Questioning Medicine

Packer M et al. Tirzepatide for heart failure with preserved ejection fraction and obesity. N Engl J Med 2024 Nov 16; [e-pub].https://doi.org/10.1056/NEJMoa2410027  In the industry-funded SUMMIT trial (NCT04847557), investigators examined cardiovascular outcomes of tirzepatide — an agonist of glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptors — over a longer period in patients with HFpEF and obesity.  The 731 study participants had elevated filling pressures or an elevated N-terminal pro–B-type natriuretic peptide (NT-proBNP) level, and a heart failure exacerbation event within the prior 12 months or a decreased estimated glomerular filtration rate <70 mL/min/1.73 m2. They were randomized to once-weekly subcutaneous tirzepatide (up to 15 mg) or placebo for at least 52 weeks with a median follow-up of 104 weeks.Compared with placebo, tirzepatide resulted in significantly fewer primary-endpoint events (adjudicated heart-failure worsening or cardiovascular death) — 10% vs. 15% (hazard rati

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

STROKE part 3 CME

CME FOR FREEE 

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

Beran A et al. Early diagnostic paracentesis improves outcomes of hospitalized patients with cirrhosis and ascites: A systematic review and meta-analysis. Am J Gastroenterol 2024 Nov; 119:2259. (https://doi.org/10.14309/ajg.0000000000002906) BOTTOM LINE (if you don’t like to read)- While it might not be fun to have the conversation with the ER provider saying you NEED A DIAGNOSTIC PARACENTESIS PRIOR TO THE PATIENT COMING TO THE FLOOR, just remember that every 33 times we have that conversation, we are saving a life and decreasing the length of stay by 5 days on average.  We have all had the admission from the ER on a patient that needs a paracentesis but it is the weekend so they are going to just admit for antibiotics and then IR can come do it on Monday.  Guidelines recommend diagnostic paracentesis in all patients hospitalized with cirrhosis and ascites, but they do not recommend specific timing of inpatient paracentesis. (Biggins SW et al. Diagnosis, evaluation, and management of ascites, spontaneous bact

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

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

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

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

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

You get the CME knowledge without the CME payment!

 10% of hospitalized patients have penicillin allergy listed in their records, fewer than 1% of patients have true allergies. Use of more-expensive and broader-spectrum antibiotics is associated with longer and more-expensive hospital stays and more side effects, nosocomial infections, and resistant organisms.  Blumenthal KG et al. Reaction risk to direct penicillin challenges: A systematic review and meta-analysis. JAMA Intern Med 2024 Sep 16; [e-pub]. (https://doi.org/10.1001/jamainternmed.2024.4606)   researchers examined the safety of direct penicillin challenges (without preceding skin tests) for delabeling patients without true allergies. Among more than 9000 patients in these studies, 438 experienced reactions (3.5%), with only 5 reactions classified as severe: 3 episodes of anaphylaxis, 1 delayed rash with fever, and 1 kidney injury. No fatalities were reported.NNH of 1800  The PENFAST score is a good tool to help decide which patients can undergo direct oral challenge safely (NEJM JW Gen Med Aug 1 20

Efficacy and Safety of a Novel Low-Dose Triple Single-Pill Combination Compared With Placebo for Initial Treatment of HypertensionJ Am Coll Cardiol 2024 Aug 30;[EPub Ahead of Print], A Rodgers, A Salam, AE Schutte, WC Cushman, HA de Silva, GL Di Tanna, D Grobbee, K Narkiewicz, DB Ojji, NR Poulter, MP Schlaich, S Oparil, W Spiering, B Williams, JT Wright, A Gutierez, A Sanni, P Lakshman, D McMullen, G Ranasinghe, C Gianacas, M Shanthakumar, X Liu, N Wang, P Whelton    randomized, double-blind, placebo-controlled trial of a new single-pill combination comprising low doses of telmisartan, amlodipine, and indapamide for treating hypertension in 295 adults with mild to moderate hypertension. baseline systolic BP of 130 to 154 mm Hg during a placebo run-in, and had a low estimated 10-year risk for cardiovascular disease (<10%). The primary efficacy outcome was difference in change in home SBP from randomization to week 4  patients were randomized in a double-blind manner into three different arms: GMRx2 at a qua

In 2011, the Endocrine Society published a guideline on “Evaluation, Treatment, and Prevention of Vitamin D Deficiency”   Now, the Society has issued an updated guideline, Demay MB et al. Vitamin D for the prevention of disease: An Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2024 Aug; 109:1907. (https://doi.org/10.1210/clinem/dgae290)  Previously, the Endocrine Society had labeled vitamin D status as “deficient” when serum hydroxyvitamin D (25[OH]D) was lower than 20 ng/mL, and “insufficient” when serum 25(OH)D was 20 ng/mL to 29 ng/mL. Now, the Society “no longer endorses specific 25(OH)D levels to define vitamin D sufficiency, insufficiency, and deficiency.”  Why is that--- because no clinical research has not established distinct thresholds of serum levels that can be tied confidently to specific clinical outcomes. In the general population of adults (age range, 19–74), neither routine vitamin D supplementation nor routine testing of 25(OH)D levels are recommended. What about >

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

 Because glucagon-like peptide-1 (GLP-1) receptor agonists can slow gastric emptying, they might confer risk for residual gastric contents — and possibly aspiration!!!! Should we stop the glp-1 Should we stop the glp-1-- Anesthesiologists and gastroenterologists have weighed in on this concern and on QM I say just do whatever the anesthesiologist want because they have the final say!!  Sen S et al. Glucagon-like peptide-1 receptor agonist use and residual gastric content before anesthesia. JAMA Surg 2024 Jun; 159:660. per American Society of Anesthesiologists [ASA] guidelines; Prior to surgery, patients had fasted at least 2 hours for clear liquids, 6 hours for light meals, and 8 hours for full meals   researchers performed gastric ultrasound just prior to elective surgery in 62 patients who were using weekly injected GLP-1 agonists (semaglutide, dulaglutide, or tirzepatide) and in 62 nonusers (controls).  The prevalence of residual gastric contents was significantly higher in the GLP-1 group than in the cont

Oropharyngeal dysphagia is highly prevalent in hospitalized patients with Alzheimer disease or other dementias. These patients often are prescribed thick liquid diets Makhnevich A et al. Thick liquids and clinical outcomes in hospitalized patients with Alzheimer disease and related dementias and dysphagia. JAMA Intern Med 2024 May 6; [e-pub]. Researchers conducted a retrospective propensity-matched analysis, ≈4500 patients with Alzheimer disease or other dementias who were hospitalized with clinical concern for dysphagia and received thick liquid diets and matched to ≈4500 patients who had received thin liquid diets.  Hospital mortality was similar in the two groups. Compared with patients who received thin liquids, those who received thick liquids were significantly less likely to be intubated (odds ratio, 0.7) but were significantly more likely to have respiratory complications, including pneumonia (OR, 1.7) In this end you are preventing intubation by 30 percent but causing pna by 70% --- neither are good

Feedback and Financial Incentives for Reducing Cell Phone Use While Driving: A Randomized Clinical Trial | Public Health | JAMA Network Open | JAMA Network  Question  Can behavioral interventions decrease handheld cell phone–based driver distraction?   17663 and ended up with 2020 participantsProgressive 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 w

Noncontrast CT Selected Thrombectomy vs Medical Management for Late-Window Anterior Large Vessel Occlusion | Neurology 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 commo