Questioning Medicine

PODCAST · health

Questioning Medicine

Join Andrew on a medical rollercoaster as we ask a medical question and answer it based on recent published papers.  

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    Episode 428: 435. Evolocumab, Statin and CKD, PCN allergy, MRI vs Rotator Cuff

    https://pubmed.ncbi.nlm.nih.gov/41903215/  Evolocumab to Reduce First Major Cardiovascular Events in Patients Without Known Significant Atherosclerosis and With Diabetes: Results From the VESALIUS-CV Trial https://pubmed.ncbi.nlm.nih.gov/41769754/  Association between statin therapy as primary prevention and mortality in adults 50 years and older with chronic kidney disease without other indications https://pubmed.ncbi.nlm.nih.gov/41921035/  Direct Oral Challenge for Penicillin Allergy: The International Network of Antibiotic Allergy Nations (iNAAN) Study https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2844659  Incidental Rotator Cuff Abnormalities on Magnetic Resonance Imaging  https://www.acpjournals.org/doi/10.7326/ANNALS-25-02772   Rapid Evaluation of Artificial Intelligence Technology Used for Ambient Dictation in Primary Care: Comparing the Quality of Documentation of Artificial Intelligence–Generated and Human-Produced Clinical Notes

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    Episode 427: 434. 6 Articles From Arb to Patient Perspective to Cervical Cancer Screening

    https://agsjournals.onlinelibrary.wiley.com/doi/10.1111/jgs.70463  Angiotensin Receptor Blockers Versus Calcium Channel Blockers for First-Line Antihypertensive Therapy and Survival in Adults Aged 75Years or Older  https://www.clinicalkey.com/#!/content/playContent/1-s2.0-S0140673626003673?returnurl=https:%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0140673626003673%3Fshowall%3Dtrue&referrer=https:%2F%2Fpubmed.ncbi.nlm.nih.gov%2F Pharmacological blood-pressure lowering for the prevention of cardiovascular disease and death across the full spectrum of chronic kidney disease severity: an individual-participant data meta-analysis  https://pubmed.ncbi.nlm.nih.gov/42033454/   Overdiagnosis in atrial fibrillation screening with wearables  https://pubmed.ncbi.nlm.nih.gov/41766353/   Patients' perspectives on deprescribing in swedish primary care: an exploratory survey study  https://pubmed.ncbi.nlm.nih.gov/41627785/   Reducing short-acting beta-agonist overprescribing in general practice: Evaluation of a quality improvement programme in East London  https://pubmed.ncbi.nlm.nih.gov/42024880/   Screening for Cervical Cancer: A Recommendation From the Women's Preventive Services Initiative

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    Episode 426: 433. Salt, Statins, and Stents

    Donato J, et al. Things We Do For No Reason™: Low salt diets for patients with acute heart failure. J Hosp Med 2026 Feb 4; [e-pub]. DOI: 10.1002/jhm.70278.Some guidelines now recommend "normal sodium intake" for patients with acute and chronic HF, which means avoiding excessive sodium intake and staying under 4 to 5 g daily.https://academic.oup.com/eurjhf/article-abstract/26/4/730/8328801?redirectedFrom=fulltext&login=trueLuo Y, et al. Measuring public preferences for statin therapy: Using the smallest worthwhile difference. JAMA Intern Med 2026 Feb 16; [e-pub]. DOI: 10.1001/jamainternmed.2025.7958. It's honestly kind of beautiful - and a little frustrating. But it's also a reminder that medicine isn't math; it's human. People don't just want statistics; they want clarity, control, and context. A one-percent drop means one thing on paper, and something very different when you're trying to remember if you already took today's pill. Kang J, et al. Aspirin versus clopidogrel for chronic maintenance monotherapy after percutaneous coronary intervention: 10-year follow-up of the HOST-EXAM trial. Lancet 2026 Apr 11; 407:1439. DOI: 10.1016/S0140-6736(26)00422-8.Over ten years, about 25 out of 100 patients on clopidogrel had one of these events, compared to about 29 out of 100 on aspirin. Statistically, that’s a hazard ratio of 0.86, with a p value of 0.005, and it translates into an absolute risk reduction of just over 3 percent and a number needed to treat of about 33. In other words, if you treat 33 stable post‑PCI patients with clopidogrel rather than aspirin for ten years, you prevent one net adverse event.Looking only at thrombotic events—cardiovascular death, non‑fatal MI, ischemic stroke, ACS readmission, or stent thrombosis—clopidogrel again came out ahead: roughly 17 percent vs 20 percent, hazard ratio 0.82, p around 0.002. This difference was largely driven by fewer strokes and fewer rehospitalizations for acute coronary syndromes.Now for bleeding. You might worry that better antithrombotic protection would mean more bleeding. In fact, the opposite happened. Any clinically relevant bleeding, BARC type 2 or higher, occurred in about 9 percent of clopidogrel patients versus almost 11 percent on aspirin, with a hazard ratio of 0.81. Major bleeding—BARC type 3, including haemorrhagic stroke—was also lower on clopidogrel: about 5.6 percent vs 7.7 percent. Haemorrhagic stroke itself was cut roughly in half.

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    Episode 425: 432. CME LECTURE- Under Pressure, Blood Pressure

    432.  CME LECTURE-  Under Pressure, Blood Pressure

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    Episode 424: 431. Gout should we treat to a number? Is Co-testing needed?

    https://www.sciencedirect.com/science/article/abs/pii/S2665991326000342?via%3Dihublancet rheumatology A treat-to-target strategy versus symptom-driven management of gout in the Netherlands (GO TEST Overture): a multicentre, open-label, pragmatic, superiority, randomised controlled trial  The question on the table: Is chasing a serum urate level below six milligrams per deciliter worth the effort? Or are we just torturing our patients with more lab draws and dose titrations than they actually need? What’s the Real Takeaway?So — is it worth chasing six? Probably yes, but let's keep expectations realistic.Think of it like aiming for LDL targets in dyslipidemia — specific numbers keep us intentional,The bottom line: when your gout patient agrees to start urate-lowering therapy,  don’t expect miracles overnight. Lower urate just tilts the odds for fewer flares — it doesn’t guarantee smooth sailing for every patient.https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2846208 HPV, Cytology, and Cotest Cervical Cancer Screening and the Risk of Precancer  Let’s start with the basics. For years the Pap test, or cytology, has been the main tool for catching early changes on the cervix. More recently, we’ve added tests that look directly for HPV, the virus that actually causes most cervical cancers. Some places now do both at the same time, called “cotesting.” It sounds like more must be better, right?A big study out of British Columbia followed over eight thousand women for up to ten years after they had both tests done at the same visit. The researchers wanted to know: if your HPV test is negative, does adding that extra Pap result actually help keep you safer in the long run?Here’s what they found. If a woman’s HPV test was positive and her Pap looked abnormal, her chance of developing a significant precancer over time was pretty high, more than 40%. If the HPV test was positive but the Pap looked normal, the risk was lower, but still real—over 20%. Those are the folks we definitely want to follow closely.But once the HPV test was negative, the story changed. Whether the Pap looked normal or a bit off, the risk of serious precancer over the following years stayed very low—well under 5%, and for most women under 1%. In fact, women who were HPV‑negative had almost the same low risk as women whose HPV and Pap were both negative, but adding that Pap test made screening more complicated and more expensive for very little extra benefit.So what does this mean in plain language? If your HPV test is negative, you’re in a very low‑risk group for cervical precancer for many years, even if your Pap result isn’t perfectly pristine. Doing both tests on everyone, every time, doesn’t buy much extra safety, but it does add cost and can lead to more follow‑up procedures that many women don’t actually need.

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    Episode 423: 430. Hormone Replacement Therapy and the Black Box Warning

    Let’s rewind to the early 2000s. Flip phones were cool, low-rise jeans were a crime, and the Women’s Health Initiative—WHI—dropped what became the medical equivalent of a headline: “Hormone Therapy Increases Risk!” The study looked at one very specific regimen: an oral pill with conjugated equine estrogens—yes, horse estrogens—and medroxyprogesterone acetate, or MPA, taken every day by women with an average age of 63.Now, 63 is not “just hit menopause.” That’s about 12 years past menopause for most women. So we were basically taking a therapy usually started around 50, testing it in women in their early 60s, and then pretending that result applied to everyone, at every age, on every dose, with every type of hormone, in every form—patch, pill, gel, ring, cream, you name it.Imagine testing one fast-food burger in 63-year-olds and then announcing: “All food is dangerous. Consider only lettuce, and maybe not too much of that either.”Let’s do a quick myth-versus-reality lightning round.Myth: “All hormone therapy causes breast cancer.”Reality: The best current data do not support a blanket statement like that. In many analyses, especially for women who start near menopause, breast cancer risk is small, nuanced, and depends on the specific regimen and individual risk factors. Estrogen alone has even been associated with lower breast cancer mortality compared to placebo in long-term WHI follow‑up.Myth: “You should take as little as possible for as short as possible, no matter what.”Reality: Your dose and duration should match your symptoms, your risk profile, and your goals. There is no magical stopwatch at 5 years where your body alarms go off. It’s a conversation, not a countdown.Myth: “Vaginal estrogen is as risky as full-body hormone therapy.”Reality: Local vaginal therapies were unfairly swept under the same warning umbrella, despite very different absorption and risk profiles. The new product-specific approach is meant to fix that.

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    Episode 422: 429. Rivaroxaban vs Apixaban = The Battle of the Blood Thinners!

    — rivaroxaban versus apixaban.Yes, folks, this is The Battle of the Blood Thinners!And spoiler alert — one of them came out looking like the overachiever in a safety class... while the other probably needs a little extra padding on its report card.The SetupSo here’s the story. For years, observational studies hinted that apixaban — we’ll call it “Api” because we’re friendly like that — might be gentler when it comes to bleeding compared to rivaroxaban — or “Riva,” who sounds like she’d stir drama on a reality show.But now, for the first time ever, we’ve got a head-to-head trial. Picture a randomized cage match… but with 2,800 patients who probably just wanted their deep vein thrombosis or pulmonary embolism treated quietly.These brave participants, average age 58, were split—half got apixaban, half got rivaroxaban. Researchers then followed them for three suspense-filled months.The Results (and the Punchline)Here’s the headline:Clinically relevant bleeding was twice as likely with rivaroxaban compared to apixaban.Yup—7.1% versus 3.3%. That’s a difference big enough to make any hematologist clutch their coffee mug a little tighter.And if you love a good number — the number needed to harm here is 26. That means for every 26 patients you put on rivaroxaban instead of apixaban, one extra person might have a bleeding episode you wish hadn’t happened.Major bleeding? Rivaroxaban also took home that dubious award — 2.4% versus 0.4%.Ouch. That’s like comparing a paper cut to an artery leak.Why the Difference?The researchers think rivaroxaban’s longer initial high-dose period may explain the extra bleeding drama early in treatment.

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    Episode 421: 428. Asthma and Stroke --- A breathless combination

    Minocycline in Acute Ischemic Stroke (EMPHASIS trial)A multicenter, double-blind RCT in China studied 1,724 patients with acute ischemic stroke treated within 72 hours of onset. Patients received either a 4.5-day course of oral minocycline or placebo. Minocycline works by inhibiting microglial activation, which contributes to post-stroke inflammation. Primary outcome: 52.6% of minocycline patients vs. 47.4% of placebo patients achieved good functional recovery (mRS 0–1) at 90 days (p=0.0061). Safety: No difference in adverse events. Practice impact: Clinicians are cautiously optimistic; further positive trials could lead to selective use of minocycline in AIS patients. 2. Tenecteplase for Basilar Artery Stroke (TRACE-5 trial)This phase 3 RCT in China tested IV tenecteplase given within 24 hours of ischemic basilar artery occlusion against standard medical care (both groups could undergo thrombectomy). Results: At 90 days, 38% of tenecteplase patients vs. 29% of controls had no or minimal disability (mRS 0–1 or baseline). Safety: Similar rates of intracranial hemorrhage (2–3%) and mortality (29–31%). Practice impact: Promising expansion of the thrombolytic window for severe posterior strokes; more evidence needed before routine use outside research settings.

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    Episode 420: 427. Kawasaki disease-no, not the motorcycle company

    Today, we're talking about Kawasaki disease-no, not the motorcycle company, though sometimes treating it does feel like trying to ride one at full speed through uncertainty.For decades, high-dose aspirin was basically the holy water of Kawasaki treatment. Eighty to a hundred milligrams per kilogram per day-because apparently, kids with vasculitis also needed a little side of tinnitus. But here's the twist: new research says... maybe we didn't need all that aspirin after all.Researchers at one hospital decided to mix things up. First, they treated 300 kids with the traditional high-dose aspirin. Then they switched the policy and gave the next 200 kids low-dose aspirin-3 to 5 mg/kg/day. Everyone got IVIG, because we're not completely reckless. And the results? Drumroll please-no difference. That's right. About 20% of kids in both groups needed IVIG a second time, and their coronary arteries looked... equally fine. The median max Z-score was 1.6 in both groups. (For the non-cardiologists out there, that's comfortably under aneurysm territory, which starts at 2.0.) Basically, the low-dose kids did just as well-and none of them had to choke down near-toxic amounts of aspirin. So, high-dose: meet low benefit. Low-dose: meet my new best friend.

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    Episode 419: 426. Go Big or Go Partial? The Knee Replacement Showdown

    Setting the stagePicture this: your knee is like a three-room apartment. You've got a medial room, a lateral room, and a patellofemoral room. In isolated anteromedial osteoarthritis, just one room is trashed. The rest of the apartment still looks like something you'd put on a rental listing. So surgeons have two choices: Option A: Total knee arthroplasty, or TKA - bulldoze the entire apartment and rebuild it. Option B: Medial unicompartmental knee arthroplasty, or UKA - fix the one bad room and leave the rest alone. Previous work suggested that partial knees can actually hold up pretty well when only that medial compartment is involved. But we needed a high-quality, double-blind, multicenter randomized trial to really settle the argument-because if there's anything surgeons love more than power tools, it's being right. The Danish showdownEnter Denmark, land of bicycles, universal healthcare, and apparently, a lot of unicompartmental knees. UKA is done more often there than in many other countries, which means they actually have surgeons who are very good at it. In this new trial, 350 patients with isolated anteromedial osteoarthritis were randomized to either: Medial unicompartmental knee arthroplasty (UKA), or Total knee arthroplasty (TKA). All participating surgeons had substantial experience with both procedures-important, because UKA is more technically demanding. This is not the operation you want someone learning from a YouTube video the night before. And here's the fun methodological twist: for the first year, both the patients and the evaluators were blinded to which procedure had been done. That's right-people walking around with brand-new metal hardware in their knees, and no one was allowed to know which version they got. It's like the orthopedics version of a mystery box subscription. What did they measure?The primary outcome was improvement on a standardized 48-point scale reflecting pain and function over 2 years-essentially, "how good does your knee feel, and what can you do with it?"  They also looked at a bunch of secondary outcomes: different aspects of pain, day-to-day function, range of motion, and so on. So: same surgeons, similar patients, blinded follow-up, partial versus total. Let's talk results. Drumroll: who won?At the 2-year mark: The average improvement on the primary pain-and-function scale was better with UKA than with TKA. The mean difference was 3.5 points, and the threshold for "minimal clinically important difference" was considered 4 points. So UKA got very close-call it "clinically almost important, but statistically clearly better."

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    Episode 418: 425. Triptan initiation and cerebrovascular events

    Kalapura C, et al. Triptan initiation and cerebrovascular events in patients with migraine: A nationwide cohort study. J Am Heart Assoc 2026 Feb 17; 15:e043409. DOI: 10.1161/JAHA.125.043409.  Today, we're talking triptans - those long-trusted migraine relievers - and a new study that asks a not-so-relaxing question: could they slightly raise the risk of ischemic stroke? Let's break it down. Researchers analyzed data from 870,000 adults with migraine and no previous vascular events. The median age was 40, and about three-quarters were women. The team compared those who started triptans with those who didn't, adjusting carefully for age, health, and baseline risk factors. Here's the headline number: over roughly seven years, people who started triptans had an ischemic stroke rate of 3.4 per 1000 person-years, compared to 1.7 per 1000 for nonusers. That's an absolute risk difference of just 0.17% per year, or, in practical terms, about one additional stroke for every 588 people treated annually. So yes - there's a difference, but we're not talking about a massive public health crisis. It's more "tiny spark," not "raging inferno." Now, the nuance. The patients in this analysis were relatively young and healthy. That small risk bump might carry more weight in older populations or in people with multiple vascular risk factors - things like hypertension, high cholesterol, or smoking. In other words, if you have a few checkmarks on the cardiovascular risk list, triptans may deserve a second thought before reaching for the prescription pad. But for most migraine patients? Nothing earth-shattering here. Triptans remain highly effective and, for many, life-changing. The key phrase is informed decision-making. As one clinician commented about the findings, it's all about balance: avoid triptans in patients with known cardiovascular disease, but for others, it's a reasonable discussion. If the medication helps someone reclaim their day from the grip of a migraine, a small increase in vascular risk may be worth it - as long as everyone's eyes are open to the trade-off. It's another reminder that medicine rarely deals in absolutes. Every "yes" has a "maybe," and every prescription deserves a conversation - preferably one that doesn't start with a panicked Google search at 2 a.m. So, the clinical takeaway: triptans may modestly increase ischemic stroke risk, but in context, they remain safe for most healthy migraine patients. Awareness matters more than alarm.

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    Episode 417: 424. GLP1 and NAION

    Li H-Y, et al. GLP-1 receptor agonists and risk of optic nerve or vision-threatening events in patients with type 2 diabetes or cardiometabolic diseases: A meta-analysis of randomized controlled trials. Diabetes Care 2026 Mar 1; 49:526. DOI: 10.2337/dc25-1929.Heberer K, et al. New-onset nonarteritic anterior ischemic optic neuropathy and initiators of semaglutide in US veterans with type 2 diabetes. JAMA Ophthalmol 2026 Feb 12; [e-pub]. DOI: 10.1001/jamaophthalmol.2025.6262.Noh Y, et al. Glucagon-like peptide 1 receptor agonists and risk of nonarteritic anterior ischemic optic neuropathy in patients with type 2 diabetes. Diabetes Care 2026 Feb 17; [e-pub]. DOI: 10.2337/dc25-2577.    Nonarteritic anterior ischemic optic neuropathy is the kind of diagnosis that makes every clinician's stomach drop: sudden, often permanent vision loss, and not much we can do about it. It has always been rare, but a growing body of work is now pointing to a possible link with one of the most widely discussed drug classes in medicine: GLP-1 receptor agonists. Three new studies add fuel to that conversation. First, a large meta-analysis pooled 20 randomized trials with about 80,000 participants-mostly people with type 2 diabetes followed for roughly three years. In that dataset, GLP-1 agonists did not increase a composite of serious ocular events and did not show a signal for ischemic optic neuropathy specifically. On the surface, that sounds reassuring. But the observational data tell a more worrying story. In a U.S. veterans cohort of around 100,000 patients with type 2 diabetes already on metformin, investigators compared add-on semaglutide to add-on empagliflozin over a median of two years. The rate of NAION was higher with semaglutide-about 123 versus 67 events per 100,000 person-years. A separate analysis using a U.K. primary care database of roughly 500,000 people with type 2 diabetes found a similar pattern: those starting a GLP-1 agonist had a higher 1-year risk of NAION than those starting a DPP-4 inhibitor (18.5 vs. 7.2 events per 100,000 person-years). These new results line up with prior observational work suggesting roughly a doubling of NAION incidence among GLP-1 users. So why the disconnect with the meta-analysis of randomized trials? It's almost certainly about design rather than biology. None of the trials were built to capture rare, unexpected eye events: vision outcomes weren't prespecified, routine eye exams weren't mandated, and the definitions of ocular safety events were inconsistent. In that setting, a signal as uncommon as NAION can easily be undercounted or missed entirely. What should clinicians do with this? For most patients, the cardiometabolic benefits of GLP-1 agonists will still far outweigh a very small absolute risk of a rare optic neuropathy. But when we start or continue these drugs, especially in patients who already have vascular risk factors for eye disease, it's reasonable to add one more line to the counseling script: there is a rare association with NAION, and any sudden change in vision warrants urgent evaluation. This isn't a reason to abandon GLP-1s-but it is a reminder that even our most promising therapies can carry risks we only discover once they're widely used.

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    Episode 416: 423. CME-- Discharge Questions Answered in 2025

    CME-- Discharge Questions Answered in 2025

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    Episode 415: 422. Finerenone restores fertility?

    Lin Z, et al. Antifibrotic drug finerenone restores fertility in premature ovarian insufficiency. Science 2026 Feb 5; 391:eadz4075. DOI: 10.1126/science.adz4075. Premature ovarian insufficiency is usually one of those diagnoses that shuts the door on fertility: ovarian function is lost before age 40, mature follicles are scarce to nonexistent, and we have no reliable way to turn things back on. In most textbooks, that's the end of the story. A group in Hong Kong is now asking a different question: what if the problem isn't just the follicles, but the neighborhood they live in? In aged mice, they found that the ovarian stroma becomes fibrotic and stiff, and that this mechanical stiffness itself seems to suppress follicle maturation. Loosen up the stroma, and previously dormant follicles begin to wake up. To turn that concept into something clinically relevant, the team screened nearly 1,300 drugs that are already approved for other human uses, looking for agents that could activate follicles in mice. Ten made the cut. One of them, finerenone-an oral nonsteroidal mineralocorticoid receptor antagonist better known to nephrologists and cardiologists-also reduced collagen production in the ovarian stroma, effectively softening the tissue environment. That observation led to a small, first-in-human trial. Fourteen women with POI-associated infertility received finerenone 20 mg twice weekly, with monthly ultrasound monitoring. Over 3 to 7 months, follicular development was seen in all participants, and eight produced mature oocytes. IVF was attempted when possible, and early embryos were obtained in three women; longer-term follow-up and pregnancy outcomes are still pending. It's a fascinating mechanobiology story: instead of stimulating the follicle directly with gonadotropins or growth factors, the intervention targets the physical properties of the follicular niche. But there are important caveats. The study is tiny, uncontrolled, and POI is not an absolute guarantee of infertility-spontaneous ovulation and pregnancy do occasionally occur. Without a control group and without live-birth data, we cannot know yet how much of this signal represents true drug effect versus background noise. For now, finerenone should stay firmly in the realm of clinical trials when it comes to fertility. But conceptually, this work opens a new front: treating infertility not just as an endocrine or genetic problem, but as a disease of tissue mechanics. If future studies confirm these findings, we may be looking at the beginnings of a paradigm shift in how we think about "irreversible" ovarian failure-and a new source of hope for patients who today are told their options are exhausted.

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    Episode 414: 421. Scabies and DUKE criteria

    Stavropoulou E, et al. Reassessing the 2023 International Society for Cardiovascular Infectious Diseases Duke clinical criteria for infective endocarditis: Impact of excluding fever and updating diagnostic definitions. Clin Infect Dis 2025 Dec 31; [e-pub]. DOI: 10.1093/cid/ciaf737.  Big takeaways About 35% of patients truly had IE. Fever showed up in 80% of patients both with and without IE, so it did not help distinguish them. Dropping fever from the criteria actually made them better:   Sensitivity improved: 77% (no-fever) vs 74% (standard). Specificity improved a lot: 80% vs 49%. "Possible IE" shrank from 39% to 17%, meaning fewer gray-zone cases. Only 0.4% of patients without IE were incorrectly labeled as having IE.  Both are widely used and both can work for regular (non-crusted) scabies. The SCRATCH trial: who won?In the SCRATCH trial from France, researchers treated about 1000 people in 300 households with confirmed scabies. Each household was randomized to: Whole-body 5% permethrin cream on days 0 and 10, orOral ivermectin (weight-based) on days 0 and 10.They then checked who was cured at day 28. Here's what they found:Household cure ratesPermethrin: 88% curedIvermectin: 72% curedTranslation: For every 6 households treated with permethrin instead of ivermectin, one extra household was fully cured (NNT  6). Index (main) patient cure ratesPermethrin: 92%Ivermectin: 77%That's one extra person cured for about every 7 treated with permethrin instead of ivermectin (NNT  7). Side effectSkin irritation-type reactions: 14% with permethrin vs 10% with ivermectin.So permethrin wins on cure, with a small trade-off in local skin reactions. 

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    Episode 413: 420. Frail and CODE LVO PLUS antibiotics don't help viral illness

    we look at CODE LVO and what does being frail even mean?????vaccines may not help baby and antibiotics still don't help viral illness

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    Episode 411: CME - sodium, potassium, calcium

    CME - sodium, potassium, calcium

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    Episode 410: 418. Beta Blockers Post MI, PSA, Youtube,

     10.1016/j.jaip.2025.07.005.40675327All of the videos were found to be useful or very useful, 99% were of moderate or high reliability, and 99% had moderate to excellent educational quality  Prostate-specific antigen levels among participants receiving annual testing. JAMA Oncol 2025 Nov; 11:1341 10.1001/jamaoncol.2025.3386.40965920PSA levels at or above 4.0 ng/mL fell below that threshold on the next annual test 30% of the time. 10.1016/S2665-9913(25)00250-4.During 10 years of follow-up, patients in the PKA and TKA groups did not differ significantly in pain, function, or quality of lifehttps://www.nejm.org/doi/full/10.1056/NEJMoa2508026?query=TOCAmong patients who underwent CABG for an acute coronary syndrome, ticagrelor plus aspirin did not result in a lower incidence of death, myocardial infarction, stroke, https://www.nejm.org/doi/full/10.1056/NEJMoa2509907?query=TOCIn this trial, a high-dose inactivated influenza vaccine did not result in a significantly lower incidence of hospitalization for influenza or pneumonia than a standard dose among older adults.  https://www.nejm.org/doi/full/10.1056/NEJMoa2509834?query=TOCAmong community-dwelling adults 65 to 79 years of age, there appeared to be fewer hospitalizations for influenza or pneumonia with high-dose inactivated influenza vaccine than with the standard dose but the NNT is like 1500! https://pmc.ncbi.nlm.nih.gov/articles/PMC12594118/Afib should not be screened even if the authors say yes https://pubmed.ncbi.nlm.nih.gov/40997143/defines the US cost-effectiveness threshold as $120 000 per quality-adjusted life year gained,  https://pubmed.ncbi.nlm.nih.gov/40481660/In CKD, electronic letter nudges for patients or primary care practices did not differ from no letters for prescriptions of guideline-recommended RASis or SGLT2is at 6 months.  https://www.clinicalkey.com/#!/content/playContent/1-s2.0-S0140673625015922?returnurl=https:%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0140673625015922%3Fshowall%3Dtrue&referrer=https:%2F%2Fclinician.nejm.org%2Fβ-blocker therapy on clinical outcomes in patients with myocardial infarction and mildly reduced (40–49%)  https://www.nejm.org/doi/10.1056/NEJMoa2512686#ap2&uccLastUpdatedDate=2025-12-12%2005%3A34%3A29.658%20%2B0000&rememberMe=falseIn this meta-analysis including individual-patient data from five randomized trials, beta-blocker therapy did not reduce the incidence of death from any cause, myocardial infarction, or heart failure in patients with an LVEF of at least 50% after myocardial infarction without other indications for beta-blockers.

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    Episode 409: 417. Aspirin, Pre-diabetes, Menopause, Type 1 Diabetes, HPV Vaccine and more!!!!

    Wolfe R, Broder JC, Zhou Z, et al. Aspirin, cardiovascular events, and major bleeding in older adults: extended follow-up of the ASPREE trial. Eur Heart J. 12 Aug 2025. [Epub ahead of print]. https://pubmed.ncbi.nlm.nih.gov/40796244/ Donocan LE et al. Closed-loop insulin delivery in type 1 diabetes in pregnancy: The CIRCUIT randomized clinical trial. JAMA 2025 Oct 24; [e-pub]. (https://doi.org/10.1001/jama.2025.19578) https://jamanetwork.com/journals/jama/fullarticle/2822766 https://onlinelibrary.wiley.com/doi/full/10.1002/art.24894?msockid=3f10fb6c3d086e4c32e2ede23c9e6fbc https://pubmed.ncbi.nlm.nih.gov/41118187/ https://pubmed.ncbi.nlm.nih.gov/41115754/  https://pubmed.ncbi.nlm.nih.gov/41138956/ 

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    Episode 408: 416. Car Seats, Beta-Blockers after a Heart Attack, Oral Semaglutide, High-Dose influenza vaccine

    Beta-Blockers after Myocardial Infarction without Reduced Ejection Fraction - https://www.nejm.org/doi/full/10.1056/NEJMoa2504735?query=WB  McGuire DK et al. Oral semaglutide and cardiovascular outcomes in high-risk type 2 diabetes. N Engl J Med 2025 Mar 29; [e-pub]. (https://doi.org/10.1056/NEJMoa2501006) Interactive Virtual Presence to Remotely Assist Parents With Car Seat Installation https://pubmed.ncbi.nlm.nih.gov/41077424/  Effectiveness of high-dose influenza vaccine against hospitalisations in older adults (FLUNITY-HD): an individual-level pooled analysis  https://pubmed.ncbi.nlm.nih.gov/41115437/ 

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    Episode 407: 415. Do Air Filters Lower Blood Pressure?

    https://pubmed.ncbi.nlm.nih.gov/40767818/This is a great example for students and residents to look and see that the abstract does not always match what the paper actually says

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    Episode 406: 414. Resistant Hypertension, Physical Therapy, Steroids for Pneumonia

    Efficacy and safety of Baxdrostat in uncontrolled and resistant hypertension compared to placebo in phase three when there are MRA available that are cheap and availableA randomised trial of physical therapy for meniscal tear and knee pain discovers that home exercises are just as good as inperson physical therapya Pragmatic trial of glucocorticoids for community acquired pneumonia that I don't think you can trust

  24. 367

    Episode 405: 413. 4 Articles to Scare You-- COPD, Cirrhosis, ETOH, and Ablation

    gabapentin may increase COPD exacerbationsBenzo for ETOH might be long gone..guess what is going to replace itAnticoagulation after ablation.... what do you do with it?BBlocker in those with cirrhosis and varices

  25. 366

    Episode 404: 412. Liver Transplant - The One Referral I Doubt You Are Doing Correctly

    Clinicians should refer patients for liver transplant evaluation after any decompensation event—such as ascites or variceal bleeding—regardless of MELD score. After a first decompensation, 5-year mortality is 20–30%; after a second, it rises to 80–90%. Refractory ascites carries a 50% 1-year mortality, and overt hepatic encephalopathy has a 25–40% 1-year mortality. After an initial variceal bleed, the 1-year rebleeding risk is 60% without prophylaxis. There are no strict BMI or age cutoffs, and frailty has minimal effect on post-transplant outcomes. Substance use, including alcohol, is not a contraindication to referral—current guidelines no longer require a 6-month abstinence period. CitationsKing LY et al. Guidance for timely referral to liver transplantation. Clin Gastroenterol Hepatol 2025 Aug 5; [e-pub]. (https://doi.org/10.1016/j.cgh.2025.07.032)

  26. 365

    Episode 403: 411. Gabapentin and Emergency Carotid Artery Stenting in Stroke

    Study Summary: Emergent Carotid Stenting in Acute Stroke ThrombectomyA multicenter registry study in Catalonia (2017–2023) evaluated outcomes in 578 patients with acute ischemic stroke and tandem lesions (large-vessel occlusion plus extracranial carotid stenosis). Patients were divided into two groups: those who received emergent carotid artery stenting (E-CAS) and those who did not (non-CAS).Key Findings: Favorable outcomes (modified Rankin Scale 0–2) were more common in the E-CAS group at: 90 days: 46% vs. 37% 1 year: Odds ratio 1.35 Recanalization rates were higher with E-CAS: 92% vs. 73% No significant differences in: Hemorrhagic transformation at 36 hours (though a trend toward higher rates with E-CAS) 1-year mortality Conclusion:Emergent carotid stenting during thrombectomy may improve functional outcomes and recanalization without significantly increasing bleeding or mortality. However, as this was not a randomized trial, results should be interpreted cautiously. Further randomized studies are needed.  Ezcurra-Díaz G et al. Emergent carotid artery stenting in patients with acute ischemic stroke with tandem lesions: One-year follow-up results from the SECURIS study. Neurology 2025 Oct 7; 105:e214067.    Gabapentinoids for Postoperative Pain: No Benefit FoundStudy Overview: A large randomized, placebo-controlled trial in the U.K. (GAP study) evaluated the effectiveness of gabapentin for postoperative pain in 1,200 patients undergoing various cardiac, thoracic, and abdominal surgeries.Intervention: Gabapentin group: 600 mg pre-op, then 300 mg twice daily for 2 days post-op Control group: Placebo Key Findings: Slight pain reduction at 1 hour post-op (4.0 vs. 3.5 on 11-point scale) No difference in pain at later time points No differences in: Opioid use Serious adverse events Length of hospital stay Commentary: Despite widespread off-label use, this large, well-designed trial found no meaningful benefit of gabapentin for postoperative pain. While short-term use appeared safe, prolonged use may pose risks (e.g., sedation, falls, respiratory depression). Clinicians are advised to reconsider routine perioperative use of gabapentinoids.  Baos S et al. Gabapentin for pain management after major surgery: A placebo-controlled, double-blinded, randomized clinical trial (the GAP study). Anesthesiology 2025 Oct; 143:851.

  27. 364

    Episode 402: 410. When You Shouldn't Double Down But Instead Hit for Another

    This massive meta-analysis of 484 randomized, double-blind, placebo-controlled trials (104,176 participants) quantified the blood pressure–lowering effects of major antihypertensive drug classes and their combinations. It introduces a new intensity-based classification system and an online calculator to predict BP-lowering efficacy based on drug, dose, and baseline BP.Study Design: 484 trials, 104,176 participants 5 major drug classes: ACE inhibitors, ARBs, β-blockers, calcium channel blockers (CCBs), and diuretics Focus: Placebo-corrected reduction in systolic BP (SBP) Mean baseline BP: 154/100 mm Hg Mean follow-up: 8.6 weeks Key Findings Monotherapy (Standard Dose): Average SBP reduction: 8.7 mm Hg By class: ACE inhibitors: 6.8 mm Hg ARBs: 8.5 mm Hg β-blockers: 8.9 mm Hg CCBs: 9.5 mm Hg Thiazide diuretics: 10.8 mm Hg Dose Doubling:Adds ~1.5 mm Hg SBP reduction (except β-blockers, which add only ~0.5 mm Hg) Dual Therapy (Standard Dose of Each): Average SBP reduction: 14.9 mm Hg Dose doubling adds ~2.5 mm Hg more Triple Therapy: SBP reduction: Up to 22.5 mm Hg (quadruple therapy even higher in one trial)

  28. 363

    Episode 401: 409. The Effects of Upper Extremity and Lower Extremity Aerobic Exercise Training in Patients with Peripheral Arterial Disease:

    Practice Pearls: “Skip Leg Day” (Sometimes)For PAD patients who can’t tolerate leg workouts, upper body aerobic training is a strong, evidence-backed alternative. It’s not just a workaround—it’s a workout. CitationAhiskali GN, Demirel A, Yamikan H, Kutukcu EC. The Effects of Upper Extremity and Lower Extremity Aerobic Exercise Training in Patients with Peripheral Arterial Disease: A Systematic Review. J Vasc Surg. 2025. doi: 10.1016/j.jvs.2025.07.060

  29. 362

    Episode 400: 408. CME Obesity and MASH

    GLP1 drugs work but they likely need lifestyle modificationsNo convincing evidence GLP1 cause thyroid cancer in humans BUT contraindication if family history existStopping therapy usually results in weight gainInsurance coverage for weight loss is limited and variable  Semaglutide for type 2 diabetes max dose is 2.0 mg weekly Semaglutide for weight loss has a goal dose of 2.4 mg weekly Diagnose steatotic liver disease with imaging and 1 metabolic risk factor (or biopsy) After diagnosis check FIB-4: Low risk, continue to monitor with FIB-4 every 2-3yrs  Intermediate risk, order VCTE and consider referral if >F1  High risk order a VCTE and referral (20% end with SLD) 2 FDA approved medications for liver fibrosis are not cheap, expect insurance push back

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  31. 360

    Episode 398: 406. Update of Medical Articles

    All of these articles have been talked about on questioning medicine social media on tik tok and instagram but here is an update of my recent reading

  32. 359

    Episode 397: 405. 4 New Medical Articles That Are Deceiving

    Buelt, Andrew | 2:13 PM (1 hour ago) |  | to mehttps://jamanetwork.com/journals/jama/fullarticle/2833338 Conclusions and Relevance  These results support use of metformin for treatment of symptomatic knee osteoarthritis in people with overweight or obesity. Because of the modest sample size, confirmation in a larger clinical trial is warranted.    Lee S et al. Live zoster vaccination and cardiovascular outcomes: A nationwide, South Korean study. Eur Heart J 2025 May 5; [e-pub]. (https://doi.org/10.1093/eurheartj/ehaf230) In a new South Korean study, researchers evaluated nearly 1.3 million people (age ≥50) who were entered into a nationwide database. In an analysis adjusted for numerous confounders and with an average follow-up of 6 years, people who received a VZV vaccine had significantly lower risk (by ≈25%) for overall adverse cardiovascular events, heart failure, cerebrovascular disorders, ischemic heart disease, thrombotic disorders, and arrhythmias.  https://pubmed.ncbi.nlm.nih.gov/40658956/ Conclusion: Findings indicate that VNPs were more effective than NRT for smoking cessation in this population. Given the challenges for cessation among these socially disadvantaged populations, VNPs present a promising treatment option for this priority group.   https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0326804   We did not find that haloperidol was arrhythmogenic or increased mortality in these largely short-duration trials. Further research to clarify actual clinical outcomes related to QTPmeds is important to inform safe prescribing practices.

  33. 358

    Episode 396: 404. albuterol/budesonide, DOAC in 4 Days, Statins for AAA

    https://www.nejm.org/doi/10.1056/NEJMoa2504544  During follow-up ranging from 12 to 52 weeks, fewer patients had severe exacerbations in the albuterol/budesonide group than in the albuterol group (5% vs. 9%). Patients in the albuterol/budesonide group had less than half the total exposure to systemic glucocorticoids as those in the albuterol group (mean, 23 vs. 62 mg per year).   Clinical Practice: This study supports the use of an as-needed combination of albuterol and budesonide in reducing severe asthma exacerbations in patients with mild asthma who are inadequately controlled by SABA alone. This aligns with current recommendations by the Global Initiative for Asthma (GINA), which advocates for an inhaled corticosteroid plus a fast-acting bronchodilator as rescue therapy across all treatment steps for patients aged 12 years and older.   https://www.clinicalkey.com/#!/content/playContent/1-s2.0-S0140673625004398?returnurl=https:%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0140673625004398%3Fshowall%3Dtrue&referrer=https:%2F%2Fpubmed.ncbi.nlm.nih.gov%2F  Clinical Recommendation: The findings support the practice of initiating DOAC treatment within 4 days of an acute ischemic stroke in patients with atrial fibrillation, as it reduces the risk of early recurrent ischemic stroke without increasing hemorrhagic complications. This challenges the traditional approach of delaying anticoagulation to avoid potential bleeding risks.   https://www.ahajournals.org/doi/full/10.1161/CIRCULATIONAHA.125.074544?rfr_dat=cr_pub++0pubmed&url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org  reduce the necessity for surgical intervention. Clinical Recommendations: Given their proven cardiovascular benefits, safety profile, and cost-effectiveness, high-dose statins should be strongly considered for patients with small AAAs, particularly those without contraindications. Future Directions:

  34. 357

    Episode 395: 403. COVID Maternal Booster And Cervical Self Swabs

    https://publications.aap.org/pediatrics/article/156/1/e2024070175/202234/Infant-Antibodies-After-Maternal-COVID-19?autologincheck=redirected  Objective:The study aimed to evaluate the kinetics and duration of maternally derived antibodies in infants up to 6 months old, following maternal COVID-19 vaccination during pregnancy or postpartum. Study Design:A prospective multicenter cohort study was conducted across nine U.S. academic sites, enrolling infants born to mothers vaccinated with 2- (n=280) or 3-dose (booster) monovalent mRNA vaccines during pregnancy (n=202) or postpartum (n=36). Primary Outcomes: Antibody Levels: Significantly higher geometric mean titers (GMTs) of binding and neutralizing antibodies (nAb) were observed at birth and 2 months in infants of mothers who received a booster dose during pregnancy compared to those who received 2 doses or were vaccinated postpartum. Sustained Antibody Levels: Higher titers against the vaccine strain persisted up to 6 months in infants of boosted mothers, although not for the Omicron BA.1 and BA.5 variants.    https://pubmed.ncbi.nlm.nih.gov/40478588/   Objective:The study aimed to determine if mailed self-collection kits for CCS, with or without additional patient navigation, could improve screening participation compared to standard telephone reminders. Study Design:This was a pragmatic, parallel, single-blinded, randomized clinical trial conducted within a publicly funded safety-net health system in Houston, Texas. It included 2474 participants who were overdue for CCS. Primary Outcomes: Participation Rates: Among those who received a telephone reminder and mailed self-collection, 41.1% participated in screening, compared to 17.4% who received a telephone reminder alone. When patient navigation was added to mailed self-collection, participation increased to 46.6%. Effectiveness: Self-collection kits significantly improved participation, with a relative participation of 2.36 times higher than telephone reminders alone. Adding patient navigation further modestly increased participation to 2.68 times higher.

  35. 356

    Episode 394: 402. Cardiovascular Risk Factors, Zilebesiran, Shared Decision Making

    https://www.nejm.org/doi/10.1056/NEJMoa2415879?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed Key Findings: Classic Risk Factors: The five risk factors examined were hypertension, hyperlipidemia, underweight and overweight or obesity, diabetes, and smoking. These factors are estimated to account for about 50% of the global burden of cardiovascular disease. Lifetime Risk Estimates: Among individuals free of these risk factors at age 50, the lifetime risk of cardiovascular disease was 13% for women and 21% for men. For those with all five risk factors, the lifetime risk jumped to 24% for women and 38% for men. Significance of Risk Factor Modification: Adjusting certain risk factors during midlife, particularly managing hypertension and quitting smoking, led to the most significant gains in life expectancy free of disease. For instance, controlling hypertension between ages 55 and 60 yielded the most additional life-years free of cardiovascular disease. Quitting smoking during the same period was associated with the most additional life-years free of death from any cause.    https://jamanetwork.com/journals/jama/fullarticle/2834632 Study Design: This was a phase 2, randomized, double-blinded trial with participants enrolled from 150 sites across 8 countries. The study spanned from January 2022 to June 2023, with analyses completed by March 2024. Participants received indapamide, amlodipine, or olmesartan as background therapy. Those with a specified range of 24-hour mean ambulatory systolic blood pressure (SBP) were then randomized to receive either a single subcutaneous dose of 600 mg zilebesiran or placebo. Efficacy Results: At 3 months, zilebesiran significantly reduced the 24-hour mean ambulatory SBP compared to placebo across all cohorts: Indapamide: -12.1 mmHg Amlodipine: -9.7 mmHg Olmesartan: -4.5 mmHg Similar reductions were observed in office SBP measurements at 3 months.    https://pubmed.ncbi.nlm.nih.gov/40578930/   Primary Outcomes: Discontinuation of Opioid Therapy: Patients in the greater SDM group were less likely to discontinue opioid therapy 3 months post-baseline compared to those in the lesser SDM group (Relative Risk: RR of 0.56). Opioid Prescribing Frequency: Over a 12-month period, patients in the greater SDM group experienced more frequent opioid prescriptions (RR of 1.24). Secondary Outcomes: Physical Function: Interestingly, physical function was slightly worse in the greater SDM group, but this difference was not deemed clinically significant. Back-related Disability: Both greater opioid use and SDM were associated with increased back-related disability and worse physical function, yet these findings were also not clinically significant. No significant SDM x opioid therapy interaction effects were observed, indicating that more frequent opioid use coupled with SDM did not lead to better patient outcomes in pain, function, or health-related quality of life (HRQOL).

  36. 355

    Episode 393: 404. 3 quick articles you might want to know about (oral semaglutide, tiktok, and GLP1 thyroid cancer)

    GLP1 might cause thyroid cancer in mice but the evidence is drastically lacking in humansOral semaglutide is expensive for an NNT of 50 at 4 yrsTiktok videos of skin care are a scam

  37. 354

    Episode 392: 403. 3 Papers, 1 Podcast - One Guideline Changer

    https://jamanetwork.com/journals/jama/article-abstract/2834040amiloride is realistically equal to spironolactone for resistant HTNhttps://journals.lww.com/ajg/abstract/2025/05000/higher_rate_of_spontaneous_bacterial_peritonitis.24.aspxprophalaxis antibiotics might not be neededhttps://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2834317If you got a friend in weight loss-- or at least in maintaining weight loss

  38. 353

    Episode 391: 402. Functional disability after clinically significant extracranial bleeding: a secondary analysis of ASPREE

    https://www.jthjournal.org/article/S1538-7836(25)00109-6/fulltextAntithrombotic agents, like aspirin and anticoagulants, are essential for treating many cardiovascular conditions. However, a common side effect is bleeding, with extracranial bleeding—bleeding outside the brain and spinal cord—being quite prevalent. This study, a secondary analysis of the Aspirin in Reducing Events in the Elderly, or ASPREE trial, aimed to explore how clinically significant extracranial bleeding affects the development of functional disability in otherwise healthy older adults.What did the researchers find?Summary of Findings: Incidence of Bleeding: Out of nearly 19,000 participants, about 2.9%, or 547 individuals, experienced clinically significant extracranial bleeding. Functional Independence Impact: Those who experienced such bleeding had a more than two-fold increase in the risk of developing dependence on activities of daily living, or ADLs. Specifically, the hazard ratio for ADL dependence was 2.46, indicating a significant association. Types of Bleeding: Both gastrointestinal (GI) bleeding and other non-GI extracranial bleeding showed similar risks, with hazard ratios of 2.29 and 2.68 respectively. Importantly, these associations held true whether participants were on aspirin or a placebo. Strengths of the Study: Large Sample Size: With nearly 19,000 participants, the study provides robust data. Rigorous Data Collection: Bleeding events were meticulously documented and adjudicated by medical professionals. Comprehensive Analysis: The detailed follow-up and frequent assessments allowed for thorough monitoring of participants' health outcomes over several years. Weaknesses of the Study: Granular Data Absence: Specific details about hospitalization, such as length of stay or the number of transfusions, were not available. Data Collection Frequency: Bleeding events were assessed continuously, whereas ADL dependence was assessed biannually. This discrepancy could lead to challenges in pinpointing the exact onset of functional dependence relative to bleeding events.

  39. 352

    Episode 390: 401. Add-On Treatment With Zilebesiran for Inadequately Controlled Hypertension

    https://jamanetwork.com/journals/jama/article-abstract/2834632SummaryThe article examines the effectiveness and safety of zilebesiran, an RNA interference therapeutic agent, when used in combination with standard first-line antihypertensive drugs for patients with inadequately controlled hypertension. The phase 2, prospective, randomized, double-blinded trial was conducted over multiple international sites with patients treated with either indapamide, amlodipine, or olmesartan. The primary outcome measured was the change in 24-hour mean ambulatory systolic blood pressure (SBP) at three months.Key findings from the study showed that a single subcutaneous dose of zilebesiran significantly reduced 24-hour mean ambulatory and office SBP at three months compared to placebo, across all background treatments. This indicates that zilebesiran can be an effective adjunctive treatment to standard oral antihypertensive therapies, providing sustained blood pressure control.Strengths Innovative Approach: The use of RNA interference to target hepatic synthesis of angiotensinogen introduces a novel mechanism to control blood pressure. Methodological Rigor: The study used a double-blinded, placebo-controlled design across multiple international sites, enhancing the reliability and generalizability of the results. Significant Findings: The results indicated significant reductions in SBP with zilebesiran, especially when added to indapamide and amlodipine, showing its potential effectiveness as an additive therapy. Well-Tolerated: Despite instances of hyperkalemia, hypotension, and acute kidney failure, most events were mild and resolved without the need for medical intervention, highlighting a favorable safety profile for zilebesiran. Weaknesses Short Duration: The study's follow-up period was limited to six months. Long-term efficacy and safety of zilebesiran need to be evaluated in future studies. Sample Size and Specificity: The study's sample size might be insufficient to capture rare adverse events, and the exclusion of patients with high cardiovascular risk might limit the applicability of the results to broader, real-world populations. EIght Background Therapies: Although the study included three commonly used antihypertensive drugs, the varying responses could indicate the need for more comprehensive studies including other first-line therapies.

  40. 351

    Episode 389: 400. CRP, Lipoprotein A, LDL for cardiac risk assessment

    https://www.nejm.org/doi/full/10.1056/NEJMoa2405182?query=recirc_Semantic  Key Takeaways Extended Predictive Value of Biomarkers: High-sensitivity C-reactive protein (CRP), LDL cholesterol, and lipoprotein(a) levels were found to be predictive of cardiovascular events over a 30-year period. These markers contribute independently to long-term cardiovascular risk beyond traditional 10-year risk estimates. Study Design and Population: The study enrolled 27,939 initially healthy U.S. women who were followed for 30 years. The primary endpoint was the occurrence of a first major adverse cardiovascular event, including myocardial infarction, coronary revascularization, stroke, or death from cardiovascular causes. Predictive Strength of Biomarkers: Among the biomarkers, high-sensitivity CRP showed the strongest association with future cardiovascular events (hazard ratio for top quintile: 1.70). LDL cholesterol and lipoprotein(a) also significantly predicted risk, albeit to a slightly lower degree (hazard ratios: 1.36 and 1.33, respectively).  NOT STATIN WITH CRP Implications for Clinical Practice: Combining all three biomarkers may offer the best method for identifying high-risk individuals who might benefit from early intervention.   YOU HAVE TO PROSPECTIVELY VALIDATE THIS The study supports extending cardiovascular prevention strategies beyond traditional risk assessments. Lifestyle and pharmacologic interventions should target multiple pathways, including lipid levels and inflammation. Key Limitations Study Population: The study cohort predominantly consisted of female health professionals who are mostly White (94%), which may limit generalizability. The results may not extend to males or more diverse populations without further studies. Absence of Repeated Measures: Biomarkers were measured only at baseline without repeated measures over time. This limits the ability to observe changes in biomarker levels and their association with risk over time. Statin Use Data: Increasing use of statins over the study period was not thoroughly considered in initial analyses, and detailed data on adherence and duration are lacking. Sensitivity analyses attempted to account for this by censoring data at the time of first statin prescription, but residual confounding may be present. Concerns with Study Design Cohort Composition: The study's focus on health professionals might have led to better access to healthcare and healthier lifestyle choices, potentially skewing outcomes. Non-White participants were underrepresented, raising concerns about the applicability of findings to more diverse groups. Single Time Point Measurement:Only baseline biomarker levels were used for long-term prediction, which may not account for variability and changes in risk factors over time.

  41. 350

    Episode 388: 399. Use of albumin-adjusted calcium measurements in clinical practice

    Desgagnés N et al. Use of albumin-adjusted calcium measurements in clinical practice. JAMA Netw Open 2025 Jan 21; 8:e2455251. (https://doi.org/10.1001/jamanetworkopen.2024.55251)Overall, total calcium levels (just the ones we would get back on a basic cmp) correlated better with ionized calcium than did formula-corrected calcium levels. Formulas with stronger correlation than total calcium levels were either complex (e.g., requiring blood pH measurement) or derived locally (i.e., not generalizable). Many formulas overestimated calcium at low calcium levels; the Payne formula misclassified 41% of patients, whereas the total calcium level only misclassified 25% of patients.

  42. 349

    Episode 387: 398. Which is Better, Tirzepatide or Semaglutide?

    https://www.nejm.org/doi/10.1056/NEJMoa2416394At 72 weeks, the mean percentage decrease in weight was significantly greater with tirzepatide than with semaglutide (20% vs. 14%). Gastrointestinal side effects occurred frequently in both groups but led to discontinuation of treatment in only 3% and 6% of participants in the tirzepatide and semaglutide groups, respectively. Injection-site reactions were more common with tirzepatide than with semaglutide (9% vs. <1%) but didn't cause participants to stop treatment.

  43. 348

    Episode 386: 397. What is the new drug for smoking cessation?

    https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2832701In this multisite trial, 800 adults who smoked 10 or more cigarettes daily (mean duration of smoking, ≈35 years) were randomized to 6 or 12 weeks of cytisinicline or to placebo. In the 6-week group,15% of cytisinicline recipients and 6% of placebo recipients were abstinent (defined by self-report and breath carbon monoxide <10 ppm) during weeks 3 to 6. In the 12-week group, 30% of cytisinicline recipients and 9% of placebo recipients were abstinent during weeks 9 to 12.

  44. 347

    Episode 385: 396. Vitamin D and Kids (CME)

    What does the evidence and the guidelines say about the use and testing of Vitamin D in kids

  45. 346

    Episode 384: 395. How accurate is the BMI?

    Aryee EK et al. Prevalence of obesity with and without confirmation of excess adiposity among US adults. JAMA 2025 Apr 17; [e-pub]. (https://doi.org/10.1001/jama.2025.2704)The rate of obesity was 39.7% based on BMI and 39.1% based on excess adiposity. Among participants with obesity based on BMI, 98% also had excess adiposity; in other words, essentially the same individuals were considered as obese by both criteria.

  46. 345

    Episode 383: 394. Does the time of day effect bronchodilator responsiveness?

    In an hour-by-hour analysis, patients we suspect to have asthma are significantly more likely to have positive bronchodilator responses early in the morning; with each passing hour before testing, there was small decrease (8%) in positive response. Patients also were more likely to have positive responses in the winter. Knox-Brown B et al. Effect of time of day and seasonal variation on bronchodilator responsiveness: The SPIRO-TIMETRY study. Thorax 2025 Mar 11; [e-pub]. (https://doi.org/10.1136/thorax-2024-222773)

  47. 344

    Episode 382: 393. CME-- Vitamin D and Adults

    Vitamin D and Adults and what you should do with Vitamin D

  48. 343

    Episode 381: 392. Outpatient Management of COPD - CME

     a cme lecture on the outpatient management of COPD

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Join Andrew on a medical rollercoaster as we ask a medical question and answer it based on recent published papers.

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