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All of these articles have been talked about on questioning medicine social media on tik tok and instagram but here is an update of my recent reading

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.

https://www.nejm.org/doi/10.1056/NEJMoa2504544

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:

https://publications.aap.org/pediatrics/article/156/1/e2024070175/202234/Infant-Antibodies-After-Maternal-COVID-19?autologincheck=redirected

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.

https://www.nejm.org/doi/10.1056/NEJMoa2415879?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed

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).

GLP1 might cause thyroid cancer in mice but the evidence is drastically lacking in humans

Oral semaglutide is expensive for an NNT of 50 at 4 yrs

Tiktok videos of skin care are a scam

https://jamanetwork.com/journals/jama/article-abstract/2834040
amiloride is realistically equal to spironolactone for resistant HTN

https://journals.lww.com/ajg/abstract/2025/05000/higher_rate_of_spontaneous_bacterial_peritonitis.24.aspx
prophalaxis antibiotics might not be needed

https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2834317
If you got a friend in weight loss-- or at least in maintaining weight loss

https://www.jthjournal.org/article/S1538-7836(25)00109-6/fulltext
Antithrombotic agents, like aspirin and anticoagulants, are essential for treating many cardiovascular conditions. However, a common side effect is bleeding, with extracranial bleeding—bleeding outside the brain and spinal cord—being quite prevalent. This study, a secondary analysis of the Aspirin in Reducing Events in the Elderly, or ASPREE trial, aimed to explore how clinically significant extracranial bleeding affects the development of functional disability in otherwise healthy older adults.

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.

https://jamanetwork.com/journals/jama/article-abstract/2834632

Summary

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.

https://www.nejm.org/doi/full/10.1056/NEJMoa2405182?query=recirc_Semantic

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.

Desgagnés N et al. Use of albumin-adjusted calcium measurements in clinical practice. JAMA Netw Open 2025 Jan 21; 8:e2455251. (https://doi.org/10.1001/jamanetworkopen.2024.55251)


Overall, total calcium levels (just the ones we would get back on a basic cmp) correlated better with ionized calcium than did formula-corrected calcium levels. Formulas with stronger correlation than total calcium levels were either complex (e.g., requiring blood pH measurement) or derived locally (i.e., not generalizable). Many formulas overestimated calcium at low calcium levels; the Payne formula misclassified 41% of patients, whereas the total calcium level only misclassified 25% of patients.

https://www.nejm.org/doi/10.1056/NEJMoa2416394

At 72 weeks, the mean percentage decrease in weight was significantly greater with tirzepatide than with semaglutide (20% vs. 14%). Gastrointestinal side effects occurred frequently in both groups but led to discontinuation of treatment in only 3% and 6% of participants in the tirzepatide and semaglutide groups, respectively. Injection-site reactions were more common with tirzepatide than with semaglutide (9% vs. <1%) but didn't cause participants to stop treatment.

https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2832701


In this multisite trial, 800 adults who smoked 10 or more cigarettes daily (mean duration of smoking, ≈35 years) were randomized to 6 or 12 weeks of cytisinicline or to placebo. In the 6-week group,15% of cytisinicline recipients and 6% of placebo recipients were abstinent (defined by self-report and breath carbon monoxide <10 ppm) during weeks 3 to 6. In the 12-week group, 30% of cytisinicline recipients and 9% of placebo recipients were abstinent during weeks 9 to 12.

What does the evidence and the guidelines say about the use and testing of Vitamin D in kids

Aryee EK et al. Prevalence of obesity with and without confirmation of excess adiposity among US adults. JAMA 2025 Apr 17; [e-pub]. (https://doi.org/10.1001/jama.2025.2704)

The rate of obesity was 39.7% based on BMI and 39.1% based on excess adiposity. Among participants with obesity based on BMI, 98% also had excess adiposity; in other words, essentially the same individuals were considered as obese by both criteria.

In an hour-by-hour analysis, patients we suspect to have asthma are significantly more likely to have positive bronchodilator responses early in the morning; with each passing hour before testing, there was small decrease (8%) in positive response. Patients also were more likely to have positive responses in the winter. 

Knox-Brown B et al. Effect of time of day and seasonal variation on bronchodilator responsiveness: The SPIRO-TIMETRY study. Thorax 2025 Mar 11; [e-pub]. (https://doi.org/10.1136/thorax-2024-222773)

Vitamin D and Adults and what you should do with Vitamin D

 a cme lecture on the outpatient management of COPD

CME

FREE CME KNOWLEDGE

Free CME

CME for FREE

https://www.nejm.org/doi/full/10.1056/NEJMoa2405923?query=clinical-medicine

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.

• Estimated 5-year incidence of recurrent VTE was similar in the reduced-dose and full-dose groups (2.2% and 1.8%).
  
  
• Estimated 5-year bleeding incidence was significantly lower with reduced-dose than with full-dose treatment (2.1% vs. 4.0% for major bleeding; 8.6% vs. 11.5% for clinically relevant nonmajor bleeding).
  
  
• Outcomes with apixaban and rivaroxaban were similar.
  
  

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)

https://www.nejm.org/doi/full/10.1056/NEJMoa2405404

NNT of 4! systemic metronid and topical clinda bid for one week

What Was Studied?

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.

Metformin while not necessarily first line therapy for diabetes depending on the patients co-morbid conditions it is certainly highly ranked on the list of medications!

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

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2825813


Conclusions and Relevance  In this randomized clinical trial assessing simultaneous vs sequential administration of mRNA COVID-19 and IIV4 vaccines, reactogenicity was comparable in both groups. These findings support the option of simultaneous administration of these vaccines.

https://www.bmj.com/content/388/bmj-2024-081164


systematic review and meta-analysis on prehabilitation before surgery, published in the BMJ in February 2025.Prehabilitation aims to prepare patients for surgery through interventions like exercise, nutrition, and psychological support. This study looked at which prehabilitation components are most effective for improving key outcomes after surgery.The researchers analyzed 186 randomized trials with over 15,000 participants. They used advanced statistical methods to compare different prehabilitation approaches.The key findings were:

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. 

Mammograms

379. REPORT mammogram part 1

https://jamanetwork.com/journals/jama/article-abstract/2828218

DCIS is a non-invasive form of breast cancer, meaning the abnormal cells are contained within the milk ducts. For years, the standard treatment has been surgery, often followed by radiation and/or hormone therapy - the same treatments used for invasive breast cancer. But is this aggressive approach always necessary for low-risk DCIS?(Transition Music - Short and subtle - 2 seconds)

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)

Association of Duration of Recognized Hypertension and Stroke Risk: The REGARDS Study

(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 CI et al. Association of dose of inhaled corticosteroids and frequency of adverse events. Am J Respir Crit Care Med 2025 Jan; 211:54. (https://doi.org/10.1164/rccm.202402-0368OC)

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.

Gao FM et al. A systematic review and meta-analysis on the safety and efficacy of sodium–glucose cotransporter 2 inhibitor use in hospitalized patients. Diabetes Care 2024 Dec 1; 47:2275. (https://doi.org/10.2337/dc24-0946)

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.

Is accelerated surgery for hip fracture better for high-risk patients?

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)

Today, we're discussing two groundbreaking studies from 2024 that challenge our understanding of β-blocker therapy for secondary prevention after myocardial infarction, or MI.Let's start with a Swedish study Beta-Blockers after Myocardial Infarction and Preserved Ejection Fraction | New England Journal of Medicine that included over 5,000 patients with normal left ventricular ejection fraction after an MI

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

Methods Monday  --- Accuracy of Event Rate and Effect Size Estimation in Major Cardiovascular Trials: A Systematic Review | Cardiology | JAMA Network Open | JAMA Network

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

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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.

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2821168

A team of researchers set out to change that by developing a comprehensive algorithm.The process involved a multidisciplinary panel of 11 expertss with extensive experience in managing urinary retention. These experts evaluated about 100 clinical scenarios to create an initial flow sheet. The algorithm was then refined through interviews with 33 frontline clinicians from various specialties.So, what does this new algorithm recommend? Let's break it down:First, bladder scanning is the preferred method for evaluating patients with urinary retention symptoms. It's also recommended for asymptomatic patients who haven't voided in 3 hours

.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

https://jamanetwork.com/journals/jama/article-abstract/2822097


Design, Setting, and Participants  Nested case-control study using population-based linked administrative datasets among adults aged 66 years or older who received at least 1 oral antibiotic between 2002 and 2022 in Ontario, Canada. Cases were those who had an emergency department (ED) visit or hospitalization for serious cADRs within 60 days of the prescription, and each case was matched with up to 4 controls who did not.

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.

https://www.nejm.org/doi/full/10.1056/NEJMoa2407001


Conclusions

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)

Allaudeen N et al. Medications for alcohol-use disorder and follow-up after hospitalization for alcohol withdrawal: A multicenter study. J Hosp Med 2024 Dec; 19:1122. (https://doi.org/10.1002/jhm.13458)

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).

Real‐world use of glucocorticoids and clinical outcomes in adults hospitalized with community‐acquired pneumonia on medical wards - Malecki - 2024 - Journal of Hospital Medicine - Wiley Online Library

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)

2024 ESC guidelines propose a simple new BP categorization:

• 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

Question  Does adding centralized mailed fecal immunochemical testing and patient navigation to usual care improve colorectal cancer (CRC) screening in US federally qualified health centers?

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

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 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!

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