Questioning Medicine

Does a Coronary Artery Calcium (CAC) scan still earn its place in modern cardiovascular prevention? This podcast cuts through the headlines to examine the recent research, challenge overconfident conclusions, and put CAC testing under the microscope alongside the PREVENT risk equation.Each episode brings a sharp, evidence-first look at what calcium scoring can—and cannot—tell us about heart-attack risk. We unpack study methods, question the assumptions behind new publications, and ask the practical questions clinicians and patients actually need answered: When does CAC meaningfully change care? Who benefits most? And in an era of PREVENT, does a scan add actionable information beyond the numbers?Clear-eyed, clinically grounded, and never afraid to interrogate the data, this is the podcast for anyone who wants the real value of CAC—not just the latest claim.

OMED lecture on how to understand medical stats

CME

OMED lecture

Xin X, et al. Optimal exercise modalities and dosages for blood pressure reduction in adults with prehypertension and established hypertension: A network meta-analysis and dose–response relationship study. J Am Heart Assoc 2026 May 14; 15:e044003. DOI: 10.1161/JAHA.125.044003. Vosooney A, et al. Screening for Cervical Cancer: A Recommendation From the Women’s Preventive Services Initiative. Obstet Gynecol 2026 Jul; 148:e3. DOI: 10.1097/AOG.0000000000006315. Castells A, et al. Effect of invitation to colonoscopy versus faecal immunochemical test screening on colorectal cancer mortality (COLONPREV): A pragmatic, randomised, controlled, non-inferiority trial. Lancet 2025 Apr 12; 405:1231. DOI: 10.1016/S0140-6736(25)00145-X.Castells A, et al. Colonoscopy versus biennial FIT screening: A post hoc sustained-strategy analysis of the COLONPREV Trial. Gut 2026 Jun 10; [e-pub]. DOI: 10.1136/gutjnl-2026-338896.  Diercks D, et al. Evaluation and management of chest pain from cardiovascular causes in female patients. BMJ 2026 Jan 30; 392:e086177. DOI: 10.1136/bmj-2025-086177.  https://www.sciencedirect.com/science/article/pii/S0140673626008767?via%3Dihub   Lancet. 2026 May 23;407(10543):2015-2026. Yanik EL, et al. Associations of sleep and shift work with osteoarthritis risk. Arthritis Care Res (Hoboken) 2026 Jan 22; [e-pub]. DOI: 10.1002/acr.70040.  Noma H, et al. Angiotensin receptor blockers versus calcium channel blockers for first-line antihypertensive therapy and survival in adults aged 75 years or older. J Am Geriatr Soc 2026 Apr 26; [e-pub]. DOI: 10.1111/jgs.70463. https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/215256s029lbl.pdf

Jafari K, et al. Risk factors for pediatric deep neck infection revisit after emergency department discharge for pharyngitis or localized neck symptoms. Ann Emerg Med 2026 May; 87:605. DOI: 10.1016/j.annemergmed.2025.10.007.In a “look-back” analysis of some 800 children admitted with deep neck infection, 18% had at least one ED discharge before admission. The most common discharge diagnoses were fever, pharyngitis/tonsillitis, and localized neck symptoms.In a “look-forward” analysis, 0.01% of about 400,000 children diagnosed with pharyngitis/tonsillitis and 0.07% of almost 60,000 children presenting with nontraumatic neck symptoms were subsequently admitted with a deep neck infection. Klausen MK, et al. Once-weekly semaglutide versus placebo in patients with alcohol use disorder and comorbid obesity: A randomised, double-blind, placebo-controlled trial. Lancet 2026 May 2; 407:1687.Heavy drinking decreased from 17 days per month at baseline to 13 with placebo and 10 with semaglutide — a significant 3-day difference.Days without any alcohol use in the past month increased from 9 at baseline to 11 with placebo and 12 with semaglutide, though this difference was not significant (P=0.051). https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2848777Conclusions and Relevance  In this RCT of 651 AWS, varenicline sampling was efficacious, with potentially superior outcomes compared with NRT.    https://jamanetwork.com/journals/jama/fullarticle/2848997Conclusions and Relevance  Among childbearing physicians in training, a parental support package significantly mitigated postpartum burnout. https://pubmed.ncbi.nlm.nih.gov/42120723/. These data demonstrate orforglipron's potential as a globally scalable option for minimizing weight changes after injectable therapy. Trial limitations include the absence of a comparator arm involving continued use of injectable obesity-management medications and the trial's 1-year duration. https://pubmed.ncbi.nlm.nih.gov/42104164/mong 263 clinicians (107 residents, 156 specialists), specialists scored higher than residents (median, 46 [IQR, 42-50] vs 41 [IQR, 36-46]; P < .001; r = 0.32). ChatGPT correctly diagnosed 53 of 61 cases (86.9%), Gemini 50 (82.0%), and Copilot 44 (72.1%). Both ChatGPT and Gemini exceeded the upper bound of the specialist population median 95% CI (47.17).  https://www.nejm.org/do/10.1056/NEJMdo008444/full/Among patients with noncardioembolic ischemic stroke or high-risk TIA treated with antiplatelet therapy, asundexian at a daily dose of 50 mg resulted in lower risks of ischemic stroke and major cardiovascular events than placebo, without a higher risk of major bleeding.

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

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

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.

432.  CME LECTURE-  Under Pressure, Blood Pressure

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.

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.

— 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.

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.

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.

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."

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.

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.

CME-- Discharge Questions Answered in 2025

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.

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 takeawaysAbout 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. 

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

CME song --Check the Lytes

CME - sodium, potassium, calcium

 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.

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/ 

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/ 

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

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

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

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)

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 1.35Recanalization 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 mortalityConclusion: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-opControl group: PlaceboKey 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 pointsNo differences in:Opioid useSerious adverse eventsLength of hospital stayCommentary: 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.

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 participants5 major drug classes: ACE inhibitors, ARBs, β-blockers, calcium channel blockers (CCBs), and diureticsFocus: Placebo-corrected reduction in systolic BP (SBP)Mean baseline BP: 154/100 mm HgMean follow-up: 8.6 weeks Key Findings Monotherapy (Standard Dose):Average SBP reduction: 8.7 mm HgBy class:ACE inhibitors: 6.8 mm HgARBs: 8.5 mm Hgβ-blockers: 8.9 mm HgCCBs: 9.5 mm HgThiazide 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 HgDose doubling adds ~2.5 mm Hg more Triple Therapy:SBP reduction: Up to 22.5 mm Hg (quadruple therapy even higher in one trial)

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

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 weeklyDiagnose 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

OMED COPD CME

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

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.

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:

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.

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/2834632Study 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 mmHgAmlodipine: -9.7 mmHgOlmesartan: -4.5 mmHgSimilar 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).

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

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

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.

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.StrengthsInnovative 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.WeaknessesShort 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.

https://www.nejm.org/doi/full/10.1056/NEJMoa2405182?query=recirc_Semantic  Key TakeawaysExtended 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 CRPImplications 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 THISThe study supports extending cardiovascular prevention strategies beyond traditional risk assessments.Lifestyle and pharmacologic interventions should target multiple pathways, including lipid levels and inflammation.Key LimitationsStudy 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 DesignCohort 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.

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.

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.

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.

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

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.

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)

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

 a cme lecture on the outpatient management of COPD

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https://www.nejm.org/doi/full/10.1056/NEJMoa2405923?query=clinical-medicine Mineralocorticoid receptor antagonists have been shown to reduce mortality in patients after myocardial infarction with congestive heart failure. Whether routine use of spironolactone is beneficial after myocardial infarction is uncertain.  Recent attempts to improve outcomes with intensified renin–angiotensin–aldosterone inhibition have not shown improvements in outcomes.7,8 A trial of routine aldosterone antagonism with spironolactone in addition to standard therapy among 1603 patients after myocardial infarction without heart failure showed no improvement in outcomes.9  https://pubmed.ncbi.nlm.nih.gov/27102506/   “ In a non-pre-specified exploratory analysis, the odds of death were reduced in the treatment group (3 [0.5%] vs. 15 [2.4%]; HR: 0.20; 95% CI: 0.06 to 0.70) in the subgroup of ST-segment elevation MI (n = 1,229), but not in non-ST-segment elevation MI (p for interaction = 0.01).”’ However, there was a significant reduction in mortality in the subgroup of 1229 patients with ST-segment elevation myocardial infarction (STEMI), a finding that highlights the need for a large trial.  We conducted the CLEAR trial to evaluate whether routine use of spironolactone is beneficial in patients after myocardial infarction.

Estimated 5-year incidence of recurrent VTE was similar in the reduced-dose and full-dose groups (2.2% and 1.8%).Estimated 5-year bleeding incidence was significantly lower with reduced-dose than with full-dose treatment (2.1% vs. 4.0% for major bleeding; 8.6% vs. 11.5% for clinically relevant nonmajor bleeding).Outcomes with apixaban and rivaroxaban were similar.Couturaud F et al. Extended treatment of venous thromboembolism with reduced-dose versus full-dose direct oral anticoagulants in patients at high risk of recurrence: A non-inferiority, multicentre, randomised, open-label, blinded endpoint trial. Lancet 2025 Mar 1; 405:725. (https://doi.org/10.1016/S0140-6736(24)02842-3)

https://www.nejm.org/doi/full/10.1056/NEJMoa2405404NNT of 4! systemic metronid and topical clinda bid for one week

What Was Studied?The EMPA-KIDNEY trial followed 6,609 CKD patients at risk of disease progression. Participants were randomly assigned to receive empagliflozin (10 mg daily) or a placebo for a median of 2 years. After this ‘active’ phase, 4,891 patients entered a 2-year post-trial observational period where neither group received the trial drug, but doctors could prescribe open-label SGLT2 inhibitors. The goal? To see if empagliflozin’s benefits persisted after stopping treatment.Key FindingsSustained Kidney Protection:Over the entire 4-year period (active + post-trial), empagliflozin reduced the risk of kidney disease progression or cardiovascular death by 21% (HR 0.79). The number needed to treat (NNT) to prevent one event was 24 patients over 4 years.Post-Trial Benefits:Even after stopping the drug, the empagliflozin group saw a 13% lower risk of the primary outcome during the post-trial phase alone (HR 0.87).Specific Outcomes:Kidney disease progression: 23.5% (empagliflozin) vs. 27.1% (placebo).Death or end-stage kidney disease: 16.9% vs. 19.6%.Cardiovascular death: 3.8% vs. 4.9%.Safety: No increased risk of noncardiovascular deaths (5.3% in both groups).LimitationsObservational Post-Trial Phase: After the active trial, 40-43% of both groups used open-label SGLT2 inhibitors, potentially diluting the observed benefit.Selection Bias: Only 74% entered post-trial follow-up, and outcomes relied on local lab data (not centralized measurements).Short Post-Trial Window: Effects beyond 2 years post-discontinuation remain unknown.Should This Change Practice?Yes. Here’s why:Longer-Term Reassurance: Empagliflozin’s benefits persist for ~1 year after stopping, supporting its role even if patients discontinue it later.Broad Applicability: The trial included diverse CKD patients, not just those with diabetes.Strong Safety Signal: No excess noncardiovascular deaths—critical for chronic conditions requiring lifelong management.For clinicians, this reinforces SGLT2 inhibitors as a first-line therapy for CKD, regardless of diabetes status. The modest NNT (24 over 4 years) highlights its clinical meaningfulness in a high-risk population.

Metformin while not necessarily first line therapy for diabetes depending on the patients co-morbid conditions it is certainly highly ranked on the list of medications! I know often metformin is stopped while coming into the hospital for fear of potentially lactic acidosis or an increase in AKI with contrast studies however this ‘belief’ is largely based on myth and misconception. Metformin's contraindications should be contraindicated - PMC I also know that often metformin is held at discharge if the patients GFR is near or around 30 However, two new studies. Stopping Versus Continuing Metformin in Patients With Advanced CKD: A Nationwide Scottish Target Trial Emulation Study - ClinicalKey 4,278 Scottish residents with a diagnosis of type 2 diabetes were identified as prevalent metformin users with incident CKD stage 4. (it was stopped when they reached CKD 5) Results:Compared with continuing metformin, stopping metformin was associated with a lower 3-year survival (63.7% [95% CI, 60.9-66.6] vs 70.5% [95% CI, 68.0-73.0]; HR, 1.26 [95% CI, 1.10-1.44])    (THAT WOULD BE ROUGHLY A NNT OF 14) Interestingly the thing we think metformin prevents (MACE) was the same in both groups  (HR, 1.05 [95% CI, 0.88-1.26]). Could it be possible that metformin saves your life on some other mechanism that we don’t totally understand?? Discontinuing metformin was associated with a higher risk of death from respiratory diseases (HR, 1.51 [95% CI, 1.06-2.12]) MAYBE THAT IS THE SECRET!?  Trial 2Clinical outcomes following discontinuation of metformin in patients with type 2 diabetes and advanced chronic kidney disease in Hong Kong: a territory-wide, retrospective cohort and target trial emulation study - ScienceDirect 33,586 metformin users with new-onset eGFR < 30 ml/min/1.73 m2 were included in the study and 7500 (22.3%) of whom discontinued metformin within 6 months whereas 26,086 (77.7%) continued use of metformin. They were followed for a median duration of 3.8 (IQR: 2.2–6.1) years, This time, those in which metformin was discontinued had higher risk of MACE (weighted and adjusted HR = 1.40, 95% CI: 1.29–1.52),AND once again if you stopped the metformin you had a higher incidence of death  (HR = 1.22, 1.18–1.27). BUT get this, if you stopped the metformin you had higher rates of progression to END STAGE KIDNEY DISEASE (HR = 1.52, 1.42–1.62)!!!Yes, stopping metformin was associated with all the badness of the heart and kidneys  PS- no association observed for the risk of lactic acidosis (still) Obviously, these are both observational studies so there could be unaccounted for confounders that can only truly be ruled out with an RCT. Now that metformin is $4 a month at Walmart and the new fancy diabetic drugs are $20-$40 per day it is very unlikely we will see the proper drug company run trial anytime in the near future. However it does seem possible and even reasonable we continue metformin even at smaller doses (500mg daily or 500mg BID) may actually decrease the one thing we are all trying to fight against…..death

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2825813Conclusions and Relevance  In this randomized clinical trial assessing simultaneous vs sequential administration of mRNA COVID-19 and IIV4 vaccines, reactogenicity was comparable in both groups. These findings support the option of simultaneous administration of these vaccines.

https://www.bmj.com/content/388/bmj-2024-081164systematic review and meta-analysis on prehabilitation before surgery, published in the BMJ in February 2025.Prehabilitation aims to prepare patients for surgery through interventions like exercise, nutrition, and psychological support. This study looked at which prehabilitation components are most effective for improving key outcomes after surgery.The researchers analyzed 186 randomized trials with over 15,000 participants. They used advanced statistical methods to compare different prehabilitation approaches.The key findings were:Exercise-only prehabilitation reduced complications by about 50% compared to usual care.Nutritional prehabilitation alone reduced complications by about 38%.Combining exercise, nutrition, and psychosocial support reduced complications by about 36%.For hospital length of stay, exercise plus psychosocial support was most effective, reducing stays by about 2.5 days on average.Multicomponent prehabilitation including exercise, nutrition and psychosocial support was best for improving quality of life and physical recovery after surgery.When looking at individual components, exercise and nutrition consistently showed the most benefit across all outcomes.However, there are important limitations to consider. The overall certainty of evidence was low to very low for most comparisons. This was mainly due to potential bias in the original trials and imprecision in the results.So what does this mean for clinical practice? While not definitive, this study suggests that exercise and nutritional prehabilitation, either alone or as part of multicomponent programs, likely benefit surgical patients. Clinicians should consider incorporating these approaches when preparing patients for surgery.However, we still need large, high-quality trials to confirm these findings before making strong recommendations. Future research should focus on well-designed studies looking at the outcomes that matter most to patients and healthcare systems.In summary, this study provides promising evidence for prehabilitation, particularly exercise and nutrition-based approaches. 

Mammograms

379. REPORT mammogram part 1

https://jamanetwork.com/journals/jama/article-abstract/2828218DCIS is a non-invasive form of breast cancer, meaning the abnormal cells are contained within the milk ducts. For years, the standard treatment has been surgery, often followed by radiation and/or hormone therapy - the same treatments used for invasive breast cancer. But is this aggressive approach always necessary for low-risk DCIS?(Transition Music - Short and subtle - 2 seconds) Host: That's the question the COMET trial, or Comparing an Operation to Monitoring, With or Without Endocrine Therapy for Low-Risk DCIS, set out to answer. This large, randomized trial enrolled nearly 1000 women with newly diagnosed, low-risk DCIS across 100 centers in the US between 2017 and 2023. Participants were randomly assigned to either guideline-concordant care, meaning surgery with or without radiation, or active monitoring, involving regular check-ups with imaging and physical exams, reserving surgery only if the DCIS progressed to invasive cancer. The study focused on women who had hormone receptor-positive, grade 1 or 2 DCIS without evidence of invasive cancer.(Transition Music - Short and subtle - 2 seconds)  Host: The Major Finding: After a median follow-up of about 3 years, the study found that active monitoring was not inferior to surgery in terms of the rate of invasive cancer developing in the same breast. Specifically, the 2-year cumulative rate of ipsilateral invasive cancer was 4.2% in the active monitoring group and 5.9% in the guideline-concordant care group. This difference was statistically non-significant, meeting the pre-defined criteria for non-inferiority.(Transition Music - Short and subtle - 2 seconds) Host: This means that, at least in the short term, women with low-risk DCIS who chose active monitoring did not have a higher risk of developing invasive cancer compared to those who underwent surgery.(Transition Music - Short and subtle - 2 seconds  )Host: So, how should this change practice? For carefully selected women with low-risk DCIS, active monitoring could be a reasonable and safe alternative to immediate surgery. This approach could avoid the risks and side effects associated with surgery, radiation, and hormone therapy, such as pain, altered body image, and other long-term complications.(Transition Music - Short and subtle - 2 seconds) Host: Important Considerations: This study focused on low-risk DCIS. Active monitoring requires strict adherence to follow-up appointments and imaging. Further research is needed to determine the long-term outcomes of active monitoring and to identify which patients are most suitable for this approach. Patients considering active monitoring should have a thorough discussion with their healthcare provider to weigh the risks and benefits and make an informed decision.(Transition Music - Short and subtle - 2 seconds)

Association of Duration of Recognized Hypertension and Stroke Risk: The REGARDS Study   (Transition Music - Short and subtle - 2 seconds)Host:  Hypertension is a well-known risk factor for stroke, but this study, led by Dr. George Howard and colleagues, asks a fascinating question: Does the duration of hypertension matter, even when blood pressure is managed? (Transition Music - Short and subtle - 2 seconds)Host: The researchers used data from the REGARDS study, a large, long-term study looking at racial and geographic differences in stroke. They followed over 27,000 stroke-free participants for over 12 years, tracking who developed stroke and how long they had been diagnosed with hypertension. Participants were grouped by duration of hypertension: normotensive (no hypertension), 5 years or less, 6 to 20 years, and 21 years or more. (Transition Music - Short and subtle - 2 seconds)Host:  So, what did they find? Several key findings emerged. First, people with longer durations of hypertension were taking more antihypertensive medications, suggesting it becomes harder to manage blood pressure over time. Second, even with medication, their average systolic blood pressure (the top number) was higher. (Transition Music - Short and subtle - 2 seconds)  Host: Most importantly, the study found a clear association between the duration of hypertension and stroke risk. Compared to people with normal blood pressure, those with hypertension for 5 years or less had a 31% increased risk of stroke. That risk jumped to 50% for those with hypertension for 6 to 20 years, and a staggering 67% for those with hypertension for 21 years or more. These increased risks remained even after the researchers accounted for factors like age, race, sex, and other stroke risk factors.(Transition Music - Short and subtle - 2 seconds) Host: Key Takeaway: This study strongly suggests that the duration of hypertension significantly impacts stroke risk, independent of blood pressure levels at a single point in time.(Transition Music - Short and subtle - 2 seconds)  Host: What does this mean for you? It reinforces the importance of preventing or delaying the onset of hypertension in the first place. Early lifestyle interventions, such as diet and exercise, can play a crucial role. If you're already diagnosed with hypertension, work closely with your doctor to manage your blood pressure effectively and consider how long you've had the condition as part of your overall risk assessment. The longer you have hypertension, the more vigilant you may need to be.

Bloom CI et al. Association of dose of inhaled corticosteroids and frequency of adverse events. Am J Respir Crit Care Med 2025 Jan; 211:54. (https://doi.org/10.1164/rccm.202402-0368OC)  Bloom and colleagues' study, published in the American Journal of Respiratory and Critical Care Medicine in January 2025, provides significant insights into the safety profile of inhaled corticosteroids (ICS) for asthma patients7. The research, which analyzed data from two large UK databases, reveals important associations between ICS dosage and adverse events.  GINA GUIDELINES+ step 1 is ics formoterol OR low dose ICS--- as you move up ICS is always in the picture like a bad ex girlfriend in the family picture…. You can never just cut it out—sure you can go on photo shop and make em bigger or smaller like you can go with ICS but you cant cut them out. Key FindingsLow-dose ICS: No significant increase in adverse events7.Medium to high-dose ICS: Associated with increased risks of:Major adverse cardiovascular events (MACE)Cardiac arrhythmiaPulmonary embolism (PE)Hospitalization for pneumonia71Risk-Benefit Analysis:Absolute risk of adverse events was lowNumber needed to harm (NNH) for 12 months of ICS use:Medium dose (201-599 mcg): MACE (473), arrhythmia (567), PE (1221), pneumonia (230)High dose (≥600 mcg): MACE (224), arrhythmia (396), PE (577), pneumonia (93)3Time-dependent risks:Highest risk observed at 12 monthsMACE risks increased in the first 60 days but returned to baseline after ICS cessation1Implications for Asthma ManagementGuideline adherence: Use the lowest effective ICS dose37.Risk assessment: Consider patient-specific factors when prescribing medium to high-dose ICS.Monitoring: Increased vigilance for potential adverse events in patients on higher ICS doses.Step-down approach: Consider dose reduction once asthma is well-controlled1.Alternative strategies: Explore options like low-dose ICS/formoterol for maintenance and relief, or biologics for frequent exacerbators1.This study underscores the importance of balancing asthma control with potential risks of higher ICS doses. While ICS remain a cornerstone of asthma treatment, clinicians should aim for the lowest effective dose and regularly reassess the need for high-dose therapy.

Gao FM et al. A systematic review and meta-analysis on the safety and efficacy of sodium–glucose cotransporter 2 inhibitor use in hospitalized patients. Diabetes Care 2024 Dec 1; 47:2275. (https://doi.org/10.2337/dc24-0946) Trial ResultsSGLT-2 inhibitors, crucial in managing diabetes, kidney disease, and heart failure, have shown promising results in hospitalized patients1. The meta-analysis, covering 23 randomized controlled trials with 20,000 participants, revealed:No significant increase in ketoacidosis rates (0.21 vs. 0.14 per 100 person-years)1Lower mortality and fewer readmissions in heart failure patients1Reduced incidence of acute kidney injury overall1These findings suggest that SGLT-2 inhibitors can be safely continued or initiated in hospitalized patients, particularly those with heart failure1.LimitationsHowever, it's important to note some limitations:Potential underpowering: The study might not have had enough statistical power to detect small differences in ketoacidosis rates1.Risk underestimation: Including outpatient follow-up periods may have diluted the true risk of ketoacidosis during hospitalization1.Patient diversity: Only 30% of participants had diabetes, which might not fully represent the typical hospital population1.ConclusionWhile the results are encouraging, caution is still advised. The study supports current recommendations for SGLT-2 inhibitor use in hospitalized patients, especially those with heart failure, but emphasizes the need for careful monitoring and individualized decision-making1.This concludes our brief podcast on SGLT-2 inhibitors in hospitalized patients. Thank you for listening, and stay tuned for more updates on diabetes care and management.

Is accelerated surgery for hip fracture better for high-risk patients? A recent substudy of the HIP ATTACK trial has shed new light on this topic. The original trial, published in 2020, compared accelerated surgery (within 6 hours) to standard-timing surgery (within 24 hours) for hip fracture patients. While the initial results showed only marginal benefits, this new analysis focuses on a specific group: patients with elevated cardiac troponin levels at hospital arrival--- THE SICK GUYS7.Here's what the researchers found:For patients with elevated troponin levels - about a quarter of those tested - accelerated surgery was associated with significantly lower mortality. The numbers are striking: 10% mortality in the accelerated surgery group compared to 23% in the standard surgery group. This translates to a number needed to treat of just 87.Interestingly, for patients with normal troponin levels, there was no significant difference in mortality between the two surgical approaches7.These findings suggest that for high-risk patients - those with elevated troponin levels - immediate surgery without further work-up or delay could lead to better outcomes. It's a paradigm shift in how we approach these cases .However, it's important to note that we're still awaiting results from the HIP ATTACK-2 study, which will provide more definitive evidence on whether accelerated surgery is superior to standard timing in these patients7.In conclusion, this study highlights the potential benefits of tailoring surgical timing to individual patient risk factors. For those with elevated troponin levels, rapid intervention could be life-saving.   Borges FK et al. Myocardial injury in patients with hip fracture: A HIP ATTACK randomized trial substudy. J Bone Joint Surg Am 2024 Dec 18; 106:2303. (https://doi.org/10.2106/JBJS.23.01459)Cornell C. Patients presenting with acute myocardial injury with hip fracture have greater survival with rapid surgical care. J Bone Joint Surg Am 2024 Dec 18; 106:e50. (https://doi.org/10.2106/JBJS.24.00583)

Today, we're discussing two groundbreaking studies from 2024 that challenge our understanding of β-blocker therapy for secondary prevention after myocardial infarction, or MI.Let's start with a Swedish study Beta-Blockers after Myocardial Infarction and Preserved Ejection Fraction | New England Journal of Medicine that included over 5,000 patients with normal left ventricular ejection fraction after an MI5. The researchers compared long-term beta-blocker therapy with no beta-blocker treatment. Surprisingly, after 3.5 years, there was no significant difference in the primary endpoint of all-cause death or recurrent MI between the two groups5. This suggests that for patients with preserved heart function after an MI, long-term beta-blocker use may not provide additional benefits.  Now, let's turn to a French study involving 3,700 patients who were already on β-blockers following an MI Beta-Blocker Interruption or Continuation after Myocardial Infarction | New England Journal of Medicine7. This trial compared continuing β-blocker therapy to stopping it. After three years, the results showed a slightly higher incidence of adverse events in the group that stopped β-blockers, primarily due to more hospitalizations for cardiovascular reasons7.What do these studies tell us? Well, they suggest that the benefits of β-blockers might be more modest in our current era of advanced revascularization techniques and modern medical therapies for post-MI patients8. However, it's crucial to note that the Swedish study focused on low-risk patients with normal heart function and they say well there was a lower event rate than expected!!! That is EXPECTED WHEN THE OTHER MEDICATIONS WORK!!! ,8.It's important to remember that these findings don't necessarily apply to all post-MI patients. Those with reduced heart function or other specific indications may still benefit significantly from β-blocker therapy7.In conclusion, while these studies provide valuable insights, there are other trials currently being done to help us better answer this question of what to do with the betablocker post mi

Methods Monday  --- Accuracy of Event Rate and Effect Size Estimation in Major Cardiovascular Trials: A Systematic Review | Cardiology | JAMA Network Open | JAMA Network  During the design of a randomized clinical trial (RCT), estimation of the expected event rate and effect size is a key component to calculating the sample size. Overly optimistic estimation of event rates and effect sizes may lead to underpowered trials. If you expect 1 event per 100 people and you are looking for 5 events then you only need to enroll….. 500 people but if the actual event rate is 1 per 200 people then in order to get 5 events you need to enroll 1000 people!! You can see enrolling 500 people instead of 1000 would underpower your trial  This article, published in JAMA Network Open in April 2024, presents a systematic review of 344 contemporary cardiovascular randomized clinical trials (RCTs) to evaluate the accuracy of estimated event rates and effect sizes1. The key findings are:Event rates were frequently overestimated:Median observed event rate: 9.0% (IQR, 4.3%-21.4%)Median estimated event rate: 11.0% (IQR, 6.0%-25.0%)61.1% of trials overestimated the event rate1Effect sizes were often overestimated:Median observed effect size: 0.91 (IQR, 0.74-0.99)Median estimated effect size: 0.72 (IQR, 0.60-0.80)82.1% of trials overestimated the effect sizeThe drug companies think their drug is way better than it is or observed to be in trials1Device trials were independently associated with decreased accuracy of event rate estimation compared to drug trials1.The study concludes that the frequent overestimation of event rates and effect sizes in cardiovascular RCTs may contribute to underpowered trials and the inability to adequately test trial hypotheses1. This finding has implications for trial design—if we are not accurate or realistic about the interventions we are likely to underpower the study which means you have to do the whole thing all over again or likely all over again and risk FDA rejecting you drug.

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2821168A team of researchers set out to change that by developing a comprehensive algorithm.The process involved a multidisciplinary panel of 11 expertss with extensive experience in managing urinary retention. These experts evaluated about 100 clinical scenarios to create an initial flow sheet. The algorithm was then refined through interviews with 33 frontline clinicians from various specialties.So, what does this new algorithm recommend? Let's break it down:First, bladder scanning is the preferred method for evaluating patients with urinary retention symptoms. It's also recommended for asymptomatic patients who haven't voided in 3 hours.If a bladder scanner isn't available, the algorithm suggests using either an intermittent straight catheter (ISC) or an indwelling urinary catheter (IUC), with a preference for ISC initially.Now, let's talk about when to catheterize based on bladder scanner volumes. For symptomatic patients, catheterization is recommended when the volume is 300 mL or more. For asymptomatic patients, the threshold is higher at 500 mL or more.Lastly, the algorithm provides guidance on when to transition from intermittent to indwelling catheterization. If a patient needs an ISC more frequently than every 4 hours, or if their output is 500 mL or more every 4 hours, it's appropriate to switch to an IUC

https://jamanetwork.com/journals/jama/article-abstract/2822097Design, Setting, and Participants  Nested case-control study using population-based linked administrative datasets among adults aged 66 years or older who received at least 1 oral antibiotic between 2002 and 2022 in Ontario, Canada. Cases were those who had an emergency department (ED) visit or hospitalization for serious cADRs within 60 days of the prescription, and each case was matched with up to 4 controls who did not.Exposure  Various classes of oral antibiotics.Main Outcomes and Measures  Conditional logistic regression estimate of the association between different classes of oral antibiotics and serious cADRs, using macrolides as the reference group.Results  During the 20-year study period, we identified 21 758 older adults (median age, 75 years; 64.1% female) who had an ED visit or hospitalization for serious cADRs following antibiotic therapy and 87 025 matched controls who did not. In the primary analysis, sulfonamide antibiotics (adjusted odds ratio [aOR], 2.9; 95% CI, 2.7-3.1) and cephalosporins (aOR, 2.6; 95% CI, 2.5-2.8) were most strongly associated with serious cADRs relative to macrolides. Additional associations were evident with nitrofurantoin (aOR, 2.2; 95% CI, 2.1-2.4), penicillins (aOR, 1.4; 95% CI, 1.3-1.5), and fluoroquinolones (aOR, 1.3; 95% CI, 1.2-1.4). The crude rate of ED visits or hospitalization for cADRs was highest for cephalosporins (4.92 per 1000 prescriptions; 95% CI, 4.86-4.99) and sulfonamide antibiotics (3.22 per 1000 prescriptions; 95% CI, 3.15-3.28). Among the 2852 case patients hospitalized for cADRs, the median length of stay was 6 days (IQR, 3-13 days), 9.6% required transfer to a critical care unit, and 5.3% died in the hospital.Conclusion and Relevance  Commonly prescribed oral antibiotics are associated with an increased risk of serious cADRs compared with macrolides, with sulfonamides and cephalosporins carrying the highest risk. Prescribers should preferentially use lower-risk antibiotics when clinically appropriate.

https://www.nejm.org/doi/full/10.1056/NEJMoa2407001ConclusionsNo participants receiving twice-yearly lenacapavir acquired HIV infection. HIV incidence with lenacapavir was significantly lower than background HIV incidence and HIV incidence with F/TDF. Among 5338 participants who were initially HIV-negative, 55 incident HIV infections were observed: 0 infections among 2134 participants in the lenacapavir group (0 per 100 person-years; 95% confidence interval [CI], 0.00 to 0.19), 39 infections among 2136 participants in the F/TAF group (2.02 per 100 person-years; 95% CI, 1.44 to 2.76), and 16 infections among 1068 participants in the F/TDF group (1.69 per 100 person-years; 95% CI, 0.96 to 2.74)

Allaudeen N et al. Medications for alcohol-use disorder and follow-up after hospitalization for alcohol withdrawal: A multicenter study. J Hosp Med 2024 Dec; 19:1122. (https://doi.org/10.1002/jhm.13458)   Hospital admission for alcohol withdrawal is a problem when it comes to readmission. They just come back--- In this retrospective study of ≈600 patients (96% men) admitted for alcohol withdrawal at 19 Veterans Affairs hospitals during 1 year (2018–2019), researchers evaluated prescription rates of medications for alcohol use disorder (AUD; e.g., naltrexone, acamprosate, disulfiram, gabapentin, topiramate) and scheduled follow-up appointments.The objective of this study was to evaluate the effects of medications for AUD and follow-up appointments on readmission and abstinence.Neither prescription of AUD agents (to 51% of patients) at hospital discharge nor scheduled follow-up appointments at discharge were associated with 30-day readmissions or 6-month alcohol abstinence.Only direct discharge to residential AUD treatment programs was associated significantly with fewer readmissions (odds ratio, 0.4) and alcohol abstinence (OR, 2.5). Additionally, being discharged with a primary care appointment and actually attending the appointment was associated with fewer hospital readmissions (OR, 0.3).

Real‐world use of glucocorticoids and clinical outcomes in adults hospitalized with community‐acquired pneumonia on medical wards - Malecki - 2024 - Journal of Hospital Medicine - Wiley Online Library This was a retrospective cohort study of 11,500 patients with CAP who were admitted to general medicine units in 7 Canadian hospitals, researchers compared outcomes for patients who received systemic corticosteroids. Patients were excluded if they were admitted to the intensive care units or had COPD or COVID-19 infection. Between those that got steroids and those that didn’t get steroids there was no differences in intensive care admissions, hospital length of stay, or 30-day readmissions. HOWEVER, In an adjusted analysis, patients who received systemic corticosteroids were significantly more likely to die in the hospital than were patients who didn't receive steroids (8.0% vs. 6.3%; P=0.03).  LET’S BE CLEAR THIS IS FOR NON-SEVERE PNA!! If you have severe pna and are going to the ICU then the evidence and guidelines clearly indicate steroids are appropriate. Critical Care Medicine (lww.com) 

2024 ESC guidelines propose a simple new BP categorization:Non-elevated: less than 120/70 mm Hg in the office (pharmacological treatment is not recommended).Elevated: 120 to 139/70 to 89 mm Hg (pharmacological treatment is recommended for some, depending on cardiovascular disease [CVD] risk and follow-up BP measurements).Hypertension: 140/90 mm Hg or greater (confirmation and prompt pharmacological treatment is recommended).    lifestyle interventions are particularly critical for individuals with an elevated BP but a low predicted risk of CVD. Adults in this group are common and account for up to one-third of all CVD events,  2024 ESC Guidelines provide two major new lifestyle approaches for managing elevated BP and hypertension.  first new option is potassium supplementation, either by dietary supplementation or potassium-enriched salt substitutes. The mechanistic and observational data supporting the benefits of potassium supplementation on BP are not new. However, recent CVD outcomes trials demonstrate the benefits of potassium supplementation where clinically appropriate.  Potassium-enriched salts typically contain 75% sodium chloride and 25% potassium chloride, while dietary potassium sources include foods such as bananas (450 mg per medium-sized banana), unsalted boiled spinach (840 mg per cup), and mashed avocado (710 mg per cup)  The second new option is to increasingly understand the BP-lowering benefits of resistance exercise training.4 Not everyone can perform the aerobic exercises traditionally recommended in BP management guidelines, and resistance exercise offers an important alternative for both clinicians and patients.  ANY EXERCISE 

Question  Does adding centralized mailed fecal immunochemical testing and patient navigation to usual care improve colorectal cancer (CRC) screening in US federally qualified health centers? pragmatic randomized clinical trial was conducted Patients were enrolled and randomly assigned to usual care alone (control group) or intervention (2,001 participants per group). Intervention participants received mailed screening outreach materials including an introductory letter, FIT kit packet with instructions and return postage, and two reminder letters if necessary, in addition to usual care. Navigation to facilitate follow-up colonoscopy was offered to intervention participants with positive results of mailed FIT. The researchers found that intervention participants were THREE TIMES more likely than controls to complete screening within six months of randomization (30.0 versus 9.7 percent). Overall, positive FIT results in the intervention arm completed follow-up colonoscopy within six months more often than those in the control arm. This means more colonoscopies which SHOULD mean more cancer Advanced colorectal neoplasia defined as advanced adenoma or CRC.was detected in 1.4 and 0.7 percent of intervention and control participants, respectively. Make it easy for people—we are in an era of EASY. Lets make medicine easy

Packer M et al. Tirzepatide for heart failure with preserved ejection fraction and obesity. N Engl J Med 2024 Nov 16; [e-pub].https://doi.org/10.1056/NEJMoa2410027  In the industry-funded SUMMIT trial (NCT04847557), investigators examined cardiovascular outcomes of tirzepatide — an agonist of glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptors — over a longer period in patients with HFpEF and obesity.  The 731 study participants had elevated filling pressures or an elevated N-terminal pro–B-type natriuretic peptide (NT-proBNP) level, and a heart failure exacerbation event within the prior 12 months or a decreased estimated glomerular filtration rate <70 mL/min/1.73 m2. They were randomized to once-weekly subcutaneous tirzepatide (up to 15 mg) or placebo for at least 52 weeks with a median follow-up of 104 weeks.Compared with placebo, tirzepatide resulted in significantly fewer primary-endpoint events (adjudicated heart-failure worsening or cardiovascular death) — 10% vs. 15% (hazard ratio, 0.62) — HOWEVER--Death from any cause WAS NO DIFFERENT! (hazard ratio, 1.25; 95% CI, 0.63 to 2.45) (Table 2 and Fig. S4). ALSO-- Adjudicated worsening heart-failure event resulting in hospitalization, intravenous drugs in an urgent care setting, or intensification of oral diuretic therapy is great but not what we care about If I just have to increase your oral meds is that really worsening heart failure or you just eating too much on thanksgiving day??? What do we care about here— Hospitalizations—and worsening heart-failure event resulting in hospitalization —was 3.3% in tirzepitide and 7.1% in the control group. Which is a difference of 4 percent and a NNT of 25 to prevent hospitalizatoins  The other primary endpoint was…Kansas city cardio questionnaireand significantly greater improvement (by approximately 7 points) in the Kansas City Cardiovascular Questionnaire clinical summary score (assessed at 52 weeks).  Interpreting the Kansas City Cardiomyopathy Questionnaire in Clinical Trials and Clinical Care: JACC State-of-the-Art Review | Journal of the American College of Cardiology   As will be developed further, a change of 5 points is considered to be a small but clinically important change, whereas changes of 10 and 20 points are considered moderate-to-large and large-to-very large clinical changes.  On good RX – a two year script of terzep 15mg that was used in this study would cost around – 24,000 or roughly 1000$ per month. That means we have to spend 2.4 million dollars to prevent 4 hospitalistzations from heart failure at 2 yrs!

Wang Z et al. Safety of triptans in patients who have or are at high risk for cardiovascular disease: A target trial emulation. Mayo Clin Proc 2024 Nov; 99:1722. (https://doi.org/10.1016/j.mayocp.2024.03.023) How unsafe are triptans triptans — the mainstays of migraine therapy — are vasoactive, the U.S. FDA considers them to be contraindicated in patients with cardiovascular (CV) disease or elevated CV risk.  many patients with migraine (including those with CV disease) request triptans because they work how bad are they??Within 60 days of starting treatment, 52 patients who received triptans and 13 who received nontriptans experienced major adverse CV events — a significant difference (1.5% vs. 0.4%; relative risk, 4.0).  Compared with nontriptans, triptans are associated with elevated risk for major adverse CV events in patients with migraine and established CV disease or elevated CV risk; however, the absolute risk difference in this study was small (1.1%). 

STROKE part 3 CME

CME FOR FREEE 

CME --- Stroke- UIA, CHAD-VASC, HAS-BLED, SPARC, PFO

Beran A et al. Early diagnostic paracentesis improves outcomes of hospitalized patients with cirrhosis and ascites: A systematic review and meta-analysis. Am J Gastroenterol 2024 Nov; 119:2259. (https://doi.org/10.14309/ajg.0000000000002906) BOTTOM LINE (if you don’t like to read)- While it might not be fun to have the conversation with the ER provider saying you NEED A DIAGNOSTIC PARACENTESIS PRIOR TO THE PATIENT COMING TO THE FLOOR, just remember that every 33 times we have that conversation, we are saving a life and decreasing the length of stay by 5 days on average.  We have all had the admission from the ER on a patient that needs a paracentesis but it is the weekend so they are going to just admit for antibiotics and then IR can come do it on Monday.  Guidelines recommend diagnostic paracentesis in all patients hospitalized with cirrhosis and ascites, but they do not recommend specific timing of inpatient paracentesis. (Biggins SW et al. Diagnosis, evaluation, and management of ascites, spontaneous bacterial peritonitis and hepatorenal syndrome: 2021 practice guidance by the American Association for the Study of Liver Diseases. Hepatology 2021 Aug; 74:1014. BUT NOW we have a meta-analysis of 7 observational studies (>78,000 patients), patients who underwent diagnostic paracentesis within 12 to 24 hours after admission had significantly better outcomes compared with patients who had more-delayed or no paracentesis! Those that underwent diagnostic paracentesis within 12 to 24 hours after admission had significantly lower rates of acute kidney injury (24% vs. 35%. NNT 9). They had shorter hospital LOS (5 fewer days!), and lower in-hospital mortality (7% vs 10% NNT 33). When you looked at the subgroup of patients that underwent paracentesis within 12 hours of admission —in-hospital mortality also was significantly lower with paracentesis within 12 hours versus later paracentesis (12% vs. 26% NNT 7). 

Acupuncture vs Sham Acupuncture for Chronic Sciatica From Herniated Disk: A Randomized Clinical Trial | Complementary and Alternative Medicine | JAMA Internal Medicine | JAMA Network  In a randomized trial, acupuncture reduced pain and disability better than a sham procedure did.  In this trial from China, 216 adults (mean age, 51) were randomized to undergo 10 sessions of acupuncture or sham procedures during 4 weeks. All patients had moderate-to-severe unilateral leg pain attributed to imaging-confirmed disk herniation; mean duration of symptoms was 3 years (range, 1.3–10 years). Patients taking pain-modifying medications or with prior lumbar disk surgery were excluded.   The sham procedure consisted of blunt needles inserted into adhesive foam pads placed over non-acupoints. Patients who received acupuncture reported greater leg-pain relief at 4 weeks than did patients who received sham procedures (mean decrease on a 0–100-mm visual analog scale, 31 vs. 15 mm),    Improvements in pain and disability scores from baseline began persisted to 1 year.   At first I thought WHOA this is amazing- We do 10 sessions and you are better 1 yr later! Seems to good to be true and like free money, it probably is

And now a secondary analysis of the trial focused on the timing of major ischemic events and the potential tradeoffs of benefits and risks,------ maybe there is magic sauce where the benefit is drastically greater than risk and vice versa! Guan L et al. Duration of benefit and risk of dual antiplatelet therapy up to 72 hours after mild ischemic stroke and transient ischemic attack. Neurology 2024 Oct 8; 103:e209845. (https://doi.org/10.1212/WNL.0000000000209845)  The goal is less ischemic events with the DAPT but there is a risk of more bleeding and maybe if we tease out the data we can find the exact right time—not too much, not too little but just right.  They found the benefit of decrease ischemic stroke was front-loaded, with roughly a 1.5% absolute risk reduction (ARR) for major ischemic events in the first week, a 0.5% ARR in the second week, and a nonsignificant 0.29% ARR in the third week. The bleeding risk was constant right around ARR 0.1% Thus three weeks remains reasonable to rec DAPT—remember at three weeks the decrease ischemic event rate in absolute terms was 0.3 and the bleeding risk was around 0.1……. the real magic does appear to be in the first week when the risk of repeart event is around 1.5%

The full podcast -- not sure why the last one cut off early. Question and answer from ACOI

Liu H et al. Arm position and blood pressure readings: The ARMS crossover randomized clinical trial. JAMA Intern Med 2024 Oct 7; [e-pub]. (https://doi.org/10.1001/jamainternmed.2024.5213)   study replicated some of the “real-world” shortcuts that often occur when we check BP, such as measuring BP while the patient is sitting up on an exam table.===In this U.S. trial of 133 adults, researchers assessed the effect of nonstandard arm positions on BP readings by measuring each patient's BP in three different arm positions (order of measurement was determined by a randomization protocol):arm supported on a desk, with cuff at heart level (reference position)hand supported in the laparm unsupported at the sideInvestigators otherwise followed standard guidance for office BP measurements.  Lap and side positions led to significantly higher readings (by 4 mm Hg to 6 mm Hg for both systolic and diastolic measurements) than did the desk position.     

Stopping Trials Early for Benefit: Insights From Recent Pivotal Trials in Chronic Kidney Disease - ScienceDirect   There are 4 major reasons why trials might be stopped early: 1) unequivocal benefit; 2) unacceptable harm; 3) futility; and 4) administrative reasons (enrollment or funding concerns).   trials stopped early for benefit tend to overestimate benefit, a phenomenon referred to as random-high.  trials that stopped early, especially those with <500 events, fail to provide reliable and valid estimates of treatment effect, often overestimating it by nearly 30% Trials stopped early for harm or futility are less problematic as such data are not used to promote medications. Published results were based on accrual of 69%, 75%, 93%, and 87% of planned events in CREDENCE, DAPA-CKD, EMPA-KIDNEY, and FLOW, respectively.

You get the CME knowledge without the CME payment!

 10% of hospitalized patients have penicillin allergy listed in their records, fewer than 1% of patients have true allergies. Use of more-expensive and broader-spectrum antibiotics is associated with longer and more-expensive hospital stays and more side effects, nosocomial infections, and resistant organisms.  Blumenthal KG et al. Reaction risk to direct penicillin challenges: A systematic review and meta-analysis. JAMA Intern Med 2024 Sep 16; [e-pub]. (https://doi.org/10.1001/jamainternmed.2024.4606)   researchers examined the safety of direct penicillin challenges (without preceding skin tests) for delabeling patients without true allergies. Among more than 9000 patients in these studies, 438 experienced reactions (3.5%), with only 5 reactions classified as severe: 3 episodes of anaphylaxis, 1 delayed rash with fever, and 1 kidney injury. No fatalities were reported.NNH of 1800  The PENFAST score is a good tool to help decide which patients can undergo direct oral challenge safely (NEJM JW Gen Med Aug 1 2023 and JAMA Intern Med 2023; 183:883). In general, if a patient has a history of severe immediate reaction (angioedema or anaphylaxis), a recent urticarial reaction (within 5 years), or any severe delayed reaction (e.g., Stevens–Johnson syndrome, serum sickness, drug reaction with eosinophilia, drug-induced cytopenia, organ injury), I would refer to an allergist for evaluation. Bottom line We have far more patients who should have their penicillin allergy delabeled than we have allergists to perform these challenges. Primary care clinicians and hospitalists can do this easily by giving one dose of amoxicillin (500 mg) and watching the patient for 1 to 2 hours; intramuscular epinephrine and oral antihistamines must be available, but are seldom needed.  

Efficacy and Safety of a Novel Low-Dose Triple Single-Pill Combination Compared With Placebo for Initial Treatment of HypertensionJ Am Coll Cardiol 2024 Aug 30;[EPub Ahead of Print], A Rodgers, A Salam, AE Schutte, WC Cushman, HA de Silva, GL Di Tanna, D Grobbee, K Narkiewicz, DB Ojji, NR Poulter, MP Schlaich, S Oparil, W Spiering, B Williams, JT Wright, A Gutierez, A Sanni, P Lakshman, D McMullen, G Ranasinghe, C Gianacas, M Shanthakumar, X Liu, N Wang, P Whelton    randomized, double-blind, placebo-controlled trial of a new single-pill combination comprising low doses of telmisartan, amlodipine, and indapamide for treating hypertension in 295 adults with mild to moderate hypertension. baseline systolic BP of 130 to 154 mm Hg during a placebo run-in, and had a low estimated 10-year risk for cardiovascular disease (<10%). The primary efficacy outcome was difference in change in home SBP from randomization to week 4  patients were randomized in a double-blind manner into three different arms: GMRx2 at a quarter dose, GMRx2 at a half dose, or placebo. After 4 weeks, the authors reported a placebo-corrected reduction in clinic BP measurements of 8.0/4.0 mm Hg in the GMRx2 quarter-dose arm and 9.5/4.9 mm Hg in the GMRx2 half-dose arm.  The results stateBoth quarter- and half-dose combinations significantly reduced home and clinic systolic blood pressure (BP) measurements compared with placebo. The reductions in home systolic BP were 7.3 mm Hg and 8.2 mm Hg for quarter- and half-dose combinations, respectively.  good2024 European Society of Cardiology guidelines for the management of elevated BP and hypertension BadWHY use PLACEBO RANT!! YOU wouldn’t give to your motherUse a standard of care!! You have a new med you want to sell for millinos and billions prove it beats the current standardAnd only a 4 week study—sure you are proving just proof of lowering bp so I am ok with a short term but maybe you get the most benefit at 4 weeksna and regress to the mean after 12 weeks or 6 months    

In 2011, the Endocrine Society published a guideline on “Evaluation, Treatment, and Prevention of Vitamin D Deficiency”   Now, the Society has issued an updated guideline, Demay MB et al. Vitamin D for the prevention of disease: An Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2024 Aug; 109:1907. (https://doi.org/10.1210/clinem/dgae290)  Previously, the Endocrine Society had labeled vitamin D status as “deficient” when serum hydroxyvitamin D (25[OH]D) was lower than 20 ng/mL, and “insufficient” when serum 25(OH)D was 20 ng/mL to 29 ng/mL. Now, the Society “no longer endorses specific 25(OH)D levels to define vitamin D sufficiency, insufficiency, and deficiency.”  Why is that--- because no clinical research has not established distinct thresholds of serum levels that can be tied confidently to specific clinical outcomes. In the general population of adults (age range, 19–74), neither routine vitamin D supplementation nor routine testing of 25(OH)D levels are recommended. What about >75—NOT RECOMMENDED!  They do suggest vit sup for possible to lower mortality but acknowledge that this effect was small and bordline statistical significance ___ relative risk, 0.96; 95% confidence interval, 0.93–1.00 – to it hit the line of no effect on flawed bias studies! Come on!!!!!An evidence review showed no conclusive evidence that supplementation lowered risks for fractures, falls, or infections in this age group The common practice of ordering routine 25(OH)D levels is not recommended,. Obtaining serum 25(OH)D levels in relatively healthy people and prescribing vitamin D supplements to get levels ≥30 ng/mL (or even higher) is not supported by this guideline. FINALLY—you want to give then go ahead and give a reasonable amount but don’t test. Don’t research. Don’t target a level. JUST DONT

Huijberts I et al. Collateral-based selection for endovascular treatment of acute ischaemic stroke in the late window (MR CLEAN-LATE): 2-year follow-up of a phase 3, multicentre, open-label, randomised controlled trial in the Netherlands. Lancet Neurol 2024 Sep; 23:893. (https://doi.org/10.1016/S1474-4422(24)00228-X)    The modified Rankin Scale (mRS) score at 2 years was the primary outcome. The median mRS at 2 years was 4 in the EVT group and 6 in the control group. For functional independence (mRS, 0–2), the rates were 35% in the EVT patients and 27% in the control group. Mortality at 2 years did not differ between the treatment groups.   However, about 12 patients need to be treated to provide one additional patient with functional independence, a higher number needed to treat than observed in studies of EVT provided in the early time window (e.g., N Engl J Med 2015; 372:2285) Still 24 hours AFTER a stroke!! amazing

 Because glucagon-like peptide-1 (GLP-1) receptor agonists can slow gastric emptying, they might confer risk for residual gastric contents — and possibly aspiration!!!! Should we stop the glp-1 Should we stop the glp-1-- Anesthesiologists and gastroenterologists have weighed in on this concern and on QM I say just do whatever the anesthesiologist want because they have the final say!!  Sen S et al. Glucagon-like peptide-1 receptor agonist use and residual gastric content before anesthesia. JAMA Surg 2024 Jun; 159:660. per American Society of Anesthesiologists [ASA] guidelines; Prior to surgery, patients had fasted at least 2 hours for clear liquids, 6 hours for light meals, and 8 hours for full meals   researchers performed gastric ultrasound just prior to elective surgery in 62 patients who were using weekly injected GLP-1 agonists (semaglutide, dulaglutide, or tirzepatide) and in 62 nonusers (controls).  The prevalence of residual gastric contents was significantly higher in the GLP-1 group than in the control group (56% vs. 19%). After adjustment for confounders, GLP-1 users remained significantly more likely than controls to have residual gastric contents. Sen S et al. Glucagon-like peptide-1 receptor agonist use and residual gastric content before anesthesia. JAMA Surg 2024 Jun; 159:660.     We still don't know the overall clinical consequences of residual gastric contents in GLP-1 users who undergo elective surgery under anesthesia. For now, clinicians who provide preoperative consultation should try to find out policies of local anesthesiology groups. 

Oropharyngeal dysphagia is highly prevalent in hospitalized patients with Alzheimer disease or other dementias. These patients often are prescribed thick liquid diets Makhnevich A et al. Thick liquids and clinical outcomes in hospitalized patients with Alzheimer disease and related dementias and dysphagia. JAMA Intern Med 2024 May 6; [e-pub]. Researchers conducted a retrospective propensity-matched analysis, ≈4500 patients with Alzheimer disease or other dementias who were hospitalized with clinical concern for dysphagia and received thick liquid diets and matched to ≈4500 patients who had received thin liquid diets.  Hospital mortality was similar in the two groups. Compared with patients who received thin liquids, those who received thick liquids were significantly less likely to be intubated (odds ratio, 0.7) but were significantly more likely to have respiratory complications, including pneumonia (OR, 1.7) In this end you are preventing intubation by 30 percent but causing pna by 70% --- neither are good and neither is a clear winner Rant on ‘what we know to be true’ and measure it This large study supports a hypothesis that thick liquids minimize the volume of aspiration, which explains the decrease in intubations. However, thick liquids also are more difficult to clear from the airway when aspiration occurs, leading to more respiratory complications.