Questioning Medicine

The incidence of new-onset diabetes was basically the same but statistically significantly higher for those individuals on low-to-moderate–intensity statins compared with placebo 1.2 vs 1.3% annually which is a very small difference.

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

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

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

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

379. REPORT mammogram part 1

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2820369
With as many as 1 in 3 US adults using multivitamin supplements, the question as to whether these supplements reduce mortality

They used

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

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

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

Question What is the strength of association between surrogate markers used as primary end points in clinical trials to support Food and Drug Administration (FDA) approval of drugs treating nononcologic chronic diseases and clinical outcomes?

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

I get it

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

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

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

Most surrogate markers used as primary end points in clinical trials to support FDA approval of drugs treating nononcologic chronic diseases lacked high-strength evidence of associations with clinical outcomes from published meta-analyses.
https://jamanetwork.com/journals/jama/article-abstract/2817850

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.