STROKE part 3 CME

CME FOR FREEE 

 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. 

Nurse Practitioners prescribe medications off the beers list at the same rate at primary care physicians, hard to tell what this means for patient care and patient outcomes. 


https://www.acpjournals.org/doi/10.7326/M23-0827?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed

Using the Brain Care Score seem to be effective in predicting the risk of dementia

• 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.

Even when starting DAPT within 72hours of symptom onset for individuals with minor stroke or TIA the benefit of DAPT for the first 21 days was still seen at 90 day follow up in the form of less recurrent stroke

https://www.nejm.org/do/10.1056/NEJMdo007334/full/

In those high risk patients -- usually with lung or GI cancer they did benefit from primary prevention VTE prophalaxis with a NNT of 6-7 for VTE and death at 6 months. 

https://pubmed.ncbi.nlm.nih.gov/37733336/#:~:text=Conclusions%20and%20relevance%3A%20In%20this,safety%20concerns%2C%20and%20with%20reduced

Just get he biopsy at less than 6 weeks after starting therapy as the yield was the same at 2 weeks as it was at 4-6 weeks


https://pubmed.ncbi.nlm.nih.gov/36642440/

Evidence against baby walker is not enough regarding its negative effect on child development. This subject needs to be addressed more, considering a large number of baby walker users worldwide.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5703622/


Surveillance System data from 1990 to 2014 

 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

During average follow-up of in this study the incidence of prostate cancer was less than 1% — and not significantly different 
 Remember most of these pts had testosterone levels around 350 ish give or take so the safety of longer-duration treatment — or treatment resulting in higher blood levels of testosterone — remains unclear.

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

From a mean score of 45 points at baseline, mood improved by about 5 points in the placebo group and 6 points in the testosterone group — a statistically significant but small difference. I think you will be hard pressed to find anyone that thinks this is clinically significant except for maybe the authors of the paper when they write that it is beneficial in their conclusion

https://academic.oup.com/jcem/advance-article-abstract/doi/10.1210/clinem/dgae026/7516050?redirectedFrom=fulltext&login=true

Erectile disfunction should be treated with the appropriate medications like the PDE5 inhbitors—not testosterone—testosterone may make it so you flirt half a time more a day but that is not likely worth the harm that comes with even in the placebo small doses seen in the traverse trial

https://academic.oup.com/jcem/article-abstract/109/2/569/7244351?redirectedFrom=fulltext&login=true

even at very small some would argue barely even treating doses of testosterone patients had an increase rate of fractures with a NNH of 100—when you add this to the 1 risk of aki and 2 percent risk of arthymia the harms vs benefit conversation to use testosterone seems to be leaning heavy towards harms

https://www.nejm.org/doi/full/10.1056/NEJMoa2308836?query=recirc_curatedRelated_article

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

Risk of progression from prediabetes to 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

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

Take away

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

Use the PE Severity Index. If low risk and that is the only reason for admission, then the patient is safe for discharge

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)60824-6/abstract

https://www.acpjournals.org/doi/10.7326/M23-2442

american college of physicians says- 

No need to start colon cancer screening prior to 50. stop at age 75 or with 10 yrs of life left and FIT testing can be every other year and Cologuard is not recommended. 

https://www.acponline.org/acp-newsroom/acp-issues-updated-guidance-for-colorectal-cancer-screening-of-asymptomatic-adults

While weight loss may be beneficial for individuals with knee osteoarthritis, it does not see to have a protective or beneficial effect for those with hip osteoarthritis. 

https://agsjournals.onlinelibrary.wiley.com/doi/10.1111/jgs.18371

In patients with HIV and cv risk score of 4.5% there was a NNT of 106 at 5 yrs of follow up to prevent 1 MACE

https://www.acpjournals.org/doi/10.7326/M22-2643?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed

A cuff 1-2 sizes too large underestimated bp by 4-9mm Hg BUT a cuff 1-2 sizes too small overestimated the BP 4-20mm Hg

https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2807853

GLP1 agonist likely lead to retained gastric products but this effect is larger for once weekly injections than once daily pills.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10204182/

During 28 months of follow-up, absolute risks for progression from CIN2 to CIN3 (or worse) were as follows:

• 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)

>10% unintentional weight loss is most likely associated with 

• 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)

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

PDE5i are bad if your health if you have cardiovascular disease and a provider that didn't read the paper and only looked at the abstract. Go ahead and write for PDE5i for your patients that need it and do not change your practice based on this study. 

https://www.sciencedirect.com/science/article/pii/S0735109723080749?via%3Dihub#mmc1

Doxy 100mg BID x7days for chlamydia- and consider treating the partner unless you live in West Virginia. 

https://www.cdc.gov/std/treatment-guidelines/chlamydia.htm

Overall incidence of zoster (defined as the presence of the specific diagnostic code in the medical record, accompanied by a prescription for acyclovir) was lower among vaccine recipients, with vaccine protective efficacy estimated to be 64% after a single dose and 76% after two doses.



Zerbo O et al. Effectiveness of recombinant zoster vaccine against herpes zoster in a real-world setting. Ann Intern Med 2024 Jan 9; [e-pub]. (https://doi.org/10.7326/M23-2023. opens in new tab)

• Compared with complication rates in the National Lung Screening Trial, this real-world study had approximately twice the rate of procedural complications (31% vs. 18%) and major complications (i.e., acute respiratory failure, lung collapse or cardiac arrest; 21% vs. 9%).

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)

Ask about and stop aspirin in patients taking it for primary prevention


Li DK et al. Trends in upper gastrointestinal bleeding in patients on primary prevention aspirin: A nationwide emergency department sample analysis, 2016–2020. Am J Med 2023 Dec; 136:1179. (https://doi.org/10.1016/j.amjmed.2023.08.010)

At 25yrs the odds of still having your appendix if you were initially managed nonoperatively was 60%.

https://jamanetwork.com/journals/jamasurgery/article-abstract/2808133

Although an observational trial, it appears lactated ringers is better than normal saline for those individuals with acute pancreatitis to prevent organ failure or local complications. 

https://journals.lww.com/ajg/fulltext/2023/12000/lactated_ringers_use_in_the_first_24_hours_of.29.aspx

2300 steps daily was needed to decrease cardiovascular-related mortality. 4000 steps daily decreased all-cause mortality. Each additional step seem to lower mortality risk. 

https://pubmed.ncbi.nlm.nih.gov/37555441/#:~:text=Conclusion%3A%20This%20meta%2Danalysis%20demonstrates,2337%20steps%20for%20CV%20mortality.

Consider ablation in patients who have an EF < 35% and atrial fibrillation the NNT for all cause mortality was 7 at 18 months 

https://www.nejm.org/doi/full/10.1056/NEJMoa2306037

Sleep restriction therapy led by nurses with only 4 hours of education significantly improved patients insomnia at 6 months.

More info HERE ___>
https://thrive.kaiserpermanente.org/care-near-you/northern-california/sanjose/wp-content/uploads/sites/7/2015/10/sleep-restriction-rev2_tcm28-557887.pdf

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)00683-9/fulltext#:~:text=Results%20indicate%20superiority%20of%20nurse,at%20established%20cost%2Deffectiveness%20thresholds.

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

Kansas City Cardiomyopathy Questionnaire clinical summary score was improved by 7.8 in those individuals with HFpEF that took semaglutide for one year compared to those that took placebo. This is a small difference on a validated score and would cost 16-20K per year. more research is needed. 

https://www.nejm.org/doi/full/10.1056/NEJMoa2306963

When taking Ferrous Fumarate a little bit of vitamin C or an 8 ounce glass of orange juice with an otherwise empty stomach will improve the absorption- this absorption is decreased with food and coffee.  

https://onlinelibrary.wiley.com/doi/10.1002/ajh.26987

https://www.nejm.org/doi/full/10.1056/NEJMoa2307563

Semaglutide and CAD but no diabetes decreases events NNT of 66 at 40 months but a predicted price tag of 3.5 million dollars.

Olanzapine 2.5mg for weight gain with advance cancer NNT of 50 for >5% weight gain


https://pubmed.ncbi.nlm.nih.gov/36977285/

ACC/AHA just came out with new guidelines on AFIB if you need some light reading material! (big take home rhythm not rate, and not equal, read below for more information)

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.

Effectiveness and Safety of Enteric-Coated vs Uncoated Aspirin in Patients With Cardiovascular Disease: A Secondary Analysis of the ADAPTABLE Randomized Clinical Trial | Clinical Pharmacy and Pharmacology | JAMA Cardiology | JAMA Network

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

214. NEW FORMAT-- What is the best drunk for alcohol use disorder?

https://jamanetwork.com/journals/jama/article-abstract/2811435

systolic

CME for the cost of free fifty free

 (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

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. 

I give CME and you listen for free. You can't collect the CME but YOU CAN be a little smarter. These are some must know articles you need to know if you are a hospitalist. 

What about oral??

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.

Lindholt JS, Søgaard R, Rasmussen LM, et al. Five-year outcomes of the Danish cardiovascular screening (DANCAVAS) trial. N Engl J Med 2022;387(15):1385-1394.

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.