Questioning Medicine

In 2011, the Endocrine Society published a guideline on “Evaluation, Treatment, and Prevention of Vitamin D Deficiency”   Now, the Society has issued an updated guideline, Demay MB et al. Vitamin D for the prevention of disease: An Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2024 Aug; 109:1907. (https://doi.org/10.1210/clinem/dgae290)  Previously, the Endocrine Society had labeled vitamin D status as “deficient” when serum hydroxyvitamin D (25[OH]D) was lower than 20 ng/mL, and “insufficient” when serum 25(OH)D was 20 ng/mL to 29 ng/mL. Now, the Society “no longer endorses specific 25(OH)D levels to define vitamin D sufficiency, insufficiency, and deficiency.”  Why is that--- because no clinical research has not established distinct thresholds of serum levels that can be tied confidently to specific clinical outcomes. In the general population of adults (age range, 19–74), neither routine vitamin D supplementation nor routine testing of 25(OH)D levels are recommended. What about >

Huijberts I et al. Collateral-based selection for endovascular treatment of acute ischaemic stroke in the late window (MR CLEAN-LATE): 2-year follow-up of a phase 3, multicentre, open-label, randomised controlled trial in the Netherlands. Lancet Neurol 2024 Sep; 23:893. (https://doi.org/10.1016/S1474-4422(24)00228-X)    The modified Rankin Scale (mRS) score at 2 years was the primary outcome. The median mRS at 2 years was 4 in the EVT group and 6 in the control group. For functional independence (mRS, 0–2), the rates were 35% in the EVT patients and 27% in the control group. Mortality at 2 years did not differ between the treatment groups.   However, about 12 patients need to be treated to provide one additional patient with functional independence, a higher number needed to treat than observed in studies of EVT provided in the early time window (e.g., N Engl J Med 2015; 372:2285) Still 24 hours AFTER a stroke!! amazing

 Because glucagon-like peptide-1 (GLP-1) receptor agonists can slow gastric emptying, they might confer risk for residual gastric contents — and possibly aspiration!!!! Should we stop the glp-1 Should we stop the glp-1-- Anesthesiologists and gastroenterologists have weighed in on this concern and on QM I say just do whatever the anesthesiologist want because they have the final say!!  Sen S et al. Glucagon-like peptide-1 receptor agonist use and residual gastric content before anesthesia. JAMA Surg 2024 Jun; 159:660. per American Society of Anesthesiologists [ASA] guidelines; Prior to surgery, patients had fasted at least 2 hours for clear liquids, 6 hours for light meals, and 8 hours for full meals   researchers performed gastric ultrasound just prior to elective surgery in 62 patients who were using weekly injected GLP-1 agonists (semaglutide, dulaglutide, or tirzepatide) and in 62 nonusers (controls).  The prevalence of residual gastric contents was significantly higher in the GLP-1 group than in the cont

Oropharyngeal dysphagia is highly prevalent in hospitalized patients with Alzheimer disease or other dementias. These patients often are prescribed thick liquid diets Makhnevich A et al. Thick liquids and clinical outcomes in hospitalized patients with Alzheimer disease and related dementias and dysphagia. JAMA Intern Med 2024 May 6; [e-pub]. Researchers conducted a retrospective propensity-matched analysis, ≈4500 patients with Alzheimer disease or other dementias who were hospitalized with clinical concern for dysphagia and received thick liquid diets and matched to ≈4500 patients who had received thin liquid diets.  Hospital mortality was similar in the two groups. Compared with patients who received thin liquids, those who received thick liquids were significantly less likely to be intubated (odds ratio, 0.7) but were significantly more likely to have respiratory complications, including pneumonia (OR, 1.7) In this end you are preventing intubation by 30 percent but causing pna by 70% --- neither are good

Feedback and Financial Incentives for Reducing Cell Phone Use While Driving: A Randomized Clinical Trial | Public Health | JAMA Network Open | JAMA Network  Question  Can behavioral interventions decrease handheld cell phone–based driver distraction?   17663 and ended up with 2020 participantsProgressive email--- already a select population Outcome-- Proportion of drive time engaged in handheld phone use in seconds per hour (s/h) of driving. Median baseline handheld phone use was 216 (IQR, 72-480) s/h.  Participants were randomly assigned to 1 of 6 trial arms for a 7-week intervention period: (1) control; (2) feedback, with weekly push notification about their handheld phone use compared with that of similar others; (3) standard incentive, with a maximum $50 award at the end of the intervention based on how their handheld phone use compared with similar others; (4) standard incentive plus feedback, combining interventions of arms 2 and 3; (5) reframed incentive plus feedback, with a maximum $7.15 award each w

Noncontrast CT Selected Thrombectomy vs Medical Management for Late-Window Anterior Large Vessel Occlusion | Neurology Most studies that have shown a benefit from endovascular thrombectomy (EVT) for ischemic stroke in the late time window (6 to 24 hours after time last known well) have used either perfusion imaging or advanced imaging to identify core infarct volume. Whether plain CT alone can identify EVT candidates in the late time window is unknown. multinational cohort study that looked at Consecutive patients presenting within 6–24 hours of time last seen well with proximal anterior LVO stroke that were either selected for EndoVascular therapy by Noncontrast CT or medically managed  The primary outcome was 90-day ordinal shift on the modified Rankin scale. Symptomatic intracranial hemorrhage (sICH) and mortality at 90 days were key safety outcomes.  results Functional independence (mRS 0–2) was observed in 40% of the EVT group and 18% of the MM-alone group. Symptomatic ICH was nonsignificantly more commo

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