Questioning Medicine

https://www.nejm.org/doi/full/10.1056/NEJMoa2516491https://www.ahajournals.org/doi/10.1161/CIR.0000000000001466

Silvain J, et al. Discontinuation of β-blockers in stable patients with previous myocardial infarction, preserved left ventricular ejection fraction, and no heart failure: A pooled analysis of individual patient data. Lancet 2026 Aug 30; [e-pub]. DOI: 10.1016/S0140-6736(26)01426-1. PubMed https://jamanetwork.com/journals/jama/fullarticle/2854257 https://research.ebsco.com/c/536ryc/viewer/pdf/yggxxbydhz https://www.nejm.org/doi/full/10.1056/NEJMoa2601598?query=clinical-medicine Jover R, et al. Colonoscopy intervals and colorectal cancer incidence after adenoma removal. N Engl J Med 2026 Sep 17; 395:1051. DOI: 10.1056/NEJMoa2603816. PubMed https://www.nejm.org/doi/full/10.1056/NEJMoa2607978?query=clinical-medicine

we unpack whether rivaroxaban followed by aspirin improves thromboprophylaxis after hip and knee arthroplasty, put oral GLP-1 therapy orforglipron head-to-head with dapagliflozin for type 2 diabetes, and examine new evidence on venous thromboembolism after mechanical restraint in psychiatric hospitals. We also translate updated pediatric functional-constipation guidance, the newest ACG recommendations for colonic diverticulitis, and real-world data on blood-pressure control and mortality among U.S. veterans—then finish with a practical look at whether a lumbar belt can truly ease nonspecific low-back pain.Shivakumar S, et al. Rivaroxaban then aspirin vs. aspirin alone after total hip or knee arthroplasty. N Engl J Med 2026 Jul 12; [e-pub]. DOI: 10.1056/NEJMoa2603649. PubMed https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(26)00800-7/abstract https://pubmed.ncbi.nlm.nih.gov/42393373/ Welch M, et al. Orforglipron compared with dapagliflozin in adults with type 2 diabetes and inadequate glycaemic control with metformin (ACHIEVE-2): A multicentre, randomised, non-inferiority, open-label, phase 3 trial. Lancet 2026 Jul 11; 408:125. DOI: 10.1016/S0140-6736(26)00800-7. PubMed Viuff JH, et al. Venous thromboembolism after mechanical restraint in psychiatric hospitals: Population based cohort and self-controlled case series study. BMJ 2026 Jul 1; 394:e100016. DOI: 10.1136/bmj-2026-100016. PubMed Gordon M, et al. European Society for Paediatric Gastroenterology, Hepatology and Nutrition/North American Society for Pediatric Gastroenterology, Hepatology and Nutrition guidelines for treatment of functional constipation in children aged 0–18 years. J Pediatr Gastroenterol Nutr 2026 May 20; [e-pub]. DOI: 10.1002/jpn3.70447. PubMed Peery AF, et al. ACG clinical guideline: Colonic diverticulitis. Am J Gastroenterol 2026 Jul; 121:1549. DOI: 10.14309/ajg.0000000000004047. Yamada M, et al. Blood pressure control and mortality among US veterans. Hypertension 2026 Apr 7; [e-pub]. DOI: 10.1161/HYPERTENSIONAHA.125.25787. Grange L, et al. Lumbar belt for nonspecific low back pain: A randomized clinical trial. JAMA Netw Open 2026 Aug 3; 9:e2629793. DOI: 10.1001/jamanetworkopen.2026.29793. PubMed

OMED lecture on how to understand medical stats

OMED lecture

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://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

432. CME LECTURE- Under Pressure, Blood Pressure

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.

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.

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."

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.

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.