Questioning Medicine

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2820369With as many as 1 in 3 US adults using multivitamin supplements, the question as to whether these supplements reduce mortality They usedthree large observational cohort studies with nearly 400,000 participants (median age, 62) who were followed for as long as 27 years (mean, 20 years); these studies included data on diet, self-reported multivitamin use, and mortality.  In adjusted analyses, daily multivitamin use was associated with a very small, but significant (4%), higher all-cause mortality risk. (multivariable-adjusted hazard ratio, 1.04; 95% CI, 1.02-1.07) Results from the current study — casting some doubt on a mortality benefit of multivitamin use — are unlikely to change the feelings of reassurance that many patients gain.

https://www.acpjournals.org/doi/10.7326/M23-3236Angiotensin-converting–enzyme (ACE) inhibitors or angiotensin-receptor blockers (ARBs) seldom are initiated among patients with chronic kidney disease (CKD) stage 4 or 5, despite guideline recommendations for these agents--- 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines - ScienceDirect “In adults with hypertension and CKD (stage 3 or higher or stage 1 or 2 with albuminuria [≥300 mg/d, or ≥300 mg/g albumin-to-creatinine ratio or the equivalent in the first morning void]), treatment with an ACE inhibitor is reasonable to slow kidney disease progression “   Angiotensin-Converting Enzyme Inhibitors or Angiotensin-Receptor Blockers for Advanced Chronic Kidney Disease: A Systematic Review and Retrospective Individual Participant–Level Meta-analy

Composite outcomes You add multiple outcomes together… this is great because you can increase the event rate.. if you are just looking at death lots of people might now die but if you look at death and hospitalizations well then it is easier to get to your expected event rate because its much easier to be hospitalized. This make it so you can have smaller sample sizes and it wont be nearly as expensive. The problem is all the events are given the same importance and we know they are not the same importance to patients Death and hospitalizations NOT THE SAME PE and death—not the same 3 questions to asked. Part of the endpoints of similar importance to patient's?Due to the more or less significant endpoints occur with the same frequency?Due to the endpoints share similar relative risk reductions?

ening, the offer of a blood-based screening test boosted CRC screening by 17.5 percentage points over usual care.That is becauseCRC screening proportions were 17.5 percentage points higher in the blood test group versus usual care (30.5% vs 13.0%; OR 2.94, 95% CI 2.34 to 3.70; p<0.001). So more people are screened for colon cancer but who cares if they get screened if your screening test does a terrible job of telling me stage 1 or precancer lesions. A history and physical will tell you stage 3 and 4 and a lot of the time even stage 2. Blood, change in size, or frequency. Take away bottom line is--- This sounds cool. This sound awesome. This sounds like it would be great for pateints that don’t want to do other forms of coloncancer screening which I do talk about on episode 237. HOWEVER for me this is a no go, the reason I want to screen is to catch cancer early. That is one of the pillars of cancer screening. To catch it early and have something you can do with the results that will change the outcome. Th

https://pubmed.ncbi.nlm.nih.gov/38945140/The primary outcome was a composite of myocardial infarction, revascularisation, hospitalisation for heart failure, stroke, or death from cardiovascular causes The mean systolic blood pressure throughout the follow-up (except the first 3 months of titration) was 119·1 mm Hg (SD 11·1) in the intensive treatment group and 134·8 mm Hg (10·5) in the standard treatment group.   During a median of 3·4 years of follow-up, the primary outcome event occurred in 547 (9·7%) participants in the intensive treatment group and 623 (11·1%) in the standard treatment group (hazard ratio [HR] 0·88, 95% CI 0·78-0·99; p=0·028).primarily driven by a reduction in the risks of stroke, heart failure, and death from cardiovascular causes. Serious adverse events of syncope occurred more frequently in the intensive treatment group (24 [0·4%] of 5624) than in standard treatment group (eight [0·1%] of 5631; HR 3·00, 95% CI 1·35-6·68).  

INHALE-3, a randomized trial, 123patients with type 1 dm that compared the efficacy of an inhaled insulin regimen (Afrezza) plus degludec insulin (Tresiba®) against usual care over 17 weeks The study's primary endpoint was a change in HbA1c levels, a critical marker of long-term blood glucose control.  More participants using the inhaled insulin regimen experienced significant improvements in HbA1c levels compared to those on usual care.21% of those on inhaled insulin had an HbA1c improvement of greater than 0.5%, while only 5% of those with standard care.  21 – 5 that is an absolute difference of 16% (NNT of 6.25) And they found a bunch of things when they went back like more people with a1c >7 reached their goal—which was not their end point they just found it and like to talk about   inhaled insulin and degludec was not for everyone: and everyone is missing this—we know how many people had an improvement in their a1c by 0.5% but how many had a worsening??? well 26% of the patients in the inhaled insulin

What is a quick and easy way to calculate the NNT

What is the different between Absolute and Relative risk reduction

https://heart.bmj.com/content/108/12/964https://www.ahajournals.org/doi/10.1161/JAHA.116.003815We have a study that says leads to increase all cause death with calcium supplementsWe have a study that says calcium supplement leads to increase in coronary artery calcium Foods that are high in calcium besides dairy include things like kale, spinach, broccoli, chia sees, collard greens…Hard for me to believe someone with a diet of excess kale and spinach will have an increase in all cause mortality anytime soon. It is easy for me to believe that supplements in a pill don’t fix the problems like we wish—we see this all the time with some many electrolytes and nutrients—there is a difference between taking a pill and eating a nutritious diet

https://evidence.nejm.org/doi/full/10.1056/EVIDoa2300311Peanut consumption, starting in infancy and continuing to age 5 years, provided lasting tolerance to peanut into adolescence irrespective of subsequent peanut consumption, demonstrating that long-term prevention and tolerance can be achieved in food allergy. (Funded by the National Institute of Allergy and Infectious Diseases and others; ITN070AD, ClinicalTrials.gov number, NCT03546413.)

https://jamanetwork.com/journals/jama/article-abstract/2819352Conclusions and Relevance  In this study, 10 years after diagnosis, 49% of men remained free of progression or treatment, less than 2% developed metastatic disease, and less than 1% died of their disease. Later progression and treatment during surveillance were not associated with worse outcomes. These results demonstrate active surveillance as an effective management strategy for patients diagnosed with favorable-risk prostate cancer.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11179824/This study did something smart in that they broke it down by white black Chinese and then also had 36 lab test they were looking at and they then found look for a black male this one particular blood test apo2 or whatever had better predictive value but that is cherry picking data with lots of data points and we don’t have risk calculators just for black or just for white or just for Chinese population. Blood test are hot things – we want to be able to drill down someone risk to a factions of a nats rear end but that just isn’t life—all the test and decision tools give us a rough estimate—the goal is to know are we looking at an 8% risk, an 18% risk or a 28% risk. It doesn’t really matter if it is 8.2  or 8.3 or 8.4 Botoom line—I get it we want to do more and be more precise but by getting extra blood test we are also costing the system more money and more energy so until you give me a study that shows it better with then a usuable risk calculator for that

https://www.nejm.org/doi/full/10.1056/NEJMoa2309002In this placebo-controlled trial, postexposure prophylaxis with nirmatrelvir–ritonavir for 5 or 10 days did not significantly reduce the risk of symptomatic SARS-CoV-2 infection.https://www.nejm.org/doi/full/10.1056/NEJMoa2309003https://www.nejm.org/doi/full/10.1056/NEJMoa2118542Pfizer has some serious problems! #pfizer

Risk of Nonarteritic Anterior Ischemic Optic Neuropathy in Patients Prescribed Semaglutidethis paper out in JAMA makes you think this is an issue but likely just too much noise with only 17 patietns and didnt control for confoundershttps://jamanetwork.com/journals/jamaophthalmology/fullarticle/2820255

Be careful, most observational data have a large amount of confounders not accounted for and even when accounted for you can never account for all the confounders

https://www.ahajournals.org/doi/10.1161/CIR.0000000000001251. Diagnosis:To establish a PAD diagnosis, the resting ankle–brachial index (ABI) remains the initial test of choice in patients with suggestive history or exam findings. The ABI result should be reported as normal (1–1.4), borderline (0.91–0.99), abnormal (≤0.9) or noncompressible (>1.4). TREATMET Low-dose rivaroxaban 2.5mg BID, in addition to daily aspirin, is now recommended to decrease the risk for major adverse cardiovascular events (MACEs) and major adverse limb events in patients with symptomatic PAD who are not at increased bleeding risk. This is based on the COMPASS trial Cardiovascular Outcomes for People Using Anticoagulation Strategies - American College of Cardiology (acc.org) and as a reminder inclusion criteria was “Atherosclerosis in ≥2 vascular beds or two additional risk factors (current smoking, diabetes, renal insufficiency, heart failure, or nonlacunar ischemic stroke ≥1 month)” In pts with symptomatic PAD—single antiplatelet w

https://jamanetwork.com/journals/jama/article-abstract/2818624Conclusion--“Cardiovascular biomarkers were strongly associated with fatal and nonfatal cardiovascular events and mortality. The addition of biomarkers to established risk factors led to only a small improvement in risk prediction metrics for atherosclerotic cardiovascular disease, but was more favorable for heart failure and mortality.” For 10-year incident atherosclerotic cardiovascular disease in younger people (aged <65 years), the combination of high-sensitivity cardiac troponin I, N-terminal pro-B-type natriuretic peptide, and high-sensitivity C-reactive protein resulted in a C statistic improvement from 0.812 (95% CI, 0.8021-0.8208) to 0.8194 (95% CI, 0.8089-0.8277)  So this paper is saying look “Cardiovascular biomarkers were strongly associated with fatal and nonfatal cardiovascular events and mortality.” Not wrong these labs improve outcomes but when you look at the c stats we go from 0.81 to 0.82… remember as we talked about yesterday

What are c statisticsC-statistic gives the probability a randomly selected patient who experienced an event (e.g. a disease or condition) had a higher risk score than a patient who had not experienced the event.Obviously there are people with low scores that still have events and people with high scores that never have events but the goal is the decision score gives us an idea of who is most likely. ·       The idea or educated estimate can be turned into a C score-  and c scores are kind of like grades== a score of 1 is absolue perfect model it means the model perfectly predicts those group members who will experience a certain outcome and those who will not.·       But we know in medicine that isn’t possible  IF ·       A value of 0.5 means that the model is no better than predicting an outcome than random chance.·       Values over 0.7 indicate a good model.·       Values over 0.8 indicate a strong model.  

https://pubmed.ncbi.nlm.nih.gov/38598573/In fully vaccinated adults with a risk factor or unvaccinated patients without a risk factor who have symptomatic COVID-19, does paxlovid--nirmatrelvir-ritonavir reduce the duration of symptoms or the likelihood of hospitalization?   Nirmatrelvir-ritonavir (Paxlovid) was shown in its initial randomized trial to reduce hospitalization and death in unvaccinated adults with at least one risk factor for severe disease when the ancestral variant of SARS-CoV-2 was predominant.But it is important that drugs be evaluated in the correct target population patients who have been vaccinated or have the Omicron variant.This industry-sponsored study enrolled 2 groups of patients: (1) fully vaccinated adults with symptomatic, confirmed infection with SARS-CoV-2 and at least one risk factor for severe disease,(2) unvaccinated adults with a symptomatic infection but no risk factorsThe onset of symptoms was within the past 5 days. Patients (N = 1296) were randomized to receive the stand

https://www.nejm.org/doi/10.1056/NEJMoa2314063Randomized trials have shown the benefit of endovascular thrombectomy in patients with acute stroke due to large-artery occlusion in the anterior circulation and a large baseline infarct (core) In these trials,1-5 a large core was defined by an ASPECTS value of 5 or less, but because of concerns about the deleterious effects associated with the reperfusion of large infarcts,8 patients with the largest infarcts (ASPECTS value, 0 or 1) were excluded from enrollment Now, researchers have compared EVT plus medical therapy to medical therapy alone in patients who could be treated within 6.5 hours of stroke onset and had a large amount of ischemic tissue The primary outcome was the modified Rankin scale (mRS) score and the major safety outcome was all-cause mortality, both at 90 days.  a 3-year period, 333 patients  cerebral vessel occlusion in the anterior circulation The median NIH Stroke Scale score was 21, and the median baseline infarct volume was 135 mL;  Median t