10% of hospitalized patients have penicillin allergy listed in their records, fewer than 1% of patients have true allergies.

Use of more-expensive and broader-spectrum antibiotics is associated with longer and more-expensive hospital stays and more side effects, nosocomial infections, and resistant organisms.

Blumenthal KG et al. Reaction risk to direct penicillin challenges: A systematic review and meta-analysis. JAMA Intern Med 2024 Sep 16; [e-pub]. (https://doi.org/10.1001/jamainternmed.2024.4606)

 researchers examined the safety of direct penicillin challenges (without preceding skin tests) for delabeling patients without true allergies. Among more than 9000 patients in these studies, 438 experienced reactions (3.5%), with only 5 reactions classified as severe: 3 episodes of anaphylaxis, 1 delayed rash with fever, and 1 kidney injury. No fatalities were reported.

NNH of 1800

The PENFAST score is a good tool to help decide which patients can undergo direct oral challenge safely (NEJM JW Gen Med Aug 1 2023 and JAMA Intern Med 2023; 183:883). In general, if a patient has a history of severe immediate reaction (angioedema or anaphylaxis), a recent urticarial reaction (within 5 years), or any severe delayed reaction (e.g., Stevens–Johnson syndrome, serum sickness, drug reaction with eosinophilia, drug-induced cytopenia, organ injury), I would refer to an allergist for evaluation.

Bottom line

We have far more patients who should have their penicillin allergy delabeled than we have allergists to perform these challenges. Primary care clinicians and hospitalists can do this easily by giving one dose of amoxicillin (500 mg) and watching the patient for 1 to 2 hours; intramuscular epinephrine and oral antihistamines must be available, but are seldom needed. 

Efficacy and Safety of a Novel Low-Dose Triple Single-Pill Combination Compared With Placebo for Initial Treatment of Hypertension

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

In 2011, the Endocrine Society published a guideline on “Evaluation, Treatment, and Prevention of Vitamin D Deficiency”

 Now, the Society has issued an updated guideline, Demay MB et al. Vitamin D for the prevention of disease: An Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2024 Aug; 109:1907. (https://doi.org/10.1210/clinem/dgae290)

Previously, the Endocrine Society had labeled vitamin D status as “deficient” when serum hydroxyvitamin D (25[OH]D) was lower than 20 ng/mL, and “insufficient” when serum 25(OH)D was 20 ng/mL to 29 ng/mL. Now, the Society “no longer endorses specific 25(OH)D levels to define vitamin D sufficiency, insufficiency, and deficiency.” 

Why is that--- because no clinical research has not established distinct thresholds of serum levels that can be tied confidently to specific clinical outcomes.

In the general population of adults (age range, 19–74), neither routine vitamin D supplementation nor routine testing of 25(OH)D levels are recommended.

What about >75—NOT RECOMMENDED!  They do suggest vit sup for possible to lower mortality but acknowledge that this effect was small and bordline statistical significance ___ relative risk, 0.96; 95% confidence interval, 0.93–1.00 – to it hit the line of no effect on flawed bias studies! Come on!!!!!

An evidence review showed no conclusive evidence that supplementation lowered risks for fractures, falls, or infections in this age group

The common practice of ordering routine 25(OH)D levels is not recommended,. Obtaining serum 25(OH)D levels in relatively healthy people and prescribing vitamin D supplements to get levels ≥30 ng/mL (or even higher) is not supported by this guideline.

FINALLY—you want to give then go ahead and give a reasonable amount but don’t test. Don’t research. Don’t target a level. JUST DONT

Huijberts I et al. Collateral-based selection for endovascular treatment of acute ischaemic stroke in the late window (MR CLEAN-LATE): 2-year follow-up of a phase 3, multicentre, open-label, randomised controlled trial in the Netherlands. Lancet Neurol 2024 Sep; 23:893. (https://doi.org/10.1016/S1474-4422(24)00228-X)

 The modified Rankin Scale (mRS) score at 2 years was the primary outcome. The median mRS at 2 years was 4 in the EVT group and 6 in the control group. For functional independence (mRS, 0–2), the rates were 35% in the EVT patients and 27% in the control group. Mortality at 2 years did not differ between the treatment groups.

 However, about 12 patients need to be treated to provide one additional patient with functional independence, a higher number needed to treat than observed in studies of EVT provided in the early time window (e.g., N Engl J Med 2015; 372:2285)

Still 24 hours AFTER a stroke!! amazing

Because glucagon-like peptide-1 (GLP-1) receptor agonists can slow gastric emptying, they might confer risk for residual gastric contents — and possibly aspiration!!!! Should we stop the glp-1

Should we stop the glp-1-- Anesthesiologists and gastroenterologists have weighed in on this concern and on QM I say just do whatever the anesthesiologist want because they have the final say!!

Sen S et al. Glucagon-like peptide-1 receptor agonist use and residual gastric content before anesthesia. JAMA Surg 2024 Jun; 159:660.

per American Society of Anesthesiologists [ASA] guidelines; Prior to surgery, patients had fasted at least 2 hours for clear liquids, 6 hours for light meals, and 8 hours for full meals 

researchers performed gastric ultrasound just prior to elective surgery in 62 patients who were using weekly injected GLP-1 agonists (semaglutide, dulaglutide, or tirzepatide) and in 62 nonusers (controls).

The prevalence of residual gastric contents was significantly higher in the GLP-1 group than in the control group (56% vs. 19%). After adjustment for confounders, GLP-1 users remained significantly more likely than controls to have residual gastric contents.

Sen S et al. Glucagon-like peptide-1 receptor agonist use and residual gastric content before anesthesia. JAMA Surg 2024 Jun; 159:660.

We still don't know the overall clinical consequences of residual gastric contents in GLP-1 users who undergo elective surgery under anesthesia. For now, clinicians who provide preoperative consultation should try to find out policies of local anesthesiology groups. 

Oropharyngeal dysphagia is highly prevalent in hospitalized patients with Alzheimer disease or other dementias. These patients often are prescribed thick liquid diets

Makhnevich A et al. Thick liquids and clinical outcomes in hospitalized patients with Alzheimer disease and related dementias and dysphagia. JAMA Intern Med 2024 May 6; [e-pub].

Researchers conducted a retrospective propensity-matched analysis, ≈4500 patients with Alzheimer disease or other dementias who were hospitalized with clinical concern for dysphagia and received thick liquid diets and matched to ≈4500 patients who had received thin liquid diets. 

Hospital mortality was similar in the two groups. Compared with patients who received thin liquids, those who received thick liquids were significantly less likely to be intubated (odds ratio, 0.7) but were significantly more likely to have respiratory complications, including pneumonia (OR, 1.7)

In this end you are preventing intubation by 30 percent but causing pna by 70% --- neither are good and neither is a clear winner

Rant on ‘what we know to be true’ and measure it

This large study supports a hypothesis that thick liquids minimize the volume of aspiration, which explains the decrease in intubations. However, thick liquids also are more difficult to clear from the airway when aspiration occurs, leading to more respiratory complications.

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 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.

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 common with EVT than with MM alone (8.5% vs. 1.4%), but overall mortality was lower with EVT (24% vs. 32%).

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2820369

With as many as 1 in 3 US adults using multivitamin supplements, the question as to whether these supplements reduce mortality

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.

https://www.acpjournals.org/doi/10.7326/M23-3236

Angiotensin-converting–enzyme (ACE) inhibitors or angiotensin-receptor blockers (ARBs) seldom are initiated among patients with chronic kidney disease (CKD) stage 4 or 5, despite guideline recommendations for these agents--- 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines - ScienceDirect

“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).