Podcasts about pradaxa

Are you still a little confused about the redesign of Part D of this AEP?  There are some changes you need to understand.  There is also a solution to help your clients get their prescription drugs.  It's the Canadian Medstore.  In this episode of The Broker Link, The Brokerage Inc. Executive Vice President, Josh Slattery talks with Bill Hepscher about the top drugs offered by The Candian Medstore you can offer your clients for only $50 a month. Those drugs include:  Eliquis (5 mg) Xarelto (20 mg) Farxiga (10 mg) Pradaxa (150 mg) Breo Ellipta (200 mcg) Ventolin HFA (100 mcg) Spiriva (18 mcg) Janumet (50/1000 mg) Januvia (100 mg) Symbicort (200/6 mcg) You can find a direct link to the Canadian Medstore on our website, www.thebrokerageinc.com.  You can also sign up on the Sunfire customer intake form.  You can find that information on our website too.      

Join Ben and Rahul for their discussion with Jake and Tor, breaking down the recent 495 million Dollar verdict in a product liability case against Abbott Laboratories for pre-term infant formula that increases the risks for developing necrotizing enterocolitis. Hear how Jake and Tor navigated this difficult case and won this epic battle. About Jacob Plattenbergerhttps://www.torhoermanlaw.com/team/jake-plattenberger/Jacob Plattenberger has taken hundreds of depositions, argued in countless hearings, and tried over 35 cases to a jury.His experience in and out of the courtroom has made him a passionate advocate for those injured due to the negligence of others.Jake started his career trying cases at one of the busiest civil courthouses in the country – the Richard J. Daley Center in downtown Chicago.He started out doing insurance defense because he knew that afforded him the best opportunity to get courtroom experience.“When I was working on the defense side, I always knew that I was going to be a plaintiff's lawyer. I knew that being able and willing to try a case to a jury was a skill that I needed to have if I was going to be able to offer my clients the best legal representation. Insurance companies and corporate defendants need to believe you when you say you will take them to trial – they need to fear that.”This type of real trial experience is exceedingly rare in complex civil litigation and having seen it from the defense side gives Jake an added advantage.At TorHoerman Law, Jake manages our Chicago office where he leads trial teams in nationwide, complex litigations such as:Representing dozens of workers across the United States who were exposed to Diacetyl at work and now suffer lung diseaseeg. The Juul/E-cigarette LitigationThe Incretin Mimetics Products Liability Litigation, currently pending in the Southern District of California, where he was named to the Plaintiff's Steering CommitteeVarious Transvaginal Mesh multidistrict litigations that are currently pendingJake also maintains a personal injury practice in Chicago, representing people and their families who have been victims of catastrophic auto and truck accidents, products liability, maritime accidents, premises liability, and medical negligence.Jake believes that to successfully represent his clients, it is absolutely necessary to get personally involved.Jake's quote below perfectly reflects that belief! Notable Cases & ResultsIncretin Mimetics – Products Liability Litigation, MDL Case No. 13MD2452 AJB (MDD). Appointed to the Plaintiff's Steering Committee by Judge Battaglia in the MDL. The case is pending.JUUL E-Cigarettes – Products Liability Litigation, JCCP No. 5052. Appointed to the Plaintiff's Steering Committee by Judge Anne Jones in the JCCP. The case is pending.Diacetyl – Leads the Diacetyl litigation for TorHoerman Law. Previous settlements and verdicts have exceeded $5,000,000.00 to date. Litigation is currently ongoing.Actos Related Cases, MDL Case No. 11 L 10011, Et. Al. – Actively participated in managing the case for TorHoerman Law which resulted in a $2.4 billion settlement.Gadolinium-based Contrast Agents Litigation Case No. 279 and Products Liability Litigation MDL No. 1909 – Managed the cases for TorHoerman Law which resulted in a large, confidential settlement.Bus Accident – Handled a bus accident injury case in which an individual was thrown from a seat. Resulted in a $850,000.00 settlement.Auto Accident – Handled an auto accident injury case that resulted in a $650,000.00 settlement.Slip and Fall – Handled a slip and fall accident that occurred on a sightseeing boat in Chicago. Resulted in a $490,000.00 settlement. Personal LifeJake was born and raised in Chicago.He now lives in the Chicago suburbs, where his two young sons keep him busy.When he isn't working, Jake is a lifelong Bears and Cubs fan and loves participating in the (mostly) healthy rivalry between the Cubs and Cardinals fans at TorHoerman Law.   About Tor Hoermanhttps://www.torhoermanlaw.com/team/tor-hoerman/Tor Hoerman is a nationally recognized attorney who has served in the field for more than 25 years.He is most well-known as the founder of the personal injury law firm TorHoerman Law, LLC (THL). Early Life & EducationTor was born the youngest of four boys on July 16, 1969, in Bethesda, Maryland to Kirk and Greta Hoerman.With his father serving as a Captain in the Navy, Tor often moved towns during his childhood, eventually landing in the Chicago metropolitan area.In Chicago, Tor lived in the Great Lakes Naval Base and Lake Bluff before his family settled in Lake Forest, which is where he attended high school.Despite repeatedly switching homes, Tor made the most of his situation.In high school, he played football, basketball, and baseball, and he earned varsity letters in each of these sports.In addition to varsity recognition, he was recognized as an All-county athlete and awarded the Booster Club Athlete of the Year his senior year.Outside of sports, Tor coached little league baseball, served as a summer camp counselor, and worked as a summertime janitor at his former high school after graduating.Tor attended Depauw University and majored in Political Science.He played NCAA baseball and football at Depauw, and he was the captain of the baseball team.After graduating from Depauw in 1991, Tor enrolled in the Chicago-Kent College of Law.During law school, Tor bartended at a local bar and clerked for Kravolec, Jambois & Schwartz, LLC. Legal CareerAfter graduating from law school in 1995, Tor took on a job doing insurance defense at Bolero, Cart & Stone, LLC, where he worked reluctantly for a year and a half.One day at work, Tor received a phone call from Steve Jambois, his former employer throughout law school, asking if he wanted a job on the plaintiff's side of insurance law.Tor immediately accepted the job, kickstarting decades to come of fighting corporations on behalf of harmed individuals.Tor's Transition to Medical Malpractice LitigationTor returned to Kravolec, Jambois & Schwartz to fight on behalf of medical malpractice victims, which mostly consisted of high-intensity trial work in the Chicago courthouse.After seven years at the Jambois firm, Hoeman was recruited by the Simmons law firm, based in an Illinois suburb of St. Louis, to start and lead a branch of the practice that focused on pharmaceutical litigation.Leading the Pharmaceutical Practice at Simmons Law FirmTor became a partner of what is now Simmons, Hanly, and Conroy and led the pharmaceutical practice for seven years.One of Tor most notable achievements while leading the practice was his work against Purdue Pharma and its reckless distribution of OxyContin.Tor was the first to file a case alleging Purdue Pharma's wrongdoing in distributing OxyContin and failing to adequately warn healthcare providers and the public of the risks of addiction.Achieving Justice Against Purdue PharmaHe led the litigation process and got Purdue Pharma to agree to a large settlement, which was distributed to thousands of accidental addicts.Tor took a step further to achieve justice in this case, assisting the Department of Justice in obtaining guilty pleas by Purdue Pharma representatives who had a direct role in contributing to the opioid epidemic. Founding TorHoerman LawHaving garnered success leading the pharmaceutical branch at the Simmons firm, Tor amicably decided to split from Simmons in 2009 and start his own pharmaceutical and personal injury practice called TorHoerman Law, LLC (THL).After negotiating the terms of the split, Tor struck a deal that allowed him to bring his entire staff from Simmons to his new practice, which summed up to more than 25 lawyers and staff members.Expansion and Success of THLTor opened offices in Edwardsville, IL; Clayton, MO; and Chicago, IL to kickstart operations; all three offices remain open today.In the time since opening THL, Tor and his team have litigated many pharmaceutical malpractice and personal injury cases.Notable Successes at THLTor's most notable successes while operating THL are perhaps co-leading the litigations against Boehringer Ingelheim's Pradaxa and Takeda's Actos.Through intense research and vetting, Tor was able to find substantial evidence indicating Actos causes bladder cancer and Pradaxa causes internal bleeding.He then presented the evidence to the companies, which decided to settle the cases.Tor played a significant role in negotiating these settlements, which ended up being $650 million for Pradaxa and $2.4 billion for Actos.Tor has also had major success in several other product liability lawsuits, such as Zelnorm, Gadolinium-based Contrast Agents, and Incretin Mimetics.We've outlined these cases, a few other notable cases, and their correlating results in the section below.Recognition & AwardsHis successes with these cases and beyond earned him the distinction as a Top 25 Notable Alumni from the Chicago-Kent School of Law, which was awarded to him and 24 other lawyers out of the tens of thousands who have graduated from the school since its founding in 1888.Tor is also recognized as a Top 100 National Trial Lawyer by the National Trial Lawyers Organization. Notable Cases & ResultsPradaxa (Dabigatran Etexilate) – Products Liability Litigation, MDL 2385 – Appointed by Judge Herndon as national lead counsel in the MDL. After protracted litigation successfully negotiated a $650 million settlement.Actos Related Cases, MDL Case No. 11 L 10011, Et. Al. – Appointed by Judge Dooling as lead counsel in Cook County consolidated docket (over 4400 cases). After protracted litigation, he was one of four lead negotiators (along with Pete Flowers, Mark Lanier, and Andy Birchfield) on a $2.4 billion settlement.Incretin Mimetics Products Liability Litigation, MDL Case No. 13MD2452 AJB (MDD) – Appointed as lead counsel by Judge Battaglia in the MDL. The case is pending.OxyContin – Represented thousands of “accidental addicts”. After protracted litigation, he negotiated a large settlement and assisted the DOJ in obtaining guilty pleas by corporate representatives.Zelnorm Litigation., Case No. 280 – Appointed lead counsel in NJ state court consolidation, took the major depositions and negotiated a confidential settlement.Gadolinium-based Contrast Agents Litigation Case No. 279 and Products Liability Litigation MDL No. 1909 – Appointed by Judge Polster as both the state and federal liaison and lead counsel in the Cook County consolidated docket. He negotiated large, confidential, individual settlements. Involvement in the Legal CommunityIn addition to his litigation work, Tor is on the Board of Managers of the Illinois Trial Lawyer Association and an Executive Board Member of the Mass Torts Trial Lawyer Association.He also attends national legal conferences on a yearly basis. Personal LifePersonally, Tor is the proud father of Casey, Kirsten and Quinn, and husband of Jessica.He tries to stay active, including still playing baseball.

In this episode, we review evidence-based guidelines for the emergency reversal of warfarin, dabigatran, and the oral Xa inhibitors (apixaban, edoxaban, and rivaroxaban). Key Concepts Reversal of anticoagulation is indicated in patients with major hemorrhage or when emergency surgery is necessary. Reversal of warfarin (Coumadin®) involves a fast-acting, short-term solution (usually prothrombin complex concentrates [PCC]) and a slower-acting, long-term solution (intravenous vitamin K). Idarucizumab (Praxbind®) is the preferred reversal strategy for dabigatran (Pradaxa®). Idarucizumab is a monoclonal antibody fragment specific that binds and inactivates dabigatran. If idarucizumab is unavailable, PCCs are recommended. Andexanet alfa (Andexxa®) is the preferred reversal strategy for oral Xa inhibitors and has FDA approval specific to apixaban and rivaroxaban. Andexanet alfa is a decoy factor Xa protein with higher binding affinity than human clotting factor Xa. There are several barriers to use with andexanet alfa that has led to low utilization in hospitals. If andexanet alfa is unavailable, PCCs are recommended. References Baugh CW, et al. Anticoagulant Reversal Strategies in the Emergency Department Setting: Recommendations of a Multidisciplinary Expert Panel. Ann Emerg Med. 2020;76(4):470-485. Cuker A, Burnett A, Triller D, et al. Reversal of direct oral anticoagulants: Guidance from the Anticoagulation Forum. Am J Hematol. 2019;94(6):697-709. doi:10.1002/ajh.25475 Tomaselli GF, et al. 2020 ACC Expert Consensus Decision Pathway on Management of Bleeding in Patients on Oral Anticoagulants: A Report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol. 2020;76(5):594-622.

This week on Pharm5: OTC Narcan (naloxone) Higher dose Rybelsus (semaglutide) iPLEDGE REMS in discussion WHO COVID-19 guidance for healthy kids Pradaxa (dabigatran) recall   Connect with us! Listen to our podcast: Pharm5 Follow us on Twitter: @LizHearnPharmD   References: FDA approves first over-the-counter naloxone nasal spray. U.S. Food and Drug Administration. http://bit.ly/42O0I8a. Accessed March 29, 2023. Hoffman J. Over-the-counter Narcan could save more lives. but price and stigma are obstacles. The New York Times. http://bit.ly/3lWSrhF. Published March 28, 2023. Accessed March 30, 2023. Oral semaglutide 25 mg and 50 mg demonstrate superior reductions in HbA1c and body weight versus 14 mg in people with type 2 diabetes in the PIONEER PLUS phase 3 trial. Novo Nordisk. http://bit.ly/3nBDJNG. Published March 24, 2023. Accessed March 30, 2023. Ozempic® (semaglutide) injection-A1C control within your control for a range of T2D patient Needs1,2,4,5. novoMEDLINK. http://bit.ly/40ISVHv. Accessed March 30, 2023. FDA panel votes to modify isotretinoin iPLEDGE REMS. Medscape. http://bit.ly/3FZIU0c. Published March 29, 2023. Accessed March 30, 2023. The iPLEDGE REMS Prescriber Guide. iPLEDGE REMS. http://bit.ly/3lU85ue. Published October 2021. Accessed March 30, 2023. Hassan C, Regan H. Who experts revise covid-19 vaccine advice, say Healthy Kids and teens low risk. CNN. http://bit.ly/3KlyOJt. Published March 29, 2023. Accessed March 30, 2023. Mueller B, Hoffman J. Routine childhood vaccinations in the U.S. slipped during the pandemic. The New York Times. http://bit.ly/3ziptMc. Published April 21, 2022. Accessed March 30, 2023. Birth-18 years immunization schedule – healthcare providers. Centers for Disease Control and Prevention. http://bit.ly/3JXI3y7. Published February 10, 2023. Accessed March 30, 2023. Ascend Laboratories LLC. issues voluntary nationwide recall of dabigatran etexilate capsules, USP 75 mg and 150 mg, due to the detection of N-Nitroso-Dabigatran (NDAB) impurity. U.S. Food and Drug Administration. http://bit.ly/3TUrGXN. Accessed March 30, 2023.

Agradece a este podcast tantas horas de entretenimiento y disfruta de episodios exclusivos como éste. ¡Apóyale en iVoox! ¿Es lo mismo Adiro que Pradaxa? ¿Y que el clopidogrel? A veces nos lleva a duda y en mostrador esa duda queda mal. Hoy os explico la diferencia teórica y práctica entre ellos. Ah! Quédate al final para saber una curiosidad más de marketing y de la utilidad del mundo animal. Espero que os guste! Escucha este episodio completo y accede a todo el contenido exclusivo de Claridad Farmacéutica. Descubre antes que nadie los nuevos episodios, y participa en la comunidad exclusiva de oyentes en https://go.ivoox.com/sq/919207

In this episode, Professor Jan Beyer-Westendorf and Professor Rupert Bauersachs discuss the latest real-world evidence for the extended treatment of patients with venous thromboembolism (VTE). They focus on data published from the all-comer Dresden NOAC Registry, which provides important insights on the adherence patterns of patients with VTE on anticoagulation treatment beyond 12 months. Our experts also discuss the FIRST and SWIVTER registries, and how their findings highlight the importance of patient preference in maintaining patient persistence with extended treatment in order for patients to gain the full benefits of their treatment. The views and opinions expressed throughout this podcast are those of the speakers based on their expertise and do not necessarily reflect those of Bayer. • You can read the most up to date CHEST guidelines here: https://journal.chestnet.org/article/S0012-3692(21)01507-5/fulltext • The Dresden NOAC Registry showed high persistence of patients with VTE on rivaroxaban, these results can be viewed here: https://www.thrombosisresearch.com/article/S0049-3848(21)00515-6/fulltext • EINSTEIN CHOICE investigated the extended treatment of VTE patients with rivaroxaban versus aspirin, results from the trial can be found here: https://www.nejm.org/doi/full/10.1056/nejmoa1700518 • The FIRST registry is the largest real-world evidence registry for rivaroxaban to date, read about its findings on treatment adherence here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8606029/ • Read more about the insights from the SWIVTER registry here: https://www.thiemeconnect.com/products/ejournals/abstract/10.1160/TH16-03-0209 • The EINSTEIN EXTENSION study our experts discuss in this podcast can be found here: https://www.nejm.org/doi/full/10.1056/nejmoa1007903 Extended treatment VTE podcast-draft1 4 • The pooled results from the EINSTEIN PE and EINSTEIN DVT studies are available here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3850944/ • For anticoagulant dosing information, see the European labels for apixaban (Eliquis) (http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_- _Product_Information/human/002148/WC500107728.pdf), dabigatran (Pradaxa) (http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_- _Product_Information/human/000829/WC500041059.pdf), edoxaban (Lixiana) (http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_- _Product_Information/human/002629/WC500189045.pdf), rivaroxaban (Xarelto) (https://www.ema.europa.eu/documents/product-information/xarelto-epar-productinformation_en.pdf) and warfarin (https://www.medicines.org.uk/emc/product/3064/smpc) Recording approval: PP-XAR-ALL-2638-1 Shownotes approval: PP-XAR-ALL-2639-1

Welcome to the age of PHARMAKIA (Sorcery, witchcraft and drugs i.e. potions) administered by Big Pharmaceutical Magnates et al. All donations and support for the show to be sent to: $Aigner2019(Cashapp).

Regular blueberry consumption may reduce risk of dementia, study finds University of Cincinnati, May 11, 2022 Researchers found that adding blueberries to the daily diets of certain middle-aged populations may lower the chances of developing late-life dementia. The findings were recently published in the journal Nutrients.  Krikorian said his team has been conducting research on the benefits of berries for people with greater risk for Alzheimer's disease and dementia for several years.  The researchers enrolled 33 patients from around the Cincinnati area between the ages of 50-65 who were overweight, prediabetic and had noticed mild memory decline with aging. Krikorian said this population has an increased risk for late-life dementia and other common conditions.  Over a period of 12 weeks, the patients were asked to abstain from berry fruit consumption of any kind except for a daily packet of supplement powder to be mixed with water and consumed either with breakfast or dinner. Half of the participants received powders that contained the equivalent of one-half cup of whole blueberries, while the other half received a placebo.  Krikorian said those in the blueberry-treated group showed improvement on cognitive tasks that depend on executive control.   Patients in the blueberry group also had lower fasting insulin levels, meaning the participants had improved metabolic function and were able to more easily burn fat for energy.   Krikorian said the blueberry group displayed an additional mild degree of higher mitochondrial uncoupling, a cellular process that has been associated with greater longevity and reduced oxidative stress. Oxidative stress can lead to symptoms like fatigue and memory loss.  Regular exercise with dietary advice linked to better mobility in frail older people Yale University, May 11, 2022 A program of regular exercise along with expert dietary advice is linked to a reduction in mobility problems among frail older people living in the community, finds a trial published by The BMJ today. The combination of aerobic (walking), strength, flexibility, and balance exercises alongside personalized nutritional counseling reduced mobility disability by 22% over three years. Their findings are based on 1,519 men and women (average age 79 years) with physical frailty and sarcopenia (a combination of reduced physical function and low muscle mass) recruited from 16 clinical sites across 11 European countries between 2016 and 2019. Women in the intervention group lost less muscle strength (0.9 kg at 24 months) and less muscle mass (0.24 kg and 0.49 kg at 24 months and 36 months, respectively) than control women, but no significant group differences were seen in men.  Study: Side effects emerge after approval for many US Yale University, May 9, 2022  Almost one-third of new drugs approved by U.S. regulators over a decade ended up years later with warnings about unexpected, sometimes life-threatening side effects or complications, a newanalysis found. The results covered all 222 prescription drugs approved by the U.S. Food and Drug Administration over ten yers.  The 71 flagged drugs included top-sellers for treating depression, arthritis, infections and blood clots. Safety issues included risks for serious skin reactions, liver damage, cancer and even death. “The large percentage of problems was a surprise,” and they included side effects not seen during the review process, said Dr. Joseph Ross, the study's lead author at Yale University.”We know that safety concerns, new ones, are going to be identified once a drug is used in a wider population. That's just how it is,” Ross said.  While most safety concerns were not serious enough to prompt recalls, the findings raise questions about how thoroughly drugs are tested before approval The study counted black-box warnings for dozens of drugs; these involved serious problems including deaths or life-threatening conditions linked with the drugs. There were also dozens of alerts for less serious potential harms and three drug withdrawals because of the potential for death or other serious harm. Among the drugs with added warnings: Humira, used for arthritis and some other illnesses; Abilify, used for depression and other mental illness; and Pradaxa, a blood thinner. The withdrawn drugs and the reason: Bextra, an anti-inflammatory medicine, heart problems; Raptiva, a psoriasis drug, rare nervous system illness; and Zelnorm, a bowel illness drug, heart problems. Exercise during pregnancy may yield metabolic benefits in grandchildren Harvard University, May 11, 2022 If grandma liked working out, her pain may be your gain. It may seem unlikely, but recent research out of the Joslin Diabetes Center says it just might be the case. Laurie Goodyear, a professor of medicine at Harvard Medical School, has found that a grandmother's exercise during pregnancy may make her grandchildren healthier metabolically, with less body fat, better insulin control and, in some, healthier bones. We are looking for epigenetic alterations in the DNA, because epigenetic alterations can be changed as rapidly as two generations. We analyze micro RNAs, some methylation situations in the F1 generation eggs and sperm to see what's going on. We are currently investigating how mothers' exercise affects their children's gametes. I'm confident in saying that women who are pregnant should try to be as physically active as they can, depending, of course, on the condition of their pregnancy. There's strong human data showing that exercise during pregnancy improves the mother's health; numerous animal studies showing improved first-generation health; and now we have evidence that maternal exercise will positively impact the health of the second generation. I'm not an obstetrician, and there are certainly conditions where a woman cannot perform exercise during pregnancy, but, when medically approved, being physically active is important—for the mother, the first generation, and now even the grandchildren. New Study Finds Simply Believing You Can Do Something To Improve It Is Linked With Higher Wellbeing University Of Southern Denmark And University Of Copenhagen, May 11, 2022 The number of people struggling with poor mental health and mental disorders has been rising around the world over the past few decades. Those who are struggling are increasingly facing difficulties accessing the kind of support they need – leaving many waiting months for help, if they even qualify for treatment. In our recent study, we asked 3,015 Danish adults to fill out a survey that asked questions about mental health – such as whether they believe they can do something to keep mentally healthy, whether they had done something in the past two weeks to support their mental health, and also whether they were currently struggling with a mental health problem. We then assessed their level of mental wellbeing using the Short Warwick–Edinburgh Mental Well-being Scale, which is widely used by healthcare professionals and researchers to measure mental wellbeing. As you'd expect, we found that mental wellbeing was highest among those who had done things to improve their mental health compared with the other participants. Interestingly, however, we found that – whether or not our respondents had actually taken action to improve their mental wellbeing – people who believed they could do something to keep mentally healthy tended to have higher mental wellbeing than those who didn't have this belief. So while it's most beneficial to take steps to improve your mental health, even just believing that you can improve it is associated with better overall mental wellbeing.The effect of night shifts—gene expression fails to adapt to new sleep patterns McGill University (Quebec).  May 7, 2022  Have you ever considered that working night shifts may, in the long run, have an impact on your health? A team of researchers from the McGill University has discovered that genes regulating important biological processes are incapable of adapting to new sleeping and eating patterns and that most of them stay tuned to their daytime biological clock rhythms. “We now better understand the molecular changes that take place inside the human body when sleeping and eating behaviours are in sync with our biological clock. For example, we found that the expression of genes related to the immune system and metabolic processes did not adapt to the new behaviours,” says Dr. Boivin, a full professor at McGill University's Department of Psychiatry. It is known that the expression of many of these genes varies over the course of the day and night. Their repetitive rhythms are important for the regulation of many physiological and behavioural processes. “Almost 25% of the rhythmic genes lost their biological rhythm after our volunteers were exposed to our night shift simulation. 73% did not adapt to the night shift and stayed tuned to their daytime rhythm. And less than 3% partly adapted to the night shift schedule. “We think the molecular changes we observed potentially contribute to the development of health problems like diabetes, obesity, cardiovascular diseases more frequently seen in night-shift workers on the long term,” explains Dr. Boivin.  Videos: 1. Will the Future Be Human? – Yuval Noah Harari (Start @ 2:13) 2. The Invention Of Whiteness.. (Start @ 0:28) 3. Jonathan Pie's Rant On Cultural Appropriation 4. Breakthrough deaths comprise increasing proportion of those who died from COVID-19 (5:44)

This episode is also available as a blog post: https://mdforlives.blog/2021/08/10/pradaxa-first-oral-anticoagulant-for-children/ --- Send in a voice message: https://anchor.fm/mdforlives/message

Este podcast é oferecido por HiDoctor – o software médico mais usado em consultórios e clínicas no país O resumo da semana de 12/07 a 16/07 traz as seguintes publicações: - Metanálise de ensaios clínicos randomizados de ivermectina para tratar a infecção por SARS-CoV-2 apresenta descobertas positivas (Open Forum Infectious Diseases) - Vacina da Pfizer como 2ª dose em indivíduos que receberam 1ª dose da vacina da AstraZeneca induziu resposta imune robusta, com perfil de reatogenicidade aceitável (The Lancet) - Etexilato de dabigatrana (Pradaxa) se torna a primeira opção oral de anticoagulante para uso em pacientes pediátricos (U.S. Food and Drug Administration) - Programa de triagem neonatal para doença falciforme foi lançado na África (The Lancet Haematology) - Estimulação do nervo occipital reduziu substancialmente a frequência de ataques na cefaleia em salvas crônica intratável com medicamentos (The Lancet Neurology) - Antidepressivos ISRSs e ISRSNs se mostraram eficazes para transtornos de ansiedade, obsessivo-compulsivo e relacionados ao estresse (PLOS Medicine) - Maior frequência de interrupções do tempo sentado traz benefícios para o metabolismo pós-prandial no diabetes tipo 2 (Diabetes Care) - Pessoas com diabetes tipo 1 e transtornos alimentares têm riscos consideravelmente aumentados de cetoacidose diabética e morte (Diabetes Care) - Doxiciclina por 7 dias foi superior à azitromicina em dose única para o tratamento da Chlamydia trachomatis retal assintomática (The New England Journal of Medicine) Veja mais notícias em news.med.br.

Here are the links for everything discussed in Episode 64. Times are also below so feel free to skip around and get to the drugs that interest you. (1:23) New pediatric indication for Ultomiris for PNH (5:18) Pradaxa now approved for VTE in pediatric patients (9:34) Rx to OTC switch of Astepro CDC updates on COVID-19 & influenza reporting Connect with The Rx Daily Dose:Twitter      Instagram      YouTube      Linkedin       WebsiteEmail: therxdailydose@gmail.comConnect with Ian Parnigoni PharmD. on social media:Twitter       Instagram       Linkedin  ★ Support this podcast on Patreon ★

Dental's pharmacology expert, Tom Viola, RPh, joins the show to talk about the U.S. Food and Drug Administration (FDA) approving dabigatran etexilate (Pradaxa) oral pellets for the treatment of venous thromboembolism (VTE) in children aged 3 months to less than 12 years. Viola discusses what dental practices need to know about this.

This week the FDA approved a first-in-class switch for an antihistamine nasal spray, a new oral contraceptive, and Pradaxa was approved to prevent venous thromboembolism in pediatric patients. Meanwhile, real-world data on the efficacy of the COVID-`9 treatment remdesivir has been published. 

Episode 3: James Horowitz interviews Rachel Rosovsky on DOACs. Dr. Rosovsky is the Director of Thrombosis Research in the Division of Hematology at Mass General Hospital. She is also an Assistant Professor at Harvard and a member of the Board of Directors of the PERT Consortium.  Dr. Horowitz is the Director of the CCU at NYU Langone Health and the Co-Chair of the Interdisciplinary Resuscitation Committee. He is also an Assistant Professor or Medicine and a member of the Board of Directors of the PERT Consortium. Directly acting oral anticoagulants.   FDA approved DOACS: Xarelto (rivaroxaban), Eliquis (apixaban), Savasya (edoxaban), Pradaxa (dabigatran). All DOACs have similar efficacy in terms of VTE occurrence and better safety profile compared compared to Coumadin. MOA: Dabigatran: directthrombin inhibitor.   Rest of the DOACs: factor X inhibitors. DOACS usually do not need monitoring. Most common interaction noted with drugs like ketoconazole (CYP3A4). Dosing: Dabigatran and Edoxaban: Overlap with parenteral enoxaparin for 5 to 10 days is needed. Apixaban and Rivoraxaban: Need loading dose. For apixaban it is 10 mg 2 times a day for 7 days followed by 5 mg 2 times a day.  Rivaroxaban: 15 mg 2 times a day for 21 days followed by 20 mg once a day. (Xarelto need to be taken with food) Only 55% of the patients with Coumadin remain in therapeutic range. Drug reversal agents for DOACs Dabigatran reversal: Idarucizumab Xarelto and Eliquis reversal: Andexenat Alpha. Factors in deciding candidacy for DOACs: DOACs in patients with Child-Pugh score B/C cirrhosis should not be used. Renal failure with CrCl 120 kg, based on ISTH guidelines. (higher the BMI may have increased risk of bleeding with better efficacy, potentially due to absorption issues-- levels can fluctuate) Drug monitoring for DOACs: No standardized methods. Not routinely done. It should be considered in patients with extremes of weight and patients who have gone gastric/bariatric surgeries, because all DOACs are absorbed get into upper GI tract. Pregnancy and Venous thromboembolism: No DOACs in pregnancy. Enoxaparin is the treatment of choice -1 mg/kg every 12 hours up to week 36 followed by changing them to unfractionated heparin. (subcutaneous calculated dose). Patients who had prior DVTs/PEs and become pregnant may need prophylactic dose of enoxaparin (40 mg subcutaneous once a day) Cancer and VTE: VTE is a second leading cause of death in cancer patients. Drug of choice was enoxaparin over warfarin. Edoxaban Vs Enoxaparin: Edoxaban with less recurrent VTE, but worse bleeding profile (most bleeds in gastric cancer patients) Rivaroxaban Vs Enoxaparin: Rivaroxaban with less recurrent VTE, but worse bleeding profile (most bleeds in gastric cancer) Cancer patients who may not be good candidate: a) GI cancer b) needing many procedures c) liver/renal failure d)brain mets.  Provoked vs Unprovoked and extended a/c: Unprovoked PE: Two-year risk of recurrence 25% or higher. Provoked by surgery [mainly orthopedic surgery, pregnancy, long hospital stay]: risk of recurrence 1% at one year, 3% at 5 years. Flying is a weak risk factor to be considered as provoked. Amplify-Ext trial: 70% decrease risk of recurrence with low dose apixaban without an increased risk of bleeding in unprovoked VTE. Einstein Choice trial: 70% decrease risk of recurrence with low dose rivaroxaban without an increased risk of bleeding. 60% of patients had provoked VTE with ongoing risk factors. (i.e. Obese patients, patients who are immobile, and are still immobile). Cancer screening following PE: 5-10% of patients with VTE would be diagnosed with malignancy in next 5 years. Recommendation is to do age appropriate cancer screening. Valves and DOACS: (increase risk of ischemic events)   Reference: Rali P, Gangemi A Moores A et al. Direct-Acting Oral Anticoagulants in Critically Ill Patients. Chest. 2019 Sep;156(3):604-618.

Show Notes Jeff: Welcome back to EMplify the podcast corollary to EB Medicine's Emergency medicine Practice. I'm Jeff Nusbaum and I'm back with Nachi Gupta. This month, we are tackling a topic for which the literature continues to rapidly change - we're talking about the ED management of patients taking direct oral anticoagulants or DOACs, previously called novel oral anticoagulants or NOACs. Nachi: Specifically, we'll be focusing on the use of DOACs for the indications of stroke prevention in atrial fibrillation and the treatment and prevention of recurrent venous thromboembolisms. Jeff: This month's article was authored by Dr. Patrick Maher and Dr. Emily Taub of the Icahn School of Medicine at Mount Sinai, and it was peer reviewed by Dr. Dowin Boatright from Yale, Dr. Natalie Kreitzer from the University of Cincinnati, and Dr. Isaac Tawil from the University of New Mexico. Nachi: In their quest to update the last Emergency Medicine Practice issue on this topic which was published in 2013, they reviewed over 200 articles from 2000 to present in addition to 5 systematic reviews in the cochrane database, as well as guidelines from the American Heart Association, European society of cardiology, and the american college of cardiology. Jeff: Thanks to a strong literature base, Dr's Maher and Taub found good quality evidence regarding safety and efficacy of the DOACs in relation to warfarin and the heparin-based anticoagulants. Nachi: But do note that the literature directly comparing the DOACs is far more limited and mostly of poor quality. Show More v Jeff: Fair enough, we'll take what we can get. Nachi: Well, I'm sure more of those studies are still coming. Jeff: Agree. Let's get started with some basics. Not surprisingly, DOACs now account for a similar proportion of office visits for anticoagulant use as warfarin. Nachi: With huge benefits including reduced need for monitoring and a potential for reduced bleeding complications, this certainly isn't surprising. Jeff: Though those benefits are not without challenges - most notably the lack of an effective reversal agent and the risk of unintentional overdose in patients with altered drug metabolism. Nachi: Like all things in medicine, it's about balancing and finding an acceptable risk/benefit profile. Jeff: True. Let's talk pathophysiology for a minute - the control of coagulation in the human body is a balance between hemorrhage and thrombosis, mediated by an extensive number of procoagulant and anticoagulant proteins. Nachi: Before the development of the DOACs, vitamin K antagonists controlled the brunt of the market. As their name suggests, they work by inhibiting the action of vitamin K, and thus reducing the production of clotting factors 2, 7, 9, and 10, and the anticoagulant proteins C and S. Jeff: Unfortunately, these agents have a narrow therapeutic window and many drug-drug interactions, and they require frequent monitoring - making them less desirable to many. Nachi: However, in 2010, the FDA approved the first DOAC, a real game-changer. The DOACs currently on the market work by one of two mechanisms - direct thrombin inhibition or factor Xa inhibition. Jeff: DOACs are currently approved for stroke prevention in nonvalvular afib, treatment of VTE, VTE prophylaxis, and reduction of major cardiovascular events in stable cardiovascular disease. Studies are underway to test their safety and efficacy in arterial and venous thromboembolism, prevention of embolic stroke in afib, ACS, cancer-associated thrombosis, upper extremity DVT, and mesenteric thrombosis. Nachi: Direct thrombin inhibitors like Dabigatran, tradename Pradaxa, was the first FDA approved DOAC. It works by directly inhibiting thrombin, or factor IIa, which is a serine protease that converts soluble fibrinogen into fibrin for clot formation. Jeff: Dabigatran comes in doses of 75 and 150 mg. The dose depends on your renal function, and, with a half-life of 12-15 hours,

Show Notes Jeff: Welcome back to EMplify the podcast corollary to EB Medicine’s Emergency medicine Practice. I’m Jeff Nusbaum and I’m back with Nachi Gupta. This month, we are tackling a topic for which the literature continues to rapidly change - we’re talking about the ED management of patients taking direct oral anticoagulants or DOACs, previously called novel oral anticoagulants or NOACs. Nachi: Specifically, we’ll be focusing on the use of DOACs for the indications of stroke prevention in atrial fibrillation and the treatment and prevention of recurrent venous thromboembolisms. Jeff: This month’s article was authored by Dr. Patrick Maher and Dr. Emily Taub of the Icahn School of Medicine at Mount Sinai, and it was peer reviewed by Dr. Dowin Boatright from Yale, Dr. Natalie Kreitzer from the University of Cincinnati, and Dr. Isaac Tawil from the University of New Mexico. Nachi: In their quest to update the last Emergency Medicine Practice issue on this topic which was published in 2013, they reviewed over 200 articles from 2000 to present in addition to 5 systematic reviews in the cochrane database, as well as guidelines from the American Heart Association, European society of cardiology, and the american college of cardiology. Jeff: Thanks to a strong literature base, Dr’s Maher and Taub found good quality evidence regarding safety and efficacy of the DOACs in relation to warfarin and the heparin-based anticoagulants. Nachi: But do note that the literature directly comparing the DOACs is far more limited and mostly of poor quality. Show More v Jeff: Fair enough, we’ll take what we can get. Nachi: Well, I’m sure more of those studies are still coming. Jeff: Agree. Let’s get started with some basics. Not surprisingly, DOACs now account for a similar proportion of office visits for anticoagulant use as warfarin. Nachi: With huge benefits including reduced need for monitoring and a potential for reduced bleeding complications, this certainly isn’t surprising. Jeff: Though those benefits are not without challenges - most notably the lack of an effective reversal agent and the risk of unintentional overdose in patients with altered drug metabolism. Nachi: Like all things in medicine, it’s about balancing and finding an acceptable risk/benefit profile. Jeff: True. Let’s talk pathophysiology for a minute - the control of coagulation in the human body is a balance between hemorrhage and thrombosis, mediated by an extensive number of procoagulant and anticoagulant proteins. Nachi: Before the development of the DOACs, vitamin K antagonists controlled the brunt of the market. As their name suggests, they work by inhibiting the action of vitamin K, and thus reducing the production of clotting factors 2, 7, 9, and 10, and the anticoagulant proteins C and S. Jeff: Unfortunately, these agents have a narrow therapeutic window and many drug-drug interactions, and they require frequent monitoring - making them less desirable to many. Nachi: However, in 2010, the FDA approved the first DOAC, a real game-changer. The DOACs currently on the market work by one of two mechanisms - direct thrombin inhibition or factor Xa inhibition. Jeff: DOACs are currently approved for stroke prevention in nonvalvular afib, treatment of VTE, VTE prophylaxis, and reduction of major cardiovascular events in stable cardiovascular disease. Studies are underway to test their safety and efficacy in arterial and venous thromboembolism, prevention of embolic stroke in afib, ACS, cancer-associated thrombosis, upper extremity DVT, and mesenteric thrombosis. Nachi: Direct thrombin inhibitors like Dabigatran, tradename Pradaxa, was the first FDA approved DOAC. It works by directly inhibiting thrombin, or factor IIa, which is a serine protease that converts soluble fibrinogen into fibrin for clot formation. Jeff: Dabigatran comes in doses of 75 and 150 mg. The dose depends on your renal function, and, with a half-life of 12-15 hours, is taken twice daily. Note the drastically reduced half-life as compared to warfarin, which has a half-life of up to 60 hours. Nachi: The RE-LY trial for afib found that taking 150 mg of Dabigatran BID had a lower rate of stroke and systemic embolism than warfarin with a similar rate of major hemorrhage. Dabigatran also had lower rates of fatal and traumatic intracerebral hemorrhage than warfarin. Jeff: A separate RCT found similar efficacy in treating acute VTE and preventing recurrence compared with warfarin, with reduced rates of hemorrhage! Nachi: Less monitoring, less hemorrhage, similar efficacy, I’m sold!!! Jeff: Slow down, there’s lots of other great agents out there, let’s get through them all first... Nachi: Ok, so next up we have the Factor Xa inhibitors, Rivaroxaban, apixaban, edoxaban, and betrixaban.As the name suggests, these medications work by directly inhibiting the clotting of factor Xa, which works in the clotting cascade to convert prothrombin to thrombin. Jeff: Rivaroxaban, trade name Xarelto, the second FDA approved DOAC, is used for stroke prevention in those with nonvalvular afib and VTE treatment. After taking 15 mg BID for the first 21 days, rivaroxaban is typically dosed at 20 mg daily with adjustments for reduced renal function. Nachi: The Rocket AF trial found that rivaroxaban is noninferior to warfarin for stroke and systemic embolism prevention without a significant difference in risk of major bleeding. Interestingly, GI bleeding may be higher in the rivaroxaban group, though the overall incidence was very low in both groups at about 0.4% of patients per year. Jeff: In the Einstein trial, patients with VTE were randomized to rivaroxaban or standard therapy. In the end, they reported similar rates of recurrence and bleeding outcomes for acute treatment. Continuing therapy beyond the acute period resulted in similar rates of VTE recurrence and bleeding episodes to treatment with aspirin alone. Nachi: Next we have apixaban, tradename Eliquis. Apixaban is approved for afib and the treatment of venous thromboembolism. It’s typically dosed as 10 mg BID for 7 days followed by 5 mg BID with dose reductions for the elderly and those with renal failure. Jeff: In the Aristotle trial, when compared to warfarin, apixaban was superior in preventing stroke and systemic embolism with lower mortality and bleeding. Rates of major hemorrhage-related mortality were also nearly cut in half at 30 days when compared to warfarin. Nachi: For the treatment of venous thromboembolism, the literature shows that apixaban has a similar efficacy to warfarin in preventing recurrence with less bleeding complications. Jeff: Unfortunately, with polypharmacy, there is increased risk of thromboembolic and hemorrhage risks, but this risk is similar to what is seen with warfarin. Nachi: And as compared to low molecular weight heparin, apixaban had higher bleeding rates without reducing venous thromboembolism events when used for thromboprophylaxis. It’s also been studied in acute ACS, with increased bleeding and no decrease in ischemic events. Jeff: Edoxaban is up next, approved by the FDA in 2015 for similar indications as the other Factor Xa inhibitors. It’s recommended that edoxaban be given parenterally for 5-10 days prior to starting oral treatment for VTE, which is actually similar to dabigatran. It has similar levels of VTE recurrence with fewer major bleeding episodes compared to warfarin. It has also been used with similar effects and less major bleeding for stroke prevention in afib. In the setting of cancer related DVTs specifically, as compared to low molecular weight heparin, one RCT showed lower rates of VTE but higher rates of major bleeding when compared to dalteparin. Nachi: Next we have Betrixaban, the latest Factor Xa inhibitor to be approved, back in 2017. Because it’s utility is limited to venous thromboembolism prophylaxis in mostly medically ill inpatients, it’s unlikely to be encountered by emergency physicians very frequently. Jeff: As a one sentence FYI though - note that in recent trials, betrixaban reduced the rate of VTE with equivalent rates of bleeding and reduced the rate of stroke with an increased rate of major and clinically relevant non-major bleeding as compared to enoxaparin. Nachi: Well that was a ton of information and background on the DOACs. Let’s move on to your favorite section - prehospital medicine. Jeff: Not a ton to add here this month. Perhaps, most importantly, prehospital providers should specifically ask about DOAC usage, especially in trauma, given increased rates of complications and potential need for surgery. This can help with destination selection when relevant. Interestingly, one retrospective study found limited agreement between EMS records and hospital documentation on current DOAC usage. Nachi: Extremely important to identify DOAC use early. Once the patient arrives in the ED, you can begin your focused history and physical. Make sure to get the name, dose, and time of last administration of any DOAC. Pay particular attention to the med list and the presence of CKD which could point to altered DOAC metabolism. Jeff: In terms of the physical and initial work up - let the sites of bleeding or potential sites of bleeding guide your work up. And don’t forget about the rectal exam, which potentially has some added value here - since DOACs increase the risk of GI bleeding. Nachi: Pretty straight forward history and physical, let’s talk diagnostic studies. Jeff: First up is CT. There are no clear cut guidelines here, so Drs. Maher and Taub had to rely on observational studies and expert opinion. Remember, most standard guidelines and tools, like the canadian and nexus criteria, are less accurate in anticoagulated patients, so they shouldn’t be applied. Instead, most studies recommend a low threshold for head imaging, even with minor trauma, in the setting of DOAC use. Nachi: That is so important that it’s worth repeating. Definitely have a low threshold to CT the head for even minor head trauma patients on DOACs. Basically, if you’re on anticoagulation, and you made it to the ED for anything remotely related to your head, you probably win a spin. Jeff: I suspect you are not alone with that stance... There is, however, much more debate about the utility of follow up imaging and admission after a NEGATIVE scan. Nachi: Wait, is that a thing I should routinely be doing? Jeff: Well there’s not great data here, but in one observational study of 1180 patients on either antiplatelet or anticoagulant therapy, a half a percent of them had positive findings 12 hours later, and importantly none required surgical intervention. Nachi: Certainly reassuring. And for those with positive initial imaging, the authors recommend repeat imaging within 4-6 hours in consultation with neurosurgical services or even earlier in cases of unexpected clinical decline. Jeff: Interestingly, though only a small retrospective study of 156 patients, one study found markedly reduced mortality, 4.9% vs 20.8% in those on DOACs vs warfarin with traumatic intracranial hemorrhage. Nachi: Hmm that actually surprises me a bit with the ease of reversibility of warfarin. Jeff: And we’ll get to that in a few minutes. But next we should talk about ultrasound. As always with trauma, guidelines recommend a FAST exam in the setting of blunt abdominal trauma. The only thing to be aware of here is that you should have an increased index of suspicion for bleeding, especially in hidden sites like the retroperitoneum. Nachi: And just as with traumatic head bleeds, a small observational study of those with blunt abdominal trauma found 8% vs 30% mortality for those on DOACs vs warfarin, respectively. Jeff: That is simply shocking! Let’s also talk lab studies. Hemoglobin and platelet counts should be obtained as part of the standard trauma work up. Assessing renal function via creatinine is also important, especially for those on agents which are renally excreted. Nachi: Though you can, in theory, test for plasma DOAC concentrations, such tests are not routinely indicated as levels don’t correspond to bleeding outcomes. DOAC levels may be indicated in certain specific situations, such as while treating life-threatening bleeding, development of venous thromboembolism despite compliance with DOAC therapy, and treating patients at risk for bleeding because of an overdose. Jeff: In terms of those who require surgery while on a DOAC - if urgent or emergent, the DOAC will need to be empirically reversed. For all others, the recommendation is to wait a half life or even multiple half-lives, if possible, in lieu of level testing. Nachi: Coagulation tests are up next. Routine PT and PTT levels do not help assess DOACs, as abnormalities on either test can suggest the presence of a DOAC, but the values should not be interpreted as reliable measures of either therapeutic or supratherapeutic clinical anticoagulant effect. Jeff: Dabigatran may cause prolongation of both the PT and the PTT, but the overall correlation is poor. In addition, FXa inhibitors may elevate PT in a weakly concentration dependent manner, but this may only be helpful if anti-fXa levels are unavailable. Nachi: Which is a perfect segway into our next test - anti-factor Xa level activity. Direct measurements of the anti-Fxa effect demonstrates a strong linear correlation with plasma concentrations of these agents, but the anticoagulant effect does not necessarily follow the same linear fashion. Jeff: Some labs may even have an anti-FXa effect measurement calibrated specifically to the factor 10a inhibitors. Nachi: While measuring thrombin time is not routinely recommended, the result of thrombin time or dilute thrombin time does correlate well with dabigatran concentrations across normal ranges. Jeff: And lastly, we have the Ecarin clotting time. Ecarin is an enzyme that cleaves prothrombin to an active intermediate that can be inhibited by dabigatran in the same way as thrombin. The ECT is useful for measuring dabigatran concentration - it’s not useful for testing for FXa inhibitors. A normal ECT value could be used to exclude the presence of dabigatran. Nachi: So I think that rounds out testing. Let’s move into the treatment section. Jeff: For all agents, regardless of the DOAC, the initial resuscitation follows the standard principles of hemorrhage control and trauma resuscitation. Tourniquet application, direct pressure, endoscopy for GI bleeds, etc... should all be used as needed. And most importantly, for airway bleeding, pericardial bleeding, CNS bleeding, and those with hemodynamic instability or overt bleeding, those with a 2 point drop in their hemoglobin, and those requiring 2 or more units of pRBC - they all should be considered to have serious, life threatening bleeds. This patient population definitely requires reversal agents, which we’re getting to in a minute. Nachi: A type and screen should also be sent with the plan to follow standard transfusion guidelines, with the goal of a hemoglobin level of 7, understanding that in the setting of an active bleed, the hemoglobin level will not truly be representative. Jeff: Interestingly, in the overdose literature that’s out there, bleeding episodes appear to be rare - occurring in just 5% of DOAC overdose cases. Nachi: Finally, onto the section we’ve all been waiting for. Let’s talk specific reversal agents. Praxbind is up first. Jeff: Idarucizumab or Praxbind, is the reversal agent of choice for dabigatran (which is also called pradaxa). According to data from the RE-LY trial, it reverses dabigatran up to the 99th percentile of levels measured in the trial. Nachi: And praxbind should be given in two 2.5 g IV boluses 15 minutes apart to completely reverse the effects of dabigatran. Jeff: As you would expect given this data, guidelines for DOAC reversal recommend it in major life-threatening bleeding events for patients on dabigatran. Nachi: Next up is recombinant coagulation factor Xa (brand name Andexxa), which was approved in 2018 for the FXa inhibitors. This recombinant factor has a decoy receptor for the FXa agents, thus eliminating their anticoagulant effects. Jeff: Recombinant factor Xa is given in either high or low dose infusions. High dose infusions for those on rivaroxaban doses of >10 mg or apixaban doses >5 mg within the last 8 hours and for unknown doses and unknown time of administration. Low dose infusions should be used for those with smaller doses within the last 8 hours or for last doses taken beyond 8 hours. Nachi: In one trial of 352 patients, recombinant factor Xa given as an IV bolus and 2 hour infusion was highly effective at normalizing anti-FXa levels. 82% of the assessed patients at 12 hours achieved hemostasis, but there were also thrombotic events in 10% of the patients at 30 days. Jeff: And reported thrombotic events aren’t the only downside. Though the literature isn’t clear, there may be limited use of recombinant factor Xa outside of the time of the continuous infusion, and even worse, there may be rebound of anti-Fxa levels and anticoagulant effect. And lastly, the cost is SUBSTANTIAL. Nachi: Is there really a cost threshold for stopping life threatening bleeding…? Jeff: Touche, but that means we need to save it for specific times and consider other options out there. Since this has only been around for a year or so, let’s let the literature play out on this too... Nachi: And that perfectly takes us into our next topic, which is nonspecific reversal agents, starting with prothrombin complex concentrate, also called PCC. Jeff: PCC is FDA approved for rapid reversal of vitamin K antagonist-related hemorrhagic events and is now being used off label for DOAC reversal. Nachi: PCC comes in 3 and 4 factor varieties. 3-factor PCC contains factors 2, 9, 10 and trace amounts of factor 7. 4 factor PCC contains factors 2, 9 10, as well as purified factor 7 and proteins C and S. Jeff: Both also contain trace amounts of heparin so can’t be given to someone with a history of HIT. Nachi: PCC works by overwhelming the inhibitor agent by increasing the concentration of upstream clotting factors. It has been shown, in healthy volunteers, to normalize PT abnormalities and bleeding times, and to achieve effective bleeding control in patients on rivaroxaban, apixaban, and edoxaban with major bleeding events. Jeff: In small studies looking at various end points, 4 factor PCC has been shown to be superior to 3 factor PCC. Nachi: Currently it’s given via weight-based dosing, but there is interest in studying a fixed-dose to decrease both time to medication administration and cost of reversal. Jeff: Guidelines currently recommend 4F PCC over 3F PCC, if available, for the management of factor Xa inhibitor induced bleeding, with studies showing an effectiveness of nearly 70%. As a result, 4F PCC has become an agent of choice for rapid reversal of FXa inhibitors during major bleeding events. Nachi: Next we have activated PCC (trade name FEIBA). This is essentially 4Factor PCC with a modified factor 7. Though traditionally saved for bleeding reversal in hemophiliacs, aPCC is now being studied in DOAC induced bleeding. Though early studies are promising, aPCC should not be used over 4factor PCC routinely as of now but may be used if 4Factor PCC is not available. Jeff: Next we have recombinant factor 7a (trade name novoseven). This works by activating factors 9 and 10 resulting in rapid increase in thrombin. Studies have shown that it may reverse the effect of dabigatran, at the expense of increased risk of thrombosis. As such, it should not be used as long as other agents are available. Nachi: Fresh Frozen Plasma is the last agent to discuss in this section. Not a lot to say here - FFP is not recommended for reversal of any of the DOACs. It may be given as a part of of a balanced massive transfusion resuscitation, but otherwise, at this time, there doesn’t seem to be a clear role. Jeff: Let’s move on to adjunct therapies, of which we have 3 to discuss. Nachi: First is activated charcoal. Only weak evidence exists here - but, according to expert recommendations, there may be a role for DOAC ingestions within 2 hours of presentations. Jeff: Perhaps more useful than charcoal is our next adjunct - tranexamic acid or TXA. TXA is a synthetic lysine analogue with antifibrinolytic activity through reversible binding of plasmin. CRASH-2 is the main trial to know here. CRASH-2 demonstrated reduced mortality if given within 3 hours in trauma patients. There is very limited data with respect to TXA and DOACs specifically, so continue to administer TXA as part of your standard trauma protocol without modification if the patient is on a DOAC, as it’s likely helpful based on what data we have. Nachi: Next is vitamin K - there is no data to support routine use of vitamin K in those taking DOACs - save that for those on vitamin K antagonists. Jeff: Also, worth mentioning here is the importance of hematology input in developing hospital-wide protocols for reversal agents, especially if availability of certain agents is limited. Nachi: Let’s talk about some special circumstances and populations as they relate to DOACs. Patients with mechanical heart valves were excluded from the major DOAC trials. And of note, a trial of dabigatran in mechanical valve patients was stopped early because of bleeding and thromboembolic events. As such, the American College of Cardiology state that DOACs are reasonable for afib with native valve disease. Jeff: DOACs should be used with caution for pregnant, breastfeeding, and pediatric patients. A case series of 233 pregnancies that occurred among patients on a DOAC reported high rates of miscarriage. Nachi: Patients with renal impairment are particularly concerning as all DOACs are dependent to some degree on renal elimination. Current guidelines from the Anticoagulation Forum recommend avoiding dabigatran and rivaroxaban for patients with CrCL < 30 and avoiding edoxaban and betrixaban for patients with CrCl < 15. Jeff: A 2017 Cochrane review noted similar efficacy without increased risk of major bleeding when using DOACs in those with egfr > 30 (that’s ckd3b or better) when compared to patients with normal renal function and limited evidence for safety below this estimated GFR. Nachi: Of course, dosing with renal impairment will be different. We won’t go into the details of that here as you will probably discuss this directly with your pharmacist. Jeff: We should mention, however, that reversal of the anticoagulant in the setting of renal impairment for your major bleeding patient is exactly the same as we already outlined. Nachi: Let’s move on to some controversies and cutting-edge topics. The first one is a pretty big topic and that is treatment for ischemic stroke patients taking DOACs. Jeff: Safety and efficacy of tPA or endovascular therapy for patients on DOACs continues to be debated. Current guidelines do not recommend tPA if the last DOAC dose was within the past 48 hours, unless lab testing specific to these agents shows normal results. Nachi: Specifically, the American Heart Association suggests that INR and PTT be normal in all cases. ECT and TT should be tested for dabigatran. And calibrated anti-FXa level testing be normal for FXa inhibitors. Jeff: The AHA registry actually included 251 patients who received tpa while on DOACs, which along with cohort analysis of 26 ROCKET-AF trial patients, suggest the risk of intracranial hemorrhage is similar to patients on warfarin with INR < 1.7 and to patients not on any anticoagulation who received tpa. However, given the retrospective nature of this data, we cannot exclude the possibility of increased risk of adverse events with tpa given to patients on DOACs. Nachi: Endovascular thrombectomy also has not been studied in large numbers for patients on DOACs. Current recommendations are to discuss with your stroke team. IV lysis or endovascular thrombectomy may be considered for select patients on DOACs. Always include the patient and family in shared decision making here. Jeff: There are also some scoring systems for bleeding risk to discuss briefly. The HAS-BLED has been used to determine bleeding risk in afib patients taking warfarin. The ORBIT score was validated in a cohort that included patients on DOACs and is similarly easy to use, and notably does not require INR values. Nachi: There is also the ABC score which has demonstrated slightly better prediction characteristics for bleeding risk, but it requires high-sensitivity troponin, limiting its practical use. Jeff: We won’t say more about the scoring tools here, but would recommend that you head over to MD Calc, where you can find them and use them in your practice. Nachi: Let’s also comment on the practicality of hemodialysis for removal of the DOACs. Multiple small case series have shown successful removal of dabigatran, given its small size and low protein binding. On the other hand, the FXa inhibitors are less amenable to removal in this way because of their higher protein binding. Jeff: Worth mentioning here also - dialysis catheters if placed should be in compressible areas in case bleeding occurs. The role of hemodialysis for overdose may be limited now that the specific reversal agent, praxbind, exists. Nachi: In terms of cutting-edge tests, we have viscoelastic testing like thromboelastography and rotational thromboelastometry. Several studies have examined the utility of viscoelastic testing to detect presence of DOACs with varying results. Prolongation of clotting times here does appear to correlate with concentration, but these tests haven’t emerged as a gold standard yet. Jeff: Also, for cutting edge, we should mention ciraparantag. And if you’ve been listening patiently and just thinking to yourself why can’t there be one reversal agent to reverse everything, this may be the solution. Ciraparantag (or aripazine) is a universal anticoagulant reversal agent that may have a role in all DOACs and heparins. It binds and inactivates all of these agents and it doesn’t appear to have a procoagulant effect. Nachi: Clinical trials for ciraparantag have shown rapid and durable reversal of edoxaban, but further trials and FDA approval are still needed. Jeff: We’ve covered a ton of material so far. As we near the end of this episode, let’s talk disposition. Nachi: First, we have those already on DOACs - I think it goes without saying that any patient who receives pharmacological reversal of coagulopathy for major bleeding needs to be admitted, likely to the ICU. Jeff: Next we have those that we are considering starting a DOAC, for example in someone with newly diagnosed VTE, or patients with an appropriate CHADS-VASC with newly diagnosed non-valvular afib. Nachi: With respect to venous thromboembolism, both dabigatran and edoxaban require a 5 day bridge with heparin, whereas apixaban and rivaroxaban do not. The latter is not only easier on the patient but also offers potential cost savings with low risk of hemorrhagic complications. Jeff: For patients with newly diagnosed DVT / PE, both the American and British Thoracic Society, as well as ACEP, recommend using either the pulmonary embolism severity index, aka PESI, or the simplified PESI or the Hestia criteria to risk stratify patients with PE. The low risk group is potentially appropriate for discharge home on anticoagulation. This strategy reduces hospital days and costs with otherwise similar outcomes - total win all around. Nachi: Definitely a great opportunity for some shared decision making since data here is fairly sparse. This is also a great place to have institutional policies, which could support this practice and also ensure rapid outpatient follow up. Jeff: If you are going to consider ED discharge after starting a DOAC - there isn’t great data supporting one over another. You’ll have to consider patient insurance, cost, dosing schedules, and patient / caregiver preferences. Vitamin K antagonists should also be discussed as there is lots of data to support their safety outcomes, not to mention that they are often far cheaper…. As an interesting aside - I recently diagnosed a DVT/PE in an Amish gentleman who came to the ED by horse - that was some complicated decision making with respect to balancing the potentially prohibitive cost of DOACs with the massive inconvenience of frequently checking INRs after a 5 mile horseback ride into town... Nachi: Nice opportunity for shared decision making… Jeff: Lastly, we have those patients who are higher risk for bleeding. Though I’d personally be quite uneasy in this population, if you are to start a DOAC, consider apixaban or edoxaban, which likely have lower risk of major bleeding. Nachi: So that’s it for the new material for this month’s issue. Certainly, an important topic as the frequency of DOAC use continues to rise given their clear advantages for both patients and providers. However, despite their outpatient ease of use, it definitely complicates our lives in the ED with no easy way to evaluate their anticoagulant effect and costly reversal options. Hopefully all our hospitals have developed or will soon develop guidelines for both managing ongoing bleeding with reversal agents and for collaborative discharges with appropriate follow up resources for those we send home on a DOAC. Jeff: Absolutely. Let’s wrap up with some the highest yield points and clinical pearls Nachi: Dabigatran works by direct thrombin inhibition, whereas rivaroxaban, apixaban, edoxaban, and betrixaban all work by Factor Xa inhibition. Jeff: The DOACs have a much shorter half-life than warfarin. Nachi: Prehospital care providers should ask all patients about their use of anticoagulants. Jeff: Have a low threshold to order a head CT in patients with mild head trauma if they are on DOACs. Nachi: For positive head CT findings or high suspicion of significant injury, order a repeat head CT in 4 to 6 hours and discuss with neurosurgery. Jeff: Have a lower threshold to conduct a FAST exam for blunt abdominal trauma patients on DOACs. Nachi: Assessment of renal function is important with regards to all DOACs. Jeff: While actual plasma concentrations of DOACs can be measured, these do not correspond to bleeding outcomes and should not be ordered routinely. Nachi: The DOACs may cause mild prolongation of PT and PTT. Jeff: Idarucizumab (Praxbind®) is an antibody to dabigatran. For dabigatran reversal, administer two 2.5g IV boluses 15 minutes apart. Reversal is rapid and does not cause prothrombotic effects. Nachi: Recombinant FXa can be used to reverse the FXa inhibitors. This works as a decoy receptor for the FXa agents. Jeff: Vitamin K and FFP are not recommended for reversal of DOACs. Nachi: Consider activated charcoal to remove DOACs ingested within the last two hours in the setting of life-threatening hemorrhages in patient’s on DOACs. Jeff: Hemodialysis can effectively remove dabigatran, but this is not true for the FXa inhibitors. Nachi: 4F-PCC has been shown to be effective in reversing the effects of the FXa inhibitors. This is thought to be due to overwhelming the inhibitor agent by increased concentrations of upstream clotting factors. Jeff: tPA is contraindicated in acute ischemic stroke if a DOAC dose was administered within the last 48 hours, unless certain laboratory testing criteria are met. Nachi: Emergency clinicians should consider initiating DOACs in the ED for patients with new onset nonvalvular atrial fibrillation, DVT, or PE that is in a low-risk group. Jeff: So that wraps up Episode 31! Nachi: As always, additional materials are available on our website for Emergency Medicine Practice subscribers. If you’re not a subscriber, consider joining today. You can find out more at ebmedicine.net/subscribe. Subscribers get in-depth articles on hundreds of emergency medicine topics, concise summaries of the articles, calculators and risk scores, and CME credit. You’ll also get enhanced access to the podcast, including any images and tables mentioned. PA’s and NP’s - make sure to use the code APP4 at checkout to save 50%. Jeff: And the address for this month’s cme credit is www.ebmedicine.net/E0819, so head over there to get your CME credit. As always, the [DING SOUND] you heard throughout the episode corresponds to the answers to the CME questions. Lastly, be sure to find us on iTunes and rate us or leave comments there. You can also email us directly at EMplify@ebmedicine.net with any comments or suggestions. Talk to you next month!

* Use coupon code PODCAST25 for 25% off this webcast * Webcast URL: https://www.theknowledgegroup.org/webcasts/navigating-mass-torts-litigation/ A large number of mass torts filed over the previous year involve drugs including Xarelto, Risperdal, Opioids and Pradaxa. One notable case is the mass tort against pharmaceutical giant Hoffmann La-Roche with over 500 lawsuits claiming that users of the company's acne drug Accutane, developed inflammatory bowel disease. The New Jersey Supreme Court ruled in favor of Hoffmann La-Roche with its dismissal of the mass tort case. The Court said that the plaintiffs failed to prove that Roche failed to provide internal research to the Food and Drug Administration (FDA). Understanding mass tort case verdicts such as this, as well as the upcoming ones, is critical in devising effective litigation strategies. Join a panel of key thought leaders and professionals assembled by The Knowledge Group as they bring the audience to a road beyond the basics of bringing or defending against a mass tort lawsuit and as they delve into the depth-analysis of the current trends and recent court rulings. Speakers will also provide the audience with practical strategies in bringing out the best in these lawsuits in a rapidly evolving legal climate. For anymore information please click on the webcast url at the top of this description.

Bloody Oral Anticoagulants – BCC talk 2014 The use of the New Oral Anticoagulant Drugs present unique challenges for the Intensive Care practitioner 1. The NOACs now have PBS approval for non-valvular AF, below knee DVT, DVT prophylaxis and low volume PE 2. There is no specific antidote for NOAC related bleeding but don’t despair there are some things that can help 3. Routine coagulation testing does not reflect drug levels or anticoagulation activity Global sales of Dabigatran topped $1billion in 2012.  This talk outlines the pharmacodynamics and pharmacokinetics of the NOACs. Limitations and cautions of use are outlined with a review of the extensive literature. Clinical cases involving the NOACs are presented. The timing of stopping the agents before minor or major surgery, the approach to a patient with intracranial haemorrhage taking oral anticoagulants and the challenges faced when patients have an Acute Kidney Injury whilst taking these

Nieuwe antistollingsmedicijnen met de merknamen Pradaxa en Xarelto worden sinds twee jaar vergoed door de Nederlandse zorgverzekeraars. Deze veel duurdere noac’s, de Nieuwe Orale Anti Coagulantia, kwamen versneld op de markt omdat ze grote voordelen zouden hebben ten opzichte van de traditionele bloedverdunners. Minder bijwerkingen, en een vaste dagelijkse dosis waardoor patiënten niet meer naar de trombosedienst hoeven om de stolling te laten controleren en daarmee de dosis van het medicijn te laten bepalen. De Gezondheidsraad eiste bij de invoering van de vergoeding een onderzoek in Nederland naar de effectiviteit en de veiligheid van de nieuwe middelen. Om ze zo te kunnen vergelijken met de oude, spotgoedkope bloedverdunners.Zijn de noac’s inderdaad veiliger ? Is er echt geen controle van de stolling meer nodig ? En hoe staat het met de studie waar de Gezondheidsraad om vroeg? Eerder, in december 2012 besteedde Argos aandacht aan de toen net ingevoerde Noac’s. Nu, ruim twee jaar later, kijken we of de waarschuwingen die medici toen uitten, bewaarheid zijn geworden. Argos over sterfgevallen, misleiding en het uitblijven van een beloofd onderzoek. Een reportage van Helene van Beek.

Famed legal writer John Grisham calls them Rainmakers. We've celebrated their legendary victories in cinematic works such as "A Civil Action" and "Erin Brockovich." In Hollywood, these plaintiffs attorneys are often portrayed as Davids to their opposing Goliaths of corrupt industry. But who are they in real life? In this special edition of Lawyer 2 Lawyer, hosts Bob Ambrogi and J. Craig Williams interview titans of the courtroom Mike Papantonio, Howard Nations, Thomas Girardi, and Fred Levin. In the first segment of this show, they reveal their most respected defense counsel, discuss the traits of successful trial attorneys, as well as evaluate the contingency fee model. In the second segment, Bob and Craig interview Fred Levin about his new biography which covers his very colorful life and career. Tune in to hear about his victories and his defeats. Mike Papantonio was instrumental in the creation of The Trial Lawyer Hall of Fame. In addition to being a senior partner at Levin, Papantonio, Thomas, Mitchell, Rafferty and Proctor, Mike co-hosts his nationally syndicated talk show (Ring of Fire) with esteemed co-hosts Robert F. Kennedy, Jr. and Sam Seder. Mr. Papantonio is also nationally known for his success in mass tort litigation, recipient of multiple prestigious awards (like Trial Lawyer of the Year and the Perry Nichols), and accomplished author of several motivational books for lawyers. Howard Nations is an inductee at The Trial Lawyer Hall of Fame whose national practice is currently working on litigation for Actos bladder cancer, defective hip implants, transvaginal mesh, Pradaxa, and the BP Deepwater Horizon oil spill. As a pioneer in courtroom technology, Howard was the first attorney to have computer-generated liability and medical animations admitted into evidence at trial. Among his many awards, he is the recipient of the W. McKinley Smiley, Jr., Lighthouse Award; the Belli Society's Mel Award; and MTMP's Clarence Darrow Award. Thomas Girardi is an inductee at The Trial Lawyer Hall of Fame who's commonly known for his work in Anderson v. Pacific Gas and Electric (the case made famous by the Erin Brockovich film). Among his numerous headlines, Mr. Girardi secured a 4.85 billion dollar settlement from Merck for Vioxx, a 785 million dollar verdict from Lockheed for personal injuries, and a 1.7 billion dollar settlement from the State of California for manipulating natural gas prices. Fred Levin is commonly referred to as the man who brought down Big Tobacco by helping to secure the largest settlement in US history. To date, he has won over 100 jury verdicts and settlements worth at least one million dollars. During his very colorful career he represented heavyweight boxing champion Roy Jones Jr., helped start the national firm of Johnnie Cochran, be-friended multiple Presidential candidates, and been investigated for murder twice. Today, Mr. Levin still practices as a senior partner at Levin, Papantonio, Thomas, Mitchell, Rafferty and Proctor. Special thanks to our sponsor, Clio.

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In this episode, we discuss the new drug class of Novel Oral Anticoagulants (NOACs), which include dabigatran (Pradaxa), rivaroxaban (Xarelto), and apixaban (Eliquis).

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