Questioning Medicine

CME for the cost of free fifty free

 (https://www.healthquality.va.gov/guidelines/MH/mdd/VADoDMDDCPGFinal508.pdf) clearly state there is insufficient evidence to support this activity and testing. This is mainly because of low quality evidence and concern of bias given commercially funded studies.  (https://www.aafp.org/pubs/afp/issues/2023/0100/poems-pharmacogenic-testing-antidepressants.html)American Psychiatric Association Psychiatry.org - Genetic Testing to Improve Psychiatric Medication ChoiceHarvard https://www.health.harvard.edu/blog/gene-testing-to-guide-antidepressant-treatment-has-its-time-arrived-2019100917964First primeAs I mention in my response email PRIME the primary outcomes per clinnicaltrials.gov were depression remission at 24 weeks, which was not statically significant. And then a use of fewer medications that have a potential gene-drug interaction which from what I can find was a ‘theoretical' interaction not an actual increase in adverse events. Effect of Pharmacogenomic Testing for Drug-Gene Interactions on Medication Selection and Remission of Symptoms in Major Depressive Disorder: The PRIME Care Randomized Clinical Trial | Depressive Disorders | JAMA | JAMA Network“The PREPARE Study https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5113234/#:~:text=Open%2Dlabel%20placebo%20reduced%20minimum,0.02%25%20in%20the%20TAU%20arm. When patients were told they were getting placebo for back pain and it helped their back pain!The current VA/DoD guidelines clearly state, “For patients who cannot tolerate a statin, we suggest a washout period followed by a rechallenge with the same or a different statin or lower dose, and if that fails, a trial of intermittent (nondaily) dosing”. https://www.healthquality.va.gov/guidelines/CD/lipids/VADoDDyslipidemiaCPG5087212020.pdf (full disclosure and bias I helped write them)  N-of-1 Trial of a Statin, Placebo, or No Treatment to Assess Side Effects | NEJM was published in the NEJM and then a few weeks later Statin treatment and muscle symptoms: series of randomised, placebo controlled n-of-1 trials (bmj.com) was published in the BMJ.  Around that same time a publication in JAMA https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2773490 showed that using pharmacogenetic testing resulted in no worse LDL levels (soft endpoint) at one year but also no better

I give CME and you listen for free. You can't collect the CME but YOU CAN be a little smarter. These are some must know articles you need to know if you are a hospitalist. 

What about oral?? Lewis GD et al. Effect of oral iron repletion on exercise capacity in patients with heart failure with reduced ejection fraction and iron deficiency: The IRONOUT HF randomized clinical trial. JAMA 2017 May 16; 317:1958. (http://dx.doi.org/10.1001/jama.2017.5427. opens in new tab) randomized, 225 patients with symptomatic systolic HF for 16-weeks to either  oral iron polysaccharide 150 mg twice daily and placebo in 225 patients with symptomatic systolic HF (median left ventricular ejection fraction, 25%) At 16 weeks, the groups did not differ on the primary endpoint of peak oxygen consumption (VO2) or on secondary endpoints, including 6-minute walk distance and quality of life as measured with the Kansas City Cardiomyopathy Questionnaire. Thus as you mentioned not only is it not well tolerated it also doesn't appear to work which might be a better reason to not give it.https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0279166Vitamin D2 supplementation was associated with a 48.8% reduction in suicide/self-harm risks, and vitamin D3 with a 44.8% reduction, both highly significant (P < .001).   this sounds great but it is purely relative reduction not absolute because the absolute numbers wereUnadjusted suicide attempt/intentional self-harm rates in the D2 sample were 0.27% for those treated versus 0.52% for those untreated. The corresponding percentages for D3 were 0.20% versus 0.36%, respectively.Which equals a NNT of roughly 400 and 625 over 8 yrs, respectfully.IF this was true then that actually isn't too bad (not good or great but not terrible) but this was a retrospective observational trial so they just looked at a lot of people and said what can we find and publish.So what are other reasons that someone would not commit suicide??My first thought is ‘you only get put on vit d if you go to the doctor” (which is true)And typically the people that go to the doctor for their health care a little more about their health than someone who commits suicideClearly this isn't a universal answer but possibleAnother thought isthe vet that goes to the doctor and gets prescribed vit d feels like someone “cares for him/her” so maybe it has nothing to do with the vit d but just the sense of reassurance that someone cares about them?? Based on this I still wouldn't/wont write for vitamin d unless you need cheap placebo since we cant actually write for placeboD'Andrea E et al. Comparing effectiveness and safety of SGLT2 inhibitors vs DPP-4 inhibitors in patients with type 2 diabetes and varying baseline HbA1c levels. JAMA Intern Med 2023 Feb 6; [e-pub]. Sodium–glucose cotransporter-2 (SGLT-2) inhibitors are used to manage type 2 diabetes but also have protective cardiovascular and renal effects.  Do these benefits and adverse effects vary according to baseline level of hyperglycemia SGLT-2 inhibitors were compared with propensity-score–matched patients who initiated dipeptidyl peptidase-4 (DPP-4) inhibitors, within three categories of HbA1c: 9%. After mean follow-up of 8 months, initiation of SGLT-2 inhibitors was associated with significantly lower risks for major adverse cardiovascular events and hospitalization for heart failure, DUH we know this works in people that don't have diabetes why is it a surprise that it works in those with uncontrolled or controlled diabetes. To me this points to the problem that A1C is a number, it is not the problem, a bad A1C says there could be a problem in the future but in itself the A1C is a number!Buelt, Andrew | Apr 19, 2023, 3:25 PM | | to meTreat-to-Target or High-Intensity Statin in Patients With Coronary Artery Disease: A Randomized Clinical Trial | Cardiology | JAMA | JAMA Network JAMA. 2023;329(13):1078-1087. doi:10.1001/jama.2023.2487  randomized noninferiority trial 4400 patients Question  Is treatment to a goal low-density lipoprotein cholesterol (LDL-C) level between 50 and 70 mg/dL noninferior to a strategy using high-intensity statin therapy among patients with coronary artery disease? To assess whether a treat-to-target strategy is noninferior to a strategy of high-intensity statins for long-term clinical outcomes in patients with coronary artery disease.Patients were randomly assigned to receive either the LDL-C target strategy, with an LDL-C level between 50 and 70 mg/dL as the target, or high-intensity statin treatment, which consisted of rosuvastatin, 20 mg, or atorvastatin, 40 mg.  Which isn't HIGH in my book that that is fine.  Primary end point was a 3-year composite of death, myocardial infarction, stroke, or coronary revascularization with a noninferiority margin of 3.0 percentage points. The primary end point occurred in (8.1%) in the treat-to-target group and (8.7%) in the high-intensity statin group  Worst conclusion ever“Conclusions and Relevance  Among patients with coronary artery disease, a treat-to-target LDL-C strategy of 50 to 70 mg/dL as the goal was noninferior to a high-intensity statin therapy for the 3-year composite of death, myocardial infarction, stroke, or coronary revascularization. These findings provide additional evidence supporting the suitability of a treat-to-target strategy that may allow a tailored approach with consideration for individual variability in drug response to statin therapy.” Let's see if something that's much more difficult and costly and more blood draws and more work and more office appointments is non inferior to something that's easier such as take this medication and that it………………………………... Then why it is, we recommend the much more difficult thing.     Treat-to-Target or High-Intensity Statin in Patients With Coronary Artery Disease: A Randomized Clinical Trial | Cardiology | JAMA | JAMA Network JAMA. 2023;329(13):1078-1087. doi:10.1001/jama.2023.2487  randomized noninferiority trial 4400 patients Question  Is treatment to a goal low-density lipoprotein cholesterol (LDL-C) level between 50 and 70 mg/dL noninferior to a strategy using high-intensity statin therapy among patients with coronary artery disease? To assess whether a treat-to-target strategy is noninferior to a strategy of high-intensity statins for long-term clinical outcomes in patients with coronary artery disease.Patients were randomly assigned to receive either the LDL-C target strategy, with an LDL-C level between 50 and 70 mg/dL as the target, or high-intensity statin treatment, which consisted of rosuvastatin, 20 mg, or atorvastatin, 40 mg.  Which isn't HIGH in my book that that is fine.  Primary end point was a 3-year composite of death, myocardial infarction, stroke, or coronary revascularization with a noninferiority margin of 3.0 percentage points. The primary end point occurred in (8.1%) in the treat-to-target group and (8.7%) in the high-intensity statin group  Worst conclusion ever“Conclusions and Relevance  Among patients with coronary artery disease, a treat-to-target LDL-C strategy of 50 to 70 mg/dL as the goal was noninferior to a high-intensity statin therapy for the 3-year composite of death, myocardial infarction, stroke, or coronary revascularization. These findings provide additional evidence supporting the suitability of a treat-to-target strategy that may allow a tailored approach with consideration for individual variability in drug response to statin therapy.” Let's see if something that's much more difficult and costly and more blood draws and more work and more office appointments is non inferior to something that's easier such as take this medication and that it………………………………... Then why it is, we recommend the much more difficult thing.        Hydrochlorothiazide and Prevention of Kidney-Stone Recurrence | NEJMN Engl J Med 2023; 388:781-791  Thiazide diuretic agents are widely used for prevention of the recurrence of kidney stones, but data regarding the efficacy of such agents as compared with placebo are limited.  double-blind RCT  patients with recurrent calcium-containing kidney stones were randomized to hctz 12.5 mg, 25 mg, or 50 mg once daily or placebo once daily.  primary end point, a composite of symptomatic or radiologic recurrence of kidney stones. Symptomatic= The visible passage of a stone and radiologic =Appearance of new stones on CT 416 patients were randomized and followed for almost 3yrs primary end-point event occurred in (59%) in the placebo group (59%) in the 12.5-mg hydrochlorothiazide group (56%) in the 25-mg group(49%) in the 50-mg group  (rate ratio, 0.92; 95% CI, 0.63 to 1.36) No difference in any of the subgroups that was looked at there was no difference in the stone composition if it was calcium oxalate or calcium phosphate there was no difference Some women and people of race were underrepresented in this study but when you have a well done study that is the best we have the burden of proof now falls on you to prove there is benefit… for me this goes against board questions and what I thought was true and will lead me to stopping HCTZ if I am using it for prevention of kidney stones. 

Lindholt JS, Søgaard R, Rasmussen LM, et al. Five-year outcomes of the Danish cardiovascular screening (DANCAVAS) trial. N Engl J Med 2022;387(15):1385-1394.     Study design: Randomized controlled trial (nonblinded) Looking to see if intensive screening protocol for cardiovascular disease reduce cardiovascular events or mortality in older men? Danish study, 46,611 men aged 65 to 74 years were randomly assigned to receive an invitation to screening or usual careThe screening program included non-contrast electrocardiographically gated CT to measure coronary artery calcium, look for aneurysms, and detect atrial fibrillation; ankle-brachial index measurements for peripheral arterial disease (PAD) and hypertension; and blood tests for diabetes and hyperlipidemiaThose who accepted screening were more educated, more likely to be employed, and had a somewhat lower rate of hospitalization for cardiovascular events in the previous 5 years. (the rich white gullible ceo male)The screened group was more likely to be given lipid-lowering drugs and antithrombotics, and they were more likely to have repair of an aortic aneurysm.In the entire population, stroke was less likely (HR 0.93; 0.86 - 0.99) but there were no significant differences in myocardial infarction, aortic dissection, or aortic rupture. The authors estimated that 97.4% of men who received preventive therapy of some kind as a result of screening experienced no mortality benefit after almost 6 yrs of follow up. This is basically a really small absolute benefit which we could also see in just placing a pt on a statin. We don't need vip medicine we need pcp that have time to calculate risk and place pt on statin when indicated.     Goldberg RB, Orchard TJ, Crandall JP, et al, for the Diabetes Prevention Program Research Group. Effects of long-term metformin and lifestyle interventions on cardiovascular events in the diabetes prevention program and its outcome study. Circulation 2022;145(22):1632-1641. Study design: Randomized controlled trial (nonblinded) What is the long-term impact of treating prediabetes on mortality and cardiovascular outcomes? Go way back original Diabetes Prevention Program study randomized 3234 overweight or obese adults with impaired glucose tolerance ("prediabetes") to receive metformin 850 mg twice daily, an intensive exercise program, or placebo and followed them for 3 years Patients were invited to participate in a long-term open-label follow-up study This article reports long-term cardiovascular and mortality outcomes for each group. Patients in the intervention groups were less likely to have been given a diagnosis of T2DM (55% for metformin and 53% for lifestyle vs 60% for placebo; P = .001; number needed to treat [NNT] = 17) There was no difference between either intervention group and placebo with regard to the risk of cardiovascular death, nonfatal stroke, or nonfatal myocardial infarction. There was also no significant difference in the composite of all 3 outcomes for the original metformin group versus the placebo group (hazard ratio [HR] 1.03; 95% CI 0.78 - 1.37) or for those in the original lifestyle group versus the placebo group (HR 1.14; 0.87 - 1.50). More is less or rather more meds is less diagnosis but no difference in things we actually care about     Skjerven HO, Lie A, Vettukattil R, et al. Early food intervention and skin emollients to prevent food allergy in young children (PreventADALL): a factorial, multicentre, cluster-randomised trial. Lancet 2022;399(10344):2398-2411. Study design: Randomized controlled trial (single-blinded) Does the early introduction of allergenic foods prevent the development of food allergy? investigators randomized healthy newborns, singletons or twins, with at least 35 weeks' gestational age (concealed allocation) to receive no intervention (n = 597), a skin intervention (n = 575), a food intervention (n = 642), or a combined intervention (n = 583). The skin intervention consisted of 5- to 10-minute baths with added petrolatum-based emulsified oil followed by topical cetirizine cream applied to the face. This intervention was to occur at least 4 days per week from age 2 weeks to 8 months, The food allergy intervention consisted of sequentially adding allergenic foods (peanuts, cow's milk, wheat, then eggs) to the infants' regular diet at weekly intervals starting at age 3 months. Overall, 95% of the infants in each group were breastfed at 3 months The researchers had final data on 99.9% of the participants!   based on structured parental interviews, skin testing, and oral challenges  The researchers classified the development of food allergy at 36 months as probable, none, or unclear.  There was no significant difference, however, between the infants who were exposed to skin interventions and those who were not exposed (2.1% vs 1.6%). BUT BUT BUT Food allergy occurred in 1.1% of infants in the interventions using food (food intervention and combination intervention) compared with 2.6% in not using food (no intervention and skin intervention; number needed to treat = 63; 95% CI 37-196).   Lewis E, Merghani K, Robertson I, et al. The effectiveness of leucocyte-poor platelet-rich plasma injections on symptomatic early osteoarthritis of the knee: the PEAK randomized controlled trial. Bone Joint J 2022;104-B(6):663-671. Study design: Randomized controlled trial (double-blinded) Allocation: Concealed recruited adults with at least 4 months of knee pain (with or without swelling) who had mild degeneration on their x-rays (if plain x-rays found no signs of degeneration, they used magnetic resonance imaging to confirm the diagnosis). The participants were randomized to receive 3 weekly saline injections (n = 28), or a single PRP injection followed by 2 weekly saline injections (n = 47), or 3 weekly PRP injections (n = 27). . The clinician performing the injections was unmasked but had no other involvement in the study procedures. the participants were evaluated at 6 weeks, 12 weeks, 6 months, and 12 months after enrollment Using intention-to-treat analysis looking at pain, function, and quality of life, at no point in the study were PRP injections, singly or serially, superior to saline injections.

Efficacy and Safety of Intensive Versus Nonintensive Supplemental Insulin With a Basal-Bolus Insulin Regimen in Hospitalized Patients With Type 2 Diabetes: A Randomized Clinical Study | Diabetes Care | American Diabetes Association (diabetesjournals.org)   randomized noninferiority study from Emory University, 224 hospitalized patients with longstanding type 2 diabetes  Both groups received basal/bolus insulin; both the starting dose and subsequent changes were specified by the study protocol. Additional premeal SSI was added to scheduled premeal bolus doses.randomized to either intensive SSI (at BG >140 mg/dL) or nonintensive SSI (at BG >260 mg/dL) before meals and at bedtime.  Mean baseline glycosylated hemoglobin (HbA1c) was 9%, and 60% of patients were using insulin at home. Patients with a presenting glucose level of >400 mg/dL or diabetic ketoacidosis were excluded.  Outcome---Mean daily BG level, hypoglycemia, severe hyperglycemia, percent of BGs in the target range (70–180 mg/dL), and the amount of total, basal, or prandial insulin used did not differ between groups. However, significantly fewer patients in the nonintensive group than in the intensive group received SSI (34% vs. 91%).   COMMENTAlthough this is a single-center study, its results are persuasive and suggest that a less-intense SSI regimen can achieve similar glucose outcomes in hospitalized patients with type 2 diabetes who are receiving basal/bolus insulin. It also could decrease nursing treatment burden. As we move slowly toward more continuous glucose monitoring in hospitals, reducing use of SSI is another opportunity to achieve similar results with less staff burden and more patient comfort.  Comparative Effectiveness and Safety Between Apixaban, Dabigatran, Edoxaban, and Rivaroxaban Among Patients With Atrial Fibrillation: A Multinational Population-Based Cohort Study: Annals of Internal Medicine: Vol 175, No 11 (acpjournals.org) In a retrospective study, investigators accessed five electronic health databases from Europe and the U.S. to compare >500,000 new DOAC users with newly diagnosed atrial fibrillation. Follow up varied from 1.5 to 4.5 years.   In propensity score–adjusted analyses, patients who received apixaban had significantly less gastrointestinal (GI) bleeding did those who received any of the other three drugs (hazard ratios, 0.7–0.8). This result was consistent among older patients and those with chronic kidney disease (CKD). Risk for stroke or other systemic embolism, intracranial hemorrhage, and all-cause mortality did not differ significantly among DOACs.    COMMENTThis is the largest comparison of individual DOACs, and it demonstrates similar efficacy among all agents. Although apixaban was associated with less GI bleeding, absolute percentages of GI bleeds ranged from ≈2% to ≈3.5% for all DOACs; therefore, apixaban's statistically significant safety benefit might amount to marginal clinical benefit for any individual patient. I might turn to apixaban for patients at high risk for GI bleeding (and those with CKD), but all DOACs remain reasonable options for preventing thromboembolism in most patients with atrial fibrillation. Ellenbogen MI et al. Safety and effectiveness of apixaban versus warfarin for acute venous thromboembolism in patients with end-stage kidney disease: A national cohort study. J Hosp Med 2022 Oct; 17:809. (https://doi.org/10.1002/jhm.12926. opens in new tab)  . In an industry-funded retrospective study, investigators used a national database (years, 2014–2018) and propensity score–adjusted analysis to compare outcomes among >11,500 patients with ESRD and newly diagnosed VTE who received either apixaban or warfarin.Only 2% of patients received apixaban in 2014, but 47% received apixaban in 2018.during the 6 months following initiation of therapy, apixaban — compared with warfarin  associated with significantly lower incidence of major bleeding (10% vs. 14%), including intracranial bleeding (1.8% vs. 2.5%) and gastrointestinal bleeding (8.6% vs. 10.4%). Recurrent VTE and all-cause mortality were similar in the two groups.   VTE and creatine clearence less than 30 then I think apixaban is the drug of choice—I would like to see this study don't with afib and done with exclusively

YES!! Marketing!! No man wants to admit his gonads dont work so they would never say I have hypogonadism. Most men would never say I have andropause cause that is too close to menopause but if you call it low testosterone then all of a sudden men come out of the wood work like cave men to get some of this magical drug they have heard so much about.YES LIKE LOW T WILL KILL YOU!!!! "could kill you". -https://abcnews.go.com/Health/ActiveAging/story?id=3247773&page=1https://www.acpjournals.org/doi/10.7326/M19-0882?_ga=2.162179964.190727375.1667239768-1195431333.1667239768&"It is estimated that approximately 35% of men older than 45 years of age and 30-50% of men with obesity or type 2 diabetes have hypogonadism". from endocrine.org. https://www.endocrine.org/patient-engagement/endocrine-library/hypogonadism However, for a 30 yr old male the low end of normal is around 300 ng/dL! YET this is what most websites and recommendations use as the treatment cutoff for all men. 50, 60, 70 yr olds. we compare those testosterone levels of 30 yrs old and make them the standard for 50, 60 ,70 yr olds. ​​https://www.nejm.org/doi/full/10.1056/NEJMp038207study found that just watching sports can raise and lower your testosterone levels depending if your team wins or loses. https://pubmed.ncbi.nlm.nih.gov/9811365/20 minutes apart had variations between the two lab values of 18–28% half of the time and about 25% of the time the variation in the lab test between  27–54%!! Same blood, same person, 20 minutes a part and the test results are 15-54% different!!!!! There is no lab test in the world that i know of with such huge variation.DJ BrambillaAB O'DonnellAM Matsumotoet al.Clin Endocrinol2007;67:853–62A study from journal of urology in 2014 showed that testosterone differences in time appears to be of significant concern in those younger than 45 but those older than 45 can likely have their test time frame expanded with no harm or issue.  Welliver RC Jr, Wiser HJ, Brannign RE, et al. Validity of midday total testosterone levels in older men with erectile dysfunction. J Urol. 2014;192:165-169.https://pubmed.ncbi.nlm.nih.gov/26360789/#:~:text=Objective%3A%20Since%20testosterone%levels%20exhibit,diagnostic%20test%20for%20androgen%20deficiency.A study in jama internal medicine found that about 25% of those individuals prescribed testosterone had not even had a testosterone level measured even once in the previous year.https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/1691925?resultClick=3

coffee saves your life-- maybe, careful for confounders heart failure hospital admission is really hard to preventmoderate dose statin is most important..but ezetmibe and moderate dose is equal to high dose statinI think we should take out all kidney stones and the evidence says there will be lest hospitalizations if we do thatEHR can help us and remind us to check and PTHrobotic surgery is not all that is seems to be-- or at least not yetvit. D and fish oil dont help dry eyes....or much of anything for that matterstop injecting Hyaluronic acid into the knee

 skin exam, ddp4, IUD, oral hypertension medication

https://www.ahajournals.org/doi/abs/10.1161/CIRCULATIONAHA.122.059410?af=RThe Biomarkers say REDUCE-IT was a scamhttps://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2791663NO! Just NO-- stick with the calculator for nowhttps://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.122.059038start the SLGT-2 inhibitors early! maybe an early dischargehttps://pubmed.ncbi.nlm.nih.gov/35849407/If we could get the EMR to do it automatically else you cant expect providers tohttps://pubmed.ncbi.nlm.nih.gov/35727595/the head CT for psych stuff can probably be put on holdhttps://eprints.whiterose.ac.uk/180135/continue the disease modifying agents

mammograms and pink ribbons-- lets talk evidence

mammograms-- we all know them, but lets discuss

Association of Receipt of the Fourth BNT162b2 Dose With Omicron Infection and COVID-19 Hospitalizations Among Residents of Long-term Care Facilities | Geriatrics | JAMA Internal Medicine | JAMA Networkcareful what you believe and always question medicine- even if it is about covid vaccineUse and Cost of Low-Value Health Services Delivered or Paid for by the Veterans Health Administration | Cancer Screening, Prevention, Control | JAMA Internal Medicine | JAMA Network low value care exist in the VA but also in the community-- you need a comparative arm to figure out how bad you are doing or good you are doing. Supplemental Vitamin D and Incident Fractures in Midlife and Older Adults | NEJM You can also check a level if you are trying to make the diagnosis of rickets. ELSE no need to check anyone, if you really believe in it or your patient really believes in in then just start 2000IU and continue to take as long as they feel indicated because it likely is not doing any benefit but realistically it is not doing any harm at that dose either (there has been harm seen at super high doses 50,000IU)listener question---- My question is what is the smallest doses statin I need to convince patient to take to benefit. For me the answer is that yes high dose is better than moderate dose for those needing secondary prevention, but any dose is better than no dose for both primary and secondary prevention. If the patient isn't taking the medication it doesn't matter how good the drug is so ultimately if they are very serious about their risk reduction then go ahead and try and push higher dose statin else just take any dose the patient is willing to take and be happy they are you getting some sort of risk reduction that drastically beat ‘nothing'/placebo.

Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension - Wilding - - Diabetes, Obesity and Metabolism - Wiley Online Library   “”””One year after withdrawal of once-weekly subcutaneous semaglutide 2.4 mg and lifestyle intervention, participants regained two-thirds of their prior weight loss, with similar changes in cardiometabolic parameters.”””  investigators assessed the changes in body weight among patients who were started on semaglutide therapy and subsequently stopped.  The weight regain was accelerated immediately after treatment withdrawal and slowed at week 80.   The results showed that while on semaglutide, participants lost an average of 17.3% of their baseline weight. However, once semaglutide was discontinued, participants regained 11.6% of lost weight by the 1-year follow-up.  The net weight changes at week 120 were 5.6% (SD, 8.9) in the semaglutide arm and 0.1% (SD, 5.8) in the placebo arm.  Furthermore, cardiovascular in htn and glycemic category reverted back to baseline. A life long drug and expensive.. this is sad but shows how chronic obesity is and it remains one of the biggest challenges in medicine    Papi A et al. Albuterol–budesonide fixed-dose combination rescue inhaler for asthma. N Engl J Med 2022 May 15; [e-pub]. (https://doi.org/10.1056/NEJMoa2203163. opens in new tab)   Global Initiative for Asthma (GINA) guidelines. opens in new tab recommend avoiding albuterol for all patients and using inhaled corticosteroids (ICS)/formoterol as a rescue inhaler. Although the National Asthma Education and Prevention Program (NAEPP) guidelines. opens in new tab have not gone that far, they do recommend using as-needed ICS/albuterol for mild asthma.  3100 adolescents and adults with uncontrolled moderate-to-severe asthma were randomized to either high- or low-dose albuterol/budesonide (180/160 µg or 180/80 µg) or albuterol alone (180 µg) as a rescue inhaler while continuing their current ICS or ICS/LABA (long-acting β-agonist) therapy. After 24 weeks, severe exacerbations requiring systemic steroids for rescue were significantly less common in both the low and the high-dose budesonide/albuterol group than in the albuterol group (annualized rate, 0.45 vs. 0.59). This doesn't tell us if ICS/fomoterol as rescue is better or worse than albuterol ICS but it does say or should remind us that albuterol alone is no longer indicated for maintenance for rescue for anything.  Ancel K, Keys M. How to Eat Well and Stay Well the Mediterranean Way. Coronary Artery Disease in Seven Countries. Circulation. 1975;41(4 Suppl):11-211.     1002 patients aged between 20 and 75 years with established coronary heart disease and randomly assigned them to either a Mediterranean diet or a low-fat diet. The follow-up period was 7 years. The primary outcome was a composite of major CV events, myocardial infarction, revascularization, ischemic stroke, peripheral artery disease, and CV death.  To ensure that cost was not a barrier, extra-virgin olive oil was provided free of charge to the Mediterranean group (1 L per week per household), and free healthy food packs rich in complex carbohydrates were given to the low-fat group. here were 111 events in the low-fat group and 87 events in the Mediterranean group, representing a 25% reduction in events in favor of the Mediterranean diet (HR, 0.745; P = ·040).  For men, the reduction was 33% (HR, 0.669; P = ·013). For women, there was no difference between the groups. However, there were only 175 women in the trial, so the lack of effect may be just due to the small number. The lipid profile and glucose levels of the participants did not change significantly during the study—which is a huge knock for all the lipid hypothesis people out there.

a couple points over the last podcast

Acute low back pain, chronic low back pain, back pain with sciaticain the end unless red flags hold on imaging for 6weeksNSAIDS for acute low back painexercise and spinal manipulative therapy for chronic low back painbe conservative and don't write for drugs that don't work like gabapentin or pregablin

196. Medical Update -- PICC lines, PRE-Diabetes, Sleep in the Hospital, Ortho Surgery!

European Heart JournalBariatric surgery and cardiovascular disease: a systematic review and meta-analysisEur Heart J 2022 Mar 04;[EPub Ahead of Print], SL van Veldhuisen, TM Gorter, G van Woerden, RA de Boer, M Rienstra, EJ Hazebroek, DJ van Veldhuisen  39 studies, all prospective or retrospective cohort studies, showed Bariatric surgery is associated with a reduced hazard ratio (HR) of CV morality (0.59), all-cause mortality (0.55), incident HF (0.50), myocardial infarction (0.58) and stroke (0.64) Authors state “”The present systematic review and meta-analysis suggests that bariatric surgery is associated with reduced all-cause and CV mortality, and lowered incidence of several CV diseases in patients with obesity. Bariatric surgery should therefore be considered in these patients.””” Here is the problem and I have said it before—“no randomized control trials examining the effect of bariatric surgery on CV outcomes,”Among frail patients with AF, OAC treatment was associated with a positive net clinical outcome. Direct OACs provided lower incidences of stroke, bleeding, and mortality, compared with warfarin. Just talked recently about continue doac in hospice and everyone agrees that is bad but ultimately there are very few conditions in which you should not resume anticoag—even in those with GI bleed, falls, or subachrnoid hemerage—the data suggest the pts are better off back on anticoag. Well this study looked at the frail. In this retrospective cohort study analyzed 83 635 patients  with mean age 78.5 those individuals who were on ORAL anticoag(doac or warfarin) had overall lower risks of ischemic stroke (HR, 0.91) and cardiovascular death (HR, 0.52), with no significant difference in major bleeding (HR, 1.02),   Bottom line- restart the OAC – even in the frail to prevent the outcomes we really care about like stroke and death    Dave CV et al. Risks for anaphylaxis with intravenous iron formulations: A retrospective cohort study. Ann Intern Med 2022 Mar 29; [e-pub]. (https://doi.org/10.7326/M21-4009. opens in new tab) Anaphylaxis occurs rarely with intravenous (IV) iron does happen but how often does it happen??  It is a mystery—till now Using a retrospective cohort design, investigators assessed 167,000 U.S. Medicare patients who received IV iron products between 2013 and 2018. Patients who had received IV iron within the previous year and those with end-stage renal disease, HIV infection, history of anaphylactic reaction, or recent transfusions were excluded. This is the perfect study for observational data. We know it happens so we look at a large data set and try to see how often it happens. In this population of older adults, the rate of anaphylaxis for iron dextran was ≈0.1%, but it was closer to 0.01% for iron sucrose, ferric gluconate, and ferric carboxymaltose (can give once== carboxy and dextran). As indications have broadened for use of IV iron in managing various clinical conditions (e.g., heart failure, chronic kidney disease) when iron deficiency is present, clinicians might use these data to inform selection of a preparation.  A lot depends on cost and availability but these are good numbers to have in your head for the anaphylaxis event rate... Sure it might take 5 years or even 10 years but some of the outcomes like MI and HF will easily hit in the first 5-10 years!! This RCT could be done tomorrow! Instead we continue to do this observational studies and say look how great this procedure is!! Well maybe it is ‘healthy' patient bias—you have two pts with BMI of 40 but one seems motivated is working out eating better- trying to take all the right steps and the other hasn't left the couch in 6 years. The one that is active then gets referred for bariatric surgery and when we match them up we say LOOK AT THIS THE BARIATRIC SURGERY person did so much better. WEEELLLLLL that pt was likely going to do better anyways!!! AT this point everyone know that bariatric surgery seems to have great CV outcomes in retrospective and prospective observational trials we have done enough of them.. THIS analysis had 39 STUDIES—39!!!! We don't need 30 more we need and RCT!!!     Katz PO et al. ACG clinical guideline for the diagnosis and management of gastroesophageal reflux disease. Am J Gastroenterol 2022 Jan; 117:27. (https://doi.org/10.14309/ajg.0000000000001538. opens in new tab) Much of this guideline is worthwhile for nongastroenterologists.  An empirical 8-week trial of a proton-pump inhibitor (PPI), given once daily, is recommended for a patient who has classic heartburn and regurgitation but no alarm symptoms.  PPIs should be taken 30 to 60 minutes before a meal, because they bind to proton pumps that have been stimulated by meals. Bedtime dosing is discouraged because this is less effective than a predinner dose in acid control GERD is thought to contribute to various extraesophageal symptoms, including chronic cough, hoarseness, and laryngitis; however, a causal relation often is unclear in any given patient. For patients with extraesophageal symptoms — but no heartburn or regurgitation — the authors argue against empirical PPI therapy  After 8 weeks you STOP the PPI--PPI nonresponders, and PPI responders whose symptoms return after an 8-week PPI course, should be evaluated with Endoscopy about 2 to 4 weeks off PPIs.  If endoscopy is normal, ambulatory pH monitoring (off treatment) is the next step. authors encourage intermittent or “on-demand” (rather than indefinite) PPI therapy in patients with no history of high-grade esophagitis or Barrett esophagus. IF requires ongoing PPI therapy for symptom control should use the lowest effective dose.I do like these guidelines cause they seem to be great at making sure PPI are stopped (ideally). I do hate these guidelines cause getting a scope after 8 weeks of a PPI with reoccurring symptoms seems like a lot of scopes will be done. Especially because some people get rebound gerd when going off of a PPI. As the authors state “One area of controversy relates to abrupt PPI discontinuation and potential rebound acid hypersecretion, resulting in increased reflux symptoms. Although rebound acid hypersecretion has been demonstrated to occur in healthy controls, strong evidence for an increase in symptoms after abrupt PPI withdrawal is lacking.”  -- none of this is super strong evidence!!! This seems like a lot of scopes.The fear of progression to adenocarcinoma with Barrett's Esophagus would make for an easy decision for prolonged PPI use, however, a systematic review and meta-analysis published in PLoS One - Hu Q, Sun TT, Hong J, et al. Proton Pump Inhibitors Do Not Reduce the Risk of Esophageal Adenocarcinoma in Patients with Barrett's Esophagus: A Systematic Review and Meta-Analysis. PLoS One 2017;12(1):e0169691. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0169691 found no protective effect.1And even though long term use of PPI is associated with many bad outcomes even the authors state -  “””“PPIs are the most effective medical treatment for GERD. Some medical studies have identified an association between the long-term use of PPIs and the development of numerous adverse conditions including intestinal infections, pneumonia, stomach cancer, osteoporosis-related bone fractures, chronic kidney disease, deficiencies of certain vitamins and minerals, heart attacks, strokes, dementia, and early death. “” the authors go on to say “””Those studies have flaws, are not considered definitive, and do not establish a cause-and-effect relationship between PPIs and the adverse conditions. High-quality studies have found that PPIs do not significantly increase the risk of any of these conditions except intestinal infections. .”””  THIS IS ALSO GARBAGE!!! The reason the high quality studies don't show this is because most studies are only 8-12 weeks long PPI you need long term trials which most people are on and you have to power your study so large to find a super rare outcome that observational data is the best we are ever going to have for this particular finding. I know the authors knew this but it didn't fit their agenda…Which is my last point—although we will never know—all but one of the authors has or is taking big pharma money. Take home if you are following the guideslines-- start PPI only for Gerd like symptoms. Make sure taking the PPI correctly. Stop after 8 weeks. If it reoccurs then 2-4 weeks later off the PPI they need a scope and if the scope is normal then they need PH monitoring. Then the rec is for PRN PPI.  

SUMMARY--What diuretic do you usually write for during CHF hospitalizations??   If you said furosemide you are not alone  One in a study in JACC 2013 looked at HF hospitalizations in 2009 and 2010 – In total 251,472 patients got a loop diuretic during their hospitalization and almost 87% got just furosemide, about 3% only got bumex, while only 0.4 received only torsemide.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4038646/#R11  What is the difference between bumetanide and furosemide? Nothing—or at least nothing we care about. No hard outcomes, no patient oriented outcomes.  Bumetanide is stronger—An article from 2015 in American Heart Journal states bumetanide is about 40 times stronger than furosemide- thus at times you might have your sphincter tighten when you go to write for 120-160mg of furosemide but feel comfortable writing for 3-4mg of bumex. They also discuss how bumetanide also appears to have a higher more consistent bioavailability at around 80-100% while furosemide seems to range from 10-100% depending on the study. Conclusion: the benefits for bumetanide are there in theory but no hard outcomes that I could find. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4346710/  What about torsemide??The bioavailability of torsemide is 76% to 96% and as I mentioned before furosemide hangs out around 10% to 100%. In addition, furosemide bioavailability can decrease by up to 30% with food while torsemide is not affected by food consumption.https://oce.ovid.com/article/00006562-199701000-00009https://pubmed.ncbi.nlm.nih.gov/3709617/  HOWEVER, no patient cares about bioavailability they want to know if they will live longer or live better (patient oriented outcomes)??  First paper- 2001 Nov;111(7):513-20.American Journal of Medicine we have a paper titled“Open-label randomized trial of torsemide compared with furosemide therapy for patients with heart failure” This was open-label trial of 234 patients who were randomized to torsemide or furosemide and followed for 1 yr. The outcome was heart failure readmissions and it occurred significantly less in the torsemide group, only 17% of the time compared to 32% in the furosemide group. https://pubmed.ncbi.nlm.nih.gov/11705426/ That is almost a 50% relative reduction for heart failure hospitalization at one year! This is an outcome both patients and hospitalist would love to see! Second paper-In 2002- a year later-European Journal of Heart Failure a paper titledTorasemide in chronic heart failure: results of the TORIC studyThis was the published results of the ‘TOrasemide In Congestive Heart Failure (TORIC)' study- It was an open-label, non-randomised, post-marketing surveillance trial. The individuals who were prescribed torsemide on top of their other CHF medications for 12 months had almost a 50% relative reduction in mortality!! That may not seem like a lot but remember this is only 12 months and the outcome was DEATH! In absolute terms roughly 2% of participants died in the torsemide group and 4% died in the furosemide/other diuretic group. PLUS, those in the torsemide group also had an improvement in their NYHA functional heart class.https://pubmed.ncbi.nlm.nih.gov/12167392/  Finally, there is a meta-analysis from 2019 in Journal of Cardiovascular Medicine titledTorsemide versus furosemide and intermediate-term outcomes in patients with heart failure: an updated meta-analysis  Which looked at a total of 14 randomized trials and just over 8000 pts and found torsemide to have both fewer heart failure hospitalizations and those individuals taking torsemide were more likely to have an improvement in their new york heart association class but they didnt find a difference in mortality.https://pubmed.ncbi.nlm.nih.gov/30950982/ Currently there is 6000 pt randomized trial that is underway and will be done in august 2023. https://clinicaltrials.gov/ct2/show/NCT03296813  That is it, that is all that I could find!!!! However, with the evidence clearly in favor of torsemide, why have I never even considered it before doing this lecture?? Likely 2 problems 1) It is what we have always done and it is hard to change practice! Furosemide was approved for medical use in 1964.Torsemide was approved in 1993. We as providers get into a rut, the next drug we prescribe is likely to be one of the most recent drugs we prescribed. If you show me the last 10 hypertension medications you prescribed then with almost 90-100% certainty I can guess the next one that you are going to prescribe.  2) There use to be a cost issue when furosemide was generic and torsemide was not. However, now these are both old drugs and per goodrx down here in Florida they only differ by about 1.50$ per month, but we are saving hospitalizations which cost 1000$.  A paper from 2000 in Pharmacoeconomics titled “Healthcare costs of patients with heart failure treated with torasemide or furosemide” found torsemide average hospitalization cost per patient each year was $1000 while those in the furosemide group had an average cost of $1500 dollars, and this was back when torsemide wasn't nearly as cheap as it is now.  I know I have given you a lot of numbers but a good take away is- Torsemide compared to furosemide has a NNT at 10.5 months to prevent a heart failure hospitalization around 6!!! https://pubmed.ncbi.nlm.nih.gov/10977385/ https://www.medscape.com/viewarticle/771976_8  Even if the number is off a little because of study design flaws like blinding and sample size the evidence does appear to continually point the direction of benefit towards torsemide. Even if you doubled it, a NNT of 12, it is still really good.

Gibbons RC et al. Ultrasound-versus landmark-guided medium-sized joint arthrocentesis: A randomized clinical trial. Acad Emerg Med 2022 Feb; 29:159. (https://doi.org/10.1111/acem.14396. opens in new tab)Use a ultrasound for arthrocentesis when possible Circ Arrhythm Electrophysiol 2022 Mar; 15:e010646. (https://doi.org/10.1161/CIRCEP.121.010646)Apple AirPods Pro and their wireless charging case, the Microsoft Surface Pen, and the Apple Pencil second generation — also have strong enough magnetic fields to affect current-generation CIEDs.https://pubmed.ncbi.nlm.nih.gov/34862940/first of all empiric therapy with clarithromycin is no longer effective for treating Helicobacter. You have two choices. The choices are thus: 14-day bismuth quadruple therapy or rifabutin triple therapy,Andreadis K, Chan E, Park M, et al. Imprecision and preferences in interpretation of verbal probabilities in health: a systematic review. J Gen Intern Med 2021;36(12):3820-3829. . The interpretation of "common" which means- accepted definition of 1% to 10%.But people thought it meant 59% (on average) --------59% is basically all the time that is great odds and would bankrupt vegas TAKE HOME!!In studies asking for preference, a majority of patients prefer numbers rather than word-based estimates of risk. Risks and Benefits of Early Rhythm Control in Patients With Acute Strokes and Atrial Fibrillation: A Multicenter, Prospective, Randomized Study (the RAFAS Trial) | Journal of the American Heart Association (ahajournals.org) The main findings were that early rhythm control led to a lower risk of stroke at 12 months (3 [1.7%] vs 6 [6.3%]; HR, 0.251; P = .034). There was no difference in risk of recurrent stroke at 3 months. 

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00572-9/fulltextOld calculators use old studies and can over exaggerate the calculated effecthttps://pubmed.ncbi.nlm.nih.gov/33970197/We know when to start medication but it is so hard to prospectively know when to stop medication like anticoagulationhttps://pubmed.ncbi.nlm.nih.gov/34074830/2 Kiwi a day will increase your bowel movementshttps://pubmed.ncbi.nlm.nih.gov/34100866/We want to believe routine checkups work but realistically they don't work for patient oriented outcomes--but they make people 'feel good'-- what we do isn't always the doing, it's just being therehttps://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)01063-1/fulltextDAPT following a stent-- but then just maybe we should stay with plavix and not aspirin

https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2782015coffee is ok with atrial fibrillation -- just don't go crazy is probably good advicehttps://jamanetwork.com/journals/jamanetworkopen/fullarticle/2781351Hearing loss sucks and can really change your whole physical functionhttps://www.bmj.com/content/374/bmj.n1511elective orthopedic procedures with good evidence are limitedhttps://jamanetwork.com/journals/jama/fullarticle/2781859PRP injections -- work about as well as vitamin D-- just stophttps://www.bmj.com/content/374/bmj.n1446muscle relaxants for back pain improve pain at 2 weeks 8 points on 100 point scalehttps://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2781311STOP GIVING LEVOTHYROXINE to a majority of normal or subclinical normal peoplehttps://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2781806antibiotics will always be given if they are always given

Extended Follow-up of Local Steroid Injection for Carpal Tunnel Syndrome: A Randomized Clinical Trial | Neuropathy | JAMA Network Open | JAMA Network Looked at just over 100 patients with carpal tunnel syndrome and randomized them to injection of 80 mg methylprednisolone, 40 mg methylprednisolone, or saline and there was no difference except for an extra 60 days delaying surgery but still surgery.Associations Between Sleep Position and Nocturnal Gastroesop... : Official journal of the American College of Gastroenterology | ACG (lww.com)  The aim of this study was to investigate the effect of spontaneous sleep positions on the occurrence of nocturnal gastroesophageal reflux and in the end stay on your left side. Lee CG et al. Effect of metformin and lifestyle interventions on mortality in the diabetes prevention program and diabetes prevention program outcomes study. Diabetes Care 2021 Dec; 44:2775. (https://doi.org/10.2337/dc21-1046. opens in new tab)DONT TREAT PRE-DMEffect of Anticoagulant Therapy for 6 Weeks vs 3 Months on Recurrence and Bleeding Events in Patients Younger Than 21 Years of Age With Provoked Venous Thromboembolism: The Kids-DOTT Randomized Clinical Trial | Pediatrics | JAMA | JAMA NetworkBIG TIME ARTICLE—FINALLY WE HAVE EVIDENCE cause nothing worse than saying—we have no evidence for thatadvances the field by bringing uniformity and consensus to the issue of length of anti-thrombotic therapy for a first-episode of provoked VTE in children.

Writing Group for the CODA Collaborative. Patient factors associated with appendectomy within 30 days of initiating antibiotic treatment for appendicitis. JAMA Surg 2022 Jan 12; [e-pub]. Now, investigators have explored in a secondary analysis of  The CODA Collaborative. A randomized trial comparing antibiotics with appendectomy for appendicitis. N Engl J Med 2020 Oct 5; [e-pub]. (data from a previous randomized antibiotics-versus-surgery trial (NEJM JW Gen Med Dec 1 2020 and N Engl J Med 2020; 383:1907). Have looke at the data to see could we predict factors that make you more likely to appendectomy and fail antibiotic therapy.  They identified 735 patients who had been randomized to antibiotic treatment; 154 (21%) of these patients underwent appendectomy within 30 days. Overall, 29% of patients in the antibiotics group underwent appendectomy within 90 days (41% of those with appendicolith vs. 25% without). The authors suggest hey maybe this appendicolith is the magic answer of who will fail therapy—maybe!! BUT remember this is secondary analysis so this is only hypothesis generating even a secondary analysis of a rct is just hypothesis. You need a new RCT to actually show causation.  Also as stated in the editorialists note that in subsequent analyses of this same data set, nearly 50% of patients underwent appendectomy within 2 years, regardless of the presence of an appendicolith, so an initial nonsurgical approach might only delay surgery. Some say 50% still going to surgery is terrible but I say even if 50% prevented from having surgery that is still 50% of people are being prevented from a surgery      Acetazolamide to Prevent Adverse Altitude Effects in COPD and Healthy Adults | NEJM Evidence Trial 1 was a randomized, double-blind, parallel-design trial in which 176 patients with COPD were treated with acetazolamide capsules (375 mg/day) or placebo- COPD patients had oxygen saturation measured by pulse oximetry of 92% or greater  primary outcome in trial 1 was the incidence of the composite end point of altitude-related adverse health effects (ARAHE)== Criteria for ARAHE included acute mountain sickness (AMS) and symptoms or findings relevant to well-being and safety, such as severe hypoxemia, requiring intervention. In trial 1 of patients with COPD, 68 of 90 (76%) receiving placebo and 42 of 86 (49%) receiving acetazolamide experienced ARAHEThe number needed to treat (NNT) to prevent one case of ARAHE was 4EVEN at NNT of 4 you  have to realize that still 50% of those with COPD required intervention to go back down to lower level.   Trial 2 comprised 345 healthy lowlanders.The primary outcome in trial 2 was the incidence of acute mountain sickness AMS assessed at 3100 m by the Lake Louise questionnaire score (the scale of self-assessed symptoms ranges from 0 to 15 points, indicating absent to severe, with 3 or more points including headache, indicating acute mountain sickness AMS).In trial 2 of healthy individuals, 54 of 170 (32%) receiving placebo and 38 of 175 (22%) receiving acetazolamide experienced acute mountain sickness AMS  The NNT to prevent one case of acute mountain sickness AMS was 10 (95% CI, 5 to 141).So use the acetazolamide still 1 in 5 individuals experience acute mountain sickness    Annals for Hospitalists Inpatient Notes - Clinical Pearls—Stopping, Starting, and Optimizing Guideline-Directed Medical Therapy in Patients Hospitalized for Heart Failure With Reduced Ejection Fraction | Annals of Internal Medicine (acpjournals.org) Treat with??Foundational medical therapy for HFrEF consists of comprehensive disease-modifying quadruple medical therapy, including angiotensin receptor–neprilysin inhibitors (ARNIs), β-blockers, mineralocorticoid receptor antagonists, and sodium–glucose cotransporter-2 inhibitors (1). Quadruple medical therapy is estimated to cumulatively reduce the relative risk for death by 73% over 2 years, with a number needed to treat of 3.9 to save 1 life  compared with traditional therapy using an ACEI and a β-blocker, treating a 55-year-old patient with comprehensive disease-modifying quadruple therapy projects to increase life expectancy by more than 6 years Approximately 1 in 4 patients hospitalized for worsening HFrEF die or are rehospitalized within 30 days of discharge --- Deferring in-hospital initiation is consistently associated with medications never being initiated in the outpatient setting, or initiated after substantial delaySTART THEM IN THE HOSPITAL-- There is no evidence to suggest that “go slow,” “one medication change at a time,” or “defer to outpatient” approaches improve medication tolerance or accomplish anything beneficial  If you mix a bunch of moon pies in a trash can you get what sounds like a great time but if you mix a bunch of cow pies in a trash can you just get poop Clearly seen in this next article Vitamin D supplementation for the treatment of migraine: A meta-analysis of randomized controlled studies - ClinicalKey  meta-analysis aims to explore the efficacy of vitamin D for migraine patients. Six RCTs and 301 patients were included in the meta-analysis. On average these people were having around 7 migraines per months and compared to control the vit d group decrease headache days by about 1.5 per month compared to placebo or UC So you say vit d works for something!!Not so fast Remember I would like a 25 yr old cut my hair by not 5 five year olds…. Sadly these studies were 5 yr olds UC could be nothing. Well vit d beating nothing isn't hard, we know placebo is real Even beating placebo isn't hard when it is open label or you are not blinded to the active arm. If I say, yes you are getting this drug vit d that will help your headaches you are going to believe it much more than if I just give you a pamphlet.  The authors in the discussion state “Higher vitamin D levels is associated with lower risk of migraine “ Well ya that is true but having a higher vitamin d level is also associated with going outside more. And going outside more is associated with no having a migraine.  High vit d level is amazing!! I love it but replacing it still seems to do nothing however if you want a high level and want to go outside and get a high level then I think that is a great idea and speaking of great ideas—    Here is a sad but enlightening article— Home pregnancy test use and timing of pregnancy confirmation among people seeking health care - ClinicalKey The researchers found that 74% of survey respondents took a home pregnancy test as the first step in confirming a suspected pregnancy;  Respondents who took home pregnancy tests confirmed pregnancy 10 days earlier than those who first tested at a clinic. (duh statements- if you test at home you find out sooner, this is so obvious an a no brainer--- BUT Confirmation of pregnancy at greater than 7 weeks' gestational age was higher among adolescents, Latina versus white women, food-insecure versus -secure women, and people with unplanned pregnancies. Those that did not test at home cited concerns about test accuracy (42%) and difficulties accessing one (26%). While overall 1/5 21% confirmed pregnancy at ≥7 weeks gestation, confirmation at ≥7 weeks was higher among adolescents versus young adults (47%!! vs 13%, p = 0.001), Latina versus white women (28% vs 11%, p = 0.02), food insecure versus secure women (28% vs 17%, p = 0.06), and people with unplanned versus planned/mistimed pregnancies (25% vs 13%, p = 0.07). Latina and food insecure women discover their pregnancy at the same time or rate as individuals with unplanned pregnancy!!! one in 5 confirm pregnancy at 7 weeks gestation or later and in those Latina, poor, or unplanned It is ¼ at >7weeks this obviously effects prenatal care and Gestational bans in the first trimester will disproportionately prevent young people, people of color, and those living with food insecurity from being able to access abortion.This is tough but it is this data that reminds me and should remind us that life is not equal and healthcare is not equal and certain populations and groups do need our help more than others.

https://pubmed.ncbi.nlm.nih.gov/33734980/if you lay flat with a blood draw you may have psuedoanemiahttps://jamanetwork.com/journals/jama/fullarticle/2782300Men and UTI-- 7 dayshttps://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2782461don't get a UA prior to a procedure for screeninghttps://www.nejm.org/doi/full/10.1056/NEJMoa2026845cardiogenic shock- dobutamine vs milrinone https://pubmed.ncbi.nlm.nih.gov/34259820/Dont use a CAChttps://pubmed.ncbi.nlm.nih.gov/33637192/CKD = SBP

Yes this is a CME lecture but yes you get it for the expensive price of Free Fifty Free....

Contraception 2021 Sep 20;[EPub Ahead of Print], D Grossman, S Raifman, N Morris, A Arena, L Bachrach, J Beaman, MA Biggs, C Hannum, S Ho, EB Schwarz, M GoldSTUDY DESIGNThis is an interim analysis of an ongoing prospective cohort study conducted at five sites. Clinicians assessed patients in clinic and, if they were eligible for medication abortion and ≤63 days' gestation, electronically sent prescriptions for mifepristone 200 mg orally and misoprostol 800 mcg buccally to a mail-order pharmacy, which shipped medications for next-day delivery. Participants completed surveys three and 14 days after enrollment, and we abstracted medical chart data for this interim analysis.  In this prospective cohort study, researchers estimated the effectiveness, feasibility, and acceptability of medication abortion with mifepristone dispensed by a mail-order pharmacy with next-day delivery after in-person clinical assessment. The researchers found that complete medication abortion occurred for 96.9% of participants; 88.4% reported being very satisfied receiving medications by mail, and 89.6% said they would use the mail-order service again if needed. Of the 4.9% who experienced adverse events, none were related to mail-order dispensing. This research suggests that mail-order pharmacy dispensing of mifepristone is effective and acceptable to patients, providing further evidence that the in-person dispensing requirement for this medication should be removed.  IMPLICATIONSThe in-person dispensing requirement for mifepristone, codified in the drug's Risk Evaluation and Mitigation Strategy, should be removed.      Stevens SM et al. Antithrombotic therapy for VTE disease: Second update of the CHEST Guideline and Expert Panel Report. Chest 2021 Aug 2; [e-pub]. (https://doi.org/10.1016/j.chest.2021.07.055)  The ninth edition of the CHEST Clinical Practice Guidelines for managing venous thromboembolism (VTE) — published in 2012 and updated in 2016 — now has a second update, which addresses 14 clinical questions and offers 32 guidance statements for clinicians who manage patients with VTE. The 2012 guideline (Chest 2012; 141:Suppl:e419S and the 2016 update (NEJM JW Emerg Med Feb 2016 and Chest 2016; 149:315) both are publicly available.Key Recommendations Patients with isolated subsegmental pulmonary embolism (PE): Rule out proximal deep venous thrombosis (e.g., with ultrasonography). If risk for recurrent VTE is low, surveillance is recommended over anticoagulation. If risk for recurrent VTE is high, anticoagulation is recommended. (Weak recommendation, low-certainty evidence) Patients with incidentally discovered asymptomatic PE (other than isolated subsegmental PE): Same initial and long-term anticoagulation that patients with symptomatic PE receive should be used. (Weak recommendation, moderate-certainty evidence) Patients with cancer-associated VTE: Direct-acting oral anticoagulants (DOACs; i.e., apixaban, edoxaban, or rivaroxaban) should be used for the treatment phase of therapy (strong recommendation, moderate-certainty evidence). Caveat: for patients with luminal gastrointestinal malignancies, apixaban or low-molecular-weight heparin is preferred to reduce bleeding risk. Patients with antiphospholipid syndrome: Warfarin (target international normalized ratio, 2.5) is recommended over DOAC therapy during the treatment phase for VTE. (Weak recommendation, low-certainty evidence) Catheter-assisted mechanical thrombectomy: Recommended for patients with PE and hypotension who also have high bleeding risk, failed systemic thrombolysis, or shock that is likely to lead to death before systemic thrombolysis can take effect. (Weak recommendation, low-certainty evidence) Initial anticoagulation setting: Outpatient treatment is recommended over hospitalization in patients with low-risk PE, if access to medications and outpatient care is available. (Strong recommendation, low-certainty evidence) Treatment-phase anticoagulants: DOACs are recommended over warfarin. (Strong recommendation, moderate-certainty evidence) Extended-phase therapy (beyond 3 months) for VTE: Extended anticoagulation should be offered to patients with unprovoked VTE — i.e., with no major or minor transient risk factors. Risk for recurrent VTE, risk for bleeding, and patients' values and preferences should be considered in decisions about extended anticoagulation therapy. (Strong recommendation, moderate-certainty evidence) Low-dose apixaban or rivaroxaban is recommended over full doses of these agents. (Weak recommendation, very low-certainty evidence) Aspirin is recommended for patients who are stopping anticoagulation. (Weak recommendation, low-certainty evidence) Ingason AB et al. Rivaroxaban is associated with higher rates of gastrointestinal bleeding than other direct oral anticoagulants: A nationwide propensity score–weighted study. Ann Intern Med 2021 Oct 12; [e-pub]. (https://doi.org/10.7326/M21-1474) The study used icelands National databank to compare GI bleeding among almost 6000 patients receiving  apixaban, dabigatran, and rivaroxaban for the first time.  Patients were followed for 1-1/2 years and GI bleeding was verified by review of the medical records.  Once there was a propensity score analysis it was deemed that rivaroxaban had significantly high rates of minor and major gastrointestinal bleeding compared to apixaban with a number needed to treat of around 40 or 50.  However there was no difference between rivaroxaban and dabigatran.  I think this goes to what we have all seen and that the bleeding risk among most anticoagulate medications is not equal but unfortunately which medication the insurance companies will pay for it is also not equal.  However if your patient is at large risk for GI bleed likely should consider not using rivaroxaban                     Chen R et al. Comparative first-line effectiveness and safety of ACE (angiotensin-converting enzyme) inhibitors and angiotensin receptor blockers: A multinational cohort study. Hypertension 2021 Sep; 78:591. (https://doi.org/10.1161/HYPERTENSIONAHA.120.16667) In this retrospective study of patients who initiated monotherapy for hypertension, researchers used eight large observational databases to compare outcomes for 2.3 million new users of ACE inhibitors and nearly 700,000 new users of ARBs.  Myocardial infarction, stroke, and heart failure occurred with similar frequency in the two groups, after extensive adjustment for demographic and clinical variables. However, cough, angioedema, pancreatitis, and gastrointestinal bleeding occurred significantly more often in ACE-inhibitor users than in ARB users.            Long-Term Risk for Major Bleeding During Extended Oral Anticoagulant Therapy for First Unprovoked Venous Thromboembolism: A Systematic Review and Meta-analysis: Annals of Internal Medicine: Vol 174, No 10 (acpjournals.org) What happens if you extend anticoagulation past the 3 to 6 months for an individual who has a first unprovoked venous thromboembolism.  Often this is a debate in the clinical practice of while you seem low risk so maybe we should discontinue this anticoagulation or well you had his lab value is off to me we should continue anticoagulation.  The scary thing is you do not want to discontinue the anticoagulation and the may have a massive saddle embolism and die!  It is easy to start a medication but it is always so hard to stop the medication.  this study looked at that exact question --it looked at 14 randomized control trials and 13 cohort studies with just over 17,000 patients taking either vitamin K antagonist or DOACs.  The patient had to have received a minimum of at least 9 months of anticoagulation in order to be enrolled in the final analysis and they looked at patients who had had extended anticoagulation up to 5 years.In the end the incidence of major bleeding with warfarin was 1.7 events per year per 100 patients and much lower with the DOACs at 1.12 events per year per 100 people.  While that does not sound like a lot with the newer agents he has remember that is only after 1 year if he looked at the 5-year cumulative incidence of major bleeding for those individuals on either warfarin or a DOAC it was 6.3% which is certainly at significant risk of bleeding especially when you consider that the case fatality rate was 8.3% expirationThat was a whole bunch of numbers but basically I guess with this meta-analysis is really saying is that the current recommendations for anticoagulation after a unprovoked venous thromboembolism are 3 to 6 months and if you are going to extend that out to 9 months or a year or even up to 5 years he better have a darn good reason given that the eventual rates of bleeding are so high and the mortality rate from those bleeds are also so high.  

Davidson KW et al. Screening for prediabetes and type 2 diabetes: US Preventive Services Task Force recommendation statement. JAMA 2021 Aug 24; 326:736. (https://doi.org/10.1001/jama.2021.12531)  The Task Force found moderate-certainty evidence that screening is beneficial for nonpregnant adults (age range, 35–70) who are overweight (i.e., body-mass index [BMI], ≥25 kg/m2) or obese (BMI, ≥30 kg/m2) and have no symptoms of diabetes. Referring patients for, or directly providing, effective preventive interventions is recommended (B recommendation).  The main change from the 2015 recommendation is the lower age threshold for screening — 35 rather than 40. The decision was made because of the increasingly younger age of onset for diabetes and the known benefits of intervention at a wide range of ages. Notably, the USPSTF found little direct evidence that screening improves clinical outcomes;   Lifestyle modifications and metformin are considered appropriate interventions for preventing or delaying onset of diabetes; however, metformin is not approved for this specific use by the U.S. FDA. ---- NO NO NO NO NO NO NO you cant do that..    Aringer M et al. European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) SLE classification criteria item performance. Ann Rheum Dis 2021 Feb 10; 80:775. (https://doi.org/10.1136/annrheumdis-2020-219373) Diagnosising SLE—its always lupus till its not lupus but new diagnosis criteria In 2019, the European League Against Rheumatism and the American College of Rheumatology published the following classification criteria for systemic lupus erythematosus (SLE; Ann Rheum Dis 2019; 78:1151):·                     Positive antinuclear antibody (ANA) test with titer ≥1:80 is a required “entry criterion.”·                     If the ANA criterion is met, points are assigned from seven clinical categories and three immunologic test categories; a criterion is not counted if another cause is more likely than SLE.  A score ≥10 is considered to be consistent with SLE. When these criteria were validated, sensitivity for SLE was 96%, and specificity was 93%. But ANA what about ANA Sensitivity and specificity of ANA were 99.5% and 19.4%, respectively. NEXT  Gómez-Outes A et al. Meta-analysis of reversal agents for severe bleeding associated with direct oral anticoagulants. J Am Coll Cardiol 2021 Jun 22; 77:2987. (https://doi.org/10.1016/j.jacc.2021.04.061)Use of direct oral anticoagulants (DOACs) is associated with about a 3% annual risk for major bleeding, though that varies by age, comorbidity profile, and concomitant therapies.  investigators examined clinical outcomes associated with the use of 4-factor prothrombin complex concentrate (4PCC), idarucizumab, or andexanet for severe DOAC-associated bleeding.These drugs are greatBut if you do bleed then about 20% of the time we cant get hemostasis with mortality around 18% DESPITE getting reversal agents.. This is good to talk to your patients about— The risk of bleeding in 1 and 33 per year..Out of every 3300 people treated about 20 people will have a bleed that isn't controlled and 18 of those people will die.It sounds like a lot but remember without these drugs the risk of stroke is much much higher, of course depending on your comorbid conditions. NEXT  Cardiovascular risk prediction in type 2 diabetes before and after widespread screening: a derivation and validation study - ClinicalKeyLancet, The, 2021-06-12, Volume 397, Issue 10291, Pages 2264-2274, Copyright © 2021 Elsevier Ltd Formulas for cardiovascular (CV) risk calculations are based on population studies and generally include diabetes as a major risk factor. Do formulas that were derived when diabetes usually was diagnosed at later stages overestimate CV risk for people in whom diabetes is diagnosed early?? Basically long ago we diagnosed in DM at a1c of 12 not we diagnosis it at a1c of 6-6.5-7—even prediabetes at a1c of 5.5……Those are not the same population so now are we over diagnosing CV risk??? The answer for this new zeeland study was yes--In this modern diabetic population, the median 5-year risk for an adverse CV event, as estimated by the new formula, was 4.0% in women and 7.1% in men. The older formula overestimated median risk in women (14.7%) and in men (17.1%).This is has to do with new Zealand not the the more recent and commonly used American pooled cohort equation but even that I would love to see put through the ringer as many of the studies were done back in the 90s, over thirty years ago, when we were quite as sharp about diagnosing diabetes yet…either way you have to remember the ascvd risk score is for discussion it is not evidence based gold it is a conversation starter   Next DVT – I am always confused when people say airline travel is a risk factor. I have sat on my couch for 6 hours without moving and I never got a dvt so why would being on a plane for 3 hours. Well maybe it is something I don't understand about air travel because as this paper Munger JA et al. Television viewing, physical activity and venous thromboembolism risk: The REasons for Geographic and Racial Differences in Stroke (REGARDS) study. J Thromb Haemost 2021 Jun 2; [e-pub]. They looked to see if tv watching was associated with DVT and it was not – it didn't matter if you just watched a little bit of tv per day or over 4 hours of tv per day, there was no association with increase DVT and TV hours per day once accounting for total activity.. yes those that are watching TV move less and are more obese but is it he TV watching or just all the risk factors…. This article says it is the risk factors. Last articleKelly CR et al. Prevention, diagnosis, and treatment of Clostridioides difficile infections. Am J Gastroenterol 2021 Jun; 116:1124. (https://doi.org/10.14309/ajg.0000000000001278)    Oral vancomycin or fidaxomicin generally is favored for treating patients with nonsevere CDI, but metronidazole is acceptable for low-risk patients — especially when cost is a factor. Patients with severe CDI should be treated with either oral vancomycin or fidaxomicin (but not metronidazole). Severe disease is defined as having a leukocytosis >15,000 white blood cells/mm3 or a creatinine level of >1.5 mg/dL. Fecal microbiota transplantation (FMT) should be considered for refractory or severe CDI. *******A first recurrence should be treated with tapering/pulsed-dose vancomycin or fidaxomicin if it was not the initial therapy. ********A patient experiencing a second or further recurrence of CDI should be treated with FMT, delivered via a colonoscope or capsules, with enemas used when colonoscopy or capsules are not available. Repeat FMT can be used to treat a recurrence within 8 weeks of initial FMT. *****Patients with recurrent CDI who are not FMT candidates or have relapsed after FMT can be given long-term oral vancomycin prophylaxis to prevent recurrences. Oral vancomycin prophylaxis also can be considered when patients with recurrent CDI are given systemic antibiotics.

I've found that I can often increase compliance with statins by having pt take them 3x/week or QOD.  I try this often especially in my secondary prevention group. I understand "any statin is better than none", but do data support this approach?   -- any is better than none! No rct with this but yes data supports every other day but that is observational..what about vascepa in reducing CAD risk both primary and secondary risk? Vascepa is now the first and only drug approved by the FDA as an adjunct to maximally tolerated statin therapy to reduce the risk of myocardial infarction, stroke, coronary revascularization, and unstable angina requiring hospitalization in adult patients with elevated triglyceride (TG) levels (≥150 mg/dL) and established cardiovascular disease or diabetes mellitus and two or more additional risk factors for cardiovascular diseaseReduce it trial---The big trial which showed all the promise used mineral oil as a placeboAND then we have evaporate trial—which showed steady plaqueThe groups didn't start off the same!When you do an RCT- everything is random and therefor EVERYTHING IS EQUAL—but that idnt happen. And yes the people were blinded but they don't say that the people reading the CT was blindedThe placebo group had higher CRP and dramatically worse cholesterol panels after taking mineral oilThen most recently we have the strength it trial- which showed no difference and should have had high bioavailability! Like LDL that went up 50 points in the placebo group!! That shouldn't happen!What about fibrates for triglycerides > 400 or 500 to prevent complications like pancreatitis? No – no- no- no evidence for fibrates, period, throw them away. DRUGECTOMY for everyoneGiven evidence is only for patient to age 79, what do you recommend for patients over 79 with high lipids or on who are on a statin if concern for risk of negative cognitive effects of statins in this group?   Remember 5 years or less to live. stop the statin. And the cognitive declinePlease comment on lipophilic vs hydrophilic statins and possible detrimental effects on cognition.If cognitive risk is so small, why is there a black-box warning? It makes it difficult to convince the patient to take a statin when they read this warning.ano M, Bell KL, Galasko D, et al. A randomized, double-blind, placebo-controlled trial of simvastatin to treat Alzheimer disease. Neurology 2011;77(6):556-563.In this multicenter trial, the authors gave simvastatin or placebo to 406 patients with mild to moderate Alzheimer disease, aged at least 50 years, with a Mini-Mental State Examination score between 12 and 26, who otherwise would not have been taking a statin. Simvastatin was no better than placebo in slowing cognitive deterioration in patients with mild to moderate Alzheimer disease. (LOE = 1b)Steenland K, Zhao L, Goldstein FC, Levey AI. Statins and cognitive decline in older adults with normal cognition or mild cognitive impairment. J Am Geriatr Soc 2013;61(9):1449-55.These researchers serially assessed approximately 3500 elderly patients for 3.4 years. The elders did not have dementia at baseline and approximately one third were using a statin. After 3.4 years of follow-up, the rate of cognitive decline among statin users was comparable with that of nonusers. https://www.ahajournals.org/doi/10.1161/circ.128.suppl_22.A10589Results: Significantly higher proportional reporting ratios (PRRs) were observed for lipophilic statins, which more readily cross the blood-brain barrier, (range: 1.48-3.50) compared to hydrophilic statins (range: 0.68-1.60). However, fluvastatin, lovastatin, and pitavastatin (lipophilic) had relatively few adverse reports in the AERS database. The signal of higher risk of cognitive dysfunction was observed for the lipophilic statin atorvastatin (PRR = 2.68, 95% confidence interval: 2.52-2.85) followed by simvastatin (PRR = 2.20, 95% confidence interval: 2.02-2.40).Conclusions: Inconsistent with the FDA class warning, highly lipophilic statins with specific pharmacokinetic properties (atorvastatin and simvastatin) appear to confer a significantly greater risk of adverse cognitive effects compared to other lipophilic statins and those with hydrophilic solubility properties.“Keep in mind that cohort studies are unable to account for 2 important phenomena: the healthy-user effect and reverse causality. The healthy-user effect, the primary explanation for older theories of the "benefits" of hormone replacement, refers to the observation that healthy people are more likely to use preventive measures and that the outcomes are due to good health, not the intervention. In reverse causality, we find that patients in declining health stop using treatments because they no longer perceive a potential benefit. It takes a randomized trial to overcome these phenomena.”Last but not leastZhou Z et al. Effect of statin therapy on cognitive decline and incident dementia in older adults. J Am Coll Cardiol 2021 Jun 29; 77:3145. (https://doi.org/10.1016/j.jacc.2021.04.075)They followed 18,846 study participants for a median of 4.7 years. Participants' median age was 74 years, and 56% were women. With 85,557 person-years of follow-up, the investigators identified 566 incident cases of dementia. Statin use was associated with nonsignificant increases in all-cause dementia (hazard ratio, 1.16) and probable Alzheimer disease (HR, 1.33; 95% CI 1.00 to 1.77). Statin use was not associated with mild cognitive impairment, but there was a nonsignificant increase in association with Alzheimer disease (HR, 1.44).Any thoughts on coronary CTA (rather than calcium score) or carotid intimal medial thickness as a tool for risk assessment?          No—no prospective RCT—all retrospective. And the people are baseline high risk to begin with. if you would choose one single best statin for primary and secondary prevention, which one would you pick?  The one the pt will takeshould take a statin if it increases LFT??         YES remember we are decreasing heart attacks and strokes!! We have no evidence on was a smell increase in your LFT does long term but we have evidence that long term these drugs have a 30% RR reduction in heart attacks and strokes!Some patients like to take Co Q10 with their statin. What is your experience with this?  Taking it for muscle aches and remember there is no real difference in muscle aches compared to placebo. If you don't check cholesterol but every 10 years, how do you know that further risk reduction is needed for secondary prevention or additional medication to statin is needed  -- you do it based on their risk reduction! There are 3 criteria – 1. 1 event in last 12 months. 2. 2 eents in their life. 3. An event with 3 or more risk factors. what are the real risks of statins increasing risks of DM? depends where you read—cocochane has the HR at 1.18 but that is a 2 yr study. For our calculation of the risk of diabetes the answer likely lies between 0.4% and 4%, and we have chosen what we believe to be a conservative estimate of 2% as a midway point in this credible interval.The raw numbers of 270 and 216 new onset diabetes cases from 24 months of exposure to a statin and a placebo (respectively) can be extrapolated, assuming that increased diabetes risk is likely to continue linearly with exposure. This yields 675 and 540 cases at 5 years. How long do you do washout between statin? No hard science to this they have not randomized different months of wash out as far as I am aware of so 3-6 months and you will be fine. Anything to say about Nexletol?Is there any benefit in obtaining lipoprotein profiles? NO—not for the events we care about. There is evidence that you can get this panels and then you could add a drug or increase a dose and decrease a lab value but we treat patients not lab values and there is no evidence It improves patient orientated outcomes. WHATPCSK9 DO YOU USE? Whatever insurance will pay for and remember they are still really really really expensive and IV only so this should be dead last line and only in the highest of the highest of the highest risk. 

DYSh out information on DYSlipidemia: An Evidence-based Update on Cholesterol ManagementPlease contact me for more information:    Andrew Buelt, D.O.  andrewbuelt@gmail.com Questioning Medicine PodcastAthrosclerotic Cardiovascular Disease Risk Calculator (ASCVD) 10 yr ASCVD risk calculator developed in 2013 ASCVD event defined as nonfatal myocardial infarction, coronary heart disease (CHD) death, fatal or nonfatal stroke Development of ASCVD calculator used African-American and White men and women age 40 to 79 yrs old (not hispanic, watch for inclusion drift)  Risk assessment should occur every 5 yrs in moderate risk individuals and can occur more frequently if the patient is nearing a cutoff for treatment Serum Lipid Level Lipid levels are stable over long durations of time Serum lipid lab values have high intra-test variability Testing more frequently than every 10 years leads to overdiagnosis from lab error and not true changes in serum lipid levels.  Primary PreventionTreatment Statins are the only currently approved drug to reduce cardiovascular events in primary prevention patients  Primary prevention statins should be used for those with diabetes, LDL ≥ 190, ASCVD 10 yr risk of 11.25% No trial has EVER looked at treatment titration to a specific cholesterol number compared to standard treatment dose...EVER Coronary Calcium Scoring  No prospective RCT exist Largest observational study currently in existence had 5,185 patients, 58 patients were correctly reclassified, 292 patients incorrectly reclassified, 4,835 patients had no benefit or harm other than lost time, money, resources (0.3% benefit, 6.7% harm, 93% no benefit or harm) Secondary Prevention Define as individuals with previous angina, MI with or without intervention, ischemic stroke/TIA, peripheral arterial disease (claudication or abdominal aortic aneurysm) Treatment -First Line Treatment = Statin High dose statin reduces major adverse cardiovascular events by 1% more than moderate dose statin High dose statin cause adverse events WITH therapy discontinuation 1% more often moderate dose statin  ANY dose statin is better than no statin Statins cause myalgias at a rate that is not statistically different from placebo Second line treatmentIncrease statin dose to max tolerated then add Ezetimibe Third line treatmentPCSK9 inhibitor

part 1-- you dont get the CME but you get the information

PodcastGregory J, Huynh B, Tayler B, et al. High-dose vs standard-dose amoxicillin plus clavulanate for adults with acute sinusitis. A randomized clinical trial. JAMA Network Open 2021;4(3):e212713Study design: Randomized controlled trial (double-blinded) primary care offices with sinus symptoms consistent with currently accepted clinical criteria for acute bacterial sinusitis. andomly received (concealed allocation assignment) either a standard-dose regimen of amoxicillin 875 mg plus clavulanate 125 mg plus placebo twice daily for 7 days or a high-dose regimen of amoxicillin 875 mg plus clavulanate 125 mg plus amoxicillin 875 mg twice daily for 7 days. They planned to have 240 patients enrolled in the trial but then COVID happened and the authors say “  At an unplanned interim analysis prompted by COVID-19 restrictions” made us look at the data and then stop the trial. They found that there was NO difference between the high dose and the standard dosea global rating of "a lot better" or "no symptoms" occurred in 44.3% of patients in the standard-dose group compared with 36.4% of patients in the high-dose group  79 randomized to the standard dose and 78 to the high dose; 9 and 12, respectively, withdrew or were lost to follow-up  Because of the high drop-out rate, the investigators assigned a negative outcome to everyone in the standard-dose group and a positive outcome to everyone in the high-dose group; the group difference in the primary outcome was still not significant.DONT DO SOEMTHING STAND THEREChina L, Freemantle N, Forrest E, et al, for the ATTIRE Trial Investigators. A randomized trial of albumin infusions in hospitalized patients with cirrhosis. N Engl J Med 2021;384(9):808-817.Study design: Randomized controlled trial (nonblinded)in hospitalized patients with decompensated cirrhosis dose Routine daily albumin infusions to target an albumin level of 30 g/L or more prevent infection, kidney dysfunction, or death?  The intervention group (n = 380) received a daily 20% albumin infusion at 100 mL per hour to target an albumin level of at least 30 g/L for a maximum of 14 days or until discharge. The control group (n = 397) received standard care. The primary outcome was a composite of new infection from any cause, kidney dysfunction, or in-hospital death between trial day 3 and trial day 15 or day of discharge (whichever occurred earlier). There was no significant difference detected in the composite endpoint with an approximately 30% event rate in both groups.And whats worseThe intervention group had more severe and life-threatening adverse events, including pulmonary edema or fluid overload (6.1% vs 2.0%) and lung infections (3.9% vs 2.0%). We all want to do something but do nothing, just stand thereOr dont just do something let your patients do somethingScarinci IC, Li Y, Tucker L, et al. Given a choice between self-sampling at home for HPV testing and standard of care screening at the clinic, what do African American women choose? Findings from a group randomized controlled trial. Prev Med 2021;142:106358. Clinical questionDoes giving women the option of doing home self-sampling for human papillomavirus increase the rates of cervical cancer screening? study identified 12 rural, underserved towns and randomized the towns to either  (1) a visit from a Black female community health worker with information about cervical cancer screening and encouragement to have a free Pap test at the local health department (standard care), or (2) a visit in which they were given the choice of a free Pap test at the health department or the option to do free home self-sampling for HPV (choice).  Among women in the standard care group, only 16 of 170 (9.4%) were ultimately screened, compared with 63 of 165 (38.2%) in the choice group.We all want to do something but do nothing, just stand thereClinical questionWhat is the effect of a delayed prescription approach for children with respiratory tract infection? Mas-Dalmau G, Villanueva López C, Gorrotxategi Gorrotxategi P, et al, for the DAP PEDIATRICS GROUP. Delayed antibiotic prescription for children with respiratory infections: a randomized trial. Pediatrics 2021;147(3):e20201323. Study design: Randomized controlled trial (nonblinded)

Delay of Pregnancy Among Physicians vs Nonphysicians JAMA Intern Med 2021 May 03;[EPub Ahead of Print], MC Cusimano, NN Baxter, R Sutradhar, E McArthur, JG Ray, AX Garg, S Vigod, AN Simpson It has been hypothesized based on just rumor and people repeating it that women physicians are more likely to delay childbearing than nonphysicians. This population-based retrospective cohort study looked to see if that was true. They compared childbirth rates among physician and compared it to nonphysicians Physicians were less likely to experience childbirth at younger ages (HR for childbirth at 15–28 years, 0.15; P < .001) and more likely to experience childbirth at an older age (HR for 29–36 years, 1.35; P < .001; HR for ≥37 years, 2.62; P < .001). BUT BUT BUT do they delay child birth all together?? Well in simple terms, NO. female physicians have children rates equal to that of nonphysician women over time, although the time Basically this says what lots of us know in the women try not to have children during med school or residency because the cutoff was age 28 and if you go through it as fast as possible you are 29-30 provided you take the fast route possible. I think this makes sense an I would have liked to see them separate it out by age even a little more but overall I think residency and med schools should change the mantra and how the handle women becoming pregnant during training. It seems odd to me that so much emphasis these days is on burn out and making sure you have family time but often women are punished for having children during training years…..you cant have your cake and eat it to, you cant say one thing but do another…..although to me that is exactly what it seems like. Gender, Race, Ethnicity, and Sexual Orientation of Editors at Leading Medical and Scientific Journals: A Cross-sectional Survey | Medical Journals and Publishing | JAMA Internal Medicine | JAMA Network You have to know who was in the room… If a bunch of old white men created the machine or law or toy then it will be bias towards then and on the counter to that if a bunch of black or asiain people made the same law, toy, machine then it will be bias towards them and their perception of reality. It is our own individual bias that exist no matter how hard we try to fight it. This paper looked to see what is the general break down of the editorial staff of major medical and science journals and while there was a nice almost 50/50 split of men and women the mean age was 51 yrs old and white made up 77% with Hispanic and black only making up 5% COMBINED!! I am not saying we need to hire all Hispanic or black editors for major medical journals but maybe a few more… I say it like this, if I was an editor for lets say Jama internal medicine and in my previous life I was a vascular surgeon, Don’t you think even if I fought it that my bias would be to publish more papers that have something to do with vascular surgery or could somehow be related to vascular surgery. Our perception of reality is what we choose to see and the publication of paper is no different Annals for Hospitalists Inpatient Notes - A Critical Look at Procalcitonin Testing in Pneumonia | Annals of Internal Medicine (acpjournals.org) We all want a test that will help us—we all would love for procal to work but does it?? In addition, the 2019 joint guideline on community-acquired pneumonia (CAP) from the American Thoracic Society and Infectious Diseases Society of America recommends against the use of PCT testing to guide initiation of empirical antibiotic therapy for radiologically confirmed pneumonia (strong recommendation, moderate evidence) This is largely based on a study of 1735 patients admitted with CAP who had bronchs or procedures to identify pathogens… viral and bacterial pathogens were identified in 24% and 14% of cases, respectively. the negative predictive value of a PCT value less than 0.1 ng/mL was 82.4% (95% CI, 71.2% to 86.9%). Said differently, approximately 1 in 5 patients with microbiologically confirmed bacterial CAP had a negative PCT test result (2). failing to initiate antibiotics in nearly 20% of patients with confirmed bacterial CAP is unacceptable and not a good test! Now you could say but andrew—24% plus 14% is only roughly 40% what about the other 60% of people that didn’t have a confirmed source you cant just throw them out.. sure you are correct and if you include everyone then the egative predictive value of PCT increased to 93.9% (CI, 91.9% to 95.5%). BUT that is still missing 1 in 10 which is a lot! We think NNT of 25 at 2-3 years of a trial are good. This is if we should start therapy for an infection that could kill you or at least put you in the ICU and it is missing 1 in 10! If you really don’t know the diagnosis then can a procal be helpful in the context of the rest of your History and physical, sure, it is not completely worthless it is another data point. However, I will say I almost never order it but if it is already ordered I wont not look at it. My fear is that in much of the country procal became this golden, it can never be wrong, lab test and that is just simply not true. Sure there is an idea to trend procal and maybe we will discontinue antibiotics early but a major of pna is community acquired pna and the recommendations are for only 5 days of antibiotics as is. So maybe you decrease it by a day—is there really that much resistance that occurs from day 4 to day 5?? I doubt it but I have no evidence for or against that statement so I will leave it to you. The Problem of Aducanumab for the Treatment of Alzheimer Disease | Annals of Internal Medicine (acpjournals.org) Fda0 nov 2020- FDA statistician recommended this drug not be approved But via the “accelerated approval” pathway It was approved Accelerated approval is intended for products expected to provide a meaningful advantage over available therapies for a serious disease but for which there is uncertainty about clinical benefit. Under accelerated approval, a drug is approved on the basis of its effect on a surrogate marker of a disease—in this instance, brain β-amyloid levels—rather than clinical outcomes, such as signs or symptoms of Alzheimer disease. I will grant you we have nothing good for alzheimers and I do seriously mean there is no good medication for it but to approve it based on no clinical outcomes is potentially harmful or just a really expensive placebo because it will have no effect just like every other drug we have tried Aducanumab's phase 1 study showed lower levels of β-amyloid levels for those on the drug BUT SADLY aducanumab's phase 3 trials shows an unclear relationship between β-amyloid reductions and cognitive improvements so we have a drug the improves a surrogate outcome of amyloid levels but decreasing amyloid levels have never consistently proven or shown to improve cognitive outcomes EVEN IN THEIR OWN PHASE THREE TRIALS the company says it will continue to do research while the drug is on the market and expect it done by 2030 BUT until that time they are going to be collecting a lot of money for the next 9 years The drug's annual price per patient—$56 000— 56k per patient per yar for the next 9 years on a drug that we don’t know if it works for anything that we care about! This is a sad day—or a sad approval by the FDA and I can only wonder who was paying who to make this happen as the last line of this paper almost perfectly states “The FDA has approved a first-in-class product for Alzheimer disease on the basis of reduction in β-amyloid plaques. We all must wait for evidence of whether this in fact benefits patients." And with that! 

1) nurses commit more suicide and average population (doctors don't) 2) AK will turn in to SCC at a rate of about 2% per year 3) STOP SMOKING (even if you gain weight) 4) zofran is about equal to the rest for pregnant patients and the outcomes we care about 5) Tubes in the ear for children with acute otitis media?? It works about the same as medical management Association of US Nurse and Physician Occupation With Risk of Suicide | Nursing | JAMA Psychiatry | JAMA Network This retrospective cohort study used US data from 159 372 suicides reported in the National Violent Death Reporting System from 2007 to 2018. Researchers found that suicide was more common among nurses compared with the general population (sex-adjusted incidence, 23.8 per 100,000 vs 20.1 per 100,000; RR, 1.18). By sex, the physician suicide rate was not different from that of the general population Ten-Year Follow-up of Persons With Sun-Damaged Skin Associated With Subsequent Development of Cutaneous Squamous Cell Carcinoma | Dermatology | JAMA Dermatology | JAMA Network authors use Kaiser Permanente Northern California data to investigate a patient’s risk of SCC after an AK in more than 200,000 patients with AKs ( they give a bunch of fancy results but I am just going to tell you exactly what you need to know or want to know and that is what is the risk of AK turning into SCC and the answer is about 2% per year. An absolute risk is straightforward to use when thinking about patients: these results suggest that, if you see 10 patients with AKs on a given clinic day, one of them will have an SCC in the next 5 years. People don’t want to quit smoking, usually because it is addictive but some of the things they tell themselves is they smoke to stay skinny Sahle BW et al. Weight gain after smoking cessation and risk of major chronic diseases and mortality. JAMA Netw Open 2021 Apr 1; 4:e217044. (https://doi.org/10.1001/jamanetworkopen.2021.7044) prospective cohort study, looked at weight gain and associated mortality in about 17,000 adults over 8 years, during the 8 years of follow up 47% never smoked, 22% continued to smoke, and 31% quit smoking. participants who quit smoking gained on average 3.1 kg or almost 7 pounds compared with those who continued to smoke those who quit and gained weight had a hazard ratio for all-cause mortality around 0.30 compared to those who continued to smoke. This means if your risk of dying is 1 if you continue to smoke then if you stop smoking your risk of dying goes down to 0.3! This is insanely large, we have no drugs that give this big of a benefit and certainly not for mortality. That is a 70% decrease in mortality It just goes to show that although treatment is good, prevention, and discontinuing cigarette smoking is better. Comparison of Pregnancy Outcomes of Patients Treated With Ondansetron vs Alternative Antiemetic Medications in a Multinational, Population-Based Cohort | Clinical Pharmacy and Pharmacology | JAMA Network Open | JAMA Network Ondansetron is frequently used to treat nausea and vomiting during pregnancy. Although some studies reported important safety signals, few studies have been sufficiently large to assess rare pregnancy outcomes. Data from 456 963 pregnancies were included to evaluate exposure to ondansetron during pregnancy was compared with exposure to other commonly used antiemetics to minimize confounding by indication. primary outcome was fetal death, defined as either spontaneous abortion or stillbirth. there was no association between ondansetron exposure during pregnancy and increased risk of fetal death, spontaneous abortion, stillbirth, or major congenital malformations compared with exposure to other antiemetic drugs. Somethings we do in medicine we do because no one really questions it— Tympanostomy Tubes or Medical Management for Recurrent Acute Otitis Media | NEJM performance of tympanostomy-tube placement for recurrent acute otitis media has been the commonplace observation—OBSERVATION!! Previous trials of tympanostomy-tube placement for recurrent acute otitis media historically have many flaws For Example most were conducted before the introduction of pneumococcal vaccine (which is important later) they are of small size uncertain validity of diagnoses of acute otitis media short periods of follow-up so what if we could have a study that made acute otitis media diagnoses by a validated otoscopists, used a standardized protocol for treating episodes looked at 250 children and used a follow up of at least 2 yrs what if we could have that study???? WE ARE IN LUCK Tympanostomy Tubes or Medical Management for Recurrent Acute Otitis Media | NEJM this trial involves 250 children 6 to 35 months of age who had a history of recurrent acute otitis media to undergo tympanostomy-tube placement or receive nonsurgical medical management, with the option of tympanostomy-tube placement in the event of treatment failure The primary measure was the average number of episodes of acute otitis media per child-year (rate) during the 2-year follow-up period. episodes of acute otitis media per child-year during a 2-year period was 1.48±0.08 in the tympanostomy-tube group and 1.56±0.08 in the medical-management group (P=0.66). episodes of acute otitis media per child-year during a 2-year period was 1.48±0.08 in the tympanostomy-tube group and 1.56±0.08 in the medical-management group (P=0.66). – which mean NO DIFFERENCE to be fair the authors did a per protocol analysis which is inappropriate, you should do an intention to treat. Intention to treat is real life, it is what group is the person assigned to. If they are assigned to a drug or a treatment and don’t get the drug or treatment or in this case procedure, that is real life that is what really happens but when you want to find a positive outcome you do a per protocol analysis. A per protocol is just the people that finished the protocol, it will typically over exaggerate the effects of treatment. Well in this study 10% of the children in the tympanostomy-tube group did not undergo tympanostomy-tube placement and 16% of the children in the medical-management group underwent tympanostomy-tube placement at parental request, the per-protocol analysis, which gave corresponding episode rates of 1.47±0.08 and 1.72±0.11, respectively—which was significant. However that is not how you should ever look at data from an RCT and I find it interesting that the authors did in this paper. The true take home and conclusions of this paper are stated perfectly by the authors--- ‘Among children 6 to 35 months of age with recurrent acute otitis media, the rate of episodes of acute otitis media during a 2-year period was not significantly lower with tympanostomy-tube placement than with medical management. ‘ And although not powered for this they did show that among children who received pneumococcal vaccine tympanostomy-tube placement was not superior to medical management in reducing the rate of episodes of acute otitis media. So maybe this is not only a win for getting your kid vaccinated but a dagger for pediatric ENT physician everywhere. I can see it now, all the ENT physicians move to California where all the of the antivaxers live!

Donanemab doesn't work for alzheimers if you actually read the study. Mammograms should be done every other year and starting at age 50. Blue-blockers don't prevent eye strain on the computer and sleep varies but at this time the evidence doesnt suggest it causes obesity https://www.nejm.org/doi/full/10.1056/NEJMoa2100708 new drug donanemab vs placebo = 257-patient double-blind randomised TRAILBLAZER-ALZ trial. the authors say “In patients with early Alzheimer’s disease, donanemab resulted in a better composite score for cognition and for the ability to perform activities of daily living than placebo at 76 weeks, although results for secondary outcomes were mixed. “ but lets review individuals with a Mini-Mental State Examination (MMSE) score of 20-28 were included in the study The primary outcome was the change in the Integrated Alzheimer’s Disease Rating Scale at 76 weeks. (iADRS; range, 0 to 144, with lower scores indicating greater cognitive and functional impairment) the change in the iADRS score at 76 weeks was -6.86 in the donanemab group and -10.06 in the placebo group (difference, 3.20; 95% confidence interval [CI], 0.12 to 6.27; P=0.04). SADLY--—both groups still got worse just not as worse with donanemab. There was no benefit of donanemab over placebo seen on the secondary outcomes, ((((((Secondary outcomes included the change in scores on the Clinical Dementia Rating Scale–Sum of Boxes (CDR-SB), the 13-item cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-Cog13), the Alzheimer’s Disease Cooperative Study–Instrumental Activities of Daily Living Inventory (ADCS-iADL), and the Mini–Mental State Examination (MMSE), as well as the change in the amyloid and tau burden on PET.)))))) So you have a 3 point change on a 144 point scale with no other positive findings and you say BAM look at this fantastic drug we have…Although there were no safety concerns I think my listeners will know I think this is a perfect study to question medicine and maybe save in a drawer to give students about the importance of stastical vs clinical significance and how small changes on big scales can give you a positive study but that doesn’t mean it was a positive study clinically speaking.. Recommendations From Breast Cancer Centers for Frequent Screening Mammography in Younger Women May Do More Harm Than Good | Breast Cancer | JAMA Internal Medicine | JAMA Network This is from the “less is more” series and it tackles one of my most favorite discussions—the benefits of mammograms- who should get them?? How often should they get them? What age should we begin? The CDC says-- “Women aged 40 to 44 years should have the choice to start breast cancer screening once a year with mammography if they wish to do so. The risks of screening as well as the potential benefits should be considered. Women aged 45 to 49 years should be screened with mammography annually.” “The most recent (2016) US Preventive Services Task Force (USPSTF) breast cancer screening recommendations for women with average risk advise biennial screening in women aged 50 to 74 years” What about 40-49? Well the USPSTF says they do not recommend it but think it should be dicussed in a shared decision making conversation The AAFP says exactly what the USPSTF says – which is usually a safe and great bet—(rant on what told brian about USPSTF) American cancer society says yearly at age 40, start yearly mammograms at 45, transition to every other year at age 55. ACOG says mammograms every 1-2 years from women 40-49 then annually after that. And when no one agrees that means the evidence is borderline at best OR it is borderline with heavy bias from big pharmat. Every society agrees on the big ticket items like treating blood pressure but when it starts to vary by society then you know that the actual evidence is terrible. So lets talk about risk and benefits and should you do it starting at age 40? first- lets start with how often—yearly or every other year??? EVERY other year Biennial mammography is preferred because it has benefits similar to those of annual screening but with fewer harms. The problem with mammograms is the false positive rate—obviously the more test you have the more likely you are to have a positive- debateable if that is true or false positive. Over 10 yrs if done annualy the false positive rate is 61% but if done every other year then you are doing less test and that rate of having a false positive result drops to 42% Now false positives are bad because of the stress they put on the families and the women but that is mental health and hard to quantify because we can never randomize people to get false positive results and true positive results… so lets talk numbers…. As in numbers of biopsies If you get annual mammograms for 10 yrs you have a 7% risk of undergoing biopsy but if you get mammograms every other year then your risk is 4.8% So we do less test, we have less false positives, we do less unnecessary biopsies AND there is not real difference in breast cancer mortality among younger women between annual and biennial screening. But now lets look at the age--- a paper titled Benefits and harms of breast cancer screening with mammography in women aged 40–49 years: A systematic review In the journal in international journal of cancer Was a systematic review looking at evidence from RCTs on the benefits and harms of breast cancer screening with mammography in women aged 40–49 years. They found “The results showed no significant effect on breast cancer mortality (Age trial: RR 0.93 (95% CI 0.80–1.09); CNBSS‐I: HR 1.10 (95% CI 0.86–1.40)) nor on all‐cause mortality (RR 0.98, 95% CI 0.93–1.03) in women aged 40–49 years offered screening.” Over‐diagnosis of invasive breast cancer evaluated 20 years after completion of the of screening was estimated to be 48%. They say—and I quote- “Based on the current evidence from randomised trials, extending mammography screening to younger age groups cannot be recommended. ‘ The recommendation for annual mammography in women younger than 50 years is, at best, confusing for patients – I think the evidence is clear for screening every other year and start at 50 with a conversation starting at 40. so just maybe the USPSTF got it right. Do blue-blocking lenses reduce eye strain from extended screen time? A double-masked, randomized controlled trial - American Journal of Ophthalmology (ajo.com) Measures of eye strain included critical flicker-fusion frequency, saccadic eye movements, near point of accommodation, near point of convergence, and blink rate. blue-blocking lenses during 2 hours of computer use did not alter subjective nor clinical measures of eye strain. - sad but I think the authors are spot on when they say “ "it is extremely unlikely that blue light is a contributory factor to eye strain associated with computer use." This next paper is a real sleeper, titled “Association of Sleep Duration and Variability With Body Mass IndexSleep Measurements in a Large US Population of Wearable Sensor Users” Which was a retrospective cohort study of sleep data from 200,000 De-identified individuals using a commercially available wearable device such as Fitbit They were looking at the Association between sleep and the associated BMI And their major findings were “(1) individual sleep durations and patterns are highly variable, and (2) shorter sleep duration and greater sleep variability were both associated with higher BMI” Taking those one by one, it didn’t take any study to understand individuals vary in their duration and pattern of sleep. This is an obvious statement from maybe even your own household. Some People are early risers and some people are night owls. But I am most interested in the second major finding which was that shorter sleep duration and greater sleep variability was associated with a higher BMI. How did they find this? Well they used a BMI cutoff of obesity, so a BMI of 30 and they looked to see if it was associated with a shorter sleep duration or a more variable sleep pattern and they found that indeed it was associated with both. However, when you look at the numbers you will find that the sleep duration of those individuals who had a BMI greater than 30 had a sleep duration of 6.6 hours per night while those who had BMI under 30 longer sleep duration at 6.8 hours per night. This was a pvalue of 0.001. but when you break it down that is on 15 minutes!!!! this is pure association not causation. Use your brain, does and extra 15 minutes of sleep really prevent you from being obese? or does 15 minutes less of sleep make you obese??? Sad this is the data that will be used in future studies and future meta analysis. other authors will look at this data or this abstract and say look at the positive Association with sleep and lower BMI. Using this logic then even 1 extra minute should have significant power. Or just maybe, just maybe this is another example of data mining, an example of large data which can find trends that are likely not significant. Remember the more people you enroll or look at in a study the more likely you find a small difference is a very real difference statistically speaking but the more people you enroll or look at the more you need to question if the statistical finding is plausible or clinically significant. I think my take home is that sleep is important but this data does not prove that extra time sleeping either prevents or causes you to have a BMI< 30 and its sad that this sort of data is even allowed to be published in major journals like jama internal medicine.

Circulation Bariatric Surgery and Cardiovascular Outcomes in Patients With Obesity and Cardiovascular Disease: A Population-Based Retrospective Cohort Study Circulation 2021 Apr 13;143(15)1468-1480, AG Doumouras, JA Wong, JM Paterson, Y Lee, B Sivapathasundaram, JE Tarride, L Thabane, D Hong, S Yusuf, M Anvari Patients with CVD who underwent bariatric surgery were matched 1:1 with similar CVD patients who did not undergo bariatric surgery. primary outcome was major adverse cardiovascular events (MACE) (first occurrence of all-cause mortality, myocardial infarction, coronary revascularization, cerebrovascular events, and heart failure hospitalization) n follow-up of 4.6 years, the primary outcome was lower in the surgery group compared with the control group occurred in 11.5% (151/1319) of the surgery group and 19.6% (259/1319) of the controls that is roughly a NNT of 12. But enough with the observational trials- do what we want to see or don’t do it. And while observation studies annoy me, sometimes they are necessary evil lead to practice or board changing answers, Girometti N et al. Clinical and serological outcomes in patients treated with oral doxycycline for early neurosyphilis. J Antimicrob Chemother 2021 Mar 30; [e-pub]. (https://doi.org/10.1093/jac/dkab100) The board question is someone comes in with neurosyphilis but is allergic to penicillin- the answer on every test is always who cares give it to them anyways. You go with penicillin desensitation, with is painfully slow and annoying. But in this study retrospectively evaluated 87 patients with early neurosyphilis who either received intramuscular (IM) penicillin with oral probenecid for 14 days (71%), 200 mg oral doxycycline twice daily for 28 days (18%), 2 g IM or intravenous ceftriaxone daily for 14 days (3%), a majority did get the penicillin but . All patients attained seroreversion to a negative rapid plasma regain [RPR] or a fourfold decline in RPR titer. And At 30 days after completion of therapy, 91% of patients receiving parenteral penicillin therapy and 100% of doxycycline recipients achieved symptomatic resolution. But enough of the observation data lets move onto a viewpoint in JAMA Industry-Sponsored Speaker Programs—End of the Line? | Law and Medicine | JAMA | JAMA Network November 16, 2020 for only the 6 times in 20 years the the Office of Inspector General (OIG) for the US Department of Health and Human Services (HHS) issued a Special Fraud Alert on “abuse risks associated with the offer, payment, solicitation, or receipt of remuneration” relating to industry-sponsored speaker programs Now when I was a resident I took a free dinner but I was never invited back because I would ask a bunch of hard questions about the methods of the study that the speaker wasn’t prepared to answer. It was entertainment, education, and a free meal. SINCE becoming an attending I have not been to one and I said that with pride. industry-sponsored speaker programs dates back to the 1950s and they have always been ‘dirty’ with physician kick backs and bias. And off these CME or speaker sponsored programs are “offered under circumstances that are not conducive to learning. ALSO lets be very clear often these drugs are not better than current standard of practice and they are more expensive which is a losing situation for our patients. But why this fraud alert issued?? Well July 1, 2020, During covid peak, Novartis quietly agreed to pay 678$ million dollar settlement for fraud charges of payment to physician and speak programs. And I quote- Novartis “violated the federal False Claims Act and Anti-Kickback Statute by providing doctors with cash payments, recreational outings, lavish meals, and expensive alcohol to induce them to prescribe Novartis cardiovascular and diabetes drugs reimbursed by federal healthcare programs.” From 2017 to 2019, drug and device companies reported paying health care professionals nearly $2 billion in compensation for services other than consulting but I suspect this will be going down significantly in the near future as it is hard to continue to issue kickbacks when you have the attention of the office of the inspector general. SOO if you are a big pharma industry sponsored event attendee that like a free industry sponsored meal, enjoy it while you can because this for the betterment of medicine and the well being of our patients is likely going away. And while we are talking about government lets talk politicians and something they did positive which is usually few and far between but on December 27, 2020, congress passed the Surprises Act — which banned “surprise billing” and in order to talk about how this is a good thing lets quickly make sure we are all on the same page. Lets say a patient gets sick and goes to the ER and then gets admitted to the hospital. Once in the hospital that patient has no control over what doctors they see. IF they see a doctor or two that are out of their network. Since insurance plans aren’t required to pay out-of-network providers their full charges, clinicians may bill the patient for the difference between the insurance payment and their charges. This ends of up being a surprise bill and usually a surprise that is a lot of money. This is terrible. You get sick, you just want to get better, you are at a hospital and you have no control if the pulmonologist or cardiologist is in your insurance plan but yet SURPRISE you get stuck with the bill. BUT BUT BUT Effective January 1, 2022, patients receiving out-of-network emergency services, air-ambulance transportation, or out-of-network nonemergency services at in-network facilities may be billed only the amount they would owe for an in-network provider. Finally lets end with a little game from JAMA internal med. Adverse Events Associated With the Addition of Aspirin to Direct Oral Anticoagulant Therapy Without a Clear Indication | Atrial Fibrillation | JAMA Internal Medicine | JAMA Network ASA and anticoagulation is done wrong all the time so lets play a game The combination of ASA with oral anticoagulation can be indicated for patients with?? The answer is certain devices (eg, left ventricular assist devices) , patients with nonvalvular atrial fibrillation and have acute coronary syndrome (ACS) and undergo percutaneous coronary intervention (PCI). And finally those with venous thromboembolism (VTE) and have acute coronary syndrome (ACS) and undergo percutaneous coronary intervention (PCI). Boom that is it! If you use combination therapy outside this setting then likely more harm than good and in this registry-based cohort study researchers looked at the medical records of almost 3300 patients and matched up Roughly 1000 patients who received a DOAC plus aspirin were matched to 1000 who received a DOAC alone. During a 12month follow-up, patients on combination therapy were more likely to experience a bleeding event and Hospitalization for bleeding. BUT Thrombotic events, did not differ between the groups. So you bleed more but you have the same risk of thrombotic events which sounds like a major losing strategy and something we should all keep in our minds for times when we can do a drugectomy and remove either the ASA or the anticoagulant, which ever is not needed. So I ask you again The combination of ASA with oral anticoagulation can be indicated for patients with?? The answer is certain devices (eg, left ventricular assist devices) patients with nonvalvular atrial fibrillation and have acute coronary syndrome (ACS) and undergo percutaneous coronary intervention (PCI). And finally those with venous thromboembolism (VTE) and have acute coronary syndrome (ACS) and undergo percutaneous coronary intervention (PCI).

Compression stocking to prevent cellulitis? NOT SO FAST! Vitamin D still doesn't work even for depression. Hip fractures are on teh decline and it is not because of drugs. A scribe cost money, but how much? What about doing an LP with anticoagulants, it is probably safer than you think. What do you do with kidney stones? Finally, there is a lot of medical waste, so stop ordering MRIs for low back pain! https://pubmed.ncbi.nlm.nih.gov/33058700/ https://pubmed.ncbi.nlm.nih.gov/32989711/ https://www.auajournals.org/doi/10.1097/JU.0000000000001318 https://jamanetwork.com/journals/jama/fullarticle/2771609 https://www.acpjournals.org/doi/10.7326/M20-0428 https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2768887 https://jamanetwork.com/journals/jama/fullarticle/2768978 https://www.nejm.org/doi/10.1056/NEJMoa1917197

1- make sure pts follow up on positive FIT test 2. symptom severity — driven particularly by catching/locking and clicking/popping — correlated significantly with the burden of cartilage damage. CARTILAGE DAMAGE!! 3. U.S. Food and Drug Administration announced it is allowing the use of the Binx Health Assay for point-of-care testing for Chlamydia trachomatis and Neisseria gonorrhoeae 4. In patients with atrial fibrillation and a bioprosthetic mitral valve, rivaroxaban was noninferior to warfarin 5. ADHD- “results favored using methylphenidate in children and adolescents, and amphetamines in adults as first-line, short-term (12 weeks or under) treatment.” 6. when it comes to PAD it is true what they say! no pain no gain- but maybe they should say no walking pain less loss and more walking pain much bigger gains in 6minute walking distance The Push for Timely Follow-up After Abnormal At-home Colon Cancer Screening Results | Cancer Screening, Prevention, Control | JAMA | JAMA Network The pandemic has brough on way more things done at home which Is good and bad More stay at home school- bad More stay at home colon cancer screening- good Article talked about a need to make sure pts if positive then get the colonoscopy. Poit out one study where only 44% completed a colonoscopy within 6 months of a positive FIT result even though 89% received a referral, Reasons for the low rates are complex. Patients who are reluctant to get a colonoscopy. and physicians don’t always convey the importance of follow-up. Other factors such as inadequate insurance, lack of transportation, or a facility backlog may be out of a patient’s control. I think in the end we just have to make sure we do our part and while I wouldn’t say scare them make sure they know the importance of this test and how likely it is that they have colon cancer based on it being positive And as a reminder Zorzi M, Hassan C, Capodaglio G, et al. Long-term performance of colorectal cancer screening programmes based on the faecal immunochemical test. Gut 2018;67(12):2124-2130. Over a 10-year period, the rates of detection of colorectal cancer (CRC) and advanced adenomas using fecal immunochemical testing (FIT) are similar to those seen in studies of screening colonoscopy. But how good is it you ask? Imperiale TF, Ransohoff DF, Itzkowitz SH, et al. Multitarget Stool DNA Testing for Colorectal-Cancer Screening. N Engl J Med 2014;370(14):1287-1297. FIT was 74% sensitive and 95% specific. Which in pt terms means for every 11 positive FIT there was 1 cancer detected on colonoscopy A positive fit has you down to a 1 in 10 chance of cancer—get the follow up! And speaking of follow up Patient-reported catching or locking of the knee and other “mechanical symptoms” (i.e., popping, clicking, or pain on pivoting) Usually gets a follow up with an ortho surgeon That patient usually goes to get an arthroscopic knee surgery for symptoms attributed to meniscal tears. BUT BUT BUT what if the text book and board question of pain or instabilitiy with (i.e., popping, clicking, or pain on pivoting) Isn’t a meniscus problem at all?? Meniscal and Mechanical Symptoms Are Associated with Cartila... : JBJS (lww.com) Farina EM et al. Meniscal and mechanical symptoms are associated with cartilage damage, not meniscal pathology. J Bone Joint Surg Am 2021 Mar 3; 103:381. (https://doi.org/10.2106/JBJS.20.01193) Researchers prospectively evaluated 565 patients (mean age, 48) who had arthroscopic knee surgery for symptoms connected to meniscus pathology. Pts were asked about the presence and severity of symptoms prior to surgery and then while in surgery, the surgeon recorded characteristics of meniscal tears and the severity of cartilage damage. In the end “We did not observe an association between meniscal pathology and preoperative patient-reported knee symptoms." Instead they found overall symptom severity — driven particularly by catching/locking and clicking/popping — correlated significantly with the burden of cartilage damage. CARTILAGE DAMAGE!! And if you had tricompartmental cartilage damage (i.e., medial, lateral, and patellofemoral). Then there was even greater symptoms severity…almost a dose response of cartilage damage to symptoms severity Perhaps the observations in this study help to explain why arthroscopic meniscal surgery has not consistently proven to be better than conservative management in randomized trials FDA Allows for First Point-of-Care Chlamydia and Gonorrhea Test to be Used in More Near-Patient Care Settings | FDA the U.S. Food and Drug Administration announced it is allowing the use of the Binx Health Assay for point-of-care testing for Chlamydia trachomatis and Neisseria gonorrhoeae, The test, which uses female vaginal swabs and male urine specimens, takes about 30 minutes and can be done right there in the office This is the first point of care test approved for Chlamydia trachomatis and Neisseria gonorrhoeae testing And I have no idea how much it will cost but my guess is a pretty penny Next article Rivaroxaban in Patients with Atrial Fibrillation and a Bioprosthetic Mitral Valve | NEJM The primary outcome was a composite of death, major cardiovascular events (stroke, transient ischemic attack, systemic embolism, valve thrombosis, or hospitalization for heart failure), or major bleeding at 12 months. In this open-label design Randomized trial of 1005 patients who were randomized to either 20 mg once daily rivaroxaban vs dose-adjusted warfarin in patients with atrial fibrillation and a bioprosthetic mitral valve In the end In patients with atrial fibrillation and a bioprosthetic mitral valve, rivaroxaban was noninferior to warfarin When it came to the composite primary outcome of death, major cardiovascular events, or major bleeding at 12 months. I have a couple problems Industry funded and open-label design – immediate bias into event rates. People doing the trial get paid ot do the trial and enroll people. They want this to work, they will try to show benefit as much as possible whenever possible. Nothing wrong with them, just human nature. This is for bioprosthetic mitral valves NOT mechanical valves HOWEVER This does seem to be consistent with observational and subgroup analysis from other studies and likely will change practice going forward. ADHD is real and what do you write for- well what if we could just get a large meta-analysis of almost 24K people Well we are in luck Comparative efficacy and tolerability of medications for attention-deficit hyperactivity disorder in children, adolescents, and adults: a systematic review and network meta-analysis - The Lancet Psychiatry Researchers examined efficacy and tolerability of data of the drugs used to treat attention-deficit/hyperactivity disorder from published and unpublished double-blind, randomized, controlled trials. In total they had 133 trials and included close to 14,000 children and 10,000 adults. They analysis was able to do indirect comparison which is when you take one study active arm and compare it to another study active arm and in the bit of statistical magic you get what appears to be results between the two active arms. So aspirin vs placebo and then Plavix vs placebo and then you can do an indirection comparison and BOOM stat magic and you have results for aspirin vs Plavix. Is it perfect? NO but is it better than nothing, usually. Some interesting results For children based on teachers' ratings only methylphenidate and modafinil were more effective compared to placebo BUT In adults modafinil didn’t beat placebo The best drug for adults was amphetamines I think one of the authors who commented on this said it best “results favored using methylphenidate in children and adolescents, and amphetamines in adults as first-line, short-term (12 weeks or under) treatment.” The authors did look for data at 26 and 52 weeks but found insufficient evidence. Which is to be expected as most mental health drugs only show improvement in the short instead of long duration but it also speaks to the importance of drug holidays when possible. These drugs have evidence for 12 weeks we have no idea what the good or bad long term effects are when taken for 12, 22, 32, or 42 years. Effect of Low-Intensity vs High-Intensity Home-Based Walking Exercise on Walk Distance in Patients With Peripheral Artery Disease: The LITE Randomized Clinical Trial | Cardiology | JAMA | JAMA Network How long or fast do you need to walk if you have PAD Does a low-intensity work just as good at high intensity? 305 participants with PAD Randomized to either low-intensity exercise, high-intensity exercise, and a nonexercise control group Participants in the walk groups were asked to walk 5 times per week for up to 50 minutes per session wearing an accelerometer to document exercise intensity and time. low-intensity group walked at a pace without ischemic leg symptoms. The high-intensity group walked at a pace eliciting moderate to severe ischemic leg symptoms. There were weekly phone calls with their ‘coach’ to help with adherence. Adherence was pretty good at around 85%!!! THAT ALONE IS IMPRESSIVE All participants did a 6 minute walk test at the beginning of the study and then again at the end of the study The primary outcome was mean change in 6-minute walk distance at 12 months In the end if you did Nothing then you decreased in for walk test distance by −15m, high intensity group GAIN 35m on their 6 minute walk test, but what about the low intensity- that is what we all care about is just a little bit of exercise beneficial. Is it ok to walk at a pace that is slow and doesn’t produce any pain and THOSE randomized to the load intensity group showed a DECREASE in their 6minute walk distance! They went down by -6.4M! No pain no gain! If you have PAD you can just lolly gag your walk around the block you have to push it. Sure a lolly gag pace wont lose you as much as doing nothing but if you push it you will see gains! I guess when it comes to PAD it is true what they say! no pain no gain but maybe they should say no walking pain less loss and more walking pain much bigger gains in 6minute walking distance

DOAC are just as safe if not safer for warfarin for valvular afib (NOT valve replacement but moderate to severe mitral stenosis). Please, just give normal lovenox for covid patients. Stop DM drugs in the elderly cause no-glycemia is more dangerous than hyperglycemia. semaglutide works as along as you keep taking it. gestational diabetes screening should be a two stop process. Effectiveness and Safety of Direct Oral Anticoagulants Versus Warfarin in Patients With Valvular Atrial Fibrillation: A Population-Based Cohort Study: Annals of Internal Medicine: Vol 0, No 0 (acpjournals.org) researchers did a New-user retrospective propensity score–matched cohort study matching roughly 28,000 new users of DOACs with new users of warfarin. During a median follow-up of roughly 130 days, primary effectiveness outcome was a composite of ischemic stroke or systemic embolism. The primary safety outcome was a composite of intracranial or gastrointestinal bleeding. the rate of stroke or systemic embolism was significantly lower among DOAC users than warfarin users (3.9 vs. 6.0 events per 100 person-years). NNT of 50 The rate of major bleeding events was also lower among DOAC users (7.1 vs. 10.6 events per 100 person-years). And a NNH 28 to prescribe warfarin This would be great because no longer need an echo prior to writing for a doac—a reminder part of this exclusion was bioprosthetic or mechanical heart valve replacement Effect of Intermediate-Dose vs Standard-Dose Prophylactic Anticoagulation on Thrombotic Events, Extracorporeal Membrane Oxygenation Treatment, or Mortality Among Patients With COVID-19 Admitted to the Intensive Care Unit: The INSPIRATION Randomized Clinical Trial | Critical Care Medicine | JAMA | JAMA Network What are the effects of intermediate-dose compared with standard-dose prophylactic anticoagulation in patients with COVID-19 admitted to the intensive care unit (ICU)? Intermediate-dose (enoxaparin, 1 mg/kg daily) (n = 276) vs standard prophylactic anticoagulation (enoxaparin, 40 mg daily) (n = 286), The primary efficacy outcome was a composite of venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or mortality within 30 days, assessed in randomized patients who met the eligibility criteria and received at least 1 dose of the assigned treatment. results Among patients admitted to the ICU with COVID-19, intermediate-dose prophylactic anticoagulation, compared with standard-dose prophylactic anticoagulation, did not result in a significant difference in the primary outcome of a composite of adjudicated venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or mortality within 30 days. Do the trial and don’t just blindly do it based on what you believe to be true or voodoo magic But interia takes over and we keep doing the same thing Lega IC et al. Glycemic control and use of high-risk antihyperglycemic agents among nursing home residents with diabetes in Ontario, Canada. JAMA Intern Med 2021 Mar 1; [e-pub]. We all know no glycemia is a lot worse then hyperglycemia- I also think we all know that The ADA recommends relaxed glycemic targets for older patients with diabetes and comorbidities population-based retrospective study, glycemic control among 15,000 Ontario nursing home residents with type 2 diabetes who were receiving at least one glucose-lowering drug. Mean glycosylated hemoglobin (HbA1c) level was 7.3%. On average, patients were receiving two glucose-lowering agents; about half of patients had HbA1c levels ≤7.0%. How intertia might be a good thing especially if it comes to semaglutide Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity: The STEP 4 Randomized Clinical Trial | Clinical Pharmacy and Pharmacology | JAMA | JAMA Network randomized clinical trial of adults with overweight or obesity, 803 participants completed a 20-week run-in of weekly treatment with subcutaneous semaglutide, 2.4 mg, with a mean weight loss of 10.6%, and were randomized to continued treatment with subcutaneous semaglutide vs placebo for an additional 48 weeks. Lets make no false predictions. 10% weight loss is a ton especially over 20 weeks BUT what happens when you stop this weight loss drug?? The primary end point was percent change in body weight from week 20 to week 68; With continued semaglutide, from week 20 to week 68 was −7.9% continued decrease in weight but you gained +6.9% with the switch to placebo (difference, −14.8 [95% CI, −16.0 to −13.5] percentage points; P 

Uterine Fibroid and heavy bleeding might have a new drug if your normal drug was giving placebo. HPV Vaccine is still awesome and very very safe. Copper IUD has a new kid in town when it comes to emergency contraception and Colchicine should not be used for secondary prevention (at least not when I read the trial) HTTPS://WWW.NEJM.ORG/DOI/FULL/10.1056/NEJMOA2008283 Treatment of Uterine Fibroid Symptoms with Relugolix Combination Therapy international, double-blind, 24-week, phase 3 trials involving women with fibroid-associated heavy menstrual bleeding. Participants were randomly assigned in a 1:1:1 ratio to receive once-daily placebo, relugolix combination therapy (40 mg of relugolix, 1 mg of estradiol, and 0.5 mg of norethindrone acetate), or delayed relugolix combination therapy (40 mg of relugolix monotherapy, followed by relugolix combination therapy, each for 12 weeks). The primary efficacy end point in each trial was the percentage of participants with a response (volume of menstrual blood loss 12 times/year) were 2.5 times more likely to be current smokers, to consume >14 alcoholic drinks/week, and to drink >6 cups of coffee daily. AND THERE WAS A –response relationship with increasing tanning frequency. Many of you will know that a dose response relationshop is one of the keys for causation in observational studies. So could it be the tanning causes the smoking, drinking, and coffee drinking.. not directly. But could it be that the personality traits that cause you do go above and beyond are active in all actions of your life?? YES When you go above and beyong you go above and beyond for everything—its almost never something like well I am crazy about working out but I eat like garbage and vice versa if you eat terrible rarely are you crazy about working out. You burn it at both ends of the stick or you don’t the problem is controlling it in a healthy way which is maybe the key to life. https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2775955?guestAccessKey=d35250c2-a79e-486c-80e9-67a886cb9ef1&utm_source=silverchair&utm_medium=email&utm_campaign=article_alert-jamainternalmedicine&utm_content=olf&utm_term=021521 #FDA tells the companies but the companies don't tell the public! (thread) #MedTwitter This should be a #publichealth issue. @MedTweetorials If there is question related to a drug products quality, safety, and efficacy then the FDA will issue a "refuse-to-file" to the COMPANY not to the public. However, shouldn't their be transparency? Over a decade ago the #FDA even had a task force for more transparency! https://fdanews.com/ext/resources/files/archives/f/FDA-2009-N-0247-0107.1.pdf https://www.fdanews.com/ext/resources/files/archives/f/FDA-2009-N-0247-0107.1.pdf I will say a "refuse-to-file" is a rare event (thank goodness). Between 2008-2017 only 4% or 103 out of 2475 applications received a refuse to file. BUT guess how many times the public was informed of these "refuse-to-file"? 15.5% of the time! Only 16/103! This is TERRIBLE! It may come as no surprise that NONE of these "refuse-to-file" letters were were published in their entirety but rather as a press release or abbreviated form. Just like there was a large push as one time for authors to post or register their #clinicaltrials I think there should be equal push for companies to register and publish their "refuse-to-file" letters. I didn’t know only copper IUD!! The New England Journal of Medicine Levonorgestrel vs. Copper Intrauterine Devices for Emergency Contraception N. Engl. J. Med 2021 Jan 28;384(4)335-344, DK Turok, A Gero, RG Simmons, JE Kaiser, GJ Stoddard, CD Sexsmith, LM Gawron, JN Sanders In this trial, the researchers randomized women to a copper IUD or levonorgestrel IUD for emergency contraception and found the levonorgestrel IUD to be noninferior to the copper for this purpose. In the US, the copper IUD is currently the only approved IUD for emergency contraception. This trial provides compelling evidence for the use of levonorgestrel for emergency contraception, providing more options for women in the 5 days following unprotected intercourse. Greenberg JC et al. Life saving therapy inhibition by phones containing magnets. Heart Rhythm 2021 Jan 4; [e-pub]. (https://doi.org/10.1016/j.hrthm.2020.12.032) he magnet in the iPhone 12 is strong enough to turn off therapies from implantable cardioverter–defibrillators. Implantable cardioverter-defibrillators (ICDs) are designed so that an application of a reasonably strong (10-gauss) magnet can inactivate the therapy. This safety feature enables the device's therapies to be suspended for surgeries with cauterization and inappropriate shocks caused by rapid atrial fibrillation (AF) and lead fractures, among other issues. Theoretical concerns have been raised about interference of ICDs by cell phones; however, this interaction in real-life patients has rarely, perhaps never, been reported. Apple's new iPhone 12 contains a powerful magnet, which enables it to correctly align with external accessories (e.g., for wireless battery charging). In an experiment with a single person with an implanted Medtronic transvenous ICD, investigators studied whether the magnet in an iPhone 12 could disable ICD therapies. And indeed, whenever the iPhone was brought near the ICD, the device's ventricular therapies were suspended. Inhibition of ICD therapies by an iPhone is a major concern. Cell phones are frequently carried in chest pockets, some of which are close to an implanted ICD. Even a turned-off iPhone might cause this interaction. Patients and physicians must be aware of this possibly harmful, potential inhibition of ventricular therapies by the iPhone 12, and patients must avoid carrying it in a left chest pocket. And speaking of, many people thought that 2020 would be the year that colchicine would find its way back into our hearts What many people call one of the top articles of 2020 was in the NEJM titled Nidorf SM, Fiolet ATL, Mosterd A, et al. Colchicine in patients with chronic coronary disease. N Engl J Med. 2020;383:1838-47. https://pubmed.ncbi.nlm.nih.gov/32865380 Which was a study that looked at the use of low-dose colchicine to reduce the risk of cardiovascular (CV) events? 5522 patients who had evidence of coronary disease and had been clinically stable for ≥6 months were randomized after a 1 month run in phase. During the run in phase pateitns got colchicine, 0.5 mg/d. 15% of the patients were not randomized after randomization. 15%! Keep that in mind Basically 1 out of 6.5 people who were attempted to enter the trial were not able to tolerate the trial Remember a run in phase false elevates the results of the treatment arm. Because instead of having 100% of people taking place and only 85% taking the active drug since 15% could tolerate side effects. You only randomize people that could take the drug so then you have 100% taking the placebo and 100% taking the active arm. This makes it difficult because we don’t get run in phases in clinical practice. And the results were AMAZING! Or at least if you just read the conclusion “””In a randomized trial involving patients with chronic coronary disease, the risk of cardiovascular events was significantly lower among those who received 0.5 mg of colchicine once daily than among those who received placebo.” Not so fast- the risk of cardiovascular events—what is that?? It is the primary end point but what does it mean??? primary end point was a composite of cardiovascular death, spontaneous (nonprocedural) myocardial infarction, ischemic stroke, or ischemia-driven coronary revascularization. If you add enough outcomes you will always always find something…so you need to look at the individual outcomes MI = NNT- 81 ischemia-driven coronary revascularization= NNT 65 (which makes sense, cheating way to add more numbers to your outcome) cardiovascular death- no difference ischemic stroke, no difference now if you are actually reducing the number of heart attacks you would expect to see a decrease in the cardiovascular deaths but remember there was no difference in cardiovascular death. So if you are seeing a decrease in heart attacks and more patients are under going revascularization then these are suppose to be good things so why no change in cardiovascular deahts??? And people say yes but there was a trend towards decrease in cardiovascular dath with 20 in the colchicine arm and 25 in the placebo arm. BUT what no one is talking about is there was was more non cardiovascular deaths in the colchicine arm 53 vs 35 in the placebo arm. HR 1.51 (95% CI 0.99–2.31) which would cross one and suggest not significant but remember it is all a continuum that we make up it is not that at this rate it works and at this rate absolutely no benefit. So when you have 5 few cardiovascular deaths in the colchicine arm but 18 more noncardiovascular deaths in the colchicine arm it works out to a net increase of 13 more deaths from any cause in the colchicine arm. THIS IS BAD We don’t want more death! So was this just magic skills on the part of the trials where you move a few deaths this way and you slide a few more that way so you can say “there was a trend toward decrease cardiovascular death” or was this that maybe colchicine causes increase in nonCV death. OR Is it that MI and revascularization are really not that important?? Or is it that MI and revascularization are soft endpoints…. You ask 10 difference cardiologist if a patient needs to go for a cardiac cath and you might get 10 different answers. I don’t have the answer but I will tell you many people think this was a big practice changer in 2020 and everyone should get colchicine and I think well I think Based on a study that had 1 out of every 6 patients drop out during the run in phase and was only able to show a change in two very soft end points with no change in all cause death and almost a stastically significant negative change in the nonCVD death, I will not be prescribing this medication for my patients for secondary CV prevention anytime soon.

Part 2 of the top articles of 2020 1) statins and the nocebo effect 2) VA DOD Lipid guidelines- Don't check more than every 10 years! 3) blood in the urine and what to do about it per the newest guidelines. 4) SGLT2i, FLOZINS!!! The data and how to use it in practice with really really sick patients

A two part podcast on the top published articles of 2020

SGLT2 inhibitors and GLP1 agonists administered without metformin compared to other glucose‐lowering drugs in patients with type 2 diabetes mellitus to prevent cardiovascular events: A systematic review - Escobar - 2021 - Diabetic Medicine - Wiley Online Library Yes these fancy new drugs work with and without metformin but that does not mean these drugs should be first line!! Effect of a Single High Dose of Vitamin D3 on Hospital Length of Stay in Patients With Moderate to Severe COVID-19: A Randomized Clinical Trial | Complementary and Alternative Medicine | JAMA | JAMA Network Yep even 200,000IU of vit D does nothing except raise your vit d level. Diet and acne: review of the evidence from 2009 to 2020 - Dall’Oglio - - International Journal of Dermatology - Wiley Online Library What you eat does mess with your acne, or at least says this large observational trial. Statin treatment and muscle symptoms: series of randomised, placebo controlled n-of-1 trials | The BMJ The muscle aches with statins is a common event that it occurs as frequently with the active drug as it does with placebo

Semaglutide works for weight loss but at what co$t? BOARD CHANGER- New gonorrhea guidelines Diabetes drugs are expensive for our patients and we can't forget that. Children find it hard to tell what facial expression you are giving when you have a mask on! https://www.nejm.org/doi/10.1056/NEJMoa2032183 industry-conducted trial published in the New England Journal of Medicine. Researchers randomized nearly 2000 participants without diabetes who were either overweight with at least one weight-related comorbidity or obese to receive All2.4 mg subcutaneous semaglutide or placebo weekly for 68 weeks. mean bmi 38. weighing at 105 lbs. Mean weight loss was significantly greater with semaglutide than placebo (15% vs. 2%), as was the percentage of patients losing >5% of body weight (86% vs. 32%). difference is 31lbs-- over 68weeks or 16 months.. the drug cost 734$ per month. that is 11,744 for treatment or 379 per pound. not worth it to me twitter and say shouldnt you have the conversation?!? BOARD CHANGER The CDC now recommends treating uncomplicated gonorrhea with a single 500-mg intramuscular dose of ceftriaxone, according to updated guidelines in MMWR. The recommendation applies to urogenital, anorectal, and pharyngeal infections. Previously, the CDC recommended ceftriaxone plus oral azithromycin. The authors note that azithromycin resistance is "an increasing concern." Nationwide, the percentage of N. gonorrhoeae isolates with reduced susceptibility to azithromycin increased from 0.6% in 2013 to 4.6% in 2018. Among the recommendations: People weighing ≥150 kg should be given a single 1-g dose of ceftriaxone. In patients for whom a chlamydial infection has not been ruled out, doxycycline 100 mg orally twice a day for 7 days is also recommended. For patients with cephalosporin allergy, an intramuscular dose of gentamicin (240 mg) plus an oral dose of azithromycin (2 g) may be considered. In cases where intramuscular ceftriaxone can't be given, an oral dose of cefixime (800 mg) is an option, but the authors note it may not be as effective. For pharyngeal gonorrhea, there are no reliable alternative therapies and test-of-cure is recommended. Update to CDC's Treatment Guidelines for Gonococcal Infection, 2020 | MMWR BOARD ANSWER CHANGER https://news.wisc.edu/can-blocking-a-frown-keep-bad-feelings-at-bay/ remember that article back in 2010 which basically showed those people to get botox had decrease ability to defer emotions or facial expressions of others?? It was out of the university of wisconin and not they are back at it with this article---- https://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0243708 Children’s emotion inferences from masked faces: Implications for social interactions during COVID-19 Plos one This study took 81 7-13yr old child to see how children perceived others’ emotions as partial information about the face was presented pictures of stereotypical facial configurations associated with sadness, anger, and fear posed by male and female models. Pictures were presented in unaltered format (i.e., with no covering) or digitally altered to be (a) covered with a surgical face mask that obscured the mouth and nose, or (b) covered with sunglasses that obscured the eyes and eyebrows The primary question addressed by this study is whether masks meaningfully degraded children’s ability to infer others’ emotions “Accuracy between the faces that wore masks and shades did not differ” And that was the others conclsuions “These data suggest that while there may be some challenges for children incurred by others wearing masks, in combination with other contextual cues, masks are unlikely to dramatically impair children’s social interactions in their everyday lives” But that doesn’t tell the whole story Because when you look at the results you see that both sunglasses and mask did present a challenge for kids compared to no mask or no sunglasses. About a 10% absolute difference or a 33% realtive difference and althought you cant really use NNT in this type of trial if you were that would be a NNH of 10. For every 10 kids, 1 kid has a dramatic impairment in their ability to infer others emotions with the use of mask or sunglasses This is not me being antimask. This is not me saying that mask are the devil. This is me saying there are real effects to what we are doing and we have to be prepared for them and one of them might be children that are not able to infer emotions as well. Update to CDC's Treatment Guidelines for Gonococcal Infection, 2020 new guidelines regarding treatment of gonorrhea- Prior recommendations had included treating a patient for both gonorrhea and chlamydia when there was a positive gonorrhea test regardless of chlamydia results. These updated guidelines recommend not treating a patient for chlamydia if the patient is diagnosed with gonorrhea if testing shows no chlamydia infection. Treatment for both is still recommended if chlamydia status is unknown. Dosing for gonorrhea treatment was also increased from ceftriaxone 250mg IM to 500mg IM, and treatment for coinfection with chlamydia was changed from azithromycin to doxycycline with a longer course of 7 days. https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/10.1001/jamainternmed.2020. 2922?guestAccessKey=3ed2a6bb-bc67-4b5e-955c- 08cc5b7bedf6&utm_source=silverchair&utm_medium=email&utm_campaign=article_alert- jamainternalmedicine&utm_content=etoc&utm_term=120720 ben franklin is linked to the famous saying “a penny saved is a penny earned” well I wonder what he would say about our next and last paper titled- Out-of-Pocket Costs for Novel Guideline-Directed Diabetes Therapies Under Medicare Part D Which did exactly as the article suggests and looked at the cost of novel diabetic agents under Medicare part D which covers almost 45,000,000 people. They reviewed 6 drug classes and projected annual out-of-pocket costs Across near 3000 Part D plans commonly covered GLP-1RAs, SGLT2is, and DPP-4is had monthly list prices between $434 to $935 compared with $3 to $11 for metformin, sulfonylureas, and TZDs. What does that mean for your patient, how does that translate into real world information?? Well, annual costs for common novel agents were $5202 to $11 225 with only $31 to $136 for traditional drugs And the Projected annual out-of-pocket cost for novel drug regimen were $1231 to $1981, compared with $250 to $355 for traditional regimens. Considering at best these new agents have a NNT of 20 the variability to prevent one nonfatal event that approaches 100K needs to be seriously looked at.

Also ask yourself, did this study compare their treatment to the 'gold standard' and if the answer is no they compared it to a straw man, then think big Pharma, or authors that needed publication for their job. We can't treat what we don't know exist and 30-50% of the time COVID19 is asymptomatic. Combined Oral Contraception DO NOT have an increase risk of DVT and long term the risk are very minimal if a DVT does develop while on COC. Speaking of studies that should have never been done- Multicentre, prospective, randomised study comparing the diagnostic yield of colon capsule endoscopy versus CT colonography in a screening population (the TOPAZ study) | Gut (bmj.com) Diagnostic Yield of Colon Capsule Endoscopy vs CT Colonography in a Screening Population | PracticeUpdate The authors of this multicenter, prospective, randomized study compared the diagnostic yield of colon capsule endoscopy (CCE) with that of CT colonography (CTC) for colon cancer screening in an average-risk adult population. First you had either a CCE or a CTC and then the findings were confirmed with colonoscopy. The sensitivity and specificity of CCE for polyps ≥6 mm were 79.2% and 96.3%, respectively, compared with 26.8% and 98.9%, respectively, with CTC. The sensitivity and specificity of CCE for polyps ≥10 mm were 85.7% and 98.2%, respectively, compared with 50% and 99.1%, respectively, with CTC. They authors say this may work for people who refuse colonoscopy. Which is true it might but we have a fit test—it cost pennies—why in the world do we need this test?!? Its more money its more invasive its not better than FIT….. This is a study we didn’t need till I read the 30 line conflict of interest and I knew exactly why we needed this trial—to keep big pharm in business Colon cancer is scary cause most of the time we don’t know we have it and speaking of thigs we don’t know we have Asymptomatic SARS-CoV-2 Infections Among Persons Entering China From April 16 to October 12, 2020 | Global Health | JAMA | JAMA Network China controlled their cases because Beginning April 1, 2020, persons entering China via air, sea, or land have been mandatorily tested for SARS-CoV-2 infection by PCR test at border checkpoints. retrospective cohort study looked at All international entrants found to have SARS-CoV-2 infection via a positive PCR test result at China’s border checkpoints from April 16 to October 12 were included in this study. 3103 had confirmed COVID-19 cases, AMONG THOSE 1612 (51.9%) never developed symptoms through day 13 and were considered to have asymptomatic SARS-CoV-2 infection. The Proportion of SARS-CoV-2 Infections That Are Asymptomatic: A Systematic Review: Annals of Internal Medicine: Vol 0, No 0 (acpjournals.org) Purpose: To estimate the proportion of persons infected with SARS-CoV-2 who never develop symptoms. And results found- about 1/3 of people had no symptoms and if you test positive and have no symptoms then about 75% of the time you will never have symptoms. WE will never be able to stop what we don’t even know about. WE can never and I repeat NEVER flatten a curve on something that you may not even know you have 33% of the time. Efficacy and safety of antidepressants for the treatment of back pain and osteoarthritis: systematic review and meta-analysis | The BMJ Prescribe antidepressants for depression not for pain Design Systematic review and meta-analysis. Objective To investigate the efficacy and safety of antidepressants for back and osteoarthritis pain compared with placebo. Pain and disability were primary outcomes. Pain and disability scores were converted to a scale of 0 (no pain or disability) to 100 (worst pain or disability). Results 33 trials (5318 participants) were included. Back pain- serotonin-noradrenaline reuptake inhibitors (SNRIs) reduced back pain (mean difference −5.30, 95% confidence interval −7.31 to −3.30) at 3-13 weeks SNRIs reduced sciatica at two weeks or less (−18.60, −31.87 to −5.33) but not at 3-13 weeks (−17.50, −42.90 to 7.89). tricyclic antidepressants (TCAs) did not reduce sciatica at two weeks or less but did at 3-13 weeks (−15.95, −31.52 to −0.39) and 3-12 months (−27.0, −36.11 to −17.89). SNRIs reduced disability from back pain at 1-13 weeks around 1-3 points—TO WHAT SIGNIFCANT CLINCALY ON 100 point scale. osteoarthritis- SNRIs reduced osteoarthritis pain (−9.72, −12.75 to −6.69) at 3-13 weeks TCAs and other antidepressants did not reduce pain or disability from back pain. ReplyForward 8000 women from 2004-2006- to be included you could not be pregnant or postpartum and aged ≤ 50 years, without active cancer There were 220 women had either a first distal dvt, first prox dvt, or a first PE Of these women, 47.3% (n/N = 104/220) were on COC pills at the time of their VTE event. Overall, 27.6% of patients developed venous thromboembolism (VTE)

The Drug Addiction Treatment Act of Under the Act, physicians may apply for a waiver to prescribe buprenorphine for the treatment of opioid addiction or dependence outside of an opioid treatment program (OTP). The Drug Addiction Treatment Act of 2000 was authored by Senator Orrin Hatch (R-UT), Senator Joe Biden (D-DE), and Senator Carl Levin (D-MI). DATA 2000 waiver Why would biden reverse this—it was one of the things I think we all agree upon is a good thing!! I thought it must be the money – its always the money But I found a few reasons reasons why Confirmation bias--- Under the Act, physicians may apply for a waiver to prescribe buprenorphine for the treatment of opioid addiction or dependence outside of an opioid treatment program (OTP) Money== Biden received $6.3m from pharma, compared to $1.6m for Trump, Polack FP, Thomas SJ, Kitchin N, et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N Engl J Med. 2020;383:2603-15. https://pubmed.ncbi.nlm.nih.gov/33301246 Randomized placebo-controlled trial. Randomized placebo-controlled trial. Of either BNT162b2 (BioNTech/Pfizer), given intramuscularly in two 30-mcg doses 21 days apart (n = 21 720 received vaccine), or saline placebo (n = 21 728). Bottom line: “ A two-dose regimen of BNT162b2 conferred 95% protection against Covid-19 in persons 16 years of age or older.” BUT WHAT DOES THIS MEAN?!?! Does it mean that if we inject everyone that only 5% of the population will get covid19?

Autoimmune mothers likely don't actually have more ADHD kids. If you patient is in the hospital we now have a RCT to answer the question about ACEI starting or stopping. Finally, there are problems around COVID we don't even know about and it has nothing to do with contracting COVID19. Association of Maternal Autoimmune Disease With Attention-Deficit/Hyperactivity Disorder in Children | Attention Deficit/Hyperactivity Disorders | JAMA Pediatrics | JAMA Network Doesn't say what the authors think that it says – or perhaps it does and that is the problem with most studies in pregnancy…. The authors conclusions were “In this cohort study, maternal autoimmune diseases were associated with increased ADHD among children.” Wiat autoimmune disorders in mom and boom big time risk of ADHD in children! Better brain has true celiac so this is something I am interested—it sparked my attention! population-based cohort analysis of 831,718 infants and mothers in the end the researchers matched almost 13,000 children whose mother's had an autoimmune disease with approximately 50,000 children whose mothers did not have an autoimmune disease and when they crunch through all of the numbers those individuals whose mothers did not have an autoimmune disease were diagnosed with ADHD 5.48 cases per 1000 boys and 1.70 per 1000 girls BUT if your mom had an autoimmine disease then your risk of ADHD SHOT UP. From 5.5 for boys to 6.9 and from 1.7 for girls to 2.3. Yes that’s right an extra case of ADHD for every 700boys and an extra case of ADHD for every 2000 girls--- multiple things about the study- first of all not very impressed by the findings. Ousley is a cohort study so they're just looking at groups of patient's at different points of time. However may be the mothers who have autoimmune disorders are more likely to go to the doctor for their illness and thus more likely to take the child to the doctor. Or mothers who have autoimmune disorders are probably more likely to have health insurance for their medical condition and thus more likely once again to take their children to the doctor. After all he can be diagnosed with ADHD or any other illness unless you go to the doctor to get the diagnosis. Next this is a perfectly example of absolute and relative risk reduction which is often miss under still by many medical students, resident's, and even attending physicians. Left look at the event rate of ADHD in girls. It was 1.7 per thousand for those individuals who did not have a mother with an autoimmune disorder and the event rate went up to 2.3 cases of ADHD per thousand for those girls whose mother has an autoimmune disorder. The difference between 1.7 and 2.3 is 0.5. Thus you could say that if you have a mother with an autoimmune disease then there is a 0.5 per thousand increase rate of ADHD. Or since 0.5 is about a third or 33% of of 1.7- I could potentially say that having a mother with an autoimmune disorder increases your risk of ADHD as a female child by 33%. In both statements I'm saying the same thing-------------- rant A reminder- The authors conclusions were “In this cohort study, maternal autoimmune diseases were associated with increased ADHD among children.” So maybe this article does say what the authors think that it said but unless you read the article you might be tricked into thinking that this was a substantial finding and worth long debates and discussion about. One of many problems with pregnancy litature is the small almost insignificant findings. you see there actually was an increase but that increase was so small---- the reason being is that most pregnancies go off without a hitch. Most pregnancies don't have any complications. Most pregnancies that are carried to term delivery are absolutely fine so when you find even a small increase in the numbers you can report regardless if it worth your time to know about or think about. The next article is the ultimate questiongin medicine article Effect of Discontinuing vs Continuing Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers on Days Alive and Out of the Hospital in Patients Admitted With COVID-19: A Randomized Clinical Trial | Critical Care Medicine | JAMA | JAMA Network Remember at the beginning of covid I did a podcast and I talked about ACE and ARBs and said I am still writing for them. This belief the are bad comes from bad evidence Actually not even evidence—just opinion pieces such as a piece in journal of htn back in may titled- Like Can angiotensin receptor-blocking drugs perhaps be harmful i... : Journal of Hypertension (lww.com) Can angiotensin receptor-blocking drugs perhaps be harmful in the COVID-19 pandemic? Some of us stopped acei on everyone. You make a fancy little drawing and explaination of a possible mechanism and many people fall victim and believe you. This is why drug reps are so successful. For majority of physicians they don't actually have the prove any benefit or outcome just a bunch of drawings with fancy words and potential mechanisms of how it could work. Others of us demand hard outcomes and appropriate clinical trials Well now we have our results in this JAMA article which is the first randomized control trial of roughly 650 patient's hospitalized with mild to moderate COVID-19 who were taking either an ACE inhibitor or an angiotensin II receptor blockers (ARBs) on admission. Patient's were then randomized to either discontinue the ACE inhibitor or angiotensin II receptor blocker or to continue it. The primary outcome was the number of days alive and out of the hospital after 30 days. The secondary outcomes included death, cardiovascular death, and COVID-19 progression And there was absolutely no difference no matter what you looked at Continue the ACE OR ARB when you patient is admitted to the hospital with mild to moderate covid19 And the last article should make you think Make you think Progression of Myopia in School-Aged Children After COVID-19 Home Confinement | Global Health | JAMA Ophthalmology | JAMA Network There are problems with covid 19 we cant even see yet. They have nothing to do with getting covid. They have to do with not getting covid. The social isolation is one of them but another one is the concern is whether home confinement 4 children may have a burden on their eyes. Less time outside = less time playing and more time inside likely in front of some sort of screen whether it be a computer screen or a TV screen or a tablet screening. So in the study the authors set out to fine if the prevalence of myopia in school children during Covid 19 was affected. The theory being that children are spending more time in front of a screen and less time outside and thus the eyes are not encouraged to grow any look for anything greater than something that is 2 feet in front of the face. This study was paced out of China however I think that the results of likely applicable to everyone. Photoscreenings have been performed annually on children in 10 elementary schools since 2015- this is usually over 100,000 children participating each year. In each ear the authors calculated an estimated prevalence of myopia And in 2020 the rates of myopia s/p covid quartine the changes were scary. For 8yr olds the prevalence in previous years was 27% and it jumped up to 37%. For seven year olds the prevalence was 16% and jumped up to 26% and for 6 year olds the prevelance of myopia was 5.7% and relatively speaking it jumped up 400% or and absolute of 21% This substantial myopic shift was not seen in any other year-to-year comparison, What does this mean?? Sure there is a change but what does it mean?? And the answer is we don’t totally know and we wont know We do know currently that 1 in 3 people with high myopia becomes severely visually impaired, mostly at working age. So the potential health problem is very bad. This is not me saying we shouldn’t have shut down at the beginning But this is me saying that it is sad some of the problems we don’t even realize we have or will have because of the covid19 pandemic Much of the pandemic became a political issue which only hurts the patient when medical clarity is clouded by political preference.

HHS Expands Access to Treatment for Opioid Use Disorder | HHS.gov U.S. Department of Health and Human Services Announcement of practice guidelines for the administration of Buprenorphine for treating opioid use disorders Jan 12- 20221 -physicians with a DEA license- only not all providers -you can only treat patients located in the state you have a medical license in (basically no tele) -Physicians utilizing this exemption will be limited to treating no more than 30 patients with buprenorphine for opioid use disorder at any one time (note: the 30 patient cap does not apply to hospital-based physicians, such as Emergency Department physicians). -ONLY buprenorphine- does not apply to methadone for the treatment of OUD. - Physicians utilizing this exemption shall place an "X" on the prescription and clearly identify that the prescription is being written for opioid use disorders

They say every dog has its day and IT think every drug has its place Anyone who says ‘that drug is bad’ or that test is bad or that anything is bad is just being closed minded or not aware of the evidence because evidence and medicine comes down to numbers. The real statement should be I don’t think that drug is beneficial enough for the harm. However that is an opinion statement, it is what you think and that is when shared decision making comes into play because maybe your patient does think it is beneficial No more clearly see than in this viewpoint in Jama titled Balancing the Risks and Benefits of Benzodiazepines https://jamanetwork.com/journals/jama/fullarticle/2775180?guestAccessKey=fe7dd94f-653f-4da0-ad1f-21fb8c60e420&utm_source=silverchair&utm_medium=email&utm_campaign=article_alert-jama&utm_content=olf&utm_term=010821 Which talks about the risk and benefits of benzos. A drug that I often here so many providers dis on with no real evidence to back it up—how do I know there is no real evidence?? Because as the authors point out To date, no published meta-analyses have compared benzodiazepines with selective serotonin reuptake inhibitors for anxiety People will often cite data from morbitiy and mortality weekly and say that rates of abuse are on on the rise and as an example- among US women aged 30 to 64 years, the rate of benzodiazepine-related deaths increased from approximately 0.5 per 100 000 population in 1999 to nearly 5 per 100 000 population in 2017; BUT BUT “I said benzodiazepine-related deaths” That is such a tricky number it just means that benzo were on board not that benzo killed them. If I said oxygen related deaths the number would be 100%. Everyone who breaths oxygen dies. and, these data do not distinguish benzodiazepine monotherapy related death from coadministration with other medications. from 1993 to 2014, the rate of benzodiazepines and opioids combined increased from 9.8 to 62.5, per 100 000 outpatient visits Sure benzos can be addictive but so can SSRI! Have you every tried to take someone off an SSRI?!? You can’t just stop it cold turkey most of the time and lets be honest if you are addicted to drugs you fix isnt coming from benzos. in 2017 among 2 005 395 admissions to publicly funded substance abuse treatment programs only 1% identified benzodiazepines as their primary drug of abuse. I am not saying benzos are perfect and give them to everyone. Of course not, and I agree fewer people needs benzos but Every dog has its day and every drugs has its use practice guideline from the American Psychiatric Association includes benzodiazepines among first-line pharmacologic treatment strategies for panic disorder I bring all this up because https://www.fda.gov/drugs/drug-safety-and-availability/fda-requiring-boxed-warning-updated-improve-safe-use-benzodiazepine-drug-class September 2020, the US Food and Drug Administration (FDA) announced an update to the boxed warning on all benzodiazepines to explicitly “address the serious risks of abuse, addiction, physical dependence, and withdrawal reactions” My fear is most physicians will see this headline, never critically think about it and mimic what they read and it will come off as “benzos are addictive, abusivie, and a terrible drug” with little thought to the limitations of the evidence. They will likely then go on writing for their SSRI which also has addictive properties with results that are slower for onset and not better than the benzo. I am not saying these are great drugs but if you are saying they are terrible drugs then you need to remember Every dog has its day. https://www.practiceupdate.com/c/111407/2/6/?elsca1=emc_enews_daily-digest&elsca2=email&elsca3=practiceupdate_primary&elsca4=primary-care&elsca5=newsletter&rid=MzU5ODQyMjUwMDM1S0&lid=20849334 Not all things are created equal and not test are created equal. This is no more clearly seen in this article in the New England Journal of Medicine tittled Racial Bias in Pulse Oximetry Measurement I often talk about exclusion and inclusion criteria on this podcast and did you know the pulse ox has not been validated in racial diverse populations. https://www.nejm.org/doi/10.1056/NEJMc2029240 In the study looking at pulse oximetry the author’s were testing for occult hypoxemia which is basically an arterial oxygen saturation of less than 88% despite the pulse oximetry satting 92-96%. This is a big deal, if I walk in the room and I see a pulse oximetry reading 94 or 95% my patients actual oxygen level is certainly above 88%. However, in the study they found that almost 12% of black patient’s had a pulse oximetry between 92-96% but a blood gas oxygen of less than 88% and this only occurred 3-1/2% of the time in white patient’s. So what you do with this information? Well I think the best way to use it is on the lower end of the pulse oximetry say 92 or 93 or 94% in your black patient’s you should consider increasing their oxygen as the percent of occult hypoxemia at increased as patient’s or approaching 92% pulse oximetry and started 0 cases of occult hypoxemia at 96% pulse oximetry. This may not be the most practice changing article of the year but certainly something I think is important for everyone to be aware of. 1 unhealthy lifestyle begets another unhealthy lifestyle. That is from JAMA network open in a paper titled Maciejewski ML et al. Association of bariatric surgical procedures with changes in unhealthy alcohol use among US veterans. JAMA Netw Open 2020 Dec 21; 3:e2028117. (https://doi.org/10.1001/jamanetworkopen.2020.28117) Which propensity matched just over 2000 patients that were getting Roux-en-Y gastric bypass surgery or a laparoscopic sleeve gastrectomy to individuals who were not getting bariatric surgery and after 8 years of follow-up those individuals who had surgery were almost twice as likely to have an healthy alcohol use disorder. Was at that the gastric bariatric surgeries caused alcohol use disorder? not likely. Realistically most people who are obese are eating from something. Most we will run 20 or 30 miles are running from something. And most he will drink in excess or drinking from something. While a simple surgery can fix your ability to eat and consume large amounts of food and can’t fix the underlying damage or trauma or mental state of mind which caused unhealthy consumption of food in the first place, thus 1 unhealthy lifestyle fixed with surgery begets another unhealthy lifestyle. Less is more or so says this article in jama internal medicine titled - Treatment and Outcomes of Inpatient Hypertension Among Adults With Noncardiac Admissions Among adults with noncardiac admissions, is treatment of hypertension during the admission or antihypertensive treatment intensification at discharge associated with better outcomes? We have all had the nurse or the pharmacist call us right before discharge and say this patient was give one or two doses of this bp med during this hospital stay, Do want them to go home with this dose? https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2774562?guestAccessKey=92cef46d-2a66-4714-870f-105561a4041c&utm_source=silverchair&utm_medium=email&utm_campaign=article_alert-jamainternalmedicine&utm_content=olf&utm_term=122820 Which sometimes can seem like a confusing question but in this study of almost 23,000 patient’s hospitalized for a non-cardiovascular diagnosis those individuals who were discharged with medications had worse outcomes at 30 days and at one year. What are these outcomes I’m referring to? Really important outcomes that we carry out such as stroke and myocardial infarction. In fact there was no interval in which hypertensive treated patients had better outcomes than those individuals who were left untreated. The absolute numbers were small such as a myocardial infarction rate from 0.6 up to 1.2% and normally you might be used to me saying this is such a small increase why do we care about it but in this circumstance the reason we care is because we are giving medication in hopes that we are doing a good thing and preventing hypertension but in all actuality we are causing harm by doing more so as this segment states when he comes to the management of the med rec for a hypertensive patient while in the hospital….. Less seems to truly be more

Dr sprouse-- Endo saying that Vit D below 30 leads to 2nd hyperparathyroidism due to calcium absorption deficiency and downstream consequences of that condition leads to poor bone health. He agreed all the other outcomes don’t have good evidence. I think 30 is the recommendation from the endo society. MY RESPONSE Well just to be clear they are right and they are wrong Yes it MAY, key word is MAY (it’s a not a universal truth), cause a secondary hyperparathyroid. HOWEVER, as I am sure you have already thought, this is a lab value. WE DON’T CARE ABOUT LAB VALUES, we care about patients. We treat patients, not lab values. So realistically who cares!?!?!? They will say well we care because it leads to broken bones and fractures!?!?! Then say really?? Based on what data because in this trial of almost 700 women who underwent BMD testing at baseline and 2 years later there was no difference between vitamin d and placebo https://asbmr.onlinelibrary.wiley.com/doi/full/10.1002/jbmr.3958 And they will say yes but that showed no difference because those individuals already had baseline high vit. D And you say—OOOO so you think something magical happens at the cutoff of 30 that makes it so these patients now magically benefit from vit d And they will say “that is correct” And you say, “well what about this article that talks about the analytic and biological variance of vit d to be about 50%, which basically means that you need to see a 50% change to even say that there is a real difference and a lab value of 30 COULD actually mean the real number falls anywhere between about 19 and 41 because lab values are just point estimates but in all actually there are 95% CI that surround each lab value or point estimate.” “Thus shouldn’t this magical number actually be 41?” https://www.bmj.com/content/368/bmj.m149 They will say “I have no idea what you are talking about, all lab values are 100% accurate” (this is a really really hard concept for people to grasp) Then you say- “well that is really interesting because this study actually found those individuals with baseline enrollment vit d level of 30 actually had worse volumetric BMD when taking higher levels of vit d” https://jamanetwork.com/journals/jama/fullarticle/2748796 They will say something like “yes, but that didn’t have a true placebo group and we fail to observe the rule of dose measurement” (which basically says that if you give some that is good and with increasing doses you should see more of an effect, it was be quantifiable to the same amount of the dose increase but it will be quantifiably greater. Think of blood pressure pills, you get most bang for your buck on the lowest dose, higher doses give you more but it is not at the same rate) And you say “well I can see you are really stuck on this magical cutoff of 30 even though the lab measurement is variable and appears to be completely made up and you don’t believe in dose response BUT what about this article that took 260 women with vit levels between 8 and 26 and randomized them to vitamin d levels achieved above 30 (which ended up being 3500IU daily as baseline level was 22) for 3 years and found no difference in bone density between the placebo group and the vit d group” https://asbmr.onlinelibrary.wiley.com/doi/full/10.1002/jbmr.3521 They will say, “Yes, but Andrew that is only one study and you can’t look at one study” You then say, “O well what about this meta-analysis and SR in Lancet Endocrinology that looked at 81 RCT and over 53K people that found and I quote “Our findings suggest that vitamin D supplementation does not prevent fractures or falls, or have clinically meaningful effects on bone mineral density. There were no differences between the effects of higher and lower doses of vitamin D. There is little justification to use vitamin D supplements to maintain or improve musculoskeletal health. This conclusion should be reflected in clinical guidelines.” https://www.clinicalkey.com/#!/content/journal/1-s2.0-S2213858718302651 They will say “Yes but you see it is those individuals with a vit d 30 and

NEW covid19 vaccine I am sure many of you have heard it is the first of its kind. It uses mRNA technology. I am not going to discuss what that means ebcasue so many people already have on other podcasts and publications but the question is should you get the vaccine. I have read many opinons on this from experts for example Dr. Michal Elovitz, a preterm labor researcher and obstetrician at the University of Pennsylvania. Said its possible the mRNA and the bubble it travels in, made of lipid nanoparticles, could cross the placenta, and This might, in theory, cause inflammation in utero that could be harmful to the developing fetal brain” she went on to say, “It’s also possible the new vaccines could be totally safe in pregnancy, like the flu shot.” No pregnant patients were enrolled in the accessible trials, although some people got pregnant during the course of the study. Researchers are monitoring them to see how they do. We have not even tested this on pregnant animals—we have no idea if this is safe for pregnant women and this is exactly what I am talking about when I say inclusion drift. It was something that big pharm thrives on. You get your drug approved in one condition or pt population then you market the drug as this great drug and then quickly the providers forget that the benefit found in the trial was only under perfect conditions with mean age of 25 yrs old and no health problems…. The chance you will see the same benefit in your 75 year old HONDA is almost impossible….. BUT as long as you prescribe the drug they don’t care about your individual patient and their lack of benefit because they care about selling more drugs.. in the drug company world this is comparible to a bait and switch seen by car salesman. Show you the fancy benefits with the drug seen in their perfect patients and perfect environment then take your money or your patients money for much less impressive results. Studying pregnant people requires extra effort in safe study design and recruitment efforts, Anything you do to a pregnant woman also has a chance of affecting the developing offspring pregnant women are often just excluded altogether. https://pubmed.ncbi.nlm.nih.gov/21766440/ a paper from 2011 Evolving knowledge of the teratogenicity of medications in human pregnancy Which looked at all 172 FDA drugs approved from 2000 to 2010 and guess hoa many had known teratogenic risk??? Whatever you said the answer is wrong because they found most had “undetermined” risk -- in fact “The teratogenic risk in human pregnancy was "undetermined" for 168 (97.7%) of drug treatments approved between 2000 and 2010.” “we have adequate data on the risk of birth defects in less than 10 percent of medications approved by the Food and Drug Administration since 1980. “ If someone on rounds says “med student, tell me the risk of this medication and in pregnancy” you are going to be right 9 out of 10 times if you say “we have no FDA proven data on that” And speaking of the FDA what did they say about this -- F.D.A. left the choice of whether or not to get the Covid-19 vaccine up to pregnant women, · The American College of Obstetricians and Gynecologists per usual isn’t worth their weight in feathers as they said- “ACOG recommends that COVID-19 vaccines should not be withheld from pregnant individuals who meet criteria for vaccination based on Advisory Committee on Immunization Practices recommended priority groups.” I swear the ability to critically think or form your own opinion must occur some place around the second year of OB/gyn residency because their guidelines and opinions are almost always the least imformative or evidence based documents to ever be published. In their released statement they try to state some small crappy observational studies One which showed if you were preg and had covid you were more likely to go to the ICU—well ist hat cause you are sick or because you are pregnant and have covid and realistically back in April if you were pregnant and had covid and even sneezed you were admitted to the ICU The other was a morbidity and mortality weekly report which 598 hospitalized pregnant women with COVID-19- now most of these women were hospitalized for labor and delivery and then were asymptomatic and tested positive for covid19 And of those almost 600 women hospitalized lets get to the scary part 16.2% were admitted to an intensive care unit (ICU), and 8.5% required invasive mechanical ventilation. Which sounds scary but we care about is pregnancy loss And turns out 2.2% of the women had a pregnancy loss Which is scary but we know spontaneous abortion is a real thing especially at