematuria and proteinuria, hematuria, only 80% is bladder, prostate or urethra disease. Quantify the proteinuria, screening for glomerular disease and its severity. 3g: glomerular disease is present. Hyaline casts (Tamm Horsfall) made in Loop of Henle tell us that there is low flow through the tubules. (Generally a pre-renal issue). Granular cast or muddy brown cast which is pathognomonic for ATN which is generally the diagnosis. RBC cast is generally concerning for acute glomerulonephritis may want to consider a nephron consult. Renal U/S is generally recommended for every new AKI. This evaluate for size, hydronephrosis, 2 kidneys, cortical thickness. Management of AKI is managing electrolytes and acidosis. Volume expansion. Trial of vasopressors, dialysis. No benefit to diuretics. Adjusting appropriate drug dosages for patient with AKI. Furosemide stress test can be implemented as diagnostic test to determine the severity of the AKI in volume resus oliguria patient. AKI in the hospital are likely something we did iatrogenic meds, CT contrast, hemodynamics, obstruction, sepsis, volume depletion. Acute Interstitial Nephritis:  Triad of rash, AKI and peripheral eosinophilia very rare (

This week we review a critically important neurodevelopmental issue affecting infants who have single ventricle palliation - namely hearing loss. How common is hearing loss seen and what role does IV furosemide play in this finding amongst single ventricle patients? Are there techniques to avoid this complication and yet still use this commonly used diuretic agent? We discuss this important issue and study with Dr. Ari Joffe, Professor of Pediatrics University of Alberta - Stollery Children's Hospital who is the senior author of this week's work. doi: 10.1097/PCC.0000000000001807

This week we review a critically important neurodevelopmental issue affecting infants who have single ventricle palliation - namely hearing loss. How common is hearing loss seen and what role does IV furosemide play in this finding amongst single ventricle patients? Are there techniques to avoid this complication and yet still use this commonly used diuretic agent? We discuss this important issue and study with Dr. Ari Joffe, Professor of Pediatrics University of Alberta - Stollery Children's Hospital who is the senior author of this week's work. doi: 10.1097/PCC.0000000000001807

Furosemide (frusemide) is a commonly used loop diuretic.  Also known by the commercial name, Lasix, it is well established drug but is prone to some common myths.  To help kill the dogma, we review a recently published paper discussing 10 myths regarding this frequently used medication.

Author: Nick Hatch, MD Educational Pearls:   Quick review on typical treatments for acute CHF: Nitrates are a mainstay to reduce preload Furosemide has fallen out of favor in regards to urgency but still essential; it can also be utilized in those with poor renal function Before going into the weeds: Phlebotomy can be used to remove volume and may be helpful in certain clinical scenarios Trapping venous blood by using blood pressure cuffs on three of four extremities was a very early treatment of CHF   References: Alzahri MS, Rohra A, Peacock WF. Nitrates as a Treatment of Acute Heart Failure. Card Fail Rev. 2016 May;2(1):51-55. doi: 10.15420/cfr.2016:3:3. PubMed PMID: 28785453; PubMed Central PMCID: PMC5490950. Paterna S, Di Gaudio F, La Rocca V, Balistreri F, Greco M, Torres D, Lupo U, Rizzo G, di Pasquale P, Indelicato S, Cuttitta F, Butler J, Parrinello G. Hypertonic Saline in Conjunction with High-Dose Furosemide Improves Dose-Response Curves in Worsening Refractory Congestive Heart Failure. Adv Ther. 2015 Oct;32(10):971-82. doi: 10.1007/s12325-015-0254-9. Epub 2015 Oct 31. PubMed PMID: 26521190; PubMed Central PMCID: PMC4635178. Huijskes RV, Hoogenberg K, Wiesfeld AC, Pijl ME, van Gelder IC. Phlebotomies as a treatment of serious heart failure due to haemochromatosis: a case report. Neth Heart J. 2009;17(11):438-41. Burch, George E., and Nicholas P. DePasquale. "Congestive Heart Failure—Acute Pulmonary Edema." JAMA 208.10 (1969): 1895-1897.   Summary by Travis Barlock, MS4  | Edited by Erik Verzemnieks, MD

Will the ashes of the late, great entertainer David Cassidy be spread over the grounds at Saratoga? Plus, a new study aims to find out exactly how Lasix works in horses.

Author: Nick Hatch, MD Educational Pearls:   Recent study argues that CHF patients receiving furosemide within 60 minutes of arrival had a lower in-hospital mortality than those receiving it after (2.3% vs. 6.0%, p=0.002). Flaw in study is that there were significant baseline differences between groups.   References: Matsue Y et al. Time-to-Furosemide Treatment and Mortality in Patients Hospitalized With Acute Heart Failure. JACC 2017. PMID: 28641794

This week we discuss some recent publications relevant to EM: ADRENAL, Idarucizumab and Time to Furosemide. https://media.blubrry.com/coreem/content.blubrry.com/coreem/Podcast_Episode_141_0_Final_Cut.m4a Download Leave a Comment Tags: ADRENAL, CHF, Corticosteroids, Furosemide, Idarucizumab, Journal Club, Journal Update, Sepsis Show Notes Read More Core EM: Idarucizumab for Reversal of Dabigitran Core EM: Idarucizumab for Reversal of Dabigitran II First10EM: Idarucizumab: Plenty of Optimism, Not Enough Science EM Lit of Note: The Door-to-Lasix Quality Measure EMS MED: When It's More Complicated Than A Tweet: Door-To-Furosemide And EMS

This week we discuss some recent publications relevant to EM: ADRENAL, Idarucizumab and Time to Furosemide. https://media.blubrry.com/coreem/content.blubrry.com/coreem/Podcast_Episode_141_0_Final_Cut.m4a Download Leave a Comment Tags: ADRENAL, CHF, Corticosteroids, Furosemide, Idarucizumab, Journal Club, Journal Update, Sepsis Show Notes Read More Core EM: Idarucizumab for Reversal of Dabigitran Core EM: Idarucizumab for Reversal of Dabigitran II First10EM: Idarucizumab: Plenty of Optimism, Not Enough Science EM Lit of Note: The Door-to-Lasix Quality Measure EMS MED: When It’s More Complicated Than A Tweet: Door-To-Furosemide And EMS REBEL EM:

Welcome to March's papers of the month. We know we're biased but we've got 3 more superb papers for you this month! First up we review a paper looking at oxygen levels in patient's with a return of spontaneous circulation following cardiac arrest, is hyperoxia bad news for this patient cohort as well as the other areas we've recently covered? Secondly we have a look at a paper reviewing the association between time to i.v. furosemide and outcomes in patients presenting with acute heart failure, you may want to have a listen to our previous podcast on the topic first here. Lastly, when you see a pregnant patient with a suspected thromboembolic event, can you use a negative d-dimer result to rule out the possibility? We review a recent paper looking at biomarker and specifically d-dimers ability to do this.  We'd love to hear from you with any thoughts or feedback you have on the podcast. And we've now launched of Critical Appraisal Lowdown course, so if you want to gain some more skills in critical appraisal make sure you go and check out our online course here. Enjoy! Simon & Rob References & Further Reading Association Between Early Hyperoxia Exposure AfterResuscitation from Cardiac Arrest and Neurological Disability: A Prospective Multi-Center Protocol-Directed Cohort Study. Roberts BW. Circulation. 2018 The DiPEP (Diagnosis of PE in Pregnancy) biomarker study: An observational cohort study augmented with additional cases to determine the diagnostic utility of biomarkers for suspectedvenous thromboembolism during pregnancy and puerperium. Hunt BJ. Br J Haematol. 2018 Time to Furosemide Treatment and Mortality in PatientsHospitalized With Acute Heart Failure. Matsue Y . J Am Coll Cardiol. 2017 MDCALC; Framingham Heart Failure Diagnostic Criteria REBEL.EM; Door to Furosemide in AHF Modified Rankin Scale

The post Furosemide (Lasix) Nursing Pharmacology Considerations appeared first on NURSING.com.

Speaker 1:                        Hi everyone. As a quick introduction, this is the full length recording of Anwar Chahal's interview with Calum MacRae from August 2017. A portion of this interview was included in episode seven of the Circulation Cardiovascular Genetics podcast "Getting Personal: Omics of the Heart". As we couldn't fit everything into that regular podcast episode, we've released the unedited version as a special, feature-length podcast. Enjoy. Dr Anwar Chahal:            My name is Dr. Anwar Chahal. I'm a Cardiology Fellow in Training from London, U.K., and I'm doing my research fellowship here at the Mayo Clinic, and I'm very honored and delighted to have our guest, Dr. Calum MacRae. I searched for Dr. Calum MacRae's biography online and it came up with a Wikipedia page talking about somebody who's a rugby coach. So, Dr. MacRae, I hope that's not another one of strings to your bow, that's something else that you manage to squeeze in amongst everything else that you do in your busy and punishing schedule. Dr Calum MacRae:          I did play a little rugby in my day, but I haven't coached any, I can assure you. Dr Anwar Chahal:            So, you are the Chief of Cardiovascular Medicine, you are an MD, PhD by training, and you are Associate Professor at Harvard Medical School, and your expertise, amongst many other things, internal medicine, cardiovascular diseases, but in particular, inherited cardiovascular conditions. Is there anything else that you would add to that? Dr Calum MacRae:          No, I'm a big fan of generalism, and I am quite interested in cardiovascular involvement in systemic disease as well, but largely as a means of keeping myself abreast with the biological mechanisms in every system that seems to be relevant to cardiovascular disease. Dr Anwar Chahal:            So, that reminds me. Once I heard you talk, and you mentioned to all those people that were considering cardiovascular genetics the importance of phenotype and actually how people have become increasingly super-super-specialized, becoming the bundle branch block experts or the world's authority on the right coronary cusp of the aortic valve, and how things were now going full-circle as people actually need better and better, more general understanding so that we can accurately phenotype. And you once joked that you'd actually done residency three times, so you know the importance of having a good generalist base, so could you expand a little bit on that? Dr Calum MacRae:          Well, I have to tell you, it wasn't a joke. I did actually do residency three times. But, I think the most important element of that theme is that biological processes do not, unfortunately, obey the silos in which medical subspecialists operate. So it is increasingly important to have a broad-based vision of how phenotypes might actually impact the whole organism. That's particularly true because it helps us ratify disease, so that there are mechanistic insights that come from the different cell types and tissues and biological processes that are affected.                                            I think, in general, that is something that we've all appreciated, but as time goes by and people become more and more specialized, it's less regularly implemented in day to day clinical practice. And so, particularly as molecular medicine becomes more and more penetrant in clinical disease management, I think you're going to see a return toward some generalism. Obviously, procedural specialties are the exception in many ways in this setting, because you need concentrated procedural skill. But in general, particularly for translational scientists or scientists who are interested in the underlying mechanisms of disease I think, I see a general movement towards a degree of generalism. Dr Anwar Chahal:            Indeed, and in terms of, as you say, trying to understand those disease processes and trying to, let's say for example, make sense of the incredible amounts of information that can now be gathered with genomics and high throughput omics, you believe that it is actually more of a requirement to be able to understand that now that we can gather this high resolution and broad depth of data? Dr Calum MacRae:          Yes, I agree. I think one of the core elements of modern clinical medicine is that the phenotypes have, in the last 50 to 100 years, we've really focused more on improving the resolution of existing phenotypes than expanding the phenotypic space. To be completely frank, I think we've extracted a lot of the information content that we can from the phenotypic space that we've explored, and what we need to begin to do is to find ways to systematically expand that phenotypic space.                                            I think there are a lot of reasonable ways of doing it just by thinking about other subspecialties. So, for example, in cardiovascular disease, we've focused very heavily on anatomy and physiology, but we haven't really done much in the way of cell biology. Whereas, in immunology, partly because there's access to those cell types, it's possible to do much more detailed cellular phenotyping. In neuroscience, we're now doing functional MRI, and looking at individual subsets of cells in the brain, and their function in the context of particular challenges.                                            My general thesis would be that the type of strategy would serve us well and that there's also, I think, an important mismatch between the dimensionality of phenotyping that we currently undertake and the scale of the genome and epigenome, transcriptome, et cetera. So, it's not surprising that we can't be convoluted genome of 10 to the nine variants with a phenome that are present only really has about a 10 to the four phenotypes. And so, I think some systematic right-sizing of that balance will be necessary.                                            There are lots of things that we record that we don't even think of as phenotypes, and there are phenotypes that we record that we don't really think about how to optimize the information of content. And so that's one of the things that we have begun to invest time and energy in. And thanks to the support of the American Heart Association, Verily, and AstraZeneca, as part of the One Brave Idea, we have elected to fully focus on that area in particular in coronary disease. But I think it's a generalizable problem with much of modern medicine that we tend to have focus on phenotypes that, in many instances, date back to the turn of the last century rather than to modern molecular and cellular biology. Dr Anwar Chahal:            So, you beautifully brought us to the first question, which was to ask you about One Brave Idea. Could you just, for our listeners who aren't familiar with that, just give a little bit of a background on One Brave Idea, and you've already thanked the people who have funded that, but how did you actually reach the point where you thought that this is something that really, really needs to be done? What's the process of reaching that point of bringing this idea to fruition? Dr Calum MacRae:          I think we had recognized in many instances that the families that we were seeing in cardiovascular genetics clinics were much smaller, the diseases appeared to be less penetrant than the original families that we studied when we cloned many of the disease genes. This was work that I did as a post-doctoral fellow in John and Christine Simons lab many years ago.                                            One of the things that was pretty obvious was that there were subtle pre-clinically or sub-clinically affected individuals in almost every family. And that made me ... That implies that the average family is so different from the extreme family. Is it something to do with either the resolution with which we were assessing disease or are we actually just measuring the wrong elements of the underlying genetic trait? So that, for example, is a dilated cardiomyopathy family actually a family that is susceptible to dilated cardiomyopathy in the context of some unmeasured conditioning variable, maybe a viral infection or an exposure. And because we're not measuring the exposure, or we're not measuring the underlying diaphysis, we're only measuring the final state, so we only classify people as being affected if they actually have an extreme phenotype. Are we, therefore, missing the core elements of the biology?                                            As part of doing that, we began to look outside the heart for other phenotypes, and one of the things we recognized ... This was in cardiomyopathy ... Was that different cardiac phenotypes were really aggregates of much more granular, multi-system phenotypes. So there would be families who would have dilated cardiomyopathy, but they would also actually have abnormalities, for example, of the distal interruptus muscles, and no other muscle group in their entire body. And in fact, the distal interruptus muscle phenotype was much more obvious than any cardiomyopathic phenotype.                                            So you start to understand that either other extra cardiac or electrical phenotypes, or maybe even sometimes neurofunction phenotypes are more penitent features of some of these disorders, albeit rare disorders. And so that immediately leads you to think are most of the common traits that we look after really aggregates of things that really only share the relative frequency of the core phenotype, which often dates back to decades earlier when phenotyping was at a much more superficial level.                                            So that vicious cycle perpetuates itself if we never look more deeply or look outside the constraints of a particular subspecialty. And so we have begun many, probably almost four years ago, to build a sort of next generation phenotyping clinic where we tried to bring either cell biology or molecular biology from outside the heart into phenotyping patients in a cardiovascular clinic. That idea was in our DNA, that's probably not the right way to say it, but it's something that we had worked on in a cardiomyopathy setting. Dr Anwar Chahal:            Right. Dr Calum MacRae:          And so then when the RFP for One Brave Idea came out, it seemed like a natural expansion of that to try and think about how you could apply new phenotyping in current disease. One of the inferences from that line of thought is to move, essentially, beyond ideally much upstream of the shared final common pathway so that you can begin to identify discreet underlying mechanisms.                                            And then, given the success of cardiologists, and cardiology in general, in prevention, it became obvious that really what we wanted to do was to try and understand not just disease, but also wellness. And to do that in a way where we could potentially detect the transition from wellness to the very first stages of the disease or the diseases that we have labeled as atherosclerosis or coronary artery disease.                                            That was the genesis of the central idea of the application and something that, obviously, we were excited to get the chance to pursue as a result of the generosity of the funders, and the vision of Nancy Brown at AHA and Andy Conrad at Verily, to not only award funding in a different way, but to also really try and drive us to think differently about how we executed on a research product. How we move forward, not with a five-year plan, but with a rapid cycle early hypothesis testing, fail fast and fail early, if you are going to fail, strategy. Rethink not just the focus of the research project, but the mechanisms by which you execute on it.                                            I think one of the core elements of this is, obviously, we want to make sure in doing this that we build on all of the incredible work that's been done in the last 25 or 30 years in coronary disease, whether it's the pharmacologic work, or the genetics work that has emerged in the last few years. Those are all important building blocks, and what can you do that leverages all of that existing data and adds to it? Phenotype is obviously one of the most important areas where you can bring something to the table that add to existing genotypes and also layers in on top of existing pathophysiologic models.                                            From my standpoint, it was an efficient strategy, and one that we hoped would also help us engage the people throughout the community in different ways of using data that might already have been collected or we were going to be able to collect for the first time. Dr Anwar Chahal:            In terms of One Brave Idea, where is that right now in terms of execution, as you mentioned? What's the progress so far, and is anything that's come out already that you can share with us? Dr Calum MacRae:          Yeah, of course. So we have begun a variety of different approaches to thinking through the best way of exploring this phenotypic space. One of the obvious things is you can take a couple of strategies to move into this unknown unknown. One of them is to take an incremental approach to move slowly from the areas where we have already established knowledge, and to move into new areas from that home base. And the other is to take a more agnostic strategy, which is to say are there orthogonal ways of thinking where you could look at a particular type of biology in a very focused way in coronary disease. You can define that in lots of different ways. You can say maybe we do it at an organelle level, or maybe we do it at some orthogonal component. The microbiome might be an obvious one. Another one that has been considered would be nutritional or other common environmental exposures.                                            The nice thing about the flexibility of the funding is that we can afford to test multiple different hypotheses early on, see which of them has the best signal, and then invest more deeply in those that have shown early signal. At the moment, we have multiple active projects that are really testing those initial hypotheses. Is there a way of moving from the known genes that cause coronary artery disease and trying to understand are there novel phenotypes that are associated with those. And then another approach would be to take people with very early or pre-clinical disease and test areas of biology that have never been tested in atherosclerosis or in coronary disease in a systematic way.                                            We could imagine lots of ways of doing it, but you might think about, lets say, looking at endocytosis, a process that we know already is affected by the core genes in familial hypoglycemia, but we've never really found ways to measure that in a rigorous fashion. In large populations of individuals, are there different ... Well, we know already there are different forms endocytosis, but are there discreet port ablations that might affect those.                                            Another way of looking this might be to pick an organelle. Pick the peroxisome, or pick the nucleolus, pick some other element and ask how does the function of this organelle change in individuals who have early coronary disease. Where its boring each of these types of things systematically, and trying to learn not just which are the most important areas to focus on, but also trying to learn are there strategies that are useful that you could use in another disease. In other words, are there generalizable approaches to expanding phenotypic space that makes sense.                                            I think one of the things that perhaps we underestimate about a genome is that it is the only bounded dataset in all of biology at the moment. There are no other bounded datasets. There is an infinite number of potential exposures. There's an infinite number of potential phenotypes that we could record, or at least as far as we know, are there ways of beginning to establish the boundaries of the phenome, the boundaries of the exposure or the exposal and how do we begin to do that in a way that efficiently yields new information. That's where we, as a consortium, have focused in the last few months.                                            We're also, obviously, investing time and energy in thinking how do we begin to remodel the way in which research is evaluated and funded. The strategy that we've taken there is almost like a not-for-profit venture fund where we try and bring in ideas that we think might be able to leverage what's known already and move the field faster towards new pathways or new approaches to prevention, which are the core deliverables of the One Brave Idea award. As part of doing that, we obviously get the chance to interact with lots of exciting and creative scientists and that's something we're looking forward to doing in lots of different venues. We're reaching out to lots of people and lots of people are reaching out to us. We're trying to find ways to evaluate and prioritize science and then bring that science to fruition through novel approaches to funding it, either directly or as a joint venture with a foundation or some other funding source, or even as a joint venture with a commercial partner to try and move the field forward as efficiently as possible. Dr Anwar Chahal:            Thank you very much for that, and I'm sure we all eagerly look forward to the results that are going to be coming out from One Brave Idea over the next few years. I'd like to now move on to genomic medicine training and you were involved in a statement that was put out regarding this. I think training across the world has increasingly recognized the importance of genetics and genomics, but I just want to share one little anecdote.                                            My wife is a primary care physician, and I was visiting the GP practice where she works, and she'd mentioned that I had an interest in genetics and genomics. One of the partners came out with one of these reports that a patient had sent their sample to a private company, got this analyzed, brought it in to the clinic appointment and asked for an interpretation. The GP partner said to me, "I've absolutely no idea what any of these numbers, values, et cetera, mean, and I actually am looking forward to my retirement, because I really don't want to have to cover all this. Can you help me with it?"                                            I sort of remember hearing Dr. Weinshilboum talk here at Mayo Clinic, who's really pushed forward pharmacogenomics, and he's been arguing for quite some time, as I've heard you say as well, that genomics and genetics is just going to be a part of the medical record in the same way that hemoglobin or a chest x-ray is. People better catch on because it's here, it's available commercially. People can send their samples directly, without the doctor's involvement, and then it's trying to make sense of all of that.                                            I think, as a community, research and clinical, we have to take this very seriously. I'd be grateful for your insights on that, and then if you could then tell us what would be the best way for the up and coming generation and for programs to incorporate that into their training? Dr Calum MacRae:          So, I think you're right. There is a general tendency in the public domain to test a variety of different genotypes. And in many instances, I think, the key elements are how do we as a profession, conceive of these tests? I think one of the things that we forget, perhaps at our peril, is that many of these things are problems that we've encountered before. There's a natural cycle of different tests in medicine where they start off in the academic medical centers, they propagate into the periphery, and then eventually they're assimilated as part of internal medicine.                                            I think the scale of genomics is obviously somewhat broader than many individuals have seen in the types of data that they deal with on a day to day basis. But I think that's something that's happening in everybody's life. In every aspect of your life, you have many more channels to deal with. You have many more choices in the supermarket to deal with.                                            So, I don't see this as a sort of existential challenge to medicine. Quite the opposite. In my experience, the core things that we need to remember is that DNA is no different from any other assay except for the fact that it's relatively straightforward to do DNA diagnostics. It's technically not as sensitive a set of biochemical issues, as are many other assays that we use in day to day clinical practice.                                            The other thing that I think is perhaps a key element is it, as I said a few minutes ago, it's a bounded dataset, and it's stable for your whole life. You only need to have it tested once. So, to sort of invert the typical diagnostic paradigms, instead of a primary test being interpreted in the context of an ongoing clinical event, the test may have been present for decades, and the result will evolve over time, in light of the changing phenotype or some new information with respect to that genotype.                                            What I've actually looked on genomics as is almost an organizing principle for the way that you build care. In fact, I see quite frequently, we now probably have an average one or two new patients a month in my clinic who bring their entire whole genome with them, either an axiom or a whole genome. And so, we've begun to really get to know quite well how to manage patients. Obviously, there are a selective of patients. But one of the things that I have found is that patients are really quite astute in understanding that genotype and phenotype are not deterministic relationships. What you have to do is always interpret these things in context of a probabilistic understanding.                                            Most patients, I think, when they're told this, understand that we're going to learn much more about genomics going forward than we will ever imagine we could know at the present. That will involve lots of different things. It will involve new ways of displaying data, new ways of thinking about the data in the clinical context. I actually think one of the most interesting things about genomics, and to be honest, any assay is that they rarely reach any form of maturity until they are used in the clinic, until they are actually used in implementation. For example, many genetic tests at the moment, don't change therapy and they don't change outcomes. But partly, that's because they've never been studied in that context.                                            One of the things that I think Glen [inaudible 00:26:58] has to be really congratulated for is his focus on pharmacogenomics as being one of the early areas in which this will really move forward. I believe that by immersing ourselves in it, by actually trying it in the clinic, we're going to learn much more.                                            Part of that gets back to the original topic that we spoke about, which is phenotype. The only way to really begin to understand collection of phenotype is if you do it in the context of existing genotype, I think. And so, as we move into new phenotypic areas, we're not going to be able to test everything and everybody. I think there, the genome will end up being an important framework, lifelong framework for the management of a patient's diagnosis, prognostication, and then therapy, potentially in that order.                                            I think you need a whole different set of skills. You need a whole different set of technologies. But most importantly, you need information that you can interpret in the context of the person in front of you. Until you can make mechanistically important insights with one person, it's going to be very difficult for genomics to really change medical care. That's something that I think we should be focusing on.                                            I think we've tended to have an associate of strategy for genetics. We haven't driven it into the clinic. As we drive tests into the clinic, whether it's troponin T or whatever, you begin to understand much better how to use them. Although, sometimes, that can also go in quite extreme directions that you may not necessarily anticipate. Troponin originally was a stratification tool for acute coronary syndromes, and now it's virtually a diagnosis in its own right. And I think you'll see that tendency revert over time as people begin to understand the biology of troponin, of isoform switching, and peripheral tissues of the way in which troponin may represent very different disease biologies.                                            At the moment, it seems like it's a very simple and straightforward yes/no type of test. There's no such thing in medicine, and I think that's what we're learning about genomics. Instead of conceiving it as a series of ten to the nine yes/no tests, we're going to end up with a very different vision and view of how it can be implemented in clinical practice. And that can only come from having clinicians and geneticists work together on this. In fact, one of the things that we've been doing in the partners environment with some of our colleagues, and I have NIH funding to do this with Heidi Rehm, with Sandy Aronson, and with Sean Murphy, is to think about how we display data, but also how we collect information in light of that genomic data that helps in an iterative way and a learning fashion, informed genotype/phenotype relationships in a much more probabilistic manner than we have done to date. There are lots of efforts in that space, that just happens to be one that I'm involved in. But I think it's a generalizable approach that you're going to see moving into the clinic in the next few years.                                            From the standpoint of training, I think what you want to do is to get exposure to all types of genetic information so you understand common alleles, rare alleles, genomics, and individual panels. I think the best way of doing that is to have that be part of training programs. In fact, with one of my junior colleagues, Dr. Aaron Aday, we recently wrote a short piece highlighting how important it will be for all of us to come together to think about how do we start to introduce the concepts of genomics into standard clinical training programs. And that's something we're working on fairly avidly at the Brigham, and I'm sure there are ... I know there are efforts at many other institutions to do similar things. Dr Anwar Chahal:            That article was published in Circulation in July of this year, if anybody wants to download that. I think if we talk to clinical trainees and ask them what are their concerns about training, as you know, training can be very long in cardiology, which is a procedurally based specialty, whether or not you become an invasive proceduralist at the end of it, there is that component at the beginning. Do you think a standard, in the U.S. a standard three-year program with two years of clinical and one year of research, can incorporate that at a sound enough level to allow somebody to practice? Do you think we're going to look at increasingly a one-year, or a six-month, sort of add-on fellowship for those interested more on the inherited side or more on the genomic side?                                            I, like yourself, trained in London, and the training programs are longer in the U.K. It was probably six years when you were there, it shortened to five, and now increasingly, it's going to become six and maybe even more with a general fellowship for five years, and then a super-advanced fellowship. Inherited cardiovascular conditions, certainly there, has become a module that is encouraged for people to take and then become somewhat certified in inherited cardiovascular conditions. What do you think there, in terms of incorporating all of that as well as learning basics of echo, and device therapy, and catheterization, what are your thoughts? Dr Calum MacRae:          Again, I look at this as a spectrum. There's a trajectory for all of these types of innovation and knowledge. It starts off being super-specialized, it goes into a more general location, and then eventually, it's an integral part of everybody's clinical practice. I do think that what you're going to see is rather than, and this is already, I think, the case in many elements of medicine. Medicine has already exceeded the knowledge base, even when I was training, by probably a log order in terms of the complexity and extent of content, not that I trained that long ago.                                            One of the core elements that I think that we're seeing is that we need to move medicine from what I believe has become somewhat deprofessionalized state, to one where you're actually focusing not on the actual core knowledge that you bring with you to the table, but actually the way in which you integrate knowledge. So, I think the focus of training is going to change somewhat. It has had to change in other fields. Medicine, I think, for a long time favored that sort of single, comprehensive approach in one mind. And medicine is going to become more of a team sport, and it's also going to become more of a knowledge integrator profession that it has been for some time.                                            It's interesting, when medicine started, there was so little knowledge that you really had to have almost every physician be an experimentalist using [inaudible 00:34:48] of one experiments in front of them. I think the way that I see medicine evolving is that as the knowledge base and the rigor of that knowledge base improves, many of the things that we think of as professional activity today, will actually devolve through primary care and, to be honest, into the community. There are many things where the rigor of the underlying [inaudible 00:35:12] are as such that there's no reason for a licensed provider to be involved. We allow our patients to install their own wireless networks without a technician. I'm sure most of them could look after their own lipids pretty effectively if they were given the right information.                                            So, a lot of stuff will begin to move in that direction. And as that happens, I think the way in which information is displayed, the way in which data are collected, and the workflow around integrating information will change. That doesn't get past the point that you brought up, which is that that will probably take a couple of decades, and in the interim, I think people are going to end up training in modules of subspecialty, but I think one of the things that I sometimes like to ask myself is what's the end game? Where is this going to end up? And can we build systems that train directly for that end game, rather than going through these intermediate steps. I think that's something where I think we tried, in the short piece that we wrote in Circulation, to argue that everybody should have some exposure, and that that exposure can change over time. We should be equipping people, not to know genomics, but to be able to learn how genomics is impacting their patients for the next 50 years.                                            That model of professional training is actually the one that really was the dominant model until maybe 100 years ago. And then, for reasons that don't quite seem obvious to me at least at the moment, we sort of tended to slowly move to more of a learned knowledge base that was then applied. Physicians sort of steadily got to the point where we're now data entry clerks. The actual amount of professional and intellectual engagement has, I think, slowly diminished in many medical subspecialties and medical specialties.                                            The opportunity that genomics and other advancements in technology in medicine bring is the chance to, I think, reprofessionalize ourselves to move from just simply defining ourselves in terms of the knowledge base that we each bring to the table, but defining ourselves rather in terms of how we put the knowledge together around individual problems and individual patients. It's a very much more patient-centered biological approach than perhaps we've had over the last couple of decades.                                            I think these are ... I'm obviously stating a lot of this somewhat in extremes, but I think that these are general trends that you see in medicine. They've happened in other fields as well, and people have overcome them. It's usually a function of changing the workflow itself, of changing the way in which the information ends up in the professional's hands and how you collect the data that you use, then, to interpret the existing knowledge. That, I believe, we haven't really reworked probably since Ozler's time.                                            It is amazing that we still have workflow ... I mean, it's amazing in lots of ways. It's an amazing tradition, but it is quite interesting that we still have workflow that is probably largely dependent on what Ozler liked to do when he was growing up in terms of the times of day that he got up and his workflow. That's sort of instantiated in many ways in everything that we do. Nothing entirely wrong with it, but there's a lot happened since then that we haven't really changed. Medicine is not yet, in many instances, a 24/7 profession, and yet most other things that have much less in the way of impact on society, are already 24/7 professions in many settings.                                            So, I think you're going to see a lot of demographic changes in medicine that come from the advent of technology and other industries. And I think those will all transform the way that we imagine training in medicine, along the same sort of timeline as some of the traditional approaches that you described, building out a training module and then having a subgroup of people do a six-month or a year of extra training. I see that as a short-term solution. I think, ultimately, longer term solutions are changing the whole workflow of medicine. Dr Anwar Chahal:            What have you done in your own program at the Brigham to introduce genomic medicine training for fellows? Dr Calum MacRae:          We are building out ... Obviously we have a fairly large cardiovascular genetics clinic. I think probably the largest in the world. We have now seven, soon to be eight, providers working only and wholly in cardiovascular genetics. We therefore have the ability to have our fellows rotate through our genetics clinic. We have inpatient and outpatient genetics services. And we also, obviously, involve our fellows in a lot of the academic pursuits going on in both our genetics and genomics programs in the cardiovascular clinic.                                            As we do, our colleagues are no longer in training. We have regular, in our clinical conference slot, we have, several times a year, a genetics component. And then, what we have also, is an integrated training program with clinicians and pathologists that is really bringing the individuals who are understanding the technical aspects of the genetic testing with the individuals who are learning and understanding the clinical aspects of that testing. And so, we imagine over time that this will evolve into potentially the type of specialist module that you described. But also, into a fixture that goes all the way through our two-year clinical training program.                                            We've sort of taken the point of view that we probably need to do a bit of both. We need to, given what I've said in the last few minutes, that we need to take a thread that recognizes a short term and intermediate term need for specialization, but also recognizes that we have to equip every one of our trainees, and every one of our physicians with the ability to begin to learn the underlying sides of genomics, and the underlying approaches to using genomics in every aspect of clinical cardiology. And so, we're doing both of those things, and have active efforts in both. Dr Anwar Chahal:            You mentioned integration with pathologists, but for our colleagues who are not clinicians, what about the research angle, and the scientists, when they're in training? Is that integrated so that we are getting this meeting of minds that is essential? Dr Calum MacRae:          Absolutely. In fact we, thanks to a variety of efforts at Brigham Women's, we have now at least three separate venues in which this occurs. I mentioned cardiovascular genetics clinic. We also have a genomic medicine clinic, which I'm one of the clinical co-directors for, where we actually have cases that come through routine clinical care that seem as if they would benefit from whole genome or whole axiom sequencing. And then we have a weekly conference that's actually led by Dick Maas and Shamil Sunyaev, two of our genetics colleagues, and taped in specialists from Althrop Medicine as well as scientists from the entire Harvard Medical School environment. So we bring everybody together around mechanistically solving individual clinical cases.                                            And then the third venue is one that's part of a national network, the Undiagnosed Diseases Network. We are one of the sites on the national NIH-funded UDN network. And there again, one of the themes is identifying individuals or families who would benefit from both rigorous genomic analyses as well as much deeper phenotyping. That's been a program that I think has been very exciting, and one that we, again, have learned a huge amount from in terms of how do you begin to build the infrastructure that brings, not just the fresh clinician to see the patient, but somebody who ... A whole team of people, who understand and can evaluate all the biological aspects that are relevant in that patient.                                            It also brings to bear the scientific expertise that you might need in order to make a mechanistic connection between genotype and phenotype in that one individual. And some of that involves animal remodeling. In cancer, for example, there's a concept that has emerged over the last two to three years of what's called co-clinical modeling. Once you've identified some of the genomic features, it allows you to begin to model in an animal, in parallel with the trajectory of the patient, and individual [crosstalk 00:44:54]- Dr Anwar Chahal:            As some people call them. Dr Calum MacRae:          Exactly. Creating an avatar. And in many instances, that's an avatar that includes multiple different disease models. We have begun to do that in the cardiovascular space. I think, obviously it's early days yet, but I think there are lessons to be learned about how you build the types of infrastructure that allow people to move beyond this state where a patient's outcome is dependent on him seeing the right doctor, on the right day, at the right time.                                            There are actually systems that funnel the patients into the right venue based on objective criteria at every stage. I think that's the type of reorganization, re imagination of the medical system that we need. We sort of duplicate things in lots of different areas, and you're still dependent on hitting the right specialist, on the right day, at the right time. Or not seeing a specialist. Seeing a generalist on the right day, at the right time, who is able to put everything together. Or even hitting somebody who has the time to listen to your story in a way that helps you identify the exposure or the genetic basis of your condition.                                            If we recreate the professional environment that I talked about earlier, I think in ways that are both traditional and novel at the same time, I think we will do ourselves a great service and build a platform that lets all of the technologies, including genomics that we've talked about today, begin to impact patients in a real way on a regular basis. Dr Anwar Chahal:            Thank you for that. One question I think is important to look at from the other side, you've gone from One Brave Idea to one revolution in medicine if I can be so bold. You mentioned so many other services are 24/7. You give an example, you can book your hotel in Shanghai sat in the Midwest, and you can change your booking on an app on a phone, and yet in medicine, it's so difficult to arrange an appointment. We have resisted that 24/7 service, aside from the acutes. But for the sort of chronic workload that we have, the 24/7 model has been resisted. What do you think are some of the challenges? Because I can almost hear members of our profession saying, "Well, who wants a 24/7 service and who wants to provide that 24/7 service?", and is it always necessary to have that 24/7 service?                                            As you say, so many things, such as hypertension treatment, you mentioned lipid management, could actually be done reasonably well by patients who are well trained. And certainly in heart failure, you can teach patients to take their Furosemide or their Lasix by weighing themselves and adjusting it, and can do it relatively well, and relatively safely. What do you think are the challenges to get the profession to realize that this is what's going to happen, and they've got to get on board? Dr Calum MacRae:          Well, I don't think you want to make it somehow mandatory. I think there are elements. Every patient is different. I think that's something we've used as a chivalrous for many decades as a profession. The reality is that we don't do very well. It takes, from the time a medication hits the guidelines, not the trials are finished, but the time that it gets accepted into the guidelines, let's say as a Class I recommendation. The average time to reaching equilibrium in the population is 12 to 15 years in cardiovascular disease. So you'd hate to be the person who got that drug in the 11th year, if you actually end up having your event in year three or four. And yet you can upgrade software for your phone, and hundreds of millions people upgrade it in the first couple of days after a release.                                            So, we have to build systems that allow us to be as efficient as every other element of our lives, and yet don't, in any way, diminish the importance of the personal interaction, the healing interaction that comes from a patient provider encounter. I think we do ourselves a disservice if we just imagine everything in exactly the same way as it's always been. A lot of it just requires us to make relatively modest changes to the types of things that we do, and to cede some control over some elements of it.                                            People are not dependent on making cyclical appointments to have doses of drugs tritrated. But once we've identified that a drug needs to be on board as a result of a primary indication, that we allow the titration to take place in an efficient and cost-effective manner. I think a lot of what we do is driven by how we get paid. A lot of ... And that's not criticism, it's natural in every single profession on the planet. You do things the way that the system is set up to have them be done.                                            And so, I think with relatively little in the way of systems engineering, you can have a 24/7 system without having 24/7 physicians. There are some areas, obviously intensive care units, where you do have 24/7 coverage already, but people are so used to having asynchronous care that being able to literally come home after a night shift and make their reservation for a restaurant the following evening, on their phone, often on another continent, it is a little bit strange that we literally can't book patients into your own clinic without calling up a couple of people.                                            I just think that some of this is resistance for resistance's sake. Some of it is people actually simply restating the things that we all believe are important parts of medical encounters. I think we just have to be creative about how we move from here to there. I think the thing that I find perhaps most interesting is that somehow the creativity of physicians is not fully exploited. We haven't really asked doctors and patients to come up with new approaches to how care is delivered, to how patients are seen. But I think if we allowed venues where that could happen, that would be actually the way in which we would evolve a very different system.                                            I think some of that, as I said, just goes back to the way in which everything is structured. All of the payment models, all of the ... Even the types of places that we see patients, are very much anchored in history. They're legacy items and there are lots of reasons why that's the case. Medicine, you can't show up with a minimally viable product. You need something that works perfectly day one, because of the liability. And so, what we need are just to rethink the way in which we even move medicine forward. What we know we can't do is just keep doing what we're doing, and changing modestly, rearrange the deck chairs.                                            What we need to actually be able to do is find places where we can actually, or venues where we can change things and test new models of care in a relatively low risk situation. I think you already see lots of payers, the federal government, and the NIH all thinking about how you can do that. Some of the [inaudible 00:52:55] efforts, some of the ... Even the NHGRI efforts in genomics. One of the nice things about genomics is because it's a new tool, it allows you to reinvent the way in which medicine is delivered. And so, I believe things as diverse as the precision medicine initiative, and as some of the most fundamental ways in which NIH funding is being restructured, will all potentially impact the way in which creativity and innovation start to evolve within the healthcare system.                                            I don't want to sound revolutionary. We're all doing all of this, all of the time. It's just not structured in a way that seems to very efficiently reach reduction to practice across the entire medical ecosystem. Part of what I think we need to do is, as a profession, build better ways of identifying where the innovation is occurring, and I will tell you I think it's occurring almost evenly across the entire medical universe, it's just that it doesn't propagate. All medicine, at the moment, is quite local. I think the things that you start to see happening in the industry that will change it are the fact that medicine is becoming much more like every other area of endeavor. It's becoming linked by technology. And once information flows more efficiently, I think a lot of the things that sound as if they're revolutionary, will end up actually just seeming like a series of obvious conclusions, based on the information that we've gleaned from early outlets or success stories.                                            Many of the things that I've mentioned today, they're not revolutionary at all. There are entire healthcare systems that use these approaches. But they just haven't become generalized because of the way that medicine works. And so, I think that's one of the reasons that I'm a believer that technology in particular will have a transformative effect, just on the way that doctors talk to other doctors or relate to their patients, and the way in which creativity and innovation propagate through the medical system will change very rapidly as a result of that.                                            And that's one of the great benefits of the electronic health record. I don't think EHR's now are perfect. In fact, in many ways, they're where other industries were 15 or 20 years ago. The supply chain in many large retail organizations was much more sophisticated in the mid-80s than the average EHR is. But what they've done is begin to collect the data in the right place, and in the right way, in a structured format. But as technology begins to cut across different EHR's and across different healthcare network, you'll see things, synergies begin to emerge that will accelerate the pace of change.                                            It's not by chance alone that medicine has attracted different types of people over the last 50 or 100 years. I think they'll just see the types of individuals that come to medicine be more diverse and more distinctive, and that also I think will help. More distinctive in their skillset, and that will help accelerate change in ways that again, will seem far from revolutionary fairly quickly. Dr Anwar Chahal:            Thank you for that. I wanted to come to the last section of the podcast, and sort of back to where I said it was joking, and you said I wasn't joking about doing three residencies. So, could you tell us a little bit about your own training and your own path? Originally from Scotland, through to London, and then over to the U.S.                                            And also, if you could share some of those pearls that you've picked up that aren't obvious to us in books, or sometimes are so obvious that they're elusive and not always apparent to young, up and coming trainees, both on the research side as well as the clinical. Dr Calum MacRae:          Yeah, sure. I trained in [inaudible 00:57:15] which had I think a very healthy attitude to specialism and generalism, and the relationship between them, and instilled in all of the specialists the need to always maintain some general medical capability. To this day, I still intend on general medicine for that reason.                                            I then moved, I did cardiology training in London, and was fortunate to work in a couple of hospitals, one of which had a very interesting, I supposed, quaternary care clinic which had extremely complicated patients. That's where I did my second internship, at the Ross Graduate Medical School in Hammersmith. And everybody who was an intern in that setting had already basically been board certified in internal medicine, so they'd all finished their medical training, come back to do an internship in that setting.                                            And there, I saw some amazing cases. There was an entire service for carcinoids, there was an entire service for many rare and wonderful diseases. At that point, you began to see how super-specialist knowledge can be incredibly helpful. But it can also be restrictive if it's not applied in the right way.                                            And then I did cardiology training at St. George's Hospital in London with some amazing mentors. John Camm, who many people will know from his work in atrial fibrillation and sudden death. David Warr, another very well known electrophysiologist, one of the early pioneers. Bill McKenna was my primary mentor, and he was somebody who had worked on the very earliest descriptions of hypertrophic cardiomyopathy when he had originally been at the Hammersmith, and then moved to St. George's.                                            He taught me a lot about, well many things. First of all, focus in your career, understanding the skillsets that you needed to accumulate in order to a) build a distinctive portfolio and b) to maintain your relevance by accumulating new skillsets as you move forward. And he had actually established a collaboration with Simon's. That was one of the reasons that I ended up moving to the U.S., and had a fantastic time with John and Cricket, at one of the earliest times in genetics moving into cardiovascular disease.                                            I learned a huge amount from colleagues, at that stage, both at the bench. Hugh Watkins is now chair of cardiology and lecturer of medicine now in Oxford, was a bay mate who was there a couple of years ahead of me and I learned a huge amount from him. I realized ... My wife is from New York City, from Long Island rather, and I realized I had to probably stay in the U.S. for those reasons, and I retrained at that stage in internal medicine again at the Brigham where mentors such as Marshall Wolf and, actually cardiology mentors at that stage were people like Punky Mudge and Pat O'Gara, who then helped me to adapt to the U.S. system.                                            The only thing I will tell you is that I don't think I ever learned as much as I did in each of my internships. I think the learning curve is incredibly steep. I'd been out of clinical medicine for four or five years, focusing on the lab, before I went back to my third internship. But I still think it was one of the most amazing experiences, largely because of the fact that you learn from every colleague, and you learn from every patient. I think if you go through most of your life thinking like that, I think you can end up doing very well.                                            Actually, one of the other things that's really important is actually emphasizing those personal connections. The first fellow I had at Brigham and Women's when I was an intern was Joe Hill, who's now the editor of Circulation, the chair of cardiology at UT Southwestern. Almost everybody that I know in cardiovascular medicine, I've encountered in those types of settings. Either in training settings, or in research collaborations, or at research meetings. You just begin to see a whole list of people that have worked together in different ways, and have learned from each other. I think that's one of the most powerful things to take away from research or clinical training.                                            I then was fortunate enough to get the chance to do a second cardiology fellowship at Mass General. There, I went to Mass General actually because of the focus on zebra fish genetics. I realized at that stage to really be able to study things at the scale that I thought was going to be necessary, I needed a high [inaudible 01:02:40] system, and Mark Schwartz, before he went to Novardis, on the zebra fish and the cardiovascular system, was very inspiring and I had a great time there. And then, ended up spending some fantastic years at Mass General where I eventually became the program director. But again, there I learned an incredible amount from people like Bill Dec, from Roman Desanctis, from Dolph Hutter. All of whom had very strong clinical presence, as well as from the researchers. Mark Fishman, the late Ken Bloch, and many others.                                            And then also, perhaps one of the most important people in my long term training was Peter Yurchak, who had been ... He had actually defined, I think, the training programs in U.S. cardiology about 35 years earlier. He had been the program director since its inception in the 50s until he retired in 2005 I think it was. And then I became the program director and was there until I moved back to the Brigham in 2009, and became chief in 2014.                                            I think the trajectory is really, I outline it only to highlight the fact that it took me a long time to get where I was going, but that I spent most of my life enjoying the journey. And I think that's actually one of the most important lessons I took away from it. You can end up finding situations where you feel like you might become frustrated, but in fact, if you go into them with the right attitude, and not only that, if you do it with the right people, you can take a huge amount out of it.                                            I was incredibly fortunate in the fellowship class that I had at Mass General. Mark Sabatine is now the chair of TIMI, Patrick Ellinor, who is the head of EP and a pioneer in atrial fibrillation genetics. Stan Shaw, who is now the chief scientific officer with me in One Brave Idea. Danita Yoerger, who's the head of ECHO, and an outstanding ECHO researcher at Mass General. Mark Rubenstein, who's a very successful cardiologist, and a fabulous clinician. That group of people actually, I think, together helped me realize how much you could take from training no matter how old you are, and no matter how grumpy you seem when you don't get the full nights sleep.                                            In the research side, I think the other thing that was obvious was that so many people bring so many different things to the table in research that you should never over or underestimate any aspect of the entire profession. I think I still get remarkable insights into research questions from colleagues who are clinicians, who've never done any research, just from astute observation and declaring a problem in a way that encourages investigation. I think that's one of the most important elements of training is how do you work out what you need to do, and how do you make sure that everything that you do between the start and the finish of that journey is used to help and to improve the way in which you end up doing what you ultimately find as your sort of settling point in your career.                                            I think the other thing that I will say from the standpoint of research is it's always best to try and think about blending different fields together. What you don't want to do is end up being a clone of one of your supervisors or your mentors. It's really an important thing, and I encourage this in all of our trainees the importance of being a bridge between different disciplines. I think that's something that requires real emphasis.                                            And then, finally, never ever forget that the single most important thing in all of this, whether it's the reorganization of clinical care or the core research environments, is the biology in the patients in front of you. And so, one of the things that I'm particularly and acutely aware of almost every time I see patients is that the patients often know much more about the condition that they have than you ever will. Listening to them is actually very important piece of everything that you do.                                            In fact, one of the reasons that we began to move outside the heart in our heart failure research was talking to patients about their pre-clinical elements that they found in their families. So, often, when you see a family with inherited heart disease, before the gene is identified, before anybody has a phenotype that you recognize, the patients themselves can assess who's likely to develop the disease from their intrinsic knowledge of their siblings, and their cousins, and their other family members.                                            So, for example, one of the families that I've worked on intensely, there's a anxiety disorder that is a much more stable and much more specific part of the phenotype than any of the cardiac arrhythmias, and it's actually turned out to be quite a difficult anxiety disorder to define using even DFM criteria. But when we asked the family, they were very able to tell the people in the family who just were at the normal edge of neurotic from those who truly had the anxiety disorder that co-segregated eventually with the arrhythmia.                                            The lesson I've learned time and time again is that patients always are a vital and central part of the answer. And it's a pride thing to say, but particularly in genetics and genomics, I think, and particularly with the reemphasis on phenotype, that I believe is necessary, I think we do well to try and make sure our research and our clinical care, our discovery, and our disease management are very tightly aligned. And I think technology is one of the ways that will help that happen. That actually is part of what being a professional really is. If you go back to the early professional guilds, that's exactly how they were formed. It was groups of experimentalists who were interested in particular problems that formed the original professions in European cities during the Renaissance. I think that's something that we would do well to think about as we continue to remodel medicine in the 21st century. Dr Anwar Chahal:            Thank you for that. Lots of important points there, and I guess your emphasis that enjoying the journey rather than thinking about the destination, but did you always know where your destination would be? And, in fact, that brings me to another question. Have you actually reached your destination, or is your journey still ongoing? Dr Calum MacRae:          So, exactly. I think that's the key thing. You don't need to necessarily know where you're going to stop. You just need to know where you're headed. That's something I actually tell people as they're interviewing for fellowship or residency, that part of what people are looking for when they talk to you is that you have thought through and organized your life around your goals. And those goals can change. Nobody's going to hold you ...

Generic Name Furosemide Trade Name Lasix Indication edema, hypertension Action prevents reabsorption of sodium and chloride in the kidneys, increase excretion of water, sodium, chloride, magnesium, potassium Therapeutic Class diuretics Pharmacologic Class loop diuretics Nursing Considerations use caution with liver… The post Furosemide: Lasix (diuretics) appeared first on NURSING.com.

What's your favorite way of giving furosemide to the critically ill, fragile, dyspneic congestive heart failure patient? Is it worth putting in an IV catheter just to give furosemide IV? (No). Does it matter what route you give it?

What's your favorite way of giving furosemide to the critically ill, fragile, dyspneic congestive heart failure patient? Is it worth putting in an IV catheter just to give furosemide IV? (No). Does it matter what route you give it?

Gregory Martin, MD, discusses some of the topics from his presentation during the 36th Critical Care Congress, "Furosemide and Albumin in ARDS." Dr. Martin is assistant professor of medicine at Emory University in Atlanta, Georgia, and the section head of pulmonary and critical care division at Grady Memorial Hospital where he is also the director of the medical and coronary ICUs.

Despite a wealth of data, the mechanism of the direct dilator effect of furosemide on the systemic arterial and venous systems is far from being satisfactorily understood. Therefore, we investigated whether furosemide is capable of stimulating the production of the endogenous vasodilators nitric oxide and prostacyclin in primary cultured bovine aortic endothelial cells by an enhanced synthesis and release of endothelium-derived kinins. Nitric oxide production was assessed in terms of intracellular guanosine cyclic-3',5' monophosphate accumulation; kinin and prostacyclin release were determined by specific radioimmunoassays. Furosemide concentration- and time- dependently increased the formation of nitric oxide and prostacyclin. Maximal increases of both autacoids were already obtained after a 5-min incubation with 3 x 10(-7) to 10(-6) mol/l of furosemide. In the same concentration range, furosemide led to an enhanced release of kinins into the supernatant of the cells. This observation was supported by the inhibitory effect of the specific B2 kinin receptor antagonist icatibant (Hoe 140) on the furosemide-induced increase of nitric oxide and prostacyclin. Thus the hemodynamic effects, and in particular the direct early dilator effect, of furosemide may be explained in part by an enhanced endothelial synthesis and release of bradykinin and related kinins, which in turn stimulates endothelial autacoid formation via B2 kinin receptor activation.

Torasemide is a new loop diuretic with a longer half-life and longer action than furosemide in healthy subjects. In order to evaluate the pharmacodynamic effects, single oral doses of furosemide (80 mg) and torasemide (20 mg), which were equipotent in healthy subjects, were given to 14 patients with cirrhosis and ascites. Before the study patients underwent an equilibration period of 4 days without diuretics. The drugs were alternated following a randomized double-blind cross-over design after a wash-out period of at least 2 days. Urine was collected at defined intervals for 24 h after drug administration and blood samples were taken before, 6 h and 24 h after medication. Torasemide induced greater cumulative 24 h diuresis (2863 ± 343 vs. 2111 ± 184 ml, p < 0.01) than furosemide. Torasemide did not differ from furosemide for cumulative 0–6 h sodium excretion (96 ± 17 vs. 92 ± 23 mmol sodium) but caused a more pronounced cumulative 6–24 h natriuresis (38 ± 11 vs. 17 ± 4 mmol, p < 0.05). Five patients exhibited a weak response to furosemide (0–36 mmol sodium/24 h, median 24 mmol; 690–1460 ml urinary volume/24 h, median 1325 ml). These patients showed significantly higher natriuresis and diuresis following torasemide (26–136 mmol sodium/24 h, median 78 mmol, p < 0.05; 1670–3610 ml urinary volume/24 h, median 2200 ml, p < 0.05). Twenty-four hours after administration of both drugs there were no significant changes in hemodynamic, renal or hormonal parameters. No adverse effects were noted with either treatment. These findings suggest that torasemide might be more advantageous than furosemide in the treatment of ascites due to cirrhosis.

Double-barrelled ion-sensitive micro-electrodes were used to measure the changes of the intracellular activities of Cl-, K+, and Na+ (aiCl, aiK, aiNa) in neurones of isolated rat sympathetic ganglia during the action of gamma-aminobutyric acid (GABA). The membrane potential of some of the neurones was manually 'voltage clamped' by passing current through the reference barrel of the ion-sensitive micro-electrode. This enabled us to convert the normal depolarizing action of GABA into a hyperpolarization. A GABA-induced membrane depolarization was accompanied by a decrease of aiCl, aiK and no change in aiNa, whereas a GABA-induced membrane hyperpolarization resulted in an increase of aiCl, aiK and also no change in aiNa. GABA did not change the free intracellular Ca2+ concentration, as measured with a Ca2+-sensitive micro-electrode, whereas such an effect was seen during the action of carbachol. pH-sensitive electrodes, on the other hand, revealed a small GABA-induced extracellular acidification. The inward pumping of Cl- following the normal, depolarizing action of GABA required the presence of extracellular K+ as well as Na+, whereas CO2/HCO3--free solutions did not influence the uptake process. Furosemide, but not DIDS, blocked the inward pumping of Cl-. In conclusion, our data show that only changes in intracellular activities of K+ and Cl- are associated with the action of GABA. Furthermore, they indicate that a K+/Cl- co-transport, and not a Cl-/HCO3- counter-transport, may be involved in the homoeostatic mechanism which operates to restore the normal transmembrane Cl- distribution after the action of GABA.

Carbachol and γ-aminobutyric acid depolarize mammalian sympathetic neurons and increase the free extracellular K+-concentration. We have used double-barrelled ion-sensitive microelectrodes to determine changes of the membrane potential and of the free intracellular Na+-, K+- and Cl−-concentrations ([Na+]i, [K+]iand [Cl−]i) during neurotransmitter application. Experiments were performed on isolated, desheathed superior cervical ganglia of the rat, maintained in Krebs solution at 30°C. Application of carbachol resulted in a membrane depolarization accompanied by an increase of [Na+]i, a decrease of [K+]i and no change in [Cl−]i. Application of γ-aminobutyric acid also induced a membrane depolarization which, however, was accompanied by a decrease of [K+]i and [Cl−]i, whereas [Na+]i remained constant. Blockade of the Na+/K+-pump by ouabain completely inhibited both the reuptake of K+ and the extrusion of Na+ after the action of carbachol, and also the post-carbachol undershoot of the free extracellular K+-concentration. On the other hand, in the presence of ouabain, no changes in the kinetics of the reuptake of K+ released during the action of γ-aminobutyric acid could be observed. Furosemide, a blocker of K+/Cl−-cotransport, inhibited the reuptake of Cl− and K+ after the action of γ-aminobutyric acid. In summary, the data reveal that rat sympathetic neurons possess, in addition to the Na+/K+-pump, another transport system to regulate free intracellular K+-concentration. This system is possibly a K+/Cl−-cotransport.