Podcasts about Baseline

July 16, 2025. Week 29. What is a natural history study (NHS)?  And why do we care? We care because we haven't done this before, heal those born with disease. Natural history studies, which examine the progression of a disease over time, can be either retrospective or prospective. Retrospective studies analyze existing data, like medical records, while prospective studies collect new data over time. Both types are valuable for understanding a disease's course and informing research and treatment strategies. ⁠NHS are critical for clinical trial design.  Size and Quality matter.  Validated scales are better than PROs regardless of what the current rhetoric is. What's going on now? USA - https://curesyngap1.org/resources/studies/syngap1-ProMMiS/ - 135+ over three sites, some with FOUR visits, and counting - Adding GCP - Collaborating with world class institutions and excellent clinicians at Stanford, Children's Colorado and, of course, CHOP. USA - https://Citizen.Health/partners/srf has almost 300 patients! Retrospective Health Data. USA - https://rare-x.org/syngap1/ is where we collect PROs. Australia - Dr. Sheffer is running a study, talk to her or Dani. Latin America - SYNGAP1 Argentina with others joining. Europe - https://www.patre.info/syngap1/  Key takeaways for Industry SYNGAP1 is well positioned to work with… Vlasskamp and Wiltrout are published, Citizen Health is growing & ProMMiS is truly exceptional – and growing, and Rare-X is collecting eight key PROs.   Additionally, there are significant international efforts in Australia, Latin America & Europe. Census: https://curesyngap1.org/blog/syngap1-census-2025-update-55-in-q2-2025-total-1636/  If you are in industry and thinking about starting another NHS for your asset, please don't.  Please instead partner with existing PAGs and NHS studies in your key geographies to move faster, have bigger N and not waste precious patients time, we need to accelerate drug development not slow it down by diluting patients and clinicians between too many studies. Baseline papers on SYNGAP1: 1998 - Huganir - SynGAP: a synaptic RasGAP that associates with the PSD-95/SAP90 protein family - https://pubmed.ncbi.nlm.nih.gov/9581761/ 2009 - Michaud - Mutations in SYNGAP1 in autosomal nonsyndromic mental retardation - https://pubmed.ncbi.nlm.nih.gov/19196676/ 2013 - Carvill - Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1 - https://pubmed.ncbi.nlm.nih.gov/23708187/ 2019 - Vlasskamp - SYNGAP1 encephalopathy: A distinctive generalized developmental and epileptic encephalopathy - https://pubmed.ncbi.nlm.nih.gov/30541864/ 2023 - Rong - Adult Phenotype of SYNGAP1-DEE - https://pubmed.ncbi.nlm.nih.gov/38045990/ 2024 - Wiltrout - Comprehensive phenotypes of patients with SYNGAP1-related disorder reveals high rates of epilepsy and autism - https://pubmed.ncbi.nlm.nih.gov/38470175/ Pubmed is at 28 (so less than one a week…) https://pubmed.ncbi.nlm.nih.gov/?term=syngap1&filter=years.2025-2025&timeline=expanded&sort=date&sort_order=asc   CURE SYNGAP1 CONNECT https://curesyngap1.org/curesyngap1connect/   SHARE BLOOD TO THE SRF BIOBANK AT CB! Read here for more information: https://curesyngap1.org/blog/fueling-research-syngap1-combinedbrain-biorepository-roadshow/    VOLUNTEER  Join us: https://curesyngap1.org/volunteer-with-srf/    SOCIAL MATTERS - 4,238 LinkedIn.  https://www.linkedin.com/company/curesyngap1/  - 1,400 followers with 575 Videos on YouTube.  https://www.youtube.com/@CureSYNGAP1    - 11,302 Twitter https://twitter.com/cureSYNGAP1  - 46k Insta https://www.instagram.com/curesyngap1/    NEWLY DIAGNOSED? New families have resources here! https://syngap.fund/Resources      Podcasts, give all of these a five star review! https://cureSYNGAP1.org/SRFApple   https://podcasts.apple.com/us/channel/syngap1-podcasts-by-srf/id6464522917    Episode 175 of #Syngap10  #RareDisease #PatientAdvocacy #SYNGAP1 #SynGAP #ProMMiS

Scott Garrard checked in with DJ live from Mountain West Media Days to talk about the Utah State Aggies and their future in college athletics.

In "What's the No. 1 Predictor of Personal Growth? (Part 1)," we explored whether shame, if it inspires growth and motivates change, has a place in our lives. In this follow-up episode, Kelsea and Rachael delve into various types of shame and how pride influences its effectiveness. Even if you missed the first part, you'll gain five valuable tips on harnessing shame for your benefit rather than letting it control you. Don't feed the beast! Discover evidence-based strategies to make lasting changes in your life that have previously been a struggle!NIH Study Link: Shame and the motivation to change the self(00:01:13) Welcome to the Podcast and a look back at part 1.(00:07:14) What will make lasting changes in our lives?(00:12:03) Where the problem comes in: the “not ok” shame.(00:19:55) Baseline values and shame around food. (00:31:06) Setting fitness goals. (00:33:30) Tip #1: Name the emotion.(00:40:00) Tip #2: Don't hold it in.(00:44:30) Tip #3: Practice empathy for yourself.(00:47:59) Tip #4: Identify your triggers.(00:52:51) Tip #5: Set some boundaries.(00:57:45) Cutting corners and your ideal.Want to leave the TTSL Podcast a voicemail? We love your questions and adore hearing from you. https://www.speakpipe.com/TheThickThighsSaveLivesPodcast⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠The CVG Nation app, for ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠iPhone⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠The CVG Nation app, for Android⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠Our ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠Fitness FB Group⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠.⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠Thick Thighs Save Lives Workout Programs⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠Constantly Varied Gear's ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠Workout Leggings⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠

In this episode of the JDE Connection, hosts Chandra and Paul dive into the topic of managing and understanding JD Edwards baseline ESUs (Electronic Software Updates), focusing particularly on how they affect system updates and customizations. Chandra shares her real-life frustrations working with a third-party software integration, which uncovered missing bugs tied to a baseline ESU. Paul provides a thorough explanation of what baselines are, why they matter, and how they reset update dependencies, making them more manageable for customers. The conversation also covers strategies for interpreting lengthy impact analysis reports, the importance of object usage tracking, and the challenges of retrofitting custom objects. 01:10 Compliance Training Badge Incentives and Jury Duty 04:34 No Jury Duty, Heat, and Construction Projects 06:20 Project Frustrations 08:15 So....What is a Baseline? 13:50 Impact Analysis Panic Button 16:50 Object Usage Tracking to the Rescue 20:12 Midwesternism of the Day Resources: Baseline FAQ's: https://support.oracle.com/epmos/faces/DocumentDisplay?_afrLoop=104746788911911&parent=EXTERNAL_SEARCH&sourceId=FAQ&id=626402.1&_afrWindowMode=0&_adf.ctrl-state=3tbauqq3x_4 Performing Impact Analysis: https://docs.oracle.com/en/applications/jd-edwards/change-management/9.2.x/eotsu/performing-an-impact-analysis-1.html Understanding Object Usage Tracking: https://docs.oracle.com/en/applications/jd-edwards/change-management/9.2.x/eotsu/understanding-object-usage-tracking.html If you have concerns or feedback on this episode or ideas for future episodes, please contact us at thejdeconnection@questoraclecommunity.org

In this week's episode, Josh and I are discuss and predicting what we will see in both college and pro football. We first give you our take on the ACC. Is there anyone who can counter Clemson? Then we take our debate to the AFC East. Will the Bills dominate it once again?

In this episode of The Mettleset Podcast, we're joined by Stephanie Rogers, Executive Vice President of Marketing for the San Francisco 49ers, one of the NFL's most storied and valuable franchises.Stephanie takes us inside the 49ers' global brand strategy, sharing how a legacy team balances tradition with forward-thinking innovation, from data-driven marketing to fan engagement that spans millions of people worldwide.We dive into Stephanie's impressive career across the PGA Tour, NHL, and now NFL, and how the world of sports marketing has evolved from the early days of digital content to today's always-on, global-first strategy. She shares the mindset behind her leadership philosophy - why “innovation is the baseline” - and how it continues to shape how teams connect with fans in deeper, more meaningful ways.We also talk about the 49ers' first-of-its-kind activation in the UAE, marking a major milestone as the first NFL team to engage in the region under the league's Global Markets Program. Stephanie reflects on the energy, appetite, and opportunities she witnessed during the team's time in Dubai, and what's next for the 49ers in the Middle East.Packed with storytelling, strategy, and practical advice for anyone looking to work in sport, this episode offers a front-row seat to the business behind one of the world's most iconic sports brands.

This week we release another What's Your Baseline? Shorts for you just to lighten up our summer break a bit. The topic is why simulation should not be in your process mining tool. And I'm fully aware that this is a controversial thing because people might think, “Well, it's convenient to have it in your process mining tool to do some what-ifs and move on.”But I honestly think it's a bad decision because you're limited to your process mining data, and, hand on heart, how many processes have you mined in your organization? So without further ado, have fun with this week's What's Your Baseline? Shorts. See you next week!(And here are the show notes from the initial release)The topic of this What's Your Baseline Shorts podcast is process simulation and why you should not have this in your process mining tool but rather as part of your design platform.We speak about these topics:Why simulation?What do you need for simulation?What are the outcomes of a simulation?What are the different types of simulation?Please reach out to us by either sending an email to ⁠hello@whatsyourbaseline.com⁠ or signing up for our newsletter and getting informed when we publish new episodes here: ⁠https://www.whatsyourbaseline.com/subscribe.

On this TeacherNerdz episode, we chat with Jocelynn Mattingly, a 3-8 grade music teacher who challenges the norm! Her Master's research reveals powerful strategies for ensuring high standards and outcomes for special education students in music. Tune in for inspiration on elevating ALL learners!SHOW LINKS: https://wakelet.com/wake/wmRlsMidamMd_GJJFVQ6D

Imagine with me…You are told in a vision from God to examine the life of X (a person or a family or a church like Eternal), and to report back to him.Most of us would tremble. A few, I'm afraid, might be too eager What to look for? Behaviors? How we speak to one another? Prayer life (or its absence)?Sunday we enter the world of the OT prophets. Jesus was steeped in their parables: they always taught in parables and he will too. They did it for a reason, always looking for one thing. Know what it is? Let's find out together. 

In this week's episode, Josh and I are discuss our 4th of July traditions and talk sports. We focus on the NBA offseason and what the Cavs have been doing. We breakdown the NBA draft and give you our assessment.

Today, we are re-releasing a “What's Your Baseline?” short from about two and a half years ago. And the topic of today is how to create good dashboards. And I do not think about how to do this mechanically with your tool of choice. I'm thinking about what is the thinking behind it. That might be because I'm currently writing on the chapter about dashboarding and storytelling in my upcoming second book, “Successful Processed Mining Projects”. So without further ado, enjoy What's Your Baseline? Shorts 6: How to create a good dashboard.(And here are the show notes from the initial release)Everyone wants to consume and understand large amounts of data. But how do you plan, design, and implement a good dashboard? In this What's Your Baseline Shorts, J-M and Roland walk you through the process and the considerations at each step, so that the next time you create a dashboard (for example as part of your Process Mining analysis) it will be stakeholder-oriented with a clear visual hierarchy that will make your users understand your message easily and quickly.In this episode, we are talking about:Identify your stakeholders and information needsDefine KPI and measuresCreate a solution designBuild the dashboardsIdentify data storiesRoll-out dashboardsPlease reach out to us by either sending an email to hello@whatsyourbaseline.com or sign up for our newsletter and get informed when we publish new episodes here: https://www.whatsyourbaseline.com/subscribe.

N Engl J Med 2004;351:2049-2057Background: Endothelial dysfunction, reduced nitric oxide availability, and increased oxidative stress occur in patients with heart failure and contribute to cardiac remodeling. In the V-HeFT I trial, combining isosorbide dinitrate (a nitric oxide donor) with hydralazine (an antioxidant) improved outcomes in patients with systolic heart failure. However, its long-term effectiveness in patients already receiving neurohormonal blockade was unclear.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber.Racial differences exist in heart failure prevalence, mechanisms, and outcomes. Patients who identify as Black may have a less active renin–angiotensin system and lower nitric oxide availability. Prior analyses suggested that Black patients respond well to isosorbide dinitrate + hydralazine and respond less to Angiotensin Converting Enzyme Inhibitors (ACEi). For example, in a subgroup analysis of the V-HeFT I trial, isosorbide dinitrate + hydralazine reduced mortality in Black but not White patients.The African-American Heart Failure Trial (A-HeFT) sought to assess the efficacy of isosorbide dinitrate + hydralazine in Black patients with systolic heart failure.Patients: Patients were eligible if they self-identified as Black (defined as African decent), and had NYHA class III or IV heart failure for at least 3 months. The left ventricular ejection fraction had to be 35% or less or less than 45% if the ventricle was dilated. In addition, patients had to be on guideline medical therapy for at least 3 months.Patients were excluded if they had acute coronary syndrome or stroke within 3 months, cardiac surgery or percutaneous coronary intervention within 3 months, significant valvular disease, hypertrophic or restrictive cardiomyopathy plus many others.Baseline characteristics: Patients were recruited from 161 centers in the United States. The trial randomized 1,050 patients – 518 randomized to receive isosorbide dinitrate + hydralazine and 532 to receive placebo.The average age of patients was 57 years and 60% were men. The average left ventricular ejection fraction was 24% and the average left ventricular internal diastolic diameter was 6.5 cm. The cause of cardiomyopathy was ischemic in 23% of the patients, hypertensive in 39%, idiopathic in 26%, and other causes constituted the rest. The NYHA class was III in 96% of the patients. The average systolic blood pressure was 126 mm Hg.Approximately 40% had diabetes, 17% had chronic kidney disease and 17% had atrial fibrillation.At the time of enrollment, 90% were taking a diuretic, 69% were taking an ACEi, 17% were taking an angiotensin receptor blocker, 74% were taking a beta-blocker, 39% were taking spironolactone and 60% were taking digoxin.Procedures: The trial was double-blinded. Patients were randomized in a 1:1 ratio to receive fixed-dose combination of isosorbide dinitrate + hydralazine or to receive placebo. The initial dose was one tablet taken three times daily, containing either placebo or a combination of 37.5 mg of hydralazine and 20 mg of isosorbide dinitrate. If no side effects, the dose was increased to two tablets three times a day.Patients had follow up by phone every month and clinic visits every 3 months.Endpoints: The primary endpoint was a composite of weighted values of all-cause mortality, first hospitalization for heart failure within 18 months, and change in quality of life at 6 months. Quality of life was assessed using the Minnesota Living with Heart Failure Questionnaire, a 21-question self-administered questionnaire in which scores range from 0 to 5, with higher scores reflecting worse quality of life.The table below summarizes how the weighted score for the primary outcome was calculated.Analysis was performed based on the intention to treat principle. The main manuscript did not mention the estimated number of events for sample size calculation but did mention that 1,100 patients would provide sufficient power with a p

As EU's trade commissioner, Maros Sefcovic travels to Washington, RTÉ's Europe Editor, Tony Connelly reports on a potential trade agreement between the EU and US.

Dr. Harold McGee, PhD, is a renowned author on the topics of food chemistry and culinary science. He explains how cooking methods, types of cookware and temperature can be used to transform food and drink flavors and presents simple but powerful ways to improve nutrient availability. We also discuss how our individual biology, genetic and cultural backgrounds shape our taste preferences. Whether you're a seasoned cook or someone who simply loves to eat, our conversation will change how you think about food and cooking, give you actionable tools to try and deepen your appreciation of the experience of eating and drinking. Read the episode show notes at hubermanlab.com. Thank you to our sponsors AG1: https://drinkag1.com/huberman Eight Sleep: https://eightsleep.com/huberman Our Place: https://fromourplace.com/huberman Mateina: https://drinkmateina.com/huberman Function: https://functionhealth.com/huberman Timestamps 00:00:00 Harold McGee 00:02:21 Food Chemistry, Using Copper, Modern vs Traditional Techniques 00:09:59 Sponsors: Eight Sleep & Our Place 00:13:33 Cooking, Food & Heat, Taste & Smell 00:22:10 Umami, Savory Tastes, Braising & Meat 00:29:56 Chemistry of Cooking & Eating, Sugars & Conjugates; Slowly Enjoying Food 00:36:14 Savory Meal & Dessert; Food Course Order; Palate Cleansers 00:43:56 Salt, Baseline & Shifting Taste Preferences 00:47:18 Sponsors: AG1 & Mateina 00:50:07 Whole vs Processed Foods, Taste & Enjoyment 00:53:37 Brewing Coffee, Water Temperature, Grind Size 01:00:33 Tea & Tannins, Growing Tea Plants; Tea & Meals, Polyphenols 01:08:16 Food Combinations, Individual Tolerance; Is there an Optimal Diet? 01:11:34 Onions & Garlic, Histamines, Tool: Reduce Crying when Cutting Onions 01:13:55 Gut Sensitivities & Food, Capsaicin & Spicy Foods 01:17:21 Supertasters & Taste Buds, Bitter Taste, Chefs 01:21:57 Sponsor: Function 01:23:45 Salt & Bitter, Salting Fruit, Beer or Coffee, Warming Beer 01:26:11 Human History of Alcohol & Chocolate 01:29:25 Wine Expense vs Taste, Wine Knowledge 01:35:49 Cheese Making, Aged Cheese & Crystals, Tyrosine; Smoke Flavors, Distilling 01:44:30 Fermentation, “Stink Fish”, Caviar, Traditional & New Foods 01:50:42 Personal Journey, Astronomy, Poetry & Food 01:54:55 Beans & Gas, Tool: Soaking Beans 01:57:23 Gut Microbiome, Fermented Foods; Kids & Food Aversions 02:00:47 Cilantro & Divergent Tastes; Microwave Popcorn, Parmesan Cheese 02:04:46 John Keats Poetry, To Autumn; Acknowledgements 02:10:48 Zero-Cost Support, YouTube, Spotify & Apple Follow & Reviews, Sponsors, YouTube Feedback, Protocols Book, Social Media, Neural Network Newsletter Disclaimer & Disclosures Learn more about your ad choices. Visit megaphone.fm/adchoices

In this week's episode, Josh and I are discuss the NBA Finals. We breakdown the game and discuss what the Thunder did to bring home their first championship. What's next? What does each team do to improve on this year? We also discuss the Stanley Cup Finals and some more news out of baseball.

What if everything we've accepted as “normal” the stress, the sickness, the disconnection is actually far from what it means to be fully human? The Real Human Baseline is a wake-up call and a roadmap. Hosted by Eva Payne, this podcast explores what life could look like if we remembered who we really are beyond the systems, the trauma, and the noise. Each episode unpacks what it means to live as an optimized human: physically, emotionally, and spiritually aligned. We'll dive into what society could become when we build from coherence instead of chaos. From nervous system regulation to regenerative education, from purpose-driven work to frequency-based healing, we paint a picture of a world you may have sensed… but never seen laid out clearly, until now. This is not about escaping reality. It's about reclaiming it. You're not here to fit into the old world. You're here to help build the new one.   0000014E 0000014E 00002B47 00002B47 000E3F70 000E3F70 00007E86 00007E86 00015498 00015498

In this episode, Scott sits down with Danielle Adams—a powerhouse productivity strategist and executive operations expert—on a mission to help overworked entrepreneurs reclaim their time without sacrificing income or impact. If you've been feeling stuck, scattered, or burnt out, this conversation offers clarity, structure, and real hope.-✨ What you'll learn:Why hustle fatigue is real—and how to reconnect with your deeper “why” to find fulfillment againThe difference between rest and escape, and why knowing yourself is the key to rechargingHow to stop being the bottleneck in your business by building systems that run without youWhy being productive isn't about doing more—it's about doing what matters mostWhat Danielle means by “schedule the life you want,” and how to start doing it today-If you're ready to finally scale your business and protect your peace, Danielle has the blueprint.---Episode Markers:(0:00) - Scott's Intro(1:05) - Becoming Lela(3:30) - Starting in Coaching & Deep Listening(4:50) - The Story Your Telling Yourself(7:15) - Conscious vs. Sub Conscious(9:30) - Difference Between Therapy & Coaching(12:15) - Pausing and Doing the Deep Work(15:10) - Internal + External Audits: The Starting Point of Deep Work(17:00) - Leaky Energy and the Myth of 'More Is Better'(19:10) - When Ego, Fear, and Success Get Tangled(20:30) - The Power of Saying No and Making Space(22:40) - Can Anyone Become That Always-Positive Person?(24:00) - Creating a Baseline of Calm and Ease(26:20) - How to Truly Take Time Off (and Not Fake It)(31:00) - Scarcity, Time, and Why We Expand to Fill It(32:45) - Two Powerful Client Transformations(36:25) - Where to Find Lela + Final Thoughts---Scott Grates' Links:Referrals Done Right Book Pre Sales - https://www.referralsdonerightbook.comReferrals Done Right FB Group - https://www.facebook.com/groups/296359076662332Insurance Agency Optimization - https://www.agencyoptimization.comScott Grates Website - https://www.scottgrates.comLove Living Local  - https://www.instagram.com/lovelivinglocal315Scott's FB - https://www.facebook.com/scott.grates.1Instagram - https://www.instagram.com/scottgratesTikTok - https://www.tiktok.com/@scott.grates---Lela's Links:Website - https://lelagrace.coIG - https://www.instagram.com/lela_graceLinkedin - https://www.linkedin.com/in/lela-tuhtan-ma-5599573

THE LANCET 2003;362:772-776Background: Angiotensin converting enzyme inhibitors (ACEi) reduce mortality and morbidity in patients with systolic heart failure (see CONSENSUS and SOLVD trials). However, registry data showed that up to 20% of patients with systolic heart failure were not taking ACEi. One of the frequent causes for intolerance to ACEi is cough. Angiotensin converting enzyme inhibitors work by blocking the conversion of angiotensin I to angiotensin II, a key step in the renin–angiotensin–aldosterone system (RAAS). Angiotensin II receptor blockers were tolerated in patients with systolic heart failure who were intolerant to ACEi. However, data on long term effectives as an alternative to ACEi were lacking.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber.The Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM)-Alternative trial sough to assess if the angiotensin-receptor blocker (ARB) candesartan, could improve outcomes in patients with systolic heart failure who are intolerant to ACEi.Patients: Eligible patients had left ventricular ejection fraction of 40% or less and NYHA class II, III or IV symptoms of at least 4 weeks duration. Patients had also to be intolerant to ACEi.Exclusion criteria were not provided in the main manuscript.Baseline characteristics: Patients were recruited from 618 centers in 26 countries. The trial randomized 2,028 patients – 1,013 randomized to receive candesartan and 1,015 to receive placebo.The average age of patients was 67 years and 68% were men. The average left ventricular ejection fraction was 30%. Cardiomyopathy was ischemic in 68% of the patients. The NYHA class was II in 48% of the patients, III in 49% and IV in 4%.Approximately 50% had hypertension, 27% had diabetes, 61% had prior myocardial infarction, 9% had stroke, 25% had atrial fibrillation and 14% were current smokers.At the time of enrollment, 85% were taking a diuretic, 46% were taking digoxin, 55% were taking beta-blockers and 24% were taking spironolactone.The most common reasons for ACEi intolerance were cough in 72% of the patients, hypotension in 13%, renal dysfunction in 12% and angioedema or anaphylaxis in 4%.Procedures: The trial was double-blinded. Patients were assigned in a 1:1 ratio to receive candesartan starting at 4 or 8mg once daily or placebo. The treatment was doubled every two weeks to a target dose of 32mg once daily.After randomization, follow up occurred at 2, 4, and 6 weeks, 6 months and every 4 months thereafter.Endpoints: The primary outcome was a composite of cardiovascular death or heart failure hospitalizations. All deaths were classified as cardiovascular unless there was a clear non-cardiac cause.Analysis was performed based on the intention-to-treat principle. The estimated sample size to have 80% power at 5% alpha was 2,000 patients. The sample size calculation assumed 18% relative risk reduction in the primary outcome with candesartan assuming a 15% annual event rate in the placebo arm.Results: The median follow up time was 34 months. The mean candesartan daily dose was 23mg at 6 months.Candesartan reduced the primary endpoint of cardiovascular death or heart failure hospitalizations (33.0% vs 40.0%, adjusted HR: 0.70, 95% CI: 0.60 – 0.81; p< 0.001). Candesartan reduced the individual components of the primary outcome - (21.6% vs 24.8%; p= 0.02) for cardiovascular death and (20.4% vs 28.2%; p< 0.001) for heart failure hospitalizations. All-cause death was also lower with candesartan (26.2% vs 29.2%, adjusted HR: 0.83, 95% CI: 0.70–0.99; p= 0.033). The number of patients who had any hospitalization as well as the total number of hospitalizations were numerically but not statistically significantly lower with candesartan (60.2% with candesartan vs 63.3%; p= 0.16) and (1,718 vs 1,835; p= 0.06).Candesartan was associated with more hypotension (3.7% vs 0.9%), more increase in creatinine (6.1% vs 2.7%) and more hyperkalemia (1.9% vs 0.3%). Angioedema occurred in three patients in the candesartan group and none in the placebo group. Cough occurred in two patients taking candesartan and four taking placebo.Authors reported no significant subgroup interactions, however, a corresponding graph was not provided.Conclusion: In patients with systolic heart failure who are intolerant to ACEi, candesartan reduced the primary composite outcome of cardiovascular death or heart failure hospitalizations with a number needed to treat of approximately of 14 patients over 34 months of follow up. Candesartan also reduced all-cause death with a number needed to treat of approximately 33 patients. Adverse events including hypotension, increase in creatinine and hyperkalemia were more common with candesartan.The reduction in the primary endpoint with candesartan was significant and offers an alternative for patients who are unable to tolerate ACEi. Of note, 72% of the patients enrolled in the trial were intolerant to ACEi due to cough. This trial did not include a head-to-head comparison between ARBs and ACEi, and therefore does not address which agent should be preferred as first-line therapy. Only 24% of participants were receiving spironolactone. The combination of ARBs with spironolactone, may increase the risk of adverse events, particularly hyperkalemia and kidney injury.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber. Get full access to Cardiology Trial's Substack at cardiologytrials.substack.com/subscribe

In this episode, we review the pharmacology, indications, adverse effects, monitoring, and unique drug characteristics of angiotensin receptor blockers (ARBs).  Key Concepts ARBs are equally efficacious as ACE inhibitors when used for hypertension, heart failure with reduced ejection fraction (HFrEF), chronic kidney disease (CKD) with proteinuria, and post-MI care. Some limited evidence suggests that they might be better in reducing albuminuria in patients with diabetes. ARBs are generally better tolerated than ACEi due to a lower risk of angioedema and dry cough.  While most ARBs are comparable to each other, small differences exists regarding hepatic metabolism (CYP metabolism for losartan, telmisartan, and azilsartan), degree of blood pressure lowering (generally better with azilsartan, olmesartan, valsartan, and candesartan), and additional pharmacological effects (telmisartan with PPAR-Y agonism, losartan with uricosuric effect). ARBs are contraindicated in pregnancy, those with bilateral renal artery stenosis, and those with previous angioedema to ARBs. The most common adverse effects include hypotension and hyperkalemia, but in rare cases acute renal impairment can also occur. Baseline serum creatinine and potassium should be monitored in patients taking ARBs. After initiation or dose adjustment, blood pressure, serum creatinine, and potassium should be repeated in 1-2 weeks. Signs and symptoms of hypotension as well as angioedema should be monitored throughout the treatment period.

The missing piece in your M.E/CFS recovery Have you ever felt like your body's stuck in shutdown mode — like it's trying to keep you hidden away in a cave? In this week's episode of the CFS Health Recovery Podcast, I'm joined by our brilliant medical consultant Dr. Olivia Lesslar. Together, we unpack a concept that's helped thousands of our clients break free from the push-crash cycle and finally make steady, consistent progress. It's called baseline - and it might just be the missing piece in your recovery. If you find yourself doing too much on a good day, then crashing for days after… Here are 4 ways we can help. 1. Join our free community to meet others, be inspired, and get more recovery info - https://www.facebook.com/groups/cfshealthrecoveryhub 2. Watch the newly released past members "Guest Panel" Workshop where they share their top 5 recovery secrets - https://www.cfshealth.com/guestpanelreplay 3. Get our free most popular recovery trainings:- Find your baseline - Stop pushing and crashing - https://www.cfshealth.com/baseline - The 3 stages of recovery and what to do in each one - https://www.cfshealth.com/the3stages - The "9 do's and don'ts" PDF - to decrease symptoms and improve energy - https://www.Cfshealth.com/pdf 4. Want to help professionally with a step-by-step recovery plan specific to you? Fill out the application form and the team will send you the details - https://www.cfshealth.com/form

In this week's episode, Josh and I are talking about the shocking blockbuster trade that the Red Sox and Giants completed. Why would the Red Sox get rid of Devers now? And will he play first base for the Giants?!

Vision is common. The discipline to execute is rare. Do you have it? In today's Episode, hosts Clark Lunt and David Shaw sit down with Shaye Wali, a former tennis champion turned entrepreneur. Shaye details his extraordinary transition from the world of professional sports to the fast-paced sectors of private lending and software development. As the founder and CEO of Baseline, a revolutionary software platform, he shares the pivotal moments and challenges that shaped his career, offering valuable insights for aspiring entrepreneurs. Shaye's story is one of focus and resilience. He recounts the immense dedication required to rebuild the tennis program at Tulane University, a testament to his early leadership and determination and desire to travel the road less paved. This experience, he explains, laid the groundwork for his future endeavors. Following his passion for finance, he began his career at Morgan Stanley, where he gained a deep understanding of capital markets and real estate investments. However, the entrepreneurial spirit beckoned. Shaye identified a significant gap in the private lending market, an industry often bogged down by inefficiencies and outdated processes. This realization was the catalyst for his move into entrepreneurship. He emphasizes that the ability to adapt to the ever-changing landscape of real estate and private lending was crucial to his success. This journey culminated in the creation of Baseline, a cutting-edge software designed to streamline the entire private lending process. "We built Baseline to empower lenders," Wali states. "Our goal is to provide a seamless, efficient platform that allows them to manage their operations, from loan origination to servicing, with greater ease and accuracy." The software aims to enhance efficiency, improve data management, and ultimately help private lenders scale their businesses. Shaye's narrative serves as a powerful example of how skills honed in one discipline can be successfully transferred to another. His journey from the tennis court to the boardroom highlights the universal importance of focus, the courage to pivot, and the drive to innovate. For those in the real estate and private lending industries, Shaye Wali's story is not just inspiring; it's a roadmap for navigating the complexities of the modern financial world.Connect with Shaye Wali: https://www.linkedin.com/in/shayewali/ or https://www.baselinesoftware.com/TakeawaysShaye's journey from tennis to tech showcases resilience.Corporate experience at Morgan Stanley shaped the entrepreneurial mindset.The importance of focus in achieving success.Transitioning from employee to entrepreneur requires courage.Private lending offers scalability and flexibility.The evolution of private lending is driven by technology.Chapters00:00 Introduction to Shaye Wali and His Journey03:27 From Pakistan to Florida: The Early Years05:28 Tennis and the Path to College06:58 Building a Tennis Program at Tulane09:46 Transitioning to Morgan Stanley12:00 The Realization of Entrepreneurial Spirit14:38 The Shift to Real Estate17:20 Navigating the Real Estate Market19:48 The Move to Private Lending22:19 Burning the Boats: Taking the Leap24:36 The Evolution into Private Lending30:11 The Journey into Private Lending35:19 Scaling the Private Lending Business40:10 Transitioning to Software Solutions46:11 The Future of Private Lending and Software49:56 Rapid Fire Insights and Final Thoughts58:30 Introduction and Call to Action59:01 Introduction to Burn Your Boats Wealth Podcast59:30 Engagement and Community Building Hosted on Acast. See acast.com/privacy for more information.

In this week's episode, Josh and I are talking about the absolute domination by the Reds in this years Ohio Cup. We talk about what the Reds did well and what the Guardians did not do. We also break down the two big moves that affect the Browns (Aaron Rodgers and Nick Chubb).

Alex Greenwood sits down with certified executive coach and PR veteran Katie Neal to tackle one of the PR world's dirtiest secrets: burnout.What makes PR a perfect storm for overwork and perfectionism? How do you tell “normal busy” from “I-can't-get-out-of-bed” exhaustion? Katie breaks it down with empathy and no-nonsense advice.In this episode you'll learn:The Burnout Spectrum: From mild fatigue to full-blown collapse—where do you fall?PR's Pressure Cooker: Why tight deadlines, client expectations, and the 24/7 news cycle fuel workaholismBoundary Bootcamp: Simple, actionable ways to carve out “off” time and actually keep itValues-Driven Work: How aligning on what matters most can guard against depletionLeadership's Role: What managers must do (and stop doing) to foster a truly sustainable cultureWhether you're just starting to feel the heat or you've already hit the wall, Katie's insights will help you reclaim your energy—and your career.Visit the Katie Neal Coaching & Consulting website.Follow Katie on LinkedIn.Take a Survey for a Chance to WinHey friends—can you do me a quick favor? I'm running a short survey to get your take on my podcasts and ⁠⁠All the Fits That's News⁠⁠ newsletter. It only takes about 2 minutes, and your feedback will help shape what comes next.Whether you're a regular listener or just pop in occasionally, I'd really value your input. Bonus: you can enter to win a $20 Amazon gift card just for participating.The survey closes once we hit our target number of responses—or by June 30, 2025, whichever comes first.

Daniel Altman explains his Baseline Profitability Index, which helps investors figure out the success of foreign investments on three criteria. 1: How much the asset's value grows; 2: Preservation of Value; 3: Ease of returning the proceeds. The top countries on the index include India and Rwanda. He discusses demand for foreign direct investment by Americans and what it means for the global economy. ======== Schwab Network ========Empowering every investor and trader, every market day.Subscribe to the Market Minute newsletter - https://schwabnetwork.com/subscribeDownload the iOS app - https://apps.apple.com/us/app/schwab-network/id1460719185Download the Amazon Fire Tv App - https://www.amazon.com/TD-Ameritrade-Network/dp/B07KRD76C7Watch on Sling - https://watch.sling.com/1/asset/191928615bd8d47686f94682aefaa007/watchWatch on Vizio - https://www.vizio.com/en/watchfreeplus-exploreWatch on DistroTV - https://www.distro.tv/live/schwab-network/Follow us on X – https://twitter.com/schwabnetworkFollow us on Facebook – https://www.facebook.com/schwabnetworkFollow us on LinkedIn - https://www.linkedin.com/company/schwab-network/About Schwab Network - https://schwabnetwork.com/about

THE LANCET 2003;362:767-771Background: Angiotensin II which plays a role in ventricular remodeling and progression of heart failure can be produced by pathways independent of angiotensin convening enzyme. Preliminary studies showed that the combination of angiotensin II blockers with angiotensin-converting enzyme inhibitors (ACEi) improves hemodynamics and reduces ventricular remodeling.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber.The Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM)-Added trial sough to assess if adding the angiotensin-receptor blocker (ARB), candesartan, to ACEi could improve outcomes in patients with systolic heart failure.Patients: Eligible patients had left ventricular ejection fraction of 40% or less within the previous 6 months, and NYHA class II, III or IV symptoms. Patients with NYHA class II symptoms had to have cardiac-related hospitalization within 6 months. Patients also had to have treatment with ACEi at a constant dose for at least 30 days.Exclusion criteria were not provided in the main manuscript.Baseline characteristics: Patients were recruited from 618 centers in 26 countries. The trial randomized 2,548 patients – 1,276 randomized to receive candesartan and 1,272 to receive placebo.The average age of patients was 64 years and 79% were men. The average left ventricular ejection fraction was 28%. Cardiomyopathy was ischemic in 62% of the patients. The NYHA class was II in 24% of the patients, III in 73% and IV in 3%.Approximately 48% had hypertension, 30% had diabetes, 56% had prior myocardial infarction, 9% had stroke, 27% had atrial fibrillation and 17% were current smokers.At the time of enrollment, 90% were taking a diuretic, 58% were taking digoxin, 55% were taking beta-blockers, 17% were taking spironolactone and all but two patients were taking ACEi.Procedures: The trial was double-blinded. Patients were assigned in a 1:1 ratio to receive candesartan starting at 4 or 8mg once daily or placebo. The treatment was doubled every two weeks to a target dose of 32mg once daily.After randomization, follow up occurred at 2, 4, and 6 weeks, 6 months and every 4 months thereafter.Endpoints: The primary outcome was a composite of cardiovascular death or heart failure hospitalizations. All deaths were classified as cardiovascular unless there was a clear non-cardiac cause.Analysis was performed based on the intention-to-treat principle. The estimated sample size to have 80% power at 5% alpha was 2,300 patients. The sample size calculation assumed 16% relative risk reduction in the primary outcome with candesartan assuming an 18% annual event rate in the placebo arm.Results: The median follow up time was 41 months. The mean candesartan daily dose was 24mg at 6 months.Candesartan reduced the primary endpoint of cardiovascular death or heart failure hospitalizations (37.9% vs 42.3%, adjusted HR: 0.85, 95% CI: 0.75 – 0.96; p= 0.01). Candesartan reduced the individual components of the primary outcome - (23.7% vs 27.3%; p= 0.021) for cardiovascular death and (24.2% vs 28.0%; p= 0.018) for heart failure hospitalizations. There was no significant reduction in all-cause death (29.5% with candesartan vs 32.4%; p= 0.105). The number of patients who had any hospitalization was similar in both groups (66.8% with candesartan vs 67.5%; p= 0.7), however, the total number of hospitalizations was lower with candesartan (2,462 vs 2,798; p= 0.023).Serum creatinine at least doubled in 7% of the patients in the candesartan group vs 6% in the placebo group. In the subset of patients taking spironolactone, serum creatinine at least double in 11% of the patients taking candesartan compared to 4% of the patients taking placebo.Hyperkalemia, defined as serum potassium of 6 mmol/L or higher, occurred in 3% of the patients in the candesartan group vs 1% in the placebo group. In the subset of patients taking spironolactone, hyperkalemia occurred in 4% of the patients taking candesartan compared to 1% of the patients taking placebo.There were two cases of angioedema in the candesartan group and three in the placebo group. All patients were taking an ACEi.There were no significant subgroup interactions, including in patients taking both beta-blockers and ACEi at baseline.Conclusion: In patients with systolic heart failure, adding candesartan to an ACEi reduced the primary composite outcome of cardiovascular death or heart failure hospitalizations with a number needed to treat of approximately of 23 patients over 41 months of follow up. The total number of all-cause hospitalizations was reduced by 336 with candesartan. All-cause death was not significantly reduced with candesartan.While the results of the trial appear impressive, the high number of adverse outcomes with candesartan in patients taking spironolactone is concerning. Spironolactone led to significant reduction in all-cause mortality in patients with systolic heart failure, as seen in the RALES trial, and should be prioritized over adding candesartan. Notably, fewer than 20% of patients in the trial were on spironolactone at baseline; if more had been, the incremental benefit of candesartan would likely have been reduced due to an increased risk of adverse effects from triple neurohormonal blockade (ACEi, ARBs, and mineralocorticoid receptor antagonists). Furthermore, spironolactone acts by blocking the aldosterone receptor, which is downstream in the renin–angiotensin–aldosterone system. Since candesartan blocks angiotensin II upstream in the same pathway, simultaneous inhibition at multiple points may lead to diminishing benefit.Finally, the differences observed in the subgroup of patients on beta-blockers between this trial and Val-HeFT remain unclear and may simply reflect the play of chance. As we previously discussed, patients receiving both an ACEi and beta-blockers had worse outcomes with valsartan in the Val-HeFT trial.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber. Get full access to Cardiology Trial's Substack at cardiologytrials.substack.com/subscribe

“He who has a why to live can bear almost any how.” — Friedrich NietzscheKevin Wathey is an expert in health tech, luxury hospitality, and peak performance.He is the co-founder of Baseline Health, a gamified platform that integrates user data, diagnostics, and DNA to deliver personalized insights and incentivize lasting habit change.Kevin is also developing Velara, an 18-acre luxury wellness resort in Costa Rica — designed to help people reconnect with themselves and extend their healthspan through personalized retreats and tech-enabled treatments.In this episode:• The mindset shift that turned Kevin's greatest challenge into his greatest strength.• Why most people fail at habit change — and the proven way to make habits stick.• What questions of self-reflection can transform your life.• How to optimize your environment for peak health and performance.Let's WIN THE DAY with Kevin Wathey!_

NWSL clubs came out of the international break a little rickety, and with plenty of fire. The guys whip around the league to hit the officiating controversy with Gotham, puzzle over Alex Straus's first game with Angel City, and debate Louisville's future (1:51). Then, they peel back the layers of a grubby contest in San Diego between the Wave and the Seattle Reign. Has San Diego been getting lucky in attack? Can the Reign continue their trench warfare in all of these 1-goal victories? Just how ridiculous was Sally Menti's finish? (27:10) Subscribe to our Patreon for only $6/month ($60/year) to get all of our exclusive bonus features! Art by Eli Elbogen  Music by Devin Drobka's Bell Dance Songs

In this week's episode (Actually it's last week, but I was a little preoccupied this week!), Josh and I are discussing and predicting the MLB All-Star teams and give you our reason why we believe each player would make it.

N Engl J Med 2001;345:1667-1675Background: Angiotensin II is a peptide hormone that is part of the renin–angiotensin–aldosterone system (RAAS). Angiotensin II is a potent vasoconstrictor and growth-stimulating hormone. Data suggested that it plays a role in ventricular remodeling and progression of heart failure. Although treatment with angiotensin-converting enzyme inhibitors (ACEi) reduce angiotensin II levels, physiologically active levels of angiotensin II may persist despite long-term therapy.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber.The Valsartan Heart Failure Trial (Val-HeFT) sough to assess whether the angiotensin-receptor blocker valsartan, could reduce mortality and morbidity when added to optimal medical therapy in patients with systolic heart failure.Patients: Eligible patients had left ventricular ejection fraction less than 40% and left ventricular dilation, in addition to having clinical heart failure for at least 3 months with NYHA class II, III or IV symptoms. Patient also had to have been receiving a fixed-dose drug regimen for at least two weeks, that could include ACEi, diuretics, digoxin, and beta-blockers.There were many exclusion criteria. We mention some here: Postpartum cardiomyopathy, acute myocardial infarction within 3 months, coronary artery disease likely to require intervention, serum creatinine >2.5 mg/dL and life expectancy less than 5 years.Baseline characteristics: Patients were recruited from 302 centers in 16 countries. The trial randomized 5,010 patients – 2,511 randomized to receive valsartan and 2,499 to receive placebo.The average age of patients was 63 years and 80% were men. The average left ventricular ejection fraction was 27%. Cardiomyopathy was ischemic in 57% of the patients. The NYHA class was II in 62% of the patients, III in 36% of the patients and IV in 2%.Approximately 26% had diabetes and 12% had atrial fibrillation.At the time of enrollment, 86% were taking a diuretic, 67% were taking digoxin, 35% were taking beta-blockers, and 93% were taking ACEi.Procedures: The trial was double-blinded. The trial had an initial run-in period for 2 - 4 weeks where patients received placebo twice daily. This was performed to confirm patients' eligibility, clinical stability and compliance.Patients were assigned in a 1:1 ratio to receive valsartan or placebo. Randomization was stratified according to whether or not they were receiving a beta-blocker.Valsartan was started at a dose of 40 mg twice a day, and the dose was doubled every two weeks to the target dose of 160 mg twice a day. Placebo doses were adjusted in a similar way.Follow up occurred at 2, 4, and 6 months and every 3 months thereafter.Endpoints: The trial had two primary end points. The first was all-cause mortality. The second was the combined end point of mortality and morbidity, which was defined as cardiac arrest with resuscitation, hospitalization for heart failure, or administration of intravenous inotropic or vasodilator drugs for four hours or more without hospitalization.The estimated sample size was 5,000 patients. The sample size calculation assumed 20% relative risk reduction in mortality with valsartan assuming 906 patients would die during the trial. This sample size would provide the trial 90% power at 0.02 alpha. Alpha was 0.02 instead of the traditional 0.05 since the trial had two primary endpoints and to adjust for the interim analyses.Results: The target valsartan dose of 160 mg twice a day was achieved in 84% of the patients. The reduction in systolic blood pressure was greater with valsartan vs placebo – mean of 5.2 ± 15.8 mm with valsartan compared to 1.2 ± 14.8 mm Hg with placebo, at 4 months.All-cause mortality was not different between both groups (19.7% with valsartan vs 19.4% with placebo, RR: 1.02, 95% CI: 0.88 – 1.18; p= 0.80). The second co-primary endpoint was reduced with valsartan (28.8% vs 32.1%, RR: 0.87, 95% CI: 0.77 – 0.97; p= 0.009). This was driven by reduction in hospitalizations for heart failure (13.8% vs 18.2%). Cardiac arrest with resuscitation was 0.6% with valsartan and 1.0% with placebo. All-cause hospitalization was numerically lower with valsartan, however, this was not statistically significance (2,856 vs 3,106; p= 0.14). The mean change in ejection fraction was higher with valsartan (4.0% vs 3.2%; p= 0.001). More patients had improvement in NYHA classification with valsartan (23.1% vs 20.7%; p

Copper Fox Metals (TSXV: CUU | OTCQX: CPFXF | FSE: HPU) has received the results of two years' worth of Environmental Baselines Studies at its Schaft Creek Copper-Gold-Molybdenum-Silver Project in northwestern British Columbia.In this interview, President and CEO Elmer B. Stewart discusses what the studies revealed, the importance of Schaft Creek's archaeological assessment, and the company's collaboration with the Tahltan Nation. He also explains how these efforts support the future of the Schaft Creek Project, particularly as it moves toward the permitting stage.Learn more about Copper Fox Metals: https://copperfoxmetals.comWatch the full YouTube interview here: https://youtu.be/-9_tqSFD4ywAnd follow us to stay updated: https://www.youtube.com/@GlobalOneMedia?sub_confirmation=1

This week on Live Life in Motion, I'm joined by Chandler Benore, Director of Operations for Baseline GVL — a new, purpose-built indoor pickleball facility coming to the Haywood Road area of Greenville, SC. Chandler shares the inspiration behind the project, what sets Baseline apart from other facilities, and how it's been designed with both serious players and social connection in mind. From court materials and layout to community features like a smoothie bar, pro shop, and outdoor patio, every detail has been carefully considered. If you're into pickleball, community-building, or just love seeing bold ideas come to life, this one's for you. Baseline GVL:https://www.instagram.com/baselinegvl/ Live Life in Motion YouTube: GO Subscribehttps://www.youtube.com/@livelifeinmotionpodcast Pelham Medical Centerhttps://www.spartanburgregional.com/locations/pelham-medical-center

Wonder why you don't look like the other women who are lifting just like you in the gym?  Build your Nutrition Baseline first.  Do this and look and feel fitter and tighter in the next 3 weeks.  Most women who train hard are missing a nutrition baseline.  They dabble with macros before having a consistent routine that already checks most of the boxes.In this episode, I share the top 3 things you need to consider in your nutrition baseline. And then, I invite you to join my 3-week coaching program to create yours, Build Your Baseline.  This round starts June 9th, click here to get signed up! [Take the Quiz] What are you missing to Be Fit, Well-Fed, and Fully Energized? Work with Jenny the Nutritionist in Create Your Shape:https://jennythenutritionist.com/create-your-shape/Follow Jenny the Nutritionist on Instagram:@jennythenutritionist

Freddie and Joel both just won masters, so you know we're talking about that, but we're also getting into a bunch of other topics. Like how to make money waterskiing, trick skiing scoring/trick values, who we think has the most “on water” time, waterski media and how it compares to wakeboard media, social media/influencers values to brands, onlyfans, and a whole lot more. Plus, the guys rip smelling salts to start the pod, and eat a Malort candy midway through. Hear all this and much more in Episode 84 of the Grab Matters Podcast!Follow Joel: https://www.instagram.com/joelpoland/Follow Freddie: https://www.instagram.com/thefredwinter/Follow Brooks (if you want): https://www.instagram.com/brkswilson/Support the show: https://www.patreon.com/GrabMattersPodcastThank you to this shows sponsors! Liquid Force: https://www.liquidforce.com/ Slingshot: https://slingshotsports.com/Malibu Just Ride Tour: https://www.malibuboats.com/just-ride-tourChapters00:00 - 1:00 Intro1:15 Masters recap16:00 Making money waterskiing24:20 Wakeboarding at the masters27:00 Water time32:30 Return to Baseline/Events39:30 LF'n Wheel of Questions57:40 Age in waterskiing58:00 Trick values1:05:45 Malibu Just Ride Tour1:06:00 Malort candy…?1:09:00 How to be a pro waterskier1:21:50 Slingshot Silhouette Challenge1:26:10 Patreon Question1:27:30 Waterski media1:40:00 Catch up with Brooks2:00:00 Social Media2:16:00 Season previewLinksReturn to Baseline: https://www.baselinewaterski.com/Brostock: https://brostock.com/Malibu Just Ride Tour: https://www.malibuboats.com/just-ride-tourShoot us a text!Patreon: https://www.patreon.com/GrabMattersPodcastWebsite: https://www.grabmatters.com/YouTube: https://www.youtube.com/@grabmatters/videosInstagram: https://www.instagram.com/grabmatters/TikTok: https://www.tiktok.com/@grabmatterspodcastFacebook: https://www.facebook.com/grabmatters

https://teachhoops.com/ n any field where performance and results matter, from the sports arena to the boardroom, possessing a "competitive edge" is often the crucial differentiator between success and mediocrity. This podcast delves into the multifaceted nature of what truly gives individuals and teams that vital advantage. We'll explore how the competitive edge isn't just about raw talent or resources, but a dynamic combination of mindset, strategic preparation, relentless innovation, and the ability to execute under pressure. Join us as we dissect the various components that forge a true competitive advantage. We'll uncover actionable strategies to help you identify your potential edges, cultivate them with intention, and sustain them in the face of evolving challenges. Whether you're an athlete, entrepreneur, professional, or anyone striving for peak performance, learn how to sharpen your unique strengths and consistently position yourself ahead of the curve. Learn more about your ad choices. Visit podcastchoices.com/adchoices

We're headed to Disney's Hollywood Studios for the next round of our “Eat It or Beat It” series—breaking down the most popular snacks in the park to determine which ones are worth the splurge and which you might want to skip. From galaxy-famous bites in Galaxy's Edge to theme park classics with a twist, we evaluate each snack based on taste, value, portion size, and overall experience.We dive into fan-favorite items like the Ronto Morning Wrap, Blue & Green Milk, and the cheesy goodness of the Umbaran Cheese Roll—plus sweet treats like the Wookiee Cookie, Lunch Box Tart, and Jack-Jack's Num Num Cookie. You'll even hear our thoughts on savory staples like Totchos, the Bavarian Pretzel at BaseLine, and the Sweet Cream Cheese Pretzel near the iconic Chinese Theatre.Whether you're team “Eat It” or “Beat It,” this episode is packed with honest takes and helpful snack strategies to make the most of your next visit to Hollywood Studios.Missed the first parts of the series? Be sure to check out:• Episode 750 – Magic Kingdom• Episode 759 – EPCOTMEI-Travel – Expertise. Ease. Value.No matter where you want to go, our trusted partner MEI-Travel, will handle the planning so you can focus on the memories. They offer free vacation planning services and have nearly 20 years of experience creating memorable vacations. Visit MEI-Travel for a fee-free, no-obligation quote today!Follow Us on Social MediaFacebook GroupFacebook: @MainStMagicTwitter: @MainStMagicTikTok:  @MSMPodcastInstagram: @MainStMagicVisit Us Onlinewww.MainStMagic.comwww.MainStreetShirts.comGet Dining Alerts!Find last-minute and hard-to-find Disney dining reservations with MouseDining.com! Get text and email alerts when popular theme park dining reservations open up. Get last-minute seating! Get the next table! Set your alerts now! Get the next reservation!Visit our Partnerswww.MSMFriends.comThanks to TFresh Productions for our theme song

Join Will from the Tennis Tribe and Michelle as they have a chance to watch some of the best doubles players on the men's tour on one of THE windiest days of the year at the 2025 BNP Paribas Open in Indian Wells, CA!  We break down their practice and make it relatable so you can use it in your own doubles practices. From serve and return strategies and what to do on blustery days!  If you have any further questions or want to continue the conversation?! Email us at podcast@tennis-warehouse.com   Shop with us for all your TENNIS needs all over the WORLD:

Circulation 1999;100:2312-2318Background: The CONSENSUS and SOLVD trials established the effectiveness of angiotensin converting enzyme inhibitors (ACEi) in reducing mortality and morbidity in patients with systolic heart failure. Both trials used enalapril with a target dose of 20mg twice a day (max dose) in the CONSENSUS trial and 10mg twice a day (medium dose) in the SOLVD trials. In real-world settings, ACEi are sometimes prescribed at lower doses, likely reflecting concerns about adverse effects or patients' tolerance. It was unclear whether the benefit from low doses of ACEi is comparable to high doses.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber.The Assessment of Treatment with Lisinopril and Survival (ATLAS) trial sought to assess the efficacy and safety of low vs high doses of ACE inhibition in patients with systolic heart failure.Patients: Eligible patients had left ventricular ejection fraction of 30% or less and had NYHA class II, III or IV despite treatment with diuretics for two or more months.Patients were excluded if they had any of the following: Acute coronary syndrome or revascularization procedure within 2 months, history of sustained or symptomatic ventricular tachycardia, known intolerance to ACEi, serum creatinine >2.5 mg/dL, or any noncardiac condition that could limit survival.Baseline characteristics: The trial randomized 3,164 patients – 1,596 randomized to the low-dose arm and 1,568 to the high dose arm.The average age of patients was 64 years and 80% were men. The average left ventricular ejection fraction was 23%. Cardiomyopathy was ischemic in 65% of the patients. The NYHA class was II in 16% of the patients, III in 77% and IV in 7%.Data on baseline comorbid conditions were not provided in the main manuscript.Procedures: The study was double blinded. At the beginning of the study, all patients received open-label lisinopril for four weeks to assess who is able to tolerate the drug. Patients who were able to tolerate lisinopril 12.5 mg to15 mg daily for two or more weeks were randomized in a 1:1 ratio to receive low-dose or high-dose ACEi. The target dose of lisinopril in the lose dose group was 2.5 to 5.0mg daily and was 32.5 to 35mg daily in the high dose group.All patients received open-label lisinopril 2.5 to 5mg daily. This dose was selected by the investigator. In addition, patients received up to three 10mg tablets of lisinopril or matching placebo.Endpoints: The primary endpoint was all-cause mortality. Secondary end points included cardiovascular mortality, all-cause hospitalization and cardiovascular hospitalizations.Analysis was performed based on the intention-to-treat principle. The estimated sample size was 3,000 patients. This sample size had 90% power at 5% alpha to detect 15% relative risk difference in the mortality between both treatment groups assuming 19% 1-year mortality in the high dose group.Results: Of the 3,793 patients who entered the initial open-label tolerability phase, 83.4% were randomized. A total of 176/3,793 (4.6%) were withdrawn for possible side effects. The median follow-up time was 46 months.Target doses were achieved in 92.7% of the patients in the low-dose group and 91.3% in the high-dose group. Study medication was discontinued by 30.6% of patients in the low-dose group and 27.2% in the high-dose group.All-cause mortality was not significantly different between both treatment groups (44.9% with low dose vs 42.5% with high dose, HR: 0.92, 95% CI: 0.82 – 1.03; p= 0.128). Cardiovascular mortality was numerically lower in the high dose group but this was not statistically significant (37.2% vs 40.2%, HR: 0.90, 95% CI: 0.81 – 1.01; p= 0.073). All-cause hospitalization was lower in the high dose group (3,819 hospitalizations vs 4,397; p= 0.021). Hospitalizations for cardiac causes and hospitalizations for heart failure were also lower in the high dose group (2,456 vs 2,923; p= 0.05) and (1,199 vs 1,576; p= 0.002), respectively.Patients in the high-dose group experienced more dizziness (19% vs 12%), more hypotension (11% vs 7%), more worsening renal function (10% vs 7%), and more hyperkalemia (6% vs 4%), but reported less cough (11% vs 13%) and had less hypokalemia (1% vs 3%).There were no significant subgroup interactions for the primary outcome.Conclusion: In patients with systolic heart failure, high dose ACE inhibition did not significantly reduce mortality compared to low-dose but it led to significantly less hospitalizations. In this trial of 3,164 patients and with a median follow up of 46 months, there were 578 less hospitalizations in the high dose group.Based on these results, we recommend up-titrating ACEi and use higher doses if tolerated. Although, side effects were more common in the high dose group, these can generally be managed with reducing the dose in the outpatient settings.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber. Get full access to Cardiology Trial's Substack at cardiologytrials.substack.com/subscribe

Huge thank you to our sponsors, Fusion Gaming Online.You can find them here: www.FusionGamingOnline.com. You want a 5% discount off all of your MTG order? Head over to Fusion Gaming Online and use exclusive promo code: CCONATION at checkout.Want your deck or topic featured on Commander Cookout Podcast?Check out the reward tiers at Patreon.com/CCOPodcast. There are a lot of fun and unique benefits to pledging. Like the CCO Discord or getting your deck featured on the show.Ryan's solo podcast, Commander ad Populum:https://www.spreaker.com/show/commander-ad-populumInterested in MTG/Commander History? Check out Commander History Podcast: https://www.spreaker.com/podcast/mtg-commander-history--6128728You can listen to CCO Podcast anywhere better podcasts are found as well as on CommanderCookout.com.Now, Hit our Theme Song!Social media:https://www.CommanderCookout.comhttps://www.Instagram.com/CommanderCookouthttps://www.Facebook.com/CCOPodcast@CCOPodcast and @CCOBrando on Twitterhttps://www.Patreon.com/CCOPodcasthttps://ko-fi.com/commandercookout

Welcome to the Social-Engineer Podcast: The 4th Monday Series with Chris Hadnagy and Mike Holfeld. Chris and Mike will be covering cutting edge global news to help people remain safe, secure and knowledgeable in a world where it is hard to know what is real and what is fake news.   Today Chris and Mike are joined by Seth Daniels. Seth is the Director of Customer Experience and a founding employee of Rapsodo Inc., an industry leader in sports technology. Seth helped launch Rapsodo in the United States in 2015, particularly on the Diamond Sports side focusing on baseball and softball. He's worked with all 30 MLB clubs, more than 90% of all D1 college programs and thousands of other amateur teams and organizations. [May 26, 2025]   00:00 - Intro 00:49 - Mike Holfeld Intro 01:03 - Today's Guest: Seth Daniels 02:01 - 24 Hours to Singapore 05:33 - Immediate Instant Reactions! 07:23 - Setting a Baseline 08:43 - Data: A Piece of the Puzzle 11:21 - Ohtani 13:06 - Age Appropriate 15:22 - Women's Sports 17:16 - Spin Doctors 19:56 - For the Hitters 22:29 - Finding the Sweet Spot 24:31 - Future Evolution 25:50 - Find Seth Daniels Online -          rapsodo.com 26:14 - Don't Forget Golf 27:13 - Wrap Up 27:31 - Next Month: Congressman Darron Soto 27:58 - Outro -          www.social-engineer.com -          www.innocentlivesfoundation.org   Find us online: -          Chris Hadnagy -          LinkedIn: linkedin.com/in/christopherhadnagy

In this week's episode of The Baseline NBA Podcast, we dive deep into our ongoing Autopsy Report series, breaking down the shocking and unceremonious playoff exits of the Boston Celtics and Cleveland Cavaliers. Once considered title contenders, both teams now face serious questions about their future with financial pressures looming and roster changes on the horizon. We analyze:What went wrong for the Celtics and CavaliersImpact of injuries, coaching decisions, and star performancesPotential offseason trades, free agency moves, and salary cap issuesFuture outlook for stars like Jayson Tatum, Jaylen Brown, Donovan Mitchell, and Darius GarlandThen, we shift gears and preview the 2025 Eastern Conference Finals between the New York Knicks and Indiana Pacers. A rivalry rekindled from last year's playoff showdown now reaches new heights. Can the Knicks finally return to the ECF for the first time since 2000, or will Tyrese Haliburton and the red-hot Pacers punch their ticket back to the Finals?PrizePicksPrizePicks (https://prizepicks.onelink.me/LME0/CLNS) (include in episode description)The basketball playoffs are here and the action is heating up on PrizePicks, THE BEST place to cash in on your favorite sports.Don't miss your last chance to add your favorite players from the court to your PrizePicks lineup! Whether it's Points, Rebounds, Assists, take your pick of More or Less for your shot to win up to 2,000 times your cash. Download the app and use code CLNS to get $50 instantly after you play your first $5 lineup!”PrizePicks also offers weekly promotions. Turn your playoff hot takes into tickets to basketball's championship series. Every Lineup you make will qualify for the Takes 2 Tickets Sweepstakes, which could get you and a guest a VIP trip to The ‘ShipEvery Tuesday, PrizePicks discounts several projections on the board, usually between 15% and 25%. They also offer Flex Fridays! Make sure you OPT IN and tap the checkbox in your lineup builder to be eligible for the Protected Play. Choose squares from any game on the board.If your lineup does not win, you get your net losses back in promo funds up to your promo limit as soon as the lineup settlesYou can also mix your selections across sports in your PrizePicks lineup! I might take Juan Soto for 2 RBIs and the Big Bodega Karl Anthony Towns for more than 26 points to combine my love of baseball and basketball.PrizePicks is simply the best place to win cash while watching sports! Join millions of users and sign up today with the promo code CLNS to get $50 after you play your first $5 lineup. The Baseline is rocking with Prize Picks and you should too. “PrizePicks. Run Your Game!”Become a supporter of this podcast: https://www.spreaker.com/podcast/the-baseline-nba-podcast--3677698/support.

Lancet 1999;353:2001-07Background: Beta-blockers directly reduce cardiac contractility and myocardial oxygen demand. For decades, they were avoided in patients with acute and chronic heart failure over concerns they would facilitate decompensation of the condition. The therapeutic cornerstones of treatment, prior to the modern era of clinical trials, focused on managing symptoms and quality of life with diuretics and inotropic agents like digoxin; however, new paradigms were arising that focused on addressing neurohormonal mechanisms of chronic disease that were over-activated in the failing heart. The first major success came with inhibition of the renin angiotensin aldosterone system with angiotensin converting enzyme inhibitors whose effect on mortality for patients with mild and severe forms of chronic heart failure were demonstrated in the V-HEFT II, CONSENSUS, and SOLVD trials. Additional benefits were demonstrated with the mineralocorticoid receptor antagonist spironolactone in the RALES trial. These drug classes primarily work by reducing afterload and volume retention. Appreciating why they work for improving cardiac performance and managing symptoms in heart failure patients is straightforward when we consider the major factors that effect cardiac stroke volume - preload, afterload and contractility; however, it is also noteworthy the effects these agents have on sudden death. How beta-blockade benefits the failing heart is less obvious (outside prevention of sudden death). Mechanistic studies in patients with chronic heart failure have consistently shown that when beta blockers are used for more than 1 month, left ventricular function improves. Beta blocker therapy appears to restore the density of beta-adrenergic receptors after they have been downregulated by the chronic overactivity of the sympathetic nervous system. The first major placebo-controlled RCT to demonstrate a mortality benefit used the non-selective beta blocker carvedilol. The trial was small and not originally designed to test mortality and was stopped early without clearly predefined stopping rules. Furthermore, 8% of total patients selected for participation in the trial were excluded prior to randomization after a 2 week, open-label run-in phase with the study drug, which saw 2% of all patients experience worsening heart failure or death representing 24 patients (the difference in total deaths between groups was 9 when the trial was stopped). The Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF) was the first large scale trial designed to test the hypothesis that beta-blockade with metoprolol controlled/extended release (CR/XL) added to optimum medical therapy reduces mortality in patients with chronic systolic heart failure.Patients: Patients were recruited from 313 sites in 13 European countries and the United States. Eligible patients were men and women between the age of 40 to 80 years with symptomatic heart failure (NYHA class II-IV) for >/= 3 months before randomization. They had to be on a diuretic and ACE inhibitor for at least 2 weeks. Other drugs, including digoxin, could also be used. Patients also had to have an EF of /=68 beats per minute.Patients were excluded if: they had an MI or unstable angina within 28 days; had an indication or contraindication for treatment with beta-blocker; beta blockade within 6 weeks; heart failure due to systemic disease (i.e., amyloidosis) or alcohol abuse; scheduled or performed cardiac transplant; an ICD; procedures such as CABG or PCI planned or performed in the past 4 months; 2nd or 3rd degree AV block unless a pacemaker was present; unstable or decompensated heart failure defined by pulmonary edema or hypoperfusion or supine systolic BP 25% deviation of the number of observed versus expected consumed placebo tablets during the run-in period.Baseline characteristics: The mean age of patients was 64 years and approximately 78% were male. Slightly more than 30% of patients were above the age of 70. The average EF was 28%. The average SBP was 130 mmHg and heart rate was 82 bpm. Most patients had mild to moderate heart failure, with 41% in NYHA Class II, 56% in Class III, and only 3% in Class IV. Ischemic cardiomyopathy accounted for 65% of cases and nonischemic causes accounted for 35%. Most patients were on an ACE inhibitor or ARB (95%) and diuretic (90%). Digoxin was used in 63%. Trial procedures: Prior to randomization, the study was preceded by a single-blind, 2-week placebo run-in period. Patients meeting eligibility were then randomized to placebo or metoprolol CR/XL. The starting dose of placebo or metoprolol CR/XL was 12.5 mg daily for patients in NYHA class III or IV and 25 mg daily for patients in NYHA class II. The dose was doubled every 2 weeks until the target dose of 200 mg daily was reached. Patients were followed every 3 months.Endpoints: The primary outcome was all-cause mortality. It was estimated that 3,200 patients would need to be followed for 2.4 years to detect a 30% relative reduction in mortality based on annual mortality rate of 9.4% in the placebo group. This would achieve at least 80% power with a 2-sided alpha of 0.04. Patients were recruited faster then planned and so the final sample size of 3,991 patients increased the power of the study.The study was monitored by an independent safety committee and predefined stopping rules for efficacy were based on all-cause mortality, done when 25%, 50%, and 75% of expected deaths had occurred. Results: The trial was stopped early after the 2nd preplanned interim analysis when 50% of expected deaths had occurred. The mean duration of follow-up at the time of stopping was 1 year. The mean daily dose of metoprolol CR/XL was 159 mg once daily, with 87% receiving 100 mg or more and 64% receiving the target dose of 200 mg daily. In the placebo group, the corresponding values were 179 mg daily, 91% and 82%. The study drug was discontinued permanently in 14% of patients in the metoprolol group and 15% in the placebo group. Six months after randomization, heart rate decreased by 14 bpm in the metoprolol group compared to only 3 bpm in the placebo group. Systolic blood pressure decreased less in the metoprolol group (-2.1 vs 3.5 mmHg).Compared to placebo, metoprolol significantly reduced all-cause mortality (7.3% vs 10.8%; RR 0.66; 95% CI 0.53—0.81). Cardiovascular mortality accounted for 91% of all deaths; with sudden death accounting for 58% and death from worsening heart failure accounting for 24% of all deaths. All 3 of these causes of death were significantly reduced by metoprolol. The relative and absolute effects on death were greatest for patients with NYHA class III heart failure.Conclusions: In this trial of stable patients with mild to moderate chronic systolic heart failure, who were optimized on an ACEi or ARB and diuretic, metoprolol CR/XL significantly reduced all-cause mortality. Approximately 30 patients would need to be treated with metoprolol compared to placebo for 1 year to prevent 1 death. This trial represents a significant win for beta blockade in patients with chronic systolic heart failure. While the NNT in this trial is slightly higher than in SOLVD, it is important to appreciate that follow-up time in SOLVD was more than 3x longer. Limitations to external validity in this trial include the run-in period and stringent inclusion and exclusion criteria. Our enthusiasm is also tempered by early stopping, which has been found to be associated with false positive or exaggerated results but this concern is mitigated to some extent in this trial because the rules for early stopping were clearly defined in the protocol.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber. Get full access to Cardiology Trial's Substack at cardiologytrials.substack.com/subscribe

Recorded- May 20, 2025   Uploaded- May 20, 2025 The final preview is here! The Pioneer Preview is ready in full for you now.   Intro- 00;00-05;00 PBL Preview- 05;00-42;30 Baseline- 05;00-10;08 Billings- 10;08-13;55 Boise- 13;55-17;21 Glacier- 17;21-19;33  Grand Junction- 19;33-22;44 Great Falls- 22;44-25;28 Idaho Falls- 25;28-28;24 Missoula- 28;24-29;17 Northern Colorado- 29;17-30;17 Oakland- 30;17-34;40 Ogden- 34;40-36;06 Rocky Mountain- 36;06-38;00 Yuba- 38;00-40;33 Prediction- 40;33-42;30 Outro- 42;30-END

N Engl J Med 1999;341:709-717Background: The renin–angiotensin–aldosterone system (RAAS) is activated in patients with systolic heart failure. While this activation initially helps increase blood volume and maintains blood pressure, chronic activation promotes cardiac fibrosis and remodeling. In patients with systolic heart failure, inhibition of the RAAS with angiotensin-converting enzyme inhibitors (ACEi) significantly reduced mortality and morbidity, as seen in the CONSENSUS and SOLVD trials.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber.Preliminary data suggested that adding the aldosterone-receptor blocker spironolactone to ACEi, reduced the levels of atrial natriuretic peptide and did not lead to serious hyperkalemia.The Randomized Aldactone Evaluation Study (RALES) sought to test the hypothesis that spironolactone would significantly reduce the risk of all-cause death in patients with severe systolic heart failure.Patients: Eligible patients had left ventricular ejection fraction of 35% or less, had NYHA class IV heart failure within the 6 months before enrollment and NYHA class III or IV at the time of enrollment, and were treated with ACEi (if tolerated) and a loop diuretic.Patients were excluded if they had primary operable valvular disease (other than mitral or tricuspid regurgitation), congenital heart disease, unstable angina, primary liver failure, active cancer or any life-threatening condition, other than heart failure, prior heart transplant or awaiting heart transplant, serum creatinine >2.5 mg/dL, or serum potassium > 5.0 mmol/L.Baseline characteristics: Patients were recruited from 195 centers in 15 countries. The trial randomized 1,663 patients – 822 randomized to receive spironolactone and 841 to receive placebo.The average age of patients was 65 years and 73% were men. The average left ventricular ejection fraction was 25%. Cardiomyopathy was ischemic in 55% of the patients and non-ischemic in the rest. The NYHA class was III in 71% of the patients and IV in 29%.Data on baseline comorbid conditions were not provided.At the time of enrollment, 100% were taking loop diuretics, 94% were taking ACEi, 73% were taking digitalis, and 10% were taking beta-blockers. The mean daily dose of ACEi were as following: 63mg for captopril, 15mg for enalapril, and 14mg for lisinopril.Note: Max daily dose is 450mg for captopril, 40mg for enalapril, and 40mg for lisinopril.Procedures: The trial was double-blinded. Patients were assigned in a 1:1 ratio to receive spironolactone 25mg PO daily or placebo.The dose could be increased to 50mg daily after 8 weeks of treatment, If the patient had worsening heart failure and had no evidence of hyperkalemia. In the event of hyperkalemia, the dose could be lowered to 25 mg every other day. Laboratory testing including potassium were performed every 4 weeks for the first 12 weeks, then every 3 months for up to 1 year and every 6 months thereafter until the end of the study.Endpoints: The primary outcome was all-cause death. Secondary end points included death from cardiac causes, hospitalization for cardiac causes and change in the NYHA class.Analysis was performed based on the intention-to-treat principle. The planned sample size was not mentioned in the methods. However, the results mention that recruitment was complete. The sample size calculation assumed 38% mortality rate in the placebo group and that spironolactone would reduce mortality by 17% (relative risk reduction). The power of the study was set at 90% with a two-sided alpha of 5%.Results: Recruitment was complete in Dec, 1996 with follow up planned through Dec, 1999. However, the study was stopped early on Aug, 1998 after interim analysis showed significant reduction in mortality with spironolactone. The mean follow up time was 24 months. After 24 months of follow up, the mean daily dose of spironolactone was 26 mg.Spironolactone reduced all-cause death (35% vs 46%, RR: 0.70, 95% CI: 0.60 - 0.82; p< 0.001). Death from cardiac causes was also reduced with spironolactone (27% vs 37%, RR: 0.69, 95% CI: 0.58 - 0.82; p

Did you know you can support The Rumcast on Patreon now and get bonus episodes, happy hours, and more? You can! Head to patreon.com/therumcast to check it out.You can watch the video version of this episode on YouTube.In this episode, we sat down with the founder and distiller behind one of the most interesting rum projects in the U.S. right now, Robyn Smith of rum et al., a chemical engineering PhD turned rum distiller.The premise behind Rum Et Al is simple but fascinating. Robyn started with a foundational, always-available rum she named Baseline. She's since released batches in which she introduces a "variable" to the Baseline recipe, such as dunder. This allows you to taste the exact differences that the variable brings to the flavor profile when tasted side by side. If you're a rum geek, it's a really cool tasting experience.During the episode, we discussed:How she went from chemical engineering PhD to rum distillerHer experience in R&D for Lost Spirits DistilleryHow rum et al. came to beAll the nerdy rum production detailsThe joys and challenges of being a one-woman operationCongeners vs. estersHow ester measurements translate to flavor profileWhat we might see from her nextAnd much more!Be sure to check out her YouTube channel, This Blog's Neat! These videos about her rum et al. releases are a great place to start:How Baseline Was MadeHow Variable (Dunderclap) Was MadeHow Variable (Tailspin) Was MadeHave you had a chance to try Robyn's rum? What stood out to you in the conversation? Let us know via email (host@rumcast.com) or social!

Stuart Knight has written, produced and starred in shows that have been seen by over one million people, has written best selling books and is the founder of The Human Connection Group. Top 3 Value Bombs 1. The more that you experiment, the more successful you will become. Throw everything at the wall and see what sticks and if it falls off the wall, figure out a way to make it stick. 2. If it is a feeling , we connect but if it's a thinking, we did not connect. 3. Don't be afraid to ask the big question because those big questions will lead to big answers and big answers lead to big relationships. Deeper Connection. With Others.​ With Yourself. The world's biggest resource for people harnessing the power of human connection - The Human Connection Group Sponsors ThriveTime Show Become the next success story, schedule a free consultation and request tickets to join Football Star, Tim Tebow and President Trump's Son, Eric Trump at Clay Clark's next business conference today at: ThrivetimeShow.com/eofire ZipRecruiter Enjoy the benefits of speed hiring with new ZipIntro! Only from ZipRecruiter. Post jobs today, talk to qualified candidates tomorrow. Try ZipIntro for free at ZipRecruiter.com/fire