Questioning Medicine

In older adults, mildly elevated TSH levels normalized in about 50% of cases during 1 to 2 years of observation.https://academic.oup.com/jcem/article/109/3/e1167/7325863?login=true

A study that was done before the widespread use of troponin only measurements for ACS (and certainly before high sensitively trop  EVER EXISTED), a trial that took place before the first statin was even FDA approved,  a trial that had no idea what DAPT was and took place PRIOR to the publication of the trial that would ultimately make aspirin post MI a standard of care, a trial that existed before a standard 90 minute door to balloon time. As a reminder this trial (ISIS) didn’t demonstrate a huge mortality benefit despite all of the things that were missing from it that are now considered standard of care. The mortality number needed to treat was 143 (13.3% vs 14.0%) https://www.nejm.org/doi/abs/10.1056/NEJMoa2401479

This translates into an absolute excess risk of ≈9 events per 1000 person-years or 1 per 110 person years. Sad differently if you treat 110 people for 1 year with a doac and an SSRI you will have one more bleed that requires hospitalization or death than if there was no SSRI.This  Risk was similar for various types of bleeding (e.g., intracranial, gastrointestinal) and did not vary with potency of SSRI.In patients with strong indications for both drugs, the relatively small absolute excess risk might be acceptable. However, in patients for whom the indication for either the SSRI or the anticoagulant is marginal, the excess bleeding risk might be a reason to avoid prescribing both drugs together.https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2816687

During follow-up participants walked on average 8300 steps and those individuals in the lowest genetic risk score developed obesity defined as a BMI greater than 30 approximately 13% of the time while those individuals in the highest genetic risk or developed obesity 43% of the time.   participants at the 75th percentile of PRS risk needed to walk 2280 more steps daily than participants at the 50th percentile to have the same relative risk reduction. Conversely, participants at the 25th percentile needed to walk 3660 fewer steps daily than those at the 50th percentile for the same relative risk reduction.https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2816822

And in the end it did not really matter because at 3 months individuals only reported a 0.16 difference in pain and a 1.6 difference in function which both were well within the noninferiority boundary.  In case you are wondering there is no difference in adverse events.bottom lineFor the outcomes of pain and function Telerehabilitation with a physiotherapist is non-inferior to in-person rehabilitation for patients with chronic knee painhttps://www.clinicalkey.com/#!/content/playContent/1-s2.0-S0140673623026302?returnurl=https:%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0140673623026302%3Fshowall%3Dtrue&referrer=https:%2F%2Fwww.jwatch.org%2F

At 1 year 50% of those individuals who had bariatric surgery were able to achieve diabetic remission but after 12 years the very same individuals that received bariatric surgery had just a 13% success rate in the remission of diabetes.Bariatric surgery certainly has an improvement in hemoglobin A1c and diabetic remission that is most evident in the first year but remains after 12 years of follow-up the patient oriented outcomes of major adverse cardiovascular events do not seem to be improved after 12 years of follow-up and may require longer follow-up if they exist at allhttps://jamanetwork.com/journals/jama/article-abstract/2815401

The company that developed Cologuard also developed this “next generation” multitarget stool DNA test, and has applied for U.S. FDA approval. The new test appears to have similar sensitivity and higher specificity than its predecessor — which means fewer false positives.  Positive predictive value (the proportion of positive tests that were true positives for cancer or advanced neoplasia) was 11%. Negative predictive value (the proportion of negative tests that were true negatives for cancer or advanced neoplasia) was 93%. The stool DNA test was substantially more sensitive than FIT (94% vs. 67% for cancer; 43% vs. 23% for advanced precancerous lesions), but slightly less specific. https://www.nejm.org/doi/10.1056/NEJMoa2310336

730 Patients were randomized to receive daily oral aprocitentan or placebo, plus a fixed-dose combination of amlodipine, valsartan, and hydrochlorothiazide.After 4 weeks, mean change in office systolic BP was 15 mm Hg with aprocitentan and 11 mm Hg with placebo; this 4 mm difference was statistically significant.What is the cost? What is the long term effects? Why didn't they compare this to the standard of care spironolactone? https://www.hcplive.com/view/fda-approves-aprocitentan-tryvio-for-treatment-resistant-hypertensionhttps://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)02034-7/abstract

The trial was terminated after  1015 patients with atrial cardiopathy had been randomized to receive either apixaban or aspirin for a mean follow-up of 1.8 years, recurrent stroke rates were identical  (40 events per group; 4.4% annualized rate). There were 7 symptomatic intracranial hemorrhages in the aspirin group and none in the apixaban group, though other major hemorrhages occurred at similar rates Aspirin is not benign and has real risk-- BTW don't give anticoagulation if the patient does not have atrial fib. https://jamanetwork.com/journals/jama/article-abstract/2814933

 TJA should not be delayed for trials of physical therapy, anti-inflammatory drug use, bracing, intra-articular steroid injections, or hyaluronic acid injections. For patients with obesity, proceed to TJA without delay, regardless of BMI. For patients with poorly controlled diabetes, recommend delaying TJA to improve glycemic control, but don't define poor control or specific HbA1c requirements. For smokers, recommend delaying TJA for a trial of smoking reduction or cessation. https://acrjournals.onlinelibrary.wiley.com/doi/10.1002/acr.25175

randomized trial comparingbeta-blocker therapy (metoprolol or bisoprolol) with no beta-blocker in 5020 patients who had a normal left-ventricular ejection fraction (LVEF) after AMI median follow-up of 3.5 years, the primary composite endpoint — all-cause death or recurrent AMI — did not differ significantly between participants randomized to a beta-blocker versus no beta-blocker (7.9% vs. 8.3%, respectively). https://www.nejm.org/doi/10.1056/NEJMoa2401479

During a mean 11 years of follow-up, current smokers' risks for cardiovascular-, cancer-, and respiratory-related deaths were 2, 3, and 13 times higher, respectively, than never smokers' risks. Former smokers who had quit <10 years before enrollment avoided roughly 50% to 60% of these excess risks. By 30 years after quitting, excess mortality was virtually eliminated.https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2811807

The primary cardiovascular end point was a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke in a time-to-first-event analysis.Improvement innonfatal stroke was not statistically significantdeath from cardiovascular causes was no significant buthold on it does appear nonfatal MI was significant and is what really drove the entire composite outcomeAll the way down to the discussion to find “An important limitation of this trial is that we included only patients with preexisting cardiovascular disease. The effects of semaglutide on primary prevention of cardiovascular events in persons with overweight or obesity but without previous atherosclerotic disease were not studied. “And that is because if you want to know the inclusion criteria you have to go to the supplementary data—WHICH NO ONE DOESThis was sneaky and planned and terrible on the part of Novo Nordisk.https://www.nejm.org/doi/10.1056/NEJMoa2307563?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&r

Bottom line(ZTLido 1.8%) is a brand name lidocaine patch currently approced for postherpetic neuralgia and will stay that why for now as it did not beat placebo for the treatment of patients with chronic nonspecific neck painFor both pain scores the pain decreased by 1.0 point with lidocaine and by 0.5 points with placebo. These differences were neither statistically significant nor deemed to be clinically important!https://pubs.asahq.org/anesthesiology/article/140/3/513/139530/Multicenter-Randomized-Placebo-controlled

 patients who have new-onset transient AF detected during a hospitalization for noncardiac surgery or medical illness and are discharged in sinus rhythm, approximately 1 in 3 have AF detected in the year after hospital discharge. Those that did not have afib only had a 5% risk (1 in 20) -- we dont know what this means for rates of patient oriented outcomeshttps://www.acpjournals.org/doi/10.7326/M23-1411?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed

Bottom line Omalizumab does seem to improve allergic reactions to peanuts but comes at a steep price tag. Likely only allergist will prescribe this drug but it is worth know about If you know or take care of anyone with severe peanut allergy.After 16 weeks, 67% of patients who took omalizumab could tolerate a 600-mg peanut protein challenge (≈2 peanuts) versus 7% of controls.Variability among patients was large: 44% of omalizumab patients could tolerate 25 peanuts whereas 14% of patients could not tolerate even 1/10 of a peanut.https://www.nejm.org/doi/10.1056/NEJMoa2312382

At ~24 weeks, ~80-90% of females report improvement in their acne with COCs, compared to 50-80% placebo, and 30-50% will have clear-almost clear skin versus 10-40% on placebo. Efficacy appears similar between individual COCs.Limitations: Most COC RCTs unblinded, many COC RCTs prohibited concurrent topical agents, no RCTS comparing COCs to topical agents, many industry-funded.https://cfpclearn.ca/tfp362/

QM on Spring Break-- but do you like the new format? Andrewbuelt@gmail.com

Diabetic patient- Empagliflozin prevents death from cardiovascular causes: NNT 46 per 3.1 yrs ($600 a month, 1 million dollars per life saved)-HFpEF- SGLT2 inhibitors do not prevent death and cost roughly $364,000 to prevent one hospitalization-HFrEF -Using Cox models, only Dapagliflozin has mortality benefit (NNT 53) and comes at a cost of $229,914 prevent one cardiovascular death. (117,126$$$ dap for hospitalization)

These findings indicate that initiation of empagliflozin in patients hospitalized for acute heart failure is well tolerated and results in significant clinical benefit in the 90 days after starting treatment.They combined HFpEF and HFrEFThey used win ratiosIndividual trials didn’t show mortality benefit but now there is?https://pubmed.ncbi.nlm.nih.gov/35228754/