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

• 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/2848777

Conclusions 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/2848997

Conclusions 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/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://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=true

Luo 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.

lancet 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.

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.

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 Setup

So 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.

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.
  
  

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.

Picture 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 showdown

Enter 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."

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.

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.

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.

 Big takeaways

• About 35% of patients truly had IE.
• Fever showed up in 80% of patients both with and without IE, so it did not help distinguish them.
• Dropping fever from the criteria actually made them better:

• Sensitivity improved: 77% (no-fever) vs 74% (standard).
• Specificity improved a lot: 80% vs 49%.
• "Possible IE" shrank from 39% to 17%, meaning fewer gray-zone cases.
• Only 0.4% of patients without IE were incorrectly labeled as having IE.

 


Both are widely used and both can work for regular (non-crusted) scabies.

The SCRATCH trial: who won?

In the SCRATCH trial from France, researchers treated about 1000 people in 300 households with confirmed scabies. Each household was randomized to:

Whole-body 5% permethrin cream on days 0 and 10, or

Oral ivermectin (weight-based) on days 0 and 10.

They then checked who was cured at day 28.

Here's what they found:

Household cure rates

Permethrin: 88% cured

Ivermectin: 72% cured

Translation: For every 6 households treated with permethrin instead of ivermectin, one extra household was fully cured (NNT  6).

Index (main) patient cure rates

Permethrin: 92%

Ivermectin: 77%

That's one extra person cured for about every 7 treated with permethrin instead of ivermectin (NNT  7).

Side effect

Skin irritation-type reactions: 14% with permethrin vs 10% with ivermectin.

So permethrin wins on cure, with a small trade-off in local skin reactions.

• All 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.2025.3386.40965920

• PSA 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 life

https://www.nejm.org/doi/full/10.1056/NEJMoa2508026?query=TOC

Among 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=TOC

In 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=TOC

Among 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%2F

β-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=false

In 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.

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/

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/

• 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.
  
  
• Citations
  King 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)
  
  

A multicenter registry study in Catalonia (2017–2023) evaluated outcomes in 578 patients with acute ischemic stroke and tandem lesions (large-vessel occlusion plus extracranial carotid stenosis). Patients were divided into two groups: those who received emergent carotid artery stenting (E-CAS) and those who did not (non-CAS).

Key Findings:

• Favorable outcomes (modified Rankin Scale 0–2) were more common in the E-CAS group at:
  • 90 days: 46% vs. 37%
  • 1 year: Odds ratio 1.35
• Recanalization rates were higher with E-CAS: 92% vs. 73%
• No significant differences in:
  • Hemorrhagic transformation at 36 hours (though a trend toward higher rates with E-CAS)
  • 1-year mortality

Conclusion:

Emergent carotid stenting during thrombectomy may improve functional outcomes and recanalization without significantly increasing bleeding or mortality. However, as this was not a randomized trial, results should be interpreted cautiously. Further randomized studies are needed.

Ezcurra-Díaz G et al. Emergent carotid artery stenting in patients with acute ischemic stroke with tandem lesions: One-year follow-up results from the SECURIS study. Neurology 2025 Oct 7; 105:e214067.

Gabapentinoids for Postoperative Pain: No Benefit Found

Study Overview: A large randomized, placebo-controlled trial in the U.K. (GAP study) evaluated the effectiveness of gabapentin for postoperative pain in 1,200 patients undergoing various cardiac, thoracic, and abdominal surgeries.

Intervention:

• Gabapentin group: 600 mg pre-op, then 300 mg twice daily for 2 days post-op
• Control group: Placebo

Key Findings:

• Slight pain reduction at 1 hour post-op (4.0 vs. 3.5 on 11-point scale)
• No difference in pain at later time points
• No differences in:
  • Opioid use
  • Serious adverse events
  • Length of hospital stay

Commentary: Despite widespread off-label use, this large, well-designed trial found no meaningful benefit of gabapentin for postoperative pain. While short-term use appeared safe, prolonged use may pose risks (e.g., sedation, falls, respiratory depression). Clinicians are advised to reconsider routine perioperative use of gabapentinoids.

Baos S et al. Gabapentin for pain management after major surgery: A placebo-controlled, double-blinded, randomized clinical trial (the GAP study). Anesthesiology 2025 Oct; 143:851.

Study Design:

• 484 trials, 104,176 participants
• 5 major drug classes: ACE inhibitors, ARBs, β-blockers, calcium channel blockers (CCBs), and diuretics
• Focus: Placebo-corrected reduction in systolic BP (SBP)
• Mean baseline BP: 154/100 mm Hg
• Mean follow-up: 8.6 weeks

Key Findings

Monotherapy (Standard Dose):

• Average SBP reduction: 8.7 mm Hg
• By class:
  • ACE inhibitors: 6.8 mm Hg
  • ARBs: 8.5 mm Hg
  • β-blockers: 8.9 mm Hg
  • CCBs: 9.5 mm Hg
  • Thiazide diuretics: 10.8 mm Hg

Dose Doubling:

• Adds ~1.5 mm Hg SBP reduction (except β-blockers, which add only ~0.5 mm Hg)

Dual Therapy (Standard Dose of Each):

• Average SBP reduction: 14.9 mm Hg
• Dose doubling adds ~2.5 mm Hg more

Triple Therapy:

• SBP reduction: Up to 22.5 mm Hg (quadruple therapy even higher in one trial)

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.

Citation

Ahiskali 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

• No convincing evidence GLP1 cause thyroid cancer in humans BUT contraindication if family history exist

• Stopping therapy usually results in weight gain

• Insurance coverage for weight loss is limited and variable 

• Semaglutide for type 2 diabetes max dose is 2.0 mg weekly Semaglutide for weight loss has a goal dose of 2.4 mg weekly
• Diagnose steatotic liver disease with imaging and 1 metabolic risk factor (or biopsy)

• After diagnosis check FIB-4:
  • Low risk, continue to monitor with FIB-4 every 2-3yrs 
  • Intermediate risk, order VCTE and consider referral if >F1 
  • High risk order a VCTE and referral (20% end with SLD)

• 2 FDA approved medications for liver fibrosis are not cheap, expect insurance push back

Buelt, Andrew | 2:13 PM (1 hour ago) |  |
to me

https://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.

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:

1. 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.
2. 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).
3. 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/

1. 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.
2. 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.
3. 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.

Key Findings:

1. 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.
2. 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.
3. Significance of Risk Factor Modification:
   • Adjusting certain risk factors during midlife, particularly managing hypertension and quitting smoking, led to the most significant gains in life expectancy free of disease.
   • For instance, controlling hypertension between ages 55 and 60 yielded the most additional life-years free of cardiovascular disease.
   • Quitting smoking during the same period was associated with the most additional life-years free of death from any cause.

https://jamanetwork.com/journals/jama/fullarticle/2834632

1. Study Design:
   • This was a phase 2, randomized, double-blinded trial with participants enrolled from 150 sites across 8 countries. The study spanned from January 2022 to June 2023, with analyses completed by March 2024.
   • Participants received indapamide, amlodipine, or olmesartan as background therapy. Those with a specified range of 24-hour mean ambulatory systolic blood pressure (SBP) were then randomized to receive either a single subcutaneous dose of 600 mg zilebesiran or placebo.
2. Efficacy Results:
   • At 3 months, zilebesiran significantly reduced the 24-hour mean ambulatory SBP compared to placebo across all cohorts:
     • Indapamide: -12.1 mmHg
     • Amlodipine: -9.7 mmHg
     • Olmesartan: -4.5 mmHg
   • Similar reductions were observed in office SBP measurements at 3 months.

https://pubmed.ncbi.nlm.nih.gov/40578930/

1. 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).
2. 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).

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:

1. Large Sample Size: With nearly 19,000 participants, the study provides robust data.
2. Rigorous Data Collection: Bleeding events were meticulously documented and adjudicated by medical professionals.
3. Comprehensive Analysis: The detailed follow-up and frequent assessments allowed for thorough monitoring of participants' health outcomes over several years.

Weaknesses of the Study:

1. Granular Data Absence: Specific details about hospitalization, such as length of stay or the number of transfusions, were not available.
2. 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.

The article examines the effectiveness and safety of zilebesiran, an RNA interference therapeutic agent, when used in combination with standard first-line antihypertensive drugs for patients with inadequately controlled hypertension. The phase 2, prospective, randomized, double-blinded trial was conducted over multiple international sites with patients treated with either indapamide, amlodipine, or olmesartan. The primary outcome measured was the change in 24-hour mean ambulatory systolic blood pressure (SBP) at three months.

Key findings from the study showed that a single subcutaneous dose of zilebesiran significantly reduced 24-hour mean ambulatory and office SBP at three months compared to placebo, across all background treatments. This indicates that zilebesiran can be an effective adjunctive treatment to standard oral antihypertensive therapies, providing sustained blood pressure control.

Strengths

1. Innovative Approach: The use of RNA interference to target hepatic synthesis of angiotensinogen introduces a novel mechanism to control blood pressure.
2. Methodological Rigor: The study used a double-blinded, placebo-controlled design across multiple international sites, enhancing the reliability and generalizability of the results.
3. 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.
4. Well-Tolerated: Despite instances of hyperkalemia, hypotension, and acute kidney failure, most events were mild and resolved without the need for medical intervention, highlighting a favorable safety profile for zilebesiran.

Weaknesses

1. Short Duration: The study's follow-up period was limited to six months. Long-term efficacy and safety of zilebesiran need to be evaluated in future studies.
2. 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.
3. 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.

Key Takeaways

1. Extended Predictive Value of Biomarkers:
   • High-sensitivity C-reactive protein (CRP), LDL cholesterol, and lipoprotein(a) levels were found to be predictive of cardiovascular events over a 30-year period.
   • These markers contribute independently to long-term cardiovascular risk beyond traditional 10-year risk estimates.
2. 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.
3. Predictive Strength of Biomarkers:
   • Among the biomarkers, high-sensitivity CRP showed the strongest association with future cardiovascular events (hazard ratio for top quintile: 1.70).
   • LDL cholesterol and lipoprotein(a) also significantly predicted risk, albeit to a slightly lower degree (hazard ratios: 1.36 and 1.33, respectively).  NOT STATIN WITH CRP
4. Implications for Clinical Practice:
   • Combining all three biomarkers may offer the best method for identifying high-risk individuals who might benefit from early intervention.   YOU HAVE TO PROSPECTIVELY VALIDATE THIS
   • The study supports extending cardiovascular prevention strategies beyond traditional risk assessments.
   • Lifestyle and pharmacologic interventions should target multiple pathways, including lipid levels and inflammation.

Key Limitations

1. Study Population:
   • The study cohort predominantly consisted of female health professionals who are mostly White (94%), which may limit generalizability.
   • The results may not extend to males or more diverse populations without further studies.
2. 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.
3. Statin Use Data:
   • Increasing use of statins over the study period was not thoroughly considered in initial analyses, and detailed data on adherence and duration are lacking.
   • Sensitivity analyses attempted to account for this by censoring data at the time of first statin prescription, but residual confounding may be present.

Concerns with Study Design

1. Cohort Composition:
   • The study's focus on health professionals might have led to better access to healthcare and healthier lifestyle choices, potentially skewing outcomes.
   • Non-White participants were underrepresented, raising concerns about the applicability of findings to more diverse groups.
2. 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.

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.

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)

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 Findings

1. Sustained 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.
2. 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).
3. 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%.
4. Safety: No increased risk of noncardiovascular deaths (5.3% in both groups).

Limitations

• Observational 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.

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 2

Clinical 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

1. Exercise-only prehabilitation reduced complications by about 50% compared to usual care.
2. Nutritional prehabilitation alone reduced complications by about 38%.
3. Combining exercise, nutrition, and psychosocial support reduced complications by about 36%.
4. For hospital length of stay, exercise plus psychosocial support was most effective, reducing stays by about 2.5 days on average.
5. 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. 

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)

(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 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 Findings

1. Low-dose ICS: No significant increase in adverse events7.
2. Medium to high-dose ICS: Associated with increased risks of:

• Major adverse cardiovascular events (MACE)
• Cardiac arrhythmia
• Pulmonary embolism (PE)
• Hospitalization for pneumonia71

1. Risk-Benefit Analysis:

• Absolute risk of adverse events was low
• Number 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)3

1. Time-dependent risks:

• Highest risk observed at 12 months
• MACE risks increased in the first 60 days but returned to baseline after ICS cessation1

Implications for Asthma Management

1. Guideline adherence: Use the lowest effective ICS dose37.
2. Risk assessment: Consider patient-specific factors when prescribing medium to high-dose ICS.
3. Monitoring: Increased vigilance for potential adverse events in patients on higher ICS doses.
4. Step-down approach: Consider dose reduction once asthma is well-controlled1.
5. 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.

Trial Results

SGLT-2 inhibitors, crucial in managing diabetes, kidney disease, and heart failure, have shown promising results in hospitalized patients

1

. The meta-analysis, covering 23 randomized controlled trials with 20,000 participants, revealed:

1. No significant increase in ketoacidosis rates (0.21 vs. 0.14 per 100 person-years)

1

1. Lower mortality and fewer readmissions in heart failure patients

1

1. Reduced incidence of acute kidney injury overall

1

These findings suggest that SGLT-2 inhibitors can be safely continued or initiated in hospitalized patients, particularly those with heart failure

1

.

Limitations

However, it's important to note some limitations:

1. Potential underpowering: The study might not have had enough statistical power to detect small differences in ketoacidosis rates

1

.

1. Risk underestimation: Including outpatient follow-up periods may have diluted the true risk of ketoacidosis during hospitalization

1

.

1. Patient diversity: Only 30% of participants had diabetes, which might not fully represent the typical hospital population

1

.

Conclusion

While 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-making

1

.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.

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 GUYS

7

.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 8

7

.Interestingly, for patients with normal troponin levels, there was no significant difference in mortality between the two surgical approaches

7

.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 patients

7

.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)

5

. 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 groups

5

. 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 Medicine

7

. 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 reasons

7

.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 patients

8

. 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 therapy

7

.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

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 sizes

1

. The key findings are:

1. 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 rate

1

1. Effect 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 size

The drug companies think their drug is way better than it is or observed to be in trials

1

1. Device trials were independently associated with decreased accuracy of event rate estimation compared to drug trials

1

.

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 hypotheses

1

. 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.

.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

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.

No 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)

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).

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)

• 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

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

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 questionnaire

and 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!

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%). 

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

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%

• 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 lap
• arm unsupported at the side

Investigators 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. 

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.

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. 

J 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 state

Both 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.

good

2024 European Society of Cardiology guidelines for the management of elevated BP and hypertension

Bad

WHY use PLACEBO RANT!! YOU wouldn’t give to your mother

Use a standard of care!! You have a new med you want to sell for millinos and billions prove it beats the current standard

And 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

 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

 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. 

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.

Question  Can behavioral interventions decrease handheld cell phone–based driver distraction?

17663 and ended up with 2020 participants

Progressive email--- already a select population

Outcome-- Proportion of drive time engaged in handheld phone use in seconds per hour (s/h) of driving.

Median baseline handheld phone use was 216 (IQR, 72-480) s/h.

 Participants were randomly assigned to 1 of 6 trial arms for a 7-week intervention period: (1) control; (2) feedback, with weekly push notification about their handheld phone use compared with that of similar others; (3) standard incentive, with a maximum $50 award at the end of the intervention based on how their handheld phone use compared with similar others; (4) standard incentive plus feedback, combining interventions of arms 2 and 3; (5) reframed incentive plus feedback, with a maximum $7.15 award each week, framed as participant’s to lose; and (6) doubled reframed incentive plus feedback, a maximum $14.29 weekly loss-framed award.

standard incentive, with a maximum $50 award at the end of the intervention based on how their handheld phone use compared with similar others---- reduced their use by −38 (95% CI, −69 to −8) s/h (P = .045);

reframed incentive plus feedback, with a maximum $7.15 award each week, framed as participant’s to lose; and (-----reframed incentive plus feedback participants reduced their use by −56 (95% CI, −87 to −26) s/h (P < .001);

doubled reframed incentive plus feedback, a maximum $14.29 ($100) weekly loss-framed award.

and doubled reframed incentive plus feedback participants reduced their use by −42 s/h (95% CI, −72 to −13 s/h; P = .007).

remember

Median baseline handheld phone use was 216 (IQR, 72-480) s/h.

Their consclusions

Findings  In this randomized clinical trial with 2020 participating auto insurance customers, the median baseline level of handheld phone while driving was 216 seconds per hour. Those randomized to interventions combining social comparison feedback and financial incentives reduced their handheld phone use while driving by 15% to 21% relative to the control group.

Most studies that have shown a benefit from endovascular thrombectomy (EVT) for ischemic stroke in the late time window (6 to 24 hours after time last known well) have used either perfusion imaging or advanced imaging to identify core infarct volume.

Whether plain CT alone can identify EVT candidates in the late time window is unknown.

multinational cohort study that looked at Consecutive patients presenting within 6–24 hours of time last seen well with proximal anterior LVO stroke that were either selected for EndoVascular therapy by Noncontrast CT or medically managed

The primary outcome was 90-day ordinal shift on the modified Rankin scale. Symptomatic intracranial hemorrhage (sICH) and mortality at 90 days were key safety outcomes.

results

 Functional independence (mRS 0–2) was observed in 40% of the EVT group and 18% of the MM-alone group. Symptomatic ICH was nonsignificantly more common with EVT than with MM alone (8.5% vs. 1.4%), but overall mortality was lower with EVT (24% vs. 32%).

They used

three large observational cohort studies with nearly 400,000 participants (median age, 62) who were followed for as long as 27 years (mean, 20 years); these studies included data on diet, self-reported multivitamin use, and mortality.

In adjusted analyses, daily multivitamin use was associated with a very small, but significant (4%), higher all-cause mortality risk. (multivariable-adjusted hazard ratio, 1.04; 95% CI, 1.02-1.07)

Results from the current study — casting some doubt on a mortality benefit of multivitamin use — are unlikely to change the feelings of reassurance that many patients gain.

“In adults with hypertension and CKD (stage 3 or higher or stage 1 or 2 with albuminuria [≥300 mg/d, or ≥300 mg/g albumin-to-creatinine ratio or the equivalent in the first morning void]), treatment with an ACE inhibitor is reasonable to slow kidney disease progression “

Angiotensin-Converting Enzyme Inhibitors or Angiotensin-Receptor Blockers for Advanced Chronic Kidney Disease: A Systematic Review and Retrospective Individual Participant–Level Meta-analysis of Clinical Trials: Annals of Internal Medicine: Vol 177, No 7 (acpjournals.org)

 In a patient-level meta-analysis of 18 randomized trials, researchers identified 1700 patients with stage 4 or 5 CKD to determine if initiating ACE inhibitors or ARBs affected progression to dialysis or death. follow-up ≈3 years.

Patients with CKD stage 4 or 5 (mean eGFR, 22 mL/minute/1.73 m2) who initiated ACE inhibitors or ARBs (vs. placebo or other antihypertensive agents) were  less likely to progress to dialysis (12% vs. 17% annually; number needed to treat, 20), mortality was similar (≈3% annually). 

You add multiple outcomes together… this is great because you can increase the event rate.. if you are just looking at death lots of people might now die but if you look at death and hospitalizations well then it is easier to get to your expected event rate because its much easier to be hospitalized. This make it so you can have smaller sample sizes and it wont be nearly as expensive.

The problem is all the events are given the same importance and we know they are not the same importance to patients

Death and hospitalizations NOT THE SAME

PE and death—not the same

3 questions to asked. 

Part of the endpoints of similar importance to patient's?

Due to the more or less significant endpoints occur with the same frequency?

Due to the endpoints share similar relative risk reductions?

That is because

CRC screening proportions were 17.5 percentage points higher in the blood test group versus usual care (30.5% vs 13.0%; OR 2.94, 95% CI 2.34 to 3.70; p<0.001).

So more people are screened for colon cancer but who cares if they get screened if your screening test does a terrible job of telling me stage 1 or precancer lesions. A history and physical will tell you stage 3 and 4 and a lot of the time even stage 2. Blood, change in size, or frequency.

Take away bottom line is---

This sounds cool. This sound awesome. This sounds like it would be great for pateints that don’t want to do other forms of coloncancer screening which I do talk about on episode 237. HOWEVER for me this is a no go, the reason I want to screen is to catch cancer early. That is one of the pillars of cancer screening. To catch it early and have something you can do with the results that will change the outcome. This does a terrible job of catching it early and if anything may give your patient a false hope or false sense of security. I understand the sex appeal of this test but this should not be used or recommended for your patients

The mean systolic blood pressure throughout the follow-up (except the first 3 months of titration) was 119·1 mm Hg (SD 11·1) in the intensive treatment group and 134·8 mm Hg (10·5) in the standard treatment group. 

 During a median of 3·4 years of follow-up, the primary outcome event occurred in 547 (9·7%) participants in the intensive treatment group and 623 (11·1%) in the standard treatment group (hazard ratio [HR] 0·88, 95% CI 0·78-0·99; p=0·028).

primarily driven by a reduction in the risks of stroke, heart failure, and death from cardiovascular causes.

Serious adverse events of syncope occurred more frequently in the intensive treatment group (24 [0·4%] of 5624) than in standard treatment group (eight [0·1%] of 5631; HR 3·00, 95% CI 1·35-6·68).  

The study's primary endpoint was a change in HbA1c levels, a critical marker of long-term blood glucose control. 

More participants using the inhaled insulin regimen experienced significant improvements in HbA1c levels compared to those on usual care.

21% of those on inhaled insulin had an HbA1c improvement of greater than 0.5%, while only 5% of those with standard care. 

21 – 5 that is an absolute difference of 16% (NNT of 6.25)

And they found a bunch of things when they went back like more people with a1c >7 reached their goal—which was not their end point they just found it and like to talk about

 inhaled insulin and degludec was not for everyone: and everyone is missing this—we know how many people had an improvement in their a1c by 0.5% but how many had a worsening???

well 26% of the patients in the inhaled insulin group had a worsening of HbA1c greater than 0.5%

compared with only 3% with standard care.

26-3== 23 100/23== 4.3 NNH

So out of 100 people that still have to give themselves insulin

This doesn’t remove insulin

But we now add inhaled insulin we should expect to see 16 people out of the 100 have a 0.5% improvement in their a1c at 4 months

And we would expect to see 23 poeople have a 0.5% worsening in their A!C

That math don’t math—people are excited about this and all I can say is maybe they are getting paid by the drug company maybe they don’t understand number needed to treat and number needed to harm but this makes no sense.

We have a study that says calcium supplement leads to increase in coronary artery calcium

Foods that are high in calcium besides dairy include things like kale, spinach, broccoli, chia sees, collard greens…

Hard for me to believe someone with a diet of excess kale and spinach will have an increase in all cause mortality anytime soon.

It is easy for me to believe that supplements in a pill don’t fix the problems like we wish—we see this all the time with some many electrolytes and nutrients—there is a difference between taking a pill and eating a nutritious diet

Peanut consumption, starting in infancy and continuing to age 5 years, provided lasting tolerance to peanut into adolescence irrespective of subsequent peanut consumption, demonstrating that long-term prevention and tolerance can be achieved in food allergy. (Funded by the National Institute of Allergy and Infectious Diseases and others; ITN070AD, ClinicalTrials.gov number, NCT03546413.)

Blood test are hot things – we want to be able to drill down someone risk to a factions of a nats rear end but that just isn’t life—all the test and decision tools give us a rough estimate—the goal is to know are we looking at an 8% risk, an 18% risk or a 28% risk. It doesn’t really matter if it is 8.2  or 8.3 or 8.4

Botoom line—I get it we want to do more and be more precise but by getting extra blood test we are also costing the system more money and more energy so until you give me a study that shows it better with then a usuable risk calculator for that particular lab I think the use of these extra lipid labs should stay on the shelf or in the research only setting.

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2820255

• To establish a PAD diagnosis, the resting ankle–brachial index (ABI) remains the initial test of choice in patients with suggestive history or exam findings. The ABI result should be reported as normal (1–1.4), borderline (0.91–0.99), abnormal (≤0.9) or noncompressible (>1.4).

TREATMET

• Low-dose rivaroxaban 2.5mg BID, in addition to daily aspirin, is now recommended to decrease the risk for major adverse cardiovascular events (MACEs) and major adverse limb events in patients with symptomatic PAD who are not at increased bleeding risk. This is based on the COMPASS trial Cardiovascular Outcomes for People Using Anticoagulation Strategies - American College of Cardiology (acc.org) and as a reminder inclusion criteria was “Atherosclerosis in ≥2 vascular beds or two additional risk factors (current smoking, diabetes, renal insufficiency, heart failure, or nonlacunar ischemic stroke ≥1 month)”

• In pts with symptomatic PAD—single antiplatelet with clopidogrel 75mg daily (NOT ASPIRIN) to lower risk of MACE. If the patient can’t get clopidogrel then aspirin will work but clopidogrel preferred!

• In patients with PAD and type 2 diabetes, the use of glucagon-like peptide-1 (GLP-1) agonists and sodium–glucose cotransporter-2 (SGLT-2) inhibitors are effective to reduce MACE.

“Cardiovascular biomarkers were strongly associated with fatal and nonfatal cardiovascular events and mortality. The addition of biomarkers to established risk factors led to only a small improvement in risk prediction metrics for atherosclerotic cardiovascular disease, but was more favorable for heart failure and mortality.”

For 10-year incident atherosclerotic cardiovascular disease in younger people (aged <65 years), the combination of high-sensitivity cardiac troponin I, N-terminal pro-B-type natriuretic peptide, and high-sensitivity C-reactive protein resulted in a C statistic improvement from 0.812 (95% CI, 0.8021-0.8208) to 0.8194 (95% CI, 0.8089-0.8277)

So this paper is saying look “Cardiovascular biomarkers were strongly associated with fatal and nonfatal cardiovascular events and mortality.”

Not wrong these labs improve outcomes but when you look at the c stats we go from 0.81 to 0.82… remember as we talked about yesterday

C-statistic gives the probability a randomly selected patient who experienced an event (e.g. a disease or condition) had a higher risk score than a patient who had not experienced the event.

A score of 1 is perfect. A score of 0.5 is a coin flip. A score of .8 is pretty good but the question we have to ask ourselves “is there a difference between 0.81 and 0.82. If you are getting a grade in school is there a real difference in the knowledge between someone that gets 81% and gets 82%.

Bottom line-

Authors might say something is beneficial and great but if they give you the c statistics you will know weather it is actually beneficial because now you know cstatics and how to use it within a study.

C-statistic gives the probability a randomly selected patient who experienced an event (e.g. a disease or condition) had a higher risk score than a patient who had not experienced the event.

Obviously there are people with low scores that still have events and people with high scores that never have events but the goal is the decision score gives us an idea of who is most likely.

·       The idea or educated estimate can be turned into a C score-  and c scores are kind of like grades== a score of 1 is absolue perfect model it means the model perfectly predicts those group members who will experience a certain outcome and those who will not.

·       But we know in medicine that isn’t possible

IF

·       A value of 0.5 means that the model is no better than predicting an outcome than random chance.

·       Values over 0.7 indicate a good model.

·       Values over 0.8 indicate a strong model.

Nirmatrelvir-ritonavir (Paxlovid) was shown in its initial randomized trial to reduce hospitalization and death in unvaccinated adults with at least one risk factor for severe disease when the ancestral variant of SARS-CoV-2 was predominant.

But it is important that drugs be evaluated in the correct target population patients who have been vaccinated or have the Omicron variant.

This industry-sponsored study enrolled 2 groups of patients: (1) fully vaccinated adults with symptomatic, confirmed infection with SARS-CoV-2 and at least one risk factor for severe disease,

(2) unvaccinated adults with a symptomatic infection but no risk factors

The onset of symptoms was within the past 5 days. Patients (N = 1296) were randomized to receive the standard 5-day course of nirmatrelvir-ritonavir or matching placebo.

the 1440 participants who were initially randomized There was no difference in duration of symptoms between groups, and no significant difference in the likelihood of hospitalization or death (0.8% vs 1.6% for placebo; difference -0.8%; 95% CI -2.0 to 0.4).

Now, researchers have compared EVT plus medical therapy to medical therapy alone in patients who could be treated within 6.5 hours of stroke onset and had a large amount of ischemic tissue

The primary outcome was the modified Rankin scale (mRS) score and the major safety outcome was all-cause mortality, both at 90 days.

a 3-year period, 333 patients  cerebral vessel occlusion in the anterior circulation

The median NIH Stroke Scale score was 21, and the median baseline infarct volume was 135 mL;

 Median time to randomization was 270 minutes after symptom onset. The EVT group had a lower median mRS score at 90 days than the medical-therapy group (4 vs. 6) and also lower mortality (36% vs. 56%).

The overall rate of death or dependency (mRS score ≥4) at 90 days was high in both groups but lower with thrombectomy (67% vs. 88%). NNT of 5

Symptomatic intracranial hemorrhage was more common with EVT (9.6% vs. 5.7%).—NNH of 25

The commonly used combined hormonal contraceptives with progestins and ethinylestradiol are associated with an increased risk of ischemic stroke (IS). 

In this Danish historical cohort study (2004-2021) we followed non-pregnant women (18-49 years) registering incident IS and ICH in relation to use of LG-IUD/non-use of hormonal contraceptives utilizing Danish high-quality registries with nation-wide coverage.

A total of 1,681,611 non-pregnant women A total of 1,681,611 non-pregnant women

The numbers get huge here however--

After adjustment incidence rate ratio for IS was 0.78 (CI: 0.70; 0.88), and for ICH it was 0.94 (CI: 0.69; 1.28)

Use of LG-IUD was associated with a 22% lower incidence rate of IS without raising incidence rate of ICH. I think IUD are unutilized and now we have data that says they have lowers rates of stroke.

A noninferiority trial is a type of randomized trial that aims to establish if treatmenet X effectiveness is not substantially less than the existing standard. Unlike superiority trials that are designed to show that one treatment is better than another, a non-inferiority trial is designed to show that a new treatment is ‘not unacceptably worse’ than the current standard therapy. You want to see if the drug you are testing is good enough compared to the standard.

Say you wanted tacos from your favorite place across town cause they have the best tacos but there is another taco place that is across the street the tacos are not as good but they are pretty close and it is a 20 second walk not a 20 minute drive. You might quickly in your mind calculate the trade off and say well the place across the street is noninferior.

Authors took 850,000 adult nonsurgical, non–intensive care unit (ICU) hospitalizations at 21 Kaiser Permanente hospitals in northern California, and did a retrospective study of inpatient pharmacologic VTE prophylaxis, investigators compared risk assessment by admitting physicians with risk assessment according to electronic health record (EHR)-

The EHR used the Padua prediction score which basically ask yes or no questions like does the pt have active cancer, previous vte, reduce mobility, elderly age, heart or resp failure. All questions that could need a human to fill out but also with could AI or HER should be answered without humans doing anything.

In 82% of 850,000 adult nonsurgical, non–intensive care unit (ICU) hospitalizations, the EHR categorized patients as low risk (i.e., not meeting indications for pharmacologic VTE prophylaxis); however, 42% of such patients (≈300,000 patients) received pharmacologic VTE prophylaxis. Among the 18% of hospitalizations where Padua score assessments indicated high risk (i.e., met indications for pharmacologic VTE prophylaxis), only one third received pharmacologic VTE prophylaxis.

There was years of making sure people give VTE but maybe we have went to far but the only way to solve this problem is give doctors fewer patient and more time or make it incorporated into the HER automatically. Make it idiot proof.

 Hospitals should begin to incorporate better validated tools within EHRs to guide clinical decision-making for inpatient VTE prophylaxis. But even without such tools, clinicians should be vigilant in applying pharmacologic VTE prophylaxis in high-risk patients and minimizing its use in patients at low risk.

Researchers randomized 5000 family physicians in Ontario, Canada, to receive either mailed feedback (with data on individual prescribing rates compared with peers' prescribing rates, plus educational information on optimal prescribing) or no mailed feedback (control group).

Clinicians in the intervention group were randomized further to (a) receiving personalized prescribing data that were adjusted, versus not adjusted, for case mix, and (b) receiving information on potential harms of antibiotics, versus not receiving such information.

Compared with controls, the intervention group had significantly lower mean rates of overall antibiotic prescribing (59 vs. 56 prescriptions per 1000 patient visits; relative rate, 0.95), apparently unnecessary antibiotic prescriptions (e.g., for viral illnesses; RR, 0.89), long-duration antibiotic prescriptions (RR, 0.85), and broad-spectrum antibiotic prescriptions (RR, 0.94) in the first 6 months after the mailings.

Only 18% of a sample of intervention physicians confirmed receipt of feedback letters.

Tells me—there has to be a personal connection. If you think this is you then you are likely to be make a change but with only 18% people confirming receipt is tells me

Physicians are burnt out—I refuse to believe they don’t care but rather they are drowning

Kityo C et al. Switch to long-acting cabotegravir and rilpivirine in virologically suppressed adults with HIV in Africa (CARES): Week 48 results from a randomised, multicentre, open-label, non-inferiority trial. Lancet Infect Dis 2024 May 28; [e-pub]. (https://doi.org/10.1016/S1473-3099(24)00289-5)307

Adults with prediabetes to lower the risk for type 2 diabetes

What is the power of a study—what is the power calculation?

Often say it is the number of people in a study. Power is the probably to correctly reject the null hypothesis. Said differently power is the probability we will correctly get a small pvalue

But a power calculation is slightly more than that it is the number of people required to adequetyly statistically calculate the number of people that would be necessary to reject your null hypothesis of no difference when there actually is a difference.

Lets say we have a blood pressure drug and we want to see if it works

Well if you only enroll a small number of people you might not be able to tell a difference between those in the active and those in the control arm

Remember depending on baseline bp you might only see a 4-5mmg hg improvement in your blood pressure and in almost every trial I have ever seen even those individuals that get the placebo have a 1-2mm hg improvement in their bp so with large confidence intervals that are likely to overlap with just a small number of people being tested you wont find a statistical difference between the two drugs. You will end up accepting the null hypothesis since you will see overlap, this is sad because maybe there is real difference but you didn’t enroll enough people to find that difference.

But lets say you want to enroll 5 million people in your trial

This is great, you will have much smaller confidence intervals and you will be able to see there is a difference and properly reject the null hypothesis and be able to get an answer but you might waist years or decades trying to enroll that many people. This is timely and expensive.

often surrogate markers are used as primary end points in clinical trials to support FDA approval of drugs

I get it

 Surrogate markers offer the advantage of reducing the duration, size, and total cost of trials

n 2018, the Food and Drug Administration (FDA) publicly released an Adult Surrogate Endpoint Table of more than 100 surrogate markers that may be used as primary end points in clinical trials that form the basis of traditional or accelerated approval of new drugs or biologics.

The authors evaluated Thirty-seven surrogate markers listed in FDA’s table of markers that can be used as primary end points in clinical trials across 32 unique nononcologic chronic diseases.

Most surrogate markers used as primary end points in clinical trials to support FDA approval of drugs treating nononcologic chronic diseases lacked high-strength evidence of associations with clinical outcomes from published meta-analyses.


https://jamanetwork.com/journals/jama/article-abstract/2817850

But with  high-intensity statins compared with placebo (4.8% vs. 3.5% annually)

Among patients with known diabetes at baseline, glycemia worsened slightly with statin therapy compared with placebo

Here is the problem- diabetes is a number—a surrogate if you will. Statins fix a surrogate but have been proven to improve patient orientated outcomes

https://www.clinicalkey.com/#!/content/playContent/1-s2.0-S2213858724000408?returnurl=https:%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2213858724000408%3Fshowall%3Dtrue&referrer=https:%2F%2Fwww.jwatch.org%2F

We don’t know that this leads to better outcomes—is the the race algorithms that lead to worse outcomes or was it access to care or is it some other factor we don’t know yet.

I think this is worth nothing and if you want to switch you certainly can but if your goal is a calculator to be used to detect primary CAD or to use in your primary CAD population EITHER seems to be just fine at this time.


https://pubmed.ncbi.nlm.nih.gov/37947085/

 randomized trial, U.K. researchers identified 519 patients (mean age, 68) with mostly moderate COPD (mean forced expiratory volume in 1 second [FEV1], 50%), ≥2 exacerbations during the previous year, and no cardiovascular (CV) indications for β-blockers. 

Patients were randomized to receive the cardioselective β-blocker bisoprolol (initially 1.25 mg daily, titrated to 5 mg if tolerated) or placebo.

At 1 year, no significant differences were noted between groups in incidence of COPD exacerbations or in other important benefits or harms.

Cardioselective β-blockers remain appropriate for COPD patients who have valid cardiovascular indications for their use, but taken these two studies together suggests that COPD patients without such indications should avoid bblockers—even cardio selective beta blockers

https://jamanetwork.com/journals/jama/article-abstract/2819083

Lets say you want to do fluids--- what is better LR or NS instead of doing individuals and room you just put whole hospitals in either LR or NS

Or you want to test if mask work for some virus—you would say this city gets all the mask in the world and this city gets zero mask…you know that If you just gave some individuals in the city a mask then maybe someone who give their extra mask to their friends and you would have cross contamination meaning that that individuals in the group end up getting the intervention you are trying to test.

Cluster RCT are GREAT for logistics and trying to figure out logistically can something or does something actually work

However cluster RCT can be harder to analyze because the clusters may not always have the same exposures or the confounders might not be equal between clusters

In our mask example that we just talked about lets assume that one village or city never has a case of covid—will it doesn’t matter if they get mask or not because they are so isolated they never get a case of it. However if  you had a perfect individual RCT the number of people in that never covid village would be exactly equal.

In the IV fluid example lets assume that one hospital gives their patients on average 20L of fluid per admission while other hospital is more reasonable in their fluid management. We know the more fluid or volume overload you are the worse your outcomes. On an individual level this wouldn’t be a problem as the same number of people would be randomized to the hospital with excess fluid exposure. So for cluster RCT while you might be able to randomize the type of fluid that cluster gets you cant control for other confounders which may throw off your result, things like exposure to the amount of fluid or type of nursing care. These excess confounders balance each other out in a individual trial as ideally individuals will have everything else the same, from volume of fluid to nursing care and the only difference will be the fluid.  

(A) Hematoma expansion ≤ 35% at 12h

(B) increase in NIHSS ≤ 7 at 12h

(C) No rescue therapy 3-12h

Results hemostatic efficacy: 76.7% andexanet vs 64.6% usual care    

30 day mortality: no difference

30 day Modified Rankin Score ≤3: no difference

Thrombotic events: almost x2 with andexanet 10.3% vs 5.6% - statistically significant. Most were strokes and MI - not trivial.

The question you should ask: How does effective is hemostatic efficacy as a marker for patient outcomes?? Yes, we don’t want the brain bleed to get bigger but patients don’t care if the bleed gets bigger if they still die or if they still are in a coma for the rest of their life.

We know from warfarin that increase in hematoma expansion leads to worse outcomes (https://pubmed.ncbi.nlm.nih.gov/21346218/). We don’t have clear data on this for the DOACs. HOWEVER, just because an expanding hematoma leads to a bad outcome that does not mean that giving a medication to decrease hematoma expansion leads to better survival or improvement in disability.

In fact the randomized, double-blind, placebo-controlled trial we have that gave recombinant activated factor VII for acute intracerebrall hemorrhage showed that rFVIIa significantly reduced the growth of the hematoma but failed to improve survival or functional outcome at 90 days. https://pubmed.ncbi.nlm.nih.gov/19959538/

So we have a trial that shows improvement in hematoma expansion. It shows no difference in mortality or Rankin scale and demonstrates twice the rates of thrombotic events.

Bottom line-- ANNEXA-I does not show clear evidence of clinical benefit but there is definite evidence of harm. The logical argument for hematoma expansion as an outcome is compelling but not proven for patient oriented outcomes.

64 141 patients with a first AF diagnosis 

Patients were categorized as CHA2DS2-VASc 1 if they had any 1 of age 65 to 74 years, congestive heart failure (HF), hypertension, diabetes, or vascular disease 

found no large differences in ischemic stroke, transient cerebral ischemia, or systemic arterial embolism among clinical risk factor subgroups of patients with AF who did not receive anticoagulant therapy and fell into (CHA2DS2-VASc score of 1

good news if you have a chadvasc score of one it doesn’t matter which 1 made you the one you have roughly the same risk for a bad event.


https://pubmed.ncbi.nlm.nih.gov/38152890/

Do I think if you stop drinking alcohol in the next thirty days you are less likely to come to the hospital for a heart attack? A stroke? Pneumonia? copd exacerbations or CHF exacerbations?? The answer is no!! not in thirty days.. sure if you drag that out for months or years then yes you are at greater risk but for only 30 days of follow up realistically should be no difference in coming back to the hospital for things that are not alcohol related.

However there was still a significant improvement or decrease in alcohol related return to the hospital.

-- This is what most supporters will look at and say ‘see we should give this medication to everyone’

This get tricky because they lump together alcojol related ED visit and alcohol related readmission in their definition of alcohol related return to the hospital---- well hello!!!! You cant get readmitted if you don’t go to the ED so the real ‘return to the hospital’ is just alcohol return to the ED and by including alcohol relatated readmission with alcohol related ED visit you are just trying to artificially inflate your finding.

I know that they were just trying to artificially manipulate their finidings because as they say “””Alcohol-related ED visits did not reach statistical significance in relative terms (IRR, 0.61 [95% CI, “””

If your patient wants fda approved medications for alcohol use disorder then give it to them!! We shouldn’t without these medications but if you are giving it to them thinking it is some magical pill with a nnt of 4 to prevent death and the patient returning to the hospital then you will be sad!

https://pubmed.ncbi.nlm.nih.gov/38551564/

Initiating medication also was associated with elevated risks for falls that required emergency room visits or hospitalizations (aHR, 1.8) and elevated risks of syncope (aHR, 1.7).

Fracture risks were elevated, compared with controls, in initiators with a  systolic blood pressure ≥140 mm Hg (aHR, 3.1), diastolic blood pressure ≥80 mm Hg (aHR, 4.4), and no recent antihypertensive medication use (aHR, 4.8).

 Now, the American Gastroenterological Association (AGA) has published a “Rapid Clinical Practice Update,”

note that evidence is insufficient to make strong recommendations about continuing or withholding GLP-1 agonists prior to endoscopy. The AGA suggests an individualized approach: GLP-1 agonists “could be withheld” in patients who take the drugs solely for obesity, but the authors worry that omitting a dose in a patient with diabetes might confer more risk than benefit. 

They say the scope should go on as long as the pt has been on an 8 hour solid fast and a 2 hour liquid fast



https://www.sciencedirect.com/science/article/pii/S1542356523008698?via%3Dihub

278 adults with moderate CAP who were hospitalized (but not in intensive care) to receive either a β-lactam antimicrobial plus clarithromycin or a β-lactam alone. (all patients met sepsis or severe sepsis criteria)

composite primary endpoint of improved respiratory symptoms and improved SOFA score by day 4 occurred in significantly more patients in the dual-antibiotic group (68% vs. 38%; number needed to treat, ≈3).

Individuals on dual antibiotics also were significantly less likely to develop sepsis (13% vs. 24%; NNT, 10), significantly more likely to be discharged and alive at 3 months (79% vs. 62%; NNT, 6), and less likely to be readmitted within 90 days (8% vs. 15%; NNT, 14; P=0.09)


https://www.clinicalkey.com/#!/content/playContent/1-s2.0-S2213260023004125?returnurl=https:%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2213260023004125%3Fshowall%3Dtrue&referrer=https:%2F%2Fwww.jwatch.org%2F

Patients with cancer of unknown primary site who received treatment concordant with tumor origins predicted by AI had significantly longer overall survival than those whose treatment was discordant with AI predictions (27 vs. 17 months).

https://www.nature.com/articles/s41591-024-02915-w

• In patients with cirrhosis and spontaneous bacterial peritonitis, to substantially limit kidney impairment and mortality (low-certainty evidence) THIS IS THE ONLY THING YOU HAVE TO REMEMBER FORGET THE REST!
• In patients with cirrhosis and ascites who undergo large volume paracentesis (LVP; >5 L) to significantly lower the incidence of paracentesis-induced hypotension, but they had no substantial improvement in recurrent ascites or renal impairment and no mortality benefit. (very-low–certainty evidence)

New guidelines on the use of albumin (remember albumin is a blood product so if you have a Jehovah’s witness or any patient that avoids blood products you need to ask them if it is ok)


https://www.sciencedirect.com/science/article/pii/S001236922400285X?via%3Dihub

Tirzepatide also known as mounjaro – 8.5 kg 

Semaglutide also known as Ozempic -3.1 kg lost

Liraglutide aka Victoza – 1.3 kg lost


Tirzepatide also known as mounjaro – 8.5 kg 

But almost all of these weight loss drugs seem to lose the effect over time and as you increase the dose and increase the weight loss you can expect to increase the GI side effects

 

https://www.bmj.com/content/384/bmj-2023-076410

Food was prepared in a study kitchen and consumed onsite or taken home.

Key difference

The intervention group was instructed to eat between 8 a.m. and 6 p.m. and to consume 80% of calories by 1 p.m. The control group was instructed to eat between 8 a.m. and midnight, with 55% of calories after 5 p.m.

Weight loss in the two groups was similar at 12 weeks (about 2.4 kg).

3 months—and no difference—


https://www.acpjournals.org/doi/10.7326/M23-3132

they also report that the medication arm had improvement on CT imaging of the sinuses which also seems like another Duh moment as I am sure it was better than nothing

my concern is this new drug or deliver of the drug is a cash price of about 800-1000 per month while just simple fluticasone is around 10$ a month. I think for now stick with the normal 10$ fluticasone but if there is no success and continue to have severe symptoms then maybe consider this if they have good insurance

bottom line is there is a new drug out there that is basically fluticasone in a fancy delivery device.. for almost all my patients and family members they will be getting regular fluticasone not this fancy delivery device that goes but the name XHANCE

https://www.clinicalkey.com/#!/content/playContent/1-s2.0-S221321982301365X?returnurl=https:%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS221321982301365X%3Fshowall%3Dtrue&referrer=https:%2F%2Fwww.jwatch.org%2F

 after adjustment for potential confounders, only heart rate >100 beats per minute and not the ECG abnormalities was associated with those adverse outcomes, and this association was noted only when potassium levels were <3.0 mmol/L.

hypokalemia is not good and certainly not hypokalemia < 3.0 but its not the proarrhythmic effects of hypokalemia that is bad it is the acute illness it is the under lying reason the patient has a potassium of less than 3.

you were randomized to receive either neuromuscular exercise (NEMEX; focusing on postural and functional stability) or progressive resistance training (PRT; focusing on muscle strength).

 primary outcome was the “chair stand test,” in which patients go from sitting to standing as many times as possible within 30 seconds. At 12 weeks, this outcome did not differ between the NEMEX and PRT groups; mean improvement in both groups was 1.5 repetitions (from a baseline of ≈11.5 repetitions).

1.5 repetitions did not meet anyones expections or criteria for clinically meaningful improvement.

Lifestyle recommendations include moderating alcohol use, quitting smoking, exercising, and losing weight if obese. Good news: Coffee need not be restricted.

The authors recommend using a risk score such as CHADS2-VASC to determine the patient’s risk of stroke; if the annual risk of stroke is between 1% and 2% anticoagulation should be considered, and if the annual risk of stroke is greater than 2% then anticoagulation is strongly recommended.

For patients who are low risk (< 1%) — for example, younger than 65 years and without any risk factors for stroke — anticoagulation is not recommended. The guidelines also do not recommend aspirin or aspirin plus clopidogrel for these patients unless there is another indication, such as coronary heart disease. 

 With regard to the choice of anticoagulant, a standard dose of a direct oral anticoagulant (DOAC) is recommended over vitamin K antagonists like warfarin. The exceptions are patients who those with moderate to several mitral stenosis, and those with a mechanical heart valve.

• Moderately aggressive fluid resuscitation with lactated Ringer's solution should be started (NEJM JW Gen Med Oct 1 2023 and Am J Gastroenterol 2023; 118:2258), defined as a bolus of 10 mL/kg followed by infusion of 1.5 mL/kg/hour (NEJM JW Gen Med Oct 15 2022 and N Engl J Med 2022; 387:989), and additional boluses can be given if a patient has evidence of hypovolemia.

Feeding-- Early oral feeding (within 24–48 hours) should begin with a low-fat solid diet (as opposed to liquid) for patients with mild AP.

Surgery-

 Patients with mild acute biliary pancreatitis should undergo cholecystectomy early, preferably before discharge.

•  Following a second episode of AP with no identifiable cause, in patients fit for surgery, we suggest performing a cholecystectomy to reduce the risk of recurrent episodes of AP.

Elevated cholesterol as a child into an adult is bad but we still don’t know if treating children with medication improves this badness but we can say if you have elevated cholesterol as a child and it resolves as an adult then that is a good sign and puts you at equal risk to someone who never had dyslipidemia


https://jamanetwork.com/journals/jama/article-abstract/2817700

As the authors suggest—my take away bottom line

These findings suggest that a low amount of weight gain or weight loss is safe in pregnant women with obesity, and might even be beneficial for those with class 3 obesity.


https://www.clinicalkey.com/#!/content/playContent/1-s2.0-S0140673624002551?returnurl=https:%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0140673624002551%3Fshowall%3Dtrue&referrer=https:%2F%2Fwww.jwatch.org%2F

Overall if you put a chair at bedside and have medstudents following then yes a provider is more likely to sit down. However- this only minimally changes patient satisfaction score 3.9% on a 100 point scale. This would take hospital change. And set up change. This although touted as positive is a negative trial for those in HR and admin


https://www.bmj.com/content/383/bmj-2023-076309

AND It was 179 minutes shorter (95% CI 146 - 213) in the intervention group than in the control group (392 minutes; standard deviation [SD] 122 vs 571 minutes; SD 188). 

Intensity of pain, was reported on a visual analog scale of 0 to 10 at several points in time, was on average 2.0 to 2.7 points lower in the intervention group.

The absolute rate of cesarean delivery was reduced by 14 percentage points in the intervention group (26 vs 12; absolute risk reduction = 14; 3 - 25; number needed to treat = 7).

Main limitation here was that those in the intervention group were trained and had a professional physiotherapist with them at all times. This is not reasonable. 

https://www.clinicalkey.com/#!/content/playContent/1-s2.0-S1836955323001212?returnurl=https:%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1836955323001212%3Fshowall%3Dtrue&referrer=https:%2F%2Fpubmed.ncbi.nlm.nih.gov%2F

As a reminder this trial (ISIS) didn’t demonstrate a huge mortality benefit despite all of the things that were missing from it that are now considered standard of care. The mortality number needed to treat was 143 (13.3% vs 14.0%) 


https://www.nejm.org/doi/abs/10.1056/NEJMoa2401479

This  Risk was similar for various types of bleeding (e.g., intracranial, gastrointestinal) and did not vary with potency of SSRI.

In patients with strong indications for both drugs, the relatively small absolute excess risk might be acceptable. However, in patients for whom the indication for either the SSRI or the anticoagulant is marginal, the excess bleeding risk might be a reason to avoid prescribing both drugs together.

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2816687

 participants at the 75th percentile of PRS risk needed to walk 2280 more steps daily than participants at the 50th percentile to have the same relative risk reduction. Conversely, participants at the 25th percentile needed to walk 3660 fewer steps daily than those at the 50th percentile for the same relative risk reduction.

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2816822

bottom line

For the outcomes of pain and function Telerehabilitation with a physiotherapist is non-inferior to in-person rehabilitation for patients with chronic knee pain


https://www.clinicalkey.com/#!/content/playContent/1-s2.0-S0140673623026302?returnurl=https:%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0140673623026302%3Fshowall%3Dtrue&referrer=https:%2F%2Fwww.jwatch.org%2F

• Positive predictive value (the proportion of positive tests that were true positives for cancer or advanced neoplasia) was 11%.
  
  
• Negative predictive value (the proportion of negative tests that were true negatives for cancer or advanced neoplasia) was 93%.
  
  
• The stool DNA test was substantially more sensitive than FIT (94% vs. 67% for cancer; 43% vs. 23% for advanced precancerous lesions), but slightly less specific.
  
  

https://www.nejm.org/doi/10.1056/NEJMoa2310336

https://acrjournals.onlinelibrary.wiley.com/doi/10.1002/acr.25175

Improvement in

nonfatal stroke was not statistically significant

death from cardiovascular causes was no significant but

hold on it does appear nonfatal MI was significant and is what really drove the entire composite outcome

All the way down to the discussion to find “An important limitation of this trial is that we included only patients with preexisting cardiovascular disease. The effects of semaglutide on primary prevention of cardiovascular events in persons with overweight or obesity but without previous atherosclerotic disease were not studied. “

And that is because if you want to know the inclusion criteria you have to go to the supplementary data—

WHICH NO ONE DOES

This was sneaky and planned and terrible on the part of Novo Nordisk.

https://www.nejm.org/doi/10.1056/NEJMoa2307563?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed

(ZTLido 1.8%) is a brand name lidocaine patch currently approced for postherpetic neuralgia and will stay that why for now as it did not beat placebo for the treatment of patients with chronic nonspecific neck pain
For both pain scores the pain decreased by 1.0 point with lidocaine and by 0.5 points with placebo. These differences were neither statistically significant nor deemed to be clinically important!


https://pubs.asahq.org/anesthesiology/article/140/3/513/139530/Multicenter-Randomized-Placebo-controlled

Omalizumab does seem to improve allergic reactions to peanuts but comes at a steep price tag. Likely only allergist will prescribe this drug but it is worth know about If you know or take care of anyone with severe peanut allergy.

After 16 weeks, 67% of patients who took omalizumab could tolerate a 600-mg peanut protein challenge (≈2 peanuts) versus 7% of controls.

Variability among patients was large: 44% of omalizumab patients could tolerate 25 peanuts whereas 14% of patients could not tolerate even 1/10 of a peanut.


https://www.nejm.org/doi/10.1056/NEJMoa2312382

• Limitations: Most COC RCTs unblinded, many COC RCTs prohibited concurrent topical agents, no RCTS comparing COCs to topical agents, many industry-funded.

https://cfpclearn.ca/tfp362/

-HFpEF- SGLT2 inhibitors do not prevent death and cost roughly $364,000 to prevent one hospitalization

-HFrEF -Using Cox models, only Dapagliflozin has mortality benefit (NNT 53) and comes at a cost of $229,914 prevent one cardiovascular death. (117,126$$$ dap for hospitalization)

They used win ratios

Individual trials didn’t show mortality benefit but now there is?

https://pubmed.ncbi.nlm.nih.gov/35228754/

They composite outcome was driven by decrease hospitalizations NOT death

https://www.nejm.org/doi/full/10.1056/NEJMoa2022190

NNT for hospitalization = 27

NNT for Cardiovascular Death = 53

N Engl J Med 2019; 381:1995-2008

number needed to treat [NNT] = 32 per 26 months

 
But the drug company did a great job of writting the paper so you think there is mortality benefit

https://www.nejm.org/doi/full/10.1056/NEJMoa2107038

death from cardiovascular causes: NNT 46 per 3.1 yrs (at $600 a month, 1 million dollars per life saved)

nonfatal myocardial infarction: NS∞

nonfatal stroke: NS∞

https://www.nejm.org/doi/full/10.1056/nejmoa1504720

Compared with propensity-score matched patients without PPI use after discharge, patients with continued PPI use were 27% more likely to develop pneumonia, 17% more likely to develop experience cardiac events, 34% more likely to be .readmitted to the hospital in the subsequent year and 17% greater risk of in increased mortality at two years.

https://journals.lww.com/ccmjournal/fulltext/2024/02000/timely_cessation_of_proton_pump_inhibitors_in.4.aspx

That said, I would still have reservations about prescribing DOACs in the small minority of patients with BMI >45 kg/m2 or body weight >330lbs due to their underrepresentation in the pivotal trials and when you look at the supplementary data you will see a weight of 262 was 95% tile so >330 would be around the 99th %tile of weight.


https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.123.066279

• For participants under 50, each five-point higher BCS is associated with a 50% lower risk of dementia or stroke
• For participants under 50, each five-point higher BCS is associated with a 59% lower risk of dementia 
  
  THE SCORE IS HERE ---->. https://www.massgeneral.org/assets/mgh/pdf/neurology/mccance-center/brain-care-score.pdf

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10725202/#:~:text=A%20five%2Dpoint%20higher%20BCS,%25)%20among%20those%20aged%20%3E59.

 230 676 children <15 months old were treated for infant walker–related injuries in US emergency departments from 1990 to 2014.

9 out of every 10 injuries were to the head and neck and 74% were injuries secondary to falling down the stairs in an infant walker

https://publications.aap.org/pediatrics/article-abstract/142/4/e20174332/37420/Infant-Walker-Related-Injuries-in-the-United?redirectedFrom=fulltext?autologincheck=redirected

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2813293

Not to sound like a broken record but

Risk of progression from diabetes to not having diabetes did not differ significantly between testosterone and placebo groups- and they looked for a change at 6,12,24,36,48 months of follow up

https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2814401?guestAccessKey=d63bbb99-4d14-4f17-a4ac-b208633827e2&utm_source=twitter&utm_medium=social_jamaim&utm_term=12573820072&utm_campaign=article_alert&linkId=310108953

The drug companies will say look how safe testosterone therapy is there was no difference in death from cardiovascular causes or myocardial infarction or stroke in those individuals randomized to testosterone therapy over placebo but in actuality this trial really showed nothing and it did show that when using placebo or minimal doses of testosterone -- ones that barely change blood levels of testosterone and have so little effect on how people feel that 60% of them stop the active arm of the trial, then and only then are the patients safe from cardiovascular risk at less than 2 years of follow up. And I am sure they will forget to mention the harm associated with testerone that was in the form of cardiac arrhythmias and acute kidney injury.

https://www.nejm.org/doi/full/10.1056/NEJMoa2215025

• 23% among women vaccinated before age 15
• 32% among women vaccinated between ages 15 and 20
• 38% among women vaccinated after age 20
• 38% among unvaccinated women

Krog L et al. Risk of progression of cervical intraepithelial neoplasia grade 2 in human papillomavirus–vaccinated and unvaccinated women: A population-based cohort study. Am J Obstet Gynecol 2023 Dec 30; [e-pub]. (https://doi.org/10.1016/j.ajog.2023.11.1235. opens in new tab)

• gastrointestinal, liver, pancreatic, and biliary cancers (relative risks, 3.1–7.4);
• Leukemia (RR, 4.2)
• Breast, prostate, and gynecologic cancers were not associated with >10% weight loss

Wang Q-L et al. Cancer diagnoses after recent weight loss. JAMA 2024 Jan 23/30; 331:318. (https://doi.org/10.1001/jama.2023.25869)

Rendle KA et al. Rates of downstream procedures and complications associated with lung cancer screening in routine clinical practice: A Retrospective Cohort Study. Ann Intern Med 2024 Jan; 177:18. (https://doi.org/10.7326/M23-0653. opens in new tab)

A HUGE piece of new is that now ablation is the cool kid on the block!!

More recent information has shown that ablation for AF is more effective than antiarrhythmic drugs for both persistent and paroxysmal AF and that earlier implementation of rhythm control strategies is an important factor for improving AF ablation success rates

I know we use to be all about rhythm and rate control are ‘equal’ and don’t worry the guidelines still say,

“Although selection of a rhythm-control therapy within a year of AF diagnosis may be considered to reduce the risk of adverse cardiovascular outcomes, early rate control may still be appropriate.” (aka you can do it acutely but that is only to get a hold of the acute situation) 

BUT

Catheter ablation of AF is now a strong class 1 recommendation—FIRST LINE in selected patients which includes those with heart failure and reduced EF. This is with good reason ---

 In STOP-AF, patients who had failed ≥1 antiarrhythmic drug (approximately 70% and 30% for 1 or 2 failed drugs, respectively) were randomized to either another antiarrhythmic drug or catheter ablation. At 1 year follow-up, catheter ablation was associated with a treatment success rate of 70%!!!

             -I have long complained based on previous guidelines a new onset afib didn’t need to be admitted and could be set home on medication and follow up with cardio BUT NOW admit and consider ablation per these guidelines!

What are the patients that the guidelines recommend ablation for????

Generally younger with few comorbidities) with symptomatic paroxysmal AF--  However, clinical trials have demonstrated improved cardiovascular outcomes with rhythm control, even with median ages in the 70s.

Patients with minimal atrial enlargement have the best outcomes, whereas increased myocardial fibrosis and more persistent forms of AF are associated with higher rates of recurrence or failure.

Basically, what they are saying is if you are going to ablate them then do it early before there is remodeling to the heart.

However it is not just healthy patients, there is also a strong recommendation for appropriate patients with AF and HFrEF who are on GDMT, and with reasonable expectation of procedural benefit, catheter ablation is beneficial to improve symptoms, QOL, ventricular function, and cardiovascular outcomes.

This is a HUGE HUGE HUGE HUGE HUGE change to what we have done for so long now and you need to be aware of it AND when you are getting ready to discharge after ablation the recommendation is,

In patients with AF who undergo successful cardioversion or ablation resulting in restoration of sinus rhythm, anticoagulation should be continued for at least 4 weeks postprocedure.

Enteric coating of aspirin delays the breakdown of the tablet until it is in the higher pH of the duodenum and has been shown to reduce gastric erosion5 but has not been shown to reduce gastrointestinal bleeding. We say take enteric coated but no study has shown that enteric coated formulation is safer then uncoated aspirin

post hoc secondary analysis of 10 678 participants with atherosclerotic cardiovascular disease from the ADAPTABLE randomized clinical trial—a reminder, (Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-term Effectiveness). In that trial they randomized 15,000 patients with coronary artery disease to take 81 mg or 325 mg of aspirin daily. 

Roughly half of the pts using 81mg and half of the pts using 325mg were on enteric coated aspirin and half on regular uncoated aspirin. - Median follow-up was ≈2 years

 primary outcomes were death, hospitalization for myocardial infarction, or hospitalization for stroke and the primary safety outcomes was major bleeding --  (hospitalization for a bleeding event with use of a blood product or intracranial hemorrhage).---between enteric-coated aspirin and uncoated aspirin among participants

and the answer was there was no difference so when your patient that needs aspirin for secondary prevention ask you should I take enteric-coated aspirin or uncoated aspirin

You can answer

Sound affect

At this time it appears the best available evidence that there likely is no difference between enteric-coated aspirin and uncoated aspirin just make sure you are taking your aspirin

 (https://www.healthquality.va.gov/guidelines/MH/mdd/VADoDMDDCPGFinal508.pdf) clearly state there is insufficient evidence to support this activity and testing. This is mainly because of low quality evidence and concern of bias given commercially funded studies. 

 (https://www.aafp.org/pubs/afp/issues/2023/0100/poems-pharmacogenic-testing-antidepressants.html)

American Psychiatric Association Psychiatry.org - Genetic Testing to Improve Psychiatric Medication Choice

Harvard https://www.health.harvard.edu/blog/gene-testing-to-guide-antidepressant-treatment-has-its-time-arrived-2019100917964

First prime

As I mention in my response email PRIME the primary outcomes per clinnicaltrials.gov were depression remission at 24 weeks, which was not statically significant. And then a use of fewer medications that have a potential gene-drug interaction which from what I can find was a ‘theoretical’ interaction not an actual increase in adverse events. Effect of Pharmacogenomic Testing for Drug-Gene Interactions on Medication Selection and Remission of Symptoms in Major Depressive Disorder: The PRIME Care Randomized Clinical Trial | Depressive Disorders | JAMA | JAMA Network

“The PREPARE Study

 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5113234/#:~:text=Open%2Dlabel%20placebo%20reduced%20minimum,0.02%25%20in%20the%20TAU%20arm. When patients were told they were getting placebo for back pain and it helped their back pain!

The current VA/DoD guidelines clearly state, “For patients who cannot tolerate a statin, we suggest a washout period followed by a rechallenge with the same or a different statin or lower dose, and if that fails, a trial of intermittent (nondaily) dosing”. 

https://www.healthquality.va.gov/guidelines/CD/lipids/VADoDDyslipidemiaCPG5087212020.pdf (full disclosure and bias I helped write them)

 N-of-1 Trial of a Statin, Placebo, or No Treatment to Assess Side Effects | NEJM was published in the NEJM and then a few weeks later Statin treatment and muscle symptoms: series of randomised, placebo controlled n-of-1 trials (bmj.com) was published in the BMJ. 

Around that same time a publication in JAMA https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2773490 showed that using pharmacogenetic testing resulted in no worse LDL levels (soft endpoint) at one year but also no better

1. Lewis GD et al. Effect of oral iron repletion on exercise capacity in patients with heart failure with reduced ejection fraction and iron deficiency: The IRONOUT HF randomized clinical trial. JAMA 2017 May 16; 317:1958. (http://dx.doi.org/10.1001/jama.2017.5427. opens in new tab)

randomized, 225 patients with symptomatic systolic HF for 16-weeks to either  oral iron polysaccharide 150 mg twice daily and placebo in 225 patients with symptomatic systolic HF (median left ventricular ejection fraction, 25%)

At 16 weeks, the groups did not differ on the primary endpoint of peak oxygen consumption (VO2) or on secondary endpoints, including 6-minute walk distance and quality of life as measured with the Kansas City Cardiomyopathy Questionnaire.

Thus as you mentioned not only is it not well tolerated it also doesn’t appear to work which might be a better reason to not give it.

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0279166

Vitamin D2 supplementation was associated with a 48.8% reduction in suicide/self-harm risks, and vitamin D3 with a 44.8% reduction, both highly significant (P < .001).   this sounds great but it is purely relative reduction not absolute because the absolute numbers were

Unadjusted suicide attempt/intentional self-harm rates in the D2 sample were 0.27% for those treated versus 0.52% for those untreated. The corresponding percentages for D3 were 0.20% versus 0.36%, respectively.

Which equals a NNT of roughly 400 and 625 over 8 yrs, respectfully.

IF this was true then that actually isn’t too bad (not good or great but not terrible) but this was a retrospective observational trial so they just looked at a lot of people and said what can we find and publish.

So what are other reasons that someone would not commit suicide??

My first thought is ‘you only get put on vit d if you go to the doctor” (which is true)

And typically the people that go to the doctor for their health care a little more about their health than someone who commits suicide

Clearly this isn’t a universal answer but possible

Another thought is

the vet that goes to the doctor and gets prescribed vit d feels like someone “cares for him/her” so maybe it has nothing to do with the vit d but just the sense of reassurance that someone cares about them??

Based on this I still wouldn’t/wont write for vitamin d unless you need cheap placebo since we cant actually write for placebo

D'Andrea E et al. Comparing effectiveness and safety of SGLT2 inhibitors vs DPP-4 inhibitors in patients with type 2 diabetes and varying baseline HbA1c levels. JAMA Intern Med 2023 Feb 6; [e-pub].

Sodium–glucose cotransporter-2 (SGLT-2) inhibitors are used to manage type 2 diabetes but also have protective cardiovascular and renal effects. 

 Do these benefits and adverse effects vary according to baseline level of hyperglycemia

SGLT-2 inhibitors were compared with propensity-score–matched patients who initiated dipeptidyl peptidase-4 (DPP-4) inhibitors, within three categories of HbA1c: <7.5%, 7.5% to 9%, and >9%.

After mean follow-up of 8 months, initiation of SGLT-2 inhibitors was associated with significantly lower risks for major adverse cardiovascular events and hospitalization for heart failure,

DUH we know this works in people that don’t have diabetes why is it a surprise that it works in those with uncontrolled or controlled diabetes.

To me this points to the problem that A1C is a number, it is not the problem, a bad A1C says there could be a problem in the future but in itself the A1C is a number!

Buelt, Andrew
| Apr 19, 2023, 3:25 PM |
|

to me

Treat-to-Target or High-Intensity Statin in Patients With Coronary Artery Disease: A Randomized Clinical Trial | Cardiology | JAMA | JAMA Network

JAMA. 2023;329(13):1078-1087. doi:10.1001/jama.2023.2487

 randomized noninferiority trial 4400 patients 

Question  Is treatment to a goal low-density lipoprotein cholesterol (LDL-C) level between 50 and 70 mg/dL noninferior to a strategy using high-intensity statin therapy among patients with coronary artery disease?

 To assess whether a treat-to-target strategy is noninferior to a strategy of high-intensity statins for long-term clinical outcomes in patients with coronary artery disease.

Patients were randomly assigned to receive either the LDL-C target strategy, with an LDL-C level between 50 and 70 mg/dL as the target, or high-intensity statin treatment, which consisted of rosuvastatin, 20 mg, or atorvastatin, 40 mg.

Which isn’t HIGH in my book that that is fine.

Primary end point was a 3-year composite of death, myocardial infarction, stroke, or coronary revascularization with a noninferiority margin of 3.0 percentage points.

The primary end point occurred in (8.1%) in the treat-to-target group and (8.7%) in the high-intensity statin group 

Worst conclusion ever

“Conclusions and Relevance  Among patients with coronary artery disease, a treat-to-target LDL-C strategy of 50 to 70 mg/dL as the goal was noninferior to a high-intensity statin therapy for the 3-year composite of death, myocardial infarction, stroke, or coronary revascularization. These findings provide additional evidence supporting the suitability of a treat-to-target strategy that may allow a tailored approach with consideration for individual variability in drug response to statin therapy.”

Let's see if something that's much more difficult and costly and more blood draws and more work and more office appointments is non inferior to something that's easier such as take this medication and that it………………………………... Then why it is, we recommend the much more difficult thing.

Treat-to-Target or High-Intensity Statin in Patients With Coronary Artery Disease: A Randomized Clinical Trial | Cardiology | JAMA | JAMA Network

JAMA. 2023;329(13):1078-1087. doi:10.1001/jama.2023.2487

 randomized noninferiority trial 4400 patients 

Question  Is treatment to a goal low-density lipoprotein cholesterol (LDL-C) level between 50 and 70 mg/dL noninferior to a strategy using high-intensity statin therapy among patients with coronary artery disease?

 To assess whether a treat-to-target strategy is noninferior to a strategy of high-intensity statins for long-term clinical outcomes in patients with coronary artery disease.

Patients were randomly assigned to receive either the LDL-C target strategy, with an LDL-C level between 50 and 70 mg/dL as the target, or high-intensity statin treatment, which consisted of rosuvastatin, 20 mg, or atorvastatin, 40 mg.

Which isn’t HIGH in my book that that is fine.

Primary end point was a 3-year composite of death, myocardial infarction, stroke, or coronary revascularization with a noninferiority margin of 3.0 percentage points.

The primary end point occurred in (8.1%) in the treat-to-target group and (8.7%) in the high-intensity statin group 

Worst conclusion ever

“Conclusions and Relevance  Among patients with coronary artery disease, a treat-to-target LDL-C strategy of 50 to 70 mg/dL as the goal was noninferior to a high-intensity statin therapy for the 3-year composite of death, myocardial infarction, stroke, or coronary revascularization. These findings provide additional evidence supporting the suitability of a treat-to-target strategy that may allow a tailored approach with consideration for individual variability in drug response to statin therapy.”

Let's see if something that's much more difficult and costly and more blood draws and more work and more office appointments is non inferior to something that's easier such as take this medication and that it………………………………... Then why it is, we recommend the much more difficult thing.

Hydrochlorothiazide and Prevention of Kidney-Stone Recurrence | NEJM

N Engl J Med 2023; 388:781-791

Thiazide diuretic agents are widely used for prevention of the recurrence of kidney stones, but data regarding the efficacy of such agents as compared with placebo are limited.

double-blind RCT

patients with recurrent calcium-containing kidney stones were randomized to hctz 12.5 mg, 25 mg, or 50 mg once daily or placebo once daily. 

primary end point, a composite of symptomatic or radiologic recurrence of kidney stones. Symptomatic= The visible passage of a stone and radiologic =Appearance of new stones on CT

416 patients were randomized and followed for almost 3yrs

primary end-point event occurred in (59%) in the placebo group

(59%) in the 12.5-mg hydrochlorothiazide group 

(56%) in the 25-mg group

(49%) in the 50-mg group  (rate ratio, 0.92; 95% CI, 0.63 to 1.36)

No difference in any of the subgroups that was looked at there was no difference in the stone composition if it was calcium oxalate or calcium phosphate there was no difference

Some women and people of race were underrepresented in this study but when you have a well done study that is the best we have the burden of proof now falls on you to prove there is benefit… for me this goes against board questions and what I thought was true and will lead me to stopping HCTZ if I am using it for prevention of kidney stones.

Study design: Randomized controlled trial (nonblinded)

Looking to see if intensive screening protocol for cardiovascular disease reduce cardiovascular events or mortality in older men?

Danish study, 46,611 men aged 65 to 74 years were randomly assigned to receive an invitation to screening or usual care

The screening program included non-contrast electrocardiographically gated CT to measure coronary artery calcium, look for aneurysms, and detect atrial fibrillation; ankle-brachial index measurements for peripheral arterial disease (PAD) and hypertension; and blood tests for diabetes and hyperlipidemia

Those who accepted screening were more educated, more likely to be employed, and had a somewhat lower rate of hospitalization for cardiovascular events in the previous 5 years. (the rich white gullible ceo male)

The screened group was more likely to be given lipid-lowering drugs and antithrombotics, and they were more likely to have repair of an aortic aneurysm.

In the entire population, stroke was less likely (HR 0.93; 0.86 - 0.99) but there were no significant differences in myocardial infarction, aortic dissection, or aortic rupture.

The authors estimated that 97.4% of men who received preventive therapy of some kind as a result of screening experienced no mortality benefit after almost 6 yrs of follow up.

This is basically a really small absolute benefit which we could also see in just placing a pt on a statin. We don’t need vip medicine we need pcp that have time to calculate risk and place pt on statin when indicated.

Goldberg RB, Orchard TJ, Crandall JP, et al, for the Diabetes Prevention Program Research Group. Effects of long-term metformin and lifestyle interventions on cardiovascular events in the diabetes prevention program and its outcome study. Circulation 2022;145(22):1632-1641.

Study design: Randomized controlled trial (nonblinded)

What is the long-term impact of treating prediabetes on mortality and cardiovascular outcomes?

Go way back

original Diabetes Prevention Program study randomized 3234 overweight or obese adults with impaired glucose tolerance ("prediabetes") to receive metformin 850 mg twice daily, an intensive exercise program, or placebo and followed them for 3 years

Patients were invited to participate in a long-term open-label follow-up study This article reports long-term cardiovascular and mortality outcomes for each group.

Patients in the intervention groups were less likely to have been given a diagnosis of T2DM (55% for metformin and 53% for lifestyle vs 60% for placebo; P = .001; number needed to treat [NNT] = 17)

There was no difference between either intervention group and placebo with regard to the risk of cardiovascular death, nonfatal stroke, or nonfatal myocardial infarction. There was also no significant difference in the composite of all 3 outcomes for the original metformin group versus the placebo group (hazard ratio [HR] 1.03; 95% CI 0.78 - 1.37) or for those in the original lifestyle group versus the placebo group (HR 1.14; 0.87 - 1.50).

More is less or rather more meds is less diagnosis but no difference in things we actually care about

Skjerven HO, Lie A, Vettukattil R, et al. Early food intervention and skin emollients to prevent food allergy in young children (PreventADALL): a factorial, multicentre, cluster-randomised trial. Lancet 2022;399(10344):2398-2411.

Study design: Randomized controlled trial (single-blinded)

Does the early introduction of allergenic foods prevent the development of food allergy?

investigators randomized healthy newborns, singletons or twins, with at least 35 weeks' gestational age (concealed allocation) to receive no intervention (n = 597), a skin intervention (n = 575), a food intervention (n = 642), or a combined intervention (n = 583).

The skin intervention consisted of 5- to 10-minute baths with added petrolatum-based emulsified oil followed by topical cetirizine cream applied to the face. This intervention was to occur at least 4 days per week from age 2 weeks to 8 months,

The food allergy intervention consisted of sequentially adding allergenic foods (peanuts, cow’s milk, wheat, then eggs) to the infants’ regular diet at weekly intervals starting at age 3 months.

Overall, 95% of the infants in each group were breastfed at 3 months

The researchers had final data on 99.9% of the participants!

based on structured parental interviews, skin testing, and oral challenges  The researchers classified the development of food allergy at 36 months as probable, none, or unclear. 

There was no significant difference, however, between the infants who were exposed to skin interventions and those who were not exposed (2.1% vs 1.6%).

BUT BUT BUT

Food allergy occurred in 1.1% of infants in the interventions using food (food intervention and combination intervention) compared with 2.6% in not using food (no intervention and skin intervention; number needed to treat = 63; 95% CI 37-196).

Lewis E, Merghani K, Robertson I, et al. The effectiveness of leucocyte-poor platelet-rich plasma injections on symptomatic early osteoarthritis of the knee: the PEAK randomized controlled trial. Bone Joint J 2022;104-B(6):663-671.

Study design: Randomized controlled trial (double-blinded)

Allocation: Concealed

recruited adults with at least 4 months of knee pain (with or without swelling) who had mild degeneration on their x-rays (if plain x-rays found no signs of degeneration, they used magnetic resonance imaging to confirm the diagnosis).

The participants were randomized to receive 3 weekly saline injections (n = 28), or

a single PRP injection followed by 2 weekly saline injections (n = 47), or

3 weekly PRP injections (n = 27).

. The clinician performing the injections was unmasked but had no other involvement in the study procedures.

the participants were evaluated at 6 weeks, 12 weeks, 6 months, and 12 months after enrollment

Using intention-to-treat analysis looking at pain, function, and quality of life, at no point in the study were PRP injections, singly or serially, superior to saline injections.

 randomized noninferiority study from Emory University, 224 hospitalized patients with longstanding type 2 diabetes 

 Both groups received basal/bolus insulin; both the starting dose and subsequent changes were specified by the study protocol. Additional premeal SSI was added to scheduled premeal bolus doses.

randomized to either intensive SSI (at BG >140 mg/dL) or nonintensive SSI (at BG >260 mg/dL) before meals and at bedtime. 

Mean baseline glycosylated hemoglobin (HbA1c) was 9%, and 60% of patients were using insulin at home. Patients with a presenting glucose level of >400 mg/dL or diabetic ketoacidosis were excluded.

Outcome---Mean daily BG level, hypoglycemia, severe hyperglycemia, percent of BGs in the target range (70–180 mg/dL), and the amount of total, basal, or prandial insulin used did not differ between groups. However, significantly fewer patients in the nonintensive group than in the intensive group received SSI (34% vs. 91%).

COMMENT

Although this is a single-center study, its results are persuasive and suggest that a less-intense SSI regimen can achieve similar glucose outcomes in hospitalized patients with type 2 diabetes who are receiving basal/bolus insulin. It also could decrease nursing treatment burden. As we move slowly toward more continuous glucose monitoring in hospitals, reducing use of SSI is another opportunity to achieve similar results with less staff burden and more patient comfort.

Comparative Effectiveness and Safety Between Apixaban, Dabigatran, Edoxaban, and Rivaroxaban Among Patients With Atrial Fibrillation: A Multinational Population-Based Cohort Study: Annals of Internal Medicine: Vol 175, No 11 (acpjournals.org)

In a retrospective study, investigators accessed five electronic health databases from Europe and the U.S. to compare >500,000 new DOAC users with newly diagnosed atrial fibrillation. Follow up varied from 1.5 to 4.5 years.

In propensity score–adjusted analyses, patients who received apixaban had significantly less gastrointestinal (GI) bleeding did those who received any of the other three drugs (hazard ratios, 0.7–0.8). This result was consistent among older patients and those with chronic kidney disease (CKD). Risk for stroke or other systemic embolism, intracranial hemorrhage, and all-cause mortality did not differ significantly among DOACs.

COMMENT

This is the largest comparison of individual DOACs, and it demonstrates similar efficacy among all agents. Although apixaban was associated with less GI bleeding, absolute percentages of GI bleeds ranged from ≈2% to ≈3.5% for all DOACs; therefore, apixaban's statistically significant safety benefit might amount to marginal clinical benefit for any individual patient. I might turn to apixaban for patients at high risk for GI bleeding (and those with CKD), but all DOACs remain reasonable options for preventing thromboembolism in most patients with atrial fibrillation.

Ellenbogen MI et al. Safety and effectiveness of apixaban versus warfarin for acute venous thromboembolism in patients with end-stage kidney disease: A national cohort study. J Hosp Med 2022 Oct; 17:809. (https://doi.org/10.1002/jhm.12926. opens in new tab)

. In an industry-funded retrospective study, investigators used a national database (years, 2014–2018) and propensity score–adjusted analysis to compare outcomes among >11,500 patients with ESRD and newly diagnosed VTE who received either apixaban or warfarin.

Only 2% of patients received apixaban in 2014, but 47% received apixaban in 2018.

during the 6 months following initiation of therapy, apixaban — compared with warfarin 

associated with significantly lower incidence of major bleeding (10% vs. 14%), including intracranial bleeding (1.8% vs. 2.5%) and gastrointestinal bleeding (8.6% vs. 10.4%). 

Recurrent VTE and all-cause mortality were similar in the two groups.

VTE and creatine clearence less than 30 then I think apixaban is the drug of choice—I would like to see this study don’t with afib and done with exclusively <15 gfr but we take what we can get and the take home is venous thromboembolism (VTE) and gfr <30 go ahead and fire away with apixaban

The EMPA-KIDNEY Collaborative Group. Empagliflozin in patients with chronic kidney disease. N Engl J Med 2022 Nov 4; [e-pub]. (https://doi.org/10.1056/NEJMoa2204233. opens in new tab)

dapagliflozin is FDA-approved to slow progression of chronic kidney disease (CKD) 

empa wanted in on the fun and money

industry-supported researchers randomized 6600 patients with or without type 2 diabetes. with CKD to receive empagliflozin (10 mg daily) or placebo.

 Enrollment criteria included estimated glomerular filtration rate (GFR) between 20 and 45 mL/minute/1.73 m2 regardless of proteinuria, or GFR between 45 and 90 mL/minute in patients with substantial proteinuria.

follow-up of 2 years,

primary composite outcome — largely comprising a 40% decline in GFR or cardiovascular-related or renal-related death

was significantly lower with empagliflozin than with placebo (13% vs. 17%).

Less progression of CKD with empagliflozin accounted for this difference; no significant differences between groups were noted for mortality

Normally I would say a decrease progression of CKD is a bs ending and this isn’t patient oriented outcome. HOWEVER,

Initiation of dialysis or receipt of a renal transplant occurred significantly less often with empagliflozin than with placebo (3.3% vs. 4.8%). At a NNT of 66.

But once again empag cost 560$ per month. Follow up was 24 months. Which means 65 people have to take a $500 per month drug for 2 years which is This is a whopping 873,000$ spent for one person to be saved renal transplant or starting dialysis.

Zheng J et al. Cost-effectiveness of empagliflozin in patients with heart failure with preserved ejection fraction. JAMA Intern Med 2022 Nov 7; [e-pub]. (https://doi.org/10.1001/jamainternmed.2022.5010. opens in new tab)

At its current price, this drug provides low value in patients with heart failure with preserved ejection fraction.

The authors did something great here and said hey if you assume a  9% reduction in cardiovascular-related mortality (the nonsignificant reduction noted in the trial), cost-effectiveness would have been somewhat more acceptable

However they also usethe cost as 327$ per month… which is very generous as I can not find that number any place!!! So even with their generous calculation it still is not worth it-- yet