Questioning Medicine

This massive meta-analysis of 484 randomized, double-blind, placebo-controlled trials (104,176 participants) quantified the blood pressure–lowering effects of major antihypertensive drug classes and their combinations. It introduces a new intensity-based classification system and an online calculator to predict BP-lowering efficacy based on drug, dose, and baseline BP.Study Design: 484 trials, 104,176 participants 5 major drug classes: ACE inhibitors, ARBs, β-blockers, calcium channel blockers (CCBs), and diuretics Focus: Placebo-corrected reduction in systolic BP (SBP) Mean baseline BP: 154/100 mm Hg Mean follow-up: 8.6 weeks Key Findings Monotherapy (Standard Dose): Average SBP reduction: 8.7 mm Hg By class: ACE inhibitors: 6.8 mm Hg ARBs: 8.5 mm Hg β-blockers: 8.9 mm Hg CCBs: 9.5 mm Hg Thiazide diuretics: 10.8 mm Hg Dose Doubling:Adds ~1.5 mm Hg SBP reduction (except β-blockers, which add only ~0.5 mm Hg) Dual Therapy (Standard Dose of Each): Average SBP reduction: 14.9 mm Hg Dose doubling adds ~2.5 mm Hg more Triple Therapy: SBP reduction: Up to 22.5 mm Hg (quadruple therapy even higher in one trial)

Practice Pearls: “Skip Leg Day” (Sometimes)For PAD patients who can’t tolerate leg workouts, upper body aerobic training is a strong, evidence-backed alternative. It’s not just a workaround—it’s a workout. CitationAhiskali GN, Demirel A, Yamikan H, Kutukcu EC. The Effects of Upper Extremity and Lower Extremity Aerobic Exercise Training in Patients with Peripheral Arterial Disease: A Systematic Review. J Vasc Surg. 2025. doi: 10.1016/j.jvs.2025.07.060

GLP1 drugs work but they likely need lifestyle modificationsNo convincing evidence GLP1 cause thyroid cancer in humans BUT contraindication if family history existStopping therapy usually results in weight gainInsurance coverage for weight loss is limited and variable  Semaglutide for type 2 diabetes max dose is 2.0 mg weekly Semaglutide for weight loss has a goal dose of 2.4 mg weekly Diagnose steatotic liver disease with imaging and 1 metabolic risk factor (or biopsy) After diagnosis check FIB-4: Low risk, continue to monitor with FIB-4 every 2-3yrs  Intermediate risk, order VCTE and consider referral if >F1  High risk order a VCTE and referral (20% end with SLD) 2 FDA approved medications for liver fibrosis are not cheap, expect insurance push back

OMED COPD CME

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 mehttps://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  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. 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). 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/   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. 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. 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: 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. 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. 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 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. 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/   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). 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 humansOral semaglutide is expensive for an NNT of 50 at 4 yrsTiktok videos of skin care are a scam

https://jamanetwork.com/journals/jama/article-abstract/2834040amiloride is realistically equal to spironolactone for resistant HTNhttps://journals.lww.com/ajg/abstract/2025/05000/higher_rate_of_spontaneous_bacterial_peritonitis.24.aspxprophalaxis antibiotics might not be neededhttps://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2834317If you got a friend in weight loss-- or at least in maintaining weight loss

https://www.jthjournal.org/article/S1538-7836(25)00109-6/fulltextAntithrombotic 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: Large Sample Size: With nearly 19,000 participants, the study provides robust data. Rigorous Data Collection: Bleeding events were meticulously documented and adjudicated by medical professionals. Comprehensive Analysis: The detailed follow-up and frequent assessments allowed for thorough monitoring of participants' health outcomes over several years. Weaknesses of the Study: Granular Data Absence: Specific details about hospitalization, such as length of stay or the number of transfusions, were not available. 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/2834632SummaryThe 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 Innovative Approach: The use of RNA interference to target hepatic synthesis of angiotensinogen introduces a novel mechanism to control blood pressure. Methodological Rigor: The study used a double-blinded, placebo-controlled design across multiple international sites, enhancing the reliability and generalizability of the results. 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. 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 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. 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. 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 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. 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. 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 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 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. 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. 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 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. 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/NEJMoa2416394At 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/2832701In 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)