Podcasts about randomized clinical trials

The FiltrateJoel TopfAC GomezSophia AmbrusoNayan AroraSpecial Guest Charles Edelstein, MD, PhD Professor, Medicine-Renal Med Diseases/HypertensionExtra-Special GuestMichelle Rheault, MD Professor of Pediatrics, University of MinnesotaEditing bySimon and Joel TopfThe Kidney Connection written and performed by by Tim YauShow NotesKDIGO ADPKD Guidelines:WebsiteGuideline PDFExecutive Summary PDFNephJC coverageConsortium for Radiologic Imaging Studies of Polycystic Kidney Disease (CRISP)Hy's Law (Wikipedia) has three components:ALT or AST by 3-fold or greater above the upper limit of normalAnd total serum bilirubin of greater than 2× the upper limit of normal, without findings of cholestasis (defined as serum alkaline phosphatase activity less than 2× the upper limit of normal)And no other reason can be found to explain the combination of increased aminotransferase and serum total bilirubin, such as viral hepatitis, alcohol abuse, ischemia, preexisting liver disease, or another drug capable of causing the observed injuryMeeting this definition yields a very high risk of fulminant kidney failure (76% in one series)Clinical Pattern of Tolvaptan-Associated Liver Injury in Subjects with Autosomal Dominant Polycystic Kidney Disease: Analysis of Clinical Trials Database (PubMed) Two of 957 patients on tolvaptan met Hy's law criteria. None had fulminant kidney failure.Effects of Hydrochlorothiazide and Metformin on Aquaresis and Nephroprotection by a Vasopressin V2 Receptor Antagonist in ADPKD: A Randomized Crossover Trial (PubMed) Patients had a baseline urine volume on tolvaptan of 6.9 L/24 h. Urine volume decreased to 5.1 L/24 h with hydrochlorothiazide and to 5.4 L/24 h on metformin.TEMPO 3:4 Tolvaptan in Patients with Autosomal Dominant Polycystic Kidney Disease (NEJM)Reprise Trial Tolvaptan in Later-Stage Autosomal Dominant Polycystic Kidney Disease ( NEJM | NephJC )Unified ultrasonographic diagnostic criteria for polycystic kidney disease by Edelstein in JASN (PubMed)Tolvaptan and Kidney Function Decline in Older Individuals With Autosomal Dominant Polycystic Kidney Disease: A Pooled Analysis of Randomized Clinical Trials and Observational Studies (PubMed)Charles' draft choice Recommendation 4.1.1.1: We recommend initiating tolvaptan treatment in adults with ADPKD with an estimated glomerular filtration rate (eGFR) ‡25 ml/min per 1.73 m2 who are at risk for rapidly progressive disease (1B).Sophia's draft choice Recommendation 1.4.2.1: We recommend employing the Mayo Imaging Classi cation (MIC) to predict future decline in kidney function and the timing of kidney failure (1B).Progression to kidney failure in ADPKD: the PROPKD score underestimates the risk assessed by the Mayo imaging classification (Frontiers of Science)AC's draft choice Recommendation 9.2.1: We recommend targeting BP to ≤ 50th percentile for age, sex, and height or ≤ 110/70 mm Hg in adolescents in the setting of ADPKD and high BP (1D).HALT-PKD Blood Pressure in Early Autosomal Dominant Polycystic Kidney Disease (NEJM)Nayan's draft choice Recommendation 6.1.2: We recommend screening for ICA in people with ADPKD and a personal history of SAH or a positive family history of ICA, SAH, or unexplained sudden death in those eligible for treatment and who have a reasonable life expectancy (1D).Screening for Intracranial Aneurysms in Patients with Autosomal Dominant Polycystic Kidney Disease (CJASN)Surgical Clipping Versus Endovascular Coiling in the Management of Intracranial Aneurysms (PubMed) Clipping is associated with a higher rate of occlusion of the aneurysm and lower rates of residual and recurrent aneurysms, whereas coiling is associated with lower morbidity and mortality and a better postoperative course.Joel's editorial pick Recommendation 6.1.1: We recommend informing adults with ADPKD about the increased risk for intracranial aneurysms (ICAs) and subarachnoid hemorrhage (1C).Joel's first draft pick The bring out your dead pick:Recommendation 4.3.1: We recommend not using mammalian target of rapamycin (mTOR) inhibitors to slow kidney disease progression in people with ADPKD (1C).Recommendation 4.4.1: We suggest not using statins specfiically to slow kidney disease progression in people with ADPKD (2D).Recommendation 4.5.1: We recommend not using metformin specifically to slow the rate of disease progression in people with ADPKD who do not have diabetes (1B).Recommendation 4.6.1: We suggest that somatostatin analogues should not be prescribed for the sole purpose of decreasing eGFR decline in people with ADPKD (2B).Perfect match: mTOR inhibitors and tuberous sclerosis complex (Orphanet Journal of Rare Diseases)Navitor Pharmaceuticals Announces Janssen Has Acquired Anakuria Therapeutics, Inc. (BioSpace) This is press release about acquiring the mTor1 inhibitor.Joel's second draft pick Recommendation 4.2.1.1: We suggest adapting water intake, spread throughout the day, to achieve at least 2–3 liters of water intake per day in people with ADPKD and an eGFR ≥ 30 ml/min per 1.73 m2 without contraindications to excreting a solute load (2D).Nayan's bonus draft Practice Point 4.7.1: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) should not be used to slow eGFR decline in people with ADPKD.Open-Label, Randomized, Controlled, Crossover Trial on the Effect of Dapagliflozin in Patients With ADPKD Receiving Tolvaptan (KIReports)SMART Trial of GLP-1ra in non-diabetics: Semaglutide in patients with overweight or obesity and chronic kidney disease without diabetes: a randomized double-blind placebo-controlled clinical trial (PubMed)Tubular SecretionsNayan: Landman on Paramount Plus (IMDB)Sophia: PassNayan: steps in with The Pitt on HBO (Wikipedia)Charles: The White Lotus, Yellowstone 1923, Poirot (IMDB)AC: The PittMichael Crichton's Estate Sends The Pitt to the Courtroom (Vulture)Joel: I Must Betray you by Ruta Sepetys (Amazon)

On Episode 50 of the Stroke Alert Podcast, host Dr. Negar Asdaghi highlights two articles from the March 2025 issue of Stroke: “Impact of Subarachnoid Hemorrhage on Human Glymphatic Function: A Time-Evolution Magnetic Resonance Imaging Study” and “Thrombolysis for Ischemic Stroke Beyond the 4.5-Hour Window: A Meta-Analysis of Randomized Clinical Trials.” She also interviews Drs. Mayank Goyal and Michael Hill about the ESCAPE-MeVO trial, presented in February at the International Stroke Conference. For the episode transcript, visit: https://www.ahajournals.org/do/10.1161/podcast.20250314.838310

Is "leaky gut" real or just another wellness buzzword? In this episode of The Gut Health Podcast, we cut through the controversy with Dr. Alessio Fasano, a renowned gastroenterologist and microbiome expert from Mass General Brigham. Dr. Fasano explains what happens when the gut's protective barrier is compromised, resulting in increased intestinal permeability, and how this can affect not only gut health but also overall well-being. While some level of intestinal permeability is essential for health, in the presence of an altered gut microbiome, it can allow harmful molecules such as bacterial endotoxins and undigested food particles to pass through the intestinal lining. This can lead to inflammation, immune system activation, and may contribute to a variety of health issues, including autoimmune diseases, gastrointestinal disorders, heart disease, and more. We explore the molecular mechanisms that control intestinal permeability, examining how factors like epigenetic changes, diet, stress, and environmental factors can all impact the integrity of the gut barrier. Dr. Fasano breaks down the latest research on how intestinal permeability interacts with the immune system and other organ systems, highlighting the complex bidirectional relationship between gut health and overall wellness. Join us as we explore cutting-edge research on gut health, from breakthrough treatments to personalized diets and biomarkers for gut permeability. Tune in for expert insights and practical strategies—like a plant-forward diet and stress management—to strengthen your gut and overall well-being. References:Effects of dietary components on intestinal permeability in health and disease. Unfermented B-fructans Fibers Fuel Inflammation in Select Inflammatory Bowel Disease Patients. High FODMAP diet causes barrier loss via lipopolysaccharide-mediate mast cell activationA Randomized Placebo-Controlled Trial of Dietary Glutamine Supplements for Post-Infectious Irritable Bowel Syndrome.Bovine Colostrum in Increased Intestinal Permeability in Healthy Athletes and Patients: A Meta-Analysis of Randomized Clinical Trials. What to do about the leaky gut?Learn more about Kate and Dr. Riehl:Website: www.katescarlata.com and www.drriehl.comInstagram: @katescarlata @drriehl and @theguthealthpodcastOrder Kate and Dr. Riehl's book, Mind Your Gut: The Science-Based, Whole-body Guide to Living Well with IBS. The information included in this podcast is not a substitute for professional medical advice, examination, diagnosis or treatment. Always seek the advice of your physician or other qualified health care provider before starting any new treatment or making changes to existing treatment.

The Filtrate:Jennie LinJoel TopfJosh WaitzmanSwapnil HiremathWith Special GuestsPedro TeixeiraJay KoynerEditor Sophia AmbrusoShow NotesThe article: A Randomized Trial of Intravenous Amino Acids for Kidney ProtectionNephJC SummaryKDIGO Clinical Practice Guideline for Acute Kidney Injury (PDF)Steve Coca study Evaluation of Short-Term Changes in Serum Creatinine Level as a Meaningful End Point in Randomized Clinical Trials (PubMed)Using Nephrocheck to prevent AKI: Prevention of cardiac surgery-associated AKI by implementing the KDIGO guidelines in high risk patients identified by biomarkers: the PrevAKI randomized controlled trial (PubMed)Brenner's Review of protein intake and renal hemodynamics: Dietary Protein Intake and the Progressive Nature of Kidney Disease: — The Role of Hemodynamically Mediated Glomerular Injury in the Pathogenesis of Progressive Glomerular Sclerosis in Aging, Renal Ablation, and Intrinsic Renal Disease (NEJM)Husain-Syed a look at preoperative renal functional reserve and risk of AKI: Preoperative Renal Functional Reserve Predicts Risk of Acute Kidney Injury After Cardiac Operation (PubMed)Dana Fuhrman review of renal functional reserve: The Role of Renal Functional Reserve in Predicting Acute Kidney Injury (PubMed)Use of SGLT2i prevented AKI in the placebo controlled trials. Clinical Adverse Events Associated with Sodium-Glucose Cotransporter 2 Inhibitors: A Meta-Analysis Involving 10 Randomized Clinical Trials and 71 553 Individuals (PubMed)Assessment of P values for demographic data in randomized controlled trials (PubMed)Tubular SecretionsSwapnil The Lord of the Rings: Rings of Power Season 2 on Amazon Prime (Wikipedia)Josh Fortnite (Website)Pedro CRRT Academy at University of Alabama Birmingham (Website)Jay Koyner Slow Horses on AppleTV (Wikipedia)Jennie Linn #KidneyWk Run Club Friday 10/25 at 6:15 am PST Meet in front of Sally's Fish House ~2 miles. Easy pace (10-12 min/mile) (Strava)Joel Topf Your Honor on Netflix (Wikipedia)

This bonus content is a reading from Platypus, the CASTAC Blog. The full post by Ana Paula Pimentel Jacob can be read at https://blog.castac.org/2024/08/foucault-dialectics-and-randomized-clinical-trials-bridges-between-medicine-and-anthropology/. About the post: I hope that other scientists understand anthropology, but at the same time, it's essential that anthropology also enters other spaces and accepts invitations outside of its own citadel. (This episode is available in additional languages on Platypus, The CASTAC Blog.)

❤️ Bonjour,Bienvenue dans cet épisode consacré aux compléments alimentaires dans le domaine de la cardiologie

Episode: 3044 Randomized Clinical Trials.  Today, statistics, evidence and medicine.

Le Mini Temps Psy du Militanpsy ! Un petit temps accordé à une grande connaissance de soi

Interview with Churl-Su Kwon, MD, MPH, author of Association of New-Onset Seizures With SARS-CoV-2 Vaccines: A Systematic Review and Meta-Analysis of Randomized Clinical Trials. Hosted by Cynthia E. Armand, MD. Related Content: Association of New-Onset Seizures With SARS-CoV-2 Vaccines

Interview with Churl-Su Kwon, MD, MPH, author of Association of New-Onset Seizures With SARS-CoV-2 Vaccines: A Systematic Review and Meta-Analysis of Randomized Clinical Trials. Hosted by Cynthia E. Armand, MD. Related Content: Association of New-Onset Seizures With SARS-CoV-2 Vaccines

Interview with Churl-Su Kwon, MD, MPH, author of Association of New-Onset Seizures With SARS-CoV-2 Vaccines: A Systematic Review and Meta-Analysis of Randomized Clinical Trials. Hosted by Cynthia E. Armand, MD. Related Content: Association of New-Onset Seizures With SARS-CoV-2 Vaccines

Even as we prioritize natural interventions in functional medicine, GLP-1 agonist drugs such as Wegovy and Ozempic offer sometimes life-changing support for those who have long struggled with resistant overweight/obesity and high blood sugar. However, there are side effects, including the risk of substantial muscle loss and sagging, aged skin ("Ozempic face" as it's indelicately known). It's a concern that hits home for me, considering the pivotal role we know that muscle plays in overall health and longevity. In this New Frontiers podcast episode I welcome back Dr. Anurag Singh to unravel the complexities of these issues. We explore the interplay between metabolic health and muscle preservation, touching on everything from the mechanisms of GLP-1 agonists and their long-term effects on aging and sarcopenia, to the promising potential of dietary and lifestyle interventions to counteract negative effects. We consider the potential for one of my all-time fave postbiotic epinutrients - Urolithin A - to assist by supporting mitochondrial health and preserving/enhancing muscle quality. This timely conversation is one you won't want to miss. Tune in and please leave us a review wherever you listen to New Frontiers. – DrKF Check out our show notes https://www.drkarafitzgerald.com/fxmed-podcast/ Guest information Anurag Singh, MD, PhDChief Medical Officer at Timeline Thank you to our sponsor Timeline Mitopure Research from Timeline care@timeline.com Timeline Discount for New Frontiers Listeners Timeline is offering DrKFs readers a 10% discount on Timeline products. Head over to Timeline and use the code KARA10 at checkout. Show Notes Study: Once-Weekly Semaglutide in Adults with Overweight or Obesity https://tinyurl.com/y3c2ypkw Pre-clinical trial (Recruiting): Effects of Urolithin A Supplementation on Glucose Metabolism in Healthy Adults 55>= Years Old...https://tinyurl.com/bdzfccr8 Study: Urolithin A improves muscle strength, exercise performance, and biomarkers of mitochondrial health in a randomized trial in middle-aged adults https://tinyurl.com/2p9pjpxc Study: Antidiabetic Effect of Urolithin A in Cultured L6 Myotubes and Type 2 Diabetic Model KK-Ay/Ta Mice with Glucose Intolerance https://tinyurl.com/2jkhmu9w Study: Urolithin A, a Gut Metabolite, Improves Insulin Sensitivity Through Augmentation of Mitochondrial Function and Biogenesis https://tinyurl.com/mvrjxxsm Study: Effect of Urolithin A Supplementation on Muscle Endurance and Mitochondrial Health in Older Adults A Randomized Clinical Trial https://tinyurl.com/fscfdd85 Study: Direct supplementation with Urolithin A overcomes limitations of dietary exposure and gut microbiome variability in healthy adults to achieve consistent levels across the population https://tinyurl.com/e6npdvyp Preprint article: Topical application of Urolithin A slows intrinsic skin aging and protects from UVB-mediated photodamage: Findings from Randomized Clinical Trials https://tinyurl.com/2m2nzd56

Assessment of Long-Term Clinical Outcomes of De Novo DCB Performance: A Comprehensive, Individual Patient Data Meta-Analysis of Randomized Clinical Trials

This week, please join author Prakriti Gaba as she discusses the article "Percutaneous Coronary Intervention Versus Coronary Artery Bypass Grafting in Patients With Left Main Disease With and  Without Diabetes: Findings From a Pooled Analysis of 4 Randomized Clinical Trials." For the episode transcript, visit: https://www.ahajournals.org/do/10.1161/podcast.20240422.957293

It can sometimes be tough to summon the motivation and energy to go to exercise. Well, there's a product for that and it's gaining popularity.Pre-workout mixtures come in powders, pills, drinks, gummies — you name it, they've got it.Norman and Tegan run through what they actually contain, and what the evidence says about their effectiveness…Got a health question? Shoot us a line @ABCHealth on Instagram, or send a voice memo to thatrash@abc.net.au. We'd love to hear from you!References: Multi-ingredient pre-workout supplements, safety implications, and performance outcomes: a brief reviewEffects of Beta-Alanine on Muscle Carnosine and Exercise Performance:A Review of the Current LiteratureCreatine Supplementation for Muscle Growth: A Scoping Review of Randomized Clinical Trials from 2012 to 2021

Moderator: James P. Rathmell, M.D. Participants: Faraj Abdallah, M.D. and Michael R. Fettiplace, M.D., Ph.D. and Ashraf S. Habib, M.D., M.B.B.Ch., M.Sc., M.H.Sc. and Jonathan Slonin, M.D., M.B.A. Articles Discussed: Analgesic Effectiveness of Liposomal Bupivacaine versus Plain Local Anesthetics for Abdominal Fascial Plane Blocks: A Systematic Review and Meta-analysis of Randomized Trials Meta-analyses of Randomized Clinical Trials in Postsurgical Pain: Verify before Trusting Liposomal Bupivacaine for Abdominal Fascial Plane Blocks: No Evidence or Lack of Relevant Evidence? Liposomal Bupivacaine, Scientific Evidence, and the Clinician's Conundrum Liposomal Bupivacaine's Plausibility Fails to Translate

Un nouvel épisode du Pharmascope est maintenant disponible! Dans de ce 133ème épisode, Nicolas, Sébastien, Isabelle discutent de quelques nouveautés pharmacothérapeutiques. Au menu: la clascotérone, les phytostérols, daridorexant et vaccin contre le RSV. Les objectifs pour cet épisode sont les suivants: Résumer les bénéfices et les risques associés à ces nouvelles thérapies Expliquer les avantages et les inconvénients de ces thérapies Discuter de la place des nouvelles thérapies dans l'arsenal thérapeutique Ressources pertinentes en lien avec l'épisode Clascotérone 1%Hebert A et coll. Efficacy and Safety of 1% Clascoterone Cream in Patients Aged > 12 Years With Acne Vulgaris. J Drugs Dermatol. 2023;22:174-81. Eichenfield LF et coll. Long-Term Safety and Efficacy of Twice-Daily Topical Clascoterone Cream 1% in Patients Greater Than or Equal to 12 Years of Age With Acne Vulgaris. J Drugs Dermatol. 2023;22:810-6. Hebert A et coll. Efficacy and Safety of Topical Clascoterone Cream, 1%, for Treatment in Patients With Facial Acne: Two Phase 3 Randomized Clinical Trials. JAMA Dermatol. 2020;156:621-30. Phytostérols pursShaghaghi MA, et coll. Water dispersible plant sterol formulation shows improved effect on lipid profile compared to plant sterol esters. J Functional Foods. 2014;6:280-9. Palmeiro-Silva YK et coll. Effects of Daily Consumption of an Aqueous Dispersion of Free-Phytosterols Nanoparticles on Individuals with Metabolic Syndrome: A Randomised, Double-Blind, Placebo-Controlled Clinical Trial. Nutrients. 2020;12:2392. DaridorexantMignot E et coll. Safety and efficacy of daridorexant in patients with insomnia disorder: results from two multicentre, randomised, double-blind, placebo-controlled, phase 3 trials. Lancet Neurol. 2022;21:125-39. Dauvilliers Y et coll. Daridorexant, a New Dual Orexin Receptor Antagonist to Treat Insomnia Disorder. Ann Neurol. 2020;87:347-56. Vaccin contre le RSVPapi A et coll; AReSVi-006 Study Group. Respiratory Syncytial Virus Prefusion F Protein Vaccine in Older Adults. N Engl J Med. 2023;388:595-608.

JAMA Statistical Editor Roger J. Lewis, MD, PhD, discusses Adjustment for Baseline Characteristics in Randomized Clinical Trial with Lars W. Andersen, MD, MPH, PhD, DMSc. Related Content: Adjustment for Baseline Characteristics in Randomized Clinical Trials

European HTN Guidelines, vitamin D, bempedoic acid, and leadless pacing, with some critical appraisal techniques thrown in, are the topics John Mandrola, MD, tackles 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. European Hypertension Guidelines New ESH Hypertension Guidelines Aim for Simplified Message https://www.medscape.com/viewarticle/993913 - 2023 ESH Guidelines for the management of arterial hypertension The Task Force for the management of arterial hypertension of the European Society of Hypertension Endorsed by the European Renal Association (ERA) and the International Society of Hypertension (ISH) https://pubmed.ncbi.nlm.nih.gov/37345492/ II. Vitamin D CV Benefit From Vitamin-D Caps Hinted in Huge D-Health Trial https://www.medscape.com/viewarticle/993996 - Vitamin D supplementation and major cardiovascular events: D-Health randomised controlled trial https://www.bmj.com/content/381/bmj-2023-075230 - Vitamin D Supplementation and Cardiovascular Disease Risks in More Than 83 000 Individuals in 21 Randomized Clinical Trials https://jamanetwork.com/journals/jamacardiology/fullarticle/2735646 III. Bempedoic Acid 'Striking' Benefit of Lipid Lowering in Primary Prevention https://www.medscape.com/viewarticle/993666 - Bempedoic Acid for Primary Prevention of Cardiovascular Events in Statin-Intolerant Patients https://jamanetwork.com/journals/jama/fullarticle/2806646 - Bempedoic Acid for High-Risk Primary Prevention of Cardiovascular Disease https://jamanetwork.com/journals/jama/fullarticle/2806647 - Bempedoic Acid and Cardiovascular Outcomes in Statin-Intolerant Patients https://www.nejm.org/doi/full/10.1056/NEJMoa2215024 IV. Leadless Pacing FDA Approves First Leadless Dual-Chamber Pacing System https://www.medscape.com/viewarticle/994033 - A Dual-Chamber Leadless Pacemaker https://www.nejm.org/doi/full/10.1056/NEJMoa2300080 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

In this episode, my guest is Tim Ferriss — a five-time #1 New York Times bestselling author, technology investor and host of the iconic podcast, The Tim Ferriss Show. We discuss Tim's process of exploration, experimentation and mastery — themes that have spanned his career that have placed him on the cutting-edge of many important fields. Tim explains what questions to ask when approaching any new endeavor in order to maximize success. He also explains how to incorporate structure and playfulness into skill and knowledge mastery, how to find and work with mentors, the key importance of location and networks in creating truly impactful things. We also discuss Tim's philanthropic efforts to support research on psychedelics for the treatment of mental health challenges and we discuss his latest creative endeavors. This episode should be of interest to a wide range of listeners, as Tim's mastery and wisdom spans athletic and mental pursuits, business, media, technology and the arts. What distinguishes Tim is his ability to thoughtfully deconstruct these processes in order to teach others how to do the same. For the full show notes, visit hubermanlab.com. Thank you to our sponsors AG1: https://drinkag1.com/huberman Maui Nui Venison: https://mauinuivenison.com/huberman LMNT: https://drinklmnt.com/huberman Levels: https://levels.link/huberman InsideTracker: https://insidetracker.com/huberman Momentous: https://livemomentous.com/huberman Timestamps (00:00:00) Tim Ferriss (00:04:08) Sponsors: Maui Nui, LMNT, Levels (00:07:43) 4-Hour Body & Development Mindset (00:15:22) Origins of Good Ideas (00:20:06) Writing & Structured Thinking (00:27:58) Writing, Night Owls (00:33:06) Sponsor: AG1 (00:34:21) Investigating Outliers; Social Media & Smartphones (00:40:37) Scientific Literacy, Randomized Clinical Trials (00:45:09) Supplement & Experiment Fails; Cold Exposure & Hyperthermia (00:50:46) Slow Carb Diet & Adherence (01:03:35) Morning Protein Intake; Fasting (01:08:48) Sponsor: InsideTracker (01:09:53) Power of Place; Building Your Network & Volunteering (01:21:43) Developing Skills; Examining Motivation & Good Questions; Simplicity (01:33:32) Early Psychedelic Exploration, Depression (01:45:38) Psychedelic Research & Mental Health Funding (01:59:00) Saisei Foundation, Journalism Fellowship, Law & Education (02:08:22) Transcranial Magnetic Stimulation (TMS), Psychedelics (02:13:28) Meditation, Transcendental Meditation, Nature (02:18:50) Extended Nature Retreats & Integration Period; “Generative Drive” (02:28:05) Mentors (02:34:53) Mind & Attention Allocation, Social Media, Boredom (02:44:12) Cockpunch (03:00:23) Suicide & Depression, Sexual Abuse, Vulnerability (03:14:22) Making Meaning from Suffering (03:19:32) Role Identity, Future (03:27:38) Parenthood, Animals & Training (03:32:21) Podcasting, Experimentation (03:36:52) Zero-Cost Support, YouTube Feedback, Spotify & Apple Reviews, Sponsors, Momentous, Social Media, Neural Network Newsletter Title Card Photo Credit: Mike Blabac Disclaimer

Guidance Recap Podcast | Adjusting for Covariates in Randomized Clinical Trials for Drugs and Biological Products

This month inside the Confident Clinician we expanded our database to include content on eye health. We provided our members with content on cataracts, dry dye, glaucoma, AMD and conjunctivitis, and included practice resources such as nutrition protocols, patient handouts and referral letters.  We also called out in this episode a free webinar we are offering our community (including you) on clinical burnout. We're providing registrants a self assessment (or the tools to assess your patients properly) and 3 key takeaways to improve your own burnout in your practice. You can register for the event here.  This podcast on fish oil and dry eye called out a specific challenge we have in research on integrative medicine, and highlights why the INQUIRY method of research actually gives us the most accurate translation from research to practice.  We highlight that if fish oil is added to standard care (eye drops) we may not fully understand the impact and that there are specific populations that are going to benefit from fish oil based on the underlying cause of their dry eye. We give you guidelines of how to use fish oil for your dry eye patients, and where we hope the research is going on this topic!      Chi, S.-C., Tuan, H.-I. & Kang, Y.-N. Effects of Polyunsaturated Fatty Acids on Nonspecific Typical Dry Eye Disease: A Systematic Review and Meta-Analysis of Randomized Clinical Trials. Nutrients 11, 942 (2019).   Molina‐Leyva, I., Molina‐Leyva, A. & Bueno‐Cavanillas, A. Efficacy of nutritional supplementation with omega‐3 and omega‐6 fatty acids in dry eye syndrome: a systematic review of randomized clinical trials. Acta Ophthalmol 95, e677–e685 (2017).

Fasting has several health benefits and has been popularised in recent times. There are many variations of fasting such as the 16:8 fast or the 5:2 diet. In the context of religion, there are several variations of fasting of religious nature.  One of the longer fasts is the month of Ramadan in Islam.  I've put together a handy factsheet to summarise the points and meal suggestions today. Click here to access it. You can connect with me in these places online:  Website:https://www.thebariatriccollective.com.au/Instagram:@thebariatriccollectiveFacebook:https://www.facebook.com/thebariatriccollectiveFree Downloads:Causes of Weight Regain Graphic Download a Free Three Day Meal Plan with RecipesReferences: Abeyasekera, Kavisha N., "Benefits of Intermittent Fasting: A Systematic Review ofRandomized Clinical Trials" (2020). Physician Assistant Studies | Student Articles. 12.https://doi.org/10.33015/dominican.edu/2020.PAS.12Patikorn C, Roubal K, Veettil SK, et al. Intermittent Fasting and Obesity-Related Health Outcomes: An Umbrella Review of Meta-analyses of Randomized Clinical Trials. JAMA Netw Open. 2021;4(12):e2139558. doi:10.1001/jamanetworkopen.2021.39558Patterson RE, Laughlin GA, LaCroix AZ, Hartman SJ, Natarajan L, Senger CM, Martínez ME, Villaseñor A, Sears DD, Marinac CR, Gallo LC. Intermittent Fasting and Human Metabolic Health. J Acad Nutr Diet. 2015 Aug;115(8):1203-12. doi: 10.1016/j.jand.2015.02.018. Epub 2015 Apr 6. PMID: 25857868; PMCID: PMC4516560.DISCLAIMER The advice provided in the podcast is general in nature and is not intended to constitute or substitute for dietetics, nutrition, professional or medical advice. You should not rely on the information presented here as medical advice. It is important to consult a medical professional for personalised medical or dietetic advice for your specific circumstances. Let's chat: Work with me 1:1 by learning about my coaching: https://simpleandeasynutrition.com/apply.html Website: https://www.thebariatriccollective.com.au/ Instagram: @thebariatriccollective Facebook: https://www.facebook.com/thebariatriccollective Email: suraya@thebariatriccollective.com.au Free Downloads: Causes of Weight Regain Graphic Download a Free Three Day Meal Plan with Recipes DISCLAIMER The advice provided in the podcast is general in nature and is not intended to constitute or substitute for dietetics, nutrition, professional or medical advice. You should not rely on the information presented here as medical advice. It is important to consult a medical professional for personalised medical or dietetic advice for your specific circumstances.

JAMA Statistical Editor Roger J. Lewis, MD, PhD, discusses Adjusting for Nonadherence or Stopping Treatments with Amanda I. Adler, MD, PhD, and Nicholas Latimer, PhD. Related Content: Adjusting for Nonadherence or Stopping Treatments in Randomized Clinical Trials

This podcast, Dr. Abby Elliott returns and the debut of Dr. Natalie Stoltman, both primary care physicians with Lakeview Clinic. They are both here for the third episode of Ridgeview Podcast CME Series: Journal Review. This is the episode where our speakers talk through new, practice changing and/or just interesting journal articles. In this episode we have six articles addressing subjects related to primary care, including antibiotic presecribing, weight loss modalities, intermittent fasting, non-alcoholic fatty liver disease, LDL levels in relation to coronary plaque, and proton pump inhibitors. The articles referenced in this podcast are linked in the attached show notes. Enjoy the podcast. Objectives:Upon completion of this podcast, participants should be able to: Identify when antibotics are warranted for pediatric infections. Compare the differences in weight change between individuals who participated in a commercial weight management program to those who participated in a "do-it-yourself (DIY)" approach. Explain intermittent fasting and its correlation to health outcomes. Define nonalcoholic fatty liver disease and explain the different treatment modalities. Explain the correlation between LDL levels and calcium scores/CTA and cardiac outcomes. Describe the best practice approach to proton-pump inhibitors (PPI) de-prescribing in ambulatory patients. Name significant/relevant findings of the journal articles being reviewed and discussed. CME credit is only offered to Ridgeview Providers & Allied Health staff for this podcast activity. After listening to the podcast, complete and submit the online evaluation form.  Upon successful completion of the evaluation, you will be e-mailed a certificate of completion within approximately 2 weeks. You may contact the accredited provider with questions regarding this program at Education@ridgeviewmedical.org. Click the link below, to complete the activity's evaluation. CME Evaluation (**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.)  DISCLOSURE ANNOUNCEMENT  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; and are property/rights of Ridgeview Medical Center & Clinics.  Any re-reproduction of any of the materials presented would be infringement of copyright laws.  It is Ridgeview's 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. Ridgeview's CME 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. Thank-you for listening to the podcast. SHOW NOTES:  *See the attachment for article discussion summaries.  Journal Article 1: "Association of Inappropriate Outpatient Pediatric Antibiotic Prescriptions with Adverse DRug Events and Health Care Expenditures" CITATION:  Butler AM, Brown DS, Durkin MJ, et al. Association of Inappropriate Outpatient Pediatric Antibiotic Prescriptions With Adverse Drug Events and Health Care Expenditures [published correction appears in JAMA Netw Open. 2022 Jun 1;5(6):e2221479]. JAMA Netw Open. 2022;5(5):e2214153. Published 2022 May 2. doi:10.1001/jamanetworkopen.2022.14153.  Available: https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2792723 Journal Article 2: "Efficacy of a Commercial Weight Management Program Compared With a Do-It-Yourself Approach: A Randomized Clinical Trial" CITATION:  Tate DF, Lutes LD, Bryant M, et al. Efficacy of a Commercial Weight Management Program Compared With a Do-It-Yourself Approach: A Randomized Clinical Trial [published correction appears in JAMA Netw Open. 2022 Sep 1;5(9):e2235316]. JAMA Netw Open. 2022;5(8):e2226561. Published 2022 Aug 1. doi:10.1001/jamanetworkopen.2022.26561  Available: https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2795182 Journal Article 3: "Intermittent Fasting and Obesity-Related Health Outcomes: An Umbrella Review of Meta-analyses of Randomized Clinical Trials" CITATION:  Patikorn C, Roubal K, Veettil SK, et al. Intermittent Fasting and Obesity-Related Health Outcomes: An Umbrella Review of Meta-analyses of Randomized Clinical Trials. JAMA Netw Open. 2021;4(12):e2139558. Published 2021 Dec 1. doi:10.1001/jamanetworkopen.2021.39558.  Available: https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2787246 Journal Article 4: "Clinical Care Pathway for the Risk Stratification and Management of Patiemts with Nonalcholic Fatty Liver Disease" CITATION:  Kanwal F, Shubrook JH, Adams LA, et al. Clinical Care Pathway for the Risk Stratification and Management of Patients With Nonalcoholic Fatty Liver Disease. Gastroenterology. 2021;161(5):1657-1669. doi:10.1053/j.gastro.2021.07.049.  Available: https://www.gastrojournal.org/article/S0016-5085(21)03384-9/fulltext?referrer=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F Journal Article 5: "Association of Coronary Plaque With Low-Density Lipoprotein Cholesterol Levels and Rates of Cardiovascular Disease Events Among Symptomatic Adults" CITATION:  Mortensen MB, Caínzos-Achirica M, Steffensen FH, et al. Association of Coronary Plaque With Low-Density Lipoprotein Cholesterol Levels and Rates of Cardiovascular Disease Events Among Symptomatic Adults. JAMA Netw Open. 2022;5(2):e2148139. Published 2022 Feb 1. doi:10.1001/jamanetworkopen.2021.48139.  Available: https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2788975 Journal Article 6: "AGA Clinical Practice Update on De-Prescribing of Proton Pump Inhibitors: Expert Review" CITATION:  Targownik LE, Fisher DA, Saini SD. AGA Clinical Practice Update on De-Prescribing of Proton Pump Inhibitors: Expert Review. Gastroenterology. 2022;162(4):1334-1342. doi:10.1053/j.gastro.2021.12.247.  Available: https://www.gastrojournal.org/article/S0016-5085(21)04083-X/fulltext?referrer=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F Please check out the additonal show notes for additional information/resources.

In this podcast, we discuss the article 'Videolaryngoscopes versus direct laryngoscopes in children: Ranking systematic review with network meta-analyses of randomized clinical trials'. We hope you enjoy. 

This week, please join authors Paul Ridker and Eric Van Belle, editorialist Robert Harrington, and Guest Editor Allan Jaffe as they discuss the original research articles "Effects of Randomized Treatment With Icosapent Ethyl and a Mineral Oil Comparator on Interleukin-1β, Interleukin-6, C-Reactive Protein, Oxidized Low-Density Lipoprotein Cholesterol, Homocysteine, Lipoprotein(a), and Lipoprotein Associated Phospholipase A2: A REDUCE-IT Biomarker Substudy" and “Cerebral Microbleeds During Transcatheter Aortic Valve Replacement: A Prospective Magnetic Resonance Imaging Cohort” and the editorial "Trials and Tribulations of Randomized Clinical Trials." Dr. Carolyn Lam:             Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to the Journal and its editors. We're your co-hosts. I'm Dr. Carolyn Lam, Associate Editor from the National Heart Center, and Duke National University of Singapore. Dr. Greg Hundley:           And I'm Dr. Greg Hundley, Associate Editor, Director of the Pauley Heart Center at VCU Health in Richmond, Virginia. Dr. Carolyn Lam:             It's double feature time Greg. We've got two totally unique and interesting papers that we'll be discussing. The first, a biomarker substudy from the REDUCE-IT trial, that is looking at the effects of randomized treatment with icosapent ethyl, versus a mineral oil comparator, on inflammatory biomarkers. Now, don't use roll your eyes at me, because I'm telling you, this has results that you may not expect, and very, very important clinical implications, and implications for clinical trials. The second paper, very much up your alley, Greg, is a prospective MRI study of cerebral microbleeds during TAVR. But okay, enough now to whet your appetite, let's now just first grab coffees, and discuss the other papers and the issue, shall we? Dr. Greg Hundley:           You bet, Carolyn. And how about if I go first? Dr. Carolyn Lam:             Please. Dr. Greg Hundley:           So, Carolyn, my first paper comes from a group of investigators led by Dr. Araz Rawshani from the Institute of Medicine, and it included 715,143 patients with diabetes, registered in the Swedish National Diabetes Register, and compared them with over two million match controls, randomly selected from the general population, to determine the role of diabetes in the development of valvular heart disease, and particularly, the relation with risk factor control. Dr. Carolyn Lam:             Huh? Interesting, diabetes and valve disease. All right. What did they find, Greg? Dr. Greg Hundley:           Right, Carolyn. So they found, that individuals with type one and two diabetes, have greater risk for stenotic lesions. Whereas, risk for valvular regurgitation was lower in type two diabetes. Patients with well controlled cardiovascular risk factors, continued to display higher risk for valvular stenosis, without a clear stepwise decrease in risk between various degrees of risk factor control. So Carolyn, diabetes and a link with valvular heart disease. Dr. Carolyn Lam:             Wow. Really interesting, Greg. Thanks. Well, the next paper is a preclinical study with really interesting clinical implications. Now, we know the human heart has limited capacity to regenerate new cardiomyocytes, and that this capacity declines with age. Now, because loss of cardiomyocytes may contribute to heart failure, it is important to explore how stimulating endogenous cardiac regeneration, to favorably shift the balance between loss of cardiomyocytes and birth of new cardiomyocytes, occurs in the aged heart. Now, these authors, Doctors Rosenzweig, from Massachusetts General Hospital, and Dr. Lee from Harvard University and colleagues, previously showed that cardiomyogenesis can be activated by, guess what? Exercise in the young adult mouse heart. However, whether exercise also induces cardiomyogenesis in aged hearts, however, is not yet known. So in today's paper, the authors aim to investigate the effect of exercise on generation of new cardiomyocytes in the aged heart. And here, we're talking about 20 month old mice, who were subjected to an eight week voluntary running protocol, and age matched sedentary animals who served as controls. Dr. Greg Hundley:           Wow, Carolyn. Really interesting evaluation of exercise on cardiomyogenesis. So what did they find? Dr. Carolyn Lam:             Endogenous cardiomyogenesis can be stimulated by exercise in aged hearts. Comparative global transcriptional analysis further revealed, that exercise and age specific changes occurred in gene programs. The regulator of calcineurin RCAN1.4 was specifically found to be induced with exercise in aged hearts, and was accompanied by reduced calcineurin activity. So what's a take-home message? Exercise induced cardiomyogenesis may counter the increased cardiomyocyte loss and reduced cardio myogenic capacity in elderly patients. Dr. Greg Hundley:           Great, Carolyn. Well from the mail bag, there's an exchange of letters to the editor from Professor Zhou and Veith regarding a prior letter to the editor from Professor Jin and associates, pertaining to the previously published article “SPARC, A Novel Regulator of Vascular Cell Function in Pulmonary Hypertension.” And also, there's a Perspective piece, from Professor Mentz entitled, “Catastrophic Disruptions in Clinical Trials.” Dr. Carolyn Lam:             There's also a Research Letter by Dr. Kumar on [entitled] “von Willebrand Factor Is Produced Exclusively by Endothelium, Not Neointima, in Occlusive Vascular Lesions in Both Pulmonary Hypertension and Atherosclerosis.” There's also this beautiful tour of Cardiology News from the literature, from Tracy Hampton, which ranges from a study linking COVID-19 to higher long term cardiovascular risks, which was published in Nature Med, to uncovering alternative metabolic pathways involving cell fate transitions, published in Nature, to designing an autonomous biohybrid fish, from human stem cell derived cardiac muscle cells, that was published in Science. Wow. Isn't that amazing, Greg? Well, let's get on now though, to our two feature papers. Shall we? Dr. Greg Hundley:           You bet. Welcome listeners, to these two feature discussions on this particular day. And our first feature today, we have with us Dr. Paul Ridker, from Brigham and Women's Hospital in Boston, Massachusetts. Dr. Bob Harrington, from Stanford University in California. And also, Dr. Allan Jaffe, from Rochester, Minnesota. Welcome to you all. And Paul, we're going to start for you. Can you describe for us, the background information that really went into the construct of your study, and what was the hypothesis that you wanted to address? Dr. Paul Ridker: Sure, Greg. So first of all, my thanks to the AHA and the Circulation for publishing this paper, we always want to support the AHA, and we're delighted to be here today for these podcasts. The field of omega-3 fatty acids has been a complicated one for a long time. Epidemiology suggested that, fish consumption would lower cardiovascular risk, and there was a number of trials done. And my friend and colleague here at the Brigham, Deepak Bhatt, was the lead of a very big trial, called REDUCE-IT. Some 8,000 plus patients who received EPA alone, and they got a terrific result. A 25% reduction in their primary endpoint. And this was a New England Journal paper, back in 2019 or so. But another friend of mine, Steve Nicholls, ran another large trial of a combination of eicosapentaenoic acid, or EPA, plus docosahexaenoic acid that's DHA called STRENGTH. And that one showed, really, no benefit. And so, there's been some controversy out there. In any event, when Deepak and his colleagues published their original paper, they said it's interesting, because they got this big risk reduction, but it wasn't apparently due to the triglyceride lowering of the drug. And so, my interest, as many people know, has largely been in inflammation biology. And so we said, well maybe we should just do a test. Well, we said, we'll measure a number of biomarkers that we know were associated with atherosclerosis, some inflammatory, some with coagulation. And so, that was the core hypothesis, was simply to look at some other markers, and see what we might learn. And sometimes, you learn things that you didn't expect. And I think, that goes to the heart of what complicated clinical trials are all about. And I'd also say perhaps, what the roles of surrogate endpoints are, as compared to hard clinical endpoints, and things that make this whole field kind of interesting. Dr. Greg Hundley:           Right. Very nice, Paul. So you mentioned REDUCE-IT, so describe a little bit more for your study. What was the study population, and what was your study design? Dr. Paul Ridker: We were fortunate enough to work with REDUCE-IT investigators, to use their biobank. They had put together, again, it's 8,000 plus patients. I think, it was two thirds secondary prevention, one third primary prevention. And when they received the combination of EPA and DHA, as I said earlier, they had about a 25% reduction in the risk of their primary endpoint, which was cardiovascular death, nonfatal AMI, nonfatal stroke, coronary revascularization, and the like. What we did is, we basically said, "Okay, since the mechanism was uncertain, why don't we go ahead and measure a series of biomarkers?" Things that a lot of us are interested in, homocysteine, LPLa, oxidized LDL, my own interest in inflammation. We measured, IL-1β, we measured, IL-6, we measured CRP. We measured another molecule, Lp-PLA2, that people have been interested in. And the hypothesis, of course, was to see what the drug did, as compared to the comparator did. And the findings were interesting to us, in that, to simplify them, the actual icosapent ethyl arm didn't do much to most of those biomarkers, very little change. But the mineral oil comparator arm had some small to modest effects on all those biomarkers, all of which went up again. Now, some of these effects are pretty small, two to 3% for things homocystine, LPLa. Others were moderate, 10 to 20% increases in oxidized LDL, Lp-PLA2. And the inflammatory markers went up about 25%, sometimes, even a little more. So it's complicated. It's important to point out, that these changes on an absolute scale are relatively small. On a percent scale, they're different. The REDUCE-IT investigators themselves, to their credit, had earlier published that, they saw some increase in LDL cholesterol as well, about 10, 11% in those who had received the mineral oil comparator. So it's not exactly what we thought we were going to find, I guess, is the simplest way to express it. Dr. Greg Hundley:           Very nice. And so, describe for us just a little bit more, any differences in men and women, and what about age? Or for example, premenopausal, postmenopausal women. Dr. Paul Ridker: No, the effects were quite consistent across all various subgroups. It's a very large study. There were, again, 8,000 patients, lots of blood samples been drawn. And I should again, commend the REDUCE-IT investigators, for allowing us to do this work with them. And again, as I point out, sometimes you find things out that weren't what you expected. And the hard part, I was glad this got tossed over with Dr. Harrington, is sort to figure out well, what's it really mean? Because again, as a clinical trial list, I will say, my instincts are to trust the primary endpoint of the trial. That's what they did. They're going to go out and lower heart attacks and strokes. And then, here we are a couple years later, trying to figure out what the mechanism might be, and just came across some puzzling results. Dr. Greg Hundley:           Very nice. Well, next listeners, we're going to turn to the editor that actually processed this manuscript, Dr. Allan Jaffe. Allan, what drew you to this particular article? Dr. Allan Jaffe:   Well, I was asked to be a guest editor this week, by the Journal, because of some conflicts that were intrinsic to the editorial board. And since I have an interest in biomarkers, and had for a long time, it made perfect sense for me to become involved. I was particularly interested in this particular area, because I was aware that there were these two trials that had found different endpoints, and that there were some controversy as to what the mechanisms might be by which these effects could occur. And so I was pleased to get involved. And I think it's a compliment to the REDUCE-IT investigators, and to Dr. Ridker, that they were willing to put the data out there so that everybody could see it. And we could then begin to look. So it was of interest to me. I thought it was important to the field, to get really good reviewers who would be, make sure that the data that would eventually be published was clear, so that readers would understand it. And so that, at the end, we'd be able to at least, come to some conclusions that we could end up having an expert in clinical trials. And I thought about Bob Harrington, right from the beginning, might be able to comment on. Dr. Greg Hundley:           Very nice. Well, Bob he's setting you up here nicely, both Paul and Allan, to really help us put these results in perspective with other studies that have been performed in this space. What are your thoughts? Dr. Robert Harrington:   So first off, Greg, thanks for having me. And Allan, thanks for inviting me to review and comment on the paper. As both Allan and Paul have indicated, that I've spent the last 30 plus years doing clinical trials of all sizes. Very small, where we try to understand mechanisms, and very large, where what we're trying to understand is clinical outcomes. And I've been intrigued in this field, because of the inconsistency of the data across the field. Where in some trials, Paul had indicated this STRENGTH, there seemed to be no effect of omega-3 fatty acids, and in REDUCE-IT, there was quite a pronounced effect of the test agent. And so, when one sees discordance in a field, one tries to understand, well, why might that be? And so in the editorial, I took the position that, well, what are we trying to do in clinical trials? And in outcomes trials, we're trying to figure out what matters to patients. Do they live longer? Do they feel better? Do they avoid bad stuff happening to them? Like having to undergo revascularization procedure. So you're trying to do things that are really clinically meaningful, but that doesn't say that you're also not trying to understand mechanism. And as Allan said, there have been some questions raised. And so, trying to understand mechanism in the edit in trials can be quite useful, not just to understand that trial results, but to really form hypothesis for a field going forward. And so, I took the approach of, we learn things from different trials, and sometimes we learn things in the same trial. Meaning that, there's mechanistic work embedded in the large trial. One of the most famous examples of this, in the GUSTO trial 30 years ago, we learned through the mechanistic substudy, that it was rapid reprofusion TIMI-3 establishment of TIMI-3 flow, that really explained the difference between TPA and streptokinase. So I was very intrigued by how we might use these data to explore the results. And I find the findings fascinating, as Paul said. It is complicated, but it raises a really fundamental issue in clinical trials. There's an assumption in a placebo control trial, that because randomization is allowing you to balance everything, except for the randomized treatment groups, and therefore, that comparison has causal information in it. There's an underlying assumption that's really important. And that is, that the placebo is inert. That it has no biological effect of its own. Well, that assumption was violated here. The placebo is not inert in this clinical trial. Now, the investigators, I think to their credit, have said, "Well, this is small, probably doesn't matter." And that might be right, but it also may be wrong. And you can't just say, well, it doesn't matter, these are small effects. As Paul said, some of the effects are small, some are medium, some are large. So what explains it? And I made a point in the editorial, you could model all of this. If you get 5% of this, and 10% of this, and 20% of this, you could make some assumptions and say, well, the magnitude of the benefit was so great that it couldn't have been overcome by this. But that's just modeling, and there's uncertainty. So for me, as a trialist, and somebody who really believes in using evidence to guide practice and to guide public policy, I think there's uncertainty here. It's likely that the treatment effect is not as large as was observed, but how large is it? And how large is important? And how large might we want to consider to put into our practice guidelines? I think all of those open questions, particularly in a field where there is inconsistency across trials, in terms of the observation of the outcome. So my conclusion is, we need more work. We need another trial, if we really want to understand this. And we need to use an inert placebo, to really understand what the contribution was. I'd like nothing better to see that it didn't matter. But I can't say that it doesn't matter because I don't know. Dr. Greg Hundley:           Well, listeners, boy, we've got kind of some interest here in that an unexpected result. So Paul, it's nice doing an interview like this listeners, because each speaker sets up the next one. Paul, Bob is saying, well, what should we do next to clarify the results here? So maybe we'll go through each of you, and start with Paul. Just describe for us, what do you think is the next study that we need to perform? Dr. Paul Ridker: Well, Greg, it's a really interesting issue. We saw it, as authors, to write as neutral a paper as we could possibly write, and sort of do our academic job and say, here are the data. And I think we did it that way because, we don't really know what the interpretation should be. On the one hand, you have a very big beneficial result, which is great for patients. And there's a prior clinical trial called JELIS, which was open label, the same drug, and also got a large benefit. And we were trying to figure out mechanism. That being said, as Bob pointed out, I think what we stumbled into is some level of uncertainty. And the question is, how uncertain would it be, and does it matter in the big picture? Allan was interesting, because the Journal asked us to use the word comparator, rather than placebo. Now this was designed as a placebo controlled trial, but our paper uses the word comparator, because of the possibility, that as Bob Harrington points out, it may not be totally inert. So the writing of this was quite carefully done. I think, at the end of the day, my REDUCE-IT colleagues, who I have great respect for, and really worked terribly hard to do the main trial, understandably feel, that the trial would've showed, and I have a lot of sympathy for that, because it's the hard endpoints we should go with. On the other hand, I have sympathy with the idea that it never hurts to have more data. And if there could be a way to have a second trial, and I might change the population a little bit, maybe I'd do it in true primary prevention. This was one third primary prevention. My colleague, Joanne Manson had done her, she had a trial where they showed some potential benefit in the black populations. Maybe you might over sample some minority groups. But just the pragmatic issues here, make it tough to have a second trial. And so, uncertainty is just part of what we, as physicians, have to learn to live with. Dr. Greg Hundley:           Allan, turning to you. What do you think is a next study to perform in this space? Dr. Allan Jaffe:   Well, I think what Paul has said is correct. That it would be very hard to generate enthusiasm funding for a large trial. But it might not be nearly as difficult to begin to explore the effects of the mineral oil comparator, versus the active agent, versus perhaps, another potential placebo, and see over time what happens in primary prevention patients, as a way of beginning to put some context around what these results might mean. So for example, it could turn out that, the active agent actually kept the values from rising as they normally would've, and mineral oil had no effect at all. Alternatively, mineral oil may well have been a negative. It had a negative effect. And I think, those are the sorts of questions that could be explored reasonably in the short term, without doing another multimillion dollar randomized trial. Dr. Greg Hundley:           And Bob, your thoughts. Dr. Robert Harrington:   Well, and I mentioned this in the editorial, Greg. I didn't make my recommendation lightly. I know that these trials are expensive. I know these trials take a great deal of time, a great deal of energy. And I know that the REDUCE-IT investigators worked enormously hard over the years to get this done. So I don't say tritely, "Oh, just do another trial." But if you think about the magnitude of the public health issue here, there are millions of people to who this kind of therapy might apply globally. And so, shouldn't we be more certain than less certain, if we want to include it, for example, in ACC/AHA guidelines? I would say, the answer to that is yes. And so, I think of it as, okay, let's make some assumptions. Let's assume, that the effect that was observed in JELIS and REDUCE-IT, is the true effect. That's ground truth. Well, there are different study designs one might think about, from an analytic perspective, using Bayesian statistics, as opposed to frequency statistics. One might think about an intense interim analysis plan, to understand where the data are going, and be able to pull in the prior data for evaluation. I would advise getting a smart group of people together, who spend their lives thinking about trials in the atherosclerotic space, and the REDUCE-IT team is pretty darn good, and say, "How could we do this efficiently?" I do think, there's enough uncertainty that it would be ethical, from an equipoise perspective, to include high risk patients in a second evaluation, because we do have uncertainty. And if we really want to nail this down, I think we could look at high risk patients with hypertriglyceridemia, and try to use some interesting design issues, and some interesting analytical issues, to try to reduce the sample size, lot of attention in interim analyses, to try to answer the question. I'd like, as I said, nothing better to say, "Oh look, REDUCE-IT was the truth." This next trial is consistent. That'd be, to me, a terrific outcome of this. On the other hand, if you said to me, "Well, the effect's not 25%, it's more in the 15% range." Well, maybe then we think about how we apply it to our patients a little differently, maybe a little more cautiously. So I don't make the recommendation lightly, as I said, but I do think that there are some conversations that could be had, being respectful of the effort and the expense that goes into these kind of things. To try to answer the question efficiently. Dr. Greg Hundley:           Very nice. Well listeners, we want thank Dr. Paul Ridker, from Brigham and Women's Hospital, Dr. Bob Harrington from Stanford University, Dr. Allan Jaffe, from the Mayo Clinic, for bringing us the results of a substudy of the REDUCE-IT trial, that assessed a variety of serum biomarkers, pertaining to systemic inflammation, and highlighting uncertainty around the mechanism regarding the efficacy of icosapent ethyl, that's been used previously for primary or secondary prevention of cardiovascular events. And next listeners, we are going to move to our second feature discussion and review some data pertaining to microbleeds in the central nervous system, during and after TAVR procedures. Welcome listeners, to our second feature discussion on this August 2nd. And we are going to explore some of the world of TAVR and its potential complications. And we have with us today, Dr. Eric Van Belle, from Lille, France. And also, Dr. Manos Brilakis, from Minneapolis, Minnesota. Welcome gentlemen. And Eric, we'll start with you. Can you describe for us a little, the background information that you use to assemble and construct your study, and describe, or list for us, the hypothesis that you wanted to address? Dr. Eric Van Belle:           Yes. Thanks a lot for the question. So we knew for many years, that some of the complication of the TAVR procedure relate to the brain. And it has been described by many others, that there were some complication in the brain of patient undergoing TAVR. And there was no previous investigation on potential bleeding or microbleeding in this population. And on the other side, there are previous publication on, of course, initially chronic microbleeding, in patient with some of, let's say, disease in the brain, but also, a possibility of acute microbleeding. And especially, in some interesting population relating to the TAVR feed, that is patient with valve disease, patient with endocarditis, or patient with assist device. In this population, microbleedings, acute microbleeding, have been described. And what is interesting, if you look at all these populations, these are population in which the Von Willebrand factor has been impacted and modified, and could be one of the reason of the microbleeding. And one of the similar feature of the patient with aortic stenosis that undergo TAVI, or TAVR, that are patient with indeed also, this kind of Von Willebrand disease. So if we put everything together that is previously, we only looked at antibody complication in those population, and that Von Willebrand disease, which is present in patient with aortic valve stenosis, could promote a bleeding, in particular, bleeding in the brain. We decided to look at the potential appearance of microbleeding, in patient undergoing TAVR procedure. Dr. Greg Hundley:           Very nice. And Eric, can you describe for us, your study design, and who was your study population? Dr. Eric Van Belle:           Yes. So basically, the study population is a basic population of patient undergoing TAVI. Just to make sure that one of the difficulty of this study, was to conduct and perform an MRI, a brain MRI, before the procedure, and as short as possible after the procedure, within three days, which is logistically challenging. And also, to make sure that we keep most of the population to undergo the MRI, we had to exclude patient with a high risk of pacemaker, or patient with pacemaker that could not undergo the MRI. But basically, without this, it's just a regular population. And if we indeed, compare to some of the previous work I was mentioning, about describing the acute MRI, it was important for us to make sure, or to be as sure as we could get, that indeed, this microbleeding, if we observe them, could be related to the procedure. And it means that, the MRI, after the procedure, should be done as short as possible. And also, that an MRI, a baseline MRI, should be performed. Because we know, that in this population, you could have some microbleedings also observed before starting the procedure. Dr. Greg Hundley:           So a cohort study design where MRIs are performed before, and then very soon after, TAVR procedures. So Eric, what did you find? Dr. Eric Van Belle:           So what we observed, the first thing that we confirmed was indeed, that in this population of that age, that is patient around 80 years old, when we do the baseline MRI, you find in about one out of four patients already, some microbleedings. And this was expected, and it is very similar to what is expected in this kind of population. But what was indeed more striking, that when we repeated the MRI after three days, we observed another 23% of patient with a new microbleedings that were observed. This is indeed the most important observation. What was also important that, the patient with microbleedings, and the location of the microbleedings, were not related to the cerebellum brain, because indeed we could observe some cerebellum arise in this population, as it is expected. And there was no relation between the two. So it's also, an important observation, suggesting that this microbleeding are not hemorrhagic transformation of cerebellum brain, for instance. And we also observed that, the risk of microbleeding, or the chance to observe the microbleeding, was increased when the procedure was longer. And also, when the total duration of anticoagulation was longer, we also observed that, when the procedure was, when we used protamine at the end of the procedure, the risk of microbleeding was less. And also, importantly, the status of the Von Willebrand factor, and indeed, an alteration of the multimer of Von Willebrand factor, was also associated with the risk of microbleeding in this population. Dr. Greg Hundley:           Very nice. So in this cohort of 84 individuals, average age around 80, undergoing TAVR procedure, and about 50/50 men and women, you had several factors. Prior history of bleeding, amount of heparin, absence of protamine, all indicating a higher risk of these microbleeds. So very practical information. Well, Manos, you have many papers come across your desk. What attracted you to this particular paper? And then secondly, how do we put these results really, in the context of maybe other complications that can occur during or after TAVR procedures? Dr. Emmanouil Brilakis: Yes, thanks so much, Greg. And also, congratulations Eric, for a wonderful paper, and thanks for sending it to circulation. I think, with increasing the number of targets, as you know, TAVR now is becoming the dominant mode for treating severe aortic stenosis. Safety is of paramount importance. And even though there's been a lot of progress, we still have issues with the safety of the procedure. So understanding how can make it safer is very important. And I think, what was unique in this paper, again, congratulations for creating this study, is that it opens a new frontier. We worry about stroke. We're all very worried about the stroke, and having the patient have a permanent neurologic damage during the procedure. But there may be more to it than the classic embolic stroke. And I think, this study opens actually, a new frontier with the micro cerebral bleeds. Now we don't completely understand, despite the study, we don't understand the functional significance from this. And I think, that's one of the areas that will need further research. But I think, trying to understand what causes them, and preventing those microbleeds, would have a very important role in the future, for making TAVR even safer than it is. Dr. Greg Hundley:           Very nice. Well, Manos, you really lead us into the kind of the next question. So Eric, what do you see as the next study to be performed in this sphere of research? Dr. Eric Van Belle:           Again, to me, and to follow with the comment of Manos, we need to include, I would say, to solve two questions. We have to solve the question of, what could really impact these microbleedings. And what would be the impact of this microbleeding on the long term outcome of this patient? So it's means that we have to set, as part of the studies that we will design, potentially studies on aortic immolation. Or let's say for instance, we could investigate the role of protamine. It has been suggested that protamine could be something interesting, so it could be tested as part of a randomized study. But this means that, as part of such randomized study on the use of protamine, for instance, you would include a last cohort of patients with MRI after the procedure. And also, a long term follow of the neurological complication, which indeed, is the missing part of our current study. We would need to have a much larger cohort of patients, to be able to reconnect the neurological outcome to the MRI outcome, and also to include this. So let's say, for me, one of the studies we would be interested to perform, is to conduct a study on the use of protamine, which is very simple, randomized, yes or no, and includes brain MRI in this population, as a systematic investigation, which is difficult to conduct. You have to know that it's difficult to do, but it will be very important. And then, to look at the long term neurological outcome. Dr. Greg Hundley:           And I see, Eric, you mentioned the long term, because really in the short term, so within six months, you really didn't see any changes in neurological functional outcome or quality of life. So Manos, just coming back to you. What do you see is the next study that should be performed in this space? Dr. Emmanouil Brilakis: Yeah, I agree actually, with Eric. The next step is, this was an 80 patient study. Right? It's a very small preliminary data, all that opens a new system for evaluation, we're still a very small number of patients. So having a larger number of patients, I think for me, the key thing is to understand the connection. Does this actually cause neurologic symptoms? What does it mean having a microbleed? I think right now, we're still confused on the study. There was not really much impact on the neurologic status of the patient. So for me, the number one thing is, to understand how it impacts the patient's quality of life, the neurologic status. Perhaps more sensitive studies, neurocognitive studies, to understand exactly how it impacts. And then after doing that, I agree with Eric, if this is a bad, something really bad, then we can find different ways to prevent them from happening. Protamine is one of them during the procedure time, and not be a very feasible one. Or it could be interesting to see if different valves, for example, have different propensity for causing those microbleeds. Dr. Greg Hundley: Very nice. Well listeners, we want to thank Dr. Eric Van Belle, from Lille, France, and also, our own associate editor, Dr. Manos Brilakis, from Minneapolis, Minnesota for bringing this very important study, highlighting that one out of four patients undergoing TAVR has cerebral microbleeds before the procedure. And then, after the procedure, one in four patients develop new cerebral microbleeds. And then, procedural and antithrombotic management, and persistence of acquired Von Willebrand factor defects, were associated with the occurrence of these new cerebral microbleeds. Well, on behalf of Carolyn and myself, we want to wish you a great week, and we will catch you next week On the Run. Dr. Greg Hundley:           This program is copyright of the American Heart Association 2022. The opinions expressed by speakers in this podcast are their own, and not necessarily those of the editors, or of the American Heart Association. For more, please visit ahajournals.org.

Episode: 3044 Randomized Clinical Trials.  Today, statistics, evidence and medicine.

TAG #35 GEDDE Steve - Glaucoma surgical trials: lessons learnedIntro:There have been many trials proving surgical intervention does indeed reduce the risk of progressive glaucoma damage for our patients. These include Treatment vs No Treatment studies as well as studies that compare different types of treatment. In this episode, I talk with Steve Gedde, from the University of Miami's Bascom Palmer Eye Institute, about lessons learned from these clinical trials.We begin by discussing the importance of Randomized Clinical Trials as the highest evidence-based medicine to compare treatments.Studies that we discuss include: the Fluorouracil Filtering Study Group; Tube vs Trab (TVT); Primary Tube vs Trab (PTVT); Ahmed Baervedlt Comparison (ABC); Ahmed vs Baerveldt. Some of the concepts and lessons learned include: reducing IOP prior to surgery to lessen the risk of choroidal hemorrhage from a sudden IOP drop; trabeculectomy offering titratable control that MIGS procedures do not; that it's harder to get a 20% reduction in IOP to count as a success if the IOP is lower than 25 pre-op; that Ahmed Valves have a better safety record but Baerveldt better pressure-lowering; and that antimetabolites have been shown to NOT be effective for tube-shunt surgery.There's quite a bit of information packed into this episode so I suggest checking the program notes for links to some relevant articles and presentations related to this topic.I'm Rob Schertzer, a Vancouver, Canada based glaucoma specialist, podcaster and HealthIT expert, and we're...talking about glaucoma.Outro:Talking About Glaucoma is a podcast of indeterminate frequency and duration. It's available for free on Apple Podcasts, Spotify, Google Podcasts, PocketCasts, and many other podcast services. Please rate the podcast on Apple Podcasts, subscribe to it, and tell your friends about it, so that it can reach more listeners and encourage me to continue to produce new episodes. Follow WestCoastGlaucoma on Instagram and Talking About Glaucoma on Facebook. Drop me a line at podcast@iguy.org with your show ideas or questions you would like to have answered on future episodes. Keep informed to prevent needless loss of vision from glaucoma. See you next time on Talking About Glaucoma.--------Steve Gedde is Professor of Ophthalmology, the John G. Clarkson Chair in Ophthalmology, Vice-Chair of Education and Residency Program Director at Bascom Palmer. --------We spoke in February 2020, one of three interviews I recorded at the last in-person American Glaucoma Society annual meeting prior to Covid. My apologies that all of these recordings were made using BOYA Dual Lapel USB-C BY-M3D mics plugged into an Android phone instead of my usual professional set-up. I've done my best to make the audio quality acceptable but the sound quality is not up to my usual high standards. Fortunately there is just one more episode with this low quality...so be sure to subscribe so you can get the good stuff when available.--------I'm Rob Schertzer, a Vancouver-based Glaucoma specialist, EMR guru and tech geek and we're...talking about glaucoma.About Steve Gedde:https://doctors.umiamihealth.org/provider/Steven+J+Gedde/524953Professor of OphthalmologyJohn G. Clarkson Chair in OphthalmologyVice Chair of Education and Residency Program DirectorSelected references:This link may have restricted access to American Glaucoma Society members. It is a lecture that Dr. Gedde delivered at the March 2020 AGS Annual Meeting in Washington DC entitled: Lessons Learned from Glaucoma Surgical Trialshttps://www.aao.org/annual-meeting-video/lessons-learned-from-glaucoma-surgical-trialsHere is a reasonably comprehensive list of glaucoma clinical trials, broken down as Treatment vs No Treatment and Treatment vs Treatmenthttps://eyewiki.aao.org/Clinical_Trials_in_Glaucoma—————————————————————————Production information:This episode was recorded February 29, 2020 during the Annual Meeting of the American Glaucoma Society in Washington, DC, unfortunately using a BOYA Dual Lapel USB-C Microphone BY-M3D - which I do not recommend. Mixing and sound levelling were finally completed to salvage the recording on February 21, 2022 using Hindenberg Journalist Pro software iZotope processing plug-ins on a Gigabyte AERO 17 computer. The narration was overdubbed using a Heil PR40 microphone. Opinions expressed in this podcast are those of the speakers and are not intended to be taken as the standard of care for glaucoma treatment. Please always weigh the complete clinical picture and involve patients with any decisions in their care.Robert M Schertzer, MD, MEd, FRCSCpodcast@iguy.orgTwitter - https://twitter.com/robschertzeror http://iguy.tv/twitterBlog - http://wholelottarob.comor http://iguy.tv/blogFacebook - https://facebook.com/talkingaboutglaucomaOffice website - https://westcoastglaucoma.comor http://iguy.tv/officeYouTube channel - https://youtube.com/robschertzerInstagram - https://instagram.com/westcoastglaucomaTheme music “Middle East Gold” ©Daniel Schertzer 2010 and published by Les Prods DOSWA Enr© 2022 DOSWA Prods Enr/Robert M Schertzer MD. MEd, FRCSC—————————————————————————iTunes Subtitle:A talk with Steve Gedde on lessons learned from glaucoma surgery randomized controlled trials.iTunes Summary:In this episode, I talk with Steve Gedde, from the University of Miami's Bascom Palmer Eye Institute, about lessons learned from these clinical trials.We begin by discussing the importance of Randomized Clinical Trials as the highest evidence-based medicine to compare treatments. Studies that we discuss include: the Fluorouracil Filtering Study Group; Tube vs Trab (TVT); Primary Tube vs Trab (PTVT); Ahmed Baervedlt Comparison (ABC); Ahmed vs Baerveldt. Some of the concepts and lessons learned include: reducing IOP prior to surgery to lessen the risk of choroidal hemorrhage from a sudden IOP drop; trabeculectomy offering titratable control that MIGS procedures do not; that it's harder to get a 20% reduction in IOP to count as a success if the IOP is lower than 25 pre-op; that Ahmed Valves have a better safety record but Baerveldt better pressure-lowering; and that antimetabolites have been shown to not be effective for tube-shunt surgery.

TAG #35 GEDDE Steve - Glaucoma surgical trials: lessons learnedIntro:There have been many trials proving surgical intervention does indeed reduce the risk of progressive glaucoma damage for our patients. These include Treatment vs No Treatment studies as well as studies that compare different types of treatment. In this episode, I talk with Steve Gedde, from the University of Miami's Bascom Palmer Eye Institute, about lessons learned from these clinical trials.We begin by discussing the importance of Randomized Clinical Trials as the highest evidence-based medicine to compare treatments.Studies that we discuss include: the Fluorouracil Filtering Study Group; Tube vs Trab (TVT); Primary Tube vs Trab (PTVT); Ahmed Baervedlt Comparison (ABC); Ahmed vs Baerveldt. Some of the concepts and lessons learned include: reducing IOP prior to surgery to lessen the risk of choroidal hemorrhage from a sudden IOP drop; trabeculectomy offering titratable control that MIGS procedures do not; that it's harder to get a 20% reduction in IOP to count as a success if the IOP is lower than 25 pre-op; that Ahmed Valves have a better safety record but Baerveldt better pressure-lowering; and that antimetabolites have been shown to NOT be effective for tube-shunt surgery.There's quite a bit of information packed into this episode so I suggest checking the program notes for links to some relevant articles and presentations related to this topic.I'm Rob Schertzer, a Vancouver, Canada based glaucoma specialist, podcaster and HealthIT expert, and we're...talking about glaucoma.Outro:Talking About Glaucoma is a podcast of indeterminate frequency and duration. It's available for free on Apple Podcasts, Spotify, Google Podcasts, PocketCasts, and many other podcast services. Please rate the podcast on Apple Podcasts, subscribe to it, and tell your friends about it, so that it can reach more listeners and encourage me to continue to produce new episodes. Follow WestCoastGlaucoma on Instagram and Talking About Glaucoma on Facebook. Drop me a line at podcast@iguy.org with your show ideas or questions you would like to have answered on future episodes. Keep informed to prevent needless loss of vision from glaucoma. See you next time on Talking About Glaucoma.--------Steve Gedde is Professor of Ophthalmology, the John G. Clarkson Chair in Ophthalmology, Vice-Chair of Education and Residency Program Director at Bascom Palmer. --------We spoke in February 2020, one of three interviews I recorded at the last in-person American Glaucoma Society annual meeting prior to Covid. My apologies that all of these recordings were made using BOYA Dual Lapel USB-C BY-M3D mics plugged into an Android phone instead of my usual professional set-up. I've done my best to make the audio quality acceptable but the sound quality is not up to my usual high standards. Fortunately there is just one more episode with this low quality...so be sure to subscribe so you can get the good stuff when available.--------I'm Rob Schertzer, a Vancouver-based Glaucoma specialist, EMR guru and tech geek and we're...talking about glaucoma.About Steve Gedde:https://doctors.umiamihealth.org/provider/Steven+J+Gedde/524953Professor of OphthalmologyJohn G. Clarkson Chair in OphthalmologyVice Chair of Education and Residency Program DirectorSelected references:This link may have restricted access to American Glaucoma Society members. It is a lecture that Dr. Gedde delivered at the March 2020 AGS Annual Meeting in Washington DC entitled: Lessons Learned from Glaucoma Surgical Trialshttps://www.aao.org/annual-meeting-video/lessons-learned-from-glaucoma-surgical-trialsHere is a reasonably comprehensive list of glaucoma clinical trials, broken down as Treatment vs No Treatment and Treatment vs Treatmenthttps://eyewiki.aao.org/Clinical_Trials_in_Glaucoma—————————————————————————Production information:This episode was recorded February 29, 2020 during the Annual Meeting of the American Glaucoma Society in Washington, DC, unfortunately using a BOYA Dual Lapel USB-C Microphone BY-M3D - which I do not recommend. Mixing and sound levelling were finally completed to salvage the recording on February 21, 2022 using Hindenberg Journalist Pro software iZotope processing plug-ins on a Gigabyte AERO 17 computer. The narration was overdubbed using a Heil PR40 microphone. Opinions expressed in this podcast are those of the speakers and are not intended to be taken as the standard of care for glaucoma treatment. Please always weigh the complete clinical picture and involve patients with any decisions in their care.Robert M Schertzer, MD, MEd, FRCSCpodcast@iguy.orgTwitter - https://twitter.com/robschertzeror http://iguy.tv/twitterBlog - http://wholelottarob.comor http://iguy.tv/blogFacebook - https://facebook.com/talkingaboutglaucomaOffice website - https://westcoastglaucoma.comor http://iguy.tv/officeYouTube channel - https://youtube.com/robschertzerInstagram - https://instagram.com/westcoastglaucomaTheme music “Middle East Gold” ©Daniel Schertzer 2010 and published by Les Prods DOSWA Enr© 2022 DOSWA Prods Enr/Robert M Schertzer MD. MEd, FRCSC—————————————————————————iTunes Subtitle:A talk with Steve Gedde on lessons learned from glaucoma surgery randomized controlled trials.iTunes Summary:In this episode, I talk with Steve Gedde, from the University of Miami's Bascom Palmer Eye Institute, about lessons learned from these clinical trials.We begin by discussing the importance of Randomized Clinical Trials as the highest evidence-based medicine to compare treatments. Studies that we discuss include: the Fluorouracil Filtering Study Group; Tube vs Trab (TVT); Primary Tube vs Trab (PTVT); Ahmed Baervedlt Comparison (ABC); Ahmed vs Baerveldt. Some of the concepts and lessons learned include: reducing IOP prior to surgery to lessen the risk of choroidal hemorrhage from a sudden IOP drop; trabeculectomy offering titratable control that MIGS procedures do not; that it's harder to get a 20% reduction in IOP to count as a success if the IOP is lower than 25 pre-op; that Ahmed Valves have a better safety record but Baerveldt better pressure-lowering; and that antimetabolites have been shown to not be effective for tube-shunt surgery.

In this episode, we discuss the teams in the Cells region of the 2022 RheumMadness Tournament. Our DEI discussion topic is increasing diversity in rheumatology clinical trials.Hosts: David Leverenz (Assistant Professor of Medicine at Duke), Guy Katz (Fellow at MGH), Michael Macklin (Resident at UPMC), Michael Cunningham (Fellow at UNC)Learn more about RheumMadness by visiting our website: https://sites.duke.edu/rheummadnessReferences: Anti-NET antibodies: Zuo Y, Yalavarthi S, Gockman K, et al. Anti-Neutrophil Extracellular Trap Antibodies and Impaired Neutrophil Extracellular Trap Degradation in Antiphospholipid Syndrome. Arthritis Rheumatol. 2020;72(12):2130-2135. doi:10.1002/art.41460 Cytokine networks: Simon Q, Grasseau A, Boudigou M, et al. A Proinflammatory Cytokine Network Profile in Th1/Type 1 Effector B Cells Delineates a Common Group of Patients in Four Systemic Autoimmune Diseases. Arthritis Rheumatol. 2021;73(8):1550-1561. doi:10.1002/art.41697 CAR-T cells (1): Mougiakakos D, Krönke G, Völkl S, et al. CD19-Targeted CAR T Cells in Refractory Systemic Lupus Erythematosus. N Engl J Med. 2021;385(6):567-569. doi:10.1056/NEJMc2107725 CAR-T cells (2): Orvain C, Boulch M, Bousso P, Allanore Y, Avouac J. Is There a Place for Chimeric Antigen Receptor-T Cells in the Treatment of Chronic Autoimmune Rheumatic Diseases?. Arthritis Rheumatol. 2021;73(11):1954-1965. doi:10.1002/art.41812 Pim kinases: Maney NJ, Lemos H, Barron-Millar B, et al. Pim Kinases as Therapeutic Targets in Early Rheumatoid Arthritis. Arthritis Rheumatol. 2021;73(10):1820-1830. doi:10.1002/art.41744 SLE clinical trial diversity: Falasinnu T, Chaichian Y, Bass MB, Simard JF. The Representation of Gender and Race/Ethnic Groups in Randomized Clinical Trials of Individuals with Systemic Lupus Erythematosus. Curr Rheumatol Rep. 2018;20(4):20. Published 2018 Mar 17. doi:10.1007/s11926-018-0728-2 RA clinical trial diversity: Strait A, Castillo F, Choden S, et al. Demographic Characteristics of Participants in Rheumatoid Arthritis Randomized Clinical Trials: A Systematic Review. JAMA Netw Open. 2019;2(11):e1914745. Published 2019 Nov 1. doi:10.1001/jamanetworkopen.2019.14745Critical race theory and SLE trial enrollment: Sneed RS, Mason M, Williams JN, et al. Using Critical Race Theory to Understand Trial Participation Among Black Individuals With Systemic Lupus Erythematosus: A Qualitative Study of Patients and Caregivers. Arthritis Care Res (Hoboken). 2021;73(10):1387-1395. doi:10.1002/acr.24635 Intro and Outro music:Cheery Monday by Kevin MacLeodLink: https://incompetech.filmmusic.io/song/3495-cheery-mondayLicense: http://creativecommons.org/licenses/by/4.0/

Today's listener requested topics are taken from @rdexampodcast on Instagram and FaceBook and covers Vitamin D Pathways, Randomized Clinical Trials, and Parallel vs Crossover Designs. This episode is sponsored by Pocket Prep. 1. What is the name for the active form of vitamin D? A. Cholecalciferol B. 7-dehydrocholesterol C. Calcitriol  D. Calcidiol 2. Which of the following is an example of an RCT? A. A study consists of two groups, A and B. Group a consisted of participants who had been smoking for 10 or more years. Group B consisted of participants who had never smoked. Both groups were followed for 10 years to see if they develop COPD. B. A study consists of two groups, A and B. Group a consisted of participants who had liver disease. Group B consisted of participants who did not have liver disease. Both groups were compared to see what proportion of them had been consuming alcohol on a regular basis for ten years C. A study examining the effects of a cholesterol drug randomly placed participants into two groups, a and b. Group a received the cholesterol drug whereas group b received a placebo. D. None of the studies mentioned are an example of an RCT   3. A study consisted of three groups. Participants were randomly assigned to groups in which they stayed throughout the study. Group A received treatment A. Group B received treatment B. Group C received a placebo. Which of the following best describes what type of design this study is an example of? A. Randomized Clinical Trial Crossover study B. Randomized Clinical Trial Parallel study C. Randomized Clinical Trial D. All of the above  

Did you know that the oral cavity has the second largest and most diverse microbiota after the gut, harboring over 700 species of bacteria? The progression of health or regression toward disease is critically influenced by the microbiota. In addition to being the initiation point of digestion, the oral microbiome is crucial in maintaining both oral and systemic health.   The oral microbiome rests within biofilms throughout the oral cavity and forms an ecosystem that maintains health in a state of homeostasis. However, particular imbalances in this state of equilibrium allow pathogens to develop and cause disease. This disruption of the oral microbiome leads to dysbiosis, which is an imbalance in the microbial community that is associated with a myriad of diseases -- most of which show up in various organs and systems throughout our entire body!In this episode, you will be learning about the multitude of negative downstream health effects of a dysbiotic oral cavity and why more of your health and wellness begins in your mouth than you may have previously thought. We will also go through the photobiomodulation research on oral health, where you will see that there are countless ways that red light therapy can help optimize your oral hygiene and oral "vigor." Lastly, you will hear about the newest piece of red light therapy technology that was developed specifically for the mouth and oral health. - Dr. Mike Belkowski talks about the following: An innovative way to use red light therapy for oral health How the oral biome impacts a multitude of health systems How connected your oral health is to gut health 70% or more of the immune system is located in the gut; however, immunity begins in the mouth Cardiovascular health A link between bacteria that causes both gum disease and Alzheimer's in the brain The direct correlation between poor dental health, tooth pain, bleeding gums, and anxiety/ depression The endocrine system Obesity and its link to the oral microbiome Nitric oxide production, how it supports the body's natural repair processes, and how red light therapy helps with it Diets that support the gut microbiome More electrons = less inflammation; ways to get free electrons Factors that affect the oral microbiome such as how you were born Photobiomodulation research as it relates to oral health (see works cited below) How the power of light reduces pain, improves quality of life, and improves functionality Low level laser therapy (LLLT) and how it is an effective treatment for canker sores, oral health, and more The Guardian - BioLight's newest red light therapy product that improves oral health - The Guardian is the first red light therapy oral care device of its kind, with patent-pending technology that implements dual LEDs, giving you the healing power from both red and near-infrared (NIR) light! - To learn even more about how you can improve your health via your oral microbiome, check out The Dental Diet, by Dr. Steven Lin or Heal Your Oral Microbiome, by Cass Nelson-Dooley. - Pre-order The Guardian here! - Listen to the Dr. Kelly Blodgett episode on oral health here - Works Cited   Cronshaw, Mark et al. “Photobiomodulation and Oral Mucositis: A Systematic Review.” Dentistry journal vol. 8,3 87. 5 Aug. 2020, doi:10.3390/dj8030087 Uslu MÖ, Akgül S. Evaluation of the effects of photobiomodulation therapy and ozone applications after gingivectomy and gingivoplasty on postoperative pain and patients' oral health-related quality of life. Lasers Med Sci. 2020;35(7):1637-1647. doi:10.1007/s10103-020-03037-8 Mikami, R., Mizutani, K., Sasaki, Y., Iwata, T., & Aoki, A. (2020). Patient-reported outcomes of laser-assisted pain control following non-surgical and surgical periodontal therapy: A systematic review and meta-analysis. PLoS One, 15(9) doi:http://dx.doi.org.weblib.lib.umt.edu:8080/10.1371/journal.pone.0238659 Zhao, H., Hu, J. & Zhao, L. The effect of low-level laser therapy as an adjunct to periodontal surgery in the management of postoperative pain and wound healing: a systematic review and meta-analysis. Lasers Med Sci 36, 175–187 (2021). https://doi.org/10.1007/s10103-020-03072-5 Hanna R, Dalvi S, Bensadoun RJ, Benedicenti S. Role of Photobiomodulation Therapy in Modulating Oxidative Stress in Temporomandibular Disorders. A Systematic Review and Meta-Analysis of Human Randomised Controlled Trials. Antioxidants (Basel). 2021;10(7):1028. Published 2021 Jun 25. doi:10.3390/antiox10071028 Zadik Y, Arany PR, Fregnani ER, et al. Systematic review of photobiomodulation for the management of oral mucositis in cancer patients and clinical practice guidelines. Support Care Cancer. 2019;27(10):3969-3983. doi:10.1007/s00520-019-04890-2 Pesevska, S., Nakova, M., Ivanovski, K., Angelov, N., Kesic, L., Obradovic, R., … Nares, S. (2009). Dentinal hypersensitivity following scaling and root planing: comparison of low-level laser and topical fluoride treatment. Lasers in Medical Science, 25(5), 647–650. doi:10.1007/s10103-009-0685-0  de-Melo, M. A. S., Passos, V. F., Alves, J. J., Barros, E. B., Santiago, S. L., & Rodrigues, L. K. A. (2010). The effect of diode laser irradiation on dentin as a preventive measure against dental erosion: an in vitro study. Lasers in Medical Science, 26(5), 615–621.doi:10.1007/s10103-010-0865-y   Aggarwal H, Singh MP, Nahar P, Mathur H, Gv S. Efficacy of low-level laser therapy in treatment of recurrent aphthous ulcers - a sham controlled, split mouth follow up study. J Clin Diagn Res. 2014;8(2):218–221. doi:10.7860/JCDR/2014/7639.4064  Imani, M., Golshah, A., SafariFaramani, R., & Sadeghi, M. (2018). Effect of Low-level Laser Therapy on Orthodontic Movement of Human Canine: a Systematic Review and Meta-analysis of Randomized Clinical Trials. Acta Informatica Medica, 26(2), 139. doi:10.5455/aim.2018.26.139-143  Rios, A., He, J., Glickman, G. N., Spears, R., Schneiderman, E. D., & Honeyman, A. L. (2011). Evaluation of Photodynamic Therapy Using a Light-emitting Diode Lamp against Enterococcus faecalis in Extracted Human Teeth. Journal of Endodontics, 37(6), 856–859.doi:10.1016/j.joen.2011.03.014  Basso, F. G., Oliveira, C. F., Fontana, A., Kurachi, C., Bagnato, V. S., Spolidório, D. M. P., … Costa, C. A. de S. (2011). In Vitro effect of low-level laser therapy on typical oral microbial biofilms. Brazilian Dental Journal, 22(6), 502–510. doi:10.1590/s0103-64402011000600011 - Don't forget to check out these health-related recommendations from previous podcast guests! - To learn more about red light therapy and shop for the highest-quality red light therapy products, visit www.biolight.shop Stay up-to-date on social media: Instagram YouTube Facebook

The paper we discuss is  K Humphreys, JC Blodgett, and TH Wagner. Estimating the Efficacy of Alcoholics Anonymous Without Self-Selection Bias: An Instrumental Variables Re-Analysis of Randomized Clinical Trials. Alcoholism: Clinical and Experimental Research. 2014; 38(11): 2688-2694.The primary outcomes from Project MATCH, which looked at the efficacy of different psychotherapeutic interventions for alcohol use disorder, can be found here.Helpful reference on instrumental variables analysis: ML Maciejewski and MA Brookhart. Using Instrumental Variables to Address Bias from Unobserved Confounders. JAMA 2019; 321(21): 2124-2125.Another example of using instrumental variable analysis to address an important question in psychiatry (this time, related to ECT and hospital re-admission): AT LoSasso. Use of Instrumental Variables Methods in Examining Psychiatric Readmissions. JAMA Psychiatry 2017; 74(8): 805-806.

Dr. Dan Rubin, statistician, Division of Biometrics IV in CDER's Office of Biostatistics sharing some thoughts draft guidance Adjusting for Covariates in Randomized Clinical Trials for Drugs and Biologics

Welcome to Teeth & Titanium Episode 10! On this episode we cover a number of topics including: -Current Events -Oscar is a home owner! -Journal Club: VSP vs TSP (traditional surgical planning) -Our viewing recommendations And more! Be sure to hit subscribe on your podcast app so you never miss an episode! Thanks to the CAOMS for their continued support. https://www.caoms.com If you would like to contact us, or would like to submit a topic for Resident Reminder or Journal club, please email us at: teethandtitaniumOMFS@gmail.com Articles cited in this episode: 1) Chen Z, Mo S, Fan X, You Y, Ye G, Zhou N. A Meta-analysis and Systematic Review Comparing the Effectiveness of Traditional and Virtual Surgical Planning for Orthognathic Surgery: Based on Randomized Clinical Trials. J Oral Maxillofac Surg. 2021 Feb;79(2):471.e1-471.e19. doi: 10.1016/j.joms.2020.09.005. Epub 2020 Sep 9. PMID: 33031773. Hosted by Dr. Wendall Mascarenhas and Dr. Oscar Dalmao

FDA 批准降钙素基因相关肽单抗用于预防偏头痛和丛集性头痛的发作JAMA Neurology 妊娠与临床孤立综合征发病的关系J Am Coll Cardiol 复杂的颈动脉斑块是引起隐源性卒中的一个原因Nature子刊 颅内恶性肿瘤的无创检测Nature子刊 合成纳米颗粒治疗胶质母细胞瘤加那珠单抗（galcanezumab）降钙素基因相关肽（CGRP）受体位于疼痛信号通路、颅内动脉和肥大细胞中，其活化被认为在偏头痛的病理生理学中起着因果作用。加那珠单抗（galcanezumab）是一种CGRP单克隆抗体。和此前在《神经科星期四 Episode 4》中介绍的治疗急性偏头痛的CGRP受体拮抗剂包括：瑞美吉泮（rimegepant）和乌布吉泮（ubrogepant）；以及《神经科星期四 Episode 14》中介绍的预防偏头痛发作的依替尼单抗（eptinezumab）属于一类药物。2018年9月，FDA批准加那珠单抗用于预防偏头痛发作；2019年6月，FDA批准加那珠单抗用于预防丛集性头痛发作。《CONQUER研究：加那珠单抗预防偏头痛的安全性和有效性的3b期临床研究》Lancet Neurology，2020年10月 (1)这项多中心、随机、双盲、安慰剂对照的3b期研究，纳入2到4类偏头痛预防药物无效的患者655例，患者年龄在18-75岁之间，有发作性或慢性偏头痛，在50岁之前发生偏头痛，入组后随机接受安慰剂或加那珠单抗（120mg q1m * 3m）。在1-3个月期间，加那珠单抗治疗的患者偏头痛发作天数比安慰剂显著减少。与基线相比，加那珠单抗组每月平均少4·1天，而安慰剂组每月平均少1·0天（p < 0·0001）。加那珠单抗和安慰剂之间治疗紧急不良事件的类型和数量相似。结论：加那珠单抗在偏头痛的预防治疗方面优于安慰剂，并且在以前的多个标准预防治疗失败的患者中有良好的耐受性。 《加那珠单抗预防发作性丛集性头痛的临床研究》New England Journal of Medicine，2019年7月(2)阵发性丛集性头痛是一种神经功能障碍，其特征是每天头痛发作，持续数周或数月。共招募患者106人，随机分配接受加那珠单抗（300mg）或安慰剂组。基线期每周丛集性头痛的平均发作次数，加那珠单抗组为17.8，安慰剂组为17.3。在第1至3周中，加那珠单抗组每周平均减少为8.7次，而安慰剂组为5.2次（P =0.04）。在第3周，头痛频率降低≥50%的患者，加那珠单抗组为71%，安慰剂组为53%。除了加那珠单抗组8%的患者有注射部位疼痛外，不良事件发生率在组间没有实质性差异。结论：与安慰剂相比，在首次注射后的1-3周内，加那珠单抗300mg ip降低了偶发性丛集性头痛的发作频率。多发性硬化多发性硬化（multiple sclerosis，MS）是以中枢神经系统白质炎性脱髓鞘病变为主要特点的自身免疫病。本病最常累及的部位为脑室周围白质、视神经、脊髓、脑干和小脑，主要临床特点为中枢神经系统白质散在分布的多病灶与病程中呈现的缓解复发，症状和体征的空间多发性和病程的时间多发性。 多发性硬化症主要的模式和病程可以分为以下几种临床亚型：临床孤立综合征（CIS）、复发缓解型（RR）、继发进展型（SP）、和原发进展型（PP）。 《前瞻性队列研究：妊娠与临床孤立综合征发病的关系》JAMA Neurology，2020年12月 (3)多发性硬化症常诊断于育龄妇女，但妊娠是否能延迟脱髓鞘或临床孤立综合征（CIS）的首次发作尚无共识。研究的目的是探讨妊娠与CIS发病时间的关系。这个国际、多中心、前瞻性研究纳入2557名女性，CIS发病的平均年龄为31岁，发病前46%至少有1次怀孕，43%至少有1次分娩。首次怀孕的平均年龄为23.3岁，首次分娩的平均年龄为23.8岁。与从未怀孕过的女性相比，有过怀孕和分娩经历的女性发生CIS的时间较晚，延迟3.3年（P < 0.001）。与从未分娩过的女性相比，分娩过的女性发病年龄也较晚，延迟3.4年（P < 0.001）。孕产次数与发病延迟无关。结论：发病前怀孕和分娩与CIS发病时间之间存在关联，但与次数无关。需要进一步的研究来帮助解释怀孕和多发性硬化症发病之间关联的机制。《前瞻性观察性队列研究：持续免疫治疗与活动性继发进展性多发性硬化症患者残疾结果的相关性》JAMA Neurology，2020年11月 (4)研究旨在评价继发进展性多发性硬化的患者中残疾累计发生率，及是否能够通过治疗延缓残疾累积的进展。这项观察性队列研究中， 招募53680例多发性硬化的患者，其中4997例继发进展型，在1621例符合纳入条件的患者中，女性患者68.0%，发病时的平均年龄为33.9岁。共有661例（40.8%）患者在继发进展性多发性硬化期间经历了叠加性复发。早期治疗方案和残疾累计发生无关。继发进展期的高复发率与轮椅依赖的残疾风险增加有关（P = 0.009）。在继发进展性多发性硬化期间经历反复复发的患者中，抑制疾病进展的治疗与残疾进展率的降低和轮椅依赖风险的降低显著相关。结论： 继发进展型多发性硬化症患者中，残疾进展率与早期病程和治疗方案无关，但是与疾病复发相关。多发性硬化的治疗多发性硬化治疗的主要目的是抑制炎性脱髓鞘病变进展，防止急性期病变恶化及缓解期复发，晚期采取对症和支持疗法，减轻神经功能障碍带来的痛苦。疾病修正治疗（disease-modifying therapy，DMT）主要包括：抗整合素α-4单抗（那他珠单抗 natalizumab），抗CD20单抗（奥瑞珠单抗 ocrelizumab、奥法木单抗 ofatumumab、利妥昔单抗 rituximab），抗CD52单抗（阿伦单抗 alemtuzumab）、干扰素（干扰素β-1a、干扰素β1-b）、富马酸类（富马酸二甲酯 dimethyl fumarate、富马酸单甲酯 monomethyl fumarate）、鞘氨醇调节剂（芬戈莫德 fingolimod、西尼莫德 siponimod、奥扎莫德 ozanimod）、免疫抑制剂（克拉屈滨 cladribine），还可使用其他免疫抑制剂如特立氟胺（teriflunomide）、硫唑嘌呤、环磷酰胺、米托蒽醌等。《OPERA I和OPERA II研究：复发相关的恶化与复发无关的进展对典型复发性多发性硬化症总体确认残疾积累的贡献》JAMA Neurology，2020年9月 (5)奥瑞珠单抗（ocrelizumab）是一种靶向CD20+B细胞的单克隆抗体，于2017年被批准用于多发性硬化的治疗。研究旨在评价复发相关的恶化（relapse-associated worsening，RAW）和复发无关的进展（progression independent of relapse，PIRA）对证实的残疾累积（confirmed disability accumulation，CDA）的影响，并评估两种治疗方法对预后的影响。这2个相同的、3期、多中心、双盲随机临床试验中，1656人纳入分析，两组平均年龄37.2-37.1岁，随机奥瑞珠单抗组（奥瑞珠单抗 600mg ivgtt q24w）或干扰素组（干扰素 ip q3w）共96周。12周后，干扰素组和奥瑞珠单抗组的残疾累积事件发生率分别为29.6%和21.1%；24周发生率分别为22.7%和16.2%。复发无关的进展事件是12周和24周复合残疾累积事件的主要影响因素，分别占干扰素组的78.0%和80.6%，占奥瑞珠单抗组的88.0%和89.1%。结论：大部分的残疾积累事件与明显的疾病复发无关，这挑战了目前多发性硬化复发和进展形式的临床区别。《ORATORIO研究的事后分析：奥瑞珠单抗治疗原发性进行性多发性硬化症的长期随访》Lancet Neurology，2020年12月 (6)ORATORIO研究是一项国际、多中心、双盲、随机对照的3期试验，招募年龄18-55岁的、原发性进行性多发性硬化症患者，随机分配奥瑞珠单抗（600mg ivgtt q24w）或安慰剂，至少120周，之后可以选择进入开放标签阶段。共451人进入完成6.5年的随访。在早期使用奥瑞珠单抗的患者，残疾进展比例较低（51.7% vs 64.8%，P=0.0018），复合进展率较低（73.2% vs 83.3%；p = 0.0023）；需要轮椅的比例较低（11.5% vs 18.9%；p = 0.0274）。在研究结束时，奥瑞珠单抗组患者T2病变体积更小（0.45% vs 13.00%， p

FDA 批准降钙素基因相关肽单抗用于预防偏头痛和丛集性头痛的发作JAMA Neurology 妊娠与临床孤立综合征发病的关系J Am Coll Cardiol 复杂的颈动脉斑块是引起隐源性卒中的一个原因Nature子刊 颅内恶性肿瘤的无创检测Nature子刊 合成纳米颗粒治疗胶质母细胞瘤加那珠单抗（galcanezumab）降钙素基因相关肽（CGRP）受体位于疼痛信号通路、颅内动脉和肥大细胞中，其活化被认为在偏头痛的病理生理学中起着因果作用。加那珠单抗（galcanezumab）是一种CGRP单克隆抗体。和此前在《神经科星期四 Episode 4》中介绍的治疗急性偏头痛的CGRP受体拮抗剂包括：瑞美吉泮（rimegepant）和乌布吉泮（ubrogepant）；以及《神经科星期四 Episode 14》中介绍的预防偏头痛发作的依替尼单抗（eptinezumab）属于一类药物。2018年9月，FDA批准加那珠单抗用于预防偏头痛发作；2019年6月，FDA批准加那珠单抗用于预防丛集性头痛发作。《CONQUER研究：加那珠单抗预防偏头痛的安全性和有效性的3b期临床研究》Lancet Neurology，2020年10月 (1)这项多中心、随机、双盲、安慰剂对照的3b期研究，纳入2到4类偏头痛预防药物无效的患者655例，患者年龄在18-75岁之间，有发作性或慢性偏头痛，在50岁之前发生偏头痛，入组后随机接受安慰剂或加那珠单抗（120mg q1m * 3m）。在1-3个月期间，加那珠单抗治疗的患者偏头痛发作天数比安慰剂显著减少。与基线相比，加那珠单抗组每月平均少4·1天，而安慰剂组每月平均少1·0天（p < 0·0001）。加那珠单抗和安慰剂之间治疗紧急不良事件的类型和数量相似。结论：加那珠单抗在偏头痛的预防治疗方面优于安慰剂，并且在以前的多个标准预防治疗失败的患者中有良好的耐受性。 《加那珠单抗预防发作性丛集性头痛的临床研究》New England Journal of Medicine，2019年7月(2)阵发性丛集性头痛是一种神经功能障碍，其特征是每天头痛发作，持续数周或数月。共招募患者106人，随机分配接受加那珠单抗（300mg）或安慰剂组。基线期每周丛集性头痛的平均发作次数，加那珠单抗组为17.8，安慰剂组为17.3。在第1至3周中，加那珠单抗组每周平均减少为8.7次，而安慰剂组为5.2次（P =0.04）。在第3周，头痛频率降低≥50%的患者，加那珠单抗组为71%，安慰剂组为53%。除了加那珠单抗组8%的患者有注射部位疼痛外，不良事件发生率在组间没有实质性差异。结论：与安慰剂相比，在首次注射后的1-3周内，加那珠单抗300mg ip降低了偶发性丛集性头痛的发作频率。多发性硬化多发性硬化（multiple sclerosis，MS）是以中枢神经系统白质炎性脱髓鞘病变为主要特点的自身免疫病。本病最常累及的部位为脑室周围白质、视神经、脊髓、脑干和小脑，主要临床特点为中枢神经系统白质散在分布的多病灶与病程中呈现的缓解复发，症状和体征的空间多发性和病程的时间多发性。 多发性硬化症主要的模式和病程可以分为以下几种临床亚型：临床孤立综合征（CIS）、复发缓解型（RR）、继发进展型（SP）、和原发进展型（PP）。 《前瞻性队列研究：妊娠与临床孤立综合征发病的关系》JAMA Neurology，2020年12月 (3)多发性硬化症常诊断于育龄妇女，但妊娠是否能延迟脱髓鞘或临床孤立综合征（CIS）的首次发作尚无共识。研究的目的是探讨妊娠与CIS发病时间的关系。这个国际、多中心、前瞻性研究纳入2557名女性，CIS发病的平均年龄为31岁，发病前46%至少有1次怀孕，43%至少有1次分娩。首次怀孕的平均年龄为23.3岁，首次分娩的平均年龄为23.8岁。与从未怀孕过的女性相比，有过怀孕和分娩经历的女性发生CIS的时间较晚，延迟3.3年（P < 0.001）。与从未分娩过的女性相比，分娩过的女性发病年龄也较晚，延迟3.4年（P < 0.001）。孕产次数与发病延迟无关。结论：发病前怀孕和分娩与CIS发病时间之间存在关联，但与次数无关。需要进一步的研究来帮助解释怀孕和多发性硬化症发病之间关联的机制。《前瞻性观察性队列研究：持续免疫治疗与活动性继发进展性多发性硬化症患者残疾结果的相关性》JAMA Neurology，2020年11月 (4)研究旨在评价继发进展性多发性硬化的患者中残疾累计发生率，及是否能够通过治疗延缓残疾累积的进展。这项观察性队列研究中， 招募53680例多发性硬化的患者，其中4997例继发进展型，在1621例符合纳入条件的患者中，女性患者68.0%，发病时的平均年龄为33.9岁。共有661例（40.8%）患者在继发进展性多发性硬化期间经历了叠加性复发。早期治疗方案和残疾累计发生无关。继发进展期的高复发率与轮椅依赖的残疾风险增加有关（P = 0.009）。在继发进展性多发性硬化期间经历反复复发的患者中，抑制疾病进展的治疗与残疾进展率的降低和轮椅依赖风险的降低显著相关。结论： 继发进展型多发性硬化症患者中，残疾进展率与早期病程和治疗方案无关，但是与疾病复发相关。多发性硬化的治疗多发性硬化治疗的主要目的是抑制炎性脱髓鞘病变进展，防止急性期病变恶化及缓解期复发，晚期采取对症和支持疗法，减轻神经功能障碍带来的痛苦。疾病修正治疗（disease-modifying therapy，DMT）主要包括：抗整合素α-4单抗（那他珠单抗 natalizumab），抗CD20单抗（奥瑞珠单抗 ocrelizumab、奥法木单抗 ofatumumab、利妥昔单抗 rituximab），抗CD52单抗（阿伦单抗 alemtuzumab）、干扰素（干扰素β-1a、干扰素β1-b）、富马酸类（富马酸二甲酯 dimethyl fumarate、富马酸单甲酯 monomethyl fumarate）、鞘氨醇调节剂（芬戈莫德 fingolimod、西尼莫德 siponimod、奥扎莫德 ozanimod）、免疫抑制剂（克拉屈滨 cladribine），还可使用其他免疫抑制剂如特立氟胺（teriflunomide）、硫唑嘌呤、环磷酰胺、米托蒽醌等。《OPERA I和OPERA II研究：复发相关的恶化与复发无关的进展对典型复发性多发性硬化症总体确认残疾积累的贡献》JAMA Neurology，2020年9月 (5)奥瑞珠单抗（ocrelizumab）是一种靶向CD20+B细胞的单克隆抗体，于2017年被批准用于多发性硬化的治疗。研究旨在评价复发相关的恶化（relapse-associated worsening，RAW）和复发无关的进展（progression independent of relapse，PIRA）对证实的残疾累积（confirmed disability accumulation，CDA）的影响，并评估两种治疗方法对预后的影响。这2个相同的、3期、多中心、双盲随机临床试验中，1656人纳入分析，两组平均年龄37.2-37.1岁，随机奥瑞珠单抗组（奥瑞珠单抗 600mg ivgtt q24w）或干扰素组（干扰素 ip q3w）共96周。12周后，干扰素组和奥瑞珠单抗组的残疾累积事件发生率分别为29.6%和21.1%；24周发生率分别为22.7%和16.2%。复发无关的进展事件是12周和24周复合残疾累积事件的主要影响因素，分别占干扰素组的78.0%和80.6%，占奥瑞珠单抗组的88.0%和89.1%。结论：大部分的残疾积累事件与明显的疾病复发无关，这挑战了目前多发性硬化复发和进展形式的临床区别。《ORATORIO研究的事后分析：奥瑞珠单抗治疗原发性进行性多发性硬化症的长期随访》Lancet Neurology，2020年12月 (6)ORATORIO研究是一项国际、多中心、双盲、随机对照的3期试验，招募年龄18-55岁的、原发性进行性多发性硬化症患者，随机分配奥瑞珠单抗（600mg ivgtt q24w）或安慰剂，至少120周，之后可以选择进入开放标签阶段。共451人进入完成6.5年的随访。在早期使用奥瑞珠单抗的患者，残疾进展比例较低（51.7% vs 64.8%，P=0.0018），复合进展率较低（73.2% vs 83.3%；p = 0.0023）；需要轮椅的比例较低（11.5% vs 18.9%；p = 0.0274）。在研究结束时，奥瑞珠单抗组患者T2病变体积更小（0.45% vs 13.00%， p

A musculação pode ser um importante remédio contra a depressão. Artigo citado:Gordon BR, McDowell CP, Hallgren M, Meyer JD, Lyons M, Herring MP. Association of Efficacy of Resistance Exercise Training With Depressive Symptoms: Meta-analysis and Meta-regression Analysis of Randomized Clinical Trials. JAMA Psychiatry. 2018 Jun 1;75(6):566-576. doi: 10.1001/jamapsychiatry.2018.0572

Ramez Kouzy, MD, Joseph Abi Jaoude, MD, and Ethan Ludmir, MD join JAMA Network Open Digital Media Editor, Seth Trueger, MD, MPH, to discuss a systematic review examining current randomized clinical trials of therapeutic agents to treat coronavirus disease 2019 (COVID-19). Read the article here: https://ja.ma/2B21PJs.  

Are you trying to keep up with the latest medical literature but now you can go out for dinner, go to pubs, and send your kids to school...oh wait no...they're still stuck at home...nevermind...your ears are still in the right place!In this months episode:...Lung ultrasound scans for heart failure follow up... (06:30)D. Araiza-Garaygordobil, R. Gopar-Nieto, P. Martinez- Amezcua, et al., A randomized controlled trial of lung ultrasound guided therapy in heart failure (CLUSTER-HF study), American Heart Journal (2020), https://doi.org/10.1016/ j.ahj.2020.06.003 ...Depression and the risk of cardiovascular disease... (09:40)Rajan, Selina et al. “Association of Symptoms of Depression With Cardiovascular Disease and Mortality in Low-, Middle-, and High-Income Countries.” JAMA psychiatry, e201351. 10 Jun. 2020, doi:10.1001/jamapsychiatry.2020.1351...The link between mental health and the immune system... (14:45)Shields, Grant S et al. “Psychosocial Interventions and Immune System Function: A Systematic Review and Meta-analysis of Randomized Clinical Trials.” JAMA psychiatry, e200431. 3 Jun. 2020, doi:10.1001/jamapsychiatry.2020.0431...When to look for primary hyperaldosteronism?... (18:00)Brown, Jenifer M et al. “The Unrecognized Prevalence of Primary Aldosteronism: A Cross-sectional Study.” Annals of internal medicine vol. 173,1 (2020): 10-20. doi:10.7326/M20-0065...Migraines are not as benign as we might think... (22:56)Kurth, Tobias et al. “Association of Migraine With Aura and Other Risk Factors With Incident Cardiovascular Disease in Women.” JAMA vol. 323,22 (2020): 2281-2289. doi:10.1001/jama.2020.7172...Technology takeover of T1 Diabetes care... (31:22)Agarwal, Shivani, and Anne R Cappola. “Continuous Glucose Monitoring in Adolescent, Young Adult, and Older Patients With Type 1 Diabetes.” JAMA vol. 323,23 (2020): 2384-2385. doi:10.1001/jama.2020.7058...ICU outcomes in the elderly, not all bad news... (36:30)Haas, Lenneke E M et al. “Outcomes of Intensive Care Patients Older Than 90 Years: An 11-Year National Observational Study.” Journal of the American Geriatrics Society, 10.1111/jgs.16624. 27 Jun. 2020, doi:10.1111/jgs.16624JOURNALBITES (42:00)Ketamine for rapid tranquillisationDiscrimination and hypertensionDOACs in end-stage renal failureClarithromycin + DOACs= bleedingHaloperidol for headachesPutting Type 2 diabetes into remission: DIRECT style....Hookworm & Multiple Sclerosis...Tanasescu, Radu et al. “Hookworm Treatment for Relapsing Multiple Sclerosis: A Randomized Double-Blinded Placebo-Controlled Trial.” JAMA neurology, e201118. 15 Jun. 2020, doi:10.1001/jamaneurol.2020.1118Check out the awesome infographics on Twitter @JournalSpotting or our website

In this episode of the Life After Series Radio Podcast, we discuss the mission and purpose of the Life After Series podcast. We'll discuss mental health, how to be kinder to ourselves, and other concerns we struggle with. In upcoming episodes, Dr. Cameron Staley will discuss different concerns we struggle with: anxiety, depression, relationship issues, and overcoming unwanted pornography. The first program The Life After Series launched was the LifeAfterPornography (LAP) online self-directed program. With LAP, we guide people through a 10 week, program based on Acceptance and Commitment Therapy (ACT) shown effective in research to reduce unwanted pornography. Instead of trying to control unwanted thoughts, emotions, or urges, ACT encourages us to get in touch with our values and begin building the life we want instead of trying to continue an unwinnable battle with ourselves. There are over 300 Randomized Clinical Trials on the effectiveness of ACT on addressing many mental health concerns. Importantly, ACT is the only approach I have found with scientific support for reducing unwanted pornography viewing! Often our attempts to fix our challenges, oftentimes becomes part of the reason why we're struggling and can actually make our problems worse. Sometimes the way we were “taught” to overcome a struggle may not be the best approach and we have to be able to take a step back and evaluate whether or not our efforts are actually working. Through mindfulness, we are able to accomplish just that! Why did Dr. Cameron Staley start LifeAfterPornography.com? He knew it was time to share what he had learned with the world about cutting edge mental health treatments for the concerns that impact us today! The LifeAfterPornography Online Program: www.LifeAfterPornography.com LifeAfterPornography Free Training: http://www.lifeafterpornography.com/LAP-starter-pack Facebook: https://www.facebook.com/thelifeafterseries/ To Learn More About LifeAferPornography… What Is LifeAfterPornography: https://youtu.be/uRsDRWV22Jc Dr. Staley's Story: https://youtu.be/1ehv9FFf_yg An Overview Of The Program: https://youtu.be/ZLnW3zx-xrw Free Lesson From The Program: https://youtu.be/W_y5xl_BOW4 Episode Highlights: Instead of focusing on getting rid of symptoms like depression, anxiety, or maybe unwanted pornography viewing...we could focus more on our values. Building a life we really want. It's [ACT] an alternative approach to the way our mind typically solves problems. Often our attempts to fix our challenge, whatever that challenge is, often becomes part of the reason why we're struggling, or maintains the struggle, or sometimes makes it even worse. Step back. And observe our attempts (to stop our problems) a little more. People have really strong beliefs about pornography...and addiction. My only goal is to be helpful. I don't believe that one approach is best. I'm just most interested in helping overcome challenges and begin living the life they want. And I've found this approach to be really helpful in a lot of situations like pornography. It's hard to have a lot of compassion for differences. People have good reasons to be heated. I care about those who have strong reactions.

The best evidence for proving cause-and-effect comes from randomized clinical trials. However, they are expensive and difficult to perform. The natural assortment of gene variants at birth can mimic randomization in some circumstances and yield important clinical information that can help physicians better care for their patients. Read the article: Mendelian Randomization  

Jonathan Hirsch is the Founder and President of Syapse, a market leader in precision oncology solutions. Jonathan is dedicated to the Syapse vision of transforming healthcare through precision medicine. As President, he works closely with healthcare providers to create a robust software platform that brings together previously fragmented clinical, molecular, and outcomes data to help physicians make better decisions for their cancer patients. Jonathan works on catalyzing national cancer data sharing networks, including Oncology Precision Network (OPeN), and served on the White House Cancer Moonshot Data Sharing Working Group. In addition to his work at Syapse, Jonathan is the Chair of the Data Committee for GBM AGILE, a global initiative to find a cure for brain cancer. He is also a member of the Global Alliance for Genomics and Health Clinical Working Group and a member of the UCSF Technology Advisory Group. Earlier in his career, Jonathan worked in Neuroscience Commercial Development at Abbott Laboratories, where he developed strategies to fund drug development through partnerships and private equity financing. His research at the Center for Molecular Neurobiology at the University of Chicago helped establish the effect of exercise on promoting hippocampal neurogenesis and combating Alzheimer's disease. Jonathan received an M.Sci. in Neuroscience from Stanford University and an A.B. in Biology and Political Philosophy from the University of Chicago. 00:00 Population Health Management & Precision Medicine. 01:45 The emphasis of Precision Medicine. 02:10 “Each Patient needs to be fully understood.” 03:00 Chris Cornue - The problem with the vague definition of Population Health. 04:00 Managing Cost Effectiveness within Precision Medicine. 07:15 Looking at the Total Cost of Care and achieving a better outcome. 08:00 Developing a Standard of Care within Precision Medicine. 09:10 Incorporating Data Sharing to improve Precision Medicine. 13:30 Randomized Clinical Trials vs. Continuous Improvement. 17:00 How Jonathan got started Syapse. 20:45 “You've really got to demonstrate the what is the ROI to the healthcare system, the hospital, the physician.” 22:00 What organizations really need to think about when implementing Precision Medicine. 22:45 Integrating Data Assets. 23:15 Providing Decision-Support Framework for Physicians. 24:00 Clinical Workflow. 24:15 Creating a Learning Framework. 25:00 You can find out more information at www.syapse.com.

Video Podcast (CC)Aired date: 10/30/2013 8:30:00 AM Eastern Time

Enhanced Video PodcastAired date: 2/16/2010 1:00:00 PM Eastern Time